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82 Life-course frailty and multimorbidity is harmful for the heart in older age: results from the mrc 1946 NSHD british birth cohort
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  1. Constantin-Cristian Topriceanu1,
  2. James Moon2,
  3. Rebecca Hardy3,
  4. Nish Chaturvedi2,
  5. Alun Hughes2,
  6. Gabriella Captur2
  1. 1University College London Medical School
  2. 2UCL Institute of Cardiovascular Science, University College London
  3. 3CLOSER, UCL Institute of Education

Abstract

Background Cardiovascular diseases are an important component of the multimorbidity syndrome which is associated with negative health outcomes resulting in a major societal economic burden. An objective way to assess multimorbidity 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, 19 to 44, 45 to 54 and 60 to 64 years) in birth cohort participants of the UK 1946 Medical Research Council National Survey of Heath and Development (NSHD). The 4 resultant frailty indices (FI0_16, FI19_44, FI45_54 and FI60_64) 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: left ventricular (LV) ejection fraction (EF), LV mass indexed to body surface area (BSA; LVmassi), BSA-indexed myocardial contraction fraction (MCFi) and LV filling pressure defined as E/e’>13. Generalized linear mixed models (glmm) with gamma distribution and log link or binomial distribution and logit link, assessed the association between FIs and echocardiographic parameters after adjustment for sex, socio-economic position and body mass index.

Abstract 82 Table 1 Associations between frailty at specific age-intervals during life-course (FI0_16, FI19_44, FI45_54 and FI60_64) and overall-life frailty (FIsum and FImean), and echocardiographic parameters (LVmassi and MCFi) at 60-64 years in the fully adjusted model.
Abstract 82 Table 2 Associations between frailty at specific age-intervals during life-course (FI60_64), step-change in deficit accumulation at various periods (FI2-1, FI3-1, FI4-1, FI4-2, FI4-3) and overall-life frailty (FImean), and echocardiographic parameters (EF and E/e’) at 60-64 years in the fully adjusted model.

Results 1,805 NSHD participants were included (834 male, mean FI60_64 0.28±0.097, range 0.07-0.70). A unit increase in frailty decreased EF by 11% and 12% for FI45_54 and FI60_64 respectively, by 10% to 12% for FI2-1, FI3-1, FI4-1 and FI4-2, and by 4% and 15% for FIsum and FImean respectively (all p<0.05). Single deficit accumulation had a significant impact on LVmassi and MCFi across all the life-course FIs and overall FIs (all p<0.05). As frailty intensified at each of the 4-time intervals, LVmassi increased by 0.91–1.42%, and MCFi decreased by 0.6–1.02%. As the whole-of-life burden of frailty increased (FIsum and FImean) LVmassi increased by 0.36 and 1.82% and MCFi decreased by 0.33 and 1.04%. One extra deficit accumulated translated into higher multiplicative odds of increasing LV filling pressure by 4.3 for FI60-64, 2.1 for FI4-1, 75.4 for FI4-2 and 78.5 for FI4-3 (all p<0.02).

Abstract 82 Figure 1 Comparing life-course frailty between participants with highest and lowest deciles in terms of EF and MCFi at 60–64 years old
(Top) The mean FIs for each age interval for the highest EF decile as assessed by echo at age 60-64 years (green) are plotted against the mean FIs of participants in the lowest decile (red).
(Bottom) The mean FIs for each age interval for the highest MCFi decile as assessed by echo at age 60-64 years (green) are plotted against the mean FIs of participants in the lowest decile (red).
Vertical bars represent standard error of the means. Wilcoxon signed-rank test p-values for median inter-decile differences are shown
EF, ejection fraction; MCFi, myocardial contraction fraction indexed to body surface area.
Abstract 82 Figure 2 Comparing life-course frailty between participants with highest and lowest deciles in terms of LVmassi and E/e’ ratio at 60-64 years old
(Top) The mean FIs for each age interval for the highest LVmassi deciles for both males and females as assessed by echo at age 60-64 years (red) are plotted against the mean FIs of participants in the lowest deciles (green).
(Bottom) The mean FIs for each age interval for the highest E/e’ decile as assessed by echo at age 60-64 years (red) are plotted against the mean FIs of participants in the lowest decile (green).
Vertical bars represent standard error of the means. Wilcoxon signed-rank test p-values for median inter-decile differences are shown
LVmassi, left ventricular mass indexed to body surface area;

Conclusion Frailty during childhood, young adulthood, middle age and older age associates with having a weaker (↓EF/MCFi), thicker (↑LVmassi) and stiffer (↑E/e’) heart in later-life. The accumulation of new deficits from one age interval to the next also associates with poorer cardiac function in later-life. It appears that multimorbidity and health deficits accumulated over the life-course strain the myocardium resulting in pathological myocardial hypertrophy potentially paving the way to later-life systolic or diastolic dysfunction in susceptible individuals

Conflict of Interest None.

  • frailty
  • multimorbidity
  • cardiovascular disease

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