Analysis of Cardiac Biomarker Racial Discrepancies

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), GDF-15, and 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.