Abstract
Background and aims
Uncontrolled blood pressure (BP) can modify the risk/benefit ratio for prescribing anticoagulants to intracerebral hemorrhage (ICH) survivors with atrial fibrillation. Adverse polygenic profiles for BP increase the risk of uncontrolled BP in ischemic stroke survivors. We thus hypothesize that adverse polygenic profiles for BP are associated with higher risk of uncontrolled BP in ICH survivors with AF.
Methods
We conducted a genetic study within the NIH All of Us Research Program. ICH survivors with AF were identified using validated SNOMED codes. BP polygenic risk was modeled through a previously developed polygenic risk score (PRS) incorporating 7.4 million genetic variants and categorized as favorable (<20th percentile), neutral, (20-80th), or adverse (>80th). Outcomes were observed BP and uncontrolled BP (>140 systolic or >90 diastolic) with multi-variable regression models used to adjust for confounders.
Results
Among 446 ICH survivors with AF (mean age 68, 46% female), mean systolic BP increased across patients in favorable, neutral and adverse PRS groups (126, 131 and 133 mmHg), as did rates of uncontrolled BP (18%, 26%, and 31%). Multivariable regression models confirmed that adverse vs favorable PRS was associated with a 7.2 mmHg higher systolic BP (SE 3.1; p=0.02) and increased odds of uncontrolled BP (OR 1.19; 95% CI 1.01-1.39).
Overall, adverse BP polygenic profiles associate with significantly worse BP control in ICH survivors with AF. Because uncontrolled BP is the most important determinant of long-term outcomes in ICH survivors, these findings support further investigation into whether polygenic profiling can inform anticoagulation decision-making in this high-risk population.
Conflict of interest
Andrew Silberfeld, Shufan Huo, Santiago Clochiatti-Tuozzo, Cyprien Rivier, Guido Falcone: nothing to disclose.