Creatinine levels and cardiovascular events in women with heart disease: do small changes matter?
BACKGROUND
Small changes in creatinine levels have been incrementally associated with increased risk for heart failure morbidity, but their association with cardiovascular events has not been evaluated in persons with established coronary heart disease (CHD).


METHODS
This was an observational study from the Heart and Estrogen/Progestin Replacement Study (HERS) and the HERS-II follow-up study. Participants were 2,763 postmenopausal women with CHD who were followed up for a mean of 4.1 years during HERS and an additional 2.7 years during HERS-II. We evaluated the association of worsened renal function (creatinine level increase > or = 0.3 mg/dL [> or =26.5 micromol/L]) during HERS with CHD outcomes (nonfatal myocardial infarction and CHD death) that occurred during HERS-II.


RESULTS
Only 194 participants (9%) had worsened renal function during HERS, and they were characterized by a greater prevalence of diabetes, lower high-density lipoprotein cholesterol and higher triglyceride levels, and increased rate of cardiovascular events during HERS (all P < 0.01). After adjustment for only baseline creatinine levels, worsened renal function was associated with HERS-II CHD events (relative hazard [RH], 1.54; 95% confidence interval [CI], 1.04 to 2.29). After adjustment for baseline characteristics, HERS cardiovascular events, and medication use, worsened renal function was no longer associated with CHD events (RH, 1.08; 95% CI, 0.70 to 1.67). However, baseline creatinine levels from HERS were remarkably strong predictors of HERS-II events.


CONCLUSIONS
Although baseline renal function was among the strongest predictors of CHD events during 7 years of HERS follow-up, we found no significant association of worsened renal function with cardiovascular outcomes after adjustment for cardiovascular risk factors and interim events.
Shlipak
Michael G
MG
General Internal Medicine Section, Veterans Affairs Medical Center, San Francisco, CA 94121, USA. shlip@itsa.ucsf.edu
Stehman-Breen
Catherine
C
Vittinghoff
Eric
E
Lin
Feng
F
Varosy
Paul D
PD
Wenger
Nanette K
NK
Furberg
Curt D
CD
D000368:Aged; D008078:Cholesterol, LDL / Q000097:blood; D003327:Coronary Disease / Q000150:complications* / Q000401:mortality; D003404:Creatinine / Q000097:blood*; D048909:Diabetes Complications; D015914:Estrogen Replacement Therapy; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications*; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000209:etiology*; D017698:Postmenopause; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
D008078:Cholesterol, LDL; D014280:Triglycerides; D003404:Creatinine