Scholars@Duke
Robert W. McGarrah III

Robert W. McGarrah III

Associate Professor of Medicine
Medicine, Cardiology
robert.mcgarrah@duke.edu
104775, 49-208J, Durham, NC 27701
300 N. Duke Street, Carmichael Building - 49-208J, Durham, NC 27701

Selected Publications

Metabolic Effects of the SGLT2 Inhibitor Dapagliflozin in Heart Failure Across the Spectrum of Ejection Fraction.

Journal Article Circ Heart Fail · November 2024 BACKGROUND: Mechanisms of benefit with SGLT2is (sodium-glucose cotransporter-2 inhibitors) in heart failure (HF) remain incompletely characterized. Dapagliflozin alters ketone and fatty acid metabolism in HF with reduced ejection fraction though similar ef ... Full text Link to item Cite

Mitochondrial metabolites predict adverse cardiovascular events in individuals with diabetes.

Journal Article JCI Insight · September 8, 2023 Metabolic mechanisms underlying the heterogeneity of major adverse cardiovascular (CV) event (MACE) risk in individuals with type 2 diabetes mellitus (T2D) remain unclear. We hypothesized that circulating metabolites reflecting mitochondrial dysfunction pr ... Full text Link to item Cite

Serum Metabolites Are Associated With HFpEF in Biopsy-Proven Nonalcoholic Fatty Liver Disease.

Journal Article J Am Heart Assoc · July 18, 2023 Background Nonalcoholic fatty liver disease (NAFLD) and heart failure with preserved ejection fraction (HFpEF) share common risk factors, including obesity and diabetes. They are also thought to be mechanistically linked. The aim of this study was to defin ... Full text Link to item Cite

Branched-chain amino acids in cardiovascular disease.

Journal Article Nat Rev Cardiol · February 2023 Research conducted in the past 15 years has yielded crucial insights that are reshaping our understanding of the systems physiology of branched-chain amino acid (BCAA) metabolism and the molecular mechanisms underlying the close relationship between BCAA h ... Full text Link to item Cite

Multimarkers of metabolic malnutrition and inflammation and their association with mortality risk in cardiac catheterisation patients: a prospective, longitudinal, observational, cohort study.

Journal Article Lancet Healthy Longev · February 2023 BACKGROUND: Complex and incompletely understood metabolic dysfunction associated with inflammation and protein-energy wasting contribute to the increased mortality risk of older patients and those with chronic organ diseases affected by cachexia, sarcopeni ... Full text Link to item Cite

Lipoprotein Subclasses Associated With High-Risk Coronary Atherosclerotic Plaque: Insights From the PROMISE Clinical Trial.

Journal Article J Am Heart Assoc · January 3, 2023 BACKGROUND More than half of major adverse cardiovascular events (MACE) occur in the absence of obstructive coronary artery disease and are often attributed to the rupture of high-risk coronary atherosclerotic plaque (HRP). Blood-based biomarkers that asso ... Full text Link to item Cite

Bending the Cardiovascular Event Curve by Evaluating the Potential Impact of Achieving Low-Density Lipoprotein Cholesterol Goal Across a Large Health System Among Secondary Prevention Patients.

Journal Article Am J Cardiol · January 1, 2023 Guidelines recommend aggressive low-density lipoprotein cholesterol (LDL-C) lowering in patients with atherosclerotic cardiovascular disease (ASCVD). However, the recommended threshold of LDL-C ≤70 mg/dL is often not achieved. We used data from the Duke Un ... Full text Link to item Cite

Risk factors for cardiovascular disease among individuals with hepatic steatosis.

Journal Article Hepatol Commun · December 2022 Cardiovascular disease (CVD) is the leading cause of mortality in adults with hepatic steatosis (HS). However, risk factors for CVD in HS are unknown. We aimed to identify factors associated with coronary artery disease (CAD) and incident major adverse car ... Full text Link to item Cite

Lipid-Lowering Therapy in Women of Childbearing Age: a Review and Stepwise Clinical Approach.

Journal Article Curr Cardiol Rep · October 2022 PURPOSE OF REVIEW: Women are less often recognized to have cardiovascular disease (CVD) risk and are underrepresented in randomized trials of lipid-lowering therapy. Here, we summarize non-pharmacologic and pharmacologic strategies for lipid-lowering in wo ... Full text Link to item Cite

Eradicating Atherosclerosis: Should We Start Statins at Younger Ages and at Lower LDL-Cs.

Journal Article Curr Cardiol Rep · October 2022 PURPOSE OF REVIEW: Given the increasing burden of cardiovascular disease, we review the literature for earlier initiation of statin therapy at younger ages and lower low-density lipoprotein cholesterol (LDL-C) levels, with the goal of preventing the develo ... Full text Link to item Cite

A saturated map of common genetic variants associated with human height.

Journal Article Nature · October 2022 Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wid ... Full text Link to item Cite

Altered branched-chain α-keto acid metabolism is a feature of NAFLD in individuals with severe obesity.

Journal Article JCI Insight · August 8, 2022 Hepatic de novo lipogenesis is influenced by the branched-chain α-keto acid dehydrogenase (BCKDH) kinase (BCKDK). Here, we aimed to determine whether circulating levels of the immediate substrates of BCKDH, the branched-chain α-keto acids (BCKAs), and hepa ... Full text Link to item Cite

Plasma metabolites associated with functional and clinical outcomes in heart failure with reduced ejection fraction with and without type 2 diabetes.

Journal Article Sci Rep · June 2, 2022 Heart failure with reduced ejection fraction (HFrEF) is increasingly treated with medications for type 2 diabetes mellitus (T2DM). Whether metabolic derangements in HFrEF and T2DM are associated with differential outcomes remains unclear. Therefore, unders ... Full text Link to item Cite

Nonalcoholic Fatty Liver Disease and Risk of Heart Failure Among Medicare Beneficiaries.

Journal Article J Am Heart Assoc · November 16, 2021 Background Nonalcoholic fatty liver disease (NAFLD) and heart failure (HF) are increasing in prevalence. The independent association between NAFLD and downstream risk of HF and HF subtypes (HF with preserved ejection fraction and HF with reduced ejection f ... Full text Link to item Cite

Relationship of Nonalcoholic Fatty Liver Disease and Heart Failure With Preserved Ejection Fraction.

Journal Article JACC Basic Transl Sci · November 2021 Although there is an established bidirectional relationship between heart failure with reduced ejection fraction and liver disease, the association between heart failure with preserved ejection fraction (HFpEF) and liver diseases, such as nonalcoholic fatt ... Full text Link to item Cite

Insulin action, type 2 diabetes, and branched-chain amino acids: A two-way street.

Journal Article Mol Metab · October 2021 BACKGROUND: A strong association of obesity and insulin resistance with increased circulating levels of branched-chain and aromatic amino acids and decreased glycine levels has been recognized in human subjects for decades. SCOPE OF REVIEW: More recently, ... Full text Link to item Cite

Circulating long chain acylcarnitines and outcomes in diabetic heart failure: an HF-ACTION clinical trial substudy.

Journal Article Cardiovasc Diabetol · August 3, 2021 BACKGROUND: Whether differences in circulating long chain acylcarnitines (LCAC) are seen in heart failure (HF) patients with and without diabetes mellitus (DM), and whether these biomarkers report on exercise capacity and clinical outcomes, remains unknown ... Full text Link to item Cite

Metabolic flexibility via mitochondrial BCAA carrier SLC25A44 is required for optimal fever.

Journal Article Elife · May 4, 2021 Importing necessary metabolites into the mitochondrial matrix is a crucial step of fuel choice during stress adaptation. Branched chain-amino acids (BCAAs) are essential amino acids needed for anabolic processes, but they are also imported into the mitocho ... Full text Link to item Cite

Association of liver fibrosis risk scores with clinical outcomes in patients with heart failure with preserved ejection fraction: findings from TOPCAT.

Journal Article ESC Heart Fail · April 2021 AIMS: Non-alcoholic fatty liver disease leads to progressive liver fibrosis and appears to be a frequent co-morbid disease in heart failure with preserved ejection fraction (HFpEF). It is well known that liver fibrosis severity predicts future liver-relate ... Full text Link to item Cite

Branched-chain α-ketoacids are preferentially reaminated and activate protein synthesis in the heart.

Journal Article Nat Commun · March 15, 2021 Branched-chain amino acids (BCAA) and their cognate α-ketoacids (BCKA) are elevated in an array of cardiometabolic diseases. Here we demonstrate that the major metabolic fate of uniformly-13C-labeled α-ketoisovalerate ([U-13C]KIV) in the heart is reaminati ... Full text Link to item Cite

Novel plasma biomarkers improve discrimination of metabolic health independent of weight.

Journal Article Sci Rep · December 7, 2020 We sought to determine if novel plasma biomarkers improve traditionally defined metabolic health (MH) in predicting risk of cardiovascular disease (CVD) events irrespective of weight. Poor MH was defined in CATHGEN biorepository participants (n > 9300), a ... Full text Link to item Cite

Muscle-Liver Trafficking of BCAA-Derived Nitrogen Underlies Obesity-Related Glycine Depletion.

Journal Article Cell Rep · November 10, 2020 Glycine levels are inversely associated with branched-chain amino acids (BCAAs) and cardiometabolic disease phenotypes, but biochemical mechanisms that explain these relationships remain uncharted. Metabolites and genes related to BCAA metabolism and nitro ... Full text Link to item Cite

Identification of Undetected Monogenic Cardiovascular Disorders.

Journal Article J Am Coll Cardiol · August 18, 2020 BACKGROUND: Monogenic diseases are individually rare but collectively common, and are likely underdiagnosed. OBJECTIVES: The purpose of this study was to estimate the prevalence of monogenic cardiovascular diseases (MCVDs) and potentially missed diagnoses ... Full text Link to item Cite

Lipoprotein (a): An Update on a Marker of Residual Risk and Associated Clinical Manifestations.

Journal Article Am J Cardiol · July 1, 2020 Lipoprotein (a) [Lp(a)] is a low-density, cholesterol-containing lipoprotein that differs from other low-density lipoproteins due to the presence of apolipoprotein(a) bound to its surface apolipoprotein B100. Multiple epidemiologic studies, including Mende ... Full text Link to item Cite

Dietary branched-chain amino acid restriction alters fuel selection and reduces triglyceride stores in hearts of Zucker fatty rats.

Journal Article Am J Physiol Endocrinol Metab · February 1, 2020 Elevations in circulating levels of branched-chain amino acids (BCAAs) are associated with a variety of cardiometabolic diseases and conditions. Restriction of dietary BCAAs in rodent models of obesity lowers circulating BCAA levels and improves whole-anim ... Full text Link to item Cite

BCAA catabolism in brown fat controls energy homeostasis through SLC25A44.

Journal Article Nature · August 2019 Branched-chain amino acid (BCAA; valine, leucine and isoleucine) supplementation is often beneficial to energy expenditure; however, increased circulating levels of BCAA are linked to obesity and diabetes. The mechanisms of this paradox remain unclear. Her ... Full text Link to item Cite

Trends in cardiorespiratory fitness: The evolution of exercise treadmill testing at a single Academic Medical Center from 1970 to 2012.

Journal Article Am Heart J · April 2019 OBJECTIVE: To identify temporal trends in the use of exercise treadmill testing (ETT) and cardiorespiratory fitness (CRF) estimated by ETT in metabolic equivalents (METs). PATIENTS AND METHODS: We compiled an ETT database of all available treadmill tests-i ... Full text Link to item Cite

Metabolomics Identifies Novel Blood Biomarkers of Pulmonary Function and COPD in the General Population.

Journal Article Metabolites · April 1, 2019 Determination of metabolomic signatures of pulmonary function and chronic obstructive pulmonary disease (COPD) in the general population could aid in identification and understanding of early disease processes. Metabolome measurements were performed on ser ... Full text Link to item Cite

High-Density Lipoprotein Particle Subfractions in Heart Failure With Preserved or Reduced Ejection Fraction.

Journal Article J Am Coll Cardiol · January 22, 2019 BACKGROUND: Circulating high-density lipoprotein particle (HDL-P) subfractions impact atherogenesis, inflammation, and endothelial function, all of which are implicated in the pathobiology of heart failure (HF). OBJECTIVES: The authors sought to identify k ... Full text Link to item Cite

Association of long-term PM2.5 exposure with traditional and novel lipid measures related to cardiovascular disease risk.

Journal Article Environ Int · January 2019 BACKGROUND: Fine particulate matter (PM2.5) exposure is associated with increased morbidity and mortality, particularly for cardiovascular disease. The association between long-term exposure to PM2.5 and measures of lipoprotein subfractions remains unclear ... Full text Link to item Cite

Propionate-induced changes in cardiac metabolism, notably CoA trapping, are not altered by l-carnitine.

Journal Article Am J Physiol Endocrinol Metab · October 1, 2018 High concentrations of propionate and its metabolites are found in several diseases that are often associated with the development of cardiac dysfunction, such as obesity, diabetes, propionic acidemia, and methylmalonic acidemia. In the present work, we em ... Full text Link to item Cite

Integration of BCAA and Lipid Metabolism by the BCKDH Kinase and Phosphatase

Conference Diabetes · July 1, 2018 Strong associations exist between branched chain amino acids (BCAA) and dysregulated glucose and lipid metabolism, but underlying mechanisms are not well understood. One factor contributing to elevated BCAA in obesity is inhibitory phosphorylation ... Full text Cite

The BCKDH Kinase and Phosphatase Integrate BCAA and Lipid Metabolism via Regulation of ATP-Citrate Lyase.

Journal Article Cell Metab · June 5, 2018 Branched-chain amino acids (BCAA) are strongly associated with dysregulated glucose and lipid metabolism, but the underlying mechanisms are poorly understood. We report that inhibition of the kinase (BDK) or overexpression of the phosphatase (PPM1K) that r ... Full text Link to item Cite

Effects of a 12-week mHealth program on peak VO2 and physical activity patterns after completing cardiac rehabilitation: A randomized controlled trial.

Journal Article Am Heart J · May 2018 BACKGROUND: Site-based cardiac rehabilitation (CR) provides supervised exercise, education and motivation for patients. Graduates of CR have improved exercise tolerance. However, when participation in CR ceases, adherence to regular physical activity often ... Full text Link to item Cite

Cardiovascular Metabolomics.

Journal Article Circ Res · April 27, 2018 Disturbances in cardiac metabolism underlie most cardiovascular diseases. Metabolomics, one of the newer omics technologies, has emerged as a powerful tool for defining changes in both global and cardiac-specific metabolism that occur across a spectrum of ... Full text Link to item Cite

Effects of Increasing Exercise Intensity and Dose on Multiple Measures of HDL (High-Density Lipoprotein) Function.

Journal Article Arterioscler Thromb Vasc Biol · April 2018 OBJECTIVE: Measures of HDL (high-density lipoprotein) function are associated with cardiovascular disease. However, the effects of regular exercise on these measures is largely unknown. Thus, we examined the effects of different doses of exercise on 3 meas ... Full text Link to item Cite

A Novel Protein Glycan-Derived Inflammation Biomarker Independently Predicts Cardiovascular Disease and Modifies the Association of HDL Subclasses with Mortality.

Journal Article Clin Chem · January 2017 BACKGROUND: Evidence suggests that systemic inflammation may adversely impact HDL function. In this study we sought to evaluate the independent and incremental predictive performance of GlycA-a novel serum inflammatory biomarker that is an aggregate measur ... Full text Link to item Cite

NMR Lipoprotein Profiling Identifies HDL Subclasses Associated With Obstructive CAD: Insights From the PROMISE Clinical Trial

Conference · 2017 Introduction: In patients at high CV risk, the molar sum of concentrations of small and medium HDL subclasses (HMSP) has significant protective associations with CV outcomes, and outperforms HDL cholesterol for risk prediction. The association of HMSP with ... Cite

The Effect of Vigorous- Versus Moderate-Intensity Aerobic Exercise on Insulin Action.

Journal Article Curr Cardiol Rep · December 2016 Due to the beneficial effects on a wide range of modern medical conditions, most professional societies recommend regular aerobic exercise as part of a healthy lifestyle. Many of the exercise-related health benefits exhibit a dose-response relationship: Up ... Full text Link to item Cite

Metabolomic Profiling Identifies Novel Circulating Biomarkers of Mitochondrial Dysfunction Differentially Elevated in Heart Failure With Preserved Versus Reduced Ejection Fraction: Evidence for Shared Metabolic Impairments in Clinical Heart Failure.

Journal Article J Am Heart Assoc · July 29, 2016 BACKGROUND: Metabolic impairment is an important contributor to heart failure (HF) pathogenesis and progression. Dysregulated metabolic pathways remain poorly characterized in patients with HF and preserved ejection fraction (HFpEF). We sought to determine ... Full text Open Access Link to item Cite

Aortic valve surgery and survival in patients with moderate or severe aortic stenosis and left ventricular dysfunction.

Journal Article Eur Heart J · July 21, 2016 AIMS: We aimed to determine the frequency of aortic valve surgery (AVR) with or without coronary artery bypass grafting (CABG), among patients with moderate/severe aortic stenosis (AS) and left ventricular systolic dysfunction (LVSD), and its relationship ... Full text Link to item Cite

Branched-chain amino acid restriction in Zucker-fatty rats improves muscle insulin sensitivity by enhancing efficiency of fatty acid oxidation and acyl-glycine export.

Journal Article Mol Metab · July 2016 OBJECTIVE: A branched-chain amino acid (BCAA)-related metabolic signature is strongly associated with insulin resistance and predictive of incident diabetes and intervention outcomes. To better understand the role that this metabolite cluster plays in obes ... Full text Link to item Cite

Metabolic Dysfunction in Heart Failure: Diagnostic, Prognostic, and Pathophysiologic Insights From Metabolomic Profiling.

Journal Article Curr Heart Fail Rep · June 2016 Metabolic impairment is an intrinsic component of heart failure (HF) pathophysiology. Although initially conceived as a myocardial defect, metabolic dysfunction is now recognized as a systemic process with complex interplay between the myocardium and perip ... Full text Link to item Cite

High-density lipoprotein subclass measurements improve mortality risk prediction, discrimination and reclassification in a cardiac catheterization cohort.

Journal Article Atherosclerosis · March 2016 BACKGROUND AND AIMS: Recent failures of HDL cholesterol (HDL-C)-raising therapies to prevent cardiovascular disease (CVD) events have tempered the interest in the role of HDL-C in clinical risk assessment. Emerging data suggest that the atheroprotective pr ... Full text Link to item Cite

Prognostic Implications of Long-Chain Acylcarnitines in Heart Failure and Reversibility With Mechanical Circulatory Support.

Journal Article J Am Coll Cardiol · January 26, 2016 BACKGROUND: Heart failure (HF) is characterized by perturbations in energy homeostasis and metabolism. The reversibility and prognostic value of circulating markers associated with these changes remain unclear. OBJECTIVES: This study sought to describe the ... Full text Link to item Cite

The heart is just a muscle.

Journal Article Circulation · March 10, 2015 Full text Link to item Cite

Pharmacological inhibition of a microRNA family in nonhuman primates by a seed-targeting 8-mer antimiR.

Journal Article Sci Transl Med · November 20, 2013 MicroRNAs (miRNAs) regulate many aspects of human biology. They target mRNAs for translational repression or degradation through base pairing with 3' untranslated regions, primarily via seed sequences (nucleotides 2 to 8 in the mature miRNA sequence). A nu ... Full text Link to item Cite

NMR-BASED LIPOPROTEIN PARTICLE PROFILING IDENTIFIES NOVEL SIGNATURES FOR CARDIOVASCULAR DISEASE

Conference Journal of the American College of Cardiology · March 2013 Full text Cite

Bradykinin B1 and B2 receptors both have protective roles in renal ischemia/reperfusion injury

Journal Article Proceedings of the National Academy of Sciences · May 2007 To explore the role of the kallikrein–kinin system in relation to ischemia/reperfusion injury in the kidney, we generated mice lacking both the bradykinin B1 and B2 receptor genes (B1RB2R-null, Bdkrb1 Full text Cite