Statins Sever the Diabetes and Coronary Disease Link


The maxim that diabetes is a coronary risk equivalent is falling out of favor.

Some experts now say that while diabetes raises a patient’s risk for developing cardiovascular events, it doesn’t pack nearly the same punch as a history of coronary disease.

One reason for this disconnect may be widespread use of statins, which seem to blunt the impact of hyperglycemia on cardiovascular disease by damping down the low-density lipoprotein (LDL) cholesterol part of the risk equation.

©Science; used with permission

Insulin-producing mouse spleen cells.

At the American Heart Association Scientific Sessions in Los Angeles, Toronto endocrinologist Dr. Lawrence Leiter ran through the up-and-down history of diabetes as a coronary-disease risk equivalent. He traced the origin of the idea to a 1998 report that analyzed data from Finland showed that the rate of a future myocardial infarction (MI) in patients with diabetes but no history of MI (about 20% over 7 years) was strikingly similar to the rate seen in patients with a history of MI but no diabetes (N. Engl. J. Med. 1998;339:229-34).

While results from some subsequent studies supported this pattern and led to the risk-equivalent concept getting enshrined in the official U.S. 2002 cholesterol-treatment guidelines, a larger number of studies showed something else: Patients with a history of MI had a substantially higher rate of subsequent MIs or cardiovascular deaths than patients with diabetes but no coronary disease history. For example, Dr. Leiter cited recent study results that analyzed outcomes of more than 1.2 million Alberta, Canada, residents over 4 years (Lancet 2012;380:807-14).

Patients with a prior MI had new MIs at a rate of 19/1,000 person-years of follow-up, compared with a rate of 5/1,000 person-years’ follow-up in patients with a history of diabetes and no prior MI.

Dr. Leiter said the misleading 1998 result that launched the risk-equivalent canard may have happened because the study was in Finland, a country with a high rate of coronary disease (and, he could have added, lots of people with high LDL levels). "The risk of cardiovascular disease in patients with diabetes is high, although not to the point that diabetes is a coronary disease risk equivalent," he said. But he still strongly endorsed using statins to reduce whatever elevated risk a patient with diabetes has. "Given that the price of statins has fallen and the safety of statins is remarkably good, one could argue that you don’t need to risk stratify diabetics to decide who to put on a statin."

More evidence of a diabetes and cardiovascular disease disconnect came in a separate talk at the meeting by Dr. Thomas Pearson, a Rochester, N.Y., preventive medicine specialist, who addressed this paradox: If diabetes and cardiovascular disease are so tightly linked, why over the past 40 years has the prevalence of obesity and diabetes in the United States soared while cardiovascular disease rates fell?

Statins are why, Dr. Pearson said, and perhaps some diet improvement, too.

"LDL is the primary determinant of atherosclerosis; reduced levels [of LDL] negate the effects of diabetes and other obesity-related risk factors," he said.

Dr. Pearson cited a 2005 study of data collected during 1960-2000 by the U.S. National Health Examination Survey that showed among obese Americans (with a body mass index of 30 kg/m2 or more) levels of elevated total cholesterol (240 mg/dL or greater) fell by more than half, from a 39% prevalence in 1960 to an 18% prevalence in 2000.

He also pointed to an epidemiologic study he collaborated on that examined LDL levels and diabetes prevalence on the Caribbean island of Grenada. Coronary disease is essentially nonexistent in Grenada, no cardiologists practice there, and Dr. Pearson said "I spent 3 years looking and never found a person with an MI."

That situation exists even though the average body mass index among middle-aged women is 30 kg/m2 (meaning that half of the women are obese), and 16% of men and 30% of women who are 55-64 years old have diabetes. But their average LDL cholesterol level is around 130 mg/dL, a relatively low level.

"Grenada is a low-LDL population that can apparently brush off diabetes," he told me. The implications go far beyond the small island nation: "If you can get your LDL cholesterol under control, the other things, like diabetes and hypertension, don’t mean as much," at least for macrovascular disease like MIs. Low LDL means no atherosclerosis, so "you don’t have diabetes, obesity, or hypertension acting on an atherosclerotic substrate."

–Mitchel L. Zoler (on Twitter @mitchelzoler)

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