Dataset Information

Protein biomarkers of cardiac remodeling and inflammation associated with HFpEF and incident events.

ABSTRACT: There is increasing evidence that HFpEF is a heterogeneous clinical entity and distinct molecular pathways may contribute to pathophysiology. Leveraging unbiased proteomics to identify novel biomarkers, this study seeks to understand the underlying molecular mechanisms of HFpEF. The discovery cohort consisted of HFpEF cases and non-HF controls from the CATHGEN study (N = 176); the validation cohort consisted of participants from the TECOS trial of patients with diabetes (N = 109). Proteins associated with HFpEF were included in a LASSO model to create a discriminative multi-protein model and assessed in the validation cohort. Survival models and meta-analysis were used to test the association of proteins with incident clinical outcomes, including HF hospitalization, mortality and HFpEF hospitalization in CATHGEN, TECOS and the Jackson Heart Study. In the derivation set, 190 proteins were associated with HFpEF in univariate analysis, of which 65 remained significant in the multivariate model. Twenty (30.8%) of these proteins validated in TECOS, including LCN2, U-PAR, IL-1ra, KIM1, CSTB and Gal-9 (OR 1.93-2.77, p < 0.01). LASSO regression yielded a 13-protein model which, when added to a clinical model inclusive of NT-proBNP, improved the AUC from 0.82 to 0.92 (p = 1.5 × 10^-4). Five proteins were associated with incident HF hospitalization, four with HFpEF hospitalization and eleven with mortality (p < 0.05). We identified and validated multiple circulating biomarkers associated with HFpEF as well as HF outcomes. These biomarkers added incremental discriminative capabilities beyond clinical factors and NT-proBNP.

SUBMITTER: Regan JA

PROVIDER: S-EPMC9684116 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Protein biomarkers of cardiac remodeling and inflammation associated with HFpEF and incident events.

Regan Jessica A JA Truby Lauren K LK Tahir Usman A UA Katz Daniel H DH Nguyen Maggie M Kwee Lydia Coulter LC Deng Shuliang S Wilson James G JG Mentz Robert J RJ Kraus William E WE Hernandez Adrian F AF Gerszten Robert E RE Peterson Eric D ED Holman Rury R RR Shah Svati H SH

Scientific reports 20221122 1

There is increasing evidence that HFpEF is a heterogeneous clinical entity and distinct molecular pathways may contribute to pathophysiology. Leveraging unbiased proteomics to identify novel biomarkers, this study seeks to understand the underlying molecular mechanisms of HFpEF. The discovery cohort consisted of HFpEF cases and non-HF controls from the CATHGEN study (N = 176); the validation cohort consisted of participants from the TECOS trial of patients with diabetes (N = 109). Proteins assoc ...[more]

PMID: 36418363

Similar Datasets

Project description:BackgroundObesity and adiposity are associated with an increased risk of heart failure with preserved ejection fraction (HFpEF); yet, specific underlying mechanisms remain unclear. We sought to examine the association of obesity-related biomarkers including adipokines (leptin, resistin, adiponectin), inflammatory markers (CRP [C-reactive protein], IL-6 [interleukin-6]), and insulin resistance (HOMA-IR) with HFpEF status, exercise capacity, and cardiovascular outcomes.MethodsWe studied 509 consecutive patients with left ventricular ejection fraction ≥50% and chronic dyspnea, who underwent clinically indicated cardiopulmonary exercise test with invasive hemodynamic monitoring between 2006 and 2017. We defined HFpEF based on the presence of elevated left ventricular filling pressures at rest or during exercise. Fasting blood samples collected at the time of the cardiopulmonary exercise test were used to assay obesity-related biomarkers. We examined the association of log-transformed biomarkers with HFpEF status and exercise traits using multivariable-adjusted logistic regression models.ResultsWe observed associations of obesity-related biomarkers with measures of impaired exercise capacity including peak VO2 (P≤0.002 for all biomarkers). The largest effect size was seen with leptin, where a 1-SD higher leptin was associated with a 2.35 mL/kg per min lower peak VO2 (β, -2.35±0.19; P<0.001). In addition, specific biomarkers were associated with distinct measures of exercise reserve including blood pressure (homeostatic model assessment of insulin resistance, leptin, adiponectin; P≤0.002 for all), and chronotropic response (CRP, IL-6, homeostatic model assessment of insulin resistance, leptin, and resistin; P<0.05 for all). Our findings suggest that among the obesity-related biomarkers studied, higher levels of leptin and CRP are independently associated with increased odds of HFpEF, with odds ratios of 1.36 (95% CI, 1.09-1.70) and 1.25 (95% CI, 1.03-1.52), respectively.ConclusionsSpecific obesity-related pathways including inflammation, adipokine signaling, and insulin resistance may underlie the association of obesity with HFpEF and exercise intolerance.

Project description:Background123Iodine-meta-iodobenzylguanidine scintigraphy is useful for assessing cardiac autonomic dysfunction and predict outcomes in heart failure (HF). The relationship of cardiac sympathetic function with myocardial remodeling and diffuse fibrosis remains largely unknown. We aimed to evaluate the cardiac sympathetic function of patients with HF and its relation with myocardial remodeling and exercise capacity.Methods and resultsProspectively enrolled patients with HF (New York Heart Association class II-III) were stratified into HF with preserved left ventricular ejection fraction [LVEF] ≥45%) and reduced LVEF. Ventricular morphology/function and myocardial extracellular volume (ECV) fraction were quantified by cardiovascular magnetic resonance, global longitudinal strain by echocardiography, cardiac sympathetic function by heart-to-mediastinum ratio from 123iodine-meta-iodobenzylguanidine scintigraphy. All participants underwent cardiopulmonary exercise testing. The cohort included 33 patients with HF with preserved LVEF (LVEF, 60±10%; NT-proBNP [N-terminal pro-B-type natriuretic peptide], 248 [interquartile range, 79-574] pg/dL), 28 with HF with reduced LVEF (LVEF, 30±9%; NT-proBNP, 743 [interquartile range, 250-2054] pg/dL) and 20 controls (LVEF, 65±5%; NT-proBNP, 40 [interquartile range, 19-50] pg/dL). Delayed (4 hours) 123iodine-meta-iodobenzylguanidine heart-to-mediastinum ratio was lower in HF with preserved LVEF (1.59±0.25) and HF with reduced LVEF (1.45±0.16) versus controls (1.92±0.24; P<0.001), and correlated negatively with diffuse fibrosis assessed by ECV (R=-0.34, P<0.01). ECV in segments without LGE was increased in HF with preserved ejection fraction (0.32±0.05%) and HF with reduced left ventricular ejection fraction (0.31±0.04%) versus controls (0.28±0.04, P<0.05) and was associated with the age- and sex-adjusted maximum oxygen consumption (peak oxygen consumption); (R=-0.41, P<0.01). Preliminary analysis indicates that cardiac sympathetic function might potentially act as a mediator in the association between ECV and NT-proBNP levels.ConclusionsAbnormally low cardiac sympathetic function in patients with HF with reduced and preserved LVEF is associated with extracellular volume expansion and decreased cardiopulmonary functional capacity.

Project description:BackgroundChronic inflammation may lead to cochlear damage, and the only longitudinal study that examined biomarkers of systemic inflammation and risk of hearing loss found an association with a single biomarker in individuals <60 years of age. The purpose of our study was to determine whether plasma inflammatory markers are associated with incident hearing loss in two large prospective cohorts, Nurses' Health Studies (NHS) I and II.MethodsWe examined the independent associations between plasma levels of markers of systemic inflammation (C-reactive protein [CRP], interleukin-6 [IL-6], and soluble tumor necrosis factor receptor 2 [TNFR-2]) and self-reported hearing loss. The participants in NHS I (n = 6194 women) were 42 to 69 years of age at the start of the analysis in 1990, while the participants in NHS II (n = 2885 women) were 32 to 53 years in 1995. After excluding women with self-reported hearing loss before the time of blood-draw, incident cases of hearing loss were defined as those women who reported hearing loss on questionnaires administered in 2012 in NHS I and 2009 or 2013 in NHS II. The primary outcome was hearing loss that was reported as moderate or worse in severity, pooled across the NHS I and NHS II cohorts. We also examined the pooled multivariable-adjusted hazard ratios for mild or worse hearing loss. Cox proportional hazards regression was used to adjust for potential confounders.ResultsAt baseline, women ranged from 42 to 69 years of age in NHS I and 32 to 53 years of age in NHS II. Among the NHS I and II women with measured plasma CRP, there were 628 incident cases of moderate or worse hearing loss during 100,277 person-years of follow-up. There was no significant association between the plasma levels of any of the three inflammatory markers and incident moderate or worse hearing loss (multivariable-adjusted pooled p trend for CRP = 0.33; p trend IL-6 = 0.54; p trend TNFR-2 = 0.70). There was also no significant relation between inflammatory marker levels and mild or worse hearing loss. While there was no significant effect modification by age for CRP or IL-6 in NHS I, there was a statistically significant higher risk of moderate or worse hearing loss (p interaction = 0.02) as well as mild or worse hearing loss (p interaction = 0.004) in women ≥60 years of age who had higher plasma TNFR-2 levels.ConclusionsOverall, there was no significant association between plasma markers of inflammation and risk of hearing loss.

Dataset Information

Protein biomarkers of cardiac remodeling and inflammation associated with HFpEF and incident events.

Publications

Protein biomarkers of cardiac remodeling and inflammation associated with HFpEF and incident events.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets