Risk prediction of future cardiac arrest by evaluation of a genetic risk score alone and in combination with traditional risk factors

Objectives: Coronary heart disease (CHD) is a leading cause of death globally, commonly through sudden cardiac death. Cardiac arrest of cardiac origin (CA) is associated with a poor prognosis and there is a great need for risk assessment and intensified preventive actions. In this study we aim to assess if a genetic risk score for CHD, composed of 50 common CHD susceptibility variants (GRS), predicts CA and to evaluate a novel composite risk score including traditional risk factors as well as GRS. Methods: The GRS score alone and in combination with traditional CHD risk factors were examined in relation to CA incidence among 23 000 middle aged subjects during 18.9 years of follow-up. The cohort excluded patients with a diagnosed history of CHD, heart failure or stroke. Results: Two-hundred-fifty-two patients suffered a cardiac arrest during the follow up, of which 181 were CA. In a multivariate model with CHD risk factors, high versus low genetic risk predicted CA with a hazard ratio (HR) of 2.49 {(95% CI 1.50–4.12) (P < 0.001)}, surpassed only by higher estimates for male sex {HR = 2.91 (95% CI 2.09–4.06) (P < 0.001)}, ages 50–65 {HR = 2.74 (95% CI 1.42–5.25) (P = 0.003)} and ages 65–74 {HR = 5.10 (95% CI 2.56–10.16) (P < 0.001)}. Smoking, dyslipidemia, hypertension and diabetes mellitus also predicted CA but with lower HRs than GRS. A novel composite risk score including CHD risk factors as well as GRS predicted CA with a HR = 110.81 {(95% CI 15.43–795.63) (P < 0.001)} for the highest (5) versus the lowest quintile (1) of the risk score. Conclusions: Genetic risk of CHD is strongly associated with incident CA and when combined with traditional CHD risk factors may identify individuals who benefit from intensified preventive pharmacological treatment.