Stiff Arteries Treatment: Comprehensive Review and Update on Management Strategies

19.02.197424.09.2021 by alexxlab

What are the main causes of arterial stiffness. How is arterial stiffness measured clinically. Which lifestyle modifications can improve arterial stiffness. What pharmacological treatments are effective for arterial stiffness. How does arterial stiffness impact cardiovascular health and prognosis.

Содержание

Understanding Arterial Stiffness: Pathophysiology and Clinical Significance

Arterial stiffness is a key marker of cardiovascular health that has garnered significant attention in recent years. But what exactly is arterial stiffness? At its core, arterial stiffness refers to the reduced elasticity of arterial walls, particularly in large conducting arteries like the aorta. This stiffening impairs the arteries’ ability to expand and contract efficiently with each heartbeat.

The arterial system serves two crucial functions:

Conducting blood from the heart to peripheral organs
Cushioning the pulsatile flow of blood, buffering forward propagation from the heart and backward resistance from peripheral arterioles

When arteries stiffen, this delicate balance is disrupted, leading to increased cardiac workload and potential damage to end organs due to excessive pulsatile stress.

The Clinical Importance of Arterial Stiffness

Why should clinicians and patients be concerned about arterial stiffness? Research has consistently shown that increased arterial stiffness is associated with:

Higher risk of cardiovascular disease (CVD)
Worse long-term clinical outcomes across various populations
Independent prediction of incident CVD and all-cause mortality in the general population

A meta-analysis of 17 longitudinal studies has solidified the role of aortic stiffness as a powerful prognostic indicator. Given these findings, developing evidence-based approaches to improve arterial stiffness has become a priority in cardiovascular medicine.

The Pathophysiology of Arterial Stiffness: A Closer Look

To understand how to treat arterial stiffness, we must first grasp its underlying mechanisms. The arterial system can be divided into two functional subsystems:

Large elastic conducting arteries (e.g., aorta, carotid arteries, iliac arteries)
Resistance muscular arteries (e.g., femoral, popliteal, and posterior tibial arteries)

The large elastic arteries store blood during systole and expel it during diastole, ensuring steady blood flow. Resistance arteries can modulate their smooth muscle tone, affecting the velocity of pressure waves conducted from the central aorta.

Arterial stiffness occurs when these vessels lose their elasticity, often due to structural changes in the arterial wall. These changes can include:

Increased collagen deposition
Fragmentation of elastin fibers
Calcification of the arterial wall
Endothelial dysfunction

The Role of Pressure Waveforms

The pressure waveform recorded in the aorta is a combination of forward-traveling waves generated by cardiac contraction and backward-traveling “echo” waves reflected from peripheral sites. In healthy, elastic arteries, these waves are timed to optimize cardiac efficiency and coronary perfusion. However, in stiff arteries, the reflected waves return earlier, increasing cardiac afterload and potentially reducing coronary perfusion.

Risk Factors Contributing to Arterial Stiffness

What factors contribute to the development of arterial stiffness? Several traditional cardiovascular risk factors have been implicated:

Age
Hypertension
Smoking
Dyslipidemia
Diabetes
Obesity
Systemic inflammation

These factors contribute to both atherosclerosis and arterial stiffness, often through overlapping mechanisms. For instance, chronic hypertension can lead to arterial wall remodeling, while systemic inflammation may promote vascular dysfunction and accelerated arterial aging.

The Impact of Age on Arterial Stiffness

How does aging affect arterial stiffness? As we age, several changes occur in our arteries:

Gradual loss of elastin fibers
Increased collagen cross-linking
Accumulation of advanced glycation end-products (AGEs)
Reduced nitric oxide production by endothelial cells

These age-related changes contribute to progressive arterial stiffening, even in the absence of other risk factors. However, the rate of this progression can be influenced by lifestyle and other modifiable risk factors.

Measuring Arterial Stiffness: Clinical Approaches and Techniques

Accurate measurement of arterial stiffness is crucial for risk assessment and treatment monitoring. What methods are available for clinicians to assess arterial stiffness?

Pulse Wave Velocity (PWV)

Pulse wave velocity is considered the gold standard for measuring arterial stiffness. How is PWV measured?

Two pressure waveforms are recorded at different arterial sites
The distance between these sites is measured
PWV is calculated as the distance divided by the time delay between waveforms

Higher PWV values indicate stiffer arteries. Carotid-femoral PWV is the most widely used and validated measure of aortic stiffness.

Cardio-Ankle Vascular Index (CAVI)

The Cardio-Ankle Vascular Index is another method for assessing arterial stiffness. What makes CAVI unique?

It’s less affected by blood pressure at the time of measurement
Reflects the stiffness of the aorta, femoral artery, and tibial artery as a whole
Provides information on both central and peripheral arterial stiffness

Other Measurement Techniques

Additional methods for assessing arterial stiffness include:

Augmentation index (AIx)
Ultrasound-based techniques (e.g., echo-tracking)
Magnetic resonance imaging (MRI) for direct visualization of arterial wall properties

Each method has its strengths and limitations, and the choice often depends on the specific clinical or research context.

Lifestyle Modifications to Improve Arterial Stiffness

Can lifestyle changes help reduce arterial stiffness? Indeed, several non-pharmacological interventions have shown promise in improving arterial elasticity:

Dietary Interventions

What dietary changes can help reduce arterial stiffness?

Long-term ω-3 fatty acid (fish oil) supplementation
Increased consumption of fruits and vegetables
Reduced sodium intake
Moderate alcohol consumption

These dietary modifications have shown particular benefits in populations with hypertension or metabolic syndrome.

Exercise and Physical Activity

How does exercise impact arterial stiffness?

Regular aerobic exercise can improve arterial elasticity
Resistance training, when properly prescribed, may also have benefits
A combination of aerobic and resistance exercise may be most effective

The intensity, duration, and type of exercise should be tailored to individual patient needs and capabilities.

Weight Management

In obese individuals, particularly those with obstructive sleep apnea, weight reduction can significantly improve arterial stiffness. This improvement is often associated with better overall cardiovascular health and reduced inflammation.

Smoking Cessation

Quitting smoking is a crucial step in improving arterial health. Smoking cessation can lead to rapid improvements in vascular function and a gradual reduction in arterial stiffness over time.

Pharmacological Treatments for Arterial Stiffness

While lifestyle modifications are crucial, pharmacological interventions often play a key role in managing arterial stiffness, especially in high-risk populations. What medications have shown efficacy in treating arterial stiffness?

Renin-Angiotensin-Aldosterone System (RAAS) Antagonists

RAAS antagonists, including ACE inhibitors and angiotensin receptor blockers (ARBs), have demonstrated significant benefits in reducing arterial stiffness. How do these medications work?

Reduce vascular inflammation
Improve endothelial function
Promote favorable arterial remodeling

These effects go beyond simple blood pressure reduction, making RAAS antagonists particularly valuable in managing arterial stiffness.

Statins (HMG-CoA Reductase Inhibitors)

Statins, primarily known for their lipid-lowering effects, have also shown promise in improving arterial stiffness. What mechanisms contribute to this benefit?

Reduction of vascular inflammation
Improvement of endothelial function
Potential modulation of vascular smooth muscle cell function

Metformin

In individuals with diabetes or metabolic syndrome, metformin has demonstrated the ability to improve arterial stiffness. This effect may be due to:

Improved insulin sensitivity
Reduced oxidative stress
Direct vascular effects independent of glucose control

Novel Therapeutic Approaches

What new treatments are being investigated for arterial stiffness?

AGE-breakers: Compounds designed to break advanced glycation end-product crosslinks
Selective androgen receptor modulators (SARMs): Potential to improve vascular function without adverse effects of traditional androgens
Renal sympathetic nerve denervation: Being studied for resistant hypertension and its effects on arterial stiffness

These emerging therapies are currently undergoing clinical trials to establish their efficacy and safety in managing arterial stiffness.

Managing Arterial Stiffness in Specific Populations

Different patient populations may require tailored approaches to managing arterial stiffness. How should clinicians approach arterial stiffness in specific groups?

Hypertensive Patients

In hypertensive individuals, a multi-pronged approach is often necessary:

Aggressive blood pressure control, often with RAAS antagonists
Lifestyle modifications, including sodium restriction and increased physical activity
Regular monitoring of arterial stiffness to guide therapy

Diabetic Patients

For patients with diabetes, managing arterial stiffness involves:

Tight glycemic control
Use of medications like metformin that have additional vascular benefits
Aggressive management of other cardiovascular risk factors

Patients with Chronic Inflammatory Diseases

In populations with chronic inflammatory conditions like rheumatoid arthritis, additional considerations include:

Use of disease-modifying anti-rheumatic drugs (DMARDs) to control inflammation
Consideration of biologic therapies, such as anti-TNF-α antibodies, which may improve arterial stiffness
Close monitoring of cardiovascular risk factors, as these patients often have accelerated vascular aging

Elderly Patients

Managing arterial stiffness in older adults requires a balanced approach:

Careful titration of antihypertensive medications to avoid hypotension
Emphasis on lifestyle modifications suitable for older adults
Consideration of comorbidities and polypharmacy

Future Directions in Arterial Stiffness Research and Management

As our understanding of arterial stiffness evolves, what future developments can we anticipate in this field?

Advanced Imaging Techniques

Emerging imaging technologies may provide more detailed insights into arterial structure and function:

High-resolution MRI for assessing arterial wall composition
Novel ultrasound techniques for real-time evaluation of arterial elasticity
Artificial intelligence-assisted image analysis for more precise quantification of arterial stiffness

Personalized Medicine Approaches

The future of arterial stiffness management may lie in more personalized treatment strategies:

Genetic profiling to identify individuals at high risk for accelerated arterial stiffening
Tailored interventions based on individual patient characteristics and biomarkers
Development of novel therapies targeting specific pathways involved in arterial stiffening

Integration with Wearable Technology

How might wearable devices contribute to arterial stiffness management?

Continuous monitoring of surrogate markers of arterial stiffness
Real-time feedback to guide lifestyle modifications
Integration with telemedicine platforms for remote patient monitoring

These advancements could revolutionize how we approach the long-term management of arterial health.

In conclusion, arterial stiffness represents a critical aspect of cardiovascular health that demands attention from both clinicians and researchers. By understanding its pathophysiology, accurately measuring its progression, and implementing targeted interventions, we can work towards reducing the burden of cardiovascular disease associated with arterial stiffness. As research in this field continues to advance, we can anticipate more refined and effective strategies for managing this important cardiovascular risk factor.

An update and comprehensive review

Abstract

Arterial stiffness has been recognized as a marker of cardiovascular disease and associated with long-term worse clinical outcomes in several populations. Age, hypertension, smoking, and dyslipidemia, known as traditional vascular risk factors, as well as diabetes, obesity, and systemic inflammation lead to both atherosclerosis and arterial stiffness. Targeting multiple modifiable risk factors has become the main therapeutic strategy to improve arterial stiffness in patients at high cardiovascular risk. Additionally to life style modifications, long-term ω-3 fatty acids (fish oil) supplementation in diet may improve arterial stiffness in the population with hypertension or metabolic syndrome. Pharmacological treatment such as renin-angiotensin-aldosterone system antagonists, metformin, and 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors were useful in individuals with hypertension and diabetes. In obese population with obstructive sleep apnea, weight reduction, aerobic exercise, and continuous positive airway pressure treatment may also improve arterial stiffness. In the populations with chronic inflammatory disease such as rheumatoid arthritis, a use of antibodies against tumor necrosis factor-alpha could work effectively. Other therapeutic options such as renal sympathetic nerve denervation for patients with resistant hypertension are investigated in many ongoing clinical trials. Therefore our comprehensive review provides knowledge in detail regarding many aspects of pathogenesis, measurement, and management of arterial stiffness in several populations, which would be helpful for physicians to make clinical decision.

Keywords: Arterial stiffness, Cardio-ankle vascular index, Pulse-wave velocity, Renin-angiotensin-aldosterone system antagonist

Core tip: Arterial stiffness has been recognized as a marker of cardiovascular disease and associated with long-term worse clinical outcomes in several populations. Age, hypertension, smoking, and dyslipidemia, known as traditional vascular risk factors, as well as diabetes, obesity, and systemic inflammation lead to both atherosclerosis and arterial stiffness. Targeting multiple modifiable risk factors has become the main therapeutic strategy to improve arterial stiffness in patients at high cardiovascular risk.

INTRODUCTION

Arteries provide not only blood flow conduits from the heart to peripheral organs, but also play a major role in hemodynamic cushioning, buffering the forward propagating flow from the heart, and the backward resistance by the peripheral arterioles, which maximize cardiovascular efficiency. Arterial stiffness characterized by higher intravascular distending pressure has been recognized as a marker of cardiovascular disease (CVD) and associated with long-term prognosis in several populations[1-4]. A recent meta-analysis including 17 longitudinal studies demonstrated that aortic stiffness was an independent predictor of incident CVD and all-cause mortality in the general population[4]. Therefore, evidence-based approaches for improving arterial stiffness are of clinical importance to reduce the hazards of subsequent CVD. This review article will discuss the latest knowledge of the pathological backgrounds, the measurements, and the effects of pharmacological and non-pharmacological interventions for arterial stiffness.

The pathophysiology of arterial stiffness

As a major component of the circulatory system, the arterial system can be functionally and structurally divided into two sub-systems: (1) the large elastic, conducting arteries (e.g., the aorta, the carotid arteries, and the iliac arteries), which store blood ejected from the heart during systole, and expel blood to the peripheral tissues during diastole, thereby ensuring a steady blood flow irrespective of cardiac cycles or concurrent blood pressure; (2) resistance muscular arteries, especially those of the lower limb (e.g., femoral, popliteal, and posterior tibial arteries), which are capable of altering vascular smooth muscle tone, allowing them to modulate the velocity of pressure wave that is conducted to the resistance muscular arteries from the central aorta[5]. The sites of aortic flow reflection are not simply anatomically determined, but also subjected to systemically structural and functional control. For example, the site of reflection is more central in the case of hypertension, atheromatous arteries or increased sympathetic activity[6].

The pressure waveform recorded at any site of aorta is the summation of the forward-traveling waveform generated by cardiac pumping force and the backward traveling wave, the ‘‘echo’’ wave reflected at peripheral sites. The summation result determines the cardiac afterload during systolic phase and the augmented backward coronary perfusion pressure during diastolic phase. When the arteries are compliant and elastic, the reflected wave merges with the incident propagating wave during diastole, thus augmenting the diastolic blood pressure and enhancing coronary perfusion[7]. On the contrary, when arteries are stiffer, pulse wave velocity increases, and both the incident and the reflected wave travel faster; therefore, the reflected wave merges with the incident wave at systole and increase systolic pressure and cardiac afterload, while, concomitantly, losing the augmented diastolic perfusion pressure[7] (Figure ). The added part on systolic pressure and cardiac afterload was named aortic augmentation index [AIx, (second/first systolic peak) × 100%][8]. In the long term, increasing pulsatility causes stretching of load-bearing elastic lamellae and mechanical stress on the wall leading to vascular structural changes and stiffening. Hence, the harm of arterial stiffness is two-sided, negatively affecting the heart and blood vessels[9] (Figure ).

The central aortic pressure waveform is the summation of forward travelling wave, P (f) and the reflected backward-travelling wave, P (b). On the top graph IA-I, is an illustration of a stiff aorta or peripheral vasoconstriction, both P (f) and P (b) travel fast and the magnitude of the reflected wave is increased, thus augmenting the systolic pressure of summated central aortic pressure waveform, P (m). In graph IA-II, is another illustration of a distensible aorta or with vasodilatation. Length and thickness of horizontal arrows correspond to the waveform velocity and the magnitude of the reflected wave, respectively. Vertical arrows indicate point of merging of P (f) and P (b).

Aortic elastic properties may be altered by several processes, resulting in increased stiffness, decreased compliance, and encompassing the diseased ventricular-arterial coupling. Mechanical and chemical stress factors include hypertension, inflammation, advanced glycation end products, etc. LV: Ventricular; PWV: Pulse wave velocity; SBP: Systolic blood pressure.

Factors affecting arterial stiffness

Age is a main determinant of stiffness in large elastic arteries[7,10]. The stiffness of these arteries increases significantly after the age of 55 years. Aging causes the degeneration and remodeling of elastic components of arterial wall. At the cellular-molecular level, an age-related decrease in intra-cellular magnesium concentration is associated with increases in stiffness[10].

Most traditional cardiovascular risk factors and CVD have an adverse effect on arterial stiffness, via endothelial dysfunction and adverse vascular remodeling. Hypertension, diabetes, dyslipidemia, and insulin resistance, which contribute to atherosclerosis, have been involved in the process of arterial stiffening. In essential hypertension, the elastic properties of large arteries are impaired, although it is not clear whether the disease itself alters the intrinsic elastic properties or this is the ultimate final effect of increase in distending pressure[11,12]. Distending pressure as estimated by 24-h pulse pressure was another major factor additionally to older age contributing to the occurrence of arterial stiffness[13]. In patients with diabetes or metabolic syndrome, arterial stiffening is consistently observed across all age groups, even in childhood[14]. Insulin resistance is dose-dependent and positively correlated with arterial stiffness[15-17]. Chronic hyperglycemia and hyper-insulinemia may increase local activity of renin-angiotensin-aldosterone system (RAAS) and expression of angiotensin type I receptor in vascular tissue and thus promote the development of arterial wall hypertrophy and fibrosis[18,19].

In addition hyperinsulinemia has proliferative effects, via unbalanced activities on growth-promoting mitogen activated kinase pathways and PI3-kinase-dependent signaling[20]. In pre-diabetic stage, impaired glucose tolerance enhances nonenzymatic glycation of proteins with covalent cross-linking of collagen and alters the mechanical properties of interstitial tissue of arterial wall[21,22].

Chronic kidney disease (CKD) is a well-known risk factor of arterial stiffness[23]. Several mechanisms have been proposed to explain the effect of CKD. For instance, upregulation of matrix metalloproteinases enhances collagen and elastin turnover through enzymatic cross-link degradation[24], causing weakening of the extracellular matrix[25]. Accumulation of advanced glycation end-products makes collagen stiffer as well[26]. In addition, CKD may cause endothelial dysfunction, which attributes to high oxidative stress, increased endothelin-1 concentrations and impairment of endothelial nitric oxide synthase and arterial relaxation[27]. Chronic inflammation and RAAS activation are also involved in the process of arterial stiffening in CKD[28,29]. CKD alters bone metabolism to promote vascular calcification by increasing osteoclast activity, fibroblast growth factor 23, osteoprotegerin which inhibit bone morphogenic proteins, and reducing pyrophosphate, Matrix G1a protein, and fetuin A levels[30].

Arterial elastic properties are impaired in young people with a family history of hypertension, diabetes or myocardial infarction[31]. It has been recognized that genetic factors may contribute to arterial stiffening as well. The latest advances in genome-wide association study have identified that some genetic variants and specific polymorphisms may affect arterial stiffness. The Framingham Heart Study showed that four regions of suggestive linkage were found in chromosomes 2, 7, 13, and 15 (LOD scores 2.0) for higher risk of arterial stiffness[32]. Potential candidate genes in these regions included the insulin-like growth factor-1 receptor, myocyte-specific enhancer factor 2A, chondroitin synthase (CHSY1), proprotein convertases (PACE4 and FURIN), b-adducin (ADD2), neurokinin-1 receptor (TACR1), a-2B adrenergic receptor (ADRA2B), and interleukin-6 (IL-6). Other candidate gene polymorphism, such as the renin-angiotensin-aldosterone genes, the Matrix and metalloproteinase genes, the endothelial cell-related genes, and the inflammatory genes, are all in undergoing investigations[33].

Lifestyle characteristics are important determinants of arterial stiffness. Cigarette smoking, including passive smoking and current smoking has an adverse impact on the arterial stiffness[34-36]. Elevated arterial stiffness has been found among patients with chronic obstructive pulmonary disease and inflammation, which are highly related to the adverse effect of smoking. Obesity, weight gain, lack of physical activity and high dietary intake of sodium chloride, which is associated with blood pressure elevation, can aggravate arterial stiffness[37-40]. Intake of caffeine, a neurotoxin has also been acknowledged of an unfavorable effect on arterial compliance[40]. Other risk factors such as chronic cytomegalovirus infection, has been known as a novel potential contributor to arterial stiffening[41]. Table lists the main demographic, clinical and lifestyle characteristics that may influence arterial stiffness.

Table 1

Demographic, clinical, and lifestyle factors associated with arterial stiffness

Age[7]

Sex[110]

Established cardiovascular disease[3]

Potential risk factors for atherosclerosis

Hypertension[11]

Dyslipidemia[2]

Cigarette smoking[63]

Chronic obstructive pulmonary disease[111]

Diabetes[14]

Obesity[3]

Obstructive sleep apnea[106]

Menopause[110]

Polycystic ovarian syndrome[112]

Hypothyroidism[113]

Chronic kidney disease[23]

Endothelial dysfunction[27]

Systemic inflammation[99]

Cytomegalovirus infection[114]

Nutritional and lifestyle aspects

Caffeine[115]

Chronic alcohol consumption[116]

Sedentary lifestyle[58]

Resistance exercise training[61]

Genes variants

Genes of the Renin-Angiotensin-Aldosterone system[33]

Genes of the extracellular matrix proteins[33]

Measurement of arterial stiffness

A stiffer vessel will conduct the pulse wave faster than a more distensible and compliant vessel. Arterial stiffness can be noninvasively evaluated by measuring pulse-wave velocity (PWV). The PWV is calculated by the distance (L) between the 2 vascular sites divided by the wave foot-to-foot time (ΔT) it takes for that forward wave to reach the end measuring point (Figure ) Currently, PWV is the most validated measurement to noninvasively quantify arterial stiffness. It is considered the gold standard index to measure arterial stiffness, given its simplicity, reproducibility, accuracy, and strong prediction of adverse CVD events[42-44]. An increase in aortic PWV by 1 m/s corresponds to an age-, sex-, and risk factor-adjusted risk increase of 14%, 15% and 15% in total CVD events, CVD mortality, and all-cause mortality, respectively[5]. Nowadays, two kinds of PWV were frequently used to evaluate arterial stiffness. Carotid-femoral PWV (cfPWV) measured by Doppler ultrasound is the most widely used measure of aortic stiffness and is regarded as the gold standard measure for evaluating arterial stiffness. Alternatively, brachial-ankle PWV (baPWV) measured by the Omron oscillometric/plethysmographic system has recently received attention because of its consistent association with CVD risk factors and its ease of use for large-scale population studies[42-44]. Based on the formula assumptions, cfPWV reflects the stiffness of descending aorta, while baPWV reflects the stiffness of both descending aorta and leg arteries. In a study conducted among healthy men aged 40-49, cfPWV strongly correlated with central PWV, and baPWV correlated with both central and peripheral PWVs[45]. The two indexes were highly correlated and the predictive values of these two PWVs were comparable[46]. Both cfPWV and baPWV have been reported to be independent predictors of subclinical coronary artery calcification, incident vascular events, incident heart failure, and all-cause mortality in the general population[47,48]. The main disadvantage of cfPWV is inevitably affected by blood pressure, which is an important confounder for CVD. In addition, cfPWV is often overestimated for the inaccurate measurement in the distance between the carotid and the femoral to measure the pulse wave[49]. Other methods for the PWV measurements include single-point, carotid–radial or femoral–tibial arterial segments. The predictive values of these more peripheral PWV measurements to incident vascular events remain unknown[50]. Aortic characteristic impedance standing for the minimal impedance for higher frequencies of pressure-and-flow harmonics and being proportional to PWV is an indirect technique, but this is rarely used alone now[51]. AIx, arterial wave reflection magnitude [(reflected/forward wave amplitude) × 100%], and pulse pressure amplification [(radial/aortic pulse pressure) × 100%], the analysis of pulse waveforms parameters of central arteries, have been associated with the development of end organ damage as well[52].

For practical purpose, femoral artery is counted as the terminal aorta. The measured distance is length. If ∆Time represents the time delay between the feet of the 2 waves, pulse wave velocity.

The stiffness parameter β is another measure of arterial stiffness. The equation for stiffness parameter β is ln(Ps/Pd) × D/ΔD, where Ps is the systolic blood pressure, Pd is the diastolic blood pressure, D is the diameter of the artery, and ΔD is the change in arterial diameter between Ps and Pd[53]. The stiffness parameter β is less affected by blood pressure; however it is limited by assessing a local segment of the artery, and becoming dependent on blood pressure for those with hypotension or moderate and severe hypertension[53]. Therefore, the cardio-ankle vascular index, CAVI, was developed to incorporate the stiffness parameter β[54]. The equation for CAVI is a [(2ρ/ΔP) × ln(Ps/Pd) × PWV²] + b, where ρ is the blood viscosity, ΔP is Ps – Pd, PWV is the pulse wave velocity from the aortic origin to the ankle region via the femoral artery, and a and b are constants for converting a CAVI value to a value obtained by Hasegawa’s method[55]. Theoretically, the CAVI is essentially intrinsic to the stiffness parameter β and thus less dependent of blood pressure than PWV. Table summarizes the merits and disadvantages of different measurements of arterial stiffness.

Table 2

A summary of the advantages and disadvantages of different measurements for evaluating arterial stiffness

	Advantage	Disadvantage
cfPWV[42-44]	Reflects the stiffness of the descending aorta The gold standard measure for arterial stiffness	Largely affected by the change of BP Overestimated for the inaccurate measurement in the distance between the carotid and the femoral arteries
baPWV[116]	Reflects the stiffness of both the descending aorta and the leg artery High association with CV risk factors Ease of use for large-scale population studies	Largely affected by the change of BP Underestimates arterial stiffness in hypertensive patients with a history of cardiovascular events
hfPWV[117]	Strongly correlated with cfPWV moderately correlated with baPWV	Require a high level of proficiency in order to obtain accurate results
faPWV[117]	Moderately correlated with baPWV	The predictive value to incident vascular events remains unknown
pAIx[110]	Assessed non-invasively and peripherally, e. g., carotid, and radial arteries Correlated well with the central AIx	Largely affected by the change of BP Not a valid surrogate of arterial compliance in the elderly and diabetic populations
The stiffness parameter β[53,54]	Independent of the change of BP	Assessing only a local segment of the artery Loss of the independence of BP for those with moderate to severe hypertension or hypotension
CAVI[118]	Independent of the change of BP A novel atherosclerotic index that incorporates PWV and BP measurements The coefficients of variation are small (< 4%), and does not require significant training	CAVI, as a cardiovascular risk marker has not to be investigated definitively in large prospective clinical trials

Therapeutic modification of arterial stiffness

Lifestyle modification: Obesity is related to insulin resistance, hypertension, obstructive sleep apnea (OSA), and eventually arterial stiffness. A meta-analysis involving 20 studies (including 3 randomized controlled trials) revealed that modest weight loss (mean 8% of initial body weight) could improve PWV values by 32% in the collected 1259 participants[56]. In addition, weight reduction was found in association with decreased CAVI values in a cohort of 47 obese individuals in Japan[57]. Effects of exercise on arterial stiffness were extensively investigated. Physical activity was associated with 35% reduction in cardiovascular mortality and 33% reduction in all-cause mortality[58]. Almost 60% of the benefits are contributed by the reduction of body weight, blood pressure and serum lipids[59], and the other 40% may be explained by the improvement of vascular hemodynamics including endothelial function, arterial compliance and remodeling[60]. Whether mode and dose of exercise affecting arterial stiffness had been recently reviewed in a meta-analysis[61]. In total, forty-two studies and 1627 participants were included in the study, which concluded aerobic exercise, but not resistant exercise or combined aerobic and resistant exercise, improved PWV weighted mean difference (WMD): -0. 63 m/s, 95%CI: -0.90 to -0.35, and AIx (WMD: -2.63%; 95%CI: -5.25 to -0.02). The benefits for improving arterial stiffness were greater in the peripheral index, baPWV (WMD: -1.01 m/s; 95%CI: -1.57 to -0.44) than in central index, cfPWV (WMD: -0.39 m/s; 95%CI: -0.52 to -0.27). There was dose-dependent relationship between exercise intensity (frequency of exercise sessions and absolute exercise intensity) and the improvement of AIx. Nevertheless, the exercise session duration was not significantly associated with the reduction of AIx[61]. In individuals with stiffer arteries (PWV ≥ 8 m/s), aerobic exercise had a larger effect in reducing PWW. In addition, the benefits of aerobic exercise were documented in subpopulations with normal health, overweight/obese, pre-hypertension, hypertension, or CKD.

Smoking cessation has been proven to decrease aortic stiffness. In one 60 wk follow-up observational study, smoking cessation group had better arterial stiffness indices (central blood pressure, -7. 1 ± 1.4 mmHg vs 1.2 ± 2.7 mmHg, P < 0.01; baPWV, -204 ± 64 cm/s vs -43 ± 72 cm/s, P < 0.01; reduced radial AIx, -6.4 ± 2.8% vs -1.0 ± 3.9%, P < 0.01)[62]. Another observational study also showed that smoking cessation was associated with improved arterial stiffness as evaluated by CAVI values[63]. Moreover, avoidance of second-hand smoke, such as workplace smoking bans, has been reported to improve PWV after introducing smoke-free workplaces[64].

Dietary and nutrient interventions: Several dietary modifications had been reported with beneficial effects on arterial stiffness. Among them, omega (ω)-3 fatty acids (fish oil) supplementation was mostly studied. In most of clinical trials, ω-3 fatty acids supplementation improved arterial stiffness, especially in the population with overweight, metabolic syndrome, diabetes or hypertension[65]. Aside from a study with acute ω-3 fatty acids administration in healthy participants, almost all ω-3 trials were long-term prescribed varying from 1. 5 to 25 mo. In this acute fish-oil supplementation study, there were no immediate reductions in parameters of arterial stiffness[66]. The lowest daily dosage of long-chain polyunsaturated fatty acids (PUFAs) that documented an effect on arterial stiffness was 540 mg eicosapentaenoic acid (EPA) along with 360 mg docosahexaenoic acid (DHA) in overweight patients with hypertension[67]. Sjoberg et al[68] introduced 2, 4, and 6 g of fish oil supplementation per day into the diets of overweight or obese adults for 12 wk. Only the highest dose group (6 g of fish oil per day) revealed significant improvement in arterial distensibility, as measured by PWV. Among healthy subjects, Chong et al[69] reported a significant improvement in PWV and AIx immediately after a long chain ω-3 PUFA-rich meal containing 4.7 g of DHA and EPA. In a randomized controlled trial in Japan, highly purified EPA administration (1.8 g/d for 3 mo) significantly reduced both PWV and CAVI values in individuals with metabolic syndrome[70]. However, other two studies using smaller amount (1.7 g of EPA/DHA per day for 12 wk and 1.8 g of EPA/ DHA per day for 12 mo) did not improve arterial stiffness among slightly overweight but relatively healthy subjects[71,72]. Accordingly, the benefits from ω-3 supplementation could be more evident using a comparable dose over a greater duration within an older age, more diseased populations.

Soy isoflavones was another nutrient, which has been studied frequently. Among five soy isoflavone interventional studies, four interventional studies showed an improvement in PWV or systemic arterial compliance in subjects taking soy isoflavone relative to their placebos[73-76], whereas one study reported no effect[77]. Notably, the majority of the soy interventions were conducted in postmenopausal women. In other studies with positive results, one study reported that consumption of alcoholic red wine might decrease AIx acutely relative to that after consumption of dealcoholized red wine[78], and a study showed that consumption of black tea flavonoids could reduce the digital volume pulse-stiffness index but not PWV[79]. Other dietary and nutritional interventions, nonetheless, reported no definite effect on arterial stiffness, such as garlic[80], conjugated linoleic acid[81], vitamins or folic acid[82-86] on PWV.

Among the minerals, salt plays a detrimental role. Consistent evidence suggest that 10-140 mmol sodium chloride supplementation per day would increase arterial stiffness in individuals with hypertension[87,88]. In a randomized clinical trial, salt reduction was associated with decreased pulse pressure across all ethnic groups including white, black and Asians, whereas PWV decreased only in blacks in response to salt reduction[87]. In addition, Gates et al[89] revealed that large elastic artery compliance was much improved in the older adults with systolic hypertension following only one-week of dietary sodium restriction.

Pharmacological therapy: Since blood pressure is the strongest modifiable factor directly leading to arterial stiffness, a number of clinical trials have been conducted to investigate the effect of antihypertensive medications on the change of arterial stiffness. Notably almost all classes of anti-hypertensive medications except diuretics and non-vasodilating beta-blockers such as atenolol could decrease arterial stiffness effectively[90,91]. Among all classes of anti-hypertensive medications, RAAS system antagonists have shown the best clinical results, probably due to their anti-fibrotic properties[91]. With regard to other modifiable risk factors, 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) could decrease arterial stiffness by lowering low-density lipoprotein cholesterol concentrations, the effect of anti-inflammation, and stabilizing the atheroma plaques[92,93]. In patients with diabetes, glycemic control with oral anti-diabetic agents with metformin and glitazone were reported to improve arterial stiffness[94,95]. Using high dose of RAAS antagonists was extremely effective in attenuating the severity of arterial stiffness in diabetic patients with hypertension[96]. Notably, pharmacological modifications to these traditional vascular risk factors have been confirmed to improve arterial stiffness evaluated by PWV or CAVI[97]. In patients with chronic inflammatory disease such as rheumatoid arthritis, several anti-inflammatory agents have been tested, but until now, only antibodies against tumor necrosis factor-alpha have been shown to improve arterial stiffness, independently of adequate blood pressure control[98,99]. In menopausal women, although the effect of sex hormone replacement therapy on arterial stiffness is uncertain, one study showed that using raloxifene, a potent selective estrogen receptor modulator may lead to positive result[100]. The phosphate binder, sevelamer was found to improve arterial stiffening in patients with end-stage renal disease[101]. Alagebrium, an advanced glycation end-products crosslink breaker, has shown to improve arterial stiffness in animal studies despite the effect was missing in a small group of older individuals[102,103]. However, further clinical trials were not conducted because of financial problems of the developing company. Currently, some ongoing trials are conducted to evaluate the effect of antidiabetic pharmacological therapy including metformin and alogliptin, the dipeptidyl peptidase 4, on the improvement of arterial stiffness in obese children and adolescents, and in adult individuals with type 2 diabetes, respectively[104,105].

Device and interventional therapy: It is well known that OSA is related to obesity and correlated with several CVD risk factors, such as hypertension and metabolic syndrome, which contributes to adverse clinical outcomes. A meta-analysis involving 15 articles, investigated the effect of continuous positive airway pressure (CPAP) on arterial stiffness in 615 patients with OSA. A significant improvement of all indices of arterial stiffness was observed after CPAP treatment (SMD = -0.74; 95%CI: -1.08 to -0.41). Neither the proportion of compliance nor the duration of CPAP use altered the outcomes after CPAP treatment[106].

Enhanced external counterpulsation (EECP), using pneumonic cuffs over the legs to inflate and deflate according to the cardiac cycle, is a non-invasive modality for treatment of symptomatic patients with coronary artery disease not amenable to revascularization procedures. In a randomized clinical trials conducted in 42 patients with coronary artery disease, central arterial stiffness and AIx were reduced following 17- and 35-sessions respectively, as well as peripheral arterial stiffness was reduced following 35 sessions in the EECP treatment group as compared with the placebo[107].

Since autonomic nervous system is involved in the pathogenesis of hypertension, its modification such as renal sympathetic denervation, and baroreflex activation therapy could attenuate arterial stiffness by improving arterial stiffness indices and central hemodynamics in patients with resistant hypertension[108,109]. However, these studies were conducted in patients with resistant hypertension, and the result may not be simply extrapolated to all the patients with arterial stiffness.

Arterial stiffness and hypertension

Clin Hypertens. 2018; 24: 17.

Young S. Oh

Vascular Biology and Hypertension Branch, Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), 6701 Rockledge Drive, Room 8106, Bethesda, MD 20892 USA

Corresponding author.

Received 2018 Aug 29; Accepted 2018 Oct 23.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.This article has been cited by other articles in PMC.

Abstract

Measures of the functional and structural properties of blood vessels can be used to assess preclinical stage of vascular disorders. Recent experimental and population studies show that arterial stiffening precedes development of high blood pressure, and can be used to predict future cardiovascular events. Arterial stiffness was also shown to be reversible in several experimental models of various conditions. Since reversing arterial stiffness could prevent development of hypertension and other clinical conditions, understanding the biological mechanisms of arterial stiffening and investigating potential therapeutic interventions to modulate arterial stiffness are important research topics. For research and application in general clinical settings, it is an important step to develop reliable devices and a standardized arterial stiffness measurement protocol.

Keywords: Hypertension, Arterial, Aortic stiffness, Cardiovascular disease, Vascular biology

Introduction

The walls of large arteries, especially the aorta, lose elasticity over time, and this process results in increased arterial stiffness. Arterial stiffening, at least in part, reflects gradual fragmentation and loss of elastin fibers and accumulation of stiffer collagen fibers in the arterial wall [1]. Increased arterial stiffness is closely linked to increased risk of hypertension and other diseases, such as chronic kidney disease and stroke [2]. In this brief review, I will discuss recent progress in relating arterial stiffness research to hypertension.

Arterial stiffness precedes hypertension

Although the causality between increased arterial stiffness and hypertension is complex because of many confounding factors (e.g., aging, diet, concurrent disease, life style, etc.), recent studies in humans and animals suggest that increased arterial stiffness can precede hypertension. For example, several research projects funded by the NHLBI (National Heart, Lung, and Blood Institute) – the NIH (National Institutes of Health) Institute focused on supporting cardiovascular research – had examined the temporal and causal relationship between arterial stiffness and hypertension [3]. Studies in five different animal models concluded that arterial stiffness precedes high blood pressure. These animal models included: (i) diet-included obesity model, (ii) elastin gene knock-out model, (iii) stroke-prone Dahl salt-sensitive rat model, (iv) klotho gene knock-out model, and (v) type 2 diabetes model. In clinical studies, a consistent temporal sequence of arterial stiffness preceding hypertension was also observed in the Framingham Heart Cohort Study [4]. However, the biological mechanisms and cellular processes whereby increased arterial stiffness alone can lead to hypertension are still not understood, encouraging further investigation.

Is arterial stiffness reversible?

Both human and animal studies have suggested that arterial stiffness is reversible. In a murine model of diet-induced obesity, the increased pulse wave velocity (PWV: the gold standard in vivo measure for arterial stiffness) in obese mice fed a high fat/high sucrose diet (HFHS) for 5 months was reduced to normal after returning obese mice to standard chow for 2 months [5]. During the 2-month period, indices of metabolic impairment of obese mice such as body weight, fat mass and hyperinsulinemia, returned to normal; PWV and high blood pressure also returned to normal. Further, Fry et al. [6] studied the potential effect of dietary resveratrol on arterial stiffness. The authors found that resveratrol, a polyphenol known to activate the deacetylase sirtuin-1, prevented the HFHS-induced inflammation and excess oxidant production in the arterial wall as well as the accompanying increase in PWV. Interestingly, administration of a sirtuin-1 specific activator (SRT1720), after 8 months of HFHS, decreased PWV to normal values within 2 weeks. The positive effect of dietary resveratrol on arterial stiffness was further replicated in non-human primates that were fed high caloric diets [7], underscoring its translational potential in humans.

Using an aging rat model (i.e., 20 month-old), Steppan et al. [8] studied the relationship between exercise, tissue transglutaminase (TG2) activity, and arterial stiffness; TG2, an enzyme catalyzing protein cross-links, is known to play a role in vascular stiffness with age [9]. The authors found that there was significant suppression of an age-associated increase in TG2 activity when animals were subjected to moderate-intensity exercise, which was correlated with increased nitric oxide bioavailability and reduced collagen depositions in the extracellular matrix. Interestingly, these biochemical changes did not translate into a significant alteration in vascular stiffness, supporting the hypothesis that once formed, the TG2 crosslinks may have a long half-life in the vascular matrix. Thus, it seems that the reversibility of vascular stiffness may be limited to a certain stage or type of vascular condition leading to stiffness.

In humans, short-term aerobic exercise (3 months) reduced arterial stiffness in older adults (> 65 years) with type 2 diabetes and might thereby lower the risk of cardiovascular morbidity and mortality [10]. A recent randomized clinical trial study (SAVE: Slow Adverse Vascular Effects of excess weight) also showed the reversibility of vascular stiffness by moderate-to-vigorous physical activity in overweight or obese young adults [11]. In addition, some anti-hypertensive medications (i.e., angiotensin converting enzyme inhibitor or angiotensin II receptor I antagonist) are shown to reduce arterial stiffness significantly [12]. Thus, arterial stiffness associated with some medical conditions can be reversed by life style change or treatment.

Conclusion and perspectives

Arterial stiffness is an important arterial phenotype and an excellent indicator of cardiovascular morbidity and mortality [13]. It is an independent predictor of hypertension and cardiovascular diseases. Recent studies in animal models showed that large artery stiffening preceded development of high blood pressure. This temporal sequence was also observed in clinical studies. Nevertheless, it should be kept in mind that the relationship between arterial stiffness and blood pressure can be complex. For example, there are patients who have high blood pressure with normal PWV values [14].

Both arterial stiffness and hypertension are positively associated with aging. Studies from animals and humans suggest that arterial stiffness can be reversible under certain conditions (Fig. ). Niiranen et al. [15] have recently studied healthy vascular aging (HVA) – defined as absence of hypertension and lack of arterial stiffness – in more than 3100 participants (aged > 50 years) of the Framingham Heart Study and have found that maintaining HVA beyond age 70 is extremely challenging. With rapid population aging, it will be important in the future to explore the possibility of prevention or reversal of arterial stiffness as a potential therapeutic strategy to control hypertension and/or hypertension-related diseases. In this regard, the European Society of Hypertension and the European Society of Cardiology published a guideline in 2013 to suggest the measurement of arterial stiffness as a way of evaluating hypertensive patients at high cardiovascular risk [2]. In recognizing the clinical importance of arterial stiffness, the American Heart Association also published a scientific statement to encourage further improvement and standardization of arterial stiffness measurements for clinical use and vascular research [13]. Once a standardized measurement protocol and reliable devices are available, arterial stiffness can provide us valuable information about the risk of hypertension, cardiovascular disease, and early vascular aging.

A simplified model of arterial stiffening and its reversibility. With aging, blood vessel structural changes and endothelial dysfunction can occur. Various factors contribute to arterial stiffening, such as changes in the composition of elastin and collagen fibers, calcification, and inflammation in the arterial wall. It seems there is a critical time zone during the process of arterial stiffening when a PM (Positive Modifier: such as exercise, healthy diet, weight loss, or anti-hypertensive drug) cannot reverse vascular stiffness. Future research is needed to characterize this critical zone

Acknowledgments

I would like to thank staff in Vascular Biology and Hypertension Branch, NHLBI, especially to Dr. Diane Reid for reading this manuscript and Dr. Zorina Galis, who encouraged me to work on this topic.

Availability of data and materials

Not applicable.

Disclosures

The views expressed in this manuscript are those of the author and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.

Author’s contributions

The author designed and wrote the manuscript. The author read and approved the final manuscript.

Notes

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable. No individual data in any form is disclosed.

Competing interests

The author declares that he has no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

2. Mancia G, et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) J Hypertens. 2013;31(7):1281–1357. doi: 10.1097/01.hjh.0000431740.32696.cc. [PubMed] [CrossRef] [Google Scholar]3. Oh YS, et al. A special report on the NHLBI initiative to study cellular and molecular mechanisms of arterial stiffness and its association with hypertension. Circ Res. 2017;121(11):1216–1218. doi: 10.1161/CIRCRESAHA.117.311703. [PMC free article] [PubMed] [CrossRef] [Google Scholar]5. Weisbrod RM, et al. Arterial stiffening precedes systolic hypertension in diet-induced obesity. Hypertension. 2013;62(6):1105–1110. doi: 10.1161/HYPERTENSIONAHA.113.01744. [PMC free article] [PubMed] [CrossRef] [Google Scholar]6. Fry JL, et al. Vascular smooth muscle Sirtuin-1 protects against diet-induced aortic stiffness. Hypertension. 2016;68(3):775–784. doi: 10.1161/HYPERTENSIONAHA.116.07622. [PMC free article] [PubMed] [CrossRef] [Google Scholar]7. Mattison JA, et al. Resveratrol prevents high fat/sucrose diet-induced central arterial wall inflammation and stiffening in nonhuman primates. Cell Metab. 2014;20(1):183–190. doi: 10.1016/j.cmet.2014.04.018. [PMC free article] [PubMed] [CrossRef] [Google Scholar]9. Santhanam L, et al. Decreased S-nitrosylation of tissue transglutaminase contributes to age-related increases in vascular stiffness. Circ Res. 2010;107(1):117–125. doi: 10.1161/CIRCRESAHA.109.215228. [PubMed] [CrossRef] [Google Scholar]10. Madden KM, et al. Short-term aerobic exercise reduces arterial stiffness in older adults with type 2 diabetes, hypertension, and hypercholesterolemia. Diabetes Care. 2009;32(8):1531–1535. doi: 10.2337/dc09-0149. [PMC free article] [PubMed] [CrossRef] [Google Scholar]11. Hawkins M, et al. The impact of change in physical activity on change in arterial stiffness in overweight or obese sedentary young adults. Vasc Med. 2014;19(4):257–263. doi: 10.1177/1358863X14536630. [PMC free article] [PubMed] [CrossRef] [Google Scholar]12. Jia G, et al. Potential role of antihypertensive medications in preventing excessive arterial stiffening. Curr Hypertens Rep. 2018;20(9):76. doi: 10.1007/s11906-018-0876-9. [PMC free article] [PubMed] [CrossRef] [Google Scholar]13. Townsend RR, et al. Recommendations for improving and standardizing vascular research on arterial stiffness: a scientific statement from the American Heart Association. Hypertension. 2015;66(3):698–722. doi: 10.1161/HYP.0000000000000033. [PMC free article] [PubMed] [CrossRef] [Google Scholar]14. Nilsson Peter M., Laurent Stephane, Cunha Pedro G., Olsen Michael H., Rietzschel Ernst, Franco Oscar H., Ryliškytė Ligita, Strazhesko Irina, Vlachopoulos Charalambos, Chen Chen-Huan, Boutouyrie Pierre, Cucca Francesco, Lakatta Edward G., Scuteri Angelo. Characteristics of healthy vascular ageing in pooled population-based cohort studies. Journal of Hypertension. 2018;36(12):2340–2349. doi: 10.1097/HJH.0000000000001824. [PMC free article] [PubMed] [CrossRef] [Google Scholar]15. Niiranen TJ, et al. Prevalence, correlates, and prognosis of healthy vascular aging in a Western community-dwelling cohort: the Framingham heart study. Hypertension. 2017;70(2):267–274. doi: 10.1161/HYPERTENSIONAHA.117.09026. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Arterial stiffness and hypertension

Clin Hypertens. 2018; 24: 17.

Young S. Oh

Corresponding author.

Received 2018 Aug 29; Accepted 2018 Oct 23.

Abstract

Keywords: Hypertension, Arterial, Aortic stiffness, Cardiovascular disease, Vascular biology

Introduction

Arterial stiffness precedes hypertension

Is arterial stiffness reversible?

Conclusion and perspectives

Acknowledgments

I would like to thank staff in Vascular Biology and Hypertension Branch, NHLBI, especially to Dr. Diane Reid for reading this manuscript and Dr. Zorina Galis, who encouraged me to work on this topic.

Availability of data and materials

Not applicable.

Disclosures

Author’s contributions

The author designed and wrote the manuscript. The author read and approved the final manuscript.

Notes

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable. No individual data in any form is disclosed.

Competing interests

The author declares that he has no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

Arterial stiffness and hypertension

Clin Hypertens. 2018; 24: 17.

Young S. Oh

Corresponding author.

Received 2018 Aug 29; Accepted 2018 Oct 23.

Abstract

Keywords: Hypertension, Arterial, Aortic stiffness, Cardiovascular disease, Vascular biology

Introduction

Arterial stiffness precedes hypertension

Is arterial stiffness reversible?

Conclusion and perspectives

Acknowledgments

I would like to thank staff in Vascular Biology and Hypertension Branch, NHLBI, especially to Dr. Diane Reid for reading this manuscript and Dr. Zorina Galis, who encouraged me to work on this topic.

Availability of data and materials

Not applicable.

Disclosures

Author’s contributions

The author designed and wrote the manuscript. The author read and approved the final manuscript.

Notes

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable. No individual data in any form is disclosed.

Competing interests

The author declares that he has no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

Arterial stiffness and hypertension

Clin Hypertens. 2018; 24: 17.

Young S. Oh

Corresponding author.

Received 2018 Aug 29; Accepted 2018 Oct 23.

Abstract

Keywords: Hypertension, Arterial, Aortic stiffness, Cardiovascular disease, Vascular biology

Introduction

Arterial stiffness precedes hypertension

Is arterial stiffness reversible?

Conclusion and perspectives

Acknowledgments

I would like to thank staff in Vascular Biology and Hypertension Branch, NHLBI, especially to Dr. Diane Reid for reading this manuscript and Dr. Zorina Galis, who encouraged me to work on this topic.

Availability of data and materials

Not applicable.

Disclosures

Author’s contributions

The author designed and wrote the manuscript. The author read and approved the final manuscript.

Notes

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable. No individual data in any form is disclosed.

Competing interests

The author declares that he has no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

High doses of vitamin D rapidly reduce arteri

image: High doses of vitamin D rapidly reduce arterial stiffness in overweight/obese, vitamin-deficient African-Americans.
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Credit: Phil Jones, Senior Photographer, Augusta University

AUGUSTA, Ga. (Jan. 2, 2018) – In just four months, high-doses of vitamin D reduce arterial stiffness in young, overweight/obese, vitamin-deficient, but otherwise still healthy African-Americans, researchers say.

Rigid artery walls are an independent predictor of cardiovascular- related disease and death and vitamin D deficiency appears to be a contributor, says Dr. Yanbin Dong, geneticist and cardiologist at the Georgia Prevention Institute at the Medical College of Georgia at Augusta University.

So researchers looked at baseline and again 16 weeks later in 70 African-Americans ages 13-45 – all of whom had some degree of arterial stiffness – taking varying doses of the vitamin best known for its role in bone health.

In what appears to be the first randomized trial of its kind, they found that arterial stiffness was improved by vitamin D supplementation in a dose-response manner in this population, they write in the journal PLOS ONE.

Overweight/obese blacks are at increased risk for vitamin D deficiency because darker skin absorbs less sunlight – the skin makes vitamin D in response to sun exposure – and fat tends to sequester vitamin D for no apparent purpose, says Dong, the study’s corresponding author.

Participants taking 4,000 international units – more than six times the daily 600 IUs the Institute of Medicine currently recommends for most adults and children – received the most benefit, says Dr. Anas Raed, research resident in the MCG Department of Medicine and the study’s first author.

The dose, now considered the highest, safe upper dose of the vitamin by the Institute of Medicine, reduced arterial stiffness the most and the fastest: 10.4 percent in four months. “It significantly and rapidly reduced stiffness,” Raed says.

Two thousand IUs decreased stiffness by 2 percent in that timeframe. At 600 IUs, arterial stiffness actually increased slightly – .1 percent – and the placebo group experienced a 2.3 percent increase in arterial stiffness over the timeframe.

They used the non-invasive, gold standard pulse wave velocity to assess arterial stiffness. Reported measures were from the carotid artery in the neck to the femoral artery, a major blood vessel, which supplies the lower body with blood. The American Heart Association considers this the primary outcome measurement of arterial stiffness.

When the heart beats, it generates a waveform, and with a healthy heart and vasculature there are fewer and smaller waves. The test essentially measures the speed at which the blood is moving, and in this case, fast is not good, Raed says.

“When your arteries are more stiff, you have higher pulse wave velocity, which increases your risk of cardiometabolic disease in the future,” says Raed.

The varying doses, as well as the placebo participants took, were all packaged the same so neither they or the investigators knew which dose, if any, they were getting until the study was complete. Both placebo and supplements were given once monthly – rather than daily at home – at the GPI to ensure consistent compliance.

Dong was also corresponding author on a study published in 2015 in the journal BioMed Central Obesity that showed, in this same group of individuals, both 2,000 and 4,000 IUs restored more desirable vitamin D blood levels of 30 nanograms per milliliter.

The 4,000 upper-limit dose restored healthy blood level quicker – by eight weeks – and was also better at suppressing parathyroid hormone, which works against vitamin D’s efforts to improve bone health by absorbing calcium, they reported.

While heart disease is the leading cause of death in the United States, according to the Centers for Disease Control and Prevention, blacks have higher rates of cardiovascular disease and death than whites and the disease tends to occur earlier in life. The authors write that arterial stiffness and vitamin D deficiency might be potential contributors.

While just how vitamin D is good for our arteries isn’t completely understood, it appears to impact blood vessel health in many ways. Laboratory studies have shown that mice missing a vitamin D receptor have higher activation of the renin-angiotensin-aldosterone system, says Raed. Activation of this system increases blood vessel constriction, which can contribute to arterial stiffness. Vitamin D also can suppress vascular smooth muscle cell proliferation, activation of garbage-eating macrophages and calcification formation, all of which can thicken blood vessel walls and hinder flexibility. Vitamin D also reduces inflammation, an underlying mechanism for obesity related development of coronary artery disease, says Raed.

Now it’s time to do a larger-scale study, particularly in high-risk populations, and follow participants’ progress for longer periods, Dong and Raed say. “A year would give us even more data and ideas,” Raed adds.

Dong notes that pulse wave velocity and blood pressure measures are complimentary but not interchangeable. “We think maybe in the future, when you go to your physician, he or she might check your arterial stiffness as another indicator of how healthy you are,” Raed says.

There were no measurable differences in weight or blood pressure measurements over the 16-week study period.

The Institute of Medicine currently recommends a daily intake of 800 IUs of vitamin D for those age 70 and older. For adolescents and adults, they recommend 4,000 IUs as the upper daily limit; 2,000 was a previous upper limit.

More than 80 percent of Americans, the majority of whom spend their days indoors, have vitamin D insufficiency or deficiency. Dong, an expert in vitamin D and a professor in the MCG Department of Population Health Sciences, says about 15 minutes daily in the “young” sun – between 10 a.m. and 2 p.m. – but before your skin starts to get pink, is the best source of vitamin D.

Foods like milk, milk products like cheese and yogurt, fatty fish like mackerel and sardines, some greens like kale and collards and fortified cereals also are good sources. The researchers say a vitamin D supplement is an inexpensive and safe option for most of us.

###

Arterial Stiffness and Cardiovascular Therapy

The world population is aging and the number of old people is continuously increasing. Arterial structure and function change with age, progressively leading to arterial stiffening. Arterial stiffness is best characterized by measurement of pulse wave velocity (PWV), which is its surrogate marker. It has been shown that PWV could improve cardiovascular event prediction in models that included standard risk factors. Consequently, it might therefore enable better identification of populations at high-risk of cardiovascular morbidity and mortality. The present review is focused on a survey of different pharmacological therapeutic options for decreasing arterial stiffness. The influence of several groups of drugs is described: antihypertensive drugs (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, beta-blockers, diuretics, and nitrates), statins, peroral antidiabetics, advanced glycation end-products (AGE) cross-link breakers, anti-inflammatory drugs, endothelin-A receptor antagonists, and vasopeptidase inhibitors. All of these have shown some effect in decreasing arterial stiffness. Nevertheless, further studies are needed which should address the influence of arterial stiffness diminishment on major adverse cardiovascular and cerebrovascular events (MACCE).

1. Introduction

The world population is aging so the number of old people is continuously increasing [1, 2]. With increasing age, arterial structure and function change, progressively leading, among other deteriorations, to arterial stiffening [3, 4]. One of the most important parameters most commonly measured and understood, being also the best surrogate for arterial stiffness, is pulse wave velocity (PWV) [5–7]. In a recent meta-analysis, aortic PWV was found to improve cardiovascular event prediction in models that included standard risk factors (arterial hypertension, smoking, diabetes, etc.) and might therefore enable better identification of high-risk populations [8, 9]. Even though this data exists, there is still no pharmacological approach regularly used in clinical practice aiming to decrease arterial stiffness. In other words, the therapeutic approach does not aim at arterial stiffness decrease per se. Although evidence of the importance of PWV is growing, there was no study reported in which a decrease of cardiovascular mortality due to reducing arterial stiffness by pharmacologic approaches had been observed. Nevertheless, we believe that there is sufficient proof of PWV being an important cardiovascular risk factor and that such a study is very much needed. Therefore, in what follows we review all known pharmacological approaches capable of decreasing arterial stiffness. Importantly, it should be noted that the effects of pharmacologic agents on stiffness are usually slight or modest, but not substantial. Thus, new therapeutic approaches to decrease arterial stiffness are highly desirable.

2. Pathophysiological Aspects of Arterial Stiffness

Conductive arteries propel the pressure wave generated by the heart, that is, the ejection of blood from the left ventricle. This wave is reflected at the impedance mismatch points (junctions of large conduit arteries, high-resistance arteries, and bifurcations), from where it travels backwards to the heart. Consequently, the observed generated wave is the sum of the forward travelling wave (moving from the heart) and the reflected wave (travelling backwards towards the heart) [10]. In young healthy subjects who have compliant arteries the reflected waves return to the ascending aorta at the time of diastole, thus leading to pressure amplification in this part of cardiac cycle, leading to an increase in diastolic blood pressure (DBP) [11]. As pulse waves travel faster in stiffer arteries, PWV measurement is consequently the best surrogate for arterial stiffness evaluation in everyday practice. It also increases with age and is a predictor of cardiovascular risk. It has been calculated that an increase in PWV by 1.0 m/s increases the risk of cardiovascular events by 14% [12].

The low blood pressure elastic modulus of the elastin component of arterial media dominates the mechanical behavior of the arterial wall, making it distensible [10]. At higher blood pressures, the wall is less extensible, due to the low elastic modulus of the collagen component of the arterial media that dominates at these pressures [13]. It can be concluded that at low blood pressures a small amount of collagen fibers is recruited. When the blood pressure rises, more and more collagen fibers are engaged, the elastin component having relatively less influence, leading to sufficient support of the arterial wall and stabilization of aortic root distension. To sum up, arterial wall compliance and distensibility progressively decrease with increasing blood pressure. Blood pressure-dependent changes in elastic modulus are nonlinear; that is, the change in elastic properties is much greater at high blood pressures than at low blood pressures [10]. Blood pressure increase leads to PWV increase. The consequence is pressure wave propagation, which is a result of the increase in amplitude of the wave travelling from the heart. It means that the top of the wave travels faster than the rest of the wave. This leads to the physiological findings of a consistent difference between blood pressure values in the ascending aorta and brachial artery. In young healthy subjects, the difference between pulse pressure (PP) and systolic blood pressure (SBP) in the ascending aorta and at the level of brachial artery can be as much as 20 mmHg, while in patients treated for hypertension it is considerably lower (6 to 11 mmHg) [11].

The arteries become stiffer with increasing age and disease (e.g., hypertension, chronic kidney disease, diabetes, and atherosclerosis). Increased stiffness results from structural changes, such as fragmentation of elastin, an increased amount of collagen, arterial calcification, glycation of both elastin and collagen, and cross-linking of collagen by advanced glycation end- products (AGE) [14–17]. These changes could be measured quantitatively in the pathology department. On the other hand, clinical evaluation of arterial mechanical properties is far more complex and a complete description of the strain-stress relationship in vivo is not possible due to uncertainties arising from nonlinear behavior, viscoelasticity, anisotropy, active tone, residual stresses, and tethering [18]. The methods most commonly used measure transit times between different sites in the arterial tree and calculate arterial PWV and measure local arterial compliance, the distensibility or stiffness index, and also the augmentation index (Aix) [19].

Increased arterial stiffness leads to increased PWV and central arterial pressure, resulting in higher arterial pulsatility. The latter leads to damage of the microcirculation in several organs, especially the highly perfused ones, such as myocardium, the kidneys, and brain (Figure 1). Taking into account that the population is aging, stiffness is an important factor in pathophysiological aspects [20].

3. Endothelial Function and Arterial Stiffness

Endothelial function and arterial stiffness are two different aspects of arterial disease, which are interconnected as their pathophysiological background is similar. Nitric oxide (NO) has been shown to contribute importantly to arterial compliance or distensibility [21]. Arterial stiffness can be regarded as composed of two distinct components: a structural and a dynamic component. These two are obviously interconnected. The structural component is represented by the collagen and elastin fibers in arterial media, as well as other connecting molecules [22]. The dynamic component is represented by the tone of smooth muscle cells, also in the arterial media. This tone is dependent on vasoactive substances released from the endothelium [23]. As mentioned above, the artery becomes stiffer due to an increase in the collagen-elastin ratio. On the other hand, the stiffer the artery gets, the greater the hemodynamic load to which its endothelium is exposed, resulting in its earlier damage. The dynamic and structural components of arterial stiffness are interconnected and lead to a vicious cycle (Figure 2).

4. Influence of Drugs on Arterial Stiffness

According to the literature, several drugs have been shown to influence arterial stiffness: antihypertensives, statins, peroral antidiabetics, AGE cross-link breakers, anti-inflammatory drugs, endothelin-A receptor antagonists, and vasopeptidase inhibitors. The majority of them act predominantly on the dynamic component of arterial stiffness and to a lesser extent on the structural component in arterial wall remodeling, whereas only AGE cross-link breakers act directly on the structural component. Influence of particular drugs or drug groups on arterial stiffness is summarized in Table 1.


Effect on arterial stiffness reduction/improvement	Drug group	Drug class/drug	References

Uniform effect	Antihypertensive	Angiotensin converting enzyme inhibitors	[25–40]
		Angiotensin receptor blockers	[38, 40–54]
		Calcium channel blockers	[32, 34, 37, 46, 49, 55–60]
		Aldosterone antagonists-spironolactone	[61–63]
	Peroral antidiabetic drugs	Glitazones-pioglitazone	[64–66]
	AGE cross-links breakers	Aminoguanidine	[67–70]

Prevailing effect	Antihypertensive	Direct renin inhibitors	[39, 71–73]
	Antihypertensive	Beta-blockers	[27, 39, 53, 54, 74–78]
	Lipid lowering drugs	Statins	[79–87]
	Peroral antidiabetic drugs	Metformin	[88, 89]
	AGE cross-links breakers	Alagebrium chloride	[16, 90–92]
	Anti-inflammatory drugs	Corticosteroids	[93]
	Endothelin-A receptor antagonists	Sitaxsentan, BQ-123	[94, 95]

Conflicting effect	Antihypertensive	Nitrates	[96]
	Antihypertensive	Aldosterone antagonists-eplerenone	[97–99]
	Peroral antidiabetic drugs	Glitazones-rosiglitazone	[100–103]
	Anti-inflammatory drugs	Antibodies against tumor necrosis factor alpha (anti-TNF-)	[104–110]
	Anti-inflammatory drugs	Acetylsalicylic acid	[111, 112]

Neutral effect	Antihypertensive	Diuretics	[34, 37, 46, 55, 59, 61, 113, 114]
Neutral effect	Vasopeptidase inhibitors	Omapatrilat	[115, 116]

4.1. Antihypertensive Drugs

Antihypertensive drugs have been implicated in arterial stiffness diminishment but vary in their degree of effect. The various antihypertensive drug classes have been more or less extensively evaluated in this regard. Unequivocally, the renin-angiotensin system inhibitors proved to be superior to all other antihypertensive drugs in reducing arterial stiffness. There are different reasons for and understanding of this phenomenon, but the most probable explanation lies in the profibrotic action of the renin-angiotensin system, as the turnover of the extracellular matrix in the arterial wall per se leads to a change in the properties of the vessel [24]. In what follows, antihypertensive drugs are listed according to the amount of evidence and their effect on arterial stiffness.

4.1.1. Angiotensin-Converting Enzyme Inhibitors

There had been some evidence that angiotensin-converting enzyme (ACE) inhibitors lead to arterial compliance improvement [25], but it was the REASON (pREterax in regression of Arterial Stiffness in a contrOlled double-bliNd) study that first evaluated the long-term influence of these drugs on arterial stiffness. This study was performed using the perindopril/indapamide combination and compared it to the use of atenolol. The former combination proved to be more efficacious in reducing systolic blood pressure as well as pulse pressure. The effect was more pronounced in the central indices. Interestingly, PWV showed a similar reduction in both groups, while on the other hand Aix was more significantly reduced in the combination group. The effect obtained in the combination group lasted even after 9 months of treatment without additional blood pressure reduction [26, 27]. In the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation) trial, the same combination of perindopril/indapamide was also evaluated, and it was this study that proved the importance of arterial stiffness and its association with cardiovascular risk [28]. The effect of ACE inhibitors on pulsatile hemodynamics in patients with stable coronary artery disease was evaluated in the PEACE (Prevention of Events with Angiotensin-Converting Enzyme Inhibition) substudy. This study showed that trandolapril moderately decreased PWV, beyond expectations and without relation to blood pressure reduction. Nevertheless, no improvement in aortic compliance or decrease in Aix was observed [29]. All the studies described were long-term studies, but even some short (evaluating acute effects) to medium (less than 6 months) term studies showed a reduction of arterial stiffness when ACE inhibitors were used [30]. These effects were obtained for most drugs in this class, that is, captopril [31], perindopril [32], trandolapril [29], enalapril [33], lisinopril [34], ramipril [35], quinapril [31, 36], and fosinopril [37]. These effects were attributed to the ACE inhibitors’ capability of chronically reducing remodeling of the small arteries, leading to reduction of reflection coefficients.

4.1.2. Angiotensin Receptor Blockers

Intuitively, it might be expected that angiotensin receptor blockers (ARBs or sartans) would produce the same effect as ACE inhibitors. In a trial with patients with resistant hypertension who were receiving three antihypertensive drugs in maximal dosages, including ACE inhibitors, the addition of valsartan for two weeks resulted in reduction of Aix [41]. When valsartan was compared to captopril, the two drugs equally reduced PWV as well as Aix [42]. As far as Aix reduction is concerned, losartan (see the LIFE (Losartan Intervention For Endpoint reduction in hypertension) [43] and OPTIMAAL (Optimal Trial in Myocardial Infarction with Angiotensin Antagonist Losartan) [44] studies) and candesartan [45, 46] were proven to reduce it. Other ARBs, such as valsartan (the VALUE (Valsartan Antihypertensive Long-Term Use Evaluation) study) [47–49], olmesartan [50], telmisartan [51], and eprosartan [52], were proven to reduce central blood pressure more than the systolic blood pressure and increase pulse pressure, while reducing Aix and PWV. In addition, when ACE inhibitor and sartan were combined, they proved to achieve even greater effect on PWV reduction in patients with chronic kidney disease [38].

4.1.3. Beta-Blockers

Beta-blockers without vasodilating properties have been shown to have a weaker effect on arterial stiffness and central pulsatile hemodynamics than vasodilating drugs of other groups. Nevertheless, they showed the same extent of reduction of arterial stiffness per se as the other mentioned drugs. The mechanism of action is through heart rate reduction, as this influences the viscoelastic properties of the arterial wall. Reduced heart rate also leads to increased wave reflections, a lower reduction in aortic than brachial systolic blood pressure, and reduced pulse pressure amplification. Peripheral vasoconstriction, achieved by, for example, atenolol, is an additional mechanism responsible for the negative effect on wave reflections [74–77]. The REASON study evaluated the effect of atenolol on pulsatile hemodynamics. In this particular study central PP slightly increased, while peripheral PP drastically decreased. Also PWV decreased substantially, while Aix increased to a substantial degree. These effects were attributed to the heart rate reduction [27]. Different studies are consistent, showing that atenolol negatively affects both pulse and systolic blood pressure (by increasing them) and wave reflections, increasing Aix, but, on the other hand, reducing aortic stiffness [53]. Thus the CAFÉ (Conduit Artery Functional Evaluation) study showed the superiority of amlodipine in this regard, leading to challenging the recommendation for the use of classical beta-blockers in hypertension treatment [32]. New, increasingly prescribed agents such as nebivolol and carvedilol, that also have vasodilating properties, seem to be more effective in improving central pulsatility. These effects appear to be related to their ability to donate NO, which dilates the small resistance arteries. The effects observed lead to pulse pressure amplification, but Aix reduction [39, 74–77].

4.1.4. Calcium Channel Blockers

Calcium channel blockers also lower PWV and reduce wave reflections, but to a lesser degree than renin-angiotensin inhibitors. The largest amount of evidence is for the dihydropyridine calcium channel blocker amlodipine [32, 34, 37, 46, 49, 55]. This drug was evaluated in the CAFÉ study, among other trials, where it proved to reduce central blood pressure more than peripheral blood pressure; it amplified pulse pressure and reduced Aix and PWV, thus displaying its destiffening effect [32]. Similar results were obtained for the other calcium channel blockers that were evaluated, namely, azelnidipine [56], barnidipine [57], nitrendipine [58], felodipine [55], lercanidipine [59], and verapamil [60].

4.1.5. Diuretics

Diuretics seem to have no beneficial effect on pulsatile hemodynamics. Many agents were studied, including hydrochlorothiazide, which showed a neutral effect on reduction of central blood pressure and a neutral effect on pulse pressure amplification [37, 55]. Consistent data is available for bendrofluazide [34, 59, 61, 113] and indapamide [37, 46, 113, 114], which also have a neutral effect on Aix and PWV, respectively.

4.1.6. Aldosterone Antagonists

The aldosterone antagonist spironolactone proved to reduce PWV and Aix when adjusted for blood pressure, compared to bendrofluazide [61]. The beneficial effect of spironolactone in this regard was also obtained in early stage chronic kidney disease and in patients with nonischemic dilated cardiomyopathy [62, 63]. Similar results were obtained for eplerenone when compared to amlodipine, but its effect proved to be much greater in reducing vascular stiffness and the collagen-elastin ratio when compared to atenolol [97, 98]. These effects were not observed in chronic kidney disease patients stages 3 and 4 [99].

4.1.7. Direct Renin Inhibitors

Direct renin inhibitor, that is, aliskiren, the only one available, was evaluated in diabetes mellitus type 1 and type 2 patients where it reduced PWV as well as Aix, thus showing a beneficial destiffening effect [39, 71, 72]. On the other hand, in patients with essential hypertension, it reduced PWV without influencing Aix [73].

4.1.8. Nitrates

Nitrates have also been studied in this regard. As vasodilating drugs, they influence the smooth muscle cells of large arteries, leading to possible arterial destiffening. Their effect was evaluated in hypertensive patients, where isosorbide mononitrate proved to amplify systolic and pulse pressure but substantially reduced Aix. On the other hand, they did not influence PWV, therefore leading to the conclusion that their effect on arterial stiffness was minimal [96].

It seems that arterial stiffness reduction can be obtained with different antihypertensive drugs. The highest effects are exerted by inhibitors of the renin-angiotensin system. Stiffness reduction seems to be correlated with the dose of antihypertensive drug. Long-term treatment also seems to have a greater effect. Mechanisms behind this are the slow extracellular matrix turnover, the long-term constant of arterial remodeling, and the necessity that the target tissue systems influence changes in arterial stiffness more than blood pressure [117].

4.2. Statins

Statins (HMG-CoA reductase inhibitors), besides their basic action in reducing low-density lipoprotein (LDL) cholesterol, also have several additional protective/beneficial effects (pleiotropic effects) on the cardiovascular system [79]. There are conflicting reports in the literature on whether statins could improve arterial stiffness directly. Rizos et al. reviewed 9 randomized controlled studies (RCT) with 471 participants. In four of them central aortic PWV was assessed; fluvastatin decreased PWV in two studies, whereas in one study the change was not significant and in another study a significant increase in PWV was observed. In the other five studies peripheral (mainly brachial-ankle) PWV was assessed; fluvastatin decreased PWV in all except one study [80]. Arterial stiffness was improved with atorvastatin (40 mg daily) in patients with ischemic heart failure [81]. Low-dose atorvastatin (10 mg daily) was shown to improve arterial stiffness in a double blind, randomized, placebo-controlled study on hypertensive and hypercholesterolemic patients after 26 weeks of treatment [82]. Similarly, it also prevented an increase in arterial stiffness in patients with chronic kidney disease [83]. Statin treatment significantly improved arterial stiffness through decrease of PWV in normotensive patients with coronary artery disease (CAD), but not in hypertensive patients with CAD [84]. The possible mechanisms behind these observed phenomena are that statins act in an anti-inflammatory and antioxidative manner in the arterial wall, which was shown only in relatively small studies [85–87].

4.3. Peroral Antidiabetic Drugs

Treatment with glitazones, peroxisome proliferator-activated receptor gamma (PPAR-) agonists, was shown not only to improve insulin resistance and glycemic control, but also to decrease arterial stiffness in patients with type 2 diabetes mellitus [64, 100, 101]. PPAR receptors were also proven to be expressed in the vascular tissue and influence vascular homeostasis [118]. In the literature it was shown that pioglitazone decreased arterial stiffness in patients with diabetes mellitus type 2 [64] and in obese glucose tolerant men [65]. For rosiglitazone there are conflicting results; in some studies it decreased PWV, which was associated with anti-inflammatory action [100–102]. In another study, eight-week treatment with rosiglitazone failed to improve arterial stiffness in patients with chronic kidney disease, but the study was small (70 patients, divided equally among treatment and placebo groups) [103]. Treatment with pioglitazone and rosiglitazone was associated with improvement in adiponectin levels [66]. Besides glitazones, metformin was also shown to reduce arterial stiffness in several studies, including women with polycystic ovary syndrome [88, 89].

4.4. AGE Cross-Link Breakers

Cross-links between collagen and elastin in the vascular wall are important in providing strength and elasticity to the vessels. Due to nonenzymatic glycation of proteins, especially collagen, AGE are formed, which accumulate and increase collagen cross-linking and consequently progressively increase arterial stiffness. Formation of AGE occurs with aging and is accelerated in diabetes mellitus and hypertension [119]. Newer therapeutics are directed at the cross-linking of collagen, a process previously thought to be irreversible. They can either block the formation of AGE (aminoguanidine) or nonenzymatically break AGE cross-links (alagebrium chloride) and could potentially decrease arterial stiffness [120]. Aminoguanidine was tested mainly in animal studies, where it decreased arterial stiffness parameters [67–69], and only in one human study [70]. Alagebrium chloride (ALT-711) was shown to decrease arterial stiffness in several animal and human studies [16, 90, 91], but not in all [92]. Drugs that block the receptor for AGE (RAGE), or serve as a sham RAGE, are under development [120].

4.5. Anti-Inflammatory Drugs

Inflammation states, such as inflammatory bowel disease [121, 122], rheumatoid arthritis, and low-grade systemic inflammation with increased C-reactive protein [123], are associated with the arterial stiffening process. Several anti-inflammatory drugs tested were shown to reduce arterial stiffness [124]. Antibodies against tumor necrosis factor alpha (anti-TNF-) were shown to be effective in improving arterial stiffness in several studies, including patients with chronic inflammatory diseases [104–107]. In contrast, in recent studies they failed to influence arterial stiffness [108–110]. Corticosteroids could also improve arterial stiffness [93]. Conflicting results were also published for acetylsalicylic acid (Aspirin), which could potentially improve arterial stiffness due to its anti-inflammatory effect [111, 112].

4.6. Endothelin-A Receptor Antagonists

The serum concentration of endothelin-1 was shown to correlate with aortic elasticity parameters in 152 subjects with essential hypertension [125]. Therefore, selective endothelin-A receptor antagonists could improve arterial stiffness. The beneficial effect of selective endothelin-A receptor antagonists (sitaxsentan, BQ-123) in improving arterial stiffness was shown in studies including patients with chronic kidney disease [94, 95]. Obviously large clinical studies are needed to definitely prove this effect.

4.7. Vasopeptidase Inhibitors

Vasopeptidase inhibitors are a new class of drugs that act on two key enzymes in the metabolism of vasoactive peptides: they inhibit ACE to reduce vasoconstriction and inhibit endopeptidase, which is involved in the degradation of several natriuretic peptides, to enhance vasodilation [126, 127]. In a study performed on 167 patients the vasopeptidase inhibitor omapatrilat reduced Aix but failed to influence arterial stiffness [115]. Vascular stiffness was also unaltered by omapatrilat in a study on stroke-prone spontaneously hypertensive rats [116]. Therefore, further studies are needed to investigate the influence of vasopeptidase inhibitors on arterial stiffness.

5. Emerging Pharmacological Approaches

New, innovative therapeutic pharmacological options are emerging and show some promise [128]. Short term, low-dose treatment with a statin and sartan separately, but particularly their combination, was shown to improve endothelial function and arterial stiffness parameters in apparently healthy participants, as well as in patients with diabetes mellitus type 1 [129–132]. This approach is oriented directly to arterial function improvement and represents a simple preventive approach against arterial aging.

6. Conclusion

Arterial stiffness progressively increases with age and was found to be a risk factor of cardiovascular disease. Therefore, besides identifying solely classical cardiovascular risk factors, it appears to be more and more important to assess arterial stiffness, which could be easily measured noninvasively and expressed as PWV. This modified or advanced approach enables better cardiovascular risk stratification. We believe that such an approach should be introduced into the treatment and prevention of cardiovascular disease. At the present there are several pharmacological agents which could influence arterial stiffness. Consequently, the present review focused on a survey of different pharmacological therapeutic options for decreasing arterial stiffness. However, new and more effective treatment is highly desirable. Furthermore, future studies should address the influence of decrease in arterial stiffness on major adverse cardiovascular and cerebrovascular events (MACCE).

Conflict of Interests

The authors declare that there is no conflict of interests regarding the publication of this paper.

Atherosclerosis

Modern cardiology in medical clinics IMMA provides consultations, diagnostics and treatment of atherosclerosis of the coronary vessels. Leading specialists of the region, in comfortable conditions, will consult, carry out diagnostic measures and, if necessary, prescribe treatment for cardiac pathology. The clinic carries out all the studies of the coronary vessels and the heart using traditional and author’s methods. Each client of the clinic can be sure that his health is in the hands of the best doctors.

In our clinics you can:

Get a consultation with a cardiologist;
Take an ECG and get a professional interpretation of the results;
Complete the ABPM procedure;
Complete Holter monitoring;
And use other services.

For more details and for any questions, please contact the number indicated on the website

What is atherosclerosis

Atherosclerosis of the coronary vessels is a chronic heart disease that occurs against the background of metabolic disorders, in particular lipid (fat) metabolism.As a result, cholesterol plaques are deposited on the inner walls of the myocardial arteries, in which the growth of defective connective tissue (sclerosis) gradually occurs. Compaction of the vessel walls leads to irreversible deformations, narrowing of the lumen, up to complete blockage.

Atherosclerosis of the vessels of the heart is the first symptom of ischemic heart disease. Without timely and correct treatment, the development of ischemic disease is inevitable.

As a rule, before the first clinical signs appear, the disease has been developing asymptomatically for a long time.According to medical statistics, atherosclerosis begins at a fairly young age and is clearly manifested by the age of 45-50. This is due to the accumulative feature of cholesterol. For many years, it can gradually envelop the walls of blood vessels until it reaches a critical level. The accumulation of trans fats interferes with full blood flow, up to a complete blockage of circulation. Asphyxia and atrophy of the heart muscle sets in.

Reasons

Atherosclerosis of the arteries of the heart develops under the influence of both social and physiological factors.In cardiology, there are more than 200 reasons provoking the progress of pathology. The most common are:

Disorders of lipid metabolism, as a result of which an excess of cholesterol accumulates in the body, which is deposited on the walls of blood vessels;
Smoking has an extremely negative effect on the heart system. Nicotine, heavy tar, damage cell membranes in blood vessels. Permeability is impaired, blood circulation deteriorates;
Hypertension.High blood pressure increases the load on the heart muscle;
Static lifestyle. Office work, lack of normal activity leads to a slowdown in metabolic processes, stagnant processes begin to develop;
Unbalanced nutrition. Eating large amounts of fried, fatty foods leads to pathologies of the circulatory system;
Genetic predisposition. If at least one close blood relative has been diagnosed with atherosclerosis of the vessels of the heart, then the risk of developing the disease increases several times;
Pol.In young and middle-aged women, the development of atherosclerosis is prevented by natural processes in the body – the synthesis of estrogen. After the onset of menopause, the risk of pathology increases;
Old age. The gradual accumulation of unhealthy fats has been going on for decades. Therefore, the older a person becomes, the greater the likelihood of a dangerous diagnosis;
Narcological diseases. The presence of alcohol or drug addiction aggravates the general state of human health, one of the complications of addictions can be atherosclerosis of the coronary arteries of the heart;

Diabetes mellitus.The clinical picture of the disease includes multiple lesions of the blood vessels, against the background of impaired metabolism. Atherosclerosis can be a complication.

Symptoms

The danger of atherosclerosis of the coronary vessels of the heart is the absence of symptoms in the early stages of development. The disease can quietly destroy arteries over the years. As a rule, the first signs appear in middle age, after 45 years. During this time, negative processes in the vessels reach a critical level and are manifested by the following symptoms:

Pain in the region of the heart, left shoulder and under the scapula;
Discomfort, burning sensation under the ribs;
Shortness of breath while walking and in a completely horizontal position;
General weakness, dizziness;
Constant slight nausea.

Nonspecific symptoms of atherosclerosis of the heart are often taken by patients for the manifestation of other diseases that have similar symptoms. This makes it difficult to make a diagnosis in the early stages, when the prognosis of treatment is favorable in the vast majority of cases.

Progressive atherosclerosis of the vessels of the heart manifests itself with more serious symptoms:

Angina pectoris. Short-term attacks of pain in the region of the heart, radiating to the scapula, arm, abdominal cavity and lower jaw.They occur after physical activity, eating spicy food, or emotional stress. Lasts no more than 15-20 minutes, symptoms disappear after rest or taking sedatives, for example, validol.
Cardiosclerosis. The process of development of atherosclerosis is in an active stage – scarring and replacement of muscle tissue with defective compounds occurs. It manifests itself as constant mild, moderate pain, swelling of the extremities, shortness of breath, rapid fatigability, and decreased physical activity.
Arrhythmia. The frequency and sequence of heartbeats are disturbed. The patient has paroxysmal pain, a feeling of cardiac arrest, dizziness, fainting, abnormal tremors in the chest region.

Heart failure. The rupture of the cholesterol plaque is accompanied by the formation of a blood clot, which clogs the artery. The blood stops carrying oxygen and nutrients. The heart stops working normally. There are strong, burning pains in the chest, nausea, the patient feels a lack of air, the limbs swell, there is a clouding of consciousness.

Important! In acute insufficiency, the risk of developing myocardial infarction increases to 90%. If the attack is accompanied by a rupture of the aneurysm, death occurs.

Depending on how quickly the patient seeks medical help, the prognosis of atherosclerosis will be positive or unfavorable. If the pathology is neglected to such an extent that foci of necrosis began to form in the myocardium, then there is a significant threat to life.

Treatment

Treatment of atherosclerosis of the coronary vessels of the heart requires a heterogeneous, comprehensive approach and a long period of time.After an accurate drawing up of the clinical picture of the disease, medications and therapeutic measures are prescribed, which include:

Hypolydemic drugs for removing excess lipids and fluid from body tissues from blood vessel cells;
Beta-blockers, inhibitors to reduce the oxygen demand of the heart. During treatment, this reduces the activity of the myocardium and the severity of symptoms.
Anticoagulants to exclude the possibility of blood clots.
Prescribing a special diet;
Prohibition of smoking, alcoholic beverages;
Moderate therapeutic physical activity to prevent stagnant processes;
Weight loss to normalize metabolic processes and remove toxic substances from the body.

Surgical intervention

Treatment of atherosclerosis involves surgical methods when the development of the disease is in the last stages and the patient’s life is in danger.The way to solve the problem is determined by the cardiologist if conservative therapy has not been successful. Modern medicine offers the following types of surgical intervention:

Coronary artery bypass grafting. Dentures are inserted into the vessels, which allow to restore blood circulation in the proper volume.
Angioplasty. Mechanical expansion of coronary vessels, by introducing special catheters with a balloon. When the balloon is inflated, the cholesterol plaque is “flattened” and, accordingly, the capacity of the vessel is restored.
Stenting. A rigid frame is introduced into the vessel cavity, which expands and fixes the lumen of the artery.

Preventive examination and early diagnosis will help to avoid dangerous surgical intervention. The initial stages of the disease respond well to treatment and prevention of dangerous complications.

Possible complications

Atherosclerosis of the aorta of the heart has two types of complications – chronic and acute. Chronic forms include vascular insufficiency, irreversible deformations of myocardial muscles, proliferation of defective connective tissue, oxygen starvation of the heart.Most often, the following pathologies appear:
Myocardial infarction is a necrotic scarring of muscle tissue associated with a lack of oxygen.

Stroke – a violation of the myocardium, leading to the death of nerve cells in the brain, due to weak or extensive hemorrhage;
Hypertension – persistent increase in blood pressure due to impaired blood circulation in the coronary vessels of the heart;
Ischemic heart disease is a pathology with absolute or partial myocardial damage.

Acute complications pose a direct threat to life and are associated with the formation of blood clots and spasms in the blood vessels. These include:

Aortic hematoma – an accumulation of blood between the walls of blood vessels. Manifested by fainting, severe chest pain. Requires immediate surgery.

Aneurysm – expansion of the vascular cavity caused by abnormal proliferation of connective tissue. A distinctive feature is a sudden rupture with large blood loss, which is asymptomatic.In most cases, it is fatal.

Important! Already at the first consultation with a cardiologist, you can find out about the presence of atherosclerosis of the coronary vessels. Visual inspection and listening – simple and, most importantly, timely, diagnostic methods will help preserve health and life.

Who is at risk

Everyone, regardless of gender and age, can get coronary atherosclerosis. This is facilitated by many factors, ranging from social causes to poor ecology.
The guidelines for the assessment of risk factors for the development of cardiovascular diseases, developed on the basis of many years of research in the field of cardiology, highlight the following indicators:

Men aged 50-55;
Severe working conditions due to professional activities;
Hereditary heart disease;
Obesity;
Smoking, including passive smoking;
Psychological disorders – stress, depression, depression;
Diseases of the thyroid gland;
Poor nutrition, the definition includes fried, fatty, sweet and flour foods, fast food.

A systemic risk assessment for the next 10 years can be set independently according to the well-known SCORE (Systemic COronary Risk Evaluation) scale proposed by American cardiologists.
The modern pace and rules of life put every second person at risk. Therefore, it is difficult to find better prevention of atherosclerosis of the heart vessels than regular preventive examinations. At the slightest suspicion, it is better to consult a cardiologist and adjust your lifestyle than to undergo long-term treatment, not always with a positive outcome.

Appointment for preventive examination

You can make an appointment with a cardiologist at the contacts indicated on the website or by contacting the nearest IMMA medical center. You will receive comprehensive information not only about the internal routine of the clinic, but also about modern research standards, methods of diagnosis and treatment. Medical and diagnostic assistance provided to patients in the cardiology department is carried out according to the recommendations of the WHO RF by doctors-cardiologists of the highest category and candidates of medical sciences.

“Cleaning blood vessels is quackery, but living with” working pressure “

Cleaning blood vessels is quackery, but living with” working pressure “is like being on a powder keg”: Chief Cardiologist of the Ministry of Health of Russia, Director of the National Medical Research Center of Cardiology Sergei Boytsov spoke about the most common misconceptions of patients with diseases of the cardiovascular system.

THE BODY THAT IS AGING FASTEST.

The first and main organ that “sheds” in most people with age is the blood vessels.”Their most frequent and significant disease is arterial hypertension,” – explains Professor Boytsov. Among Russians aged 25–65, 48% of men and a slightly smaller number of women, that is, almost every second, have hypertension. And in people over 65, the frequency of hypertension reaches 70 – 80 – 90% – with increasing age. Hypertension is the main culprit behind heart attacks, strokes and premature death. Its contribution as a risk factor is 45%, therefore, almost half the likelihood of vascular accidents and death depends on high blood pressure (other factors are smoking, excess weight, salt and alcohol abuse).With age, few people can avoid the development of hypertension, throw up his hands Fighters. The vessels become more rigid, the kidneys work worse, they cope less well with the load of removing salt from the body. And an excess of salt, as you know, is one of the main conditions for increasing pressure. But it is not all that bad. It is possible and necessary to engage in the prevention of hypertension, and if the disease has already begun, then keep it under control. At the same time, many hypertensive patients make the main and very dangerous mistake – they live with the so-called “working pressure”.

MAXIMUM THAT WE CAN ALLOW FOR YOURSELF.

Now in medicine there is no such thing as “working blood pressure”! An opinion like “I have a working pressure of 160 to 100 all the time, and I feel great” is a profound delusion! – Professor Boytsov opens his eyes to patients and their relatives. 140 by 90 mm. mercury column – the maximum pressure that we can afford if we do not want to earn a heart attack or stroke. And it is better to strive for a pressure of 130/80. Another dangerous misconception is taking medications for hypertension in courses. “I take pills for 2 weeks, and my blood pressure will return to normal, which means I’m cured”: one of the most common mistakes. Modern medicine does not recognize the course therapy of hypertension. Because this disease is forever. It is chronic, it cannot be completely cured, but it can be successfully controlled, prolonging life and preserving its quality. And for this drugs for hypertension must be taken, as cardiologists say, “indefinitely.” In other words – constantly after the examination shows the need to prescribe medication (in some cases, in the early stages, high blood pressure can be corrected with non-medication). – After you start taking the prescribed medications, after a while the pressure normalizes, but as soon as you stop taking drugs, it will start to grow again, – explains Professor Boytsov. Such a “swing” is very dangerous.

DON’T GET RID OF PLAQUES, BUT YES YES OF MONEY.

What is the best way to clean blood vessels from cholesterol? There are so many proposals, preparations and methods on the Internet “ It is impossible to clean the vessels today”, – Professor Boytsov dispels illusions. In general, “cleaning blood vessels” is a common slang. We have been living in the world of evidence-based medicine for at least two decades. And the drugs that allegedly “clean” the vessels have no evidence base. Serious science now does not engage in such “cleansing” at all. There was at one time the so-called chelation therapy aimed at dissolving cholesterol plaques.But this direction has completely discredited itself. What does modern medicine offer ? “There are statin drugs that can reduce the size of the cholesterol plaque by hardening it,” explains the doctor. In this case, the fatty component of the plaque is reduced, but today it is impossible to completely remove the formed “growths” on the walls of blood vessels. Therefore, it is important to engage in the prevention of atherosclerosis, slowing down or inhibition of the growth of plaques. This can be achieved through a healthy lifestyle and medication prescribed by your doctor.

FIRST SIGNS OF INFARCTION: DO NOT BE WRONG!

Most often, people do not quite correctly imagine the first signs of a heart attack, says the chief cardiologist. Because of this, there is a risk of wasting time, which threatens with dangerous complications, including death. The first and main signal is pain. Moreover, most often not in the region of the heart, but in the middle of the chest. Very often, the pain radiates to the left arm, shoulder, jaw, neck. Pains during a heart attack are not stabbing or cutting, they press, strangle. The second symptom is choking, a sharp feeling of lack of air. If these two symptoms persist within a few minutes, an ambulance should be called immediately. Then there is a chance not only to save lives, but also to minimize the amount of damage to the heart muscle and avoid the development of heart failure after a heart attack. The ambulance team usually takes an average of 10 minutes to diagnose myocardial infarction. If the nearest hospital where coronary angiography and stenting can be performed is less than an hour, then the patient is immediately taken there.If the road to the hospital with the necessary equipment takes more than an hour, then the doctor of the ambulance team immediately injects the patient with a drug to dissolve the blood clot that caused the heart attack, then the patient is transported. Upon arrival at the hospital, coronary angiography is performed to determine the location and extent of damage, and treatment is prescribed.

FIVE TIPS TO KEEP A HEART HEALTHY.

This is what Professor Sergei Boytsov recommends.

1.Strive for a flat stomach. To do this, you can look in the mirror or use a measuring tape. For men, the critical waist width is 102 cm and more, for women – 88 cm and more. Belly fat is the most dangerous for the cardiovascular system.

2. Be physically active. One of the best weapons against hypertension is working muscles. They actively receive blood. Blood goes out – the load on the arteries of the heart and brain decreases.

3. Do not abuse salt.Try to be undersalted when you cook. And it is advisable to remove the salt shaker from the dining table altogether so as not to sprinkle salt into the finished dishes.

4. Stop smoking. Completely, and not switching to electronic cigarettes, tobacco heating means, etc. – they all harm your blood vessels, no options.

5. Less alcohol. There are no useful doses. You can only minimize the harm of alcohol, trying to drink it as little as possible. The most dangerous thing is if you have a hangover the next morning after drinking.This means that there has been a strong intoxication, which is critically dangerous for the blood vessels and the heart.

SOURCE – KP.RU

Retinal vascular diseases | DoctorVisus.ru

Hypertensive retinopathy is a serious and most common complication of hypertension, which manifests itself in a complex lesion of the retina of the eyes and its vessels. If untreated, it can lead to serious circulatory disorders in both the optic nerve and the retina.

Hypertensive retinopathy most often affects people suffering from high blood pressure and, as a result, hypertension, renal hypertension, adrenal disease and the elderly.

In the early stages, the disease is asymptomatic, in the later stages, there is a significant deterioration in visual acuity.

Important! If the ophthalmologist has made such a diagnosis for you, we recommend that you undergo a complete examination of the visual system every six months.

Treatment

The choice of one or another method of treatment depends on the stage of the disease. In most cases, it begins with the appointment of vasodilator drugs and anticoagulants, vitamins and other medications. In the future, an ophthalmologist may prescribe laser coagulation.

Treatment of hypertensive retinopathy itself is symptomatic and is aimed at eliminating the consequences that have already arisen. The main condition for improving the condition of the retina is the relief of the main problem – high blood pressure and the causes that cause it.

Arterial obstruction of the central retinal artery can cause loss of vision instantly, literally within a few seconds, because the retina cannot tolerate the lack of oxygen. If blood circulation is not quickly restored, then in the bloodless retina, as well as in the brain, a condition similar to a heart attack develops rapidly. Eye infarction leads to the death of retinal nerve cells and irreversible loss of vision

In this case, emergency measures are taken: immediate removal of the spasm of the vessel, the introduction into the blood of a substance in order to dissolve a blood clot that clogged the vessel, and a substance that can prevent the formation of blood clots (anticoagulants and thrombolytics).

Venous obstruction of vessels of the retina is much more common than arterial and, fortunately, its course and consequences are much more favorable.

The fundus of the eye with thrombosis of the central vein is covered with many hemorrhages. This happens because the outflow of blood is blocked, but the flow continues. Then the blood begins to seep through the walls of the vessels to the outside, weak vessels burst from the pressure, and retinal edema develops.

IMPORTANT! Treatment of acute retinal vascular diseases should be started immediately.The visual forecast is determined by minutes and even seconds! Acute vascular disorders in the retina can lead to irreversible consequences with the loss of visual functions.

Treatment

In addition to antithrombotic drugs, an ophthalmologist can prescribe laser coagulation, antiVEGF therapy.

Further therapeutic measures are aimed at preventing thrombotic conditions and stopping the action of the main factors of thrombus formation. This is the prevention and treatment of cardiovascular diseases, adherence to a correct lifestyle, a rational diet, work and rest, and, of course, constant supervision by a doctor.

90,000 Peripheral neurovascular syndromes. Ailment of young age

S.A. Klyushnikov
Candidate of Medical Sciences
State Institution Research Institute of Neurology, Russian Academy of Medical Sciences

Peripheral neurovascular syndromes (NVS) are a combined lesion of neurovascular formations of the neck, shoulder girdle, trunk and extremities. These diseases are widespread among the population and can cause permanent disability in young people.The development of symptoms, as a rule, is due to the long-term pathological effect of various external and internal factors on the neurovascular bundles with impaired conduction of nerve impulses in the walls of blood vessels and directly in the tissues.

The clinical picture of NVS is characterized by a combination of pain, muscle-spastic and vegetative-vascular disorders, often with the addition of edematous-dystrophic changes in tissues. Clinical signs of NVS are conventionally divided into:
• local – soreness and muscle tension, pain points in typical places, tissue edema
• neurological – muscle atrophy, contractures, etc.
• vascular – changes in temperature and skin color (cyanosis), changes in blood pressure and pulse in one limb

Known forms of NVS are, for example, tunnel neuropathies, often also called “trapped neuropathies”. This is infringement of peripheral nerves and blood vessels by tendons and ligaments in anatomical constrictions (tunnels) through which neurovascular bundles normally pass – in hard bone canals, holes in ligaments, etc. Currently, in the development of this form of NVS, the role of congenital narrowing of the bone-connective tissue canals has been established.Compression is also possible with normal canal diameters in the case of an increase in the diameter of the nerve due to edema. A classic example is the development of neuropathy (“paralysis”) of the facial nerve, when, under the influence of some external factor (for example, hypothermia), microcirculation in the area of the facial nerve is disturbed, edema of the nerve trunk develops, while the nerve seems to compress itself in the bone canal … Some of the most common forms of neurovascular syndromes:

– Syndrome of the vertebral artery and vertebral nerve (synonyms: posterior cervical sympathetic syndrome, “cervical migraine”, etc.). The reason is irritation of the vertebral nerve in the pathology of the cervical segments of the spine, as a result of which a reflex spasm of the vertebral artery develops. Characterized by headaches, dizziness, a combination of vestibular disorders with pain points on the neck in the projection of the entrance of the vertebral artery into the spinal canal, a variety of vegetative-sensitive disorders in the head.

– Scalenus syndrome (anterior scalene muscle syndrome). It consists in the compression of the subclavian artery and brachial plexus between the anterior and middle scalene muscles in the neck.As a result, a decrease in blood pressure in one arm and a decrease in the filling and tension of the pulse develop, cyanosis and autonomic disorders appear on the arm below the place of compression, pain and numbness in the shoulder girdle and shoulder girdle, local tension of the anterior scalene muscle. It most often develops against the background of cervicothoracic osteochondrosis, abnormal cervical ribs, trauma. Scalenus syndrome often occurs in adolescents who are intensively involved in sports (chronic trauma to the anterior scalene muscle against the background of intensive skeletal growth and increased physical exertion).

– Raynaud’s Syndrome. It is characterized by the localization of vegetative-vascular and trophic disorders mainly on the fingers and toes (pallor, cyanosis), as well as suddenness, severity of vascular spasm attacks, which become more and more protracted as the disease progresses. Leading in the development of the disease is compression and irritation of the arterial vessels of the arms and legs and the vegetative plexuses surrounding them.

– Piriformis syndrome is a well-known NVS, in which there is compression of the sciatic nerve and the inferior gluteal artery by the piriformis muscle in the buttock region.The clinic resembles “radiculitis” with pain spreading to the buttock and back of the thigh, limping, vegetative-vascular and neurodystrophic manifestations, as well as signs of local lesions of the piriformis muscle, the tension and soreness of which can often be determined by touch.

– Carpal tunnel syndrome is the most common form of tunnel neuropathy. The median nerve in the carpal tunnel is compressed by the hypertrophied transverse ligament of the palm, which is clinically manifested by a feeling of “creeping” in the area of the hand and fingers, pain (especially when raising the hand up).With prolonged suffering, weakness of the muscles of the hand, trophic disorders develop. The prevalence of this syndrome increased sharply due to total computerization, since computer keyboards were unsuitable for prolonged work of fingers with poor fixation of the wrists, which caused hypertrophy of the transverse wrist ligament and the occurrence of symptoms. This prompted computer firms to switch to special ergonomic keyboards, resulting in a sharp decline in the number of new cases of this rather unpleasant suffering.

Clinical studies (neurological examination using special functional tests) and numerous laboratory and instrumental methods to determine the state of the microcirculatory bloodstream, coagulation system and blood viscosity are used to make an accurate diagnosis of NVS. Doppler ultrasound, electroneuromyography, capillaroscopy, computer thermal imaging, duplex scanning of blood vessels, magnetic resonance imaging are also used.All these methods make it possible to accurately establish the localization and nature of muscle-tonic, vegetative-vascular and neurodystrophic disorders, to distinguish one form of NVS from another, and to choose the right treatment.

Therapy for this suffering is divided into conservative and operative. Conservative treatment is used in relatively early and benign current forms and is often very effective. It is aimed primarily at the sources of neurovascular compression and vascular spasm: osteochondrosis of the spine, inflammatory and tumor processes of muscles and connective tissue, diseases of internal organs.The success of conservative treatment depends on the timeliness of the patient’s referral to a specialist. Self-medication is unacceptable in any case! Pain relievers, drugs that improve microcirculation and relieve inflammation, decongestants and venotonic drugs are used.

Antispastic drugs (muscle relaxants) are important for treatment, since muscle spasm is not only a typical symptom, but also a key pathogenetic stage in the formation of almost any form of NVS.According to the experience of the most authoritative clinics in the world, baclofen (Baklosan) is currently recognized as the leading antispastic drug, which not only effectively and quickly reduces muscle tone, but also has an undeniable analgesic effect. The latter circumstance is especially important in the treatment of NVS. Thus, the use of Baklosan and its analogues is an integral stage in the therapy of NVS.

In the therapy of NVS, blockades, needle and electropuncture, electrical stimulation and other methods of physiotherapy, exercise therapy, massage, orthopedic and spa treatment are also used.If the disease has reached a severe stage, as well as with the ineffectiveness of other methods of exposure, surgical treatment is used (dissection of pathologically altered spasmodic muscles, removal of cicatricial-fibrous overlays and ligaments, reconstructive operations on the vessels).

Multidisciplinary medical center “Vascular Clinic on Patriarch’s

The central place of any clinic is the registration desk.And our clinic is no exception. Equipped with the most up-to-date equipment, this area allows you to cope with the administration of the complex mechanism of the clinic.

On December 9, 2013, we celebrated the completion of our first year of operations. We are one year old!

Reception desk. Head of the pharmacy, senior administrator, doctor V.I. Kolmakov and Professor V.G. Lelyuk draws up the patient’s documents.

Staff room. Outside her door, our specialists and professors can get a little distracted and relax.

In a relatively small room of the clinic, there are consulting rooms, a procedure room, and rooms for instrumental diagnostics. All these rooms, together with the waiting hall, are connected by a mirrored corridor.

The administration tries to avoid queues, but given the specifics of our clinic, often parallel appointments of professors and doctors, sometimes you have to wait.We did everything so that the wait was not painful.

In the lobby next to the reception desk, for your convenience, there are printed publications, a TV, a cooler with hot and chilled water, comfortable armchairs.

The MED-info stand, constantly updated with new issues of the magazine, is always at your service – interviews, opinions of doctors and patients, problematic articles and an invariably creative approach to the published materials of the team headed by Oksana Plisenkova.

Since 2013, the clinic has been cooperating with one of the most popular periodicals at present – the MED-info magazine. We always have a sufficient number of rooms, the reading of which helps our visitors to have an interesting time.

For the convenience of our patients, each visitor receives brochures and convenient business cards of the clinic.

The clinic annually publishes calendars, business cards and other products with the symbols of the Vascular Clinic on Patriarchschikh, our friends and partners – Realnoe Vremya publishing house – always help us in this.

All workplaces of doctors and administrative personnel are equipped with modern office equipment.

The offices for the reception of specialists are equipped with comfortable functional medical furniture and sanitary ware; the center uses special detergents and disposable towels.

Doppler analyzer Angiodin Universal, used at the MPMC “Vascular Clinic on Patriarshikh” for a long-term study of the Doppler characteristics of blood flow in the cerebral arteries and registration of embolic signal flows in the spectra.

Reception room for specialist doctors. O.V.’s consultations usually take place here. Morozova, E.E. Gubar, I.E. Sinelnikova, E.A. Tenyaeva, A.G. Evdokimov and our other doctors.

Treatment room – samples are taken here for laboratory testing (with subsequent sending to the leading laboratories in Moscow, with which the MPMC “Vascular Clinic on Patriarch’s” cooperates).

Modern plumbing, disposable towels and electric dryers, exhaust ventilation allows the most demanding visitors to feel comfortable in our clinic.

Ultrasound examination room. Ultrasound system Acuson Sequoia – 512. Comfortable couches, functional chairs for doctors, air conditioning and soft blackout – we took care of your comfort during the examination.

Style, cleanliness and order have always distinguished the Vascular Clinic on Patriarch’s. According to many of our clients, the clinic does not look like something alien, it is homelike and cozy.

In the ultrasound diagnostics room. Universal ultrasound system Aplio (Toshiba, Japan). The high resolution ultrasound scans on this machine are used by both medical expert and many of our consulting professors.

It is not only patients who should be comfortable in the clinic. Our doctors are also provided with everything necessary for comfortable work: all rooms are air-conditioned, all workplaces are equipped with personal computers connected to a network.

A modern, reliable and functional system of Holter monitoring and ABPM produced by VHI Advanced Technologies is convenient both for patients (light ergomomic and miniature devices) and for doctors – software.

In accordance with a valid license, our clinic operates a small private pharmacy located next to the waiting room. This is very convenient for patients visiting our doctors and professors.

The MPMC pharmacy is headed by an experienced doctor V.I. Kolmakov. The assortment of the pharmacy includes drugs prescribed by the clinic’s consultants. Naturally, we do not sell potent drugs, tranquilizers, antibiotics.

On the shelves of the pharmacy there is always a large selection of modern antihypertensive drugs, venotonics, anti-sore agents and anticoagulants and other drugs for the treatment of various diseases.Prices are lower than the average in Moscow.

Aplio scanner (Toshiba, Japan) is used for all major types of ultrasound examinations carried out in our clinic. This ultrasound diagnostic system is highly appreciated by our oncologists, mammologists, endocrinologists, and gynecologists.

The clinic is located in courtyards near the Patriarch’s Pond, in a building built in 1905. Some of our visitors and friends compare these courtyards, wooden awnings and porches with old Italy.

Diagnostic ultrasound system Acuson Sequoia – 512 is especially in demand for examinations of the heart in children and adults, blood vessels, eyes and orbit, skin, nerves, as well as in many other applications.

We attach great importance to the prevention of diseases. Do you want to determine the level of risk of developing diseases yourself? Just go to the front desk, fill out the form and you will know exactly what to do next.

In the neighborhood of Bulgakov’s house, in the courtyard of the alleys of old Moscow, just a 10-minute walk from the Pushkinskaya and Mayakovskaya metro stations and 7 minutes from Tverskaya and Garden Ring, our clinic is located.

The special charm of the Patriarchs is the swans on the water surface of the pond and the amazing calmness and tranquility that reigns around in the morning hours. For many Muscovites, Patriarch’s Ponds are the personification of Moscow.

Patriarch’s Ponds. If you have an extra hour, come to us earlier and take a walk along Malaya Bronnaya, walk along the shore of the pond, feed the swans, have a cup of tea or coffee in a cafe. You will feel like a different person. Take some time – you won’t regret it!

Remember the adaptation of the novel by M.A. Bulgakov? It was on these benches that Berlioz, Woland and Koroviev were sitting … In this place Annushka poured sunflower oil… In the neighborhood there is also a “bad apartment” in a house on Sadovaya.

On the way to our clinic or on the way back from it, walk along the Patriarch’s – the pond is located exactly 70 meters from us. Few places in modern Moscow have preserved such places, equally beautiful both in winter and in summer, steeped in history and modern.

Patriarch’s Ponds is one of the most beautiful places in the historical center of the capital. Monument to A.I. Krylov.

Our courtyard in winter – real snowdrifts and a red grid of lights as a landmark and identification mark.

Tens of thousands of patients, thousands of trained doctors, hundreds of lectures, books, textbooks, articles. The vast cumulative experience of our professors. Professor S.E. Lelyuk examines the patient.

Ultrasound duplex scanning of brachiocephalic vessels using the Aplio scanner (Toshiba, Japan) is carried out by one of the best specialists in Russia, Professor S.E. Lelyuk – head of the MPMC and LLC “ITR”.

Several times a year, the clinic staff organizes free promotions. Traditionally, the largest of these is the World Stroke Day. During these days, hundreds of patients pass through the center. There are much more interested persons.

Metabolic disorders are very common. To identify them in a timely manner, we often carry out stress testing.To avoid unnecessary trouble, the blood glucose level is first measured with a glucometer.

90,000 Myocardial infarction and stroke: causes and treatment

Already by the end of the 50s of the twentieth century, studies have confirmed that unfavorable heredity and age can be considered important risk factors for the development of diseases of the heart and blood vessels. Both of these risk factors are non-modifiable, i.e. their influence cannot be ruled out, but they can and should be taken into account to identify groups of patients with an increased risk of cardiovascular diseases.

A person can only act on other factors. He is able to quit smoking, maintain normal blood pressure and sugar levels, reduce excess weight and monitor cholesterol levels with medical help. Such actions can slow the progression of atherosclerosis and reduce the risk of myocardial infarction and stroke. If the vascular wall has undergone significant changes, surgery may be required, followed by drug treatment.

Ischemic disease develops if atherosclerotic plaques appear in the coronary arteries feeding the heart. The plaque blocks part of the vessel lumen, reducing the amount of blood flowing to a specific area of the heart.

If, due to inflammation, mechanical damage and other factors, the integrity of the plaque is disrupted, platelets and erythrocytes immediately adhere to its lipid core, and the blood coagulation system is activated. As a result, a blood clot forms.It can completely block the lumen of the coronary artery, and myocardial cells that received nutrition from this vessel begin to die off. This is how myocardial infarction develops. And if very quickly, during the first hours, the blood flow is not restored by destroying the blood clot, the heart cells will die completely.

It is possible to save the myocardium if, no later than 2 hours after the onset of symptoms, a difficult, but extremely important manipulation is carried out: percutaneous coronary intervention. It involves passing a catheter through a peripheral vessel to the coronary artery.A balloon is inserted through the catheter, and when inflated, it is possible to restore the normal lumen of the vessel and install a stent – a metal frame that maintains the artery in an open state.

Unfortunately, in Russia it is often impossible to withstand such a strict timing of thrombolytic administration: a huge territory and insufficiently developed infrastructure. Most patients arrive at the hospital with a critical delay, and the later treatment begins, the higher the risk of complications and death.However, there is an opportunity to help people even before admission to the hospital. This is the introduction of thrombolytics at the prehospital stage.

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