| Hypertensive patients
with one genotype have much lower cardiovascular risk with diuretic
therapy than patients with the usual genotype Hypertensive patients with a certain genotype have much lower cardiovascular risk with diuretic therapy than other patients have, according to an article in the April 3rd issue of the Journal of the American Medical Association. The researchers hope that further work produces a genetic screening test to identify the people most likely to benefit from diuretic agents. About 50 million Americans have high blood pressure; about 25 million take medication for it. "If these findings are confirmed in other studies, screening for the adducin variant could identify hypertensive patients especially likely to benefit from low-dose diuretic therapy," says Dr. Bruce M. Psaty, lead author of the study. Psaty and his American coauthors studied the alpha-adducin gene in a case-control study. Adducin is a protein linked to the inner surface of cell membranes, and one particular adducin allele (Gly460Trp) is known to increase sodium retention by the kidney. Diuretics are currently recommended as first-line drug therapy for hypertension by the U.S. Joint National Committee on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure. The idea for the current study arose from the observation that diuretics and the adducin allele have opposing effects on sodium handling by the kidney. The investigators studied 323 hypertensive patients who suffered a first non-fatal myocardial infarction or stroke between 1995 and 1998. The control group included 715 hypertensive patients matched by age and sex. All participants were taking antihypertensive medications. About one third of the people in the study possessed the adducin allele in question. The effect of diuretic therapy on the risk of myocardial infarction or stroke depended on adducin genotype. Among hypertensive patients who had the usual (wild type) adducin allele, diuretics did not differ in effect from other antihypertensive medications. However, among patients with the adducin allele in question, diuretic therapy was associated with a 50 percent lower risk of myocardial infarction or stroke than other antihypertensive medications. "The finding of an adducin-diuretic interaction is a potentially important application of recent work on the human genome, but it needs to be confirmed in other studies," Psaty said. The interaction persisted when the investigators adjusted for many known risk factors. It was similar in subgroups, and it was specific to diuretics. "Most importantly,"
Psaty says, "low-dose diuretics prevent complications such
as heart attack and stroke."
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