Using Genetics to Pick the Best Blood Pressure Drug

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Blood pressure gauge in Doctors surgery

Picking the right blood pressure drug for the right person is not easy, especially when there are so many to choose from. There are five major classes of these drugs and more than 60 options total used to treat heart disease, a condition 1 in 3 Americans have. Having high blood pressure puts people at risk of heart attack and stroke, the number one killers of Americans regardless of ethnic or racial background.

Now, a new study suggests physicians may soon be able to look at a person’s genetics and match them to a treatment that promises to be the most effective and cause the fewest adverse side effects. Side effects from blood pressure medications range from vomiting to tiredness.

In the study, researchers used a large genetic database in the United Kingdom to look for associations between cardiovascular disease outcomes and variants in specific genes that code for the proteins targeted by the three classes of medicines most commonly used to treat high blood pressure. These classes included ACE inhibitors, beta-blockers and calcium channel blockers. They found certain variations in genes were associated with lowered risk of heart disease and stroke.

“A major strength of our work is that it uses genetic variants to investigate the effect of antihypertensive drugs using existing data obtained from large-scale studies,” wrote the authors of the study, which was published in the 25 June 2019 of the American Heart Association’s journal, Circulation.

The researchers also found a “previously unreported possible side effect” from one particular category of blood pressure drugs examined in the study. The genetic variants targeted by calcium channel blockers were linked to an increased risk of developing diverticulosis, a condition where small pouches develop along the walls of the large intestine. When the pouches get infected or tear, these complications can lead to hospitalization.

“As far as we know, this effect isn’t related to blood pressure at all, and this is very much a novel insight generated by the study,” said the study’s lead author, Dipender Gill, Ph.D,a clinical research fellow at Imperial College London.

The current study and ones like it have only been possible since about 2000 when electronic health records first became linked with banks of biospecimens. That allowed researchers to do comparative analyses of genetic variants and phenotypes, or phenome wide association studies (PheWASs). PheWASs are surveys designed to determine which of many phenotypes, including disease outcomes and side effects, may be associated with a given genetic variant. They differentiate between pleitropy (when one gene affects two or more phenotypes) and true clinical comorbidity. And, as exemplified by the current study, can identify links between variants and possible drug-induced side effects.

That’s important because most high blood pressure drugs are tested in older or high-risk populations for a relatively short period of time, and the trials rarely capture side effects beyond the more obvious ones.

“The real strength of the study is that it was able to assess for unexpected effects of medications on human health in an unbiased way,” said Kiran Musunuru, M.D., Ph.D.  in a press release. Musunuru is an associate professor of cardiovascular medicine and genetics at the University of Pennsylvania and was not involved in the research.

“There’s no obvious connection that would have led the medical community to suspect a link between calcium channel blockers and diverticulosis, but it appears there might be one after all,” he said. “The idea of using genetic variants that mimic the effects of medications to get a better sense of whether the drugs will be effective and safe, before the medications are used in people, will be an important element of drug development going forward.”

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