Healthy hearts

What to know and do about coronary artery disease

Even though coronary artery disease (CAD) is the most common cause of death globally (16.8% of deaths), most of us still do not grasp who is most at risk, how to know if we are at risk, ways we can prevent it, and methods of treating this disease. To learn more, BeWell spoke with Themistocles (Tim) Assimes, MD, PhD, assistant professor of medicine in the division of cardiovascular medicine at Stanford University School of Medicine. Dr. Assimes currently devotes a majority of his time performing advanced population-based research on the genetic causes of heart attacks and the common conditions that predispose people to heart attacks — including high cholesterol, smoking, diabetes, obesity, high blood pressure, and insulin resistance.

What exactly is CAD?

Coronary artery disease (CAD) is a condition that results from excessive cholesterol buildup in the wall of the major arteries that supply blood to our heart muscle. This buildup is often referred to as cholesterol plaques. The process of plaque formation begins in adolescence in a majority of people, and it occurs in many different parts of the artery concurrently. However, the rate of plaque buildup differs substantially among people. Those people who do not have risk factors for the development of cholesterol plaques usually develop fewer plaques and their plaques stay relatively small during their lifetimes. On the other hand, people with risk factors develop more plaques and their plaques tend to grow at a faster rate. The more plaque you have, the more likely you will suffer consequences of CAD.

Who is most at risk for developing CAD?

Risk factors for the development of CAD include older age, male sex, smoking, elevated blood pressure, diabetes, physical inactivity, and elevated bad cholesterol in the blood stream. Circulating cholesterol is the basic ingredient needed to form plaques within the vessel wall. One can view the other risk factors as irritants of the lining of the wall of the coronary arteries, which make it easier for circulating cholesterol to enter the blood vessel wall and contribute to plaque formation.  

How does CAD progress, and how is it treated?

A plaque that enlarges over several years to decades can eventually cause problems. If the plaque becomes progressively larger without rupturing, it will slowly but surely block the artery and decrease the flow of blood to a part of the heart. Subjects with such plaques usually begin to complain of chest discomfort when they increase their exertion levels, which goes away completely when they rest again ("stable angina"). Angina occurs under these circumstances because the heart needs more blood flow during exertion when it's beating faster and harder, but can't receive it because of the blockage from the plaque.

We can treat angina by prescribing medications that keep our blood pressure and heart rate low during exercise or by unblocking the artery with a coronary stent or a bypass procedure. 

The most dreaded complication of CAD is a myocardial infarction, or "heart attack" — which occurs when the lining of a plaque inside the vessel breaks open and spills the contents of the plaque into the blood stream. The response to this situation is similar to what happens when you accidentally cut your finger.  The artery goes into spasm and a big clot forms to stop the bleeding. When this happens inside a coronary artery in response to a ruptured plaque, blood immediately ceases flowing to a part of the heart. If the blood flow is not restored within about 4 hours, permanent loss of heart muscle tissue results. Subjects suffering from a heart attack usually suffer from angina, but in this case the angina is "unstable" — and usually more severe than "stable angina" — and the unstable angina occurs at rest without exertion and does not stop until the muscle dies.

Subjects can die from a heart attack if a plaque near the beginning of one of the main branches of the arteries of the heart ruptures — because a very large part of the heart is at risk under these circumstances. It is impossible to predict when a plaque will rupture, but — in general — the more plaques you have, and the bigger they are, the higher the chances that at least one will rupture and cause a myocardial infarction.

The best way to minimize the chances of dying or suffering permanent damage from an ongoing heart attack is to go to a hospital to undergo an emergency unblocking of the artery with an angioplasty and a stent by an interventional cardiologist. 

On average, how much of our risk is due to genetics, and how much is influenced by our lifestyle?

We can estimate the relative importance of inherited vs. environmental risk factors for developing CAD by comparing how often identical twins both develop CAD compared to fraternal twins. More recent studies have also been able to estimate the relative importance of genetics vs. the environment using unrelated individuals that have undergone very dense genetic fingerprinting. Collectively, these studies indicate that common genetic variants inherited from your parents are responsible for about 30-50% of your risk of developing CAD.

What sorts of genetic variants can contribute to an increased risk of cardiovascular disease?

About half of the genetic variants you inherit from your parents actually influence your risk of developing CAD — through effects on known risk factors such as blood pressure, cholesterol, or sugar levels. We also know that some people are more prone to smoking cigarettes because they have inherited one or more genetic variants with the genes that regulate the effects of nicotine.

The other half of the genetic variants that do not track with known risk factors of CAD appear to be affecting genes that are expressed in cells that are found in the blood vessel wall. These variants influence risk by mechanisms that are not yet well understood.    

Are there certain demographic groups who are more likely to have an increased genetic risk of cardiovascular disease?

Certain race/ethnic groups clearly suffer CAD more frequently than others, but the relative importance of inherited vs. environmental factors responsible for these differences remains unclear. CAD affects all race/ethnic groups and the main risk factors for CAD increase risk in all race/ethnic groups to a similar degree when they are present. Furthermore, the treatments for CAD work equally well in all race/ethnic groups.    

Who should get tested to see if they have an increased risk of cardiovascular disease?

Everyone should assess his or her risk of CAD on a regular basis, starting from early adulthood, with the help of his or her primary care physician. We estimate risk by measuring one's blood pressure as well as one's cholesterol and sugar levels in the blood as part of a general health assessment. We then input this information, as well as information for other risk factors, into risk calculators to estimate the chances you will have a heart attack over the next 10 or 30 years. Such risk calculators have been developed through the careful examination and follow-up of groups of people over 10 to 30 years.

What should you do if testing indicates your risk of CAD is high?

If, using these calculators, your risk of CAD over the next 10 years is high, we try to identify ways to decrease this risk — either through lifestyle changes and/or the prescribing of drugs. Medications that have been shown to improve risk factors and decrease the risk of CAD in well-conducted randomized clinical trials include: blood thinners that prevent the formation of a clot, such as aspirin; drugs that lower blood pressure; and drugs that lower bad cholesterol.  

The good news is that everyone can reduce his or her risk of CAD by maintaining a healthy weight and through regular aerobic exercise. These two lifestyle factors have beneficial effects on multiple risk factors. A diet that is low in saturated fats appears to decrease the risk of CAD, not only by making it easier to maintain a healthy weight, but also by reducing bad cholesterol levels in the blood stream. Regular aerobic exercise also appears to substantially reduce the risk of CAD through mechanisms that are independent of its beneficial effects on weight, blood pressure, and cholesterol. The increased blood flow that results from aerobic exercise probably stabilizes the lining over existing plaques, making it less likely that these plaques will rupture. Many investigators, including investigators at Stanford, are currently working on ways to better measure the benefit of aerobic exercise and to incorporate this benefit into our risk calculators.

Does genetic testing play a role in further refining the risk profile for CAD?

We are not yet administering genetic testing, routinely, for profiling people to determine their risk of CAD. However, our risk calculators indirectly assess genetic risk because they include information on risk factors such as your blood pressure and your cholesterol levels. These levels are strongly influenced by the variants you have inherited from your parents. We will likely begin to routinely genetically profile people to help determine their risk of CAD sometime in the next 10 to 15 years when (1) we identify a larger fraction of the hundreds of genetic variants that contribute to the risk of CAD and (2) the cost of genetic testing drops low enough to prompt insurers to reimburse for the testing.

… any final thoughts?

Many factors go into determining your risk of CAD, and it is important to consider these factors collectively. Some people have optimal lifestyles, but are still at high risk because they have inherited one or more genetic variants that can result in markedly increased cholesterol levels or blood pressure. Others may have a strong family history due to a genetic mutation that runs in the family, but that we still have not identified. Such individuals should be open to other interventions to reduce risk, even if their lifestyles are optimal. Review your risk with your primary care doctor on a regular basis and obtain an opinion from a specialist in the prevention of CAD when one or more of your risk factors is very strong.  

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