Kidney Function as Risk Factor and Predictor of Cardiovascular Outcomes and Mortality Among Older Adults

Am J Kidney Dis. 2021 Mar;77(3):386-396.e1. doi: 10.1053/j.ajkd.2020.09.015. Epub 2020 Nov 14.


Rationale & objective: Estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (UACR) are associated with cardiovascular events in the general population but their utility among older adults is unclear. We investigated the associations of eGFR and UACR with stroke, myocardial infarction (MI), and death among older adults.

Study design: Population-based cohort study.

Setting & participants: 1,581 participants (aged≥70 years) in the Berlin Initiative Study (BIS) without prior stroke or MI.

Exposures & predictors: Serum creatinine- and cystatin C-based eGFR, UACR categories, and measured GFR (n=436).

Outcomes: Stroke, MI, and all-cause mortality.

Analytical approach: HRs and 95% CIs derived from multivariable-adjusted Cox proportional hazards models for association analyses. Net reclassification improvement (NRI) and C statistic differences comparing the predictive benefit of kidney measures with a traditional cardiovascular risk model.

Results: During a median follow-up of 8.2 years, 193 strokes, 125 MIs, and 531 deaths occurred. Independent of UACR, when GFR was estimated using the creatinine- and cystatin C-based BIS equation, eGFR of 45 to 59mL/min/1.73m2 (vs eGFR>60mL/min/1.73m2) was associated with stroke (HR, 2.23; 95% CI, 1.55-3.21) but not MI or all-cause mortality. For those with eGFR<45mL/min/1.73m2, the HRs were 1.99 (95% CI, 1.23-3.20) for stroke, 1.38 (95% CI, 0.81-2.36) for MI, and 1.57 (95% CI, 1.20-2.06) for mortality. Compared with UACR<30mg/g, UACR of 30 to 300mg/g was not associated with stroke (HR, 0.91; 95% CI, 0.63-1.33) but was associated with MI (HR, 1.65; 95% CI, 1.09-2.51) and all-cause mortality (HR, 1.63; 95% CI, 1.34-1.98). Prediction analysis for stroke showed significant positive NRI for eGFR calculated using the cystatin C-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and the creatinine- and cystatin C-based BIS and Full Age Spectrum equations. UACR demonstrated significant positive NRIs for MI and mortality.

Limitations: eGFR and UACR categorization based on single assessments; lack of cause-specific death data.

Conclusions: eGFR of 45 to 59mL/min/1.73m2 without albuminuria was associated with stroke but not MI or all-cause mortality in older adults. In contrast, UACR of 30 to 300mg/g was associated with MI and all-cause mortality but not with stroke. Furthermore, cystatin C-based eGFR improved risk prediction for stroke in this cohort of older adults.

Keywords: Berlin Initiative Study (BIS); Chronic kidney disease (CKD); all-cause mortality; association; cardiovascular disease (CVD); creatinine; cystatin C; elderly; estimated glomerular filtration rate (eGFR); measured GFR; myocardial infarction (MI); old age; prediction; renal function; stroke; urinary albumin-creatinine ratio (UACR).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Albuminuria / epidemiology*
  • Cause of Death
  • Cohort Studies
  • Creatinine / metabolism
  • Cystatin C / metabolism
  • Female
  • Glomerular Filtration Rate*
  • Humans
  • Kidney / metabolism
  • Kidney / physiopathology
  • Kidney Function Tests
  • Male
  • Mortality*
  • Myocardial Infarction / epidemiology*
  • Proportional Hazards Models
  • Renal Insufficiency, Chronic / epidemiology*
  • Renal Insufficiency, Chronic / metabolism
  • Risk Factors
  • Stroke / epidemiology*


  • Cystatin C
  • Creatinine