New York, NY (March 22, 2000) — Researchers at Weill Medical College of Cornell University may have at long last explained the higher incidence of hypertension in African-Americans as compared with Caucasian Americans. In a paper published in the March 21 issue of Proceedings of the National Academy of Sciences (PNAS), Drs. Phyllis August, Manikkam Suthanthiran, and colleagues show that an endogenous protein called Transforming Growth Factor-Beta 1 (TGF-ß1) is produced in excess by hypertensives as compared with normotensives, and that black patients make more of this protein than whites. The researchers believe that this explains why blacks have more hypertension and more hypertensive complications (such as stroke and kidney failure) than whites. The authors also believe that inherited variations in the genes that regulate production of this protein are the biological basis for increased production of this protein in blacks.
Background and Major Points
1. Hypertension — a prevalent and remediable risk factor for stroke, cardiovascular disease, and renal failure — affects 50 million individuals in the U.S. alone. African Americans (blacks) have a higher incidence and prevalence of hypertension compared with Caucasians (whites); 33 percent of blacks are affected, compared with 25 percent of whites.
2. Even more striking is the disparity in the prevalence of severe or malignant hypertension; it is estimated to be five to seven times more prevalent in blacks compared with whites. Morbidity attributable to hypertension is also much more prevalent in blacks. For example, left ventricular hypertrophy (LVH) was three times more common in blacks compared with whites in one major program/study. The incidence of ischemic stroke and end-stage renal disease (ESRD) have also been shown to be markedly more prevalent in blacks than whites. Finally, and most disturbing, are the observations that even aggressive blood pressure control has not uniformly led to similar renal-protective benefits in blacks and whites.
3. Genetically determined renal and hormonal factors as well as several environmental influences have been proposed as contributing to the excess burden of hypertension in blacks, but, to date, there has been no unifying hypothesis for the overabundance of hypertensive diseases in the black population.
4. The authors postulate that Transforming Growth Factor-Beta 1 (TGF-ß1) may explain, if not be the cause itself of, the higher incidence of hypertension in blacks. TGF-ß1 is a protein secreted by several cell types, including peripheral blood mononuclear cells (PBMC), endothelial cells, vascular smooth muscle cells, platelets, and also renal cells. It is important in tissue repair, wound healing, and scar formation. Overproduction of TGF-ß1, however, has been shown to be an important mechanism for fibrogenesis, and has been implicated in several of the long-term chronic consequences of poorly controlled hypertension. Recent data also suggest that TGF-ß1 may have a direct pathogenic role in elevated blood pressure.
5. The authors have previously demonstrated that circulating levels of TGF-ß1 are higher in blacks than whites with end-stage renal disease (ESRD). Moreover, they have hypothesized that the increased frequency of overexpression of TGF-ß1 may contribute to the excess burden of ESRD in blacks. Finally, they have suggested that the overexpression of TGF-ß1 may be genetically determined, because DNA polymorphisms in codon 25 of the TGF-ß1 gene have been associated with hypertension.
6. In this study, the authors explore the hypotheses that, independent of renal disease, TGF-ß1 is overexpressed in hypertensives compared with normotensives, and that TGF-ß1 overexpression is more frequent in blacks compared with whites. They test their hypotheses by evaluating TGF-ß1 profiles in hypertensive and normotensive subjects.
7. The findings in this study are that TGF-ß1 is indeed overexpressed in hypertensive subjects compared with normotensive controls, and that such overexpression is more frequent in blacks compared with whites. Thus, TGF-ß1 protein levels strongly correlate with hypertension status, and race is an independent predictor of TGF-ß1 levels.
8. The authors suggest a genetic explanation for such differences. And they state that further exploration of the contribution of TGF-ß1 to hypertension and hypertensive complications in a prospective investigation may provide new insights into mechanisms of hypertension as well as suggest novel therapeutic targets.
9. Dr. Phyllis August is Chief of the Division of Hypertension and Professor of Medicine at New York Weill Cornell Medical Center. Dr. Manikkam Suthanthiran is Chair of the Department of Transplantation Medicine, Chief of the Division of Nephrology, and Professor of Medicine and Biochemistry at New York Weill Cornell Medical Center.
10. Joining Drs. August and Suthanthiran as co-authors of the study are Baogui Li, Jong O. Song, Ruchuang Ding, and Vijay K. Sharma of New York Weill Cornell Medical Center, and Joseph E. Schwartz of SUNY-Stony Brook.
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