**1. Introduction**

Hypertension is the leading cause of cardiovascular disease in the United States, affecting 29% of adults, or approximately 75 million people [1]. The economic burden of hypertension in America is enormous [2], often raising concerns about its major impact on health disparity [3–5]. When compared to other ethnic or racial groups in the United States, African American and others of African descent show a higher incidence of hypertension and its related comorbidities, including cardiovascular and end-stage renal diseases [2]. Moreover, African Americans and others of African descent may have higher blood pressure beginning in childhood, as well as a higher incidence and prevalence of hypertension across the lifespan [6–11]. The age-adjusted prevalence of hypertension in African Americans is ~45%, significantly higher than in other ethnicities, including ~32% among non-Hispanic whites and ~30% among Hispanics [2].

Major predictors of hypertension in African Americans exist. For example, impaired arterial elasticity [12–14] has been demonstrated to be more prevalent than in whites [5,15–17]. Brown et al. found in a large cohort study of untreated normotensive participants (Multi-Ethnic Study of

Atherosclerosis) that subjects who were found to have a suppressed renin phenotype were more likely to be African Americans, and had higher systolic blood pressure [18]. In a recent observational study on normotensive African Americans, aldosterone sensitivity (magnitude of the association between plasma aldosterone concentration and blood pressure) increased with age and was associated with plasma aldosterone concentration and the aldosterone-to-renin ratio, suggesting that mineralocorticoid receptor activity may increase with age, especially in African Americans [19]. Other factors that distinguish hypertension in African Americans from other ethnicities include increased awareness of diagnosis, increased intensity of treatment, poor BP control, and more resistant hypertension [20]. On the other hand, hypertensive diagnostic inertia, defined as a failure to investigate the underlying cause of hypertension, is an ongoing issue in African Americans with cardiovascular disease [21,22]. Moreover, adrenocortical hyperplasia was found to be more common in African Americans and other patients of African descent [23], suggesting the possibility of aldosterone and/or cortisol excess as an important contributor to the pathogenesis of hypertension in this ethnic group.

The regulation of blood pressure is complex. Research that examines the association of the various pathophysiological factors with incident hypertension among African Americans and others of African descent is limited, as detailed in Table 1. Despite heredity contributing 40–50% to the pathogenesis of essential hypertension and genome-wide association studies identifying ~6% of the genetic contribution [24,25], little is known about the genetic diversity of hypertension in African American populations, particularly in relation to the factors listed in Table 1. Some researchers have focused on genes implicated in altered renal sodium handling in the kidneys and volume loading, which are key players in the development of low-renin hypertension in this at-risk population [26,27]. Studies that failed to discover any relationship between African American and hypertension were limited by several factors, including variation in allele frequency, small statistical power, and the possibility of weak ancestral effects [28–30]. Large sample size studies could exclude > 95% of the genome as harboring risk loci of > 1.3 due to African or European ancestry, further suggesting the complexity of understanding the underpinning of hypertension across various ethnicities. Ongoing studies are examining genetic susceptibility and environmental factors as determinants of hypertension in African Americans [31].

**Table 1.** Examples of pathophysiological mechanisms of hypertension in individuals of African descent.


Diversity may exist within African descent population. Clinical and genetic data of African-Americans and others of African descent should be interpreted and compared with caution. Chor et al. studied blood pressure profiles of 15,103 civil servants in Brazil and found a high prevalence of high blood pressure among browns (38.2%) and blacks (49.3%) [11]. Importantly, they found that hypertensive characteristics of Brazilian brown populations were like that seen in the individuals of African descent.

Genetic sequencing has gained enormous popularity in the scientific field. Affordability and fast throughput are promising to deliver "Genetic Health Risk and Carrier Status" for as little as \$99, through direct-to-consumer salivary collection kits [43]. However, the clinical interpretation of an individual's genome, its utility in clinical practice, and the overall cost has yet to be implemented as a standard of care approach in universal clinical management guidelines. One of the major goals of understanding the genetics of hypertension includes the transfer of genomic knowledge into daily clinical practice [10], for potential gene-targeted medical therapies [5], among other useful utilities.

In this review, we briefly highlight the mechanistic and genetic underpinnings of hypertension in African Americans and other populations of African ancestry. We have focused our discussion on the biologically plausible hypertension candidate gene loci in African Americans [44]
