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Genetic Variant, Diuretics Linked To Lower Hypertensive Stroke Risk

Diuretic therapy, when compared with other hypertensive therapies, is linked to lower combined risk of myocardial infarction (MI) or stroke in hypertension patients who carry the adducin genetic variant.

A United States population-based, case-control study indicates approximately one-third of hypertensive participants carry the adducin variant.

"There was a significant interaction between the presence of the adducin Trp460 variant and the use of diuretics on the risk of the combined outcome of first, non-fatal MI or stroke," say researchers from the University of Washington in Seattle and Leiden University Medical Centre in the Netherlands. They did not find diuretic therapy associated with risk of MI or stroke among 653 carriers of the adducin wild-type genotype.

The researchers did find diuretic use was associated with a lower risk of the combined outcome of MI or stroke than use of other hypertensive medications among the 385 carriers of the adducin variant allele. The odds ratio (OR) in carriers of the adducin variant was less than half of the OR in carriers of the wild-type genotype.

They comment: "The long-term goal of research in the area of pharmacogenetics is to help clinicians individualise treatment for their patients and select drug therapies that maximise either effectiveness or safety or both.

"If the adducin variant identifies a subset of hypertensive patients who are particularly likely to benefit from diuretic therapy, it is reasonable to evaluate whether screening hypertensive patients for selected genetic polymorphisms may be indicated when selecting antihypertensive therapies."

Both case participants and controls from patients were taken from a large health organisation based in Seattle. They included 206 patients who had a first, non-fatal MI and 117 patients who had a stroke between January 1995 and December 1998. A total of 715 controls were matched to MI cases by age, sex and calendar year.

The estimates of the diuretic-gene interactions were similar when they did separate analyses for MI and stroke. The investigators add that the diuretic-adducin interaction was not confounded by traditional cardiovascular risk factors. It was also specific to diuretic therapy but was not present for other major antihypertensive drug classes nor did it differ between subgroups defined by age, sex, race, diabetes and cardiovascular disease.

Researchers say their findings need to be confirmed in other settings: "Randomised clinical trials of drug therapy for hypertension would be an ideal setting for case-only studies because drug use and genotype are by design independent."
JAMA, 2002; 287: 1680-1689. "Diuretic Therapy, the [Alpha]-Adducin Gene Variant, and the Risk of Myocardial Infarction or Stroke in Persons With Treated Hypertension"

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