A recent study by researchers at the University of Alabama at Birmingham has identified a genetic risk score that can predict how Black individuals with hypertension respond to the blood pressure medication chlorthalidone and their likelihood of developing treatment-resistant hypertension. The findings, published in JAMA Cardiology, highlight the potential for personalized medicine in hypertension management.
The genetic association study, titled "Utility of a Systolic Blood Pressure Polygenic Risk Score With Chlorthalidone Response," analyzed data from 6,000 Black participants in the Genetics of Hypertension Associated Treatments (GenHAT) study. Participants were randomly assigned to treatment with either chlorthalidone or lisinopril. Researchers calculated a systolic blood pressure polygenic risk score (ΔSBP) for each participant, encompassing over one million genetic variants.
The study revealed a significant correlation between ΔSBP and response to chlorthalidone. 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 20% increase in the ΔSBP was associated with a diminished blood pressure response to chlorthalidone. Furthermore, 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.
Validation of Findings
To validate these associations, researchers utilized two independently generated ΔSBPs. Data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study replicated the findings, reinforcing the reliability of the results.
Clinical Implications
The research suggests that ΔSBP could be used to personalize hypertension treatment in clinical settings. Individuals with lower genetic risk may benefit more from chlorthalidone, while those at an elevated risk might respond better to lisinopril. According to the authors, the ΔSBP could also 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.
Expert Commentary
In an accompanying editorial in JAMA Cardiology, Sadiya S. Khan notes the potential for precision medicine to guide blood pressure control, highlighting the importance of these findings for tailoring treatment strategies to individual genetic profiles.
