Dataset Information

Race, Natriuretic Peptides, and High-Carbohydrate Challenge: A Clinical Trial.

ABSTRACT: RATIONALE:Lower NP (natriuretic peptide) levels may contribute to the development of cardiometabolic diseases. Blacks have lower NP levels than middle-aged and older white adults. A high-carbohydrate challenge causes an upregulation of a negative ANP regulator microRNA-425 (miR-425), which reduces ANP (atrial-NP) levels in whites. OBJECTIVES:We designed a prospective trial to study racial differences in (1) NP levels among young adults, (2) NP response to a high-carbohydrate challenge, and (3) explore underlying mechanisms for race-based differences. METHODS AND RESULTS:Healthy self-identified blacks and whites received 3 days of study diet followed by a high-carbohydrate challenge. Gene expression from whole blood RNA was assessed in the trial participants. Additionally, atrial and ventricular tissue samples from the Myocardial Applied Genomics Network repository were examined for NP system gene expression. Among 72 healthy participants, we found that B-type-NP, NT-proBNP (N-terminal-pro-B-type NP), and MRproANP (midregional-pro-ANP) levels were 30%, 47%, and 18% lower in blacks compared with whites (P?0.01), respectively. The decrease in MRproANP levels in response to a high-carbohydrate challenge differed by race (blacks 23% [95% CI, 19%-27%] versus whites 34% [95% CI, 31%-38]; Pinteraction<0.001), with no change in NT-proBNP levels. We did not observe any racial differences in expression of genes encoding for NPs (NPPA/NPPB) or NP signaling (NPR1) in atrial and ventricular tissues. NP processing (corin), clearance (NPR3), and regulation (miR-425) genes were ?3.5-, ?2.5-, and ?2-fold higher in blacks than whites in atrial tissues, respectively. We also found a 2-and 8-fold higher whole blood RNA expression of gene encoding for Neprilysin (MME) and miR-425 among blacks than whites. CONCLUSIONS:Racial differences in NP levels are evident in young, healthy adults suggesting a state of NP deficiency exists in blacks. Impaired NP processing and clearance may contribute to race-based NP differences. Higher miR-425 levels in blacks motivate additional studies to understand differences in NP downregulation after physiological perturbations. CLINICAL TRIAL REGISTRATION:URL: https://clinicaltrials.gov/ct2/show/NCT03072602. Unique identifier: NCT03072602.

SUBMITTER: Patel N

PROVIDER: S-EPMC7033629 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Race, Natriuretic Peptides, and High-Carbohydrate Challenge: A Clinical Trial.

Patel Nirav N Russell Griffin K GK Musunuru Kiran K Gutierrez Orlando M OM Halade Ganesh G Kain Vasundhara V Lv Wenjian W Prabhu Sumanth D SD Margulies Kenneth B KB Cappola Thomas P TP Arora Garima G Wang Thomas J TJ Arora Pankaj P

Circulation research 20191006 11

<h4>Rationale</h4>Lower NP (natriuretic peptide) levels may contribute to the development of cardiometabolic diseases. Blacks have lower NP levels than middle-aged and older white adults. A high-carbohydrate challenge causes an upregulation of a negative ANP regulator microRNA-425 (<i>miR-425</i>), which reduces ANP (atrial-NP) levels in whites.<h4>Objectives</h4>We designed a prospective trial to study racial differences in (1) NP levels among young adults, (2) NP response to a high-carbohydrat ...[more]

PMID: 31588864

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Project description:Importance:Contemporary clinical trials of heart failure with preserved ejection fraction (HFpEF) apply natriuretic peptide (NP) thresholds to identify patients who are more likely to have the disease of interest and to enrich the baseline risk of the enrolled cohort. Objective:To determine whether age, race/ethnicity, obesity, renal function, and atrial fibrillation (AF) affect the levels of NPs in HFpEF and whether the prognostic significance of NPs varies in these clinically important subgroups. Design, Setting, and Participants:This secondary analysis of the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial (TOPCAT) evaluated the distribution and prognostic significance of NPs across 6 subgroups comprising 1057 adult patients (60%) in the Americas region of TOPCAT with symptomatic heart failure (HF) and a left ventricular ejection fraction of 45% or more with available NPs at baseline. Exposures:Natriuretic peptides were log-transformed and standardized (expressed per 1 SD, z score) and assessed in 6 subgroups: age (cutoff, 70 years), black race, body mass index (BMI; calculated as weight in kilograms divided by height in meters squared; cutoff, 30 kg/m2), waist circumference (cutoff, 102 cm for men, 88 cm for women), estimated glomerular filtration rate (cutoff, 60 mL/min/1.73 m2), and a history of AF. Main Outcomes and Measures:Time to composite cardiovascular death, hospitalization for HF, or aborted cardiac arrest at mean (SD) 2.4-year (1.5) follow-up. Results:Of 1057 participants, the mean (SD) age was 72 (10) years, 183 (17.3%) were black, the mean (SD) BMI was 33.4 (8.6) kg/m2, the mean (SD) estimated glomerular filtration rate was 64.6 (21.8) mL/min/1.73 m2, and 472 (45%) had a history of AF. Median B-type NP (n?=?698) and N-terminal pro-B-type NP concentrations (n?=?359) were 257 (interquartile range, 149-443) ng/L and 959 (interquartile range, 554-2015) ng/L, respectively. Natriuretic peptide concentrations varied by up to 0.5 SD within the 6 subgroups, being higher in older patients with nonblack race, a lower BMI, a lower waist circumference, a lower estimated glomerular filtration rate, and a history of AF. Elevated NP levels (per 1-SD increase) were independently associated with an increased risk of the primary outcome (adjusted hazard ratio, 1.36; 95% CI, 1.22-1.54; P?<?.001) consistently across all investigated subgroups (interaction P?>?.05). In TOPCAT Americas (n?=?1767), 791 (45%) were enrolled based on elevated NP levels as the qualifying criterion (as opposed to a history of HF hospitalization). This proportion was 31% (93 of 302), 34% (258 of 760), and 39% (443 of 1144) for black race, younger than 70 years, and a BMI of 30 kg/m2 or greater, respectively. Conclusions and Relevance:Natriuretic peptides remain important biomarkers of prognosis in HFpEF, even in subgroups who tend to have lower NP levels. A single, absolute NP threshold for inclusion in contemporary HFpEF trials may lead to an underrepresentation of certain demographic and clinical subgroups. Trial Registration:ClinicalTrials.gov Identifier: NCT00094302.

Dataset Information

Race, Natriuretic Peptides, and High-Carbohydrate Challenge: A Clinical Trial.

Publications

Race, Natriuretic Peptides, and High-Carbohydrate Challenge: A Clinical Trial.

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