RF32 | PSUN60 Bioactive Natriuretic Peptides Measured By Mass Spectrometry and Associations With BMI, Race, and Metabolic Markers

BACKGROUND: Natriuretic peptide (NP) hormones, atrial NP (ANP) and B-type NP (BNP), exert cardiovascular and metabolically protective effects. When measured by conventional immunoassay methods, NP levels are lower in obese, black, and insulin-resistant individuals, suggesting these groups may experience a relative NP deficiency. However, immunoassay measurements are likely poor determinants of physiologically relevant NPs as the immunoassay inadvertently captures predominantly inactive truncated peptides due to poor specificity and rapid degradation of the bioactive form. We have developed and validated a novel ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay(1) that specifically measures bioactive BNP (BNPMS) and ANP (ANPMS). Relationships between bioactive NPs measured by mass spectrometry (MS) with BMI, race, and glucose metabolism are not well-understood. METHODS: We measured bioactive BNP and ANP using a novel UPLC-MS/MS assay in 26 veterans without heart failure, diabetes, or significant cardiac/pulmonary/renal/hepatic disease. We also determined BNP using conventional immunoassay (BNPia), age, sex, race, BMI, fasting glucose, and HbA1c. We assessed relationships of NPs with continuous variables using Spearman's correlation and multivariable linear regression, and with categorical variables using Wilcoxon rank-sum. RESULTS: Among 26 veterans (aged 25-55, 69% male), 8 were lean (BMI 23.1 +/- 1.4 kg/m(2)) and 18 were obese (BMI 34 +/- 2.9 kg/m(2)). ANPMS was negatively associated with BMI (rs=-0.59, p=0.0015). Moreover, when analyzed by BMI category, ANPMS was lower in obese compared with lean individuals (mean 113.9 +/- 74.9 vs. mean 220 +/- 173.7 pg/mL, respectively, p=0.020). BNPMS was lower in blacks; all 5 black individuals had undetectably low BNPMS (<5 pg/mL), whereas whites had a higher mean BNPMS (19.3 pg/mL, p=0.011). BNPMS was negatively associated with fasting glucose (p=0.03) in multivariable regression models adjusted for age, sex, race, and BMI. BNPMS was not significantly associated with BNPia, possibly partially due to the large percentage whose BNPMS and/or BNPia was undetectably low (44% and 56%, respectively) in this non-heart failure cohort. DISCUSSION: Using a novel UPLC-MS/MS technique, we found that ANPMS is lower in obesity, and BNPMS is lower in black individuals and in those with higher fasting glucose. Our results are consistent with relationships of NPs assessed by traditional immunoassay methods from large epidemiologic studies. Our findings are particularly striking as our sample size was relatively small compared with epidemiologic studies. Our analyses of bioactive NP levels by this specific methodology support the emerging hypothesis that obese and black individuals experience a relative NP deficiency. Future large-scale studies quantifying bioactive NPs by MS are warranted to refine the phenotyping of individuals with relative NP deficiency and determine whether relative NP deficiency contributes to greater cardiometabolic risk. (1)Reference: Dillon EM et al. Active BNP Measured by Mass Spectrometry and Response to Sacubitril/Valsartan. Journal of Cardiac Failure. 2021 Nov. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 1:12 p.m. - 1:17 p.m.