Predicting cardiovascular morbidity and mortality with SCORE2 (OP) and Framingham risk estimates in combination with indicators of biological ageing

Background and Objective: Previous research assessing whether biological ageing (BA) indicators can enhance the risk assessment of cardiovascular disease (CVD) outcomes beyond established CVD risk indicators, such as Framingham Risk Score (FRS) and Systematic Coronary Risk Evaluation (SCORE2)/SCORE2-Older Persons (OP), is scarce. We explored whether BA indicators, namely the Rockwood Frailty Index (FI) and leukocyte telomere length (TL), improve predictive accuracy of CVD outcomes beyond the traditional CVD risk indicators in general population of middle-aged and older CVD-free individuals. Methods: Data included 14 118 individuals from three population-based cohorts: TwinGene, Health 2000 (H2000), and the Helsinki Birth Cohort Study, grouped by baseline age (<70, 70+). The outcomes were incident CVD and CVD mortality with 10-year follow-up. Risk estimations were assessed using Cox regression and predictive accuracies with Harrell's C-index. Results: Across the three study cohorts and age groups: (i) a higher FI, but not TL, was associated with a higher occurrence of incident CVD (P <. 05), (ii) also when considering simultaneously the baseline CVD risk according to FRS or SCORE2/SCORE2-OP (P <. 05) (iii) adding FI to the FRS or SCORE2/SCORE2-OP model improved the predictive accuracy of incident CVD. Similar findings were seen for CVD mortality, but less consistently across the cohorts. Conclusions: We show robust evidence that a higher FI value at baseline is associated with an increased risk of incident CVD in middle-aged and older CVD-free individuals, also when simultaneously considering the risk according to the FRS or SCORE2/SCORE2-OP. The FI improved the predictive accuracy of CVD outcomes beyond the traditional CVD risk indicators and demonstrated satisfactory predictive accuracy even when used independently.