Association of intrinsic capacity with incidence and mortality of cardiovascular disease: Prospective study in UK Biobank

Abstract

Background: The World Health Organization proposed the concept of intrinsic capacity (IC; the composite of all the physical and mental capacities of the individual) as central for healthy ageing. However, little research has investigated the interaction and joint associations of IC with cardiovascular disease (CVD) incidence and CVD mortality in middle- and older-aged adults.

Methods: Using data from 443 130 UK Biobank participants, we analysed seven biomarkers capturing the level of functioning of five domains of IC to calculate a total IC score (ranging from 0 [better IC] to +4 points [poor IC]). Associations between IC score and incidence of six long-term CVD conditions (hypertension, stroke/transient ischaemic attack stroke, peripheral vascular disease, atrial fibrillation/flutter, coronary artery disease and heart failure), and grouped mortality from these conditions were estimated using Cox proportional models, with a 1-year landmark analysis to triangulate the findings.

Results: Over 10.6 years of follow-up, CVD morbidity grouped (n = 384 380 participants for the final analytic sample) was associated with IC scores (0 to +4): mean hazard ratio (HR) [95% confidence interval, CI] 1.11 [1.08-1.14], 1.20 [1.16-1.24], 1.29 [1.23-1.36] and 1.56 [1.45-1.59] in men (C-index = 0.68), and 1.17 [1.13-1.20], 1.30 [1.26-1.36], 1.52 [1.45-1.59] and 1.78 [1.67-1.89] in women (C-index = 0.70). In regard to mortality, our results indicated that the higher IC score (+4 points) was associated with a significant increase in subsequent CVD mortality (mean HR [95% CI]: 2.10 [1.81-2.43] in men [C-index = 0.75] and 2.29 [1.85-2.84] in women [C-index = 0.78]). Results of all sensitivity analyses by full sample, sex and age categories were largely consistent independent of major confounding factors (P < 0.001).

Conclusions: IC deficit score is a powerful predictor of functional trajectories and vulnerabilities of the individual in relation to CVD incidence and premature death. Monitoring an individual's IC score may provide an early-warning system to initiate preventive efforts.

Keywords: biological ageing; biomarkers; incident pathologies; intrinsic capacity; mortality.

Figure 1

Association between incident cardiovascular disease (CVD) and intrinsic capacity (IC) deficit scores by sex, age categories (37–55, 55–65 and +65 years) and full sample. Data are presented as hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). (A) 37–55 years, (B) 55–65 years, (C) +65 years and (D) full sample. All analyses were adjusted for age, deprivation index, ethnicity, alcohol use, dietary intake, smoking status, physical activity, time spent using TV/CPU and body mass index category. The incremental effect of an increasing number of IC factors was assessed by comparing the HRs for the presence of 1, 2, 3 or +4 factors, using the zero factors group as the reference group. The global incidence CVD was derived from cause‐specific disease as hypertension, stroke/transient ischaemic attack stroke, peripheral vascular disease, atrial fibrillation/flutter, coronary artery disease and heart failure.

Figure 2

Hazard ratios (HRs) for cardiovascular disease (CVD) mortality and intrinsic capacity (IC) deficit scores by sex, age categories (37–55, 55–65 and +65 years) and full sample. Data are presented as HRs and corresponding 95% confidence intervals (CIs). (A) 37–55 years, (B) 55–65 years, (C) +65 years and (D) full sample. All analyses were adjusted for age, deprivation index, ethnicity, alcohol use, dietary intake, smoking status, physical activity, time spent using TV/CPU and body mass index category. The incremental effect of an increasing number of IC factors was assessed by comparing the HRs for the presence of 1, 2, 3 or +4 factors, using the zero factors group as the reference group. The global incidence CVD was derived from cause‐specific disease as hypertension, stroke/transient ischaemic attack stroke, peripheral vascular disease, atrial fibrillation/flutter, coronary artery disease and heart failure.