Systemic Inflammation and Cardio-Renal Organ Damage Biomarkers in Middle Age Agre Associated with Physical Capability Up to 9 Years Later: Findings from a British Birth Cohort Study
BACKGROUND: Physical capability, a key component of healthy aging, is
associated with cardiovascular and other risk factors across life. We investigated
whether midlife biomarkers of heart and kidney damage capturing the
cumulative impact of long-term adverse exposures were associated with the
level and decline in physical capability over 9 years of follow-up, taking account
of systemic inflammatory biomarkers and conventional cardiovascular risk
factors.
METHODS: We used data on 1736 men and women from the oldest British
birth cohort study with walking speed, chair rise speed, balance time, and grip
strength assessed at ages 60 to 64 and 69 years. We tested associations between
logged and standardized measures of cystatin C, NT-proBNP (N-terminal pro-Btype natriuretic peptide), interleukin (IL)-6, and E-selectin at age 60 to 64 years
with performance at age 69 years, adjusting for sex, height, and body mass
index; then for performance at age 60 to 64 years. These biomarkers were
mutually adjusted, and additionally adjusted for cardiovascular risk factors (pulse
pressure, total/high density lipoprotein cholesterol, glycosylated hemoglobin),
diabetes mellitus, cardiovascular and kidney disease, smoking status, and lifetime
socioeconomic position.
RESULTS: Cystatin C, NT-proBNP, and IL-6 (but not E-selectin) were inversely
associated with all outcomes, adjusted for sex, height, and body mass index.
For example, a 1-SD increase in logged NT-proBNP was associated with
weaker grip (−0.63 kg, 95% CI, −0.99 to −0.28); the equivalent association
for cystatin C was −0.60 kg (95% CI, −0.94 to −0.25) and for IL-6 was −0.76
kg (95% CI, −1.11 to −0.41). Most associations remained, albeit attenuated,
after adjustment for previous performance and mutual adjustment of the
biomarkers. NT-proBNP and IL-6 (but not cystatin C) were more strongly
associated with the outcomes than many of the conventional risk factors after
mutual adjustment.
CONCLUSIONS: Higher levels of NT-proBNP may identify those in midlife at risk
of accelerated physical decline. Before considering the use of NT-proBNP for risk
stratification, further research should untangle whether these associations exist
because the biomarker is an integrated measure of cumulative exposures to
relevant stressors across life, or whether it is marking additional risk pathways.
Randomized trials to reduce the rate of decline in physical capability or delay
incident disability could benefit from including middle-aged adults and adding
NT-proBNP and IL-6 as intermediate outcomes