Race-based Therapy for Hypertension: Possible Benefits and Potential Pitfalls

Keith C. Ferdinand; Daphne P. Ferdinand


Expert Rev Cardiovasc Ther. 2008;10(6):1357-1366. 

In This Article

Unique Aspects of Pathophysiology in US Black Individuals With Hypertension

Unique aspects of pathophysiology underlying hypertension in African-Americans are not entirely understood but contribute to greater prevalence and severity of hypertension. The epithelial sodium channels, renin-angiotensin-aldosterone system (RAAS), adrenergic receptors, nitric oxide pathways, endothelin-1 levels and TGF-B hyperexpression are all developing areas of research.[17,18,19,20,21,22,23,24,25,26]

Blacks also show higher levels of vascular resistance and/or disturbances in both endothelial-dependent and -independent vasodilatation. A cohort from the Atherosclerosis Risk in Communities study indicated that African-Americans had stiffer common carotid arteries compared with Whites.[27] There are also racial differences in vasoreactivity; Blacks may demonstrate higher minimum forearm vascular resistance, depressed vasodilation and/or increased peripheral vasoconstriction in response to β-adrenergic stimulation, attenuation in cyclic nucleotide-mediated vascular smooth muscle relaxation, depressed postischemic vasodilatation and an increased median effective concentration in response to acetylcholine.[28] Furthermore, many Blacks show slower rates of sodium excretion compared with Whites, even with comparable levels of renal function. Sodium restriction and/or increased potassium intake may lead to a greater reduction in systolic BP in African-Americans.[29,30]

Several studies have demonstrated sodium absorption and salt sensitivity are more common and severe in Black populations. A larger proportion of Blacks have lower plasma renin activity levels, relative expansion of plasma volume and a higher prevalence of salt-dependent hypertension.[29] These apparent physiological findings can be related to higher sodium intake, lower potassium intake, obesity and physical inactivity, along with higher levels of blood sodium and calcium, which blunt plasma renin activity.

Genetic factors contribute to the unique pathophysiology of hypertension in Blacks. In regard to the epithelial sodium channel and its role in sodium handling in Blacks, the T594M allele has been described in persons of African origin but not in any White populations, representing a potential increased prevalence of salt-sensitive hypertension.[31,32] In addition, Blacks may have a higher risk of the C825T polymorphism of the gene encoding the subunit of G-protein, a genetic variant associated with an increased response to thiazide diuretics.[33] Overall physiological findings confirm the recommendations for using thiazide diuretics as the basis for treatment for hypertension in Blacks, with additional agents as needed. The data also support the use of long-acting calcium channel blockers (CCBs), which are often effective in patients with low renin, salt-sensitive hypertension.

Furthermore, endothelial function and bioavailability of nitric oxide is diminished in many Blacks. Hypertension as the etiology of HF is more common in Blacks, as documented in several of the large clinical outcome trials. In the African-Americans Heart Failure Trial, which studied a cohort of 1094 patients with symptomatic systolic dysfunction, there was a 39% reduction in HF hospitalization, improved functional capacity and a remarkable 43% reduction in all-cause mortality.[34] The benefit was due to the addition of the combination of isosorbide dinitrate (a nitric oxide donor) and hydralazine (an antioxidant) to standard therapy, possibly indicating endothelial dysfunction in Blacks with HF.[34]

Other areas of research include TGF-B, often elevated in African-Americans with hypertension and an additional marker for with salt-sensitive hypertension. This inflammatory cytokine may also increase extracellular matrix turnover and fibrosis, potentially increasing target organ damage.[35] Finally, more Black patients may have a blunted nocturnal decline in BP, or absence of dipping, which may be a sign of more severe hypertension and target organ damage.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.