The predicted risk of IS for individuals with a high metaGRS (top 1%) and high levels of risk factors was maximal by age 75, reaching a cumulative incidence of 8.5% (95% CI 5.2–11.6%) for males and 5.1% (95% CI 3.1–7.1%) for females (Fig. 5a). Effective reduction in the levels of the modifiable risk factors (SBP, BMI, and smoking) to match guideline targets was predicted to result in a substantial reduction in risk, down to 2.8% (95% CI 1.7–3.9%) for males and 1.7% (95% CI 1.0–2.4%) for females by age 75, thus substantially compensating for the high genomic risk.
