Y Are Males So Difficult to Understand?

Abstract

Cardiovascular disease (CVD) remains one of the leading causes of death and disability in the Western world, accounting for 48 500 deaths and one third of all mortality in Australia in 2008.1 From 45 to 64 years of age there are significant sex differences in the mortality rates from CVD, with deaths rates in men ≈3 times that of age-matched women.2 Hypertension is the leading risk factor for the development of CVD, with men showing a higher arterial pressure than women during the ages of 20 to 65 years.3 Up until menopause, there are significant sex differences in blood pressure, vascular reactivity, and renal function.4–11 Not only are the rates of mortality sexually dimorphic but so are the symptoms experienced and disease development,4,12 resulting in a poorer outcome in men than in women. The response to treatment also differs between the sexes. For example, hypertensive women treated with an angiotensin receptor blocker have a better survival rate than women treated with an angiotensin-converting enzyme (ACE) inhibitor, whereas there is no difference in response to either agent in hypertensive men (as seen by the hazard ratio for treatment with an angiotensin receptor blocker versus treatment with ACE inhibitor of 0.69 in women and 1.10 in men).13–16 These data suggest that there are sex differences in the mechanisms underlying the development of hypertension. Despite these sex differences, the exact mechanism(s) underlying the increased morbidity and mortality in men remains elusive. Previous human studies have reported significant associations between the Y chromosome and blood pressure in Australian, Polish, and Scottish populations, suggesting that the Y chromosome may play a role17,18; however, this was not the case in a Spanish cohort.19 Further evidence from population studies suggests …