Summary

Background and objectives Higher body mass index (BMI) is paradoxically associated with lower mortality in persons with CKD, but whether cardiometabolic abnormalities modulate this association is unclear. Design, setting, participants, &measurementsParticipantswithCKD from theReasons forGeographic andRacial Differences in Stroke (REGARDS) study (n=4374) were analyzed. The harmonized criteria for metabolic syn-dromewere used to definemetabolic health, and participants were categorized into one of sixmutually exclusive categories defined by combined measures of metabolic health (metabolically healthy,,3 criteria for metabolic syndrome; metabolically unhealthy, $3 criteria) and weight status (normal weight, BMI 18.5–24.9 kg/m2; overweight, BMI 25–29.9 kg/m2; obese, BMI $30 kg/m2). Cox models were used to estimate the hazard ratio (HR) of death as a function of each category. ResultsA total of 683 deaths were observed over amean 4.5 years of follow-up. In analyses adjusted for age, race, sex, and geographic region of residence, comparedwithmetabolically healthy normalweight persons, theHRs of mortality in metabolically healthy overweight and obese persons were 0.68 (95 % confidence interval [95 % CI], 0.53 to 0.87) and 0.71 (95%CI, 0.51 to 0.98), respectively, whereas therewere no statistically significant differences in survival among metabolically unhealthy overweight or obese individuals. After further adjustment for lifestyle, clinical and laboratory factors includingmarkers of kidney function, theHRofmortality remained lower in metabolically healthy overweight individuals compared with metabolically healthy normal weight individ-uals (HR, 0.74; 95 % CI, 0.57 to 0.96). ConclusionsMetabolic abnormalities may attenuate the magnitude and strength of survival benefits associated with higher BMI in individuals with CKD