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Medical Forum / General / General / November 2004Isosorbide Dinitrate and Hydralazine in Blacks with Heart Failure: NEJM
A Possible Explanation of Why Hydralazine May be Effective in Blacks with Heart Failure: A Response to the article in the New England Journal of Medicine Copyright 2004, James Michael Howard, Fayetteville, Arkansas, U.S.A. It is my opinion that the ratio of testosterone to DHEA is critical in disease. Testosterone may actually reduce conversion of DHEAS to DHEA, thus reducing availability of DHEA. Blacks produce more testosterone than whites. DHEAS has been found to be higher in blacks (Metabolism. 2001 Aug;50(8):916-20). Hydralazine reduces testosterone secretion (J Pharmacol Exp Ther. 1994 Apr;269(1):230-7) and reduces the metabolic clearance rate of DHEAS (Am J Obstet Gynecol. 1976 Jan 15;124(2):143-8). Therefore, hydralazine may decrease the ratio of testosterone to DHEA. Recently, Nakamura, et al., stated that "...we found that cardiac production of DHEA was suppressed in failing heart. We postulated that DHEA and/or its metabolites exert a cardioprotective action through antihypertrophic effects" (Circulation. 2004 Sep 28;110(13):1787-93. Epub 2004 Sep 13). DHEA stimulates nitric oxide (Steroids 2004; 69: 279-89; Endocrinology 2003; 144: 3449-55; and J. Biol Chem 2002; 277: 21379-88). I suggest the findings of Taylor, et al., represent the amelioration of the exaggerated ratio of testosterone to DHEA in blacks by hydralazine. The increased DHEA ratio then improves nitric oxide release. James Michael Howard www.anthropogeny.com your arguments are moot because the study didn't include a caucasian group for comparison. > A Possible Explanation of Why Hydralazine May be Effective in Blacks > with Heart Failure: A Response to the article in the New England > Journal of Medicine > > Copyright 2004, James Michael Howard, Fayetteville, Arkansas, U.S.A. > your arguments are moot because the study didn't include a caucasian group > for comparison. Accutally, there was a comparison group of caucasians in previous studies. The drug combo didn't work in whites, but it did work in blacks. However, I don't think Mr. Howard's theory is correct. Women have a lower level of testerone than men, yet they still get heart failure. Jeff >> your arguments are moot because the study didn't include a caucasian group >> for comparison. [quoted text clipped - 7 lines] > >Jeff Thanks for the information. This report was about increased survival of the blacks of the study so the effect is more pronounced in blacks because they produce more testosterone. I do not see the relationship you present because women have heart failure. I do know that black women produce more testosterone than whites. >your arguments are moot because the study didn't include a caucasian group >for comparison. Thank you for your response. I heard a criticism of the original article of the same nature. However, I couched my response to the NEJM, whcih this is, in the context of the article. However, the same effect should also occur in caucasians but, perhaps, with less effect because whites produce less testosterone. >> A Possible Explanation of Why Hydralazine May be Effective in Blacks >> with Heart Failure: A Response to the article in the New England >> Journal of Medicine >> >> Copyright 2004, James Michael Howard, Fayetteville, Arkansas, U.S.A. It is my opinion that the ratio of testosterone to DHEA is critical in disease. Testosterone may actually reduce conversion of DHEAS to DHEA, thus reducing availability of DHEA. Blacks produce more testosterone than whites. DHEAS has been found to be higher in blacks (Metabolism. 2001 Aug;50(8):916-20). Hydralazine reduces testosterone secretion (J Pharmacol Exp Ther. 1994 Apr;269(1):230-7) and reduces the metabolic clearance rate of DHEAS (Am J Obstet Gynecol. 1976 Jan 15;124(2):143-8). Therefore, hydralazine may decrease the ratio of testosterone to DHEA. Recently, Nakamura, et al., stated that "...we found that cardiac production of DHEA was suppressed in failing heart. We postulated that DHEA and/or its metabolites exert a cardioprotective action through antihypertrophic effects" (Circulation. 2004 Sep 28;110(13):1787-93. Epub 2004 Sep 13). DHEA stimulates nitric oxide (Steroids 2004; 69: 279-89; Endocrinology 2003; 144: 3449-55; and J. Biol Chem 2002; 277: 21379-88). I suggest the findings of Taylor, et al., represent the amelioration of the exaggerated ratio of testosterone to DHEA in blacks by hydralazine. The increased DHEA ratio then improves nitric oxide release. James Michael Howard www.anthropogeny.com > >your arguments are moot because the study didn't include a caucasian group > >for comparison. > > Thank you for your response. I heard a criticism of the original > article of the same nature. However, I couched my response to the > NEJM, whcih this is, in the context of the article. I'm not sure you understand the fatal flaw of this paper. The authors argue that because "conventional" randomized trials may be underpowered to do subgroup analyses (such as determining whether a drug's efficacy is different among research subjects of different ethnicity), it makes more sense to design an entire clinical trial around a specific subgroup -- in this case, african americans. In reality, the only way to ethically do the study correctly would be to power the study adequately -- so that african americans, caucasians, martians, and whomever else the authors believed might benefit from a therapy can be compared. But, instead, we get a clinical trial that enrolled only african americans -- and since the isdn/hydralazine combination showed survival benefit among african american patients who received it, the authors (and drug company which heavily supported this study.. more on that later) would have us believe that african american patients with heart failure should have this patented combination drug marked and prescribed to them... The obvious question that is left unanswered is --- would patients of other ethnic groups randomized to this drug also have benefited?? We will never know. As to the conflicts of interest (see page 2055 of the article), the fact that this paper was published in the new england journal sickens me. the senior author is the holder of the patent on this combination of hydralazine and isosorbide mono and dinitrate. the drug company paid him for the right to license and market the drug. the drug company has patended the drug for use in black patients. three other authors are supported by this specific drug company with regards to funding. one other author receives consulting and lecture fees from the company. 3 authors own equity in this specific company. Bottom line: this is a cynical marketing ploy. A drug company has figured out a way to patent two widely used generic compounds by doing an ethically challenged study among one ethnic group to obtain its patent rights. However, the same > effect should also occur in caucasians but, perhaps, with less effect > because whites produce less testosterone. >> >your arguments are moot because the study didn't include a caucasian >group [quoted text clipped - 39 lines] >> effect should also occur in caucasians but, perhaps, with less effect >> because whites produce less testosterone. That is very interesting information ...and surprizing. note that this paragraph: > However, the same > > effect should also occur in caucasians but, perhaps, with less effect > > because whites produce less testosterone. was written by a previous poster and not by me. i do not share this belief. >your arguments are moot because the study didn't include a caucasian group >for comparison. He thinks DHEA and testosterone cause every known disease including hangnails anyway. -- David Wright :: alphabeta at prodigy.net These are my opinions only, but they're almost always correct. "If I have not seen as far as others, it is because giants were standing on my shoulders." (Hal Abelson, MIT) >> A Possible Explanation of Why Hydralazine May be Effective in Blacks >> with Heart Failure: A Response to the article in the New England >> Journal of Medicine >> >> Copyright 2004, James Michael Howard, Fayetteville, Arkansas, U.S.A. |
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