Sex-specific differences in hypertension and associated cardiovascular disease

Key Points Although blood pressure (BP) is lower in women than in men during the reproductive years, 50% of all cardiovascular disease (CVD)-related deaths occur in women, resulting in a greater incidence of CVD in older women than in age-matched men. The same mechanisms that regulate BP and cardiovascular function are present in both men and women, but these systems are shifted towards cardioprotective pathways in women between puberty and menopause. Sex hormones such as oestrogen and testosterone have a role in cardioprotection by modulating vasodilator and vasoconstrictor pathways, including the renin–angiotensin–aldosterone system (RAAS) and the endothelin system. The sex chromosome complement can act independently of sex hormone effects, which results in sex-specific, age-specific and tissue-specific differences in gene transcription. Obesity affects more women than men; as obesity is associated with a loss of cardioprotection, CVD occurs at an earlier age in obese women than in lean women. Women have a longer lifespan than men and develop age-related and CVD-related pathologies later in life; these beneficial outcomes might be due in part to sex differences in cell injury and repair pathways that delay the chronic accumulation of senescent cells, end-organ damage and the progression of CVD. The authors present sexual dimorphism at the molecular, cellular and tissue level and suggest that it contributes to differences in disease onset, susceptibility, prevalence and treatment responses in hypertension and cardiovascular disease. Several factors that confer relative cardioprotection in women are discussed, including biological age, sex hormones, sex chromosome complement and lifestyle. Although intrinsic mechanisms that regulate arterial blood pressure (BP) are similar in men and women, marked variations exist at the molecular, cellular and tissue levels. These physiological disparities between the sexes likely contribute to differences in disease onset, susceptibility, prevalence and treatment responses. Key systems that are important in the development of hypertension and cardiovascular disease (CVD), including the sympathetic nervous system, the renin–angiotensin–aldosterone system and the immune system, are differentially activated in males and females. Biological age also contributes to sexual dimorphism, as premenopausal women experience a higher degree of cardioprotection than men of similar age. Furthermore, sex hormones such as oestrogen and t