WASHINGTON — Even without evidence of coronary calcium on CT, a large proportion of diabetic patients are still at risk for atherosclerosis, Liviu Klein, M.D., said at a conference on cardiovascular disease epidemiology and prevention sponsored by the American Heart Association.
“Diabetics are clearly at risk for atherosclerosis. Some people believe that CAC [coronary artery calcium] is a perfect tool for discrimination, but it's not. … My concern is that the absence of CAC will be used as a reason not to treat,” Dr. Klein, a fellow in cardiovascular epidemiology and prevention at Northwestern University, Chicago, said in an interview.
About 30% of diabetic adults aged 45 and older without clinically manifest coronary heart disease have no coronary artery calcium (CAC score of 0) on CT. No previous study compared other markers of atherosclerosis in that subgroup with those of nondiabetics without CAC. The first-ever study to do so is a part of the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based cohort of 6,814 African American, white, Chinese, and Hispanic adults aged 45–84 without symptoms or history of cardiovascular disease.
A total of 350 (34%) of the diabetic participants and 2,825 (49%) of the nondiabetic participants had CAC scores of 0 on coronary CT. Diabetic subjects were older than nondiabetics (61 vs. 57 years) and were more likely to be African American (44% vs. 28%) or Hispanic (34% vs. 23%). Average body mass index (BMI), waist circumference, and triglyceride and LDL-cholesterol levels were also higher in the diabetics than in the nondiabetics, Dr. Klein reported.
On B-mode carotid ultrasound, the diabetic patients had significantly higher common and internal carotid intimal medial thickness (IMT) than did nondiabetics, both before and after adjustment for age, gender, ethnicity, and traditional risk factors for atherosclerosis, including blood pressure, cholesterol level, BMI, smoking, socioeconomic status, and use of statins and aspirin.
After adjustment, common carotid IMTs were 0.84 mm for the diabetics and 0.81 for the nondiabetics; internal carotid IMTs were 0.98 mm and 0.86 mm, respectively. Levels of intercellular adhesion molecule-1 (ICAM-1), E-selectin, interleukin-6, and C-reactive protein (CRP) were all significantly greater in the diabetic group, indicating a greater burden of atherosclerosis, Dr. Klein said.
Mean ankle-brachial index did not differ significantly between the two groups either before or after the same adjustments, nor were there differences in levels of the plaque instability markers matrix metalloproteinase (MMP)-3, MMP-9, or soluble CD40 ligand (CD40-L).
Whether diabetic patients without a history of myocardial infarction have the same risk of CHD events as nondiabetic patients with a history of MI remains controversial, despite two sets of evidence-based guidelines issued by the National Heart, Lung, and Blood Institute categorizing diabetes as a “risk equivalent” for coronary heart disease and advising that all individuals with diabetes receive intensive CHD risk factor management (JAMA 2001;285:2486–97, JAMA 2003;289:2560–72).
However, conflicting data have appeared both before and since the dissemination of those two documents (the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults and the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure).
One recent study, for example, found that diabetic patients without MI had a lower risk of CHD events and mortality from cardiovascular disease than did nondiabetic patients with MI, but stroke risk was similar between the two groups (Circulation 2004;109:855–60), while another suggested that 5-year survival among diabetics without CAC is similar to that of nondiabetic subjects without CAC (J. Am. Coll. Cardiol. 2004;43:1663–9).
But, according to Dr. Klein, there are multiple problems with these and similar studies. They have not accounted for the fact that mean CAC differs among individuals of different races. In particular, African Americans and Hispanics have lower mean CAC values than do whites, despite having higher MI rates. “We don't really know what the calcium score means,” he said.
Moreover, these new data from MESA show that even if someone with diabetes has a CAC of 0 now, that person is likely to have a significantly higher atherosclerotic burden, compared with a nondiabetic. “If you wait until a diabetic has CAC, you will have missed the chance to prevent diabetes complications. … It's not so much an issue of mortality as it is of morbidity,” Dr. Klein said at the meeting, also sponsored by NHLBI.
As it is, fewer than 25% of diabetics receive appropriate treatment for cholesterol, hypertension, and glucose. That number could drop significantly if physicians use a CAC score of 0 on CT as a threshold for intensive treatment, he noted. “The problem is the more tools you have, the easier it is to just get the test rather than committing yourself to lifestyle modification. … But in diabetics, who clearly have atherosclerosis, you have to treat them.”