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

Abstract

ObjectivesCoronary 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. MethodsThe 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. ResultsTwo-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. ConclusionsGenetic 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.