ABSTRACT
Background: Biomarkers are increasingly part of assessing and managing heart failure (HF) in adults with congenital heart disease (CHD). Objectives: To understand the response of cardiac biomarkers with therapy for acute decompensated heart failure (ADHF) and the relationship to prognosis after discharge in adults with CHD. Design: A prospective, observational cohort study with serial blood biomarker measurements. Settings: Single-center study in the inpatient setting with outpatient follow-up. Participants: Adults (≥18 years old) with CHD admitted with ADHF between August 1, 2019, and March 1, 2020. Exposure: We measured body mass, Kansas City Cardiomyopathy Questionnaire (KCCQ-12) score, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hsCRP) at enrollment, discharge, and 1st clinic follow-up visit; soluble suppression of tumorigenicity 2 (sST2) was measured at the first two time points. Measures: Univariate regression assessed the association between changes in weight, biomarkers, and changes in KCCQ-12 scores, between enrollment and discharge (Δ Hospitalization ) and between discharge and 1st clinical follow-up visit (Δ Post-discharge ). Wilcoxon rank-sum tests assessed the association between change in biomarkers, KCCQ-12 scores, and the composite outcome of cardiovascular death or rehospitalization for ADHF. Results: A total of 26 patients were enrolled. The median age was 51.9 years [IQR: 38.8, 61.2], 13 (54.2%) were women, and median hospital stay was 6.5 days [IQR: 4.0, 15.0] with an associated weight loss of 2.8 kg [IQR -5.1, -1.7]. All three cardiac biomarkers decreased during hospitalization with diuresis while KCCQ-12 scores improved; a greater decrease in sST2 was associated with an improved KCCQ-12 symptom frequency (SF) subdomain score (p = 0.012), but otherwise, there was no significant relationship between biomarkers and KCCQ-12 change. Change in hsCRP and NT-proBNP after discharge was not associated with the composite outcome (n = 8, vs. n = 16 who did not experience the outcome; Δ Post-discharge hsCRP +5.1 vs. -1.0 mg/l, p = 0.061; NT-proBNP +785.0 vs. +130.0 pg/ml, p = 0.220). Conclusions: Serial biomarker measurements respond to acute diuresis in adults with CHD hospitalized for ADHF. These results should motivate further research into the use of biomarkers to inform HF therapy in adults with CHD.
ABSTRACT
Background: Differences in sex hormone levels contribute to differences in cardiovascular disease (CVD) risk. Adipokines play a role in cardiometabolic pathways and have differing associations with CVD. Adipokine levels differ by sex; however, the association between sex hormone profiles and adipokines is not well established. We hypothesized that a more androgenic sex hormone profile would be associated with higher leptin and resistin and lower adiponectin levels among postmenopausal women, with the opposite associations in men. Methods: We performed an analysis of 1,811 adults in the Multi-Ethnic Study of Atherosclerosis who had both sex hormones and adipokines measured an average of 2.6 years apart. Sex hormones [Testosterone (T), estradiol (E2), sex hormone binding globulin (SHBG), and dehydroepiandrosterone (DHEA)] were measured at exam 1; free T was estimated. Serum adipokines (leptin, resistin, adiponectin) were measured at exams 2 or 3. We used multivariable linear regression to examine the cross-sectional associations between sex hormones and adipokines. Results: The mean (SD) age was 63 (10) years, 48% were women; 59% non-White participants. For leptin, after adjusting for demographics only, higher free T and lower SHBG, were associated with higher leptin in women; this association was attenuated after further covariate adjustment. However in men, higher free T and lower SHBG were associated with greater leptin levels in fully adjusted models. For adiponectin, lower free T and higher SHBG were associated with greater adiponectin in both women and men after adjustment for CVD risk factors. For resistin, no significant association was found women, but an inverse association with total T and bioT was seen in men. Conclusion: Overall, these results further suggest a more androgenic sex profile (higher free T and lower SHBG) is associated with a less favorable adipokine pattern. These findings may provide mechanistic insight into the interplay between sex hormones, adipokines, and CVD risk.
