The association of multi-system health status and its longitudinal changes with cardiovascular disease risk: insights from multinational cohorts study

Introduction Cardiovascular disease (CVD) is a leading global health threat, yet traditional risk assessments focus on isolated physiological factors. Objectives This study aimed to investigate the association of multi-system health status and its longitudinal changes with CVD risk across multinational cohorts. Methods We utilized data from four large-scale longitudinal studies: the China Health and Retirement Longitudinal Study (CHARLS), the Health and Retirement Study (HRS), the English Longitudinal Study of Ageing (ELSA), and the Survey of Health, Ageing and Retirement in Europe (SHARE). Multi-system health status was assessed across four domains: cognitive function, psychological condition (depression), body types (Body Mass Index), and muscle strength (grip strength). Incident CVD was the primary outcome. Group-Based Multi-Trajectory Modeling (GBMTM) identified joint trajectories of multi-system health. Results At baseline, a higher number of unhealthy systems consistently associated with increased CVD risk across cohorts, particularly for those with 3-4 unhealthy systems (CHARLS: OR=1.690, P=0.001; HRS: OR=1.580, P=0.047; ELSA: OR=2.100, P=0.005; SHARE: OR=2.007, P<0.001). We identified three distinct multi-system health trajectories: resilient/maintainer, moderate decliner, and rapid decliner/vulnerable. The rapid decliner/vulnerable class consistently showed significantly increased CVD risk compared to the resilient/maintainer class (CHARLS: OR=1.779, P<0.001; HRS: OR=1.396, P=0.003; ELSA: OR=1.383, P=0.008; SHARE: OR=1.565, P<0.001). Furthermore, a clear dose-response relationship linked a higher cumulative number of unhealthy systems to increased CVD risk (OR for 3-4 systems in CHARLS = 2.284, P<0.001; ELSA = 2.095, P=0.001; SHARE = 2.868, P<0.001). Conclusion This multi-cohort study shows that both baseline multi-system health and its longitudinal decline/cumulative burden significantly increase CVD risk. These findings emphasized the importance of a holistic, multi-system approach for CVD risk assessment and management.