Integrated trajectories of systolic and diastolic function differentially associate with risk for heart failure with preserved and reduced ejection fraction and proteomic profiles.

Aims: To jointly model longitudinal measures of left ventricular ejection fraction (LVEF) and E/A ratio in late-life, and to assess whether predicted trajectory membership is associated with heart failure risk.

Methods And Results: Using a Bayesian non-parametric trajectory approach, trajectories were modelled among 747 Jackson Heart Study participants who underwent ≥2 echocardiograms in 2000-2004 (age 65 ± 5 years), 2011-2013 (75 ± 5), and 2018-2019 (81 ± 5). Using the resulting model, we predicted trajectory membership for 4419 distinct Atherosclerosis Risk in Communities (ARIC) study participants based on single time-point measures of LVEF and E/A ratio (age 75 ± 5 years; 'testing cohort').

Association of Left Atrial Function With Mitral Regurgitation: The Atherosclerosis Risk in Communities Study.

Background: Lower left atrial (LA) function may precede LA enlargement and contribute to mitral regurgitation (MR). We examined the association of LA reservoir strain (a measure of LA function) with MR in the ARIC (Atherosclerosis Risk in Communities) study.

Methods: We analyzed ARIC participants with echocardiograms at Visits 5 (2011-2013) and 7 (2018-2019).

Risk for Heart Failure and Atrial Fibrillation Across the Lifespan for Carriers of the Amyloidogenic p.V142I Variant.

Background: To better define the importance of the amyloidogenic p.V142I allele across the life span of a carrier, we leveraged data from All of Us to provide a generalizable assessment of the population-level burden of cardiovascular risk and estimate the age at disease onset.

Methods: We included self-identifying Black participants in All of Us who provided genomic data (N=77 767).

Linking Chronic Kidney Disease to Incident Heart Failure and Adverse Cardiac Remodeling Through the Plasma Proteome: The ARIC Study.

Background: Investigation of circulating plasma proteins may reveal insights into molecular pathways that contribute to the development of heart failure (HF) among people with chronic kidney disease.

Objectives: The authors aimed to identify circulating kidney function-related plasma proteins that are associated with the risk of incident HF.

Methods: The authors studied participants of the ongoing longitudinal ARIC (Atherosclerosis Risk In Communities) study.

Differential Associations of Cardiac, Pulmonary, Arterial, and Muscle Physiological Parameters and Biomarkers With the Incidence of HFpEF and HFrEF.

Background: Postulated differences in heart failure with preserved ejection fraction (HFpEF) compared with heart failure with reduced ejection fraction (HFrEF) include greater contributions of noncardiac dysfunction to HFpEF.

Objectives: This study aims to evaluate associations of cardiac and noncardiac physiological measures with prevalent and incident HFpEF and HFrEF.

Methods: Among 5,484 ARIC (Atherosclerosis Risk In Communities) study participants attending the fifth visit (2011-2013), this study assessed associations of cardiac structure and function by echocardiogram, pulmonary function by spirometry, arterial stiffness by pulse wave velocity, muscle strength by handgrip, fat mass by bioimpedance, inflammation by plasma biomarkers, and renal function with prevalent and incident adjudicated HFpEF (ejection fraction [EF] ≥50%) and HFrEF (EF <50%) by using adjusted logistic and Cox models.

Epidemiological and Translational Study of Calprotectin and Atherosclerotic Cardiovascular Disease.

Importance: Innate immunity, particularly neutrophil activation, plays a crucial role in the pathogenesis of atherosclerotic cardiovascular disease (ASCVD). The potential of calprotectin, a biomarker of neutrophil activation, as a mechanistically informed biomarker for ASCVD in an ethnically diverse population requires further investigation.

Objective: To examine the prospective association between circulating calprotectin and ASCVD in a diverse, population-based cohort while also exploring calprotectin's mechanistic contributions to ASCVD in vitro.

Prognostic Significance of Nutritional Scores in Patients With Heart Failure: Insights From the PARAGON-HF Trial.

Background: The Controlling Nutritional Status (CONUT) and Geriatric Nutritional Risk Index (GNRI) are indices that identify individuals at risk of malnutrition. Our study sought to examine the incidence and prognostic implications of abnormal CONUT and/or GNRI in patients with heart failure with preserved ejection fraction.

Methods And Results: The CONUT score and GNRI were serially analyzed in this post hoc analysis of the PARAGON-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin-Receptor Blockers Global Outcomes in Heart Failure With Preserved Ejection Fraction) trial.

Markers of Left Atrial Myopathy: Prognostic Usefulness for Ischemic Stroke and Dementia in People in Sinus Rhythm.

Background: Various measures of abnormal left atrial (LA) structure or function (LA myopathy) are associated with a higher risk of ischemic stroke and dementia, independent of atrial fibrillation. However, limited data exist on their prognostic usefulness. Therefore, we aimed to assess the ability of markers of LA myopathy to improve the prediction of ischemic stroke and dementia.

Cross-Ancestry Comparison of Aptamer and Antibody Proteomics Measures.

Measures from affinity-proteomics platforms often correlate poorly, challenging interpretation of protein associations with genetic variants (pQTL) and phenotypes. Here, we examined 2,157 proteins measured on both SomaScan 7k and Olink Explore 3072 across 1,930 participants with genetic similarity to European, African, East Asian, and Admixed American ancestry references. Inter-platform correlation coefficients for these 2,157 proteins followed a bimodal distribution (median r=0.

Myocardial contraction fraction predicts outcomes in patients enrolled in the TOPCAT trial.

Background: Myocardial contraction fraction (MCF)-the ratio of left ventricular stroke volume to myocardial volume-is a volumetric measure of myocardial shortening that distinguishes between pathologic and physiologic hypertrophy. In this post-hoc analysis of the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial, we investigated the prognostic value of MCF and its association with heterogeneity of treatment effect in heart failure with preserved ejection fraction (HFpEF).

Methods: TOPCAT randomized patients with HFpEF to spironolactone or placebo.

Hepcidin, incident heart failure, and cardiac dysfunction in older adults: the ARIC study.

Aims: Hepcidin regulates plasma and tissue iron levels. We studied the association of hepcidin levels with the risk of incident heart failure (HF) and cardiac dysfunction in older adults.

Methods And Results: We included adults from the ongoing, longitudinal Atherosclerosis Risk in Communities (ARIC) study, who were free from prevalent anaemia and HF at Visit 5 (2011-13) and had available hepcidin and covariate data.

Multiparametric Assessment of Right Ventricular Dysfunction in Heart Failure: An Analysis From PARAGON-HF.

Background: This study aims to characterize right ventricular dysfunction (RVD) in heart failure (HF) with preserved ejection fraction and understand the cumulative prognostic value of abnormal RV echocardiographic parameters in HF with preserved ejection fraction.

Methods And Results: Data from 809 patients in the PARAGON-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin-Receptor Blocker Global Outcomes in HF With Preserved Ejection Fraction) echocardiographic substudy (55% women, mean age 74±8 years) were analyzed. Correlates of RVD (defined as tricuspid annular plane systolic excursion <1.

Effect of sacubitril/valsartan in heart failure with preserved ejection fraction across the age spectrum in PARAGON-HF.

Aims: To evaluate clinical outcomes, echocardiographic features, and the efficacy and safety of sacubitril/valsartan compared to valsartan across age groups in the PARAGON-HF trial.

Methods And Results: A total of 4796 participants ≥50 years of age with chronic heart failure (HF) and left ventricular ejection fraction (LVEF) ≥45% were divided into three age groups: <65 years (n = 825), 65-74 years (n = 1772), and ≥75 years (n = 2199). Echocardiograms of 1097 patients were analysed in a standardized fashion at a core imaging laboratory.

Cigarette Smoking, Smoking Cessation, and Heart Failure Subtypes: Insights From the Jackson Heart Study.

Background: Cigarette smoking has been associated with incident heart failure (HF). However, the association between cigarette smoking and smoking cessation with HF subtypes has not been well elucidated, particularly among Black people.

Methods And Results: We investigated 4189 (never smoker n=2934, former smoker n=761, current smoker n=464) Black participants (mean age 54 years, 64% women) without a history of HF or coronary heart disease at baseline in the Jackson Heart Study.

Association of left atrial function with vascular brain injury: The Atherosclerosis Risk in Communities study.

Background And Purpose: Lower left atrial (LA) function is associated with higher dementia risk and may be mechanistically linked through vascular brain injury, an established correlate for higher dementia risk. Using data from the Atherosclerosis Risk in Communities study, we assessed the cross-sectional association between LA function and brain magnetic resonance imaging (MRI) markers of vascular brain injury.

Methods: We included 1488 participants who were free of prevalent dementia, stroke, or atrial fibrillation and who underwent a two-dimensional echocardiogram and brain MRI in 2011-2013 (mean [± standard deviation] age 76 [± 5] years, 60% female, 27% Black).

Precision Medicine for Cardiovascular Prevention and Population Health: A Bridge Too Far?

Precision medicine aims to provide personalized clinical care guided by tools that reflect underlying pathophysiology. The need for such an approach has never been greater in cardiovascular medicine, given the large number of guideline-directed medical therapies available. However, progress has been modest to date with few precision tools available for clinicians.

Proteomic Profile of the p.K56M HFpEF Risk Variant.

A common missense variant in among African American individuals (rs5491; pK56M) has been associated with risk of heart failure with preserved ejection fraction (HFpEF), but the pathways that lead to HFpEF among those with this variant are not clear. In this analysis of 92 circulating proteins and their associated networks, we identified 7 circulating inflammatory proteins associated with rs5491 among >600 African American individuals. Using weighted coexpression network analysis, 3 protein networks were identified, one of which was associated with rs5491.

NT-proBNP and Cardiac Troponin I, but Not Cardiac Troponin T, Are Associated With 7-Year Changes in Cardiac Structure and Function in Older Adults: The ARIC Study.

Background: Higher circulating concentrations of NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI) are associated with left ventricular remodeling and with incident heart failure. The associations of these cardiac biomarkers with changes in cardiac structure and function over time are uncharacterized.

Methods: Among 2006 participants in the ARIC prospective cohort study (Atherosclerosis Risk in Communities) who were free of overt cardiovascular disease and underwent echocardiography at study visits 5 (2011- 2013) and 7 (2018-2019), we assessed the associations of NT-proBNP, hs-cTnT, and hs-cTnI concentrations at visit 5 with changes in left ventricular structure and function between visits 5 and 7 (≈7-year change) using multivariable linear regression with the biomarkers modeled as restricted cubic splines.

Association of left atrial function with frailty: The Atherosclerosis Risk in Communities (ARIC) study.

Background: Frailty is common in people with cardiovascular disease. Worse left atrial (LA) function is an independent risk factor for cardiovascular disease. However, whether worse LA function is associated with frailty is unclear.

Drug-Drug Interactions and the Clinical Tolerability of Colchicine Among Patients With COVID-19: A Secondary Analysis of the COLCORONA Randomized Clinical Trial.

Importance: Colchicine has many drug-drug interactions with commonly prescribed medications. Only pharmacokinetic studies have provided data on colchicine drug-drug interactions.

Objective: To evaluate the clinical tolerability of colchicine according to the presence or absence of a drug-drug interaction.