Associations between life-course frailty and later-life heart size and function in the 1946 NSHD British birth cohort-an epidemiological study

Abstract

Abstract Background Cardiovascular diseases are an important component of the multi-morbidity syndrome which is associated with negative health outcomes resulting in a major societal economic burden. An objective way to assess multi-morbidity is to calculate a frailty index based on medical deficit accumulation. Late-life frailty has been validated to predict mortality, but little is known about the association between life-course frailty and cardiovascular health in later-life. Purpose To study the association between life-course frailty and later-life heart size and function using data from the world's longest running birth cohort with continuous follow-up. Methods A 45-deficit frailty index (FI) was calculated at 4 age-intervals across the life-course (0 to 16 years old, 19 to 44 years old, 45 to 54 years old and 60 to 64 years old) in participants from the UK 1946 Medical Research Council (MRC) National Survey of Heath and Development (NSHD) birth cohort. The life-course frailty indices (FI0_16, FI19_44, FI45_54 and FI60_64) reflect the cumulative medical deficits at the corresponding age-intervals. They were used to derive FImean and FIsum reflecting overall-life frailty. The step change in deficit accumulation between age-intervals was also calculated (FI2-1, FI3-1, FI4-1, FI3-2, FI4-2, FI4-3). Echocardiographic data at 60–64 years provided: E/e' ratio, ejection fraction (EF), myocardial contraction fraction index (MCFi) and left ventricular mass index (LVmassi). Generalized linear mixed models with gamma distribution and log link assessed the association between FIs and echo parameters after adjustment for sex, socio-economic position and body mass index. Results 1.805 NSHD participants were included (834 male). Accumulation of a single deficit had a significant impact (p<0.0001 to p<0.049) on LVmassi and MCFi in all the life-course FIs and overall FIs. LVmassi increased by 0.89% to 1.42% for the life-course FIs and by 0.36%/1.82% for FIsum and FImean respectively. MCFi decreased by 0.62% to 1.02% for the life-course FIs and by 0.33%/ 1.04%. for FIsum and FImean respectively. One accumulated deficit translated into higher multiplicative odds (13.2 for FI60-64, 2.1 for FI4-1, 75.4 for FI4-2 and 78.5 for FI4-3) of elevated filling pressure (defined as E/e' ratio >13, p<0.0.005 to p<0.02).A unit increase in frailty decreased LV EF (%) by 11%/12% for FI45-54 and FI60-64 respectively, by 10% to 12% for FI2-1, FI3-1, FI4-1 and FI4-2, and 4%/15% for FIsum and FImean respectively (p<0.0014 to p<0.044). Conclusion Frailty during the life-course, overall life-frailty and the step change in deficit accumulation is associated with later-life cardiac dysfunction. Frailty strain appears to have its greatest impact on pathological myocardial hypertrophy (high LVmassi and low MCFi) potentially paving the way to later-life systolic or diastolic dysfunction in susceptible individuals. Funding Acknowledgement Type of funding source: None