Chapter 7

Safeguarding Your Heart

In This Chapter

Identifying the role vitamin D plays in heart disease

Understanding the link between vitamin D and coronary artery disease

Examining how vitamin D relates to high blood pressure

Discovering how vitamin D may help avoid heart failure

Preventing heart attacks resulting from deficient vitamin D

You can live without an arm or a leg, but you can’t live without your heart or several of the major arteries and veins leading to and from the heart. More than one in three Americans has cardiovascular disease or suffers from a condition that increases the risk of getting a cardiovascular disease. The numbers of people affected are staggering and include

High blood pressure: 75 million

Heart attacks: 8.5 million

Chest pain: 10.2 million

Heart failure: 5.8 million

Stroke: 6.4 million

Evidence shows there are many ways that we can reduce the chances of cardiovascular disease. These include getting more exercise, losing weight, eating more fruits and vegetables, taking in less saturated fats, and eating more fish. One of the new ways to prevent cardiovascular disease is keeping your vitamin D status high. In this chapter, I introduce you to some of that evidence.

Cardiovascular disease isn’t really a single disease but a group of related diseases. For example, coronary artery disease is a form that affects the arteries which feed the heart and cerebrovascular disease is a form that affects the blood vessels in the brain.

Considering the Link between Vitamin D and Heart Disease

Recent studies suggest that vitamin D may play a significant role in many aspects of heart and vascular health. Some even think that high vitamin D status may prevent the development of heart disease. But the reasons we develop cardiovascular disease is complex, so it’s not clear how and where vitamin D is contributing. For example, autopsies of young men killed in war have turned up early signs of cardiovascular disease. With that in mind do we need high levels of vitamin D at a very young age to avoid this problem? Also, we often find that older people with cardiovascular disease have low serum 25-hydroxyvitamin D levels. Can a supplement with vitamin D be used to stop the disease after it’s begun? Researchers simply don’t know.

However, researchers have learned some specifics about vitamin D and heart disease. For example, the farther a population is from the tropics, the higher the incidence of heart attacks, heart failure, and strokes in that group. This higher rate of disease seen with changing geography could be explained by a lower production of vitamin D by the skin. Of course, there are other risk factors in cooler climates that could account for the higher incidence of heart disease, such as greater weight, less exercise due to poor weather conditions, increased alcohol intake, and so forth. In the sections that follow I’ll show you why some researchers think the relationship between vitamin D and cardiovascular disease is real.

Coronary Artery Disease: It Can Creep Up on You

Coronary artery disease (CAD) is the term for the type of cardiovascular disease with progressive closing of arteries that supply blood to the heart. It’s also known as atherosclerotic heart disease or atherosclerosis. If a critical artery closes completely, the result is a myocardial infarction, or heart attack.

Coronary artery disease is usually a silent disease. The first sign a person gets may be the sudden severe chest pain of a heart attack, or even sudden death.

In the following sections, I explain how CAD develops and then show how vitamin D may affect the disease.

Fingering cholesterol as the culprit

Coronary artery disease results from years of accumulating fat and cholesterol in the walls of the arteries, called an atheromatous plaque. This produces a narrowing of the artery at the site of the plaque that eventually closes off the artery. See Figure 7-1.

Figure 7-1: As cholesterol accumulates, the arteries narrow.

The atheromatous plaque develops in the following way:

Damage occurs in the inner lining of the artery (the epithelium) due to high blood pressure, diabetes, smoking, or increased cholesterol levels.

White blood cells called monocytes come to the damaged area, attach, and creep under the cells lining the artery. These cells then transform into macrophages (large cells) that produce signals that cause local inflammation called cytokines. (See Chapter 3 for a discussion of how the immune system works.)

Macrophages accumulate fat, especially oxidized fat (similar to what happens when fat goes rancid). This accumulation of fat and cells is called a fatty streak. Autopsies of young accident victims show that fatty streaks first start in the arteries.

The fatty deposits and white blood cells grow and send signals to other cells in the artery to divide and multiply. As a result, the lesion begins to stick out into the lumen, the opening of the artery that blood flows through.

Blood platelets can accumulate and form clots on the irregular surface of the plaque. The clot can remain there and clog the artery, or break off and lodge in a smaller artery, completely closing off blood flow beyond it. When this happens, the tissue supplied by that artery may die if the obstruction is not opened.

At very late stages of the disease, calcium is deposited in the walls of plaques, and cells in and around the plaque cause calcification similar to what happens in bone. This can be seen in the artery by an X-ray. The calcification makes the artery brittle and hard to repair.

Looking at vitamin D’s effect on CAD

There isn’t a definitive answer regarding the role of vitamin D in CAD; however, researchers think that vitamin D could be important in three ways:

Calcium deposits in arteries

As noted in the preceding section, the accumulation of calcium in arteries is a feature of the late stages of atheromatous plaque formation. Because vitamin D is so crucial for the control of calcium and bone metabolism, people have worried that a high vitamin D status might make the plaque calcify sooner or faster. In fact, one symptom of vitamin D toxicity is that soft tissues can accumulate calcium and calcify like bone. In contrast, when 25-hydroxyvitamin D is high but not at toxic levels, some studies show it may even protect against calcium deposits in arteries.

Cholesterol reduction and vitamin D

Many doctors feel that controlling serum cholesterol and fat levels is critical to reducing the risk of cardiovascular diseases. The goal is to reduce the serum level of cholesterol, particularly a type called low-density lipoprotein cholesterol (LDL-C), and a type of fat called triglycerides. Other benefits can come from increasing a type called high-density lipoprotein cholesterol (HDL-C).

When a person has high cholesterol, cholesterol-lowering drugs called statins are given. These drugs block the production of cholesterol; however, there are some effects of these drugs that are not understood. Some have argued that they have beneficial effects on cardiovascular disease because of either a calcitriol-like (active vitamin D-like property or because they raise serum 25-hydroxyvitamin D levels).

Low levels of 25-hydroxyvitamin D have been associated with high total and LDL-C levels in Finnish men, higher serum triglyceride levels in Spanish kids, and lower levels of a protective protein called Apo A1. However, when calcium and vitamin D were given to women for more than five years, researchers found no effects on total cholesterol, HD-C, LDL-C, or triglycerides. This study used only 400 IU of vitamin D for supplementation, and most of the women studied already had high vitamin D status so we need more research to clearly say what vitamin D does to serum cholesterol levels. It’s also possible that 25-hydroxyvitamin D levels have nothing to do with preventing cardiovascular disease or causing abnormal cholesterol, but instead are reduced by a common cause that creates abnormal cholesterol levels. Remember that being overweight or obese raises LDL-C and triglycerides, lowers Apo A1, and also lowers 25-hydroxyvitamin D levels.

Still, vitamin D could have effects on cholesterol without raising or lowering their serum levels. In cell experiments, calcitriol (active vitamin D) blocks the ability of macrophages from diabetics to take up oxidized cholesterol while deletion of the vitamin D receptor increases uptake of oxidized cholesterol. Earlier I mentioned that uptake of cholesterol by macrophages is a step in the formation of atherosclerotic plaques. If calcitriol can block cholesterol uptake by macrophages in the body, then it might reduce plaque formation. Researchers need to do more experiments to find out if that is true.

There’s some new evidence that suggests vitamin D deficiency can decrease insulin sensitivity. This is part of a condition called the metabolic syndrome, an early stage of diabetes that increases a person’s chance of getting cardiovascular disease by raising LDL-C and triglyceride levels while lowering HDL-C levels. I discuss this more in Chapter 8, but if it’s true, improving vitamin D status could reduce the risk of cardiovascular disease indirectly by improving insulin sensitivity. But again, because most people with metabolic syndrome are overweight or obese, the low 25-hydroxyvitamin D levels may not have anything to do with causing the metabolic syndrome.

Levels of vitamin D and inflammation

In Chapter 5 I told you how vitamin D affects the immune system. Many of those changes suppress how much inflammation the immune system causes while fighting an infection. Cardiovascular disease, particularly coronary artery disease, leads to localized inflammation. The macrophages in plaque produce cytokines that cause damage to healthy cells and make other cells in the artery multiply. This contributes to blocking the artery. Because of this, several researchers have wondered if suppressing the production and negative effects of cytokines might be a mechanism used by vitamin D to prevent cardiovascular disease. A number of studies suggest that this might be true.

C-reactive protein (CRP) is found in the blood and rises rapidly when inflammation occurs. The liver makes C-reactive protein in response to a cytokine called interleukin-6 that comes from macrophages (inflammatory cells).

C-reactive protein is considered a general marker for heart disease risk. Low serum levels of 25-hydroxyvitamin D are associated with high levels of CRP in some but not all studies. Unfortunately two recent but small studies showed there was no reduction of CRP levels with vitamin D supplementation.

Asymmetric dimethylarginine (ADMA) is another marker in the blood for damage to the inner wall of arteries associated with inflammation. The level of ADMA is greater when the serum 25-hydroxyvitamin D level is low.

Tissue plasminogen activator (TPA) is another substance found in the blood that comes from the endothelium (the inner wall of arteries). It turns plasminogen into plasmin, a substance that breaks up clots in arteries. TPA is reduced when atheromatous plaque forms, and this increases the tendency of blood to clot. Calcitriol increases TPA levels in cultured vascular cells, and serum TPA levels are higher in people with a high vitamin D status.

A side effect of cholesterol-lowering statins is myopathy, inflammation of the muscles of the body, occurring in about 25 percent of people who take the statins. Vitamin D supplementation has been found to reduce the pain associated with myopathy, allowing the statin treatment to be continued.

High Blood Pressure: When High Numbers Are Harmful

High blood pressure is exceedingly common in the United States, occurring in one of every four people, or 75 million Americans, only three-fourths of whom are aware of their condition.

High blood pressure is a chronic medical condition discovered by measuring the pressure in one or more arteries, usually the brachial artery in the arm just below the shoulder. For the vast majority of cases (90 to 95 percent) no specific reason is known for the high blood pressure. See my book High Blood Pressure For Dummies (Wiley) for a complete discussion of this condition.

In the following sections, I give you an overview of how high blood pressure develops and tell you how vitamin D may be used to prevent or treat the condition.

Explaining high blood pressure

Having your blood pressure taken is as simple as holding your arm away from your body and enduring a few seconds of squeezing. The measurement on the arm consists of a higher value, called the systolic blood pressure, which represents the maximum pressure of the blood flowing in the artery; and a lower value, called the diastolic blood pressure, which represents the minimum pressure of the blood flowing in the artery. The diastolic pressure never goes down to zero (you hope) because that means the heart is no longer pumping.

Blood pressure was originally measured by connecting a cuff around the arm to a column of mercury and using a stethoscope to listen for sounds in the artery. The doctor would pump up the pressure in the cuff and then start deflating the cuff. During deflation, the doctor would listen for a sound through the stethoscope which is created by turbulence in the artery. When he heard a sound indicating that turbulence, he glanced at the column to see how high the mercury was (in millimeters). That number was the systolic pressure. When the sound disappeared, he again checked the column to learn the diastolic pressure.

These days, a portable aneroid gauge is often used to check blood pressure. It uses a spring and air pressure to move a needle on a scale. The observer listens for the sound of blood to start and then disappear, glancing at the numbers that the needle points to on the scale. The combination of these two numbers is the blood pressure.

An abnormal blood pressure is considered to be greater than 140 systolic and/or greater than 90 diastolic. Exceptions do exist, though. For instance, a person with diabetes or kidney disease should have a blood pressure no greater than 130 over 80, written as 130/80.

High blood pressure is a risk factor for many other diseases. It may be responsible for any or all of the following complications:

Aneurysm (a bulge ballooning out from the normal pipelike artery)

Stroke (loss of brain function when the blood supply to the brain is disrupted)

Kidney failure (loss of the ability of the kidney to filter the blood and to make urine)

Heart attack (also called myocardial infarction, is when the blood supply to a part of the heart is lost, leading to damage to parts of the heart and possibly heart failure)

Heart failure (inability of the heart to supply enough blood to the body)

Usually no symptoms occur with mild or moderate high blood pressure. If the blood pressure is much higher (in the range of 180 systolic and 110 diastolic), it’s accelerated high blood pressure. Symptoms such as headache and confusion may develop.

A number of diseases cause secondary high blood pressure, but they are rare. They include excessive or reduced thyroid hormone production, excessive production of growth hormone, Cushing’s syndrome (excessive production of the hormone cortisol by the adrenal glands), and excessive production of aldosterone (another adrenal gland hormone).

High blood pressure is a lifestyle disease, so treatment begins with weight loss and exercise. Salt reduction and increasing fruit and vegetable intake also may help for some people, whereas meditation and biofeedback have worked for others. If these treatments fail, drugs can be administered to effectively lower blood pressure to normal, but they must be taken as prescribed. Many people skip their blood pressure drugs and don’t control their blood pressure.

Clarifying vitamin D’s role in blood pressure

There is a strong geographic affect on blood pressure — the further one goes from the equator, the higher blood pressure gets. This suggests that high vitamin D production may protect against high blood pressure. This idea is supported by studies on mice that lack either the enzyme needed for the production of calcitriol or the vitamin D receptor that allows calcitriol to work — both have high blood pressure.

Several large studies show that when serum 25-hydroxyvitamin D levels are high, blood pressure is low. There is even some evidence that additional vitamin D will reduce blood pressure in people. A small study showed that a single oral dose of 100,000 IU of vitamin D3 significantly lowered blood pressure. This effect is especially true when the serum 25-hydroxyvitamin D level is low to start with.

Even still, there are several pieces of information that are still missing before we can make recommendations. We don’t have studies that tell us the lowest effective doses for reducing blood pressure. Also, there isn’t any evidence that the effect of vitamin D on blood pressure translates to a lower risk of hypertension. Finally, it’s possible that vitamin D has nothing to do with blood pressure but that lower levels of vitamin D are indicators of people who are overweight or obese, and who do not exercise or consume a healthy diet. These are factors which are known to cause high blood pressure.

If you have high blood pressure, it may be reasonable to ask your doctor to measure your 25-hydroxyvitamin D level. Take a supplement if your serum level is less that 20 ng/ml (50 nmol/L) and see if it makes a difference in your blood pressure. (See Chapter 13 for more about vitamin D supplements.)

A number of potential biological mechanisms may explain why vitamin D might lower blood pressure:

Effect on the kidneys and renal glands: The kidneys indirectly control blood pressure by controlling water excretion. They do this through the help of renin, a hormone produced in the kidney. Renin activates a chemical called angiotensinogen to create angiotensin I. Angiotensin I then changes into angiotensin II when it is activated by an angiotensin-converting enzyme. Finally, angiotensin II constricts arteries to produce high blood pressure, and it causes the release of aldosterone from the adrenal gland causing the kidneys to reabsorb more salt and water, which raises blood pressure even more. Calcitriol or vitamin D analogs are potent suppressors of the production of renin in cell and animal studies.

Effect on parathyroid hormone (PTH): In Chapter 2 we talked about how important PTH is for maintaining calcium in the blood. PTH levels increase when dietary calcium intake or vitamin D status is low in an effort to correct calcium metabolism. Elevated PTH has a small effect to raise blood pressure, but it is uncertain how this happens. One suggestion is that PTH has a direct elevating effect on renin secretion. Remember, high vitamin D status suppresses PTH, which could indirectly suppress blood pressure.

Effect on insulin resistance: Low levels of vitamin D are associated with decreased sensitivity to insulin, which is a feature of the metabolic syndrome (see Chapter 8). The body makes excessive levels of insulin to keep the blood glucose under control. Insulin has been shown to raise blood pressure.

Direct effect on blood vessels: Vitamin D deficiency may cause increased vascular resistance, which raises blood pressure. Lack of vitamin D may also cause thickening of the walls of the blood vessels and stiffening, leading to increased blood pressure. A study showed that a single 100,000 IU dose of vitamin D to vitamin D-insufficient people improved the function of the blood vessels.

Heart Failure: When the Body’s Pump Is Weak

When a person suffers from heart failure, the heart is unable to pump enough blood to supply the needs of the body. Heart failure is a relatively common condition in the elderly population over age 65, occurring in up to 10 percent of people. Evidence shows that heart failure, like high blood pressure, is associated with low blood levels of vitamin D.

In the following sections, I describe how heart failure occurs and look at how vitamin D may affect the condition.

Explaining heart failure

Heart failure occurs because the force of the heart muscle is decreased. Not all the blood is pushed out of the chambers of the heart when the muscle contracts. When the heart is called on to work harder during exercise, it can’t.

The body tries to put out sufficient blood by increasing the heart rate, which strains the heart muscle even more. Ultimately, the heart enlarges. This makes it even more likely that the heart muscle will fail, especially when it is most needed during exercise.

Heart failure can be caused by these factors:

Heart attack with loss of significant muscle.

High blood pressure.

Disease of the heart valves that prevent blood from flowing backward to the heart chamber that has just pumped it out. If a valve allows blood to flow backward, it means the heart has to work harder to get the same volume of blood to move through the heart and into the body.

Cardiomyopathy, a diminished function of the heart muscle caused by a number of abnormalities, including malnutrition, decreased but not complete cessation of blood flow to the heart muscle, inflammation, diabetes, and too much alcohol consumption.

When heart failure occurs, the patient suffers from several debilitating signs and symptoms:

Cough

Fatigue

Fluid in the lungs

Orthopnea, the need to sleep with the head raised on multiple pillows to breathe

Pulmonary edema, severe breathlessness resulting from fluid accumulation in the lungs

Shortness of breath

Swelling of the abdomen

Swelling of the feet, ankles, and legs

Treatment of heart failure requires the use of drugs called angiotensin-converting enzyme inhibitors. Salt and fluid intake is also carefully monitored. Some exercise can help improve heart function. Patients may require an implantable cardioverter defibrillator, a device that is implanted under the skin and shocks the heart if it loses its normal rhythm. The only certain treatment for a heart that is failing or has failed is transplantation of a new heart.

Heart failure is progressive. The heart muscle usually gets weaker over time. Treatment may help, but the prognosis is poor without a heart transplant.

Examining vitamin D’s role in heart health

A number of findings suggest that vitamin D plays an important role in preventing heart failure and that a lack of vitamin D increases the severity of the heart failure:

Patients with heart failure have low serum 25-hydroxyvitamin D levels.

The number of deaths due to heart failure were almost three times higher in vitamin D-deficient subjects compared to those with higher serum 25-hydroxyvitamin D (25-hydroxyvitamin D higher than 30 ng/ml [75 nmol/L]). Also, deaths from heart failure are more common in winter when skin vitamin D production is low.

Heart muscle cells have vitamin D receptors, and calcitriol has direct effects on cardiac muscle cells grown in culture.

The reasons that vitamin D might prevent heart failure are many of the same things that I’ve already discussed:

High vitamin D status is associated with improvements in many of the conditions that lead to heart failure, such as coronary artery disease and high blood pressure, as well as diabetes and obesity.

Calcitriol vitamin D inhibits the renin-angiotensin-aldosterone system, causing salt and water retention. Increased salt and water make heart failure worse by increasing blood pressure.

The excessive levels of parathyroid hormone that occur in vitamin D deficiency may damage the heart muscle by lengthening and thinning the heart muscles. Too much parathyroid hormone can also cause fibrosis, the development of excessive fibrous connective tissue that replaces heart muscle.

Calcitriol suppresses the inflammatory responses including the production of cytokines (described in Chapter 5). In the heart, cytokines destroy heart muscle.

These pieces of evidence are very promising, but I have two cautions before you get too excited about what vitamin D can do for the heart. Heart failure is a complex problem with many causes, so it’s unlikely that vitamin D is the only thing contributing to the disease. Also, no studies have yet been done showing that vitamin D supplementation improves the prognosis of people with heart failure or at high risk of heart failure. Finally, when people have heart failure they are ill and less active, and this may be why the blood levels of vitamin D are low. So rather than low levels of vitamin D causing the heart failure in the first place, it may simply be an effect of the primary disease.

Heart Attacks and Vitamin D: Seeing the Bigger Picture

In the preceding sections, you can see how adequate levels of vitamin D may control or prevent coronary artery disease, high blood pressure, and heart failure. When these conditions aren’t treated, they can lead to a heart attack. Another question that researchers are trying to answer is whether vitamin D can prevent heart attacks and, if so, how much vitamin D is needed. Researchers are also curious to learn what vitamin D can do after a person has a heart attack. The next two sections look at the work that’s being done in these areas.

Relationship of vitamin D levels and risk of a heart attack

If high vitamin D status can prevent all of the conditions that are risk factors for a heart attack (also called a myocardial infarction), it seems logical that it will also lower the risk of heart attacks. There are some good, large association studies to support this idea. These studies show that people with low vitamin D status (lower than 15 ng/ml or 37.5 nmol/L) are at the highest risk of suffer-ing a heart attack, and that people with serum 25-hydroxyvitamin D over 30 ng/ml (75 nmol/L) are most protected. This relationship holds true even after the researchers adjust for all the factors that can cause heart attacks, such as family history of heart attacks, body mass index, alcohol consumption, physical activity, diabetes, and high blood pressure. That’s still not absolute proof, but it suggests that the relationship between vitamin D and heart attacks may not be because vitamin D status is a marker for some other well known cause of the disease.

The problem with these studies is that while the statisticians attempt to adjust for factors such as family history, body weight, etc., they can only guess the true effect that these factors are having in the outcome. Ultimately, someone has to do a clinical trial in which people are randomly assigned to a vitamin D or a placebo treatment group, and the incidence of heart attacks is then examined over the next several years. Without such evidence, we don’t know for certain that an association between vitamin D and heart attacks indicates direct cause and effect.

Researchers don’t yet know the dietary or serum level of vitamin D that is required to prevent heart attacks and heart failure. However, it’s clear that having very low vitamin D status (serum 25-hydroxyvitamin D less than 15 ng/ml [37.5 nmol/L]) is the worst place to be. Make sure you keep your vitamin D intake up so that you don’t fall below this. There also seems to be a benefit of bringing your vitamin D status even higher, but researchers still have to do controlled clinical trials to be sure of that.

Can increasing vitamin D after a heart attack prevent another one?

Studies that look at the role of vitamin D after a heart attack are rare. This may be because other drugs are used after a heart attack, so it’s hard to determine whether the vitamin D or something else is having an impact on future cardiovascular events.

One study that tried to address the question was published in the American Heart Journal in June 2010. The authors looked at vitamin D levels in people who’d had an acute cardiovascular event, such as a heart attack or heart failure, but were stable at the beginning of the study. They measured vitamin D levels and followed the patients for up to eight years. The authors didn’t find a difference in future cardiovascular events between those who had high levels of vitamin D (greater than 30 ng/ml or 75 nmol/L) and those who had low levels of vitamin D (less than 15 ng/ml or 37.5 nmol/L serum 25-hydroxyvitamin D). This suggests there may be a limit to what vitamin D can do for the heart.

Realizing There’s More to Learn About Vitamin D and the Heart

Throughout this chapter I showed you a lot of amazing research that points to a relationship between vitamin D and things that affect heart health. I think we can safely say that vitamin D is doing something positive. The problem that remains is how do we use that information? Right now there is no reason to doubt that it’s important to avoid having low vitamin D status (serum 25-hydroxyvitamin D levels less than 20 ng/ml or 50 nmol/L). You can do that by following the dietary recommendations from Chapter 2.

But here’s what we don’t know. Does even higher serum 25- hydroxyvitamin D (say greater than 30 ng/ml or 75 nmol/L) give even greater protection against heart disease or hypertension? Is vitamin D better than other prevention strategies like controlling your weight, eating right, and exercising? If you have a heart condition does more vitamin D help everyone or just people with very low vitamin D status? Researchers are actively working on these and other questions, so keep your eyes peeled for new research in the future. But in the meantime, be cautious that “more” is not necessarily “better.” Some of the associational studies that suggest low levels of vitamin D increase the risk of cardiovascular disease have also suggested that higher levels increase the risk of mortality, cardiovascular disease, and certain cancers. So we won’t know what the optimum vitamin D levels are until randomized trials are done with long-term (of more than five years) followup.