Study links polygenic scores to hypertension treatment outcomes microbiologystudy

University of Alabama at Birmingham researchers have discovered that a genetic risk score can predict how Black individuals with hypertension respond to the blood pressure medication chlorthalidone and their likelihood of developing treatment-resistant hypertension.

In a genetic association study, “Utility of a Systolic Blood Pressure Polygenic Risk Score With Chlorthalidone Response,” published in JAMA Cardiology, researchers looked for links between known genetic risk factors and the effectiveness of either chlorthalidone or lisinopril treatments.

Researchers analyzed data from 6,000 Black participants in the Genetics of Hypertension Associated Treatments study. Random assignment placed participants in either the chlorthalidone or lisinopril treatment groups. Researchers then calculated a systolic blood pressure polygenic risk score (ΔSBP) for each participant, encompassing over one million genetic variants.

Findings revealed that individuals in the lowest 20% of the ΔSBP experienced an average reduction in systolic blood pressure of −10.01 mm Hg after six months of chlorthalidone treatment, compared to −6.57 mm Hg for those in the middle 20%.

Each increase of 20% in the ΔSBP was associated with a diminished blood pressure response to chlorthalidone. Additionally, participants in the highest ΔSBP group had a 67% higher likelihood of developing apparent treatment-resistant hypertension compared to those in the median quintile. No significant associations were found between the ΔSBP and blood pressure response to lisinopril.

Utilizing two independently generated ΔSBPs, researchers validated the associations. Data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study replicated the findings, reinforcing the reliability of the results.

The research shows the intriguing potential of ΔSBP to personalize hypertension treatment in clinical settings. In this case, individuals with lower genetic risk may benefit more from chlorthalidone, while those at an elevated risk would do better with lisinopril.

Beyond the current findings, the ΔSBP could reveal more targeted and effective drugs for those with treatment resistance by alerting researchers to the genetic variations mediating the current drug treatments. Future studies are recommended to validate these findings across diverse populations and other antihypertensive therapies.

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