Coronary Artery Calcium: A Clue to the Enigma of Tight Glycemic Control and Cardiovascular Disease?

  1. Alain G. Bertoni1 and
  2. Dalane W. Kitzman2
  1. 1Division of Public Health Sciences, Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina;
  2. 2Section of Cardiology, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
  1. Corresponding author: Alain G. Bertoni, abertoni{at}

Among individuals with diabetes, dyslipidemia, hypertension, and other processes contribute to the development of atherosclerosis, which underlies most cardiovascular disease (CVD), the leading cause of mortality in diabetes (1). However, people with both type 1 and type 2 diabetes are likely more susceptible to CVD due to hyperglycemia, abnormal fatty acid metabolism, and insulin resistance, which have adverse effects on the vascular endothelium (2). The impaired endothelium promotes vasoconstriction, inflammation, and thrombosis, which in turn promote the formation of atherosclerotic plaques (2). Occlusion of coronary arteries by plaque rupture and thrombosis underlies coronary heart disease (CHD) (3). Calcium is deposited in early atherosclerosis lesions; in advanced plaques, the calcification is extensive and can be detected by chest computed tomography (CT) (4). The amount of coronary artery calcium (CAC) present is correlated strongly with the overall burden of atherosclerosis in the coronary arteries (4). There is increasing consensus that CAC score is predictive of future CHD and CVD events and may improve prediction beyond that of the Framingham Risk Score (5).

How to best prevent CVD among individuals with diabetes remains the focus of much research. Since the publication of the National Cholesterol Education Program's most recent guideline, it has been common to classify all adults with diabetes as CHD risk equivalents (i.e., Framingham Risk Score >2% per year) eligible for aggressive risk factor modification (6). There is evidence of benefit for lipid-lowering, antihypertensive, and antiplatelet therapies (7). Despite data supporting a direct relationship between glucose control and CVD (8), early randomized controlled trials (RCTs) did not demonstrate that glucose control prevented …

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