Systemic Inflammation and Cardio-Renal Organ Damage Biomarkers in Middle Age Are Associated With Physical Capability Up to 9 Years Later

Circulation. 2019 Apr 23;139(17):1988-1999. doi: 10.1161/CIRCULATIONAHA.118.037332.


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-B-type 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.

Keywords: aging; cohort studies; cystatin C; inflammation; natriuretic peptides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood*
  • Blood Pressure
  • Body Height
  • Body Mass Index
  • Cholesterol / blood
  • Cystatin C / blood*
  • E-Selectin / blood
  • Follow-Up Studies
  • Glycated Hemoglobin / analysis
  • Heart Diseases / blood
  • Heart Diseases / epidemiology*
  • Heart Diseases / physiopathology
  • Humans
  • Inflammation / blood*
  • Inflammation / epidemiology
  • Inflammation / physiopathology
  • Interleukin-6 / blood*
  • Kidney Diseases / blood
  • Kidney Diseases / epidemiology*
  • Kidney Diseases / physiopathology
  • Lipoproteins, HDL / blood
  • Male
  • Middle Aged / physiology*
  • Natriuretic Peptide, Brain / blood*
  • Peptide Fragments / blood*
  • Physical Fitness / physiology*
  • Risk Factors
  • Smoking / epidemiology
  • Socioeconomic Factors
  • United Kingdom / epidemiology


  • Biomarkers
  • CST3 protein, human
  • Cystatin C
  • E-Selectin
  • Glycated Hemoglobin A
  • IL6 protein, human
  • Interleukin-6
  • Lipoproteins, HDL
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Cholesterol