The Gladstone Connection

Heart Disease: Still Deadly, Still on the Rise

Heart disease continues to be the leading cause of death in the United States, as it has been for more than a century, claiming more than 900,000 lives annually, or 38.5% of all deaths. High blood pressure, coronary heart disease (CHD), heart attack, congestive heart failure, stroke, and congenital heart defects account for more deaths than the next five major causes combined (cancer, diabetes mellitus, emphysema, accidents, and pneumonia). Two-thirds of deaths from cardiovascular disease are due to the effects of atherosclerosis on the coronary arteries and arteries in the brain and other parts of the body.

The value of lowering levels of low density lipoprotein cholesterol (LDL or “bad” cholesterol) is well known. Many studies indicate that heart attacks can be prevented by reducing LDL. This can be achieved in many cases by eating a diet low in saturated fat, trans-fatty acids, and dietary cholesterol, maintaining a healthy weight, and exercising. Excellent drugs are available to help those who cannot achieve optimal LDL levels with lifestyle changes alone. However, elevated LDL levels may be only half the equation. Only about 40% of heart disease patients have high LDL. But about 67% have low levels of high density lipoprotein cholesterol (HDL or “good” cholesterol). In fact, a low level of HDL (<40 mg/dl)—itself an independent risk factor for heart disease—is the most common lipid abnormality in patients with CHD.

The Good, the Bad, and the Unknown

LDL and HDL both transport cholesterol, which is used to make cell membranes and some hormones, but they carry it in opposite directions. LDL ferries cholesterol throughout the body, including the coronary arteries, where it can be taken up by cells in the artery wall and contribute to the build-up of atherosclerotic plaques. HDL removes excess cholesterol from the circulation and delivers it to the liver for disposal. Through a process known as reverse cholesterol transport, HDL is also thought to remove cholesterol from atherosclerotic plaques. However, there is still much to learn about HDL and its protective role in heart disease.

A balance is maintained between the influx and deposition of cholesterol by LDL and the efflux of cholesterol out of the artery wall by HDL. Atherosclerotic plaques form when the balance is tipped to deposition by excess LDL. The growing plaque slowly occludes the artery. However, if the cap over the plaque ruptures, a blood clot may completely block the artery and result in a heart attack.

	Statistics on Cardiovascular Disease in the United States Lifetime risk of CHD among 40-year-olds: 1 in 2 for men, 1 in 3 for women Daily number of deaths from CVD: Almost 2600 Aveage frequncy of death from CVD: 1 every 34 seconds Estimated yearly number of new coronary attacks: 700,000 Estimated yearly number of recurrent attacks: 500,000 Percentage of deaths from CHD with no previous symptoms: 50% of men, 64% of women Percentage of heart attack victims who die within one year:,br> 25% of men, 38% of women Estimated direct and indirect cost of CHD in 2004: $133.2 billion		Recent studies have shown benefit in aggressively reducing LDL in patients whose low levels of HDL place them at increased risk of CHD. Unfortunately, the existing guidelines do not recognize the need for substantially lower target LDL levels in these patients than in those with normal HDL. In addition, there are no drugs that raise HDL and are easily tolerated by patients. The “gold standard” guidelines, those of the National Cholesterol Education Program (NCEP), qualify patients for treatment based on LDL levels and on the risk of a coronary event, such as a heart attack or angioplasty, within 10 years, as determined with risk assessment tables. Patients are assigned to one of three categories, based on the number and severity of risk factors—age, smoking, total cholesterol level, hypertension, low HDL, and a family history of premature CHD. However, since LDL is the sole lipid criterion for initiating and establishing the goals of therapy, patients with levels below the threshold for initiating treatment might not be treated—even though they are at high risk because of their low HDL levels. A new strategy Two scientists at the Gladstone Institute of
Cardiovascular Disease, Robert W. Mahley and Thomas P. Bersot, who are specialists in lipid disorders, have developed guidelines for the management of patients with low HDL levels. These “low-HDL” guidelines were inspired by the findings of the Turkish Heart Study, an ongoing epidemiological study of risk factors for heart disease in Turkey. In that study, Dr. Mahley and his Turkish colleagues have found that Turks—a population known to have a high rate of CHD—have low levels of total cholesterol (TC) and LDL and extremely low HDL levels.

The Turkish Heart Study is an epidemiological survey of more than 10,000 persons in six regions of the country. The clear-cut regional differences in dietary fat consumption make Turkey an ideal setting for this large-scale study of the effects of diet and other environmental risk factors for heart disease. Several important findings were reported in the Journal of Lipid Research in 1995. Based on this report, the Turkish Society of Cardiology developed guidelines for managing lipid disorders in the Turkish population.

The new HDL guidelines use the TC/HDL ratio—the most sensitive indicator of lipid-related CHD risk—as well as LDL levels to identify patients for treatment. The TC/HDL ratio predicts CHD risk regardless of the absolute levels of LDL and HDL. A ratio of 3.5 or less is ideal. The low HDL guidelines also enumerate risk factors, but require only routine lipid analyses and the patient’s medical history. They do not require the calculation of a risk score or rely on LDL as the only lipid risk factor. Their simplicity should enhance physician compliance with their use.