Inflammation, Statin Pleiotropy, and Cardiovascular Prevention in Women: Established Evidence, Biological Plausibility, and Knowledge Gaps

Abstract

Cardiovascular disease remains the leading cause of death among women, yet female cardiovascular risk continues to be underrecognized, and women remain underrepresented in many cardiovascular trials. Sex-related differences in hormonal exposure, immune regulation, vascular function, pregnancy-related conditions, and clinical presentation contribute to heterogeneity in cardiovascular disease across the life course. Statins reduce atherosclerotic cardiovascular events in women and men, with no consistent evidence of treatment-effect heterogeneity by sex. In addition to lowering low-density lipoprotein cholesterol, statins influence inflammatory signaling, endothelial nitric oxide bioavailability, oxidative stress, thrombosis, and plaque biology. These effects are biologically relevant to atherosclerosis; however, current clinical evidence does not establish that LDL-independent statin effects confer a uniquely greater benefit in women. Historical pathological studies suggested that plaque erosion may contribute relatively more often to acute coronary thrombosis in selected younger women, whereas contemporary optical coherence tomography studies show similar overall frequencies of plaque rupture and erosion between sexes and important age-related variation. Evidence for a female-specific effect of statins on post-myocardial infarction remodeling, cognition, or pharmacogenomic susceptibility is also insufficient. This narrative review distinguishes established clinical evidence from mechanistic plausibility and unresolved sex-specific hypotheses. It emphasizes equitable implementation of guideline-directed lipid-lowering therapy, careful evaluation of statin-associated symptoms, and the need for adequately powered studies reporting sex-stratified estimates and formal treatment-by-sex interactions.