Coronary Disease Risk Curve of Serum Creatinine is Linear in Turkish Men,U-Shaped in Women

Abstract

Objectives

The highest levels of glomerular filtration rate are associated with increased coronary heart disease (CHD) risk, an issue we investigated in separate sexes in a population prone to metabolic syndrome.

Research Methods and Procedures

In total, 1948 participants of the Turkish Adult Risk Factor study with available creatinine determinations were studied at a mean 3.4 years’ follow-up. Using quartiles of creatinine, risk in Cox models of incident CHD or the likelihood of combined prevalent and incident CHD was assessed.

Results

Women in the lowest creatinine quartile demonstrated the lowest risk profile across diverse variables, except showing low high-density lipoprotein cholesterol and average apolipoprotein A-I and lipoprotein (a) concentrations implicating impaired atheroprotective properties. Whereas serum creatinine in men was not significantly associated with 6 proinflammatory variables comprised in linear regression analysis, apolipoprotein A-I and lipoprotein (a) were significant positive covariates in women, the latter tending to negative association in women without metabolic syndrome. In men, the highest (>1.10 mg/dL), compared with the lowest, creatinine quartile significantly predicted CHD risk, at 1.85-fold relative risks, after adjustment for established risk factors. The risk curve in women was U-shaped, the top and bottom quartiles tending to display higher risk (odds ratio, 1.28 [95% confidence interval, 0.91-1.80]) compared with the 2 intermediate quartiles.

Conclusions

Increasing serum creatinine values are associated strongly and independently with CHD risk in men but not in women in whom the risk curve is U-shaped. The phenomenon of low creatinine levels underlies some hitherto unexplained relevant observations, and low measurements may be attributed to inassayability secondary to involvement in autoimmune activation.