The Role of a Composite Fitness Score in the Association Between Low-Density Cholesterol and All-Cause Mortality in Older Adults: An Individual Patient Data Meta-Analysis

Abstract

Background In the general population an increase in low-density lipoprotein cholesterol (LDL-C) predicts higher cardiovascular disease risk, and lowering LDL-C can prevent cardiovascular disease and reduces mortality risk. Interestingly, in cohort studies that include very old populations, no or inverse associations between LDL-C and mortality have been observed. This study aims to investigate whether the association between LDL-C and mortality in the very old is modified by a composite fitness score. Methods A two-stage meta-analysis of individual participant data from the five observational cohort studies. The composite fitness score was operationalized by performance on a combination of four markers: functional ability, cognitive function, grip strength, and morbidity. We pooled hazard ratios (HR) from Cox proportional-hazards models for five-year mortality risk for 1 mmol/L increase in LDL-C. Models were stratified by high/low composite fitness score. Results Composite fitness scores were calculated for 2,317 participants (median 85 years, 60% females), of which 994 (42.9%) had a high composite fitness score, and 694 (30.0%) had a low composite fitness score. There was an inverse association between LDL-C and five-year mortality risk (HR 0.87 [95%CI 0.80-0.94]; p< 0.01), most pronounced in participants with a low composite fitness score (HR 0.85 [95%CI 0.75-0.96]; p=0.01), compared to those with a high composite fitness score (HR= 0.98 [95%CI 0.83-1.15]; p=0.78), the test for subgroups differences was not significant. Conclusion In this very old population, there was an inverse association between LDL-C and all-cause mortality, which was most pronounced in participants with a low composite fitness score.