Getting to the Heart of the Matter: Exploring the Intersection of Cardiovascular Disease, Sex and Race and How Exercise, and Gut Microbiota Influence these Relationships

Abstract

Cardiovascular disease (CVD) is the leading cause of death worldwide, with physical inactivity being a known contributor to the global rates of CVD incidence. CVD incidence, however, is not uniform with recognized sex differences as well and racial and ethnic differences. Furthermore, gut microbiota have been associated with CVD, sex, and race/ethnicity. Researchers have begun to examine the interplay of these complicated yet interrelated topics. This review will present evidence that CVD (risk and development), and gut microbiota are distinct between the sexes and racial/ethnic groups, which appear to be influenced by acculturation, discrimination, stress, and lifestyle factors like exercise. Furthermore, this review will address the beneficial impacts of exercise on the cardiovascular system and will provide recommendations for future research in the field.

Keywords: cardiovascular disease; ethnicity; heart; intestine; microbiome; physical activity.

Fig. 1.

A representation of nitric oxide signaling. Shear stress increases intracellular calcium (Ca²⁺) which enhances endothelial nitric oxide synthase (eNOS) enzymatic action. eNOS catalyzes the synthesis of L-arginine to nitric oxide. Tetrahydrobiopterin (BH4) is a critical cofactor.

Fig. 2.

A representation of free radicals being scavenged by endogenous antioxidants. Superoxide (O₂-) reacts with nitric oxide (NO) to form peroxynitrate (ONOO-). Superoxide dismutase (SOD) catalyzes the reaction of O₂- to hydrogen peroxide (H₂O₂), which participates in the formation of hydroxyl radicals ($\cdot$HO). Both catalase and glutathione peroxidase (GPx) reduce H₂O₂ to water (H₂O) and oxygen (O₂).

Fig. 3.

Working conceptual model. Race, ethnicity, gender, and sex interact (i.e., intersectionality) and are shaped by social determinants of health (SDoH) to moderate gut effects (dysbiosis, diversity, specific metabolites, gut “age”) on subclinical cardiovascular disease (CVD) (endothelial dysfunction, large artery stiffness) - driving CV health disparities and overt CVD (hypertension, coronary ischemia and vasospasm, myocardial infarction, heart failure). CV, cardiovascular.