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Blood pressure test – Mayo Clinic

Overview

A blood pressure test measures the pressure in your arteries as your heart pumps. You might have a blood pressure test as a part of a routine doctor’s appointment or as a screening for high blood pressure (hypertension). Some people use a blood pressure test at home to better track their heart health.

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Why it’s done

A blood pressure test is a routine part of most doctor appointments. Blood pressure screening is an important part of your general health. Find out when you should have a blood pressure test.

  • People age 18 and older with normal blood pressure and no heart disease risk factors should have a blood pressure test at least once every two to five years.
  • People age 40 and older — or younger with an increased risk of high blood pressure — should have a blood pressure test every year. Risk factors for high blood pressure include obesity and being Black.
  • People who have chronic health conditions, such as high or low blood pressure or heart disease, may need to have blood pressure tests more often.

Your doctor may also suggest checking your blood pressure at home. Automated home blood pressure monitors are available and easy to use. Some can be connected to your computer or cellphone, making it easy to transfer the information to an online medical record. Ask your doctor if this is an option for you.

It’s a good idea to keep a blood pressure log at home and have your doctor check your monitor once a year to make sure you are getting accurate readings.

Home blood pressure monitoring isn’t a substitute for visits to your doctor.

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Risks

A blood pressure test is simple, quick and usually painless. However, the blood pressure cuff squeezes your arm while it inflates. Some people find this slightly uncomfortable. The feeling lasts for only a few seconds.

How you prepare

No special preparations are usually needed for a blood pressure test. But the following steps may help your doctor get the most accurate measurement:

  • Do not smoke, exercise or drink caffeinated beverages for 30 minutes to an hour before the test. Such activities increase your heart rate and blood pressure.
  • Consider wearing a short-sleeved shirt so that the blood pressure cuff can be placed more easily around your arm.
  • Relax in a chair for at least five minutes before the test.
  • Tell your doctor about the medications you take. Some drugs may affect your blood pressure.

What you can expect

During the procedure

Usually, a nurse or technician takes your blood pressure while you are seated in a chair with your feet flat on the floor.

You rest your arm on a table at the level of your heart.

The blood pressure cuff is wrapped around the top part of your arm. The bottom of the cuff is just above your elbow. It’s important that the cuff fits. Readings can vary if the cuff is too big or too small.

  • For a manual blood pressure measurement, the nurse or technician places a stethoscope over the major artery in your upper arm (brachial artery) to listen to blood flow.
  • The cuff is inflated with a small hand pump.
  • As the cuff inflates, it squeezes your arm. Blood flow through the artery stops for a moment.
  • The nurse or technician opens a valve on the hand pump to slowly release the air in the cuff and restore blood flow. He or she continues to listen to blood flow and pulse and records your blood pressure.

Some blood pressure cuffs automatically inflate and measure your pulse. In this case, a stethoscope is not needed.

It takes about one minute to get a blood pressure measurement.

After the procedure

If your blood pressure is high or low, you’ll need to have at least three more blood pressure tests, spaced at least a week apart, to determine if you need treatment. Blood pressure can vary from moment to moment and day to day.

Results

Your doctor, nurse or technician can tell you your blood pressure results immediately after the test.

Blood pressure is measured in millimeters of mercury (mm Hg). A blood pressure measurement has two numbers:

  • The top number (systolic) is the pressure of the blood flow when your heart muscle contracts, pumping blood.
  • The bottom number (diastolic) is the pressure measured between heartbeats.

Here’s a look at blood pressure categories and what they mean. If your top and bottom numbers fall into two different ranges, your correct blood pressure category is the higher one.

Top number (systolic) in mm Hg And/or Bottom number (diastolic) in mm Hg Your category*
  • *Ranges may be lower for children and teenagers. Talk to your child’s doctor if you think your child might have high blood pressure.
  • †What’s considered low blood pressure can vary from person to person. The numbers given are a general guideline.
  • Source: American Heart Association
Below 90 or Below 60 Low blood pressure† (hypotension)
Below 120 and Below 80 Normal blood pressure
120-129 and Below 80 Elevated blood pressure
130-139 or 80-89 Stage 1 high blood pressure (hypertension)
140 or more or 90 or more Stage 2 high blood pressure (hypertension)

If you have high blood pressure, making a few lifestyle changes can improve your heart health.

  • Reduce salt (sodium). The American Heart Association recommends that healthy adults have no more than 2,300 milligrams (mg) of sodium a day. Ideally, most adults should limit salt to less than 1,500 mg a day. Remember to check salt content in processed foods, such as canned soups and frozen foods.
  • Eat healthy foods. Choose fruits, vegetables, whole grains and low-fat dairy foods. Eat less saturated fat and total fat.
  • Limit alcohol. Alcohol can raise your blood pressure. If you choose to drink alcohol, do so in moderation. For healthy adults, that means up to one drink a day for women and up to two drinks a day for men.
  • If you smoke, quit. You should also try to avoid secondhand smoke.
  • Lose weight. If you’re overweight, losing even 5 pounds (2.2 kilograms) can lower your blood pressure.
  • Exercise regularly. Staying active helps lower your blood pressure and manage your weight. Most healthy adults should aim for at least 150 minutes of moderate aerobic activity or 75 minutes of vigorous aerobic activity a week, or a combination of the two.

If lifestyle changes do not successfully manage your blood pressure, your doctor may recommend medication. If you have low blood pressure, your symptoms will depend on the cause. Together, you and your doctor can discuss the best treatment for you.

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Oct. 07, 2020

Low blood pressure (hypotension) | healthdirect

As blood is pumped by the heart around the body, the pressure with which it pushes against the walls of blood vessels changes.

When the heart is squeezing blood into the arteries, the pressure is high. When the heart is relaxed, the pressure is lower.

Your blood pressure is a measurement taken of the highest reading and the lowest reading. It is given as 2 figures — highest over lowest. Blood pressure is measured in ‘mmHg’, which refers to millimetres of mercury.

What is low blood pressure?

Low blood pressure is also known as hypotension.

Most doctors would say that you have low blood pressure if it is below 90/60 mmHg. Your doctor will refer to this as ‘90 over 60’.

Is low blood pressure a problem?

For some people, low blood pressure is a sign of good health. These are generally people who are very fit and who have a slow pulse. For other people, low blood pressure is a problem.

Often, people with low blood pressure can be expected to lead longer lives.

However, people who experience continuing symptoms of low blood pressure should see a doctor. Sudden, severe low blood pressure (shock) can be associated with serious medical conditions.

What are the signs and symptoms of low blood pressure?

The symptoms of low blood pressure may include:

These symptoms can occur when doing nothing. They are more likely to occur when changing position, such as standing up or when straining on the toilet.

However, often there are no symptoms and low blood pressure is often only identified as a result of a routine medical examination or during the course of an investigation for some other condition or underling illness.

Low blood pressure may be more serious in elderly people who may have an underlying illness or who may be at risk of a fall.

Check your symptoms with healthdirect’s Symptom Checker to get advice on when to seek medical attention.

What causes low blood pressure?

Apart from being very fit, people can have low blood pressure if they:

  • are overheated, either from the weather, from hot baths or showers, or from wearing too many clothes
  • have too little blood circulating, either from donating blood, from bleeding heavily, or from being dehydrated
  • are pregnant
  • are taking one of many different types of medicines
  • have a lot of drugs or alcohol in the system

People can also have low blood pressure due to medical conditions, such as if they:

There is also a particular type of low blood pressure called ‘postural hypotension’ or ‘orthostatic hypotension’. In this condition, a person’s blood pressure is normal when they are sitting or lying down, but it drops suddenly when they stand, making them feel dizzy or lightheaded. This can also occur when standing too long without moving.

Postural hypotension is fairly common, particularly in older people. It can be caused by one of the situations or conditions listed above. If it happens often, or if it causes problems, you should see your doctor about it.

When should I see a doctor?

If you think you might have symptoms of low blood pressure listed above, it’s best to see your doctor.

How is low blood pressure treated?

If there is an underlying cause for your low blood pressure, and it is giving you problems, you may need treatment for that underlying cause. But if it isn’t causing you problems, treatment won’t be needed.

Your doctor may advise you to take precautions to prevent episodes of low blood pressure, such as avoiding dehydration, hot showers or standing up too quickly.

What’s the ideal blood pressure by age

Credit: Pixabay.

Ideally, we should all strive to have a blood pressure below 120/80mmHg. However, most people have blood pressure readings in the range of 120/80mmHg or 140/90mmHg.

What is blood pressure anyway?

Pressure is simply the amount of physical force exerted on an object. In this case, blood pressure refers to the force exerted by blood pushing against the walls of blood vessels.

When blood pressure is too high, a person’s arteries are subjected to a continuous strain that, in time, can lead to life-threatening cardiovascular disease.

What do the readings of blood pressure mean?

Blood pressure is measured in ‘millimeters of mercury’ (mmHg) and is read for two values. For instance, the optimal blood pressure is 120 over 80 or 120/80mmHg.

The first value represents the systolic blood pressure, which is the highest pressure that the blood reaches when the heartbeats.

The second value is the diastolic blood pressure, which corresponds to the lowest level of blood pressure that occurs when the heart’s muscles relax between beats.

Measuring your blood pressure with a blood pressure monitor is important because having a high reading (hypertension) is not something you can notice or feel.

However, if blood pressure is measured just once and found to be high, it doesn’t necessarily mean that it’s always too high. In order to get a reliable reading, blood pressure has to be measured on several different days while you are resting.

Signs and symptoms of high blood pressure

Usually, people cannot tell they have high blood pressure unless they have it measured. Anything above 140/90 is considered high blood pressure. However, occasionally people with high blood pressure report frequent headaches.

It’s important to note that your blood pressure will vary significantly and a single high blood pressure reading isn’t necessarily a cause for concern. If the reading is above this threshold after weeks of constant measurement, then you can safely presume that you may indeed suffer from hypertension.

Why blood pressure is so important to health

Although a blood pressure of 140 over 90 is considered normal, everyone should strive to lower it even further in order to stave off heart disease and strokes.

For instance, someone with a blood pressure reading of 135/85 is twice as likely to have a heart attack or stroke as someone with a reading of 115/75

An optimal blood pressure is paramount to the structural integrity of your arteries. Imagine a copper pipe in a water supply system — after many years, it will corrode and form micro-wears from all the friction between the water flow and the pipe’s walls. Eventually, it will break, but its operating life can be extended if the water pressure doesn’t cross a critical threshold.

While this analogy isn’t perfect (arteries don’t corrode and some damage can be healed), your arteries will naturally weaken with age after countless liters of blood flowing through them.

High blood pressure increases the risk of having a heart attack, which can cause heart failure. However, poor health outcomes extend beyond the cardiovascular system.

Why your blood pressure is too high

There are a number of reasons why a person may suffer from hypertension.

As we age, blood pressure typically increases due to the wear and tear accumulated by blood vessels over the years. There are also genetic factors that may influence blood pressure. For instance, African-Caribbean and South Asia communities tend to be at a higher risk of high blood pressure. High blood pressure can also run in the family.

All other things being equal, high blood pressure is typically the result of lifestyle choices, particularly diet. Too much salt, not enough fruits and vegetables, and drinking too much alcohol can increase blood pressure. Being overweight and not exercising can also substantially increase the risk of hypertension.

Blood pressure chart

If you made it this far then you now know how to correctly read your blood pressure but perhaps you’re not entirely sure how to interpret the measurement. The chart below is a good place to start, as it shows the ranges of high, low, and normal blood pressure readings.

You may have noticed that only one of the two values needs to be higher or lower to count as either high blood pressure or low blood pressure. For instance, if your top number (systolic blood pressure) is higher than 140, then you have high blood pressure regardless of your bottom value (diastolic blood pressure). Likewise, if your bottom number is higher than 90, then you have high blood pressure regardless of the top number’s reading.

What constitutes high blood pressure by age?

It’s normal for your blood pressure to increase as you age. The table below should give you a rough estimate of what healthy levels should look like.

Age Female Male
1 – 2 80/34 – 120/75 83/38 – 117/76
3 100/59 100/61
4 102/62 101/64
5 104/65 103/66
6 105/68 104/68
7 106/70 106/69
8 107/71 108/71
9 109/72 110/72
10 111/73 112/73
11 113/74 114/74
12 115/74 116/75
13 117/75 117/76
14 120/75 119/77
15 120/76 120/78
16 120/78 120/78
17 120/80 120/78
18 120/80 120/80
19-24 120/79 120/79
25-29 120/80 121/80
30-35 122/81 123/82
36-39 123/82 124/83
40-45 124/83 125/83
46-49 126/84 127/84
50-55 129/85 128/85
56-59 130/86 131/87
60+ 134/84 135/88

Ideal blood pressure by age.

Can your blood pressure ever be too low?

Low blood pressure, also known as hypotension, is generally anything below 90/60 mmHg. If any of the two values is lower than 90 or 60 for systolic and distolic blood pressure, respectively, this counts as having low blood pressure.

Generally, this is a good thing, because it means that the risk of a stroke or heart disease is minimal. Most people with hypotension do not require treatment.

There may be instances when a person’s blood pressure is low temporarily due to medication. And, sometimes, people can have low blood pressure naturally but this is no reason for concern in and of itself — although, in some instances, low blood pressure has been associated with depression.

However, if a patient feels dizzy or like fainting and blood pressure is low, a doctor’s appointment is warranted.

How to lower your blood pressure

You might be worried by your high blood pressure, but the good news is that it can be lowered to optimal levels with some proper foresight.

Although medication may be prescribed by a doctor in order to lower blood pressure, the safest course of action is to make long lasting lifestyle changes.

Diet is extremely important in this context. First and foremost, patients suffering from hypertension should be mindful of their salt intake. In fact, you may want to cut it out entirely out of your diet. Just remember that most of the salt you eat is actually found in products that are already prepared, such as breakfast cereals, ready-made meals, and bread. Be sure to check the nutritional facts label on the products you select from the supermarket.

Eating more fruits and vegetables can also help to lower blood pressure. A healthy amount is five portions of fruit and vegetables per day, where a portion weighs roughly 80 grams. Watch out for added salts when buying frozen or tinned fruits and vegetables from your local supermarket.

A healthy diet will also help you to mitigate another important risk factor for hypertension: being overweight. Exercising and a low-calorie diet can help you reduce your weight to more healthy levels — your blood pressure drops along with those extra pounds. Additionally, doing cardio also keeps the heart healthy.

Finally, be mindful of your alcohol intake. Both men and women should limit their alcohol consumption to 14 units per week, where a unit is equivalent to a small glass of wine or half a pint of beer.

What do your blood pressure numbers mean?: Heart Health 2019

We’ve all felt the blue Velcro cuff puff around our arms and waited in silence while a health care worker silently counted.

110 over 75: good.

124 over 75: bad.

131 over 80: yikes.

What?

Blood pressure readings can be difficult to decipher. We get these readings whenever we go to the doctor or dentist, yet there is little explanation of what the two numbers mean.

Here’s a quick guide:

The first number — the top number when written — is your systolic blood pressure. That is the measurement of how much pressure your blood exerts against your artery walls when your heart pumps.

The second is your diastolic blood pressure. That represents how much pressure your blood exerts on your artery walls when your heart is at rest.

Neither of these numbers is your heart beat.

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>>Vegan and keto diets can be good for your heart

>>Take care of your mouth and you could also be taking care of your heart

>>Heart attack signs and symptoms are different for women

>>Yes, fish oil drugs can protect your heart, say two major studies

>>New cholesterol guidelines include ethnicity as ‘risk-enhancing factor’

These two readings are made in millimeters of mercury – written as mm Hg — which is how pressure of all kinds is measured. Mercury is the element that made the first pressure gauges work.

OK, so you have the numbers. Now, what do they mean?

Both numbers can indicate cardiovascular disease or other problems when they are too high.

Often, the systolic blood pressure rating is the first indication of a problem. A normal blood pressure reading is when the systolic blood pressure number is less than 120 and the diastolic is less than 80.

If the systolic number is above 120, you are considered to have “elevated” blood pressure.

You reach “high” blood pressure — also the first stage of hypertension — when your systolic blood pressure reaches the 130 to 139 range or the diastolic blood pressure reading is between 80 and 90.

An automatic blood pressure monitor that can be used at home. (PR Newswire)PR NEWSWIRE

The second stage of hypertension comes when your systolic blood pressure is 140 or higher or your diastolic is 90 or higher.

If your systolic blood pressure reaches 180 or more or your diastolic is 120 or more, you need to see a doctor immediately. That is considered a crisis stage for hypertension.

Why it all matters:

Elevated blood pressure can easily reach high blood pressure if not addressed quickly. Once you reach high blood pressure, a doctor will likely prescribe changes to diet and exercise routines. You might also be put on medications.

If not addressed, medications become more likely and you run higher risks of heart attack or stroke.

If you reach the crisis stage, you could suffer organ damage or other sometimes fatal problems.

According to the American Heart Association, the risk of death from coronary heart disease and stroke doubles with every increase of 20 mm Hg in the first number and 10 mm Hg in the second number for people over 40 years old.

— Molly Harbarger

[email protected]

503-294-5923

@MollyHarbarger

Visit subscription.oregonlive.com/newsletters to get Oregonian journalism delivered to your email inbox.

The Role of Endothelin and Endothelin Antagonists in Chronic Kidney Disease – FullText – Kidney Diseases 2020, Vol.

6, No. 1

Abstract

Background: Endothelins (ET) are a family of peptides that act as potent vasoconstrictors and pro-fibrotic growth factors. ET-1 is integral to renal and cardiovascular pathophysiology and exerts effects via autocrine, paracrine and endocrine signaling pathways tied to regulation of aldosterone, catecholamines, and angiotensin. In the kidney, ET-1 is critical to maintaining renal perfusion and controls glomerular arteriole tone and hemodynamics. It is hypothesized that ET-1 influences the progression of chronic kidney disease (CKD), and the objective of this review is to discuss the pathophysiology, and role of ET and endothelin receptor antagonists (ERAs) in CKD. Summary: The use of ERAs in hypertensive nephropathy has the potential to decrease proteinuria, and in diabetic nephropathy has the potential to restore glycocalyx thickness, also decreasing proteinuria. Focal segmental glomerular sclerosis has no specific Food and Drug Administration-approved therapy currently, however, ERAs show promise in decreasing proteinuria and slowing tissue damage. ET-1 is a potential biomarker for autosomal dominant polycystic kidney disease progression and so it is thought that ERAs may be of some therapeutic benefit. Key Messages: Multiple studies have shown the utility of ERAs in CKD. These agents have shown to reduce blood pressure, proteinuria, and arterial stiffness. However, more clinical trials are needed, and the results of active or recently concluded studies are eagerly awaited.

© 2019 The Author(s) Published by S. Karger AG, Basel


Introduction

Endothelin (ET) is a 21 amino-acid peptide characterized in humans by 3 distinct genes with unique isoforms ET-1, ET-2, ET-3; all 3 are potent vasoconstrictors and pro-fibrotic growth factors 9 [1]. ET-1, however, is the predominant vascular isoform with the greatest regulatory effect on vascular tone and is integral in the regulation of renal and cardiovascular pathophysiology. ET-1 exerts effects via autocrine, paracrine and endocrine signaling pathways and regulates both catecholamines and the renin-angiotensin-aldosterone system (RAAS) [2, 3]. ET-1 activation is mediated by endothelin converting enzymes, which cleave ET from its precursor protein big-ET-1 into its biologically active component and C-terminal fragments [4-6]. Once activated, ET-1 has wide-ranging effects on multiple areas throughout the body, including vascular smooth muscle cells and endothelium (Fig. 1) [7]. ET-1 affects vascular smooth muscle cells following cellular uptake via clathrin-mediated endocytosis and is cleared by receptors in the lung and kidney [8-11]. ET synthesis is upregulated by gene transcription induced by angiotensin, vasopressin, interleukin-1, low extracellular pH, and cyclosporine A and can be decreased by prostacyclin, nitric oxide (NO), and natriuretic peptides [12].

Fig. 1.

Production and actions of ET-1 [7]. ET-1 begins as prepro-ET-1, is converted to big ET-1, and then ET converting enzyme cleaves it into the C-terminal fragments and biologically active ET-1. Biologically active ET-1 then goes out to exert its effects on the body, mediated by ETA and ETB receptors. ET-1, endothelin-1; ETA endothelin A; ETB, endothelin B; ETBR, ETB receptors.

ET effects are moderated by the particular isoform produced as well as the method of action utilized (paracrine, autocrine or endocrine). In addition, the downstream effect of ET is also dependent on the 2 G protein-coupled receptor isoforms (ETA and ETB). In the vasculature, binding of ETA triggers vasoconstriction and mitogenesis, leading to cellular and mesangial proliferation with fibrosis. Activation of ETA also releases adrenal catecholamines and increases inotropy, elevating blood pressure (Fig. 2) [2]. ETB activation exerts an anti-hypertensive effect via vasodilation from prostaglandin, NO, and natriuresis as well as anti-mitogenic effects, which inhibit cellular proliferation and inflammation (Fig. 2) [13, 14].

Fig. 2.

Effects of ETA versus ETB activation. This figure demonstrates the different downstream effects of ETAR and ETBR activation via ET-1. ET, endothelin; ETAR, ETA receptor; ETBR, ETB receptor.

In the kidney, ET-1 is a stress-induced regulator produced by the vascular endothelium, mesangial cells, and tubular epithelium with the greatest amount of activity expressed by principal cells in the medullary collecting duct [15]. ET activation can escalate progression of chronic kidney disease (CKD) via ET-1 and ETA mediated pro-fibrotic pathways, playing a role in diseases such as diabetic nephropathy (DN), hypertensive nephropathy, focal segmental glomerular sclerosis (FSGS), and autosomal dominant polycystic kidney disease (ADPKD) [16]. Early data suggest that antagonizing ET may be a promising therapeutic avenue. Preclinical and early phase clinical studies indicate that ET antagonists may delay glomerular injury, podocyte effacement, proteinuria, and eventual scarring and sclerosis. This article will provide a comprehensive review regarding the role of ET in renal pathophysiology and specifically CKD. PubMed/Medline was searched for relevant articles using keywords “chronic kidney disease,” “CKD,” “endothelin,” “ET-1,” “endothelin antagonist,” “diabetic nephropathy,” “hypertensive nephropathy,” “focal segmental glomerular sclerosis,” and “autosomal dominant polycystic kidney disease,” and “ADPKD.” Additionally, Clinicaltrials.gov was searched for recent/current clinical trials pertaining to ET and CKD.

ET and Renal Function

ET has widespread effects including regulation of blood pressure, modifying cardiac output, altering systemic vascular resistance, as well as modulation of central and peripheral nervous system activity [2]. ET-1 is critical to maintaining renal perfusion and influences glomerular arteriole tone and hemodynamics; endogenous renal ET-1 is also integral to fluid and sodium homeostasis [2]. ET’s final downstream effects can be oppositional and are mediated by the receptor isoform bound. In the renal cortex, ET-1 binding of ETA drives afferent vasoconstriction decreasing renal blood flow and glomerular filtration rate (GFR). Additionally, ET-1 binding of ETA has proinflammatory and sclerotic effects on the kidney and research has shown increased transgenic expression of ET-1 in rats promotes renal scarring, increasing interstitial fibrosis and glomerulosclerosis [1, 17-20].

Alternatively, ETB receptors (ETBR) are expressed by the endothelial cells of the vasa recta and afferent arterioles where increased circulating volume-activated production of ET-1 and binding of ETBRs initiates vasodilation via NO production, leading to greater perfusion of the renal medulla, decreased sodium reabsorption and natriuresis [14]. Research has shown that knockout of both ETAR and ETBR in murine collecting ducts leads to worsened hypertension as well as salt retention when compared to mice with only ETBR removed [21, 22].

There is conflicting evidence as to whether sodium transport in the proximal tubule is affected by ET [2]. However, in the medullary thick ascending limb of loop of Henle, ET-1 inhibits movement of chloride and indirectly contributes to natriuresis [7, 23, 24]. The collecting duct produces the highest levels of ET-1 in the kidney and is also the area with the highest concentration of ET receptors, with ETB as the dominant receptor in the collecting duct and renal medulla overall [2, 25-30]. In mice, knockout of collecting duct ET-1 impaired sodium excretion, suggesting that ET-1 plays a crucial role in sodium regulation [2, 31]. This process results in diuresis via prevention of sodium and thus water reabsorption, most particularly in the collecting duct due to its high concentration of ETB [2, 8, 9]. This experimental evidence suggests that ET-1 is necessary for routine regulation of sodium and fluid balance throughout the nephron. Loss of renal control over sodium and fluid homeostasis curtails the kidneys ability to compensate for changes in volume status and can negatively impact renal function

Role of ET in CKD

Glomerular injury and scarring is the hallmark of CKD progression regardless of the underlying disease and increased production of ET-1 has been found in multiple diseases associated with CKD including diabetes and insulin resistance, obesity, and dyslipidemia [10, 31], Renal ET-1 production is also increased by the aging process, growth factors, inflammatory cytokines, and proteinuria [31]. Schematic representation of various mechanisms by which ET-1 is involved in the causation of CKD by increased ET-1 production can be found in Figure 3. ET-1 binding of ETA stimulates renal fibroblasts, driving increased extracellular matrix synthesis, inducing collagen production, and mesangial cell proliferation with the secretion of fibronectin and type IV collagen furthering scar formation [10, 11]. Systemic acidification stimulates renal ET-1 production, leading to acid secretion in the proximal and distal nephron as a compensatory response. Progressive renal dysfunction further worsens metabolic acidosis and ET-1 secretion contributes to CKD progression via ET-1 and ETA mediated pro-fibrotic pathways [16]. Furthermore, studies have demonstrated the potent vasoconstrictive effect of ET-1 on renal vascular beds. Exogenous ET-1 has resulted in decreased GFR, increased filtration fraction, as well as sodium and fluid retention [32, 33].

Fig. 3.

Various mechanisms involved in the causation of CKD by ET-1 [31]. ETA endothelin A; CKD, chronic kidney disease; ETAR, ETA receptor.

Recently, stress of the endoplasmic reticulum (ER) has been proposed as a mechanism of ET-1 mediated renal tubular damage. Unfolded proteins accumulate in the ER, triggering the unfolded protein response (UPR). The UPR of the ER limits transcription and translation of proteins and upregulates ER chaperone expression in an attempt to fold the proteins already collected. Over time, this pathway can lead to organ damage and cell death, as is thought to be the case in renal disease [24, 35]. Research has shown an increase in both ET-1 and ER stress in renal diseases, such as DN and acute kidney injury due to contrast, ischemia/reperfusion, or septic shock [36-44]. At this time, it is unclear whether the ET-1 upregulates the UPR or vice versa [36].

ET and E-Receptor Antagonists in DN

DN is one of the leading causes of CKD and end-stage renal disease (ESRD) worldwide [45]. One in 3 diabetic patients will develop DN, a disease characterized by glomerular podocyte damage with glomerular proteinuria, loss of glomerular basement membrane integrity, increased mesangial cellularity, and tubular-interstitial sclerosis [46]. Progressive glomerular damage from diabetes is augmented by ET-1 production; hyperglycemia induces ET-1, which directly degrades podocytes’ cytoskeleton leading to cellular apoptosis and podocyte effacement [47, 48]. Via upregulated ETA receptors, the ETA-receptor/β-arrestin-1/Src-kinase complex is formed. This leads to the phosphorylation of β-catenin, increased Snail (family of zinc- finger transcription factors with a role in epithelial-mesenchymal transition [EMT]) expression and transactivation of epidermal growth factor receptor, which all contribute to podocyte damage [34, 49, 50]. Additionally, podocytes express ET receptors which when bound to ET-1 cause intracellular levels of calcium to quickly rise, influencing proliferation and signal transduction [14, 51]. ET-enhanced glomerular damage has been demonstrated in multiple animal models including the positive linear increase of ET-1 mRNA with progressive DN in rats. Well-described inflammatory mediators, including TNF-α and reactive oxygen species (ROS), have also been positively correlated with ET-1 mRNA in diabetic mice [52]. In a streptozotocin (STZ) induced type 1 diabetes rat model, antagonism of the ET system reduced renal damage from DN [53]. Furthermore, ETAR and ETBR were greatly overexpressed in the renal cortex of rats with STZ induced diabetes [14].

Antagonism of ET has also improved outcomes in human studies; atrasentan, an ETA antagonist, reduced albuminuria in patients with DN [54]. Withdrawal of atrasentan returned albuminuria to baseline. Unfortunately, due to the widespread physiological activity of ET across multiple organ systems, ET inhibition produces significant side effects and severely restricts individuals eligible for treatment and limits its clinical usefulness. For example, ETA antagonists have been contraindicated in patients with brain natriuretic peptide >200 pg/mL, history of heart failure, severe edema, or acute decrease in estimated GFR (eGFR) [54]. However, careful patient selection and use of diuretics may make ET inhibitors useful in CKD.

ETA antagonists can also improve glomerular permeability through non-hemodynamic mechanisms including improved glomerular glycocalyx production [45, 55]. The glomerular glycocalyx is a glycoprotein coating on the luminal surface of glomerular capillaries that is necessary for maintaining capillary integrity. Boels et al. [55] utilized apolipoprotein E deficient mice as a model as their renovascular damage, high blood glucose, and hyperlipidemia closely replicate the phenotype of metabolic syndrome. Intraperitoneal injections of STZ were given to induce DN [45, 55]. Researchers have found that ET-1 signals increased heparanase in podocytes, an enzyme that degrades heparan sulfate glycosaminoglycans: the major constituent of glycocalyx. This led to renal damage and proteinuria, as the glomerular glycocalyx could no longer function properly [56, 57]. Mice given atrasentan had significantly reduced murine heparanase expression and demonstrated increased glomerular glycocalyx levels compared to controls [55]. In vitro studies of human umbilical vein endothelial cells showed decreased capillary glycocalyx thickness after incubation in the serum of uncontrolled diabetics. Adding atrasentan to the cell culture with diabetic human serum resulted in the restoration of glycocalyx thickness [55]. These results suggest that ET plays a critical role in the progression of DN, as antagonizing ET receptors restored glycocalyx thickness.

Tubulointerstitial fibrosis (TIF) is a common endpoint of many kidney diseases including CKD and DN. Central to TIF is epithelial cells transition into the mesenchymal phenotype, a process known as EMT. During EMT, cell junctions are lost and collagen synthesis is diminished. EMT has been found to be essential during processes such as fibrosis, cancer development, and wound healing. Additionally, matrix metallopeptidase 9 activation contributes to loss of epithelial cell junctions, disrupting the epithelial cell membrane and furthering the EMT process. Contraction of the cytoskeleton and cell motility is initiated by phosphorylation of MYPT-1, a member of the ET-1 mediating the RhoA/ROCK pathway. Lastly, blockage of phosphorylation of Yes-associated protein leads to increased transcription of mesenchymal cell markers such as aSMA. All of these aspects of EMT combined with the addition of collagen lead to tubule-interstitial fibrosis [58]. In rat studies, renal tubular epithelial cells underwent EMT in the presence of hyperglycemia; this may in part be due to the high ET-1 secretion triggered by high glucose levels [58]. Seccia et al. [58] suggest that the predominant ET receptor mediating the pathway of EMT is the ETBR on proximal renal tubular cells. ETBR is mostly located on endothelial cells and induces the release of NO and prostacyclin upon activation, resulting in vasodilation [59]. ET-1 binding of ETBR results in decreased epithelial cells markers such as E-cadherin, while mesenchymal cell markers aSMA and vimentin increase. The role of the ETAR in this process is unclear at this time [58].

ET and Endothelin Receptor Antagonists in Hypertensive Nephropathy

Hypertension is the second leading cause of ESRD in the United States, second only to diabetes [60]. Renal damage caused by hypertension is multifactorial and in part driven by the interplay of the RAAS and ET. Angiotensin II triggers the release of aldosterone from the adrenal cortex, which in turn increases renal ET-1 expression. Angiotensin II also directly triggers the contraction of the vascular smooth muscle of both afferent and efferent arterioles. This eventually leads to decreased renal blood flow, as well as glomerular capillary hypertension [60]. Angiotensin II also induces nicotinamide adenine dinucleotide phosphate oxidase in vascular smooth muscle cells, which drives production of ROS and increases ET-1 expression in the kidneys. ET-1 constriction of the cortex and medullary vasculature further worsens renal blood flow and promotes renal fibrosis as previously discussed. ROS production contributes to increasing arteriolar tone by decreasing NO levels and is also pro-fibrotic [60].

Currently, RAAS inhibitors are the first-line therapy for hypertensive nephropathy [60]. By inhibiting activation of angiotensin I to angiotensin II, RAAS inhibitors cut off the cytokine cascade before it amplifies resulting in improved blood pressure, decreased proteinuria, and limiting renal fibrosis [60]. Kimura et al. [61] induced hypertension in rats by giving deoxycorticosterone acetate (DOCA)-salt. The rats had their right kidney removed, and were randomly divided into 4 treatment groups: (1) DOCA-salt only, (2) nitrogen oxide synthase inhibitor Nω-nitro-L-arginine (NOARG) with DOCA-salt, (3) ETA selective receptor antagonist ABT-627, DOCA-salt and NOARG, and (4) DOCA-salt, NOARG, and nuclear factor kappa B (NF-kB) inhibitor pyrrolidinedithiocarbamate. Rats in group 2 developed the more severe renal disease compared to DOCA-salt treatment only. Nitrogen oxide synthase blockade activates NF-kB, which is genetically upstream from ET-1. Thus, upregulation of NF-kB increases ET-1 and t potentiates negative renal effects. In group 3, antagonism of ET-1 prevented all kidney damage and malfunction. In group 4, pyrrolidinedithiocarbamate usage decreased NF-kB activation, renal injury, and excess ET-1 synthesis. These results imply that the NF-kB/ET-1/ETA pathway is a major mechanism for hypertensive renal damage [61]. Additional evidence comes from a transgenic rat model of hypertension where avosentan, an ETA receptor antagonist, was beneficial in decreasing albuminuria and mortality rates compared to control rats. Furthermore, dual therapy with endothelin receptor antagonist (ERA) and valsartan (angiotensin AT1 receptor antagonist) improved outcomes compared to treatment with ERAs or valsartan alone in this rat model [62].

Despite the promising research pointing to ERAs as a possible therapeutic option in hypertensive nephropathy, the side effect profile of ERAs must be considered before clinical application. The “ASCEND” trial tested the ERA, avosentan, and was halted prior to completion due to fluid retention leading to congestive heart failure and pulmonary edema [63, 64]. Baltatu et al. [62] sought to discover whether avosentan could be useful in the treatment of hypertensive nephropathy at lower dosages in transgenic rats in hopes of limiting fluid overload. It was found that only the avosentan at the highest dose (100 mg/kg) caused the fluid overload, while the decrease in blood pressure was approximately equivalent to the change observed at the second highest dose (10 mg/kg) [62]. Rats receiving no treatment experienced a 100% mortality rate. In contrast, survival rates of transgenic rats being treated with avosentan alone as well as rats receiving both avosentan and valsartan (an angiotensin AT1 receptor antagonist) were 55. 6 and 85.7% respectively [62].

ET and ERAs in FSGS

FSGS is a podocytopathy characterized by scarring and fibrosis of segments of glomeruli and is a significant cause of proteinuria, CKD and ESRD in the United States [65]. Primary FSGS is rare in adults and accounts for 5% of ESRD cases [65]. FSGS is more common in children, but the exact incidence is not well known. Previous studies estimated a pediatric incidence of 6.9%, but more recent studies have found rates up to 23% [66]. The molecular mechanisms driving the development of FSGS are also not completely understood. Genetic mutations of structural proteins vital to podocyte architecture and function are associated with primary FSGS [67]. Alternative mechanisms include circulating factors, which damage podocytes with loss glomerular basement protein integrity and subsequent proteinuria [68]. ET has been a candidate protein and has been shown to cause pathologic changes in podocytes similar to those seen in FSGS [50]. Cultured podocytes treated with ET-1 lost cell markers indicative of podocytes including synaptopodin and acquired mesenchymal cell markers, such as aSMA. This cellular transition is similar to the EMT seen in TIF [50]. Daehn et al. [69] demonstrated that increased production of ET in FSGS also damages podocytes through oxidative stress with the injury of glomerular endothelial cells’ mitochondria and promotes adjacent podocyte apoptosis.

Despite the morbidity of FSGS, there has yet to be a specific treatment approved by the Food and Drug Administration in the United States. Therefore, the primary goal of FSGS treatment is to decrease proteinuria and first-line therapy includes a combination of corticosteroids and ACE inhibitors or angiotensin receptor blockers (ARB). Second-line therapy includes calcineurin in­hibition, typically with cyclosporine or tacrolimus [70]. Antagonizing the ET system has shown promise for decreasing proteinuria and slowing renal damage in FSGS. Buelli et al. [50] utilized the Adriamycin-induced FSGS murine model and found that these mice characteristically demonstrate an elevated renal ET-1 with parietal epithelial cells activation, pseudo-crescents formation, and eventually, Adriamycin-induced injury with progression to glomerular sclerosis. Treatment with ERAs mitigated cellular injury and inflammation with significantly improved renal function in these mice.

ET and ERAs in ADPKD

ADPKD is a disease of autosomal dominant inheritance that consists of prolific renal cyst formation that interferes with normal renal function [71]. Incidence is estimated to range between 1:400 and 1:1,000, thus rating as one of the most commonly inherited renal disorders [72]. ET-1 is integral to cyst development and fibrotic progression of ADPKD [20, 73]. ET-1 effect on renal dysfunction in ADPKD is mediated in 3 main areas. First, ET-1 modulates gene expression in response to glomerular and tubule injury by stimulating interstitial fibroblasts to express type I collagen and smooth muscle actin. Renal cyst formation and glomerular fibrosis have thus resulted from transgenic overexpression of ET-1 in murine studies. Second, ET and its receptors are increased in ADPKD affected kidneys. In mice, ETA mRNA is increased 5–10 times in ADPKD kidneys vs. healthy controls [74]. Research suggests that as kidney disease progresses and function decreases, urinary ET-1 is increased [32, 75]. Human ADPKD patients have increased ET-1 levels in cyst walls and fluid; furthermore, urinary levels of ET-1 are higher in ADPKD patients compared to controls [76, 77].

The association of ET with ADPKD could mechanistically be linked through hypertension, given ET’s many regulatory effects on renal and systemic blood pressure. However, Merta et al. [78] demonstrated that ET-1 and NO levels were significantly elevated in ADPKD patients vs. controls. Furthermore, there was no difference in ET-1 or NO levels when comparing normotensive to hypertensive ADPKD patients. This suggests that increased ET levels in ADPKD are independent of arterial hypertension [78]. Additional data suggested that imbalance between ETAR and ETBRs may be implicated in ET and disease pathogenesis of ADPKD [74]. One human study found the upregulation of ETA receptors in renal arteries, glomeruli, and cystic epithelial cells in ADPKD patients but no significant difference in ETBR levels compared to controls. Furthermore, there is evidence that ET receptors have different effects and Chang et al. [79] demonstrated that ETB blockade accelerated cystic disease progression while ETA blockade leads to tubular cell proliferation.

Current treatment for ADPKD centers on symptom reduction and slowing disease progression [80]. Targeted medication includes sirolimus (mTOR inhibitor), octreotide (a somatostatin analog), and/or tolvaptan (a selective vasopressin V2 receptor antagonist) [81]. Sirolimus and similar drug everolimus have been shown to decrease the rate at which total kidney volume (TKV) increases, however current evidence suggests they do not slow disease progression and renal damage as measured by eGFR [81-83]. Octreotide also slows increasing TKV, but like sirolimus, it has no effect on decreasing renal function [81, 84-86]. Tolvaptan has also been shown to slow increasing TKV and Torres et al. [87] demonstrated a significant reduction in loss of kidney function vs. placebo, with declining kidney function measured as a 25% decrease in the reciprocal serum creatinine level [81].

ET-1 also has utility as a noninvasive biomarker to identify disease progression in high-risk ADPKD patients. This is especially useful since disease markers such as eGFR do not change until significant renal damage has already occurred [77, 88]. Raina et al. [77] found that urinary ET-1 positively correlated with TKV, which serves as a marker for cyst enlargement (r = 0.426), however, this correlation was not statistically significant (p = 0.1) and warrants further clinical investigation.

Clinical Trials Evaluating ERAs for CKD Management

All the available clinical trials involving ERAs for CKD management are summarized in Table 1. In a study by Kohan et al. [89], it was found that atrasentan at doses of 0.75 mg and 1.75 mg/day significantly improved residual albuminuria in type II diabetes mellitus patients who were already on renin-angiotensin system blockers. Short-term results of the ASCEND study investigating the effect of ERA, avosentan, on progression of overt DN showed that avosentan significantly reduced albuminuria when added to renin-angiotensin system blockers. However, the trial was terminated prematurely after a median follow-up of 4 months due to higher cardiovascular adverse events, including fluid overload, congestive heart failure, and death [64].

Table 1.

Clinical trials of endothelin antagonists in chronic kidney disease conditions

The “Study of DN with Atrasentan” (SONAR) phase III trial was meant to determine the efficacy of atrasentan (an ERA) to treat type II DN and delay progression of kidney disease by decreasing the urine albumin-to-creatinine ratio (UACR) [90]. This trial was different than ASCEND and similar studies as it utilized a response enrichment design, where the trial only included patients likely to benefit from the experiment. Subjects included in the trial went through a Run-In Period to optimize RAS inhibitor dosage followed with the enrichment period with atrasentan to determine UACR. Afterwards, responders and non-responders were included in a double-blind treatment period [91, 92]. However, AbbVie terminated this study in 2018 due to lower than expected renal end points; not due to any safety concerns for the participants [93]. Another study that was meant to test the renoprotective effect of ERA, bosentan, was terminated due to problems in recruitment [94]. Lin et al. [95] investigated the effect of atrasentan in DN and found that up to 46% reduction in UACR can be attained without having a significant difference in the adverse effect of peripheral edema compared to controls. Further, Webb et al. [96] investigated whether changes in thoracic bioimpedance can serve as an indicator of fluid retention secondary to atrasentan in DN patients. Thoracic bioimpedance measurement has its application in congestive heart failure, as decreased thoracic bioimpedance is a sensitive indicator of pulmonary congestion even before the development of heart failure. However, in this study by Webb et al. [96], no correlation was found between thoracic bioimpedance and edema or weight gain in patients on atrasentan therapy.

A phase 2 study evaluating the efficacy and safety of sparsentan in FSGS patients (DUET study) was done to evaluate if first-in-class sparsentan decreased proteinuria in primary FSGS patients compared to ARB (irbesartan) treatment alone [97]. Sparsentan functions as both an ETA receptor antagonist and an angiotensin 1 receptor blocker. Patients were divided into 2 treatment arms: those receiving 300 mg of irbesartan once daily, and those receiving oral sparsentan (200, 400, or 800 mg) once daily [97]. The results of the study showed that the 8-week course of sparsentan was safe, well tolerated and resulted in significant reduction in proteinuria compared to irbesartan [97]. Dhaun et al. [98] evaluated the effect of ERA, sitaxsentan, in nondiabetic proteinuric CKD patients and found that the drug significantly decreased 24-h proteinuria, protein: creatinine ratio, blood pressure, and pulse wave velocity compared to placebo.

Another study was the “Zibotentan Better Renal Scleroderma Outcome Study”, which ran from October 2014 to 2017 per ClinicalTrials.gov. Zibotentan Better Renal Scleroderma Outcome Study was a phase II investigation of zibotentan, an ERA, and its effect on the progression of kidney disease due to scleroderma. The primary outcome measurement was soluble vascular cell adhesion molecule 1 level, which are reflective of renal involvement in scleroderma. Whether these levels were measured via the blood or the urine is unclear and the results of the study have not yet been published [99]. A different study by Bérézne et al. [100] tested the effect of bosentan in scleroderma renal crisis patients and found no improvement in renal outcomes.

Side Effects of ERAs

The side effect profile of ERAs is substantial and may limit their clinical usefulness. The most common adverse effect among ET blockers is fluid retention, which is due to ETB/ETA blockade. This blockade leads to a decrease in NO and PGE2 causing an increase in sodium and water reabsorption. “Dual” antagonists have an ETA: ETB selectivity <100-fold while selective antagonists work on ETA, thus theoretically resulting in less fluid retention. Individual ERAs have specific side effects that must be monitored including hepatotoxicity with patients on sulfonamide-based ERAs [101-103]. ETA/ETB antagonism is teratogenic, thus contraindicated during pregnancy, but this may be less of a concern in the aging CKD population [21]. Testicular toxicity is another rare, but serious side effect [31]. There are strict patient populations to be avoided due to the many side effects of ERAs including severe CKD and congestive heart failure which may complicate fluid retention management [31]. The “ASCEND” trial tested avosentan but was halted due to the dangerous retention of fluids [63, 64]. SONAR trial showed good outcomes when ERAs were used with diuretics [90]. Thus, a therapeutic potential may be possible at either lower dosages or if ERA’s were utilized in concert with CKD fluid management strategies aimed at ameliorating the dangerous side effects found in this drug class. In addition, any future clinical trials of ERAs for CKD will likely need to include ERA in addition to rather than in place of standard of care, which at present includes an ACEi/ARB, but could potentially be expanded to SGLT2i in the near future.

Conclusion

ETs are a family of potent vasoconstrictors and pro-fibrotic growth factors and its receptors (ETA and ETB) are integral in the regulation of renal and cardiovascular pathophysiology. However, ET activation can escalate the progression of CKD and data has suggested that antagonizing ET may be a promising therapeutic avenue. Multiple studies have shown the utility of ERAs in both diabetic and nondiabetic CKD by reducing blood pressure, proteinuria, and arterial stiffness. However, there have been no studies to date demonstrating that ERAs improve clinical outcomes in CKD. Multiple large clinical trials are needed, and the results of active or recently concluded studies are eagerly awaited for analysis and comparison to current data.

Acknowledgments

We thank Ms. Jennifer L. Clark, Grant/Medical Writer, Rebecca D. Considine Clinical Research Institute and Akron Children’s Hospital for her assistance in language editing.

Disclosure Statement

The authors have no conflicts of interest to disclose and the results in this paper have not been published previously in whole or part.

Funding Sources

There are no funding sources to declare.

Author Contributions

All authors have equally contributed to this paper.

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Author Contacts

Rupesh Raina, MD, FAAP, FACP, FASN, FNKF

Adult-Pediatric Kidney Disease/Hypertension, Department of Nephrology,

Cleveland Clinic Akron General and Akron Children’s Hospital

224 W Bowery St, Akron, OH 44307 (USA)

E-Mail [email protected]


Article / Publication Details

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Received: August 01, 2019
Accepted: October 30, 2019
Published online: December 18, 2019

Issue release date: January 2020


Number of Print Pages: 13

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ISSN: 2296-9381 (Print)
eISSN: 2296-9357 (Online)


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Vegetarian diet: panacea for modern lifestyle diseases? | QJM: An International Journal of Medicine

Abstract

We review the beneficial and adverse effects of vegetarian diets in various medical conditions. Soy-bean-protein diet, legumes, nuts and soluble fibre significantly decrease total cholesterol, low-density lipoprotein cholesterol and triglycerides. Diets rich in fibre and complex carbohydrate, and restricted in fat, improve control of blood glucose concentration, lower insulin requirement and aid in weight control in diabetic patients. An inverse association has been reported between nut, fruit, vegetable and fibre consumption, and the risk of coronary heart disease. Patients eating a vegetarian diet, with comprehensive lifestyle changes, have had reduced frequency, duration and severity of angina as well as regression of coronary atherosclerosis and improved coronary perfusion. An inverse association between fruit and vegetable consumption and stroke has been suggested. Consumption of fruits and vegetables, especially spinach and collard green, was associated with a lower risk of age-related ocular macular degeneration. There is an inverse association between dietary fibre intake and incidence of colon and breast cancer as well as prevalence of colonic diverticula and gallstones. A decreased breast cancer risk has been associated with high intake of soy bean products. The beneficial effects could be due to the diet (monounsaturated and polyunsaturated fatty acids, minerals, fibre, complex carbohydrate, antioxidant vitamins, flavanoids, folic acid and phytoestrogens) as well as the associated healthy lifestyle in vegetarians. There are few adverse effects, mainly increased intestinal gas production and a small risk of vitamin B12 deficiency.

Introduction

Lifestyle diseases such as obesity, diabetes mellitus, hyperlipidaemia, hypertension, coronary artery disease and cancer are common in industrialized countries. There is considerable epidemiological evidence suggesting that a vegetarian lifestyle is associated with a lower risk for these diseases. The beneficial effects could be due to the diet as well as the healthy lifestyle, which includes desirable weight, regular physical activity, and abstinence from smoking, alcohol and illicit drugs.1 We have already reviewed the different types of vegetarian diets and their relevance to renal disease. 2 Briefly, vegetarian diets are lower in energy and their percentage of energy from fat and cholesterol, with higher fibre and folate content than a normal mixed diet. These result in lower body weight, blood pressure and plasma lipid levels than in omnivores. The vegetarian diet has beneficial effects on the renal haemodynamic response to protein, progressive renal disease, proteinuria and glomerulosclerosis, blood pressure and hyperlipidaemia in nephrotic syndrome. We now review the beneficial and adverse effects of vegetarian diets on primary hyperlipidaemia, diabetes mellitus, cardiovascular disease, stroke, dementia, neural-tube defects, age-related macular degeneration, gastrointestinal disease and cancer.

Diabetes

Diets rich in fibre and complex carbohydrate and restricted in fat improve control of blood glucose concentration,3 delay glucose absorption,4 lower insulin requirements,5 increase peripheral tissue insulin sensitivity,6 decrease serum cholesterol and triglyceride values,3,5 aid in weight control7 and lower blood pressure in diabetic patients. 8 Studies using high-carbohydrate and high-fibre diets reported an average 40% reduction of insulin doses,9–11 a 6–27% reduction in fasting serum glucose values9,11 and a 10–32% reduction in serum cholesterol values.9–11

Cardiovascular disease

Studies have shown an inverse association between fruit, vegetable and fibre consumption and the risk for coronary heart disease. Inverse relations between vegetable consumption and myocardial infarction (odds ratio, OR, 0.79 for the highest tertile) and angina pectoris (OR 0.89) were seen in an epidemiological study of 46 693 subjects in Italy.12 Two epidemiological studies suggest that frequent consumption of nuts may provide some protection against coronary heart disease. In the Adventist Health Study, which was a prospective cohort investigation of 31 208 Seventh-Day Adventists, subjects who consumed nuts more than four times per week, had fewer definite fatal coronary heart disease events (relative risk, RR, 0. 52) and definite non-fatal myocardial infarction (RR 0.49), when compared with those who consumed nuts less than once per week. This was independent of traditional coronary risk factors such as blood pressure and relative weight, and other foods that were available for analysis, and was seen in both stratified and proportional hazards multivariate analyses.13 The nuts consumed were peanuts (32%), almonds (29%), walnuts (16%) and other nuts (23%). In the Iowa Women’s Health Study, 41 837 postmenopausal women were studied. Coronary mortality was inversely associated with nut intake in these women (RR 0.43 in women consuming nuts 2–4 times per week) after adjusting for multiple factors such as age, energy intake, body mass index, waist-hip ratio, presence of hypertension and diabetes, smoking status, use of hormone replacement therapy, alcohol intake, and level of physical activity and education.14

In a randomized, single-blind prospective interventional trial in 406 patients subjected to dietary intervention for 6 weeks, 24–48 h after acute myocardial infarction, a vegetarian diet resulted in significant decrease (34. 5%) in total cardiac end points, including non-fatal (17 vs. 25) and fatal (8 vs. 12) acute myocardial infarction, and sudden cardiac death (4 vs. 7), compared to a control diet.15 Complications such as angina pectoris, electrocardiographic changes after exercise, left ventricular hypertrophy, and ventricular ectopics (>8/min) were significantly decreased in the group eating a vegetarian diet, compared with those eating the control diet. After 1 year follow-up, cardiac events (non-fatal acute myocardial infarction, fatal acute myocardial infarction, and sudden cardiac deaths) occurred significantly less often in the intervention group than in the control group (50 vs. 82, p<0.001).16 The mean age, sex, mean body weight, blood pressure, lipoproteins, risk factors, complications, electrocardiographic changes, initial level of cardiac enzymes, drug therapy and dietary intake (mean energy, total fat calories, polyunsaturated/saturated fat ratio, dietary cholesterol, fibre and salt) were similar in both groups at entry to the study.

In four patients who had severe angina pectoris, the angina resolved within 3–18 months on instituting a vegan diet. When the health of vegans and age- and sex-matched omnivore controls using the Cornell Medical Index was assessed, female vegans had fewer symptoms of cardiovascular disease.17 In a short-term (24 days) study, stress management training (stretching/relaxation exercise and meditation) and a vegan diet produced improvements in 23 patients with ischaemic heart disease when compared with a non-intervention control group. There was a 44% mean increase in duration of exercise, a 55% mean increase in total work performed (bicycle ergometry), improved left ventricular regional wall motion and ejection fraction during exercise (exercise radionuclide ventriculography) and a 91% mean reduction in frequency of anginal episodes.18 In two prospective randomized, controlled trials, 50 patients who were subjected to comprehensive lifestyle changes (low fat, vegetarian diet, stopping smoking, stress management training and moderate exercise) for 1 year showed significant overall regression of coronary atherosclerosis as measured by quantitative coronary arteriography. Degree of adherence was directly correlated with changes in percentage diameter stenosis. In contrast, patients in the usual-care control group showed significant overall progression of coronary atherosclerosis.19,20 There were also reductions in the frequency (91%), duration (42%) and severity (28%) of angina in the experimental group. In contrast, control group patients reported a rise in frequency (165%), duration (95%) and severity (39%) of angina.19 The design of the three studies18–20 does not allow the determination of the relative contribution of each component of the intervention. There were significant reductions in total cholesterol (20.5–24.3%), LDL cholesterol (37.4%) and triglycerides (15.5%) in the intervention group compared to the control group, suggesting a significant dietary contribution.

Stroke

Mortality from stroke has been declining for many decades in Europe and North America. This decline in mortality has been attributed to multiple factors, including the increased consumption of fruits and vegetables.21 An inverse association between fruit and vegetable consumption and stroke has been suggested.22–24 In a population-based longitudinal study of 832 middle-aged men over 20 years of follow-up, for each increment of three servings of fruit and vegetable per day, there was a 22% decrease in the risk of all stroke.24 Similar results were observed for transient ischaemic attack and completed stroke, both ischaemic and haemorrhagic.

The protective effect of fruit and vegetables may be related to their potassium, antioxidant, α-linolenic acid and folate content, as well as their ability to lower serum cholesterol and blood pressure. The vegetarian diet has a blood-pressure-lowering effect.2 Increased potassium intake may decrease risk of stroke by lowering blood pressure as well as by mechanisms independent of its effect on blood pressure, as indicated by animal studies. 25 The inverse association of low plasma carotene, vitamin C levels and vitamin C intake with risk of stroke,26,27 and preliminary data from the Nurses’ Health Study28 both suggest a protective role for dietary antioxidant vitamins. A prospective study over 12 years involving 2974 middle-aged men in Switzerland showed that men with low plasma concentrations of both ascorbic acid and β-carotene had four times the risk of dying of stroke.26 In a cohort study of 730 elderly men and women in the UK followed for 20 years, stroke among those in the highest tertile of vitamin C intake (mean >45 mg per day) was significantly reduced (RR reduction, RRR, 50%) compared to the lowest tertile (mean <28 mg per day). A similar gradient of risk was present for plasma ascorbic acid concentration (RRR 30%).27 In 87 245 US female nurses, the RR of ischaemic stroke was 0.55 in women in the highest quintile of antioxidant vitamin score compared with those in the lowest. Carotene intake was the predominant contributor to the reduced risk, with modest contributions from vitamins C and E.28

Analysis of the Multiple Risk Factor Intervention Trial (MRFIT) suggests that higher levels of α-linolenic acid are independently associated with lower risk of stroke in middle-aged men at high risk for cardiovascular disease.29 A standard deviation increase (0.13%) in the serum level of α-linolenic acid was associated with a 37% decrease in the risk of stroke (p<0.05). The role of folic acid will be discussed in the section on cardiovascular disease.

Although serum cholesterol is a major determinant of atherosclerosis, its role in the pathogenesis of stroke is unclear. However, recent trials of statins for secondary prevention of coronary artery disease have consistently shown that lowering lipid levels results in lower risk of stroke as well as coronary events.30–32 Epidemiological studies indicate an inverse association between dietary intake of fat and saturated fat, and risk of stroke, supporting a beneficial effect. 33,34 The vegetarian diet, which includes fruits, vegetables, complex carbohydrates, soy bean, legumes, nuts and soluble fibre, could thus lower the risk of cardiovascular disease through multiple mechanisms such as lowering of cholesterol and the beneficial effect of antioxidant vitamins, folic acid, linolenic acid and fibre.

Mechanisms of cardiovascular prevention

At least part of the beneficial effects of vegetarian diet, with or without other lifestyle changes, probably results from a hypolipidaemic effect. In addition, vegetarian diets reduce weight and blood pressure, further improving primary and secondary prevention.

Soybean

Vegetable proteins are useful for the treatment of human hyperlipidaemia. A soy-bean-protein diet lowered the serum cholesterol to a greater degree than did a low-cholesterol, low-saturated-fat diet containing an equivalent amount of protein of animal origin. 35–37 Substantial decreases were observed in both serum cholesterol (21% after 3 weeks) and triglycerides, in patients with type IIa and IIb hyperlipoproteinaemia, including some with familial hypercholesterolaemia.35,36 A recent meta-analysis of 38 human studies derived from 29 articles with a total of more than 740 subjects showed that the consumption of soy protein resulted in significant decreases in total cholesterol (0.60 mmol/l; 9.3%), low-density lipoprotein (LDL) cholesterol (0.56 mmol/l; 12.9%) and triglycerides (0.15 mmol/l; 10.5%).38 There were no significant changes in high-density lipoprotein (HDL) cholesterol or very-low-density lipoprotein (VLDL) cholesterol concentrations. The magnitude of the lipid changes was greatest in those with the highest initial plasma cholesterol concentrations. Soy protein intake averaged 47 g per day. It was estimated that the ingestion of 25 or 50 g of soy protein per day could decrease serum cholesterol by 8. 9%.38 An intake of 30 g soy protein can be obtained by drinking two cups of soy milk and consuming one serving of meat analogue. The mechanisms of the hypocholesterolaemic effect of soy protein are unknown. It has been suggested that the beneficial effect of soy may be the result of the amino-acid pattern and peptide structure of the soy protein39 as well as from non-protein compounds such as isoflavones or phytoestrogens and saponins.38–40

Legumes

Leguminous seeds lower serum cholesterol in man.41–44 Substitution of chick peas for wheat flour decreased serum cholesterol levels by 22% by the end of 55 weeks.41 Consumption of 30 g dried legumes daily over a 3-month period resulted in a 16% decrease in serum cholesterol in hyperlipidaemia patients, compared to a 8.7% decrease in normal volunteers studied under similar conditions.42 Substitution of about 140 g dried beans (kidney, pinto, chick pea, green and red lentils) daily for other sources of starch over a 4-month period in hyperlipidaemic patients resulted in a 7% decrease in total serum cholesterol and a 25% reduction in serum triglycerides. There were no significant changes in LDL and HDL cholesterol levels.43

Nuts

Nuts are rich in protein, monounsaturated fatty acids (oleic acid), vitamins (vitamin E, B6, folic acid and niacin), minerals and fibre.45 Walnuts are, however, rich in polyunsaturated fatty acids (linoleic and α-linolenic acids). Nuts are classified as part of the USDA Food Guide Pyramid’s Meat/Meat Alternate Group and in the Mediterranean and Asian diet pyramids, have been placed on the same level as fruits, vegetables and legumes.45

Walnuts,46,47 macadamia,48 almonds,47,49 and hazelnuts46 have cholesterol-lowering properties, and a beneficial effect on the lipoprotein profile. In controlled, randomized, crossover study in 18 normocholesterolaemic men, diets rich in walnuts decreased total cholesterol (0.58 mmol/l; 12.4%), LDL cholesterol (0. 47 mmol/l; 16.3%) and triglycerides (0.11 mmol/l; 8.3%). Although HDL cholesterol was lowered by 4.9%, the LDL cholesterol to HDL cholesterol ratio was lowered significantly by 12.0%. Likewise, a randomized controlled, crossover-designed study in 30 healthy subjects showed a macadamia-nut-based, high-monounsaturated-fat diet lowered serum total cholesterol and LDL cholesterol within 4 weeks.

Soluble fibre

Soluble fibres are abundant in fruits, dried beans, legumes, guar gums, barley, psyllium and oat cereals and can lower blood lipid levels.50–52 A meta-analysis of 20 trials using oat products revealed that about 3 g per day of soluble fibre from oat products (28 g oat bran) can lower total cholesterol levels by 0.13–0.16 mmol/l, and the reduction is greater in those with initially higher blood cholesterol levels.53 Oat bran is more effective in lowering cholesterol than wheat bran or oatmeal, as it contains more water-soluble fibre β-glucan. 54 A high intake of soluble fibre can further reduce plasma cholesterol even after marked reductions in dietary saturated fat and cholesterol have been achieved. A crossover study in 43 volunteers with hyperlipidaemia subjected to a metabolic diet high in soluble fibre, but low in saturated fat and cholesterol, demonstrated a fall in total cholesterol by 4.9% and LDL cholesterol by 4.8% during the soluble-fibre period.55

Calorie restriction

Vegetarian diets are lower in energy and percentage of energy from fat and cholesterol, and vegetarians have lower body weight than omnivores.56–58 There is evidence that a low-energy diet can modulate blood lipids59 and reduce atherosclerosis and coronary deaths,60 and weight reduction may be associated with reduction in coronary artery disease and all its risk factors.61,62 With a fat-modified diet, even modest weight reduction (4. 5 kg) by obese people results in a 30% or 40% greater fall in the level of cholesterol than that resulting from the qualitative change in fat intake alone.63,64 Weight reduction may also reduce cardiac enlargement, left ventricular strain, post-exercise electrocardiographic changes and arrhythmias,61,65 possibly by reducing myocardial oxygen requirements and having other beneficial effects on cardiac indices.62

Antioxidant effects

The beneficial effect of vegetarian diet on cardiovascular disease could also be due to the presence of antioxidant vitamins such as vitamin E, vitamin C and β-carotene and flavanoids as well as folic acid, linolenic acid and fibre in fruits and vegetables. Oxidation of LDL cholesterol is an important step in the pathogenesis of atherosclerosis.66 Vitamin E,67 vitamin C,68β-carotene69 and flavanoids70 prevent the oxidation of LDL cholesterol. Four large prospective epidemiological studies found that high doses of vitamin E intake or supplementation were associated with a significant reduction in cardiovascular diseases.71–74 The relative risk reductions (RRR) ranged from 31% to 65%. Studies involving β-carotene and vitamin C gave less consistent reductions in cardiovascular disease, the RRR ranging from −2% to 46%, and −25% to 51%, respectively.71–73,75–77 Three other epidemiological studies have suggested a role for flavanoids, especially quercetin, in the prevention of coronary artery disease.78–81 However, all82–89 but one90 prospective randomized trial did not show reductions in cardiovascular disease with vitamin E, vitamin C or β-carotene supplementation. However, the prospective trials were designed to study cancer, not cardiovascular disease (fatal or non-fatal cardiovascular disease outcomes) and probably used suboptimal doses of vitamin E. 91 Furthermore, the prospective studies were of limited duration (usually a few years) and usually commenced in middle age when atherosclerosis may be well established, in contrast to epidemiological studies where intake is protracted (several years or decades) and started at a much younger age when the atherosclerosis is in the early stages.91 Ongoing large-scale and planned long-term randomized trials designed specifically to evaluate effects on cardiovascular disease will help to resolve this controversy.

Folic acid and homocysteine

An elevated plasma homocysteine concentration is an independent risk factor for atherosclerosis of coronary, cerebral and peripheral vessels92 and for deep-vein thrombosis.93 One study found that 28–42% of patients with premature vascular disease had hyperhomocysteinaemia.94 In the Physicians’ Health Study, 14 916 male physicians were prospectively followed for about 5 years. 95 Men with plasma homocysteine concentrations that were 12% above the upper limit of normal had about a three-fold increase in the risk of myocardial infarction, as compared with those with lower levels, even after correction for other risk factors. A meta-analysis of 27 studies indicated that 10% of the risk of coronary artery disease in the general population is attributable to homocysteine.96 An increase of 5 μmol/l in the plasma homocysteine concentration raised the risk of coronary artery disease by as much as an increase of 0.52 mmol/l in the cholesterol concentration.96 A prospective study involving 587 patients with angiographically-documented coronary artery disease showed a graded association between plasma homocysteine concentrations and overall mortality.97 In a cross-sectional study of 1041 elderly subjects in the Framingham Heart Study, high plasma homocysteine concentrations and low concentrations of folate and vitamin B6 were associated with an increased risk of extracranial carotid artery stenosis. 98 There was a graded relation between plasma homocysteine and the risk of carotid stenosis. Likewise a graded increase in the relative risk of stroke with increasing serum homocysteine concentration was seen in a nested case-control study.99 Total plasma homocysteine concentration was also found to be an independent risk factor for stroke and arterial thrombosis in patients with systemic lupus erythematosus.100

The predominant cause for elevated homocysteine blood concentrations is inadequate blood folate.101 Folic acid supplementation has been shown to be highly effective in reducing plasma homocysteine levels.96 Total homocysteine concentrations reach a reduced plateau when the folate intake approaches 400 μg/day.101 It has been estimated that a folic acid increase of about 200 μg/day results in an average reduction of 4 μmol/l in total homocysteine concentration and an increase in folic acid intake of 350 μg per day in men and 280 μg per day in women would potentially prevent 30 500 and 19 000 deaths from vascular causes per year, respectively, in the US. 96

Results from the Nurses’ Health Study demonstrated a significant inverse relation between dietary intake of folate and vitamin B6, and mortality and morbidity from cardiovascular disease during a follow-up of 80 082 women over a 14-year period.102 The RR of coronary heart disease between extreme quintiles were 0.69 for folate and 0.67 for vitamin B6 and 0.55 for both folate and vitamin B6. The magnitude of the inverse association for folate was similar to their parallel study among male health professionals.103 Each 100 μg/day increase in folate was associated with a 5.8% lower risk of coronary heart disease.102 In a retrospective cohort study of 5056 men and women aged 35–79 years, there was a 69% increased risk of coronary mortality among those in the lowest quartile as compared with the highest quartile of serum folate.104 In a small uncontrolled study of 38 patients with atherosclerosis of the carotid arteries, supplementation with folic acid, pyridoxine and vitamin B12 was associated with regression of plaque after a mean follow-up of 4. 4 years.105 Prospective, randomized, controlled trials will be necessary to determine the effect of folic acid supplementation on cardiovascular mortality.

Unsaturated fats

An inverse association between linolenic acid intake and coronary heart disease has been observed in several studies.106–108 In 43 757 US health professionals followed-up for 6 years, intake of linolenic acid was inversely associated with risk of myocardial infarction.107 The RR for a 1% increase in linolenic acid intake was 0.53 after adjustment for standard risk factors and intake of fibre, and 0.41 after further adjustment for intake of total fat. In a prospective secondary prevention trial, a Mediterranean α-linolenic-acid-rich diet was associated with lower cardiac deaths and non-fatal myocardial infarction.108 The risk ratio for both these endpoints combined was 0.27. The incidence of coronary disease is low in Japan, where the diet is rich in linolenic acid. 109 Foods rich in α-linolenic acid include green leafy vegetables, soybean products, grapeseed oil, canola oil, purslane, walnuts, hazelnuts and flax seed. The cardioprotective effects of α-linolenic acid may be due to its beneficial effects on platelet reactivity110 and arrhythmia.111

Fibre

In a prospective cohort study of 43 757 US male health professionals followed-up for 6 years, the age-adjusted RR for total myocardial infarction was 0.59 among men in the highest quintile of total dietary fibre intake compared with men in the lowest quintile.112 The inverse association was strongest for fatal coronary disease (RR 0.45). A 10 g increase in total dietary fibre corresponded to an RR for total myocardial infarction of 0.81. The main contributors for fibre intake were cereal (cold breakfast cereal), fruits (apples, bananas and oranges) and vegetables (peas, cooked carrots and tomato sauces). An inverse association between fibre and coronary disease has also been reported by previous smaller studies.113–115

In a new analysis of the Finnish α-tocopherol, β-carotene (ATBC) cancer prevention study in which 21 930 men were followed-up for 6 years, a high-fibre diet significantly reduced morbidity and mortality from coronary heart disease in middle-aged men who smoke.116 For men in the highest quintile of total dietary fibre intake, the RR for coronary death was 0.69 compared with men in the lowest quintile of intake. A 10 g greater daily intake of fibre appeared to lower the risk of coronary death by 17%. Cereal fibre had a stronger association with reduced coronary death than vegetable or fruit fibre. In the food group analysis, intake of rye products, potatoes, vegetable and fruit were inversely associated with coronary death. The RR in the highest quintile of vegetable consumption compared with the lowest was 0.60. A 100 g greater daily intake of vegetables was associated with a 26% lower risk of coronary death.

Dementia

Cognitive impairment has been associated with lower vitamin C intakes and lower plasma ascorbic acid levels.117–119 In 260 men and women aged >60 years in the US, those with low blood levels of vitamin C, folic acid, riboflavin or vitamin B12 had significantly lower scores on tests of memory and abstract thinking.117 In 418 elderly men and women in China, low blood levels of vitamin C, riboflavin and folic acid were associated with low scores on the Hodkinson mental test.118 In a 20-year follow-up study of 921 elderly men and women in the UK, cognitive impairment was associated with lower vitamin C intakes (OR 1.7) and lower plasma ascorbic levels (OR 1.6).119 However, as these studies were cross-sectional, the lower vitamin C status could be a consequence rather than a cause of cognitive impairment. Low vitamin E levels were associated with dementia both in older people and in subjects with Down’s syndrome. 120 In 341 patients with moderately severe Alzheimer’s disease treatment with selegeline (10 mg/day) or α-tocopherol (2000 IU/day) for 2 years slowed the progression of disease.121 The increase in median survival was 230 days for the patients receiving α-tocopherol, 215 days for those receiving selegeline, and 145 days for those receiving both, as compared with patients receiving placebo. These studies suggest that increased consumption of antioxidants such as vitamins C and E may delay cognitive impairment.

Age-related macular degeneration

Age-related macular degeneration is the leading cause of irreversible blindness in persons over the age of 65 years.122 Serum levels of carotenoids have been significantly inversely related to the risk of age-related macular degeneration.123 People with low intake of fruits and vegetables rich in vitamin A had a significantly higher risk for age-related macular degeneration compared with those whose consumption was high. 124 Adults in the highest quintile of carotenoid intake had a 43% lower risk of age-related macular degeneration, compared with adults in the lowest quintile of intake.125 Among the carotenoids, lutein and zeaxanthin were most strongly associated with a reduced risk for age-related macular degeneration. Consumption of spinach and collard greens, which are rich in lutein and zeaxanthin, were associated with a dose-dependent reduction in risk of age-related macular degeneration. Lutein and zeaxanthin form the yellow pigment in the macula, and may prevent photic damage by absorbing blue light.126 These pigments are found in green leafy vegetables, as well as fruits and vegetables of other colours such as maize, orange pepper, kiwi fruit, grapes, spinach, orange juice, zucchini and different kinds of squash.127

Gastrointestinal disease

Dietary fibre is protective against colorectal cancer. A review of 40 epidemiological studies described in 55 original reports indicated an inverse association between total dietary fibre intake and the incidence of colon cancer in 32 of the 40 studies.128 These studies were performed on vegetarians as well as non-vegetarians, and the main sources of fibre were fruits, vegetables, cereals, pulses and wheat.128 Mechanisms for the inhibitory role of fibre in colorectal carcinogenesis include reducing faecal mutagen concentrations by increasing faecal bulk, reducing the exposure of colonic mucosa to faecal mutagens by reduced faecal transit time, and inhibiting faecal mutagen synthesis through fibre-induced changes in colonic pH or bacterial metabolism.129 Fibre intake may influence colonic cell proliferation and the development of polyps in high-risk populations.130

There is an inverse relation between dietary concentration of cereal fibre and the prevalence of colonic diverticula, both in a lifespan study of rats131 and in matched groups of vegetarians and non-vegetarians. 132 Vegetarians consuming 41.5 g fibre per day had an incidence of asymptomatic diverticular disease (12%) that was significantly lower than that in non-vegetarians (33%) who consumed 21.4 g fibre per day.132 Dietary fibres shorten gastrointestinal transit time,133 and increase stool weight,134 frequency135 and water content135 thereby reducing constipation. An association between cholelithiasis and a diet low in protein, fat and crude fibre intake has been reported.135 Intake of fibre is negatively associated with gallstones.136 The fibre content of the diet influences bile salt metabolism and the concentrations of biliary lipids in bile.137,138

Cancer

Fibre and phytoestrogens

The protective role of dietary fibre against colorectal cancer has already been discussed. Epidemiological studies also suggest that the risk of breast cancer may be lowered by increasing the intake of dietary fibre and other dietary components associated with high intakes of whole grains, vegetables and fruits.139 An inverse association between breast cancer risk and consumption of fibre and fibre-rich foods has been reported,140,141 and there is a lower frequency of breast and prostate tumours in Asian countries, where soy foods, which are a rich source of fibre and phytoestrogens, are commonly consumed.142 Five case-control studies of diet and breast cancer showed decreased cancer risk to be associated with high intake of soy bean products.143–146 Three of the studies found a significantly reduced risk for premenopausal breast cancer143–145 and one a reduced risk for postmenopausal breast cancer.146 A case-control study showed that increased excretion of some phytoestrogens was associated with substantial reduction in breast cancer risk.147 Colon cancer rates are low in Japan and China, where intake of soy bean products is high.130

Mechanisms by which fibre may aid in reducing breast cancer include lowering circulating levels of oestrogens.148 Soy beans contain several classes of potentially important chemopreventing agents such as phytosterols, sitosterols, phytoestrogens, saponins, Bowman Birk inhibitor and chymostatin.149 There are two principal varieties of phytoestrogens, namely isoflavones and lignans. Isoflavones genistein and diadzein are found predominantly in soy products,150 whilst lignans are found in the fibre present in whole grains, berries, fruits, vegetables and flax seed.151 Daily ingestion of soy protein lengthens the menstrual cycle and suppresses the usual midcycle surge in pituitary gonadotropins,152 effects that are beneficial in decreasing risk of breast cancer. Phytoestrogens may exert an antioestrogenic effect by competing with estradiol for oestrogen receptors in breast tissue;153 cell-culture studies and animal experiments show that they are tumour-inhibitory.142 Animal studies also suggest that short-term exposure to dietary isoflavones neonatally or prepubertally decreases carcinogen induced breast cancer.154 These studies suggest that the protective effect of the Southeast Asian diet occurs early in life,155 and infants there are exposed to soy food early in childhood.

Antioxidants

Epidemiological studies indicate that people who consume higher dietary levels of fruits and vegetables have a lower risk of certain types of cancer158 such as breast,159 lung, oral, pancreas, larynx, oesophagus, bladder and stomach.160 Certain subgroups of the American population, such as the Mormons and Seventh-day Adventists, who are vegetarians, have a significantly lower cancer rate.161,162 The reduced risk of cancer associated with the consumption of fruits and vegetables has been postulated to be due to the presence of antioxidants such as vitamins E and C and β-carotene, and this has been well reviewed in many publications.129,163–165

Several correlational and case-control studies suggest that the consumption of vitamin C containing foods is associated with lower risk of certain cancers, particularly gastric, pancreatic, oesophageal, oral and laryngeal cancers.129,163–165 Epidemiological, animal and clinical data suggest that vitamin E reduces oral carcinogenesis.165 Supplementation with vitamin E has been reported to protect against lung cancer in non-smokers. Supplementation with vitamin E and β-carotene has been associated with a reduced prostate cancer incidence and mortality by one-third in men who smoke167,168 and combined vitamin E, β-carotene and selenium supplementation decreased total mortality by reducing the rate of stomach cancer. The prevalence of esophageal cancer was also reduced.169,170 Epidemiological studies show that increased intake of vegetables, fruits and carotenoids and elevated blood levels of β-carotene are consistently associated with reduced risk of lung cancer.156,157,171,172 Carotenoids may also reduce the risk of other cancers, such as breast, cervical, stomach and oropharyngeal, although the evidence is less extensive and consistent.172 An inverse association between breast cancer and the total intake of vitamin A (preformed vitamin A and carotenoids) was seen in several case-control studies173 and in one small prospective study.174

Recent long-term, large scale prospective trials, however, failed to demonstrate any beneficial effect of β-carotene and vitamin A, C, and E supplementation on cancer risk in populations with essentially normal intake,159,167,175,176 and have raised concern about harmful effects of these antioxidants under certain conditions.167,176 In addition, two smaller trials of β-carotene supplementation failed to demonstrate significant benefit in the prevention of recurrent skin cancer177 and colon polyps.178 The failure of supplementation with β-carotene and vitamins A, C and E to reduce cancer risk may be explained by these vitamins being markers for other nutrients present in fruits and vegetables. β-Carotene is one of 600 carotenoids that include lycopene, lutein and zeaxanthin, which are even more antioxidant than β-carotene in laboratory studies.179 Similarly, there are many other plant compounds including more than 4000 flavanoids that may be responsible for beneficial (antioxidant) effects. The beneficial effects may be the result of a complex interaction between all the potential cancer-preventing substances (carotenoids, flavanoids, folic acid, vitamins A, C and E, selenium and fibre) in physiological doses rather than pharmacological doses of a single substance.

Adverse effects of vegetarian diet

The intake of vitamin B12 is lower in vegetarian diets56,180 and deficiencies in this vitamin have been reported in vegetarians, especially vegans,56,181 and in breastfed infants of vegans.182–184

Most vegetable oils are low in saturated fatty acids. Coconut, palm and palm kernel oil, in contrast to other vegetable oils, are rich in saturated fatty acids. Coconut and palm kernel oils are more saturated than animal fats; palm oil has similar proportions of saturated fatty acids to those of animal fats.185 High intakes of saturated fatty acids have been associated with elevated plasma cholesterol levels, and concern has been expressed about the `atherogenicity’ of coconut and or palm oil in food products.185

Trans-unsaturated vegetable fats have adverse effects on cholesterol profiles, and could increase the risk of coronary heart disease.186 The Health Professionals Follow-up Study187 and the Alpha-Tocopherol, Beta Carotene Cancer Prevention Study188 showed a RR for coronary heart disease of 1.4 and 1.39, respectively, for men in the upper quintile of dietary trans-fat intake. The Framingham Study found that after the first decade of follow-up, the RR of coronary heart disease was 1.1 for each additional teaspoon of margarine eaten per day.189 The Nutrition Committee of the American Heart Association concluded that trans fat should be replaced when possible by monounsaturated or polyunsaturated oils in foods, because of its adverse effects on cholesterol profiles.190

Although serum cholesterol is a major determinant of atherosclerosis, there are conflicting reports of its role in the pathogenesis of stroke. Two ecological studies from Japan showed correlations between increased fat intake and decreased cerebrovascular mortality.191,192 A cohort study of Japanese men living in Hawaii showed inverse association between total fat and saturated fat intake and all-stroke mortality.33 In the Framingham Heart Study, which was a population-based cohort study, intakes of fat, saturated fat and monounsaturated fat but not polyunsaturated fat were associated with reduced risk of ischaemic stroke in men.34 Low serum cholesterol has been shown to be a risk factor for haemorrhagic stroke.193,194 These data imply that vegetarians have a higher risk for stroke as their intake of total fat and saturated fat is low, and their serum cholesterol level is low. However, a recent analysis of all published randomized trials of statin drugs showed that large reductions in cholesterol were associated with significant reductions in risk of stroke.195

The major side effects of vegetarian diets that are high in fibre and leguminous seeds is increased intestinal gas production, resulting in more flatulence and eructations.43,189 Soy bean has a bland but somewhat beany aftertaste that may make it unappealing to Westerners.

Conclusions

A well-balanced vegetarian diet chosen from a wide variety of foods such as fresh fruits, vegetables, whole grains, cereals, nuts, seeds, legumes, beans and soy bean is rich in monounsaturated and polyunsaturated fatty acids (α-linolenic acid), minerals, fibre, complex carbohydrate, antioxidant vitamins [vitamins E, C and carotenoids (600; β-carotene, lycopene, lutein, zeaxanthin)], flavanoids (4000), folic acid and phytoestrogens, and is restricted in saturated fat. Substitution of plant sources of protein for animal protein effectively decreases fat intake while increasing consumption of complex carbohydrate.

The burden of modern lifestyle diseases is enormous when the costs of investigation, diagnosis, treatment and primary and secondary prevention are included. Thus, dietary intervention with a vegetarian diet seems to be a cheap, physiological and safe approach for the prevention, and possibly management of modern lifestyle diseases. Ideally, it should be complemented with other healthy lifestyle practises such as regular exercise and abstinence from smoking, excessive alcohol and illicit drugs. Recognizing these benefits, the US Public Health Service has recommended a national dietary goal of increasing overall per capita consumption of fruits and vegetables in the American diet to at least five servings a day by the year 2000 to improve health and reduce disease risk.197

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Er dit blodtryk 103 over 62 (103/62)?

Blodtryk 103 over 62 skrives som 103/62.

Dit blodtryk er: Idealt!

Med hensyn til din systoliske værdi (øvre tryk) er dit blodtryk: For lavt – Hypotoni!

Hvis du har en blodtryksmåling placeret inden for to forskellige klassificeringsresultater, skal du bruge resultatet, der er inden for det højere interval. For eksempel, hvis din systoliske værdi er ‘høj-normal’ og din diastoliske værdi er ‘hypotension klasse 1’, skal du bedømme ‘hypotension klasse 1’ som din nuværende klassificering.

Hvad dine værdier betyder for dit helbred:

Din blodtryksværdi på 103 over 62 (103/62) angiver et ideelt blodtryk. Kravene til denne klassifikation er opfyldt med en systolisk værdi lavere end 120 mmHg og en diastolisk værdi lavere end 80 mmHg, dvs. lavere end 120/80.

Dette blodtryksniveau er ideelt til at undgå skader på kar og organer. Et ideelt blodtryk øger normalt din levetid.

Indhold
  1. Blodtryk 103 over 62 (103/62) i diagram og skala
  2. Hvad menes med klassifikation “Idealt blodtryk”?
  3. Virtuel blodtryksmåler til 103/62
  4. Kontroller en anden værdi

Blodtryk 103 over 62 (103/62) i diagram


Blodtryk 103 over 62 (103/62) i skala

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Betydningen af Idealt blodtryk

Dit blodtryk er ideelt.

Betingelsen for et ideelt blodtryk er en værdi, der er lavere end 120 over 80 (120/80).

Hvis din systoliske værdi stiger med 17 mmHg till 120 mmHg, og din diastoliske værdi stiger med 18 mmHg till 80 mmHg, er dit blodtryk ikke længere ‘ideelt’, men klassificeres nu som ‘normalt’.

Et normalt systolisk blodtryk er mellem 120 til 130 mmHg, mens det diastoliske tryk er mellem 80 til 85 mmHg.

Lær mere om din klassificering Idealt blodtryk her.


Virtuel Blodtryksmåler


Tjek en anden værdi


Påvirker dit blodtryk
Advarselstegn
Klassifikation af blodtryk

90,000 What to do at low pressure?

The upper limit of normal blood pressure (BP) is 140/90 mm Hg, the lower one is 90/60 mm Hg. Excess is hypertension, and a BP reading below the normal range is hypotension (hypotension).

It should be borne in mind that the level of normal (working) blood pressure is different for each person. Therefore, it is better to take into account that any pressure less than normal (individual) by 20% is hypotension.

Causes and signs of low heart pressure.

Hypotension can occur acutely or persist chronically. Hypotension is diagnosed with a chronic decrease in blood pressure.

Causes of acute hypotension: myocardial infarction, profuse bleeding, traumatic or anaphylactic shock, pulmonary embolism, peritonitis, arrhythmia attack.

Chronic hypotension can be:

  1. physiological (i.e.that is, normal – in athletes, people whose body has adapted to great physical exertion),
  2. primary – due to mental or physical overload,
  3. secondary – as a consequence of other pathologies and diseases.

Secondary hypotension is most common. She is called by:

  • anemia (more often with blood loss),
  • traumatic brain injury,
  • intoxication (alcoholic, narcotic, infections, overdose of certain drugs),
  • endocrine disorders (hypoglycemia, thyroid pathology),
  • pathology of the spine (osteochondrosis, trauma, damage to the vertebral arteries).

Low pressure symptoms:

  • dizziness, loss of consciousness, weakness, loss of memory, attention, performance,
  • headache (in the temples, in the forehead),
  • tachycardia (rapid heart rate),
  • pain in the region of the heart (lasts more than 30 minutes),
  • nausea, vomiting, flatulence, constipation.

To establish the cause of these symptoms and make a diagnosis, an additional examination is necessary (ECG, ultrasound of the heart and blood vessels, EGD) and consultation and supervision of doctors (therapist, endocrinologist, neurologist, gastroenterologist).

Should low blood pressure be treated?

Many people do not feel their BP rise or fall. This is how our body works – it adapts to moderate changes in blood pressure thanks to complex internal mechanisms. However, this does not mean that such conditions are not dangerous.

Everyone knows that arterial hypertension is often accompanied by strokes and heart attacks. However, not many people know that hypotension has the same complications!

And low blood pressure in youth can lead to hypertension in adulthood and old age.Therefore, hypotension is an absolutely real problem. For older people, hypotension is completely dangerous: the brain suffers from a lack of oxygen and nutrients (together with atherosclerosis, ischemic stroke can develop), and heart disease (atherocardiosclerosis and angina pectoris) with hypotension progresses more rapidly.

For pregnant women, low blood pressure is an extremely dangerous condition. The fetus does not receive enough nutrients and oxygen (because of this, congenital malformations arise, and premature birth or miscarriage is possible.

What to do with low pressure?

Physiological hypotension does not require special measures if it does not cause complaints in a healthy person. With a decrease in physical activity, the lowered blood pressure comes to normal values.

If hypotension is chronic primary, then it is necessary to eliminate mental or physical overload. Massages, swimming, walking in the fresh air and everything that allows a person to forget about pressing problems and relax helps in this.At home, it is recommended to add seasonings and spices (cloves, cinnamon), caffeinated drinks to food. If ineffective, it is necessary to consult a doctor and, possibly, take medications.

If hypotension is chronic secondary, then treatment of the disease that caused it is necessary.

To monitor the state of the cardiovascular system, it is recommended to use Microlife blood pressure monitors, equipped with modern technologies and additional functions.Early detection of hypotension allows for life-saving measures to be taken to increase blood pressure.

Features of the daily blood pressure profile in patients with arterial hypertension in combination with chronic viral hepatitis C | Talantseva

1. Ong K.L., Cheung B.M.Y., Man Y.B. et al. Prevalence, awareness, treatment, and control of hypertension among United States Adults 1999-2004 // J.Hypertens. – 2007. – No. 49. – P. 69-75.

2. Shalnova S.A., Balanova Yu.A., Konstantinov V.V. Arterial hypertension: prevalence, awareness, taking antihypertensive drugs and the effectiveness of treatment among the population of the Russian Federation // Ros. cardiol. zhurn. – 2006. – No. 4. – S. 45-50.

3. Krasilnikova E. I., Baranova E.I., Blagosklonnaya Ya. V. et al. Mechanisms of the development of arterial hypertension in patients with metabolic syndrome // Arterial hypertension. – 2011. – T. 17, No. 5. – S. 405-414.

4. Barsukov A.V., Talantseva M.S. Essential arterial hypertension in patients with type 2 diabetes mellitus: current issues of antihypertensive therapy in the light of evidence-based medicine // Arterial. hypertensive. – 2011. – T.17, No. 6. – S. 518-524.

5. Kozlov K.V. Pathogenetic characteristics of iron metabolism in patients with chronic hepatitis C: Abstract of the thesis. to-that honey. sciences. – SPb., 2010 .– 20 p.

6. Kobalava Zh.D., Kotovskaya Yu.V. Arterial hypertension (key aspects of diagnosis, differential diagnosis, prevention and treatment). – M .: B.I., 2001 .– 208 p.

7. White W.B., Dey H.M., Shulman P. Assesment of the daily pressure load as a determinant of cardiac function in patients with mild-no-moderate hypertension // Am. Heart J. – 1989. – Vol. 118, No. 4. – P. 782-795.

8. Yilmaz Y. Liver function tests: Association with cardiovascular outcomes // World J. Hepatol. – 2010.- Vol. 2, no. 27, suppl. 4. – P. 143.

9. Mason J.E., Starke R.D., Van Kirk J.E. Gamma-glutamyl transferase: a novel cardiovascular risk biomarker // Prev. Cardiol. – 2010. – Vol. 1, No. 13. – P. 6-41.

10. Wieckowska A., Papouchado B. G., Li Z. et al. Increased hepatic and circulating interleukin-6 levels in human nonalcoholic steatohepatitis // Am.J. Gastroenterol. – 2008. – No. 103, No. 6. – P. 1372-1379.

11. Drapkina OM RAAS and fibrosis. Hepatocardial connections // Rus. honey. zhurn. – 2011. – No. 18. – S. 1136-1139.

12. Plakhtiy L.Ya., Nagoev B.S., Otaraeva B.I., Tadeeva A.K., Tskhovrebov A.Ch. Lipid peroxidation and antioxidant protection in patients with chronic viral hepatitis C // Uspekhi sovrem.natural science. – 2010. – No. 9. – S. 141-143.

13. Sklyar L.F., Kulikova S.E. Evaluation of lipid peroxidation in patients with chronic viral hepatitis C // Sovrem. science intensive technologies. – 2005. – No. 10. – S. 62-63.

14. Lobzin Yu.V., Zhdanov K.V., Volzhanin V.M., Gusev D.A. Viral hepatitis: clinical picture, diagnosis, treatment. – SPb.: Folio, 2006 .– 183 p.

15. Guidelines for the diagnosis, treatment, dispensary observation and prevention of chronic hepatitis in the Armed Forces of the Russian Federation. – SPb .: VMA, 2010.

16. Mawatari S., Uto H., Tsubouchi H. Chronic liver disease and arteriosclerosis // Nippon Rinsho. – 2011. – Vol. 1, no. 69. – P.153.

17. T.V. Amvroseva, V.Zh. Votyakov, S.V. Orlova. et al. Virus-induced dyslipidemias as possible risk factors in the development of somatic diseases // Problems of Virology. – 1994. – No. 2. – C. 87-91.

18. Gurnitskaya M.V. The state of lipid metabolism in chronic viral liver diseases: Dis .. to-that honey. sciences. – Astrakhan, 2006.- 153 p.

19. Ryabova N.A. Features of lipid metabolism in patients with viral hepatitis C in the terminal stage of chronic renal failure and kidney recipients: Abstract of the thesis. dis. to-that honey. sciences. – SPb., 2006 .– 25 p.

How to treat low blood pressure

09/29/2017

How to deal with low blood pressure: ten ways.

Blood pressure is a value that shows how much blood presses against the walls of blood vessels – arteries. Blood pressure readings are recorded using two digits.

The first, larger number is the systolic pressure, measured when the heart contracts and fills the arteries with blood.

The second number, diastolic pressure, is measured while the heart is resting between contractions.The normal indicator for an adult is about 110/70 millimeters of mercury.

When the blood pressure is below 90/60 mm. rt. Art., or below those figures that are observed in a person in a normal state – doctors talk about low blood pressure, or arterial hypotension. More often than not, this is not a cause for concern.

It’s another matter if low blood pressure is accompanied by discomfort and unpleasant symptoms. This condition is true hypotension or low blood pressure.In such cases, you should consult a doctor and undergo an examination.


Low pressure manifestations:

  • Vertigo
  • Fainting

  • Nausea

  • Fatigue

  • Loss of concentration

  • Occipital headaches

  • Increased sweating and shortness of breath

  • Feeling of fear

Treatment for hypotension depends on the cause.For example, if the drop in blood pressure is caused by medication, the doctor will stop the drug or reduce the dosage.

The most common causes of low blood pressure are negative emotions, prolonged mental stress, and lack of physical activity.

Some dangerous causes of low blood pressure:

  • Fasting, poor nutrition
  • Heart failure and other heart diseases
  • Low blood sugar

  • Liver disease

  • Dehydration

  • Hypothyroidism (insufficient thyroid hormone)

  • Anemia

  • Taking medications such as diuretics (such as furosemide), heart medications, some antidepressants

  • Pregnancy

Blood pressure can be increased by adjusting diet and lifestyle.

We’ve put together ten ways to combat low blood pressure:

1. Drink plenty of water and other non-alcoholic beverages

Drinking fluids increases the amount of blood in the bloodstream and increases blood pressure. It is especially important for hypotensive patients to avoid dehydration in hot weather.

2. Limit alcohol intake.

Alcohol dilates blood vessels. Therefore, alcohol is contraindicated in people with hypotension or varicose veins.

3. Eat more salt.

If you have low blood pressure, add more salt to your food. But don’t get too carried away. The norm for human consumption of salt is only five grams per day. Too much salt in food can lead to heart failure.

4. Get exercise.

Regular exercise, such as running, swimming, strengthens the heart and blood vessels. Sports associated with weight lifting are contraindicated in people with hypotension.In such cases, you need to consult a sports doctor before starting classes.

5. Handle hot water with care

A hot shower dilates blood vessels and leads to a drop in pressure. It is helpful to keep a stool in the bath in case you feel dizzy.

6. Avoid sudden changes in body position.

When you get out of bed, first sit a little on the edge of the bed. A particularly strong drop in pressure occurs when a person rises abruptly from a cross-legged sitting position, or from a squatting position.Hence the next tip:

7. Sit cross-legged

Sitting cross-legged increases pressure. If you experience sudden dizziness, this may help.

8. Eat small and frequent meals.

Those who ate heavily, the pressure drops due to the fact that the blood rushes to the digestive organs. This reaction is most often triggered by foods rich in carbohydrates. To avoid this, eat small meals.And after a plentiful meal, it is worth resting. First of all, this advice applies to the elderly.

9. Wear compression stockings.

Compression stockings are designed to relieve pain from varicose veins. These stockings make it harder for blood to flow to the legs, retaining more blood in the upper body, and may help people who are prone to fainting.

10. Do not stand in one place for a long time.

In hypotensive patients, standing for a long time can lead to fainting due to the outflow of blood from the brain.

To determine the cause of low blood pressure, especially if low blood pressure is troubling, you need to consult a general practitioner or cardiologist and undergo an examination.

What methods are used to find the cause of low pressure?

Blood tests. A complete blood count will show if you have anemia or not. Additionally, you can perform a blood sugar test.

ECG – electrocardiogram. With the help of this diagnostic method, the doctor will assess the rhythm of your heart contractions, will understand if there are problems with blood flow to the heart muscle. You can even determine if you have had a heart attack in the past or not.

EchoCG – echocardiogram, or ultrasound of the heart. Allows the clinician to see the outline of the heart, evaluate its size and how it works.

Daily monitoring of ECG and blood pressure. Sometimes you need to wear the transducer all day to detect short heart rhythms and pressure surges.Over the course of the day, pressure changes depending on body position, stress level, fatigue, what you eat and drink, and the time of day. Indicators are lowest at night and rise sharply upon waking.

Stress tests. Some hidden heart problems are easier to diagnose when the heart is heavily loaded with work. During the test, you will exercise while your doctor will take a cardiogram or scan your heart with ultrasound.

Please note: discounts are available in our clinics in the fall:

daily ECG monitoring

stress echocardiography with stress

cardiogram with stress

Remember – your health is in your hands!

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