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J Am Coll Cardiol, 2003; 41:1044-1047, doi:10.1016/S0735-1097(02)02982-0
© 2003 by the American College of Cardiology Foundation
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VIEWPOINT

Insulin resistance and compensatory hyperinsulinemia

The key player between cigarette smoking and cardiovascular disease?

Gerald Reaven, MD*,* and Philip S. Tsao, PhD*

a Stanford University School of Medicine, Stanford, California, USA

Manuscript received September 5, 2002; revised manuscript received November 11, 2002, accepted November 27, 2002.

* Reprint requests and correspondence: Dr. Gerald Reaven, Division of Cardiovascular Medicine, Falk CVRC, Stanford University Medical Center, 300 Pasteur Drive, Stanford, California 94305, USA.
greaven{at}cvmed.stanford.edu

Hyperinsulinemia, dyslipidemia, and endothelial dysfunction are characteristic findings in insulin-resistant individuals, and all of these abnormalities have been identified as increasing cardiovascular disease (CVD) risk. Smokers tend to be relatively insulin resistant, hyperinsulinemic, and dyslipidemic, with evidence of endothelial dysfunction, as compared with nonsmokers, and recent epidemiologic data have suggested that CVD in smokers is primarily seen in those individuals who also have the characteristic findings of insulin resistance. Based on these observations, it is argued that insulin resistance and its consequences represent a major mechanistic link between cigarette smoking and CVD. It is also postulated that the enhanced CVD risk in smokers, resulting from hyperinsulinemia, abnormalities of lipoprotein metabolism, and endothelial dysfunction, will primarily be present in those smokers who are insulin resistant. As a corollary, it is suggested that CVD risk in individuals who cannot, or will not, stop smoking can be reduced by therapeutic efforts aimed at attenuating the adverse effects of insulin resistance and its consequences.

Abbreviations and Acronyms
  ADMA
  asymmetric dimethylarginine
  ATP-III
  Adult Treatment Panel III
  CVD
  cardiovascular disease
  HDL
  high-density lipoprotein
  LDL
  low-density lipoprotein
  TG
  triglycerides




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