Physiological measures variability and risks of heart disease and stroke: evidence from three cohort studies

The overall effect of long-term variability in physiological measures on cardiovascular health of older adults and the underlying mechanic pathway remain uncertain. We constructed a composite score (0 ~ 3) of variability in physiological measures, including blood pressure, pulse rate, and body mass index, in older adults from the China Health and Retirement Longitudinal Study (CHARLS) 2011 ~ 2015, the Health and Retirement Study (HRS) 2006/2008 ~ 2014/2016, and the UK Biobank 2006 ~ 2019. The associations of the composite score with incident risks of heart disease and stroke were assessed. The mediation roles of several biomarkers were explored. A higher composite score was related to increased incident risk of heart disease in older adults from the US and the UK and increased incident risk of stroke in all three cohorts. Upon pooling the results, each 1-point increment in the composite score was associated with a 19% (hazard ratio: 1.19; 95% confidence interval: 1.14, 1.30) and a 23% (1.23; 1.12, 1.35) increments in incident risks of heart disease and stroke, respectively. The composite score also exhibited an inverse relationship with grip strength while displaying positive associations with C-reactive protein, glycosylated hemoglobin Alc (HbAlc), and cystatin C. Reduced grip strength, elevated HbAlc, and elevated cystatin C significantly mediated the composite score-associated elevated risks of heart disease and stroke. Long-term variability in physiological measures was associated with increased incident risks of heart disease and stroke, and the associations were partially mediated through deteriorated biomarkers of muscle strength, hyperglycemia, and kidney function.