Circulating levels and prognostic cut‐offs of sST2, hs‐cTnT, and NT‐proBNP in women vs. men with chronic heart failure

Abstract

AimsTo define plasma concentrations, determinants, and optimal prognostic cut-offs of soluble suppression of tumorigenesis-2 (sST2), high-sensitivity cardiac troponin T (hs-cTnT), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in women and men with chronic heart failure (HF). Methods and resultsIndividual data of patients from the Biomarkers In Heart Failure Outpatient Study (BIOS) Consortium with sST2, hs-cTnT, and NT-proBNP measured were analysed. The primary endpoint was a composite of 1 year cardiovascular death and HF hospitalization. The secondary endpoints were 5 year cardiovascular and all-cause death. The cohort included 4540 patients (age 67 ± 12 years, left ventricular ejection fraction 33 ± 13%, 1111 women, 25%). Women showed lower sST2 (24 vs. 27 ng/mL, P < 0.001) and hs-cTnT level (15 vs. 20 ng/L, P < 0.001), and similar concentrations of NT-proBNP (1540 vs. 1505 ng/L, P = 0.408). Although the three biomarkers were confirmed as independent predictors of outcome in both sexes, the optimal prognostic cut-off was lower in women for sST2 (28 vs. 31 ng/mL) and hs-cTnT (22 vs. 25 ng/L), while NT-proBNP cut-off was higher in women (2339 ng/L vs. 2145 ng/L). The use of sex-specific cut-offs improved risk prediction compared with the use of previously standardized prognostic cut-offs and allowed to reclassify the risk of many patients, to a greater extent in women than men, and for hs-cTnT than sST2 or NT-proBNP. Specifically, up to 18% men and up to 57% women were reclassified, by using the sex-specific cut-off of hs-cTnT for the endpoint of 5 year cardiovascular death. Conclusions In patients with chronic HF, concentrations of sST2 and hs-cTnT, but not of NT-proBNP, are lower in women. Lower sST2 and hs-cTnT and higher NT-proBNP cut-offs for risk stratification could be used in women.

Sex and age differences in sST2 in cardiovascular disease

“…These data indicate the importance of analyzing sST2 and other HF biomarkers according to sex. Recent studies have demonstrated that sST2 and other HF biomarkers like high sensitivity cardiac troponin T (hs-cTnT) differ by sex and that sex-specific cutoffs are needed to enhance determination of risk for hospitalization or death from HF ( 16 , 17 ).…”

“…Patients were classified as having HFrEF (LVEF ≤ 40%), HF with mildly reduced LVEF (HFmrEF, LVEF 41–49%) or HFpEF (LVEF ≥ 50%) according to the European Society of Cardiology (ESC) guidelines ( 18 , 19 ). In 4,540 patients with chronic HF, they found that HFrEF was more prevalent in men (88% vs. 73%, p < 0.001), while HFmrEF and HFpEF occurred more often in women (10% vs. 7% and 17% vs. 5%; both p < 0.001), and men had significantly higher serum levels of sST2 and high sensitivity cardiac troponin T than women but there were no sex differences in NT-proBNP ( 17 ). Another large study by Suthahar et al examined sex differences in primary CVD biomarkers including sST2 from several large cohorts and reported that sST2 was elevated in the sera of men with chronic HF and that there was an interaction between sex and age ( 13 ).…”

“…Two recent studies examined sera levels of sST2 in large cohorts of patients to determine whether sex-specific cutoffs would enhance determination of risk for hospitalization or death ( 16 , 17 ). The study by Harmon et al examined participants from the Rochester Epidemiology Project for cardiovascular outcomes.…”

Thromboembolic Disease and Cardiac Thrombotic Complication in COVID-19: A Systematic Review

“…Troponin augmentation among patients hospitalized with COVID-19 was associated with a higher risk of death [ 48 ]. Concerns related to the increased level of natriuretic peptides suggest its non-specificity, while the reported pulmonary embolism events should only be included in the appropriate clinical context [ 102 , 103 , 104 ].…”

Biomarkers in Heart Failure: From Research to Clinical Practice

“…These facts lead us to consider whether thorough monitoring of the serum concentrations of hs-cTn should be incorporated in routine optimal guidebased management (OGBM) of HF, whereas peak concentrations of hs-cTn retain their discriminative potency in acute and chronic HF. Data from HF patients included in the Biomarkers in Heart Failure Outpatient Study (BIOS) Consortium showed a significant difference in prognostic cut-offs of hs-cTnT between male and female patients with HF, whereas there was no difference with respect to NT-proBNP concentrations [49].…”