Frailty and depressive symptoms in relation to cardiovascular disease risk in middle-aged and older adults

Abstract

As global aging accelerates, frailty and depressive symptoms have emerged as critical contributors to cardiovascular disease (CVD) risk among older adults. However, the dynamic interplay between these factors remains underexplored. Here, we examine the associations among frailty, depressive symptoms, and incident CVD using data from five international cohorts (HRS, CHARLS, SHARE, ELSA, MHAS) involving individuals aged 50 and above. Our findings reveal that frailty significantly increases CVD risk, with depressive symptoms partially mediating this relationship. Transitions into frailty elevate CVD risk, while improvements reduce it. Cross-lagged panel network analysis identifies consistent CVD predictors, including hypertension, diabetes, and mobility issues. Subgroups with stronger associations include frail males, older individuals, working or retired people, and those with unhealthy lifestyles. These results underscore the need for integrated interventions targeting frailty and depressive symptoms to prevent CVD in aging populations.

Fig. 1. Differences in frailty index across CVD.

Note: The images A, B, C, D and E illustrated the differences in frailty index across CVD by survey year in the following studies: HRS (Health and Retirement Study), MHAS (Mexican Health and Ageing Study), CHARLS (China Health and Retirement Longitudinal Study), ELSA (English Longitudinal Study of Ageing), and SHARE (Survey of Health, Ageing and Retirement in Europe), respectively. Additionally, image F presented the differences in baseline frailty index across CVD categorized by country. For all countries, the CVD group has a smaller sample size than the non-CVD group; detailed sample sizes are provided in Supplementary Table 49. T test (two-tailed independent t-test) for trend was used to compare the trends in FI and CVD across different survey waves. The years corresponding to the horizontal coordinates in images A, B, C, D, and E represented the FI using this survey period and the incident CVD at follow-up (e.g., The 2000 results in HRS corresponded to the use of FI for 2000 and the prevalence for 2002–2018, and so on). In image F, baseline FI and incident CVD at follow-up were used. Frailty index are presented as mean values, with error bars representing ± SD. The p value indicates the difference in frailty index between CVD and Non-CVD groups. **p < 0.01, ***p < 0.001. Source data are provided with this paper.

Fig. 2. Association between baseline FI, depressive symptoms and CVD.

Note: FI, frailty index; CVD, cardiovascular disease; (A) Pooled; (B) HRS, Health and Retirement Study; (C) CHARLS, China Health and Retirement Longitudinal Study; (D) SHARE, Survey of Health, Ageing and Retirement in Europe; (E) ELSA, English Longitudinal Study of Ageing; (F) MHAS, Mexican Health and Aging Study. All analyses have been adjusted for age, sex, education, employment, marital status, co-residence with children, smoking, drinking, social activity, and physical activity. In the SHARE and Pooled cohorts, we controlled the different country. In the analyses, HRS used frailty status in 2000, depressive symptoms in 2002, and incident CVD in 2004–2018; CHARLS used frailty status in 2011, depressive symptoms in 2013, and incident CVD in 2015–2018; SHARE used frailty status in 2011, depressive symptoms in 2013, and incident CVD in 2015–2019; ELSA used frailty status in 2004, depressive symptoms in 2006, and incident CVD in 2008–2018; MHAS used frailty status in 2001, depressive symptoms in 2003, and incident CVD in 2012–2018.

Fig. 3. Network structures across HRS, CHARLS, SHARE, ELSA, and MHAS.

Note: (A) HRS: Health and Retirement Study; (B) CHARLS: China Health and Retirement Longitudinal Study; (C) SHARE: Survey of Health, Ageing and Retirement in Europe; (D) ELSA: English Longitudinal Study of Ageing; (E) MHAS: Mexican Health and Aging Study. All analyses were adjusted age, sex, education, employment, marital status, co-residence with children, smoking, drinking, social activity, and physical activity. In the SHARE, we further controlled the different country. The lines in the figure represented odds ratios (OR), with values greater than 1 shown in blue and values less than 1 shown in red. Thicker lines indicate larger OR values. To enhance clarity, autoregressive effects and covariates were not displayed in the figure. Additionally, OR values within the range of 1 ± 0.3 were not presented.

Fig. 4. Association between baseline frailty status with incident CVD across subgroups.

Note: Subgroup analyses were conducted using Cox proportional hazards models (Model 4). Age was categorized into two groups (50–64 and ≥65 years). All models were adjusted for age, sex, education, employment status, marital status, co-residence with children, smoking, drinking, social activity, and physical activity. In the SHARE and pooled cohorts, country was included as a covariate. For detailed sample sizes, please refer to Table 1. Each circle represents the HR for a specific group, and the horizontal line through the circle denotes the 95% CI. The vertical dashed line represents the null value of HR = 1. Arrows indicate confidence intervals exceeding the plotting range.