Analysis of Cardiac Biomarker Racial Discrepancies

Analysis of Cardiac Biomarker Racial Discrepancies in African American Patients With Heart Failure With Reduced Ejection Fraction

The goal is to review cardiac biomarkers present on admission between African American patients with new onset Heart Failure compared to a comparable cohort of Caucasian patients to establish whether there is a clinically significant difference between the two groups regarding cardiac biomarker levels and initial Heart Failure severity.

Hypothesis: Cardiac biomarker levels in African American patients with new onset Heart Failure with Reduced Ejection Fraction will be significantly lower than a Caucasian cohort with new onset Heart Failure with Reduced Ejection Fraction.

Study Overview

• Status: Withdrawn
• Conditions: Heart Failure
• Intervention / Treatment: Other: No intervention

Detailed Description

Limited data exists on the overall impact racial and genetic differences play on expression of cardiac biomarkers, especially natriuretic peptides (NPs). NPs like atrial NP, brain NP (BNP), and C-type NP are endogenous hormones with powerful cardiovascular and metabolic effects. NPs play an active role in natriuresis and vasodilation along with lipolysis, weight loss, and insulin sensitivity, whereas NP deficiencies correlate with increased risk for developing cardiovascular comorbidities like hypertension. Many cardiac disease states like acute coronary syndrome, valvular heart disease (VHD), and atrial fibrillation (AFib) can cause significant elevations in NPs. Elevated NP levels have also been associated with liver cirrhosis, chronic renal dysfunction, and infectious sepsis. However, NP elevations are most commonly associated with heart failure (HF), and increasing BNP levels have been correlated with increasing grades of cardiac dysfunction and end-diastolic wall stress within the heart.

African American (AA) patients experience higher incidence of HF relative to the general population and are at an increased risk of mortality secondary to chronic HF compared to Caucasian patients. AA patients are three times more likely to develop HF because AA patients may suffer from a subgroup of left ventricular hypertrophy where biomarkers like N-terminal pro-BNP (NT-proBNP) are not clinically elevated. The 2021 American College of Cardiology/American Heart Association Heart Failure with Reduced Ejection Fraction (HFrEF) Treatment Guidelines endorse measurement of both BNP and NT-proBNP as biomarkers for the diagnosis and prognostication of HF; however, current treatment guidelines have not established treatment thresholds for either BNP or NT-proBNP.7 The Food and Drug Administration (FDA) approved cutoff BNP value for the diagnosis of HF is 100 pg/mL. For NT-proBNP, the optimal cutoff values for confirmatory decision limits for HF are 450, 900, and 1,800 pg/mL for ages less than 50 years, between 50 to 75 years, and older than 75 years of age, respectively.3 In clinical practice, significant heterogeneity surrounds treatment cutoffs for NT-proBNP levels for treatment of HF, as seen in many recent prominent landmark HF pharmacotherapy trials.

Within the general population, serum NP levels, especially NT-proBNP, are significantly lower in the AA population compared to Caucasians as seen in the Reasons for Geographic and Racial Differences in Stroke, Dallas Heart, and Atherosclerosis Risk in Communities studies. After accounting for traditional risk factors, racial differences in body composition, cardiac structure, and socioeconomic factors, AA patients were found to have significantly lower serum NT-proBNP levels and greater levels of markers of myocardial stress and inflammation, including high-sensitivity Troponin T (hsTnT), Growth Differentiation Factor 15 (GDF-15), and Suppression of Tumorigenicity 2(ST2). This finding may also be due to genetic differences, as percent European ancestry (PEA) in AA patients was found to have a direct impact on NT-proBNP levels in the general AA population. Of the 1656 AA patients in whom PEA data were available, a 10% increase in PEA was associated with 7% higher adjusted NT-proBNP levels.

Knowing that the general AA population has lower serum NP's compared to Caucasian patients, limited research focuses on initial NT-proBNP levels in AA patients with new-onset HF. Given that many landmark HF trials primarily enroll Caucasian patients, several questions emerge: (i) should medicine individualize treatment thresholds for NT-proBNP and other cardiac biomarkers based on race given known racial discrepancies with serum NP's and increased mortality seen in these patients? (ii) Is the trend seen in AA patients regarding serum NPs and other cardiac biomarkers still true when these patients present with new-onset HF? Our goal is to review cardiac biomarkers present on admission between AA patients with new onset HF compared to a comparable cohort of Caucasian patients to establish whether there is a clinically significant difference between the two groups regarding cardiac biomarker levels and initial HF severity.

• Study Type: Observational

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75203
      • Methodist Dallas Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Subjects that self-identify as African American or Caucasian with a new onset of Heart Failure with Reduced Ejection Fraction

Description

Inclusion Criteria:

• >18 years
• Self-identified as AA
• Self-identified as Caucasian
• NYHA class II-IV symptoms
• Left ventricle EF <40%
• First admission for HFrEF
• No echocardiography during initial admission

Exclusion Criteria:

• Patients not meeting inclusion criteria

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
New onset HFrEF AA patients	Other: No intervention; No intervention
New onset HFrEF Caucasian patients	Other: No intervention; No intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline NT-proBNP levels on admission	Collection of baseline blood tests	Chart reviews ill be done for charts generated from April 2017 to August 2020
Baseline troponin-I or troponin-T levels on admission	Collection of baseline blood tests	Chart reviews ill be done for charts generated from April 2017 to August 2020
Demographic data: Age	Age of subject in years	Chart reviews ill be done for charts generated from April 2017 to August 2020
Demographic data: Gender	male or female	Chart reviews ill be done for charts generated from April 2017 to August 2020
Demographic data: body mass index (BMI)	BMI is calculated by taking the weight in kilograms divided by height in meters squared	Chart reviews ill be done for charts generated from April 2017 to August 2020
Ejection Fraction on echocardiography during first admission	The patient has an EF <40% on echocardiography and is not on goal-directed medical therapy for HFrEF.	Chart reviews ill be done for charts generated from April 2017 to August 2020
New York Heart Association (NYHA) class	Doctors usually classify patients' heart failure according to the severity of their symptoms.	Chart reviews ill be done for charts generated from April 2017 to August 2020

Collaborators and Investigators

• Sponsor: Methodist Health System
• Investigators: Principal Investigator: Crystal Brown, PharmD, Methodist Health System

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2021
• Primary Completion (Estimated): August 15, 2027
• Study Completion (Estimated): September 15, 2028

Study Registration Dates

• First Submitted: February 3, 2022
• First Submitted That Met QC Criteria: February 3, 2022
• First Posted (Actual): February 4, 2022

Study Record Updates

• Last Update Posted (Actual): August 4, 2026
• Last Update Submitted That Met QC Criteria: July 31, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: 043.PHA.2021.A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No