Abstract

Introduction: Abnormal levels of urinary albumin concentration (UAC) and N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) have each been independently associated with an increased risk of congestive heart failure (CHF). It remains unknown whether the concomitant presence of abnormal UAC and NT-proBNP increases an individual’s risk for future CHF beyond that contributed by each biomarker. Objective: To examine the joint association between abnormal UAC and NT-ProBNP with incident CHF in participants from the SPRINT (Systolic Blood Pressure Intervention Trial) study. Methods: This analysis included 8,176 participants from SPRINT with available data on baseline UAC and NT-proBNP. UAC was measured by urine albumin-creatinine ratio (UACR). Albuminuria was defined as UACR ≥30 mg/g. Abnormal NT-proBNP was defined as levels ≥125 pg/ml. Cox proportional hazard models were used to examine the association of UAC and NT-proBNP, as well as albuminuria and abnormal NT-proBNP, with incident CHF. Results: Over a median follow-up of 3.2 years, 179 incident cases of CHF were observed. In adjusted models, the risk of incident CHF (HR 95% CI) associated with each 1 (one) unit standard deviation increase in the levels of UAC and NT-proBNP was 1.10 (1.04-1.16; p <0.001) and 1.13 (1.10-1.16; p <0.0001), respectively. A statistically significant multiplicative interaction between UAC*NT-proBNP was observed in the fully adjusted model (p <0.0001). The risk associated with the presence of abnormal UAC +/- abnormal NT-proBNP in the SPRINT cohort is depicted in the figure. Conclusions: Among SPRINT participants, we found a significant multiplicative interaction between UAC and NT-proBNP as predictors of incident CHF. Also, the risk of future CHF was over six times higher in individuals with abnormal UAC and NT-proBNP, compared with those with normal levels of both biomarkers. More studies are needed to further explore this interaction and the implications on CHF prevention.

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