Hemoglobin, Albuminuria, and Kidney Function in Cardiovascular Risk: The ARIC (Atherosclerosis Risk in Communities) Study

Background-Reduced estimated glomerular filtration rate (eGFR) and elevated urinary albumin-to-creatinine ratio (ACR) individually increase risk of cardiovascular disease (CVD). We hypothesized that these associations are stronger among people with abnormal (both low and high) hemoglobin levels. Methods and Results-Using 5801 participants with available hemoglobin measures of the ARIC (Atherosclerosis Risk in Community) study in 1996-1998, we explored the cross-sectional association of eGFR and ACR with hemoglobin levels and their longitudinal associations with CVD (heart failure, coronary heart disease, and stroke) risk through 2013. At baseline, 8.8% had anemia (<13g/dL in men and <12g/dL in women) and 7.2% had high hemoglobin (16g/dL in men and 15g/dL in women). The adjusted prevalence ratio of anemia was 2.12 (95% confidence interval, 1.59-2.82) for eGFR 30 to 59 compared with 90mL/min per 1.73m(2) and 1.45 (1.07-1.95) for ACR >= 30 compared with <10mg/g. ACR >= 30mg/g was also associated with high hemoglobin (prevalence ratio, 1.57 [1.12-2.19] compared with <10mg/g). During follow-up, there were 1069 incident CVDs among 5098 CVD-free participants at baseline. In multivariable Cox models, lower eGFR, higher ACR, and anemia were each independently associated with CVD risk, with the association of low eGFR being slightly stronger in anemia (P-for-interaction, 0.072). There was no hemoglobin-ACR interaction; however, when CVD subtypes were analyzed separately, risk of coronary heart disease and stroke associated with high ACR was slightly stronger in high hemoglobin (P-for-interaction, 0.074). Conclusions-Kidney function, albuminuria, and anemia were correlated and independently associated with CVD risk. Correlation and potential interaction for atherosclerotic CVD between albuminuria and high hemoglobin deserve further investigation.