Body mass index modifies the risk of cardiovascular death in proteinuric chronic kidney disease

Abstract

Background. In subjects with end-stage renal disease, a high body mass index (BMI) is inversely related to overall mortality, which has been coined reverse epidemiology phenomenon. This study sought to investigate this paradox as well as a possible risk modification by proteinuria on the relationship of BMI with earlier stages of chronic kidney disease (CKD) concerning cardiovascular mortality.Methods. We used the Vienna Health Screening Initiative, a longitudinal cohort study from 1990 to 2006, including 49398 volunteers (49.9 women, age 20-89 years): n = 2487 showed mild CKD (proteinuria and GFR >60 mlmin1.73 m 2) and n = 392 showed moderate CKD (GFR = 30-59 mlmin1.73 m 2). The follow-up period was 5.5 ± 4.2 years; n = 148 cardiovascular deaths occurred. Exposure variables were BMI, glomerular filtration rate (GFR) and proteinuria. Cox regression models on cardiovascular mortality with adjustment for age, sex, log(cholesterolHDL), uric acid, smoking, glucose, diabetes, mean blood pressure, hypertension and antihypertensive drug use were fitted.Results. The risk factor paradox is shown in moderate CKD (GFR = 45 mlmin1.73 m 2): hazard ratios (HR) of BMI contrasts decreased consistantly from 1.28 (95 CI 0.33-5.82) at BMI 20 kgm 2 versus 25 kgm 2 to 0.76 (95 CI 0.38-1.50) at BMI 30 kgm 2 versus 25 kgm 2 and to 0.58 (95 CI 0.13-2.64) at BMI 35 kgm 2 versus 25 kgm 2, thus showing an inverse relationship compared to mild CKDhealthy participants. Examining proteinuria as an effect modifier in this context showed that in moderate CKD (contrast: proteinuria versus no proteinuria) HR decreased more profoundly from 9.43 (95 CI 2.66-27.40) at BMI 25 kgm 2 to 3.74 (95 CI 0.93-15.70) at BMI 30 kgm 2 and to 1.95 (95 CI 0.37-22.30) at BMI 35 kgm 2, and conversely in non-proteinuric subjects, hazards for cardiovascular mortality increased in underweight as well as in overweightobese subjects in a U-shaped manner.Conclusions. Our results suggest that obese subjects with proteinuric CKD may not be counselled for weight reduction since a higher BMI was associated with a remarkably reduced risk of death.