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. 2023 Mar 1;8(3):222-230.
doi: 10.1001/jamacardio.2022.5309.

Association of Long-term Change in N-Terminal Pro-B-Type Natriuretic Peptide With Incident Heart Failure and Death

Xiaoming Jia  1 , Mahmoud Al Rifai  1   2 , Ron Hoogeveen  3 , Justin B Echouffo-Tcheugui  4 , Amil M Shah  5 , Chiadi E Ndumele  6 , Salim S Virani  1   3   7 , Biykem Bozkurt  1   7 , Elizabeth Selvin  8 , Christie M Ballantyne  1   3 , Vijay Nambi  1   3   7
Affiliations

Association of Long-term Change in N-Terminal Pro-B-Type Natriuretic Peptide With Incident Heart Failure and Death

Xiaoming Jia et al. JAMA Cardiol. .

Abstract

Importance: Most studies, especially in primary prevention patients, have evaluated N-terminal B-type natriuretic peptide (NT-proBNP) at one time point. Evaluation of change in NT-proBNP may improve risk stratification for incident cardiovascular events.

Objective: To assess the association between change in NT-proBNP and risk for incident heart failure (HF) and death.

Design, setting, and participants: Participants were recruited from 4 US communities enrolled in the Atherosclerosis Risk in Community (ARIC) study. Individuals who attended ARIC visits 2 and 4 (approximately 6 years apart) with measurements of NT-proBNP and without prevalent HF were included. Assays of NT-proBNP were conducted between 2011 and 2013, and analysis took place between July 2021 and October 2022.

Exposures: The primary exposure variable was NT-proBNP change between visits 2 and 4, modeled as change categories (<125 pg/mL or ≥125 pg/mL) and as percent change.

Main outcomes and measures: The primary outcome measures were incident HF hospitalization and all-cause death. The association between changes in cardiovascular risk factors with change in NT-proBNP was further assessed.

Results: A total of 9776 individuals (mean [SD] age, 57.1 [5.7] years at visit 2; 5523 [56.5%] women) were included in the study. Compared with participants with NT-proBNP level less than 125 pg/mL at both visits, participants with NT-proBNP level of 125 pg/mL or higher at both visits had an increase in incident HF (adjusted hazard ratio [HR], 2.40 [95% CI, 2.00-2.88]) and mortality risk (HR, 1.68 [95% CI, 1.47-1.91). Participants with NT-proBNP levels of 125 pg/mL or higher at visit 2 and less than 125 pg/mL at visit 4 had similar risk for HF and death (HR, 1.01 [95% CI, 0.71-1.43]; HR, 0.79 [95% CI, 0.61-1.01]) compared with the group with NT-proBNP levels of less than 125 pg/mL at both visits. The percent change in NT-proBNP was positively associated with HF and death (HR, 1.06 [95% CI, 1.02-1.10]; HR, 1.05 [95% CI, 1.03-1.08] per 1-SD increase, respectively). Change in systolic blood pressure, low-density lipoprotein cholesterol, triglyceride level, body mass index, and estimated glomerular filtration rate were significantly associated with change in NT-proBNP.

Conclusions and relevance: In this study, 6-year change in NT-proBNP reflected dynamic change in risk for HF events and death among community-dwelling adults without prevalent clinical HF. These results support the utility of serial NT-proBNP measurements to improve risk stratification of patients with pre-HF.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Hoogeveen reported grants from Denka Seiken paid to their institution and personal fees from Denka Seiken for consulting outside the submitted work. Dr Shah reported grants from the National Heart, Lung, and Blood Institute/National Institutes of Health during the conduct of the study; research support from Novartis and Philips Ultrasound through Brigham and Women's Hospital; and consulting fees from Philips Ultrasound and Janssen. Dr Virani reported grants from Department of Veterans Affairs, National Institutes of Health, World Heart Federation, and Tahir and Jooma Family Reserch and honorarium from American College of Cardiology Honorarium as Associate Editor for Innovations outside the submitted work. Dr Bozkurt reported personal fees from Vifor for serving on the steering committee for Care HF Trial; personal fees from Amgen, AstraZeneca, and Baxter for serving on advisory committees/consultation outside the submitted work; consulting fees from Bristol Myers Squibb, scPharmaceuticals, Baxter Healthcare Corporation, Sanofi-Aventis, Relypsa, and Amgen; and serves on the clinical event committee for GUIDE HF Trial sponsored by Abbott Vascular and data safety monitoring committee of ANTHEM trial sponsored by Liva Nova. Dr Selvin reported grants from the National Institutes of Health and the Foundation for the National Institutes of Health during the conduct of the study and outside the submitted work. Dr Ballantyne reported grants from Roche paid to their institution; personal fees from Roche for consulting during the conduct of the study; research support from the National Institutes of Health, Abbott Diagnostics, Akcea Therapeutics, Amgen, Arrowhead Pharmaceuticals, Esperion Therapeutics, Ionis Pharmaceuticals, Novartis, Regeneron Pharmaceuticals, Roche Diagnostic, National Institutes of Health, American Heart Association, and American Diabetes Association; consulted for Abbott Diagnostics, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Denka Seiken, Esperion, Genentech, Gilead, Illumina, Matinas BioPharma Inc, Merck, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, Roche Diagnostic, and Sanofi-Synthelabo. Dr Nambi reported grants from the National Institutes of Health during the conduct of the study, other support from Amgen as site principal investigator for study outside the submitted work, and stocks from Abbott Labs. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Association of Categories of Percent Change in N-Terminal Pro–B-Type Natriuretic Peptide (NT-proBNP) From Visit 2 to Visit 4 and Risk of Incident Heart Failure (HF) Hospitalization and All-Cause Death After Visit 4
Data were adjusted for age, sex, race, systolic blood pressure, diastolic blood pressure, hypertensive medication use, diabetes, fasting glucose, low-density lipoprotein cholesterol, triglyceride level, cholesterol-lowering medication use, cigarette smoking, estimated glomerular filtration rate, body mass index, and prevalent coronary heart disease. HR indicates hazard ratio. SI conversion factor: To convert NT-proBNP to nanograms per liter, multiply by 1.
Figure 2.
Figure 2.. Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Low-Density Lipoprotein Cholesterol (LDL-C), Triglycerides (TG), Body Mass Index (BMI), and Estimated Glomerular Filtration Rate (eGFR) by Deciles of Change in N-Terminal Pro–B-Type Natriuretic Peptide (NT-proBNP) Over a 6-Year Period
Data were adjusted for age, sex, race, hypertensive medication use, diabetes, cholesterol-lowering medication use, cigarette smoking, and prevalent coronary heart disease. BMI was calculated as weight in kilograms divided by height in meters squared. SI conversion factors: To convert cholesterol to millimoles per liter, multiply by 0.0259; NT-proBNP to nanograms per liter, multiply by 1; TG to millimoles per liter, multiply by 0.0113.
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