Background: Persons with HIV (PWH) on contemporary antiretroviral therapy (ART) are at elevated risk for developing age-related cardiometabolic diseases. We hypothesized that integrative analysis of cross-tissue, multimodal data from PWH could provide insight into molecular programming that defines cardiometabolic phenotypes in this high-risk group.
Methods: We enrolled 93 PWH without diabetes who were virologically suppressed on contemporary ART and obtained measures of insulin resistance, glucose intolerance, and adiposity.
Hepatic steatosis is a central phenotype in multi-system metabolic dysfunction and is increasing in parallel with the obesity pandemic. We use a translational approach integrating clinical phenotyping and outcomes, circulating proteomics, and tissue transcriptomics to identify dynamic, functional biomarkers of hepatic steatosis. Using multi-modality imaging and broad proteomic profiling, we identify proteins implicated in the progression of hepatic steatosis that are largely encoded by genes enriched at the transcriptional level in the human liver.
View Article and Find Full Text PDFBackground: Greater left ventricular (LV) wall stress is associated with adverse outcomes among patients with prevalent heart failure (HF). Less is known about the association between LV wall stress and incident HF.
Objectives: The purpose of the study was to identify clinical factors associated with wall stress and test the association between wall stress and incident HF.
Am J Respir Crit Care Med
September 2024
Rationale: Accelerated decline in lung function is associated with incident COPD, hospitalizations and death. However, identifying this trajectory with longitudinal spirometry measurements is challenging in clinical practice.
Objective: To determine whether a proteomic risk score trained on accelerated decline in lung function can assess risk of future respiratory disease and mortality.
Despite the wide effects of cardiorespiratory fitness (CRF) on metabolic, cardiovascular, pulmonary and neurological health, challenges in the feasibility and reproducibility of CRF measurements have impeded its use for clinical decision-making. Here we link proteomic profiles to CRF in 14,145 individuals across four international cohorts with diverse CRF ascertainment methods to establish, validate and characterize a proteomic CRF score. In a cohort of around 22,000 individuals in the UK Biobank, a proteomic CRF score was associated with a reduced risk of all-cause mortality (unadjusted hazard ratio 0.
View Article and Find Full Text PDFIn this study, we sought to compare protein concentrations obtained from a high-throughput proteomics platform (Olink) on samples collected using capillary blood self-collection (with the Tasso+ device) versus standard venipuncture (control). Blood collection was performed on 20 volunteers, including one sample obtained via venipuncture and two via capillary blood using the Tasso+ device. Tasso+ samples were stored at 2°C-8°C for 24-hs (Tasso-24) or 48-h (Tasso-48) prior to processing to simulate shipping times from a study participant's home.
View Article and Find Full Text PDFBackground: The biological mechanisms linking environmental exposures with cardiovascular disease pathobiology are incompletely understood. We sought to identify circulating proteomic signatures of environmental exposures and examine their associations with cardiometabolic and respiratory disease in observational cohort studies.
Methods: We tested the relations of >6500 circulating proteins with 29 environmental exposures across the built environment, green space, air pollution, temperature, and social vulnerability indicators in ≈3000 participants of the CARDIA study (Coronary Artery Risk Development in Young Adults) across 4 centers using penalized and ordinary linear regression.
The emerging field of precision nutrition is based on the notion that inter-individual responses across diets of different calorie-macronutrient content may contribute to inter-individual differences in metabolism, adiposity, and weight gain. Free-living diet studies have been traditionally challenged by difficulties in controlling adherence to prescribed calories and macronutrient content and rarely allow a period of metabolic stability prior to metabolic measures (to minimize influences of weight changes). In this context, key physiologic measures central to precision nutrition responses may be most precisely quantified via whole room indirect calorimetry over 24-h, in which precise control of activity and nutrition can be achieved.
View Article and Find Full Text PDFMetabolic dysfunction-associated steatotic liver disease (MASLD) prevalence is increasing in parallel with an obesity pandemic, calling for novel strategies for prevention and treatment. We defined a circulating proteome of human MASLD across ≈7000 proteins in ≈5000 individuals from diverse, at-risk populations across the metabolic health spectrum, demonstrating reproducible diagnostic performance and specifying both known and novel metabolic pathways relevant to MASLD (central carbon and amino acid metabolism, hepatocyte regeneration, inflammation, fibrosis, insulin sensitivity). A parsimonious proteomic signature of MASLD was associated with a protection from MASLD and its related multi-system metabolic consequences in >26000 free-living individuals, with an additive effect to polygenic risk.
View Article and Find Full Text PDFBackground: The circulating proteome may encode early pathways of diabetes susceptibility in young adults for surveillance and intervention. Here, we define proteomic correlates of tissue phenotypes and diabetes in young adults.
Methods: We used penalized models and principal components analysis to generate parsimonious proteomic signatures of diabetes susceptibility based on phenotypes and on diabetes diagnosis across 184 proteins in >2000 young adults in the CARDIA (Coronary Artery Risk Development in Young Adults study; mean age, 32 years; 44% women; 43% Black; mean body mass index, 25.
Aging is increasingly thought to involve dysregulation of metabolism in multiple organ systems that culminate in decreased functional capacity and morbidity. Here, we seek to understand complex interactions among metabolism, aging, and systems-wide phenotypes across the lifespan. Among 2469 adults (mean age 74.
View Article and Find Full Text PDFWhile frailty is a prominent risk factor in an aging population, the underlying biology of frailty is incompletely described. Here, we integrate 979 circulating proteins across a wide range of physiologies with 12 measures of frailty in a prospective discovery cohort of 809 individuals with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation. Our aim was to characterize the proteomic architecture of frailty in a highly susceptible population and study its relation to clinical outcome and systems-wide phenotypes to define potential novel, clinically relevant frailty biology.
View Article and Find Full Text PDFDespite improvements in cardiovascular care in recent decades, cardiovascular disease (CVD) remains a leading cause of death worldwide. At its core, CVD is a largely preventable disease with diligent risk factor management and early detection. As highlighted in the American Heart Association's , physical activity plays a central role in CVD prevention at an individual and population level.
View Article and Find Full Text PDFAims: Beta-blockers are proven to improve survival among patients with heart failure with reduced ejection fraction. Their efficacy in patients with heart failure with reduced ejection fraction and pacemaker devices has not been demonstrated. Our aim was to test the hypothesis that beta-blocker therapy is associated with improved survival in patients with chronic heart failure and a pacemaker rhythm on electrocardiogram (ECG).
View Article and Find Full Text PDFContext: Prior studies of the relationship between physical activity and incident type 2 diabetes mellitus (T2DM) relied primarily on questionnaires at a single time point.
Objective: We sought to investigate the relationship between physical activity and incident T2DM with an innovative approach using data from commercial wearable devices linked to electronic health records in a real-world population.
Methods: Using All of Us participants' accelerometer data from their personal Fitbit devices, we used a time-varying Cox proportional hazards models with repeated measures of physical activity for the outcome of incident T2DM.
Obesity (Silver Spring)
January 2023
Objective: Weight regain occurs after medical weight loss via mechanisms of post-weight-loss "metabolic adaptation." The relationship of inflammatory proteins with weight loss/regain was studied to determine a role for inflammation in metabolic adaptation.
Methods: Seventy-four proteins central to inflammation and immune regulation (Olink) were analyzed in plasma from up to 490 participants in a trial of medical weight-loss maintenance.
QRS duration is an established risk factor among patients with heart failure. How change in QRS duration relates to heart failure outcomes has had limited study. In this post-hoc analysis of the Beta-Blocker Evaluation of Survival Trial, we demonstrated that QRS duration change from baseline to 3 months is independently associated with long-term survival and left ventricle ejection fraction.
View Article and Find Full Text PDFThis study aimed to understand the long-term outcomes of patients with heart failure with recovered ejection fraction, identify predictors of adverse events, and develop a risk stratification model. From an academic healthcare system, we retrospectively identified 133 patients (median age 66, 38% female, 30% ischemic etiology) who had an improvement in left ventricular ejection fraction (LVEF) from <40% to ≥53%. Significant predictors of all-cause mortality, hospitalization, and future reduction in LVEF were identified through Cox regression analysis.
View Article and Find Full Text PDFBackground The optimal threshold of left ventricular ejection fraction (LVEF) that should prompt aortic valve replacement (AVR) in asymptomatic patients with high-gradient severe aortic stenosis (AS) is controversial. The aim of this study was to assess the relationship between LVEF and mortality benefit in comparing early AVR versus watchful waiting in asymptomatic patients with severe AS. Methods and Results MEDLINE, Embase, Web of Science, and Google Scholar were searched for observational studies and randomized controlled trials on adults with asymptomatic severe AS.
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