Cardiovascular disease in women with diabetes

Abstract

Cardiovascular disease (CVD) is the leading cause of death among women with diabetes, and accumulated evidence shows that diabetes abolishes the relative cardiovascular protection women otherwise have compared with men in the general population. A meta-analysis of cardiovascular outcome trials in diabetes found that women have a significantly higher relative risk than men of stroke (RR 1.28), heart failure (RR 1.30), and chronic kidney disease (RR 1.33), despite being underrepresented in these trials (28.5–35.8% of the total sample) and receiving statins, aspirin, and beta-blockers less frequently than their male counterparts.

This disparity is explained by a combination of biological and care-related factors: diabetes blunts estrogen-mediated endothelial protection and promotes microvascular dysfunction, resulting in a higher prevalence of angina/ischemia with no obstructive coronary artery disease (ANOCA/INOCA) and in less typical clinical presentations, leading to diagnostic delay. In addition, sex-specific risk windows—gestational diabetes, hypertensive disorders of pregnancy, polycystic ovary syndrome, and early menopause—identify young women with increased cardiovascular risk even before overt type 2 diabetes develops, yet these are rarely assessed systematically during cardiometabolic visits.

From a therapeutic standpoint, the American Diabetes Association's Standards of Care in Diabetes—2026 establish SGLT2 inhibitors and GLP-1 receptor agonists (including dual GIP/GLP-1 agents) as cornerstones of cardiorenal risk reduction, with demonstrated benefit on heart failure, atherosclerotic events, and progression of chronic kidney disease, independent of HbA1c level. Blood pressure targets have become more stringent (systolic <120 mmHg in high-risk patients), and nonsteroidal mineralocorticoid receptor antagonists have been incorporated for selected patients. These benefits are consistent across sexes: the gap lies not in the efficacy of these interventions, but in the intensity with which they are prescribed and in how thoroughly sex-specific risk is assessed in women.

This lecture offers a practice-oriented update: recognizing the pathophysiological and presentation-related particularities of CVD in women with diabetes, systematically incorporating reproductive history into risk stratification, and applying cardiorenal protection strategies validated by the most recent evidence with equal therapeutic intensity in women.