Sex differences in cardiovascular ageing

Abstract

Despite recent progress in identifying and narrowing the gaps in cardiovascular outcomes between men and women, general understanding of how and why cardiovascular disease presentations differ between the sexes remains limited. Sex-specific patterns of cardiac and vascular ageing play an important role and, in fact, begin very early in life. Differences between the sexes in patterns of age-related cardiac remodelling are associated with the relatively greater prevalence in women than in men of heart failure with preserved ejection fraction. Similarly, sex variation in how vascular structure and function change with ageing contributes to differences between men and women in how coronary artery disease manifests typically or atypically over the adult life course. Both hormonal and non-hormonal factors underlie sex differences in cardiovascular ageing and the development of age-related disease. The midlife withdrawal of endogenous oestrogen appears to augment the age-related increase in cardiovascular risk seen in postmenopausal compared with premenopausal women. However, when compared with intrinsic biological differences between men and women that are present throughout life, this menopausal transition may not be as substantial an actor in determining cardiovascular outcomes.

Figure 1

Patterns of cardiac ageing in men and women. ‘+’ symbols represent the presence of oestrogen receptors in the myocardium (including cardiac myocytes and fibroblasts).

Figure 2

Cardiac and vascular structural and functional ageing processes and the progression to disease in women. Throughout the life course, subclinical changes in cardiac and vascular structure and function interact with traditional pathophysiological disease mechanisms to impact an individuals increasing likelihood of developing disease across the life course. Female-specific disease modifiers and structural and functional changes predispose to different presentations and outcomes compared with men. CAD, coronary artery disease; EF, ejection fraction; HFPEF, heart failure with preserved EF; HFREF, heart failure with reduced EF.

Figure 3

Patterns of vascular ageing in men and women. ‘+’ symbols represent the presence of oestrogen receptors in the arterial vasculature (including endothelium, smooth muscle cells and extracellular matrix).

Figure 4

Age-specific death rates attributed to cardiovascular disease and breast cancer and prevalence of hypertension, compiled from US Centers for Disease Control and Prevention data collected from 1999 to 2013. In women, the age-specific death rate due to breast cancer decreases around the time of menopause whereas the age-specific cardiovascular death rate increases steadily across the lifespan (A). In men, cardiovascular death rates decline after midlife whereas continuing to steadily increase across the lifespan in women (B). Prevalence of hypertension is greater in men prior to age 45, similar between the sexes between 45 and 64, and greater in women above age 65 (C). Age-specific death rates for coronary heart disease (D) and heart failure (E).