Heterogeneous cardiovascular benefit of guideline-concordant risk-factor control according to multimodal health-reserve trajectories across HRS, ELSA, SHARE and CHARLS

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Title: Heterogeneous cardiovascular benefit of guideline-concordant risk-factor control according to multimodal health-reserve trajectories across HRS, ELSA, SHARE and CHARLS Study type: Observational prospective cohort study Brief abstract: This pre-registered multi-cohort study aims to test whether longitudinal multimodal health-reserve trajectories (physical function, cognition, depressive symptoms) modify cardiovascular disease-reduction benefit attained by guideline-concordant risk-factor control (smoking cessation, initiation of antihypertensive / antidiabetic / lipid-lowering pharmacotherapy). Main longitudinal analyses are performed on HRS, ELSA, SHARE, CHARLS. LASI, MHAS, KLoSA are restricted to cross-sectional descriptive analyses only. NHANES serves as supplementary calibration analysis, no longitudinal survival modelling. Primary outcome is incident cardiovascular disease; secondary outcome is all-cause mortality. Counting-process time-varying Cox model, GBTM group-based trajectory modelling, meta-analysis, mediation analysis, absolute-risk metrics (ARR, NNT, net-benefit) will be implemented. All deviations from a-priori plan are documented in deviation_shturl.md. Git commit-hash: d0bd8b3. Keywords: multimodal health reserve; trajectory; risk-factor control; effect modification; cardiovascular disease; older adults; harmonised cohort Preregistration template used: Open Preregistration; Embargo period: 36 months

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