A new study published in JAMA Cardiology reveals that a systolic blood pressure (SBP) polygenic risk score (PRS) can predict the blood pressure response to chlorthalidone in Black individuals with hypertension. The research suggests that genetic predisposition plays a significant role in how patients respond to antihypertensive treatment, potentially paving the way for more personalized treatment strategies.
The study, conducted as part of the Genetics of Hypertension Associated Treatments (GenHAT) study, analyzed data from 3,745 Black participants randomized to chlorthalidone treatment within the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Researchers examined the association between an SBP PRS, comprising over one million genetic variants, and blood pressure changes over a six-month period.
Differential Response Based on Genetic Risk
The findings indicated that individuals in the lowest quintile of the SBP PRS experienced a significantly greater reduction in systolic blood pressure compared to those in the median quintile. Specifically, participants in the lowest quintile had a mean SBP reduction of -10.01 mm Hg (95% CI, -11.11 to -8.90) compared to -6.57 mm Hg (95% CI, -7.67 to -5.48) in the median quintile.
"These results highlight the potential for using genetic information to tailor hypertension treatment," said the lead author of the study. "Identifying patients who are more likely to respond to specific medications could improve blood pressure control and reduce the risk of cardiovascular events."
Implications for Treatment-Resistant Hypertension
Furthermore, the study found that participants in the highest PRS quintile had a 67% higher odds of developing apparent treatment-resistant hypertension (aTRH) compared to those in the median quintile (odds ratio, 1.67; 95% CI, 1.19-2.36). aTRH was defined as the use of three antihypertensive medications with uncontrolled hypertension or the use of four or more medications regardless of blood pressure control.
This suggests that the SBP PRS could also be a valuable tool for identifying individuals at higher risk of treatment resistance, allowing for more aggressive or alternative treatment strategies to be implemented early on.
Study Details and Limitations
The study population had a median age of 65 years, with 55.1% being female. The primary outcome measured was the change in SBP and diastolic blood pressure (DBP) over six months. aTRH was assessed at year three of follow-up. The SBP PRS was stratified into quintiles for analysis.
While the study provides valuable insights, it is important to note certain limitations. The analysis was conducted within a subset of Black participants, and the findings may not be generalizable to other populations. Additionally, the study focused on chlorthalidone and lisinopril, and further research is needed to determine the utility of the SBP PRS with other antihypertensive medications.
Future Directions
The researchers emphasize the need for future studies to determine whether the SBP PRS can inform the initial choice of treatment for individuals with hypertension. Further investigation is also warranted to explore the potential of combining genetic risk scores with other clinical factors to optimize hypertension management.
Overall, this study provides compelling evidence that genetic factors influence blood pressure response to chlorthalidone in Black individuals. The SBP PRS holds promise as a tool for personalizing hypertension treatment and improving outcomes for patients at risk of treatment resistance.
