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Hoong Sern Lim, MRCP; Robert J. MacFadyen, MD, PhD, FRCP; Gregory Y. H. Lip, MD, FRCP

Arch Intern Med. 2004;164:1737-1748.

With diabetes mellitus reaching epidemic proportions, mainly secondary to obesity, the impact of cardiovascular disease due to this combination makes it a dominant public health problem during the first quarter of the 21st century. The complex interaction that results in diabetic heart disease is created by overlapping mechanisms. There is a propensity to develop premature, diffuse atherosclerotic coronary disease, which is associated with adverse short- and long-term morbidity and mortality. There are structural and functional abnormalities of the microvasculature, autonomic dysfunction, and intrinsic failure of myocardial contraction (so-called diabetic cardiomyopathy). These changes are amplified by arterial hypertension and kidney disease. In this review, we consider the role of the renin-angiotensin-aldosterone system and how it is a crucial driver of most of the pathophysiologic mechanisms behind diabetic heart disease and why in the past 5 years blocking this system in diabetic patients has emerged as a critical therapeutic intervention.

From the University Department of Medicine, City Hospital, Birmingham, England. Drs Lim and Lip are investigators in the ADVANCE trial, a large randomized trial of diabetic vascular outcomes supported by SERVIER Laboratories, and Drs MacFadyen and Lip have received funding for research, educational symposia, and lecturing from different manufacturers of drugs used for the treatment of hypertension, heart failure, and diabetes.

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