Abstract
Rationale & Objective: Lower estimated
glomerular filtration rate (eGFR) is associated
with heart failure (HF) risk. However, eGFR
based on cystatin C (eGFRcys) and creatinine
(eGFRcr) may differ substantially within an
individual. The clinical implications of these
differences for risk of HF among persons with
chronic kidney disease (CKD) are unknown.
Study Design: Prospective cohort study.
Setting & Participants: 4,512 adults with CKD
and without prevalent HF who enrolled in the
Chronic Renal Insufficiency Cohort (CRIC) Study.
Exposure: Difference in GFR estimates (eGFRdiff; ie, eGFRcys minus eGFRcr).
Outcome: Incident HF hospitalization.
Analytical Approach: Fine-Gray proportional
subhazards regression was used to investigate
the associations of baseline, time-updated, and
slope of eGFRdiff with incident HF.
Results: Of 4,512 participants, one-third had
eGFRcys and eGFRcr values that differed by
over 15 mL/min/1.73 m2
. In multivariableadjusted models, each 15 mL/min/1.73 m2
lower baseline eGFRdiff was associated with
higher risk of incident HF hospitalization (hazard
ratio [HR], 1.20 [95% CI, 1.07-1.34]). In timeupdated analyses, those with eGFRdiff less
than ?15 mL/min/1.73 m2 had higher risk of
incident HF hospitalization (HR, 1.99 [95% CI,
1.39-2.86]), and those with eGFRdiff ?15 mL/
min/1.73 m2 had lower risk of incident HF
hospitalization (HR, 0.67 [95% CI, 0.49-0.91])
compared with participants with similar eGFRcys
and eGFRcr. Participants with faster declines in
eGFRcys relative to eGFRcr had higher risk of
incident HF (HR, 1.49 [95% CI, 1.19-1.85])
compared with those in whom eGFRcys and
eGFRcr declined in parallel.
Limitations: Entry into the CRIC Study was
determined by eGFRcr, which constrained the
range of baseline eGFRcr—but not
eGFRcys—values.
Conclusions: Among persons with CKD who
have large differences between eGFRcys and
eGFRcr, risk for incident HF is more strongly
associated with eGFRcys. Diverging slopes between eGFRcys and eGFRcr over time are also
independently associated with risk of incident HF.