Pathogenesis of Hypertension in African Americans

Shawna Nesbitt, MD; Ronald G. Victor, MD

Disclosures

CHF. 2004;10(1) 

In This Article

Abstract and Introduction

Hypertension is a compelling disease process that disproportionately affects African Americans. It is the single largest risk factor for cardiovascular disease in African Americans. The end organ manifestations of hypertension are striking and include higher rates of stroke, significantly increased renal disease including end-stage renal disease requiring dialysis, higher risk of left ventricular hypertrophy, and an associated higher risk of heart failure. The cause of these more aggressive end organ phenomena is likely multifactorial and includes a mix of genetic and environmental influences. Intriguing polymorphisms of the epithelial sodium channel are consistent with patterns of hypertension seen in African Americans. Obesity, especially in African-American women, may be closely related to hypertension as a result of sympathetic nervous system stimulation.

Compared with whites and every other ethnic group in the United States, hypertension in African Americans is not only more prevalent but also starts at a younger age, is more severe, and causes much more target organ damage.[1–13] Most of the excess African-American cardiovascular deaths occur prematurely, that is, before age 65 years. Thus, the ethnic differential, measured as years of productive life lost, is two times greater for African-American women than white women and four times greater for African-American men than white men. To approach the ambitious goal set by the US Department of Health and Human Services of eliminating this ethnic gap by 2010, more research needs to be focused on heart disease in African Americans.

A wealth of epidemiologic data indicate that hypertension is the single most important risk factor for the markedly excessive rates of premature death and disability from heart attack, heart failure, stroke, and renal failure in African Americans. In contrast, the study of the genetic underpinning of the African-American disadvantage in hypertensive cardiovascular disease is in its infancy.

There is no question that environmental factors ultimately related to racism (e.g. socioeconomic disadvantage, less access to the best health care) play large roles in causing and sustaining this major public health problem.[11,14] Despite similar African heritage, Africans living in Africa or the West Indies have much less hypertension than African Americans.[15,16] In parts of rural Africa, hypertension prevalence is very low and blood pressure does not rise with age as it does in all ethnic groups throughout the United States.[15]

On the other hand, hypertension control rates in the United States are equally poor for African Americans and whites,[17] which supports the argument that genetic susceptibility factors also play a role in explaining why hypertension is more prevalent and causes more suffering in African Americans. Blood pressure aggregates in families in a dose-dependent manner: the stronger a person's family history of hypertension, the greater the risk of developing the disease.[18] Shared genes seem to account for ≈30%–50% of the individual variability in blood pressure,[18–20] which fuels the search for hypertension candidate genes.[21]

Blood pressure is the product of cardiac output times systemic vascular resistance. Hypertension could be caused by both an increase in the gain of mechanisms causing increased plasma volume and increased peripheral vasomotor tone, and a decrease in the gain of mechanisms causing decreased plasma volume and decreased vasomotor tone. To explain the greater prevalence and severity of hypertension in African Americans, putative candidate genes include those encoding components of epithelial sodium channels,[22,23] the renin-angiotensin aldosterone system,[21,24–29] α-and β-adrenergic receptors,[30,31] endothelin and endothelin receptors, kallikrein,[32] natriuretic peptides and their receptors,[33] and the nitric oxide pathway.[34] To date, there is a dearth of convincingly positive leads: there is physiologic evidence for attenuated β-adrenergic vasodilation in normotensive African Americans,[35] and sodium channel sequence variants that constitute putative hypertension candidate genes have been idenitifed.[22,23] In each case, these leads emerged from small case-control studies derived from nonrandom convenience samples. This emphasizes the need for more powerful case control studies derived from large, representative population samples. In addition, the blood pressure response to a given stressor or antihypertensive medication needs to be compared head-to-head in individuals with and without specific sequence variants. Such pharmacogenomic studies are just underway.

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