Sex and Gender Differences in the Clinical Presentation, Diagnosis, and Treatment of Cardiovascular Disease

Background Cardiovascular disease is expressed through biological processes, lived experience, and health-care systems. Biological sex influences anatomy, vascular and myocardial biology, thrombosis, inflammation, pharmacology, and reproductive exposures, whereas gender influences symptom interpretation, help-seeking behaviors, communication, care responsibilities, economic resources, clinician response, and access to treatment. These dimensions overlap but are not interchangeable. Failure to distinguish them can obscure mechanisms and perpetuate inequity. Objective To synthesize contemporary evidence on sex- and gender-related differences in the presentation, diagnosis, treatment, and outcomes of acute coronary syndrome, heart failure, stroke, arrhythmias, peripheral arterial disease, and aortic disease, and to identify practical priorities for more responsive cardiovascular care. Methods A narrative review was undertaken using targeted searches of PubMed, Scopus, and Web of Science for English-language publications from January 2015 through 15 July 2026, supplemented by seminal earlier studies and major professional guidelines. Eligible evidence included cohort studies, registries, systematic reviews, clinical trials, scientific statements, and practice guidelines. Search concepts combined cardiovascular conditions with sex, gender, women, men, symptoms, diagnosis, treatment, delay, disparity, pregnancy, menopause, and outcomes. Evidence was interpreted by separating biological sex from social, cultural, and behavioural gender influences whenever study design and reporting permitted. Results Chest discomfort remains the leading symptom of acute coronary syndrome in both women and men. Women, on average, report a greater number of accompanying symptoms, including dyspnoea, nausea, fatigue, palpitations, and back or jaw discomfort, but symptom overlap is substantial and the label “atypical” is clinically misleading. Women are more likely to experience myocardial infarction with non-obstructive coronary arteries, coronary microvascular dysfunction, spontaneous coronary artery dissection, and stress cardiomyopathy. Heart failure with preserved ejection fraction is more common in women, whereas reduced-ejection-fraction disease and sudden cardiac death are more common in men. Women with stroke more often present at older ages and may have additional non-focal symptoms, yet classic focal deficits remain central in both sexes. Sex-related differences also affect atrial fibrillation, peripheral arterial disease, aortic disease, biomarker interpretation, and imaging. Across conditions, delayed recognition, lower use of specialist testing or evidence-based treatment, and under-representation in trials can compound biological differences. Conclusions Sex and gender influence cardiovascular disease through biological, behavioural, and health-system pathways. Clinicians should use evidence-based, individualized assessment, record sex and relevant gender variables explicitly, and avoid stereotypes about “typical” male and “atypical” female presentations. Equity requires better phenotyping, representative trials, sex-disaggregated analyses, and care pathways that measure and correct unequal treatment.