Sex Differences in Cardiovascular Consequences of Hypertension, Obesity, and Diabetes: JACC Focus Seminar 4/7

Abstract

It has long been recognized that there are significant differences between the sexes affecting prevalence, incidence, and severity over a broad range of diseases. Until the early 1990s, the limited research conducted on women's health focused primarily on diseases affecting fertility and reproduction, and women were excluded from most clinical trials. For these reasons, the prevention, diagnosis, and treatment of serious chronic diseases such as cardiovascular disease in women continue to be based primarily on findings in men, and sex-specific clinical guidelines are mostly lacking. Hypertension, obesity, and diabetes, interrelated risk factors for cardiovascular disease, differ by sex in terms of prevalence and adverse effects as well as by genetics and biology. Research is needed to understand sex differences in hypertension, obesity, and diabetes to optimally inform sex-specific prevention, diagnosis, and treatment strategies for women and men. In this way, sex-specific clinical guidelines can be developed where warranted.

Keywords: cardiovascular risk factors; sex differences.

FIGURE 1. Intersection of Sex and Gender Across the Lifespan

Sex and gender have an intersectional influence on disease risk, treatment, and complications across the lifespan. Adapted from “The Trans-NIH Strategic Plan for Women’s Health Research.” NIH = National Institutes of Health.

FIGURE 2. Embedding Sex and Gender Into Clinical Research

Model for the prospective incorporation of sex and gender into clinical investigation. This model proposes a strategy to investigate the critical role of gender identity and sex in the planning, analysis, and conduct of clinical trials

FIGURE 3. Hypertension Prevalence by Sex, Age, Race/Ethnicity, and Educational Status

Age-adjusted prevalence of hypertension among adults aged ≥18 years by sex, race, and Hispanic origin in the United States. Hypertension is defined as systolic blood pressure ≥130 mm Hg, diastolic blood pressure ≥80 mm Hg, or currently taking medication to lower blood pressure.

FIGURE 4. Obesity Prevalence by Sex, Age, and Race/Ethnicity

(A) Prevalence of obesity among adults aged ≥20 years by sex and age: United States, 2015 to 2016. (B) Age-adjusted prevalence of obesity among adults aged ≥20 years by sex, race, and Hispanic origin. (C) Prevalence of obesity among youth aged 2–19 years by sex and age. (D) Prevalence of obesity among youth aged 2–19 years by sex, race, Hispanic origin.

FIGURE 4. Obesity Prevalence by Sex, Age, and Race/Ethnicity

(A) Prevalence of obesity among adults aged ≥20 years by sex and age: United States, 2015 to 2016. (B) Age-adjusted prevalence of obesity among adults aged ≥20 years by sex, race, and Hispanic origin. (C) Prevalence of obesity among youth aged 2–19 years by sex and age. (D) Prevalence of obesity among youth aged 2–19 years by sex, race, Hispanic origin.

FIGURE 5. Body Mass Index and All-Cause Mortality in Men and Women

Association of body mass index with all-cause mortality, by sex, based on an individual-participant-data meta-analysis of 239 prospective studies on 4 continents. Analyses were restricted to 3.9 million never-smokers without pre-existing chronic disease.

CENTRAL ILLUSTRATION. A Call to Action for Studying Sex Differences

The pathogenesis, epidemiology, and outcomes for hypertension, obesity, and diabetes differ in women and men and in boys and girls, demonstrating the intersection of sex and gender. However, because of a lack of specifically designed studies to examine therapeutic sexspecific responses to therapy, we lack a robust evidence base to present well-defended sex-specific guidance. Future studies should address sex and gender as outcome variables incorporated into the design of the study. Currently available data from completed and in-process studies should be explored for sex differences. RCT = randomized controlled trial; rx = treatment.