Joint Associations of Systolic Blood Pressure Polygenic Risk Score and Modifiable Risk Profiles With Incident Hypertension

Objective: To examine the associations of metabolic and behavioral risk profiles with incident hypertension and to assess whether these associations differ according to genetic predisposition, measured by a systolic blood pressure polygenic risk score (SBP-PRS), in a community-based Korean cohort. Design and method: This study included 6,173 baseline hypertension-free participants aged 40–69 years from the community-based Ansung and Ansan cohorts of the Korean Genome and Epidemiology Study (KoGES). An SBP-PRS was constructed using meta-analyzed genome-wide association study results from 125,850 KoGES participants and summary statistics from BioBank Japan, and categorized into low (<25th percentile), intermediate (25th–75th percentile), and high (>75th percentile) genetic risk groups. Metabolic and behavioral risk profiles were constructed by assigning one point to each component risk factor and summing the point. Metabolic factors included abdominal obesity, hypercholesterolemia, and prediabetes or diabetes, while behavioral factors included current smoking, heavy alcohol consumption, low physical activity, and high sodium intake. Participants were classified as having favorable, intermediate, or unfavorable risk profiles. Cox proportional hazards regression models were used to estimate hazard ratios for incident hypertension and to evaluate joint associations according to SBP-PRS strata. Five- and ten-year absolute risks of hypertension and corresponding 95% confidence intervals were estimated using 10,000 bootstrap resamples. Results: Higher SBP-PRS was associated with an increased risk of incident hypertension (HR 1.70, 95% CI 1.54–1.88 for high vs low genetic risk). Unfavorable metabolic risk profiles were strongly associated with hypertension incidence (HR 1.87, 95% CI 1.66–2.11 for unfavorable vs favorable), whereas behavioral risk profiles showed more modest associations (HR 1.27, 95% CI 1.07–1.49). In joint analyses, individuals with high genetic risk had consistently higher 5- and 10-year risks of hypertension, with smaller differences according to metabolic or behavioral risk profiles. Among individuals with low genetic risk, hypertension risk varied more clearly across metabolic and behavioral risk profiles.Conclusions: Genetic predisposition was associated with baseline risk of incident hypertension, whereas patterns of risk according to metabolic and behavioral profiles differed across levels of polygenic risk. These findings support a precision prevention approach that integrates genetic background with metabolic and behavioral risk profiles.