Revisiting sex as a biological variable in hypertension research

Abstract

Half of adults in the United States have hypertension as defined by clinical practice guidelines. Interestingly, women are generally more likely to be aware of their hypertension and have their blood pressure controlled with treatment compared with men, yet hypertension-related mortality is greater in women. This may reflect the fact that the female sex remains underrepresented in clinical and basic science studies investigating the effectiveness of therapies and the mechanisms controlling blood pressure. This Review provides an overview of the impact of the way hypertension research has explored sex as a biological variable (SABV). Emphasis is placed on epidemiological studies, hypertension clinical trials, the genetics of hypertension, sex differences in immunology and gut microbiota in hypertension, and the effect of sex on the central control of blood pressure. The goal is to offer historical perspective on SABV in hypertension, highlight recent studies that include SABV, and identify key gaps in SABV inclusion and questions that remain in the field. Through continued awareness campaigns and engagement/education at the level of funding agencies, individual investigators, and in the editorial peer review system, investigation of SABV in the field of hypertension research will ultimately lead to improved clinical outcomes.

Figure 1. Increased CVD risk in women is driven by many factors, including age, menopause, and obesity.

Figure 2. Summary of known immunological factors contributing to hypertension in men and women.

Figure 3. Summary of effects of estrogens and androgens on the immune system, central nervous system, kidneys, and gut microbiota that may affect blood pressure and the development of hypertension.

HTN, hypertension; RAAS, renin angiotensin aldosterone system.