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Special Article |

Women and Heart Disease:  The Role of Diabetes and Hyperglycemia

Elizabeth Barrett-Connor, MD; Elsa-Grace V. Giardina, MD; Anselm K. Gitt, MD; Uwe Gudat, MD; Helmut O. Steinberg, MD; Diethelm Tschoepe, MD
Arch Intern Med. 2004;164(9):934-942. doi:10.1001/archinte.164.9.934.
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Cardiovascular disease (CVD) is the primary cause of death in women, and women with type 2 diabetes mellitus are at greater risk of CVD compared with nondiabetic women. The increment in risk attributable to diabetes is greater in women than in men. The extent to which hyperglycemia contributes to heart disease risk has been examined in observational studies and clinical trials, although most included only men or did not analyze sex differences. The probable adverse influence of hyperglycemia is potentially mediated by impaired endothelial function, and/or by other mechanisms. Beyond high blood glucose level, a number of other common risk factors for CVD, including hypertension, dyslipidemia, and cigarette smoking, are seen in women with diabetes and require special attention. Presentation and diagnosis of CVD may differ between women and men, regardless of the presence of diabetes. Recognizing the potential for atypical presentation of CVD in women and the limitations of common diagnostic tools are important in preventing unnecessary delay in initiating proper treatment. Based on what we know today, treatment of CVD should be at least as aggressive in women—and especially in those with diabetes—as it is in men. Future trials should generate specific data on CVD in women, either by design of female-only studies or by subgroup analysis by sex.

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Figure 1.

Percentage of patients diagnosed with coronary vascular disease, according to risk factors. Percentage of patients diagnosed with coronary vascular disease over 10 years was estimated according to various combinations of risk factors. Each risk factor increases the percentage of patients with diagnosed coronary vascular disease. For all risk factors other than diabetes, the difference between men and women is maintained. In contrast, diabetes closes the gap between men and women (see fifth pair of columns from left). HDL-C indicates high-density lipoprotein cholesterol; plus sign, yes; minus sign, no. To convert cholesterol to millimoles per liter, multiply by 0.0259. Adapted from Kannel5 (1996), with permission.

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Figure 2.

Relative risk of cardiovascular events in people with diabetes. Except for stroke, the relative risk of cardiovascular disease (CVD) associated with diabetes is greater for women than for men. The dashed line represents a relative risk of 1 (ie, the relative risk expected of a control group). Adapted from Wilson and Kannel6 (1992), with permission.

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Figure 3.

Relative risks of coronary heart disease (CHD) in women. Relative risks of fatal CHD according to duration of diabetes mellitus (DM) and stratified by a history of CHD. The asterisk indicates that women without a history of CHD who have diabetes for more than 15 years share the relative risk of those with a history of CHD. Adapted from Hu et al18 (2001), with permission.

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Figure 4.

Hypothetical model of insulin-endothelium interaction. Nitric oxide (NO) released from the endothelial cell diffuses through the subendothelial space to the vascular smooth muscle cell, where it activates guanylate cyclase, which leads to increased cyclic guanosine monophosphate (cGMP) levels. This increase in cGMP initiates a set of reactions that ultimately leads to lower intracellular calcium (iCa) levels, resulting in relaxation of the vascular smooth muscle cell. In vivo, relaxation of the vascular smooth muscle will lead to increased blood flow. L-NMMA indicates NG-monomethyl-L-arginine.

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