Abstract 19930: Genetically elevated NT-proBNP, Cardiovascular Outcomes and Life Expectancy in Elderly Blacks and Whites
Introduction: The functional variant rs198389 in the promoter region of the B-type Natriuretic Peptide (NPPB) gene has been associated with increased gene transcription and plasma levels of NT-proBNP in whites and blacks but its relationship with cardiovascular outcomes has been understudied.
Hypothesis: We hypothesize that genetic variation in the NPPB promoter region may be associated with alterations in NP response to hypertension and with cardiovascular (CV) outcomes.
Methods: NT-proBNP levels were measured in 9617 black and white subjects with rs198389 genotyping who attended visit 4 of the ARIC Study. Genotype status was related to outcomes, adjusting for known predictors and confounders including age, race and BMI.
Results: Overall, inheritance of the A-allele (frequency 43%) was associated with lower plasma levels of NT-proBNP compared to those with the G-allele (frequency 57%; p=1.6x10-18) as previously reported. Each 10mmHg elevation in SBP in hypertensive subjects was associated with 27% higher NT-proBNP in the AA genotype, 36% higher in AGs, and 45% higher in GGs (p<1.0x10-8 for each, p-value for interaction of genotype=0.03). In mean follow up of 14.5 years, there were 3481 deaths. After covariate adjustment, there was evidence of an allelic dose response with AG and AA genotypes associated with progressively higher mortality compared to GG [HR 1.12 (1.01-1.24) and HR 1.20 (1.08-1.33), respectively]. The GG genotype was protective from both CV and non-CV death (p=0.026 and p=0.010, respectively) and conferred an increase in residual lifespan by 8 months in whites and 17 months in blacks versus AA (from 50 years of age; p=0.045 and p=0.007, respectively).
Conclusions: The rs198389 G-allele is associated with elevated basal levels of NT-proBNP and protection from CV and non-CV mortality, possibly mediated by augmented NT-proBNP release in response to increases in SBP.
Author Disclosures: S. Seidelmann: None. O. Vardeny: Research Grant; Significant; Novartis. Honoraria; Significant; Novartis. B. Claggett: None. B. Yu: None. P. Bravo: None. A. Gupta: None. C. MacRae: None. E. Boerwinkle: None. S. Solomon: Other Research Support; Modest; Abbott Laboratories, Inc; Amgen, Inc; Daiichi-Sankyo, Inc; Novartis Pharma AG; Theracos; Boston Scientific; NHLBI; Lone Star Heart; and Sanofi.. Consultant/Advisory Board; Modest; Novartis Pharma AG and Amgen, Inc.
- © 2016 by American Heart Association, Inc.