Sex-associated differences in cardiac ageing: Clinical aspects and molecular mechanisms

Despite the extensive clinical and scientific advances in prevention, diagnostics and treatment, cardiovascular diseases (CVD) remain the leading cause of morbidity and mortality worldwide for people aged 65 and over. Of all ageing-related diseases, CVD are responsible for almost one-third of deaths in the elderly, being above all cancers combined. Age is an independent and unavoidable risk factor contributing to the impairment of heart and blood vessels. As the average age of the population in industrialized countries has doubled in the last century, and almost a fifth of the world's population is predicted to be over 65 in the next decade, we can assume that the burden of CVD will fall primarily on the elderly. Evidence from basic and clinical science has shown that sex significantly influences the onset and severity of CVD. In women, CVD usually develop later than in men and with atypical symptomatology. After menopause, however, the incidence and severity of CVD increase in women, reaching equality in both sexes. Although intrinsic sexual dimorphism in cardiovascular ageing may contribute to the sex differences in CVD progression, the molecular mechanisms associated with cardiovascular ageing and their clinical value are not known in detail. In this review, we discuss the scientific knowledge available, focusing on structural, hormonal, genetic/epigenetic and inflammatory pathways, seeking to transfer these findings to the cardiovascular clinic in terms of prevention, diagnosis, prognosis and management of these pathologies and proposing possible validation of target specifics.