Publications by authors named "Christie M Ballantyne"

722 Publications

Effect of omega-3 fatty acids on cardiovascular outcomes: A systematic review and meta-analysis.

EClinicalMedicine 2021 Aug 8;38:100997. Epub 2021 Jul 8.

Brigham and Women's Hospital Heart and Vascular Center, Harvard Medical School, 75 Francis Street, Boston, MA 02115, United States.

Background: The effects of omega-3 fatty acids (FAs), such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, on cardiovascular outcomes are uncertain. We aimed to determine the effectiveness of omega-3 FAs on fatal and non-fatal cardiovascular outcomes and examine the potential variability in EPA vs. EPA+DHA treatment effects.

Methods: We searched EMBASE, PubMed, ClinicalTrials.gov, and Cochrane library databases through June 7, 2021. We performed a meta-analysis of 38 randomized controlled trials of omega-3 FAs, stratified by EPA monotherapy and EPA+DHA therapy. We estimated random-effects rate ratios (RRs) with (95% confidence intervals) and rated the certainty of evidence using GRADE. The key outcomes of interest were cardiovascular mortality, non-fatal cardiovascular outcomes, bleeding, and atrial fibrillation (AF). The protocol was registered in PROSPERO (CRD42021227580).

Findings: In 149,051 participants, omega-3 FA was associated with reducing cardiovascular mortality (RR, 0.93 [0.88-0.98];  = 0.01), non-fatal myocardial infarction (MI) (RR, 0.87 [0.81-0.93];  = 0.0001), coronary heart disease events (CHD) (RR, 0.91 [0.87-0.96];  = 0.0002), major adverse cardiovascular events (MACE) (RR, 0.95 [0.92-0.98];  = 0.002), and revascularization (RR, 0.91 [0.87-0.95];  = 0.0001). The meta-analysis showed higher RR reductions with EPA monotherapy (0.82 [0.68-0.99]) than with EPA + DHA (0.94 [0.89-0.99]) for cardiovascular mortality, non-fatal MI (EPA: 0.72 [0.62-0.84]; EPA+DHA: 0.92 [0.85-1.00]), CHD events (EPA: 0.73 [0.62-0.85]; EPA+DHA: 0.94 [0.89-0.99]), as well for MACE and revascularization. Omega-3 FA increased incident AF (RR, 1.26 [1.08-1.48]). EPA monotherapy vs. control was associated with a higher risk of total bleeding (RR: 1.49 [1.20-1.84]) and AF (RR, 1.35 [1.10-1.66]).

Interpretation: Omega-3 FAs reduced cardiovascular mortality and improved cardiovascular outcomes. The cardiovascular risk reduction was more prominent with EPA monotherapy than with EPA+DHA.

Funding: None.
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http://dx.doi.org/10.1016/j.eclinm.2021.100997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413259PMC
August 2021

Technology-Assisted Self-Selection of Candidates for Nonprescription Statin Therapy.

J Am Coll Cardiol 2021 Sep;78(11):1114-1123

Center for Cardiovascular Disease Prevention, Harvard Medical School, Boston, Massachusetts, USA.

Background: Although statins reduce cardiovascular morbidity and mortality, only about one-half of eligible patients receive treatment. Safe and appropriate consumer access to statins could have a significant positive public health impact.

Objectives: This study compares the concordance between a participant and clinician assessment of eligibility for statin therapy using a technology-assisted approach.

Methods: A total of 500 participants, 83 with limited literacy, completed an at-home Web-based application to assess appropriateness for treatment with rosuvastatin 5 mg. The Web application is designed to assess eligibility for a moderate-intensity statin based on current guidelines and deny access to individuals with contraindications to rosuvastatin. Subsequently, participants visited a research site where clinicians, blinded to the information the participant entered, performed an independent Web application assessment. The Web application is programmed for 1 of 3 rosuvastatin treatment outcomes: "OK to use," "not right for you," or "ask a doctor." The primary endpoint was the percent of participants whose self-selected eligibility for nonprescription rosuvastatin was concordant with clinician assessment.

Results: For the primary endpoint, participant selection for statin therapy was concordant with clinician selection in 481 (96.2%) of 500 participants (95% confidence interval: 94.1%-97.7%), of whom 23 (4.6%) were deemed appropriate and 458 (91.6%) were deemed inappropriate for treatment. Discordance was due to incorrect self-selection ("OK to use") in 3 cases, incorrect rejection ("not right for you") in 14 cases and an incorrect "ask a doctor" outcome in 2 cases.

Conclusions: The use of a technology-assisted approach to consumer self-selection for statin therapy resulted in participant self-selection that showed substantial agreement with clinician selection.
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http://dx.doi.org/10.1016/j.jacc.2021.06.048DOI Listing
September 2021

Endothelium-specific depletion of LRP1 improves glucose homeostasis through inducing osteocalcin.

Nat Commun 2021 Sep 6;12(1):5296. Epub 2021 Sep 6.

Department of Medicine, Section of Athero & Lipo, Baylor College of Medicine, Houston, TX, USA.

The vascular endothelium is present within metabolic organs and actively regulates energy metabolism. Here we show osteocalcin, recognized as a bone-secreted metabolic hormone, is expressed in mouse primary endothelial cells isolated from heart, lung and liver. In human osteocalcin promoter-driven green fluorescent protein transgenic mice, green fluorescent protein signals are enriched in endothelial cells lining aorta, small vessels and capillaries and abundant in aorta, skeletal muscle and eye of adult mice. The depletion of lipoprotein receptor-related protein 1 induces osteocalcin through a Forkhead box O -dependent pathway in endothelial cells. Whereas depletion of osteocalcin abolishes the glucose-lowering effect of low-density lipoprotein receptor-related protein 1 depletion, osteocalcin treatment normalizes hyperglycemia in multiple mouse models. Mechanistically, osteocalcin receptor-G protein-coupled receptor family C group 6 member A and insulin-like-growth-factor-1 receptor are in the same complex with osteocalcin and required for osteocalcin-promoted insulin signaling pathway. Therefore, our results reveal an endocrine/paracrine role of endothelial cells in regulating insulin sensitivity, which may have therapeutic implications in treating diabetes and insulin resistance through manipulating vascular endothelium.
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http://dx.doi.org/10.1038/s41467-021-25673-6DOI Listing
September 2021

Associations of High-Sensitivity Troponin and Natriuretic Peptide Levels With Outcomes After Intensive Blood Pressure Lowering: Findings From the SPRINT Randomized Clinical Trial.

JAMA Cardiol 2021 Sep 1. Epub 2021 Sep 1.

Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas.

Importance: Elevated high-sensitivity cardiac troponin T (hscTnT) and N-terminal pro-B-type natriuretic peptide (NTproBNP) levels are associated with risk of heart failure (HF) and mortality among individuals in the general population. However, it is unknown if this risk is modifiable.

Objective: To test the hypothesis that elevated hscTnT and NTproBNP levels would identify individuals with the greatest risk for mortality and HF and the largest benefit associated with intensive systolic blood pressure (SBP) lowering.

Design, Setting, And Participants: This is a nonprespecified post hoc analysis of the multicenter, prospective, randomized clinical Systolic Blood Pressure Intervention Trial (SPRINT), conducted from October 20, 2010, to August 20, 2015. A total of 9361 patients without diabetes with increased risk for cardiovascular disease were randomized to receive intensive vs standard SBP lowering. Statistical analysis was performed on an intention-to-treat basis from September 30, 2019, to July 29, 2021.

Interventions: Participants were randomized to undergo intensive (<120 mm Hg) or standard (<140 mm Hg) SBP lowering. High-sensitivity cardiac troponin T and NTproBNP levels were measured from stored specimens collected at enrollment, with elevated levels defined as 14 ng/L or more for hscTnT (to convert to micrograms per liter, multiply by 0.001) and 125 pg/mL or more for NTproBNP (to convert to nanograms per liter, multiply by 1.0).

Main Outcomes And Measures: The primary outcome of this ancillary study was HF and mortality.

Results: Of the 9361 participants enrolled in SPRINT, 8828 (5578 men [63.2%]; mean [SD] age, 68.0 [9.5] years) had measured hscTnT levels and 8836 (5585 men [63.2%]; mean [SD] age, 68.0 [9.5] years) had measured NTproBNP levels; 2262 of 8828 patients (25.6%) had elevated hscTnT levels, 3371 of 8836 patients (38.2%) had elevated NTproBNP, and 1411 of 8828 patients (16.0%) had both levels elevated. Randomization to the intensive SBP group led to a 4.9% (95% CI, 1.7%-7.5%) absolute risk reduction (ARR) over 4 years in death and HF (421 events) for those with elevated hscTnT and a 1.7% (95% CI, 0.7%-2.5%) ARR for those without elevated levels. Similarly, for those with elevated NTproBNP, the ARR for death and HF over 4 years was 4.6% (95% CI, 2.3%-6.5%) vs 1.8% (95% CI, 0.9%-2.5%) in those without elevated levels. For those with elevated levels of both biomarkers, the ARR for death and HF over 4 years was 7.8% (95% CI, 3.3%-11.3%) vs 1.7% (95% CI, 0.8%-2.3%) in those with neither biomarker elevated. No significant treatment group by biomarker category interactions were detected.

Conclusions And Relevance: Intensive SBP control led to large absolute differences in death and HF among patients with abnormal hscTnT and NTproBNP levels. These findings demonstrate that risk associated with elevation of these biomarkers is modifiable with intensive BP control. A prospective, randomized clinical trial is needed to evaluate whether these biomarkers may help guide selection of patients for intensive SBP lowering.

Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.
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http://dx.doi.org/10.1001/jamacardio.2021.3187DOI Listing
September 2021

Proteins Associated with Risk of Kidney Function Decline in the General Population.

J Am Soc Nephrol 2021 Sep;32(9):2291-2302

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Background: Proteomic profiling may allow identification of plasma proteins that associate with subsequent changesin kidney function, elucidating biologic processes underlying the development and progression of CKD.

Methods: We quantified the association between 4877 plasma proteins and a composite outcome of ESKD or decline in eGFR by ≥50% among 9406 participants in the Atherosclerosis Risk in Communities (ARIC) Study (visit 3; mean age, 60 years) who were followed for a median of 14.4 years. We performed separate analyses for these proteins in a subset of 4378 participants (visit 5), who were followed at a later time point, for a median of 4.4 years. For validation, we evaluated proteins with significant associations (false discovery rate <5%) in both time periods in 3249 participants in the Chronic Renal Insufficiency Cohort (CRIC) and 703 participants in the African American Study of Kidney Disease and Hypertension (AASK). We also compared the genetic determinants of protein levels with those from a meta-analysis genome-wide association study of eGFR.

Results: In models adjusted for multiple covariates, including baseline eGFR and albuminuria, we identified 13 distinct proteins that were significantly associated with the composite end point in both time periods, including TNF receptor superfamily members 1A and 1B, trefoil factor 3, and -trace protein. Of these proteins, 12 were also significantly associated in CRIC, and nine were significantly associated in AASK. Higher levels of each protein associated with higher risk of 50% eGFR decline or ESKD. We found genetic evidence for a causal role for one protein, lectin mannose-binding 2 protein (LMAN2).

Conclusions: Large-scale proteomic analysis identified both known and novel proteomic risk factors for eGFR decline.
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http://dx.doi.org/10.1681/ASN.2020111607DOI Listing
September 2021

Association of Longitudinal Changes in Cardiac Biomarkers With Atrial and Ventricular Arrhythmias (from the Atherosclerosis Risk in Communities [ARIC] Study).

Am J Cardiol 2021 Aug 28. Epub 2021 Aug 28.

Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota.

We evaluated the association of longitudinal changes in circulating levels of N-terminal pro B-type natriuretic peptide (NT-proBNP) and high sensitivity cardiac troponin T (hs-cTnT) with the burden of arrhythmias as captured by 2-week ambulatory ECG monitoring. This study included 1,930 Atherosclerosis Risk in Communities Study participants who wore a leadless, ambulatory ECG monitor (Zio XT Patch) at visit 6 (2016 to 2017) and had cardiac biomarkers measured at visit 6 and visit 4 (median of 19 years earlier). The mean age of participants at V6 was 79 ± 5 years, 41% were men, and 22% were black. Adjusting for demographics, body mass index, smoking, diabetes, hypertension, stroke, left ventricular mass, cardiac medications, patch wear time, visit 4 levels of NT-proBNP and hs-cTnT, and relative change in hs-cTnT, each log-transformed unit relative increase in NT-proBNP was associated with a higher likelihood of nonsustained ventricular tachycardia (odds ratio 1.29, 95% confidence interval [CI] 1.12 to 1.48), a higher number of daily atrial tachycardia episodes (geometric mean ratio [GMR] 1.16, 95% CI 1.10 to 1.21), and a higher daily ectopic burden (premature ventricular contractions -GMR 1.42, 95% CI 1.25 to 1.62; premature atrial contractions -GMR 1.40, 95% CI 1.25 to 1.57). In fully adjusted analyses, each log-transformed unit relative increase in hs-cTnT was only found to be weakly associated with a higher daily premature ventricular contraction burden (GMR 1.31, 95% CI 1.01 to 1.70). In conclusion, longitudinal change in NT-proBNP was associated with an increased atrial and ventricular arrhythmia burden.
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http://dx.doi.org/10.1016/j.amjcard.2021.07.043DOI Listing
August 2021

Racial Disparities in Modifiable Risk Factors and Statin Usage in Black Patients With Familial Hypercholesterolemia.

J Am Heart Assoc 2021 Sep 25;10(17):e020890. Epub 2021 Aug 25.

Division of Endocrinology, Metabolism and Lipid Research Washington University School of Medicine St. Louis MO.

Background Black men and women are at higher risk for, and suffer greater morbidity and mortality from, atherosclerotic cardiovascular disease (ASCVD) compared with adults of European Ancestry (EA). Black patients with familial hypercholesterolemia are at particularly high risk for ASCVD complications because of lifelong exposure to elevated levels of low-density-lipoprotein cholesterol. Methods and Results This retrospective study analyzed ASCVD prevalence and risk factors in 808 adults with heterozygous familial hypercholesterolemia from 5 US-based lipid clinics, and compared findings in Black versus EA patients. Multivariate logistic regression models were used to determine the strongest predictors of ASCVD as a function of race. No significant difference was noted in the prevalence of ASCVD in Black versus EA patients with familial hypercholesterolemia (39% versus 32%, respectively; =0.15). However, Black versus EA patients had significantly greater prevalence of modifiable risk factors, including body mass index (mean, 32±7 kg/m versus 29±6 kg/m; <0.001), hypertension (82% versus 50%; <0.001), diabetes (39% versus 15%; <0.001), and current smoking (16% versus 8%; =0.006). Black versus EA patients also had significantly lower usage of statins (61% versus 73%; =0.004) and other lipid-lowering agents. In a fully adjusted multivariate model, race was not independently associated with ASCVD (odds ratio, 0.92; 95% CI, 0.60-1.49; =0.72). Conclusions The strongest predictors of ASCVD in Black patients with familial hypercholesterolemia were hypertension and cigarette smoking. These data support wider usage of statins and other lipid-lowering therapies and greater attention to modifiable risk, specifically blood pressure management and smoking cessation.
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http://dx.doi.org/10.1161/JAHA.121.020890DOI Listing
September 2021

Greater than expected reduction in low-density lipoprotein-cholesterol (LDL-C) with bempedoic acid in a patient with heterozygous familial hypercholesterolemia (HeFH).

J Clin Lipidol 2021 Jul 10. Epub 2021 Jul 10.

Department of Medicine, Center for Cardiometabolic Disease Prevention, Baylor College of Medicine, 6655 Travis Street, Suite 320, Houston, TX 77030, USA; Section of Cardiology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA. Electronic address:

Bempedoic acid is an adenosine triphosphate-citrate lyase (ACL) inhibitor that reduces levels of low-density lipoprotein-cholesterol (LDL-C) in the plasma by inhibition of cholesterol synthesis in hepatic cells, which leads to up-regulation of hepatic LDL receptors. Bempedoic acid is approved as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) who require additional lowering of LDL-C. In this case study, we describe a patient with HeFH who had a prior excellent response to statin but unable to take the same, and a less than expected response to PCSK9i, in whom initiation of bempedoic acid led to a substantial reduction of LDL-C. Our findings suggest that patients who are quite responsive to statins may also be quite responsive to bempedoic acid, a medication that works in the same biochemical pathway as HMG-CoA reductase inhibitors. Additionally, this medication may be particularly effective at lowering LDL-C among individuals not on background statin therapy.
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http://dx.doi.org/10.1016/j.jacl.2021.07.002DOI Listing
July 2021

Mentored implementation to initiate a diabetes program in an underserved community: a pilot study.

BMJ Open Diabetes Res Care 2021 Aug;9(1)

Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.

Introduction: Community clinics often face pragmatic barriers, hindering program initiation and replication of controlled research trial results. Mentoring is a potential strategy to overcome these barriers. We piloted an in-person and telehealth mentoring strategy to implement the elehealth-supported, ntegrated Community Health Workers (CHWs), edication-access, group visit ducation (TIME) program in a community clinic.

Research Design And Methods: Participants (n=55) were low-income Latino(a)s with type 2 diabetes. The study occurred in two, 6-month phases. Phase I provided proof-of-concept and an observational experience for the clinic team; participants (n=37) were randomized to the intervention (TIME) or control (usual care), and the research team conducted TIME while the clinic team observed. Phase II provided mentorship to implement TIME, and the research team mentored the clinic team as they conducted TIME for a new single-arm cohort of participants (n=18) with no previous exposure to the program. Analyses included baseline to 6-month comparisons of diabetes outcomes (primary outcome: hemoglobin A1c (HbA1c)): phase I intervention versus control, phase II (within group), and research-run (phase I intervention) versus clinic-run (phase II) arms. We also evaluated baseline to 6-month CHW knowledge changes.

Results: Phase I: compared with the control, intervention participants had superior baseline to 6-month improvements for HbA1c (mean change: intervention: -0.73% vs control: 0.08%, p=0.016), weight (p=0.044), target HbA1c (p=0.035), hypoglycemia (p=0.021), medication non-adherence (p=0.0003), and five of six American Diabetes Association (ADA) measures (p<0.001-0.002). Phase II: participants had significant reductions in HbA1c (mean change: -0.78%, p=0.006), diastolic blood pressure (p=0.004), body mass index (0.012), weight (p=0.010), medication non-adherence (p<0.001), and six ADA measures (p=0.007-0.005). Phase I intervention versus phase II outcomes were comparable. CHWs improved knowledge from pre-test to post-tests (p<0.001).

Conclusions: A novel, mentored approach to implement TIME into a community clinic resulted in improved diabetes outcomes. Larger studies of longer duration are needed to fully evaluate the potential of mentoring community clinics.
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http://dx.doi.org/10.1136/bmjdrc-2021-002320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362735PMC
August 2021

What Do US Physicians and Patients Think About Lipid-Lowering Therapy and Goals of Treatment? Results From the GOULD Registry.

J Am Heart Assoc 2021 Aug 7;10(16):e020893. Epub 2021 Aug 7.

Saint Luke's Mid America Heart Institute and University of Missouri-Kansas City Kansas City MO.

Background Because of an increasing number and complexity of treatment options for lipid-lowering therapy in patients with atherosclerotic cardiovascular disease, guidelines recommend greater active involvement of patients in shared decision-making. However, patients' understanding and perceptions of the benefits, risks, and treatment objectives of lipid-lowering therapy are unknown. Methods and Results Structured questionnaires were conducted in 5006 US outpatients with atherosclerotic cardiovascular disease and suboptimal low-density lipoprotein cholesterol (LDL-C) control (LDL-C ≥70 mg/dL) or on a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor and in 113 physician providers as a part of the GOULD (Getting to an Improved Understanding of Low-Density Lipoprotein Cholesterol and Dyslipidemia Management) Registry. Mean age of the patients was 68±10 years, 60% were men, and 86% were White race. Across all patients, 63% believed heart disease was the leading cause of death in men and 46% the leading cause of death in women. Only 28% of patients thought the primary reason they were taking lipid-lowering medication was to lower the risk of heart attack or stroke, 68% did not know their approximate LDL-C level, and 69% did not know their LDL-C goal. Patients on PCSK9 inhibitors (versus LDL-C cohort), younger patients (versus age ≥65 years), and men (versus women) were somewhat more knowledgeable about their disease and its management. Most physicians (66%) felt that a lack of understanding of the importance and efficacy of statins was the primary factor contributing to nonadherence, as opposed to costs (9%) or side effects (1%). More education was the most commonly used strategy to address patient-reported side effects. Conclusions A large proportion of patients with atherosclerotic cardiovascular disease remain unaware of their underlying atherosclerotic cardiovascular disease risk, reasons for taking lipid-lowering medications, current LDL-C levels, or treatment goals. These data highlight a large education gap which, if addressed, may improve shared decision-making and treatment adherence. Registration URL: https://www.clinicaltrials.org; Unique identifier: NCT02993120.
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http://dx.doi.org/10.1161/JAHA.120.020893DOI Listing
August 2021

Genetic testing in ambulatory cardiology clinics reveals high rate of findings with clinical management implications.

Genet Med 2021 Aug 6. Epub 2021 Aug 6.

Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Baylor College of Medicine, Houston, TX, USA.

Purpose: Cardiovascular disease (CVD) is the leading cause of death in adults in the United States, yet the benefits of genetic testing are not universally accepted.

Methods: We developed the "HeartCare" panel of genes associated with CVD, evaluating high-penetrance Mendelian conditions, coronary artery disease (CAD) polygenic risk, LPA gene polymorphisms, and specific pharmacogenetic (PGx) variants. We enrolled 709 individuals from cardiology clinics at Baylor College of Medicine, and samples were analyzed in a CAP/CLIA-certified laboratory. Results were returned to the ordering physician and uploaded to the electronic medical record.

Results: Notably, 32% of patients had a genetic finding with clinical management implications, even after excluding PGx results, including 9% who were molecularly diagnosed with a Mendelian condition. Among surveyed physicians, 84% reported medical management changes based on these results, including specialist referrals, cardiac tests, and medication changes. LPA polymorphisms and high polygenic risk of CAD were found in 20% and 9% of patients, respectively, leading to diet, lifestyle, and other changes. Warfarin and simvastatin pharmacogenetic variants were present in roughly half of the cohort.

Conclusion: Our results support the use of genetic information in routine cardiovascular health management and provide a roadmap for accompanying research.
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http://dx.doi.org/10.1038/s41436-021-01294-8DOI Listing
August 2021

Association between circulating Galectin-3 and arterial stiffness in older adults.

Vasa 2021 Aug 4. Epub 2021 Aug 4.

Baylor College of Medicine, Houston, TX, USA.

Galectin-3 (gal-3) is a β-galactoside-binding lectin associated tissue fibrosis and inflammation. There is limited understanding of the relationship between gal-3 and vascular health. Our aim was to assess the association between gal-3 and arterial stiffness in older adults. We conducted a cross-sectional study of 4275 participants (mean age of 75 years) from the Atherosclerosis Risk in Communities (ARIC) Study. Central arterial stiffness was measured by carotid-femoral pulse wave velocity (cfPWV). We evaluated the association of gal-3 with cfPWV using multivariable linear regression. The median (interquartile range) gal-3 concentration was 16.5 (13.8, 19.8) ng/mL and mean cfPWV was 1163±303 cm/s. Higher gal-3 concentration was associated with greater central arterial stiffness after adjustment for age, sex, race-center, heart rate, systolic blood pressure, anti-hypertensive medication use, and current smoking status (β=36.4 cm/s change in cfPWV per log unit change in gal-3; 95% CI: 7.2, 65.5, p=0.015). The association was attenuated after adjusting for additional cardiovascular risk factors (β=17.3, 95% CI: -14.4, 49.0). In community-dwelling older adults, gal-3 concentration was associated with central arterial stiffness, likely sharing common pathways with traditional cardiovascular risk factors.
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http://dx.doi.org/10.1024/0301-1526/a000968DOI Listing
August 2021

Ten things to know about ten cardiovascular disease risk factors.

Am J Prev Cardiol 2021 Mar 23;5:100149. Epub 2021 Jan 23.

CGH Medical Center, Sterling, IL USA.

Given rapid advancements in medical science, it is often challenging for the busy clinician to remain up-to-date on the fundamental and multifaceted aspects of preventive cardiology and maintain awareness of the latest guidelines applicable to cardiovascular disease (CVD) risk factors. The "American Society for Preventive Cardiology (ASPC) Top Ten CVD Risk Factors 2021 Update" is a summary document (updated yearly) regarding CVD risk factors. This "ASPC Top Ten CVD Risk Factors 2021 Update" summary document reflects the perspective of the section authors regarding ten things to know about ten sentinel CVD risk factors. It also includes quick access to sentinel references (applicable guidelines and select reviews) for each CVD risk factor section. The ten CVD risk factors include unhealthful nutrition, physical inactivity, dyslipidemia, hyperglycemia, high blood pressure, obesity, considerations of select populations (older age, race/ethnicity, and sex differences), thrombosis/smoking, kidney dysfunction and genetics/familial hypercholesterolemia. For the individual patient, other CVD risk factors may be relevant, beyond the CVD risk factors discussed here. However, it is the intent of the "ASPC Top Ten CVD Risk Factors 2021 Update" to provide a succinct overview of things to know about ten common CVD risk factors applicable to preventive cardiology.
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http://dx.doi.org/10.1016/j.ajpc.2021.100149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315386PMC
March 2021

C-reactive protein levels and plaque regression with evolocumab: Insights from GLAGOV.

Am J Prev Cardiol 2020 Sep 6;3:100091. Epub 2020 Oct 6.

Monash Cardiovascular Research Centre, Victorian Heart Institute, Monash University, Melbourne, Australia.

Objective: On-treatment levels of high sensitivity C-reactive protein (hsCRP) in statin-treated patients predict plaque progression and the prospective risk of atherosclerotic cardiovascular events. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors produce additional LDL-C lowering, reduce plaque burden and improve cardiovascular outcomes in statin-treated patients. It is unknown whether residual systemic inflammation attenuates their favorable effects on plaque burden.

Methods: GLAGOV compared the effects of treatment for 78 weeks with evolocumab or placebo on progression of coronary atherosclerosis in statin-treated patients with coronary artery disease.Clinical demographics, biochemistry and changes in both the burden (percentage atheroma volume (PAV), total atheroma volume (TAV), n ​= ​413) and composition (n ​= ​162) of coronary plaque were evaluated in evolocumab-treated patients according to baseline hsCRP strata (<1, 1-3, >3 ​mg/L).

Results: The study cohort comprised 413 evolocumab-treated patients (32% low [<1 ​mg/L], 41% intermediate [1-3 ​mg/L] and 27% high [>3 ​mg/L] baseline hsCRP levels). Patients in the highest hsCRP stratum were more likely to be female and had a higher prevalence of diabetes, hypertension, and the metabolic syndrome. LDL-C levels were similar across the groups, however participants with higher hsCRP levels had higher triglyceride and lower HDL-C levels at baseline. At follow-up, the change in PAV from baseline (-0.87% [low] vs. -0.84% [intermediate] vs. -1.22% [high], p ​= ​0.46) and the proportion of patients experiencing any degree of regression (65.9% vs. 63.5% vs. 63.1%, p ​= ​0.88) was similar across hsCRP strata and when evaluated by levels of achieved LDL-C. There were no serial differences in plaque composition by hsCRP strata.

Conclusion: The ability of evolocumab to induce regression in statin-treated patients is not attenuated by the presence of enhanced systemic inflammation. This underscores the potential benefits of intensive lipid lowering, even in the presence of heightened inflammatory states.
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http://dx.doi.org/10.1016/j.ajpc.2020.100091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315612PMC
September 2020

Duration of Diabetes and Incident Heart Failure: The ARIC (Atherosclerosis Risk In Communities) Study.

JACC Heart Fail 2021 Aug;9(8):594-603

Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Objectives: This study assessed the association of diabetes duration with incident heart failure (HF).

Background: Diabetes increases HF risk. However, the independent effect of diabetes duration on incident HF is unknown.

Methods: We included 9,734 participants (mean age 63 years, 58% women, 22% Black) at ARIC (Atherosclerosis Risk In Communities) Visit 4 (1996-1998) without HF or coronary heart disease. We calculated diabetes duration at Visit 4 (baseline), utilizing diabetes status at the first 4 ARIC visits spaced 3 years apart, and self-reported diagnosis date for those with diabetes diagnosed before Visit 1. We used Cox regression to estimate associations of diabetes duration with incident HF, accounting for intercurrent coronary heart disease and other risk factors. We performed analyses stratified by age (<65 years or ≥65 years), race, sex, and glycemic control (hemoglobin A [HbA] consistently <7%, vs HbA ≥7%), with tests for interaction.

Results: Over 22.5 years of follow-up, there were 1,968 HF events. Compared to those without diabetes, HF risk rose with longer diabetes duration, with the highest risk among those with ≥15 y diabetes duration (HR: 2.82; 95% CI: 2.25-3.63). Each 5-year increase in diabetes duration was associated with a 17% (95% CI: 11-22) relative increase in HF risk. Similar results were observed across HF subtypes. The HF and diabetes duration associations were stronger among those aged <65 years, those with HbA ≥7%, those with a body mass index ≥30 kg/m, women, and Blacks (all P interactions <0.05).

Conclusions: Delaying diabetes onset may augment HF prevention efforts, and therapies to improve HF outcomes might target those with long diabetes duration.
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http://dx.doi.org/10.1016/j.jchf.2021.06.005DOI Listing
August 2021

Upper Reference Limits for High-Sensitivity Cardiac Troponin T and N-Terminal Fragment of the Prohormone Brain Natriuretic Peptide in Patients With CKD.

Am J Kidney Dis 2021 Jul 19. Epub 2021 Jul 19.

Division of Nephrology, School of Medicine, University of Maryland, Baltimore, Maryland.

Rationale & Objective: The utility of conventional upper reference limits (URL) for N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hsTnT) in chronic kidney disease (CKD) remains debated. We analyzed the distribution of hsTnT and NT-proBNP in people with CKD in ambulatory settings to examine the diagnostic value of conventional URL in this population.

Study Design: Observational study.

Setting & Participants: We studied participants of the Chronic Renal Insufficiency Cohort (CRIC) with CKD and no self-reported history of cardiovascular disease.

Exposure: Estimated glomerular filtration rate (eGFR).

Outcome: NT-proBNP and hsTnT at baseline.

Analytical Approach: We described the proportion of participants above the conventional URL for NT-proBNP (125pg/mL) and hsTnT (14ng/L) overall and by eGFR. We then estimated 99th percentile URL for NT-proBNP and hsTnT. Using quantile regression of the 99th percentile, we modeled the association of eGFR with NT-proBNP and hsTnT.

Results: Among 2,312 CKD participants, 40% and 43% had levels of NT-proBNP and hsTnT above the conventional URL, respectively. In those with eGFR <30mL/min/1.73m, 71% and 68% of participants had concentrations of NT-proBNP and hsTnT above the conventional URL, respectively. Among all CKD participants, the 99th percentile for NT-proBNP was 3,592 (95% CI, 2,470-4,849) pg/mL and for hsTnT it was 126 (95% CI, 100-144) ng/L. Each 15mL/min/1.73m decrement in eGFR was associated with a ~40% higher threshold for the 99th percentile of NT-proBNP (1.43 [95% CI, 1.21-1.69]) and hsTnT (1.45 [95% CI, 1.31-1.60]).

Limitations: Study included ambulatory patients, and we could not test the accuracy of the URL of NT-proBNP and hsTnT in the acute care setting.

Conclusions: In this ambulatory CKD population with no self-reported history of cardiovascular disease, a range of 40%-88% of participants had concentrations of NT-proBNP and hsTnT above the conventional URL, depending on eGFR strata. Developing eGFR-specific thresholds for these commonly used cardiac biomarkers in the setting of CKD may improve their utility for evaluation of suspected heart failure and myocardial infarction.
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http://dx.doi.org/10.1053/j.ajkd.2021.06.017DOI Listing
July 2021

Remnant cholesterol predicts cardiovascular disease beyond LDL and ApoB: a primary prevention study.

Eur Heart J 2021 Jul 19. Epub 2021 Jul 19.

Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Baltimore, MD, USA.

Aims: Emerging evidence suggests that remnant cholesterol (RC) promotes atherosclerotic cardiovascular disease (ASCVD). We aimed to estimate RC-related risk beyond low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB) in patients without known ASCVD.

Methods And Results: We pooled data from 17 532 ASCVD-free individuals from the Atherosclerosis Risk in Communities study (n = 9748), the Multi-Ethnic Study of Atherosclerosis (n = 3049), and the Coronary Artery Risk Development in Young Adults (n = 4735). RC was calculated as non-high-density lipoprotein cholesterol (non-HDL-C) minus calculated LDL-C. Adjusted Cox models were used to estimate the risk for incident ASCVD associated with log RC levels. We also performed discordance analyses examining relative ASCVD risk in RC vs. LDL-C discordant/concordant groups using difference in percentile units (>10 units) and clinically relevant LDL-C targets. The mean age of participants was 52.3 ± 17.9 years, 56.7% were women and 34% black. There were 2143 ASCVD events over the median follow-up of 18.7 years. After multivariable adjustment including LDL-C and apoB, log RC was associated with higher ASCVD risk [hazard ratio (HR) 1.65, 95% confidence interval (CI) 1.45-1.89]. Moreover, the discordant high RC/low LDL-C group, but not the low RC/high LDL-C group, was associated with increased ASCVD risk compared to the concordant group (HR 1.21, 95% CI 1.08-1.35). Similar results were shown when examining discordance across clinical cutpoints.

Conclusions: In ASCVD-free individuals, elevated RC levels were associated with ASCVD independent of traditional risk factors, LDL-C, and apoB levels. The mechanisms of RC association with ASCVD, surprisingly beyond apoB, and the potential value of targeted RC-lowering in primary prevention need to be further investigated.
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http://dx.doi.org/10.1093/eurheartj/ehab432DOI Listing
July 2021

Lipid Monitoring After Initiation of Lipid-Lowering Therapies: Return of Performance Measures?

Curr Cardiol Rep 2021 07 16;23(9):116. Epub 2021 Jul 16.

Department of Medicine, Baylor College of Medicine, One Baylor Plaza, M.S. BCM285, Houston, TX, 77030, USA.

Purpose Of Review: The 2015 American College of Cardiology (ACC)/American Heart Association (AHA) Focused Update of Secondary Prevention Lipid Performance Measures removed low-density lipoprotein cholesterol (LDL-C) assessment as a performance measure. This review discusses the evidence supporting the importance of lipid monitoring in the secondary prevention of atherosclerotic cardiovascular disease (ASCVD).

Recent Findings: The 2018 AHA/ACC Multisociety cholesterol guideline (as did the 2013 guideline) recommends a lipid panel after initiating lipid-lowering therapy to monitor adherence and medication efficacy. The 2018 guideline also recommends adding nonstatin therapy in very-high-risk ASCVD patients with LDL-C ≥70 mg/dL despite maximally tolerated statin therapy. The removal of LDL-C monitoring as a performance measure is not consistent with the 2018 cholesterol guidelines. Given the importance of monitoring lipid-lowering medication efficacy and adherence and optimally reducing LDL-C in very-high-risk patients with additional evidence-based nonstatin therapy, LDL-C assessment after initiating lipid-lowering therapy should be reinstated as a performance measure for patients with ASCVD.
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http://dx.doi.org/10.1007/s11886-021-01545-9DOI Listing
July 2021

Supplemental Association of Clonal Hematopoiesis With Incident Heart Failure.

J Am Coll Cardiol 2021 07;78(1):42-52

Department of Epidemiology, Brown University, Providence, Rhode Island, USA; Care New England, Center for Primary Care and Prevention, Pawtucket, Rhode Island, USA; Department of Family Medicine, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA. Electronic address:

Background: Age-related clonal hematopoiesis of indeterminate potential (CHIP), defined as clonally expanded leukemogenic sequence variations (particularly in DNMT3A, TET2, ASXL1, and JAK2) in asymptomatic individuals, is associated with cardiovascular events, including recurrent heart failure (HF).

Objectives: This study sought to evaluate whether CHIP is associated with incident HF.

Methods: CHIP status was obtained from whole exome or genome sequencing of blood DNA in participants without prevalent HF or hematological malignancy from 5 cohorts. Cox proportional hazards models were performed within each cohort, adjusting for demographic and clinical risk factors, followed by fixed-effect meta-analyses. Large CHIP clones (defined as variant allele frequency >10%), HF with or without baseline coronary heart disease, and left ventricular ejection fraction were evaluated in secondary analyses.

Results: Of 56,597 individuals (59% women, mean age 58 years at baseline), 3,406 (6%) had CHIP, and 4,694 developed HF (8.3%) over up to 20 years of follow-up. CHIP was prospectively associated with a 25% increased risk of HF in meta-analysis (hazard ratio: 1.25; 95% confidence interval: 1.13-1.38) with consistent associations across cohorts. ASXL1, TET2, and JAK2 sequence variations were each associated with an increased risk of HF, whereas DNMT3A sequence variations were not associated with HF. Secondary analyses suggested large CHIP was associated with a greater risk of HF (hazard ratio: 1.29; 95% confidence interval: 1.15-1.44), and the associations for CHIP on HF with and without prior coronary heart disease were homogenous. ASXL1 sequence variations were associated with reduced left ventricular ejection fraction.

Conclusions: CHIP, particularly sequence variations in ASXL1, TET2, and JAK2, represents a new risk factor for HF.
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http://dx.doi.org/10.1016/j.jacc.2021.04.085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313294PMC
July 2021

Statins and Your Memory: "Forget" About It?

J Am Coll Cardiol 2021 Jun;77(25):3157-3159

Section of Cardiovascular Research, Baylor College of Medicine, Houston, Texas, USA; Michael E. DeBakey Veterans Affairs Hospital, Houston, Texas, USA.

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http://dx.doi.org/10.1016/j.jacc.2021.04.076DOI Listing
June 2021

Six-year changes in N-terminal pro-brain natriuretic peptide and changes in weight and risk of obesity.

Obesity (Silver Spring) 2021 Jul;29(7):1215-1222

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.

Objective: The aim of this study was to study the prospective association between N-terminal pro-brain natriuretic peptide (NT-proBNP) and changes in weight and obesity risk in a community-based population.

Methods: Data from 9,681 participants from the Atherosclerosis Risk in Communities Study were analyzed at two time points 6 years apart. Among people without obesity at baseline, multivariable logistic regression models were used to examine the association between baseline levels of NT-proBNP and incident obesity. A multivariable linear regression model was used to examine the association between changes in NT-proBNP (visit 2 serum and visit 4 plasma samples) and changes in weight.

Results: The prevalence of obesity increased from 28% to 35% in the 6-year follow-up period. Compared with individuals in the highest NT-proBNP quartile, those in the lowest were more likely to have obesity at baseline (odds ratio 1.25; 95% CI: 1.08-1.45) and, among people who did not have obesity at baseline, were more likely to develop obesity at follow-up (odds ratio 1.35; 95% CI: 1.07-1.69). Changes in NT-proBNP were inversely associated with weight change.

Conclusions: In this prospective study, lower levels of NT-proBNP were associated with higher risk of obesity, and changes in NT-proBNP were inversely associated with changes in weight. This suggests that natriuretic peptides or their pathways may be potential targets in the treatment of obesity.
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http://dx.doi.org/10.1002/oby.23181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231730PMC
July 2021

Use of Lipid-Lowering Therapies Over 2 Years in GOULD, a Registry of Patients With Atherosclerotic Cardiovascular Disease in the US.

JAMA Cardiol 2021 Jun 16. Epub 2021 Jun 16.

St Luke's Mid America Heart Institute, University of Missouri, Kansas City, Kansas City.

Importance: Guidelines for patients with atherosclerotic cardiovascular disease (ASCVD) recommend intensive statin therapy and adding nonstatin therapy if low-density lipoprotein cholesterol (LDL-C) levels are 70 mg/dL or more. Compliance with guidelines is often low.

Objective: To track LDL-C treatment patterns in the US over 2 years.

Design, Setting, And Participants: GOULD is a prospective observational registry study involving multiple centers. Patients with ASCVD receiving any lipid-lowering therapy (LLT) were eligible. Between December 2016 and July 2018, patients were enrolled in 1 of 3 cohorts: (1) those currently receiving proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) and 2 groups not receiving PCSK9i drugs, with (2) LDL-C levels of 100 mg/dL or more or (3) LDL-C levels of 70 to 99 mg/dL. Patients had medical record reviews and telephone interviews every 6 months. Analysis was done on data collected as of October 5, 2020.

Main Outcomes And Measures: The primary outcome was the change in LLT use in 2 years. Secondary outcomes included the number of LDL-C measurements, LDL-C levels, and responses to structured physician and patient questionnaires over 2 years.

Results: A total of 5006 patients were enrolled (mean [SD] age, 67.8 [9.9] years; 1985 women [39.7%]; 4312 White individuals [86.1%]). At 2 years, 885 (17.1%) had LLT intensification. In the cohorts with LDL-C levels of 100 mg/dL or more and 70 to 99 mg/dL, LLT intensification occurred in 403 (22.4%) and 383 (14.4%), respectively; statins were intensified in 115 (6.4%) and 168 (6.3%), ezetimibe added in 123 (6.8%) and 118 (4.5%), and PCSK9i added in 114 (6.3%) and 58 (2.2%), respectively. In the PCSK9i cohort, 508 of 554 (91.7%) were still taking PCSK9i at 2 years. Lipid panels were measured at least once over 2 years in 3768 patients (88.5%; PCSK9i cohort, 492 [96.1%]; LDL-C levels ≥100 mg/dL or more, 1294 [85.9%]; 70-99 mg/dL, 1982 [88.6%]). Levels of LDL-C fell from medians (interquartile ranges) of 120 (108-141) mg/dL to 95 (73-118) mg/dL in the cohort with LDL-C levels of 100 mg/dL or more, 82 (75-89) to 77 (65-90) mg/dL in the cohort with LDL-C levels of 70 to 99 mg/dL, and 67 (42-104) mg/dL to 67 (42-96) mg/dL in the PCSK9i cohort. Levels of LDL-C less than 70 mg/dL at 2 years were achieved by 308 patients (21.0%) and 758 patients (33.9%) in the cohorts with LDL-C levels of 100 mg/dL or more and 70 to 99 mg/dL, respectively, and 272 patients (52.4%) in the PCSK9i cohort. At 2 years, practice characteristics were associated with more LLT intensification (teaching vs nonteaching hospitals, 148 of 589 [25.1%] vs 600 of 3607 [16.6%]; lipid protocols or none, 359 of 1612 [22.3%] vs 389 of 2584 [15.1%]; cardiology, 452 of 2087 [21.7%] vs internal or family medicine, 204 of 1745 [11.7%] and other, 92 of 364 [25.3%]; all P < .001) and achievement of LDL-C less than 70 mg/dL (teaching vs nonteaching hospitals, 173 of 488 [35.5%] vs 823 of 2986 [27.6%]; lipid protocols vs none, 451 of 1411 [32.0%] vs 545 of 2063 [26.4%]; both P < .001; cardiology, 523 of 1686 [30.1%] vs internal or family medicine, 377 of 1472 [25.6%] and other, 96 of 316 [30.4%]; P = .003).

Conclusions And Relevance: Of patients with ASCVD, most with suboptimal LDL-C levels at baseline, only 17.1% had LLT intensification after 2 years, and two-thirds remained at an LDL-C level greater than 70 mg/dL. Further intensive efforts are needed to achieve optimal LDL-C management in patients with ASCVD.
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http://dx.doi.org/10.1001/jamacardio.2021.1810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209562PMC
June 2021

The ARIC (Atherosclerosis Risk In Communities) Study: JACC Focus Seminar 3/8.

J Am Coll Cardiol 2021 Jun;77(23):2939-2959

Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

ARIC (Atherosclerosis Risk In Communities) initiated community-based surveillance in 1987 for myocardial infarction and coronary heart disease (CHD) incidence and mortality and created a prospective cohort of 15,792 Black and White adults ages 45 to 64 years. The primary aims were to improve understanding of the decline in CHD mortality and identify determinants of subclinical atherosclerosis and CHD in Black and White middle-age adults. ARIC has examined areas including health disparities, genomics, heart failure, and prevention, producing more than 2,300 publications. Results have had strong clinical impact and demonstrate the importance of population-based research in the spectrum of biomedical research to improve health.
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http://dx.doi.org/10.1016/j.jacc.2021.04.035DOI Listing
June 2021

Glycated Hemoglobin to Detect Subclinical Atherosclerosis in People Without Diabetes.

J Am Coll Cardiol 2021 Jun;77(22):2792-2795

Department of Medicine and Center for Cardiometabolic Disease Prevention, Baylor College of Medicine, Houston, Texas, USA.

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http://dx.doi.org/10.1016/j.jacc.2021.04.018DOI Listing
June 2021

Health care costs associated with primary care physicians versus nurse practitioners and physician assistants.

J Am Assoc Nurse Pract 2021 May 31. Epub 2021 May 31.

Department of Management, Policy and Community Heath, School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas Health Policy, Quality & Informatics Program, Michael E. DeBakey Veterans Affairs Medical Center, Health Services Research and Development Center for Innovations, Houston, Texas Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, Texas Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, Texas Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston, Texas Section of Cardiology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas.

Background: Significant primary care provider (PCP) shortage exists in the United States. Expanding the scope of practice for nurse practitioners (NPs) and physician assistants (PAs) can help alleviate this shortage. The Department of Veterans' Affairs (VA) has been a pioneer in expanding the role of NPs and PAs in primary caregiving.

Purpose: This study evaluated the health care costs associated with VA patients cared for by NPs and PAs versus primary care physicians (physicians).

Methods: A retrospective data analysis using two separate cohorts of VA patients, one with diabetes and the other with cardiovascular disease (CVD), was performed. The associations between PCP type and health care costs were analyzed using ordinary least square regressions with logarithmically transformed costs.

Results: The analyses estimated 12% to 13% (US dollars [USD] 2,626) and 4% to 5% (USD 924) higher costs for patients assigned to physicians as compared with those assigned to NPs and PAs, after adjusting for baseline patient sociodemographics and disease burden, in the diabetes and CVD cohort, respectively. Given the average patient population size of a VA medical center, these cost differences amount to a total difference of USD 14 million/year per center and USD 5 million/year per center for diabetic and CVD patients, respectively.

Implications For Practice: This study highlights the potential cost savings associated with primary caregiving by NPs and PAs. In light of the PCP shortage, the study supports increased involvement of NPs and PAs in primary caregiving. Future studies examining the reasons for these cost differences by provider type are required to provide more scientific evidence for regulatory decision making in this area.
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http://dx.doi.org/10.1097/JXX.0000000000000555DOI Listing
May 2021

Association Between Omega-3 Fatty Acid Treatment and Atrial Fibrillation in Cardiovascular Outcome Trials: A Systematic Review and Meta-Analysis.

Cardiovasc Drugs Ther 2021 Aug 31;35(4):793-800. Epub 2021 May 31.

Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.

Purpose: Data on the relationship between omega-3 fatty acid (n-3 FA) therapy with atrial fibrillation (AF) have been inconsistent. We investigate the association between n-3 FA and risk for AF by pooling data from available large, cardiovascular outcome trials.

Methods: We performed a systematic search on PubMed and Embase for studies on n-3 FA with AF as an outcome measure. Large (≥ 1000 participants) randomized controlled trials with ≥ 1-year follow-up period were included. The association between n-3 FA and risk of AF or stroke was assessed. Mantel-Haenszel random effects model was used to calculate risk ratios (RR) with 95% confidence intervals (CI). We then performed meta-regression to evaluate effect on AF by dose of n-3 FA therapy.

Results: A total of 8 randomized control trials encompassing 83,112 participants were included in the meta-analysis. Of these, five trials assessed a lower dose of n-3 FA (≤ 1 g daily, n = 61,096) while 3 trials assessed a higher dose (> 1 g daily, n = 22,016). In meta-analysis, a significant association was noted between n-3 FA treatment and risk of AF (4.0% vs 3.3%; RR 1.24, 95% CI 1.11-1.38, p = 0.0002). There was a modest but still significant association in the lower dose (n-3 FA ≤ 1 g daily) sub-group (RR 1.12, 95% CI 1.04-1.21, p = 0.004) and stronger association in the higher dose (n-3 FA > 1 g daily) sub-group (RR 1.51, 95% CI 1.26-1.80, p < 0.001; p-interaction between low versus high subgroups = 0.003). There was no increase in stroke risk (RR 1.04, 95% CI 0.90-1.20). Meta-regression demonstrated a significant association between dose of n-3 FA with risk for AF events (log RR 0.103, 95% CI 0.048-0.159, p < 0.001).

Conclusion: While overall AF event rates were low, n-3 FA treatment is associated with increased risk for AF.
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http://dx.doi.org/10.1007/s10557-021-07204-zDOI Listing
August 2021

Association Between Achieved ω-3 Fatty Acid Levels and Major Adverse Cardiovascular Outcomes in Patients With High Cardiovascular Risk: A Secondary Analysis of the STRENGTH Trial.

JAMA Cardiol 2021 May 16. Epub 2021 May 16.

Monash Cardiovascular Research Centre, Melbourne, Victoria, Australia.

Importance: In patients treated with ω-3 fatty acids, it remains uncertain whether achieved levels of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) are associated with cardiovascular outcomes.

Objective: To determine the association between plasma levels of EPA and DHA and cardiovascular outcomes in a trial of ω-3 fatty acids compared with corn oil placebo.

Design, Setting, And Participants: A double-blind, multicenter trial enrolled patients at high cardiovascular risk with elevated triglyceride levels and low levels of high-density lipoprotein cholesterol at 675 centers (enrollment from October 30, 2014, to June 14, 2017; study termination January 8, 2020; last visit May 14, 2020).

Interventions: Participants were randomized to receive 4 g daily of ω-3 carboxylic acid (CA) or an inert comparator, corn oil.

Main Outcomes And Measures: The primary prespecified end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina requiring hospitalization. The primary outcome measure was the hazard ratio, adjusted for baseline characteristics, for patients treated with the ω-3 CA compared with corn oil for the top tertile of achieved EPA and DHA plasma levels 12 months after randomization.

Results: Of the 13 078 total participants, 6539 (50%) were randomized to receive ω-3 CA and 6539 (50%) randomized to corn oil. ω-3 Fatty acid levels were available at both baseline and 12 months after randomization in 10 382 participants (5175 ω-3 CA patients [49.8%] and 5207 corn oil-treated patients [50.2%]; mean [SD] age, 62.5 [8.9] years, 3588 [34.6%] were women, 9025 [86.9%] were White, and 7285 [70.2%] had type 2 diabetes). The median plasma levels at 12 months in ω-3 CA patients were 89 μg/mL (interquartile range [IQR], 46-131 μg/mL) for EPA and 91 μg/mL (IQR, 71-114 μg/mL) for DHA with top tertile levels of 151 μg/mL (IQR, 132-181 μg/mL) and 118 μg/mL (IQR, 102-143 μg/mL), respectively. Compared with corn oil, the adjusted hazard ratios for the highest tertile of achieved plasma levels were 0.98 (95% CI, 0.83-1.16; P = .81) for EPA, and 1.02 (95% CI, 0.86-1.20; P = .85 for DHA. Sensitivity analyses based on changes in plasma and red blood cell levels of EPA and DHA and primary and secondary prevention subgroups showed similar results.

Conclusions And Relevance: Among patients treated with ω-3 CA, the highest achieved tertiles of EPA and DHA were associated with neither benefit nor harm in patients at high cardiovascular risk.

Trial Registration: ClinicalTrials.gov Identifier: NCT02104817.
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http://dx.doi.org/10.1001/jamacardio.2021.1157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126992PMC
May 2021

CD11c participates in triggering acute graft-versus-host disease during bone marrow transplantation.

Immunology 2021 Sep 2;164(1):148-160. Epub 2021 Jun 2.

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.

CD11c is a canonical dendritic cell (DC) marker with poorly defined functions in the immune system. Here, we found that blocking CD11c on human peripheral blood mononuclear cell-derived DCs (MoDCs) inhibited the proliferation of CD4 T cells and the differentiation into IFN-γ-producing T helper 1 (Th1) cells, which were critical in acute graft-versus-host disease (aGVHD) pathogenesis. Using allogeneic bone marrow transplantation (allo-BMT) murine models, we consistently found that CD11c-deficient recipient mice had alleviated aGVHD symptoms for the decreased IFN-γ-expressing CD4 Th1 cells and CD8 T cells. Transcriptional analysis showed that CD11c participated in several immune regulation functions including maintaining antigen presentation of APCs. CD11c-deficient bone marrow-derived DCs (BMDCs) impaired the antigen presentation function in coculture assay. Mechanistically, CD11c interacted with MHCII and Hsp90 and participated in the phosphorylation of Akt and Erk1/2 in DCs after multiple inflammatory stimulations. Therefore, CD11c played crucial roles in triggering aGVHD and might serve as a potential target for the prevention and treatment of aGVHD.
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http://dx.doi.org/10.1111/imm.13350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358721PMC
September 2021
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