Premature coronary artery disease in women: sex-specific risk factors, pathogenetic mechanisms and clinical implications

INTRODUCTION: Premature coronary artery disease (PCAD) in women, defined as onset ≤65 years, accounts for 20-30% of CAD cases. The clinical implications, pathogenic processes, and sex-specific risk factors of female PCAD are summarized in this review. DISCUSSION: Women have unique patterns in the traditional metabolic risk factors of smoking, diabetes, obesity, and hypertension. Elevated triglyceride-rich lipoproteins and lipoprotein(a) are highly associated with early atherosclerosis. Premature menopause, autoimmune diseases like systemic lupus erythematosus, and pregnancy difficulties like preeclampsia and gestational diabetes are among the special factors that affect women and worsen inflammation and endothelial dysfunction. PCAD progression is also influenced by inflammatory pathways (e.g. NLRP3 inflammasome activation) and genetic predispositions (e.g. 9p21 locus polymorphisms, familial hypercholesterolemia). Diagnostic delays occur because women frequently appear clinically atypically (e.g. fatigue, nausea) and show non-obstructive lesions or spontaneous coronary artery dissection (SCAD). Sex-tailored approaches are needed for management, such as aggressive lipid control, metabolic risk reduction, and psychosocial support. CONCLUSION: Female PCAD is a complex condition influenced by a combination of traditional metabolic risk factors, sex-specific factors, and genetic predispositions. Sex-specific biomarkers and multi-omics techniques should be given top priority in future studies in order to improve early detection and tailored treatment.