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 greater than or equal to0.3 mg/dL [greater than or equal to26.5 mumol/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% Cl, 0.70 to 1.67). However, baseline creatinine levels from HERS were remarkably strong predictors of HERS-II events. Conclusion: 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.