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Update On Heart Disease
Evidence Mounts for Even Lower LDL

by Wayne L. Clark

Atherosclerosis is much more prevalent in people with diabetes, especially Type 2 diabetes, who have a characteristic profile of blood fats, or “lipids,” that puts them at higher risk. They tend to have low levels of high-density lipoprotein (HDL) cholesterol, often referred to as “good” cholesterol, because it appears to protect against atherosclerosis, and high levels of triglycerides (another form of blood fat).

There is a third very important feature to the “lipid profile” typical in Type 2 diabetes and also in the metabolic syndrome. Levels of LDL cholesterol (often referred to as “bad” cholesterol) are generally the same as those in the general population or only slightly elevated in people with diabetes, but it is a different kind of LDL. The concentrations of triglycerides in LDL cholesterol change it to a smaller, denser particle. Being smaller, these particles can more easily cross the endothelium—the lining of the arteries—and enter the walls of the vessels.

Three-quarters of people with diabetes will die of complications that arise from atherosclerosis. They have a 2–4 times higher risk of heart attack and stroke, and are more likely to die in the hospital while undergoing a cardiac procedure. They also do less well following a heart attack or surgery. Atherosclerosis in the peripheral circulation, primarily in the arteries of the legs, is 2–4 times more likely in people with diabetes. This can lead to dangerous clots, pain, and the need for amputation.

The growing understanding of the higher cardiac risk for people with diabetes has been reflected in the treatment guidelines published by the ADA, the National Cholesterol Education Program, and the American College of Physicians. In the 1990’s, for instance, ADA guidelines called for medication management if LDL levels were above 130 mg/dl. Current guidelines suggest starting lipid-lowering medicines for LDL levels above 100 mg/dl, and a target of less than 70 mg/dl if the person is known to have heart disease.

The National Cholesterol Education Program (NCEP) Adult Treatment Panel III guidelines, published in 2004, call diabetes a “coronary heart disease risk equivalent.” People with diabetes carry an absolute risk of cardiac events similar to that of people without diabetes but with established heart disease. The NCEP recommends that people with diabetes be managed as if they already had known coronary artery disease.

Two follow-up studies using the TNT study reinforce this approach. The studies focused on those participants who had diabetes and those who had metabolic syndrome (a cluster of conditions that raises the risk of developing diabetes).

The first study examined the results for the 1,501 participants who had diabetes. At the end of the nearly five years of the study, their mean LDL levels were 98.6 mg/dl in the regular treatment group and 77 mg/dl in the intensive treatment group.

There was a higher incidence of cardiovascular events among the people with diabetes compared with those who didn’t have diabetes. However, the participants with diabetes on intensive atorvastatin therapy experienced a 25% reduction in the rate of major cardiovascular events compared with participants with diabetes on the regular therapy. So while the risk of the people with diabetes on the intensive therapy was still greater than that of the people who didn’t have diabetes, they experienced a similar reduction in their risk.

Of particular note was that the incidence of first stroke was reduced in the intensive-therapy group, and that risks were reduced for all in the intensive group, regardless of their level of blood glucose control (although those with a glycosylated hemoglobin [HbA1c] value of 7% or lower saw additional risk reduction).

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