Together with beta-blockers, low-dose diuretics are the preferred first line medications for treating high blood pressure, according to the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Now, recent research in the Journal of the American Medical Association suggests that a variation in a gene called alpha-adducin may help diuretics work better. Specifically, diuretics may be more effective than other blood pressure-lowering drugs at reducing risk of heart attack and stroke among people with a certain variant of the alpha-adducin gene.

About the study

Researchers at the University of Washington, Seattle, and Leiden University Medical Center in the Netherlands studied 1038 members of the Group Health Cooperative HMO in Seattle, Washington. All participants were men and women between the ages of 30 and 79 who were taking medications to treat high blood pressure. Three hundred twenty-three participants had survived a heart attack or stroke between January 1995 and December 1998 (cases) and 715 had never suffered a heart attack or stroke (controls). Controls were matched to cases in terms of age (by decade).

People were excluded from the study if their type of alpha-adducin gene was unknown or if their heart attack or stroke was a result of complications from a medical procedure. People were also excluded if they had a history of congestive heart failure or if their heart attack or stroke occurred before January 1995.

All participants underwent blood tests to determine whether they had the normal or variant alpha-adducin gene. In addition, researchers reviewed the participants’ medical records and interviewed them about their use of blood pressure-lowering drugs.

Researchers compared the number of heart attacks and strokes among people with the alpha-adducin gene variant who were taking diuretics with: 1) those who did not have the gene variant and 2) those who were not taking diuretics.

The findings

People with the variant alpha-adducin gene who were taking diuretics were 50% less likely to have a heart attack or stroke than people taking other blood-pressure lowering drugs. However, diuretics had no effect on risk of heart attack or stroke in people without this gene variant.

In calculating these statistics, the researchers accounted for the possible effects of age, sex, race, smoking, diabetes, cholesterol levels, and systolic blood pressure.

Although these results are interesting, there are limitations to this study. First, this study focused on only one variation in one gene. It is possible that other genetic factors also play a role in the risk of heart attack and stroke. Second, when analyzed alone, the reduction in stroke risk was not statistically significant. Third, cases in this study had already survived a heart attack or stroke. If these people are somehow predisposed to surviving a heart attack or stroke, then perhaps these results don’t apply to people who are not predisposed to surviving such events.

How does this affect you?

Does this mean you should be tested for the variant alpha-adducin gene before starting blood pressure medication? Not necessarily, for two reasons.

These findings suggest that people who possess the variant gene may respond better to diuretics than to other blood pressure-lowering drugs. But more research is needed to confirm these results and determine the risks and benefits of genetic testing. Dr. Bruce Psaty, lead author of this study, explains: “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.”

However, low-dose diuretics, together with beta-blockers, are currently the preferred first line medications for high blood pressure. In fact, Dr. Psaty advises that if you are taking blood pressure-lowering medication, but you aren’t taking a low-dose diuretic, you should ask your doctor why.