What Causes Heart Disease?

Although this report focuses on cholesterol, keep in mind that high cholesterol isn't the only cause of heart disease or the only characteristic that predicts an individual's risk of developing heart disease. For instance, although the Framingham Heart Study showed that having high cholesterol is risky, it also showed that having low cholesterol doesn't guarantee protection against heart disease. In that study, although heart disease risk was clearly greater among people with total cholesterol levels above 240 mg/dL, almost half of the people who developed coronary artery disease had total cholesterol levels below that mark, and many other people with levels above 240 mg/dL never developed coronary artery disease. (In the past, many large studies relied on total cholesterol levels because that was the only information available. Today, the NCEP guidelines de-emphasize the importance of a total cholesterol test in favor of a fasting lipid profile, a blood test that distinguishes HDL, LDL, and triglyceride levels.) While cholesterol values make useful cutoff points for comparisons, there is, as yet, no specific cholesterol level that guarantees that you will, or won't, develop heart disease.

Risk Factors

High LDL cholesterol is just one of the risk factors linked to heart disease. There are several others, including having high blood pressure or a family history of heart disease. Additional factors are being investigated, one or more of which may someday join the established group (see "Risk factors under investigation"). For now, the following characteristics are known to raise your risk for heart disease:

having a first-degree relative (parent or sibling) who developed heart disease before age 55 for men or age 65 for women
being a man age 45 or older, a woman age 55 or older, or a woman with premature menopause who is not taking hormone therapy
smoking cigarettes
having high blood pressure
having diabetes
having chronic kidney disease
being more than 30% over ideal body weight
being diagnosed with metabolic syndrome
having a sedentary lifestyle
having an HDL cholesterol level below 40 mg/dL.

Fast fact

Diabetes and chronic kidney disease are considered "heart disease equivalents": They pose as great a risk for heart attack as heart disease itself.

You can use the Heart Attack Calculator (see Tables 2 and 3) to figure out your risk of having a heart attack during the next 10 years, or go to the National Heart, Lung, and Blood Institute Web page at hin.nhlbi.nih.gov/atpiii/calculator.asp to calculate your risk online.

As obvious as it might sound, the people who face the highest risk of having a heart attack are those who've already had one, those who've been treated for a dangerously narrowed coronary artery, and those who have angina (chest pain). Because people who have already had one such "cardiac event" are at high risk for another, it's especially important for them to keep their cholesterol in check and to tend to other risk factors as well. In fact, if you are at high risk for heart disease, your cholesterol goal will be lower than for people with lower risk (see Table 4).

Risk factors influence your chances of having a heart attack or some other circulatory problem in a number of ways. Cigarette smoke, for example, has direct toxic effects on artery walls. High blood pressure puts stress on the walls of blood vessels, and high blood sugar from diabetes can damage the arterial lining and make platelets stickier and more likely to clot. Obesity raises the risk for coronary disease largely by promoting other risk factors, such as elevated blood pressure.

Risk factors under investigation

If you follow medical news closely, it can seem like new risk factors for heart disease are being discovered daily. While the risk factors listed below represent exciting advances in the understanding of heart disease, they are not yet ready for use in determining medical care for most patients. In order to get to that point, a risk factor must pass a few hurdles. One of the main ones is proving that treating the risk factor — or using the information it provides to treat other risks — leads to a reduction in deaths, heart attacks, or strokes.

C-reactive protein (CRP). Inflammation in the heart's arteries can lead to a heart attack. Studies have shown that elevated levels of CRP — a by-product of inflammation — may be a predictor of heart attacks. This is the most established of the risk factors under investigation.

Levels of CRP can be measured in the blood. To evaluate heart disease risk, your doctor will order a high-sensitivity CRP test (also known as a cardiac CRP test) rather than the standard CRP test.

The experts advise against widespread screening for elevated CRP, but in some cases such a blood test can provide a way to identify people who might benefit from a more aggressive effort to prevent or treat heart disease. Your doctor may want you to have a CRP test if your cholesterol levels are acceptable but you have other signs that heart trouble could be in your future, like a family history of heart disease, high blood pressure, or diabetes. Also, if you and your doctor are debating a change in your treatment plan, knowing your CRP might be useful in tipping the balance in favor of moving in one direction or another. Risk assessment is based on three levels of CRP:

low cardiovascular risk: CRP level below 1 mg/L
average cardiovascular risk: CRP level of 1–3 mg/L
high cardiovascular risk: CRP level above 3 mg/L.

A high CRP isn't a disease. Think of it as a symptom, like a fever, which signals that something is amiss and needs tending. Losing weight, stopping smoking, and exercising all lower CRP — and help with many other risk factors for heart disease. Aspirin and statins also lower CRP levels. What remains unclear is whether lowering CRP levels actually reduces the risk of having a heart attack, stroke, or dying from heart disease. Two studies reported in 2005 provided some indication it might: Both found that people with existing heart disease who used statins to lower cholesterol also reduced CRP levels. At any given cholesterol level, those people with the lowest CRP also experienced the greatest protection against a heart attack or another cardiac event. But the research continues, and as yet there is no proof that lowering CRP levels will reduce the risk of having a heart attack or stroke.

Lipoprotein(a). Lipoprotein(a), often abbreviated as Lp(a), is a molecule of LDL cholesterol with an extra protein attached. Some studies show a connection between high Lp(a) and increased risk for heart disease and stroke. Others don't. One thing seems clear — high levels are worrisome in people with high LDL. Among those with normal cholesterol, Lp(a) might be important when HDL levels are low. One problem with measuring Lp(a) levels is that the normal range varies tremendously depending on your ethnicity.

Homocysteine. While dozens of studies have suggested that elevated blood levels of this amino acid are a major risk factor for heart disease, it has not yet been proved that testing people for homocysteine and decreasing their levels will actually reduce their risk of heart disease. In fact, two studies published in 2006 found that even though folate and vitamin B reduced blood levels of homocysteine, they did not reduce the risk of heart attack, stroke, or sudden cardiac death. More studies are under way, but in the meantime, a reasonable recommendation is to do the things that are thought to lower homocysteine and known to promote a healthy heart, including taking a multivitamin and following a diet low in fat and salt and high in fruits, vegetables, and fiber.

Infectious agents. What causes arterial inflammation in the first place? A growing body of evidence suggests that metabolites (substances produced during metabolism) of blood lipids can themselves activate the same inflammatory signals that are typically engaged when the body is trying to fight off an infection. For some time, investigators thought that atherosclerosis might itself be caused by an infectious agent, but this now seems unlikely. It is possible that infections could make atherosclerosis lesions worse, but even this idea remains unproven. At the moment, there is little to justify the use of antibiotics as an effective therapy for the prevention or treatment of coronary artery disease.

Elevated fibrinogen levels. Fibrinogen is a blood protein that's essential to the clotting process and, as such, is essential to health. However, because in many cases blood clotting is the final event that blocks the coronary arteries, it's not surprising that studies have implicated elevated fibrinogen levels as a cardiac risk factor. Although fibrinogen levels can easily be tested, at present they aren't routinely measured because there's no known way to bring down high fibrinogen levels. It's also unclear whether reducing levels of fibrinogen would lower the risk for heart disease or stroke. In some cases, however, regular exercise, weight loss, and quitting smoking can reduce elevated fibrinogen. Other interventions that prevent excessive blood clotting include low-dose aspirin, low-dose alcohol, and a diet high in fish.

Protective Factors

Protective factors are the opposite of risk factors in that they help lower your chances of developing heart disease.

HDL

One of the most important protective factors is a high level of HDL ("good") cholesterol. The more HDL in your bloodstream, the lower your chances of having a heart attack; studies from Framingham and elsewhere suggest that every one-point rise in HDL is accompanied by a 2%–3% drop in heart attack risk. Some lucky people are born with a natural capacity for making high levels of HDL. Others have to work at it. The NCEP guidelines say that an HDL level below 40 is a risk factor for heart attack, and a level of 60 or more protects against heart disease.

For this reason, using a total cholesterol measurement to judge your health risk is unreliable: Increasing your HDL raises your total cholesterol level, yet it decreases your risk of heart problems. Usually, though, a high level of total cholesterol is bad news and points to a greater risk for heart disease because it ordinarily reflects a high level of the more plentiful and more harmful LDL. At the same time, a high HDL level is no guarantee against heart disease, and a low HDL level does not mean a definite date with the coronary care unit.

Exercise

Regular physical activity or exercise helps prevent heart disease in several ways. It raises the level of HDL, lowers triglyceride levels, lowers blood pressure, and tones the heart so it pumps blood more efficiently (see "Your exercise program").

Estrogen

Women usually develop heart disease later than men, but they catch up quickly. Women who've gone through menopause have two to three times as many heart attacks as women the same age who haven't yet experienced this change of life. In the United States alone, heart disease and stroke kill one woman every minute, more than 480,000 women every year. Indeed, heart disease and stroke are the leading causes of death for women in the United States, causing roughly 12 times as many deaths as breast cancer. Being female does delay the onset of heart disease, and researchers believe that before menopause, steady and plentiful production of the female hormone estrogen helps keep heart disease at bay. Normal estrogen production may also help maintain a favorable cholesterol profile — most premenopausal women have lower levels of total cholesterol and higher levels of HDL than men of the same age.

It would be logical to assume that using a drug to replace the hormones that women stop producing at menopause would provide the same benefit. That's what the medical community did assume — until results from a large 2002 study showed that women on hormone therapy had more heart attacks, strokes, and blood clots (and cases of breast cancer) than women who did not take hormones. After that, doctors stopped recommending hormone therapy for anything other than short-term control of menopausal symptoms.

Weighing the Risks

Not all risk factors are created equal; each carries a certain weight in calculations that predict heart disease. Some of your lifestyle choices and habits make a bigger difference than others in cutting your chances of developing heart disease or having a heart attack. A survey of risk-reduction strategies by Harvard researchers showed these risks and benefits:

The risk for heart attack decreases by 50% one year after a person quits smoking.
Being sedentary almost doubles the risk for coronary artery disease.
A person who maintains a healthy weight as he or she gets older, or keeps body weight near "ideal," has a 45% lower risk.
Reducing total cholesterol by 10% cuts heart attack risk by 20% to 30%.

The Framingham Heart Study team has devised a simple and rather ingenious approach to estimating your chances of developing heart disease over the next 10 years (see Tables 2 and 3). You choose the category that most closely applies to you from each of five boxes — age, total cholesterol level, smoking, HDL cholesterol level, and blood pressure. Each answer is assigned a certain number of points, and the total gives a best guess about your chances of having a heart attack or other form of coronary artery disease within the next 10 years.