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

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 49 398 volunteers (49.9% women, age 20–89 years): n = 2487 showed mild CKD (proteinuria and GFR >60 ml/min/1.73 m2) and n = 392 showed moderate CKD (GFR = 30–59 ml/min/1.73 m2). 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(cholesterol/HDL), 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 ml/min/1.73 m2): hazard ratios (HR) of BMI contrasts decreased consistantly from 1.28 (95% CI 0.33–5.82) at BMI 20 kg/m2 versus 25 kg/m2 to 0.76 (95% CI 0.38–1.50) at BMI 30 kg/m2 versus 25 kg/m2 and to 0.58 (95% CI 0.13–2.64) at BMI 35 kg/m2 versus 25 kg/m2, thus showing an inverse relationship compared to mild CKD/healthy 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 kg/m2 to 3.74 (95% CI 0.93–15.70) at BMI 30 kg/m2 and to 1.95 (95% CI 0.37–22.30) at BMI 35 kg/m2, and conversely in non-proteinuric subjects, hazards for cardiovascular mortality increased in underweight as well as in overweight/obese 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.