Role of biological sex in cardiovascular disease: the case of hypertension and related target organ damage

Andrea Rodrigues Sabbatini (Berlin-Brandenburg Center for Regenerative Therapies, Charite University Hospital, Berlin, Germany) and Georgios Kararigas (Institute of Gender in Medicine & Center for Cardiovascular Research, Charite University Hospital, and DZHK [German Centre for Cardiovascular Research], partner site Berlin, Germany) Recent data report a prevalence of hypertension of around 30–45% in the general population of highincome countries and between 20–40% in lowincome countries2–3. In fact, around the globe, 31.1% of the adult population (1.39 billion people) had hypertension in 20104. Hypertension is a complex disease influenced by characteristics of the individual, such as age, sex and sex hormones, race, body mass index (BMI), adipokines, genetic factors, and by environmental factors, lifestyle and dietary habits, such as salt intake (Figure 1). The prevalence of hypertension is higher in men than women at younger ages, but following menopause, blood pressure in women increases steeply, thereby affecting more women than men in elderly individuals. Consequently, the prevalence of hypertension is lower in women than men until 45 years of age, but it is much higher in women than men over 65 years of age. Furthermore, women are at greater risk of developing resistance to antihypertensive treatment than men. Patients with hypertension and lack of blood pressure control have a high probability of developing target organ damage, such as cardiac hypertrophy; vascular alterations, including arterial stiffness; and renal damage. The development of these cardiovascular Individual characteristics, such as age, biological sex, race, fat mass and genetic factors, have a major impact on physiological and pathological processes. Consequently, individuals can respond differently to the development and manifestation of disease, treatment, outcome and the recovery process. In fact, there are major differences in the function of the biological system of men and women, who do not differ only on the basis of their reproductive system. Sex chromosomes and sex hormones, together with other factors, interact in a complex manner, thereby leading to sex-specific protective or maladaptive mechanisms. In this context, studying the role and effects of biological sex is crucial for the identification of novel therapeutic targets, whose therapeutic exploitation will promote a personalized and improved treatment and care according to individual needs. The vast influence of biological sex is recognized in many diseases1. Here, we focus on hypertension, due to its high prevalence and importance, since it is the primary risk factor for premature death and disability worldwide.