Epigenome-Wide Association Study for All-Cause Mortality in a Cardiovascular Cohort Identifies Differential Methylation in Castor Zinc Finger 1 ().

Background DNA methylation is implicated in many chronic diseases and may contribute to mortality. Therefore, we conducted an epigenome-wide association study (EWAS) for all-cause mortality with whole-transcriptome data in a cardiovascular cohort (CATHGEN [Catheterization Genetics]). Methods and Results Cases were participants with mortality≥7 days postcatheterization whereas controls were alive with≥2 years of follow-up.

Short-Term Changes in Cardiorespiratory Fitness in Response to Exercise Training and the Association with Long-Term Cardiorespiratory Fitness Decline: The STRRIDE Reunion Study.

Background Substantial heterogeneity exists in the cardiorespiratory fitness (CRF) change in response to exercise training, and its long-term prognostic implication is not well understood. We evaluated the association between the short-term supervised training-related changes in CRF and CRF levels 10 years later. Methods and Results STRRIDE (Studies of a Targeted Risk Reduction Intervention Through Defined Exercise) trial participants who were originally randomized to exercise training for 8 months and participated in the 10-year follow-up visit were included.

Patient-Reported Reasons for Declining or Discontinuing Statin Therapy: Insights From the PALM Registry.

Background Many adults eligible for statin therapy for cardiovascular disease prevention are untreated. Our objective was to investigate patient-reported reasons for statin underutilization, including noninitiation, refusal, and discontinuation. Methods and Results This study included the 5693 adults recommended for statin therapy in the PALM (Patient and Provider Assessment of Lipid Management) registry.

Rethinking Cognitive Impairment in the Management of Older Patients With Cardiovascular Disease.

See Article by Gu et al.

Relationship Between Hospital Characteristics and Early Adoption of Angiotensin-Receptor/Neprilysin Inhibitor Among Eligible Patients Hospitalized for Heart Failure.

Background The angiotensin-receptor/neprilysin inhibitor ( ARNI ) sacubitril/valsartan reduces hospitalization and mortality for patients with heart failure with reduced ejection fraction. However, adoption of ARNI into clinical practice has been slow. Factors influencing use of ARNI have not been fully elucidated.

Association of Primary Care Providers' Beliefs of Statins for Primary Prevention and Statin Prescription.

Background The 2013 American College of Cardiology/American Heart Association Cholesterol Treatment Guideline increased the number of primary prevention patients eligible for statin therapy, yet uptake of these guidelines has been modest. Little is known of how primary care provider ( PCP ) beliefs influence statin prescription. Methods and Results We surveyed 164 PCP s from a community-based North Carolina network in 2017 about statin therapy.

Emergency Consent: Patients' and Surrogates' Perspectives on Consent for Clinical Trials in Acute Stroke and Myocardial Infarction.

Background Emergent informed consent for clinical trials in acute myocardial infarction (AMI) and stroke is challenging. The role and value of consent are controversial, and insufficient data exist regarding patients' and surrogates' experiences. Methods and Results We conducted structured interviews with patients (or surrogates) enrolled in AMI or acute stroke trials at 6 sites between 2011 and 2016.

The practice of universal screening for Lynch syndrome in newly diagnosed endometrial carcinoma.

Background: Lynch syndrome (LS) accounts for 5% of all endometrial cancer (EC) cases and 4% of all lifetime risk of developing colorectal cancer. While current guidelines recommend LS screening for all patients with newly diagnosed colorectal cancer, there is no such guideline for screening patients with EC.

Discussion: This review addresses LS screening and discusses algorithms for testing patients in the setting of newly diagnosed EC.

Body Mass Index From Early-, Mid-, and Older-Adulthood and Risk of Heart Failure and Atherosclerotic Cardiovascular Disease: MESA.

Background Obesity contributes significantly to risk of atherosclerotic cardiovascular disease (ASCVD) and especially for heart failure (HF). An elevated body mass index (BMI) in older adults might not carry the same risk as in younger adults, but measured weights at other lifetime points are often not available. We determined the associations of self-reported weights from early- and mid-adulthood, after accounting for measured weight at older age, with incident HF/ASCVD risk.

Effect of Once-Weekly Exenatide on Clinical Outcomes According to Baseline Risk in Patients With Type 2 Diabetes Mellitus: Insights From the EXSCEL Trial.

Background In the EXSCEL (Exenatide Study of Cardiovascular Event Lowering), exenatide once-weekly resulted in a nonsignificant reduction in major adverse cardiovascular events ( MACEs ) and a nominal 14% reduction in all-cause mortality in 14 752 patients with type 2 diabetes mellitus (T2 DM ) with and without cardiovascular disease. Whether patients at increased risk for events experienced a comparatively greater treatment benefit with exenatide is unknown. Methods and Results In the EXSCEL population, we created risk scores for MACEs and all-cause mortality using step-wise selection of baseline characteristics.

Porphyrin-Based SOD Mimic MnTnBu OE -2-PyP Inhibits Mechanisms of Aortic Valve Remodeling in Human and Murine Models of Aortic Valve Sclerosis.

Background Aortic valve sclerosis ( AVS c), the early asymptomatic presentation of calcific aortic valve (AV) disease, affects 25% to 30% of patients aged >65 years. In vitro and ex vivo experiments with antioxidant strategies and antagonists of osteogenic differentiation revealed that AVS c is reversible. In this study, we characterized the underlying changes in the extracellular matrix architecture and valve interstitial cell activation in AVSc and tested in vitro and in vivo the activity of a clinically approved SOD (superoxide dismutase) mimic and redox-active drug MnTnBu OE -2-PyP ( BMX -001).

Selective Serotonin Reuptake Inhibitors and Bleeding Risk in Anticoagulated Patients With Atrial Fibrillation: An Analysis From the ROCKET AF Trial.

Background There is concern that selective serotonin reuptake inhibitors ( SSRI s) substantially increase bleeding risk in patients taking anticoagulants. Methods and Results We studied 737 patients taking SSRI s in the ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Embolism and Stroke Trial in Atrial Fibrillation) trial of rivaroxaban compared with warfarin for the prevention of stroke/systemic embolism in patients with atrial fibrillation. These patients were propensity score matched 1:1 to 737 patients not taking SSRI s.

Pharmacotherapy for Atrial Fibrillation in Patients With Chronic Kidney Disease: Insights From ORBIT-AF.

Background Chronic kidney disease ( CKD ) is a common comorbidity in patients with atrial fibrillation. The presence of CKD complicates drug selection for stroke prevention and rhythm control. Methods and Results Patients enrolled in ORBIT AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) with baseline renal function and follow-up data were included (N=9019).

Shock Index Predicts Patient-Related Clinical Outcomes in Stroke.

Background The prognostic value of shock index ( SI ), heart rate divided by systolic blood pressure, in stroke for clinical outcomes other than mortality is not well understood. Methods and Results We examined the Get With The Guidelines-Stroke ( GWTG -Stroke) data to explore the usefulness of SI in predicting in-hospital outcomes in 425 808 acute stroke cases (mean age: 71.0±14.

Association of Gout With Long-Term Cardiovascular Outcomes Among Patients With Obstructive Coronary Artery Disease.

Background Epidemiological studies demonstrating a relationship between gout and cardiovascular disease are older and predate modern cardiovascular preventive therapy. We assessed the contemporary association between gout and cardiovascular disease in patients with obstructive coronary artery disease. Methods and Results Data were from the Duke Databank for Cardiovascular Diseases, which followed up patients undergoing cardiac catheterization with obstructive coronary artery disease at Duke University Medical Center (1998-2013).

Clinical endpoints and adaptive clinical trials in precirrhotic nonalcoholic steatohepatitis: Facilitating development approaches for an emerging epidemic.

Due to the increasing prevalence of nonalcoholic steatohepatitis (NASH) and its associated health burden, there is a high need to develop therapeutic strategies for patients with this disease. Unfortunately, its long and asymptomatic natural history, the uncertainties about disease progression, the fact that most patients are undiagnosed, and the requirement for sequential liver biopsies create substantial challenges for clinical development. Adaptive design methods are increasingly used in clinical research as they provide the flexibility and efficiency for identifying potential signals of clinical benefit of the test treatment under investigation and make prompt preplanned adaptations without undermining the validity or integrity of the trial.

Protocol for Moving On: a randomized controlled trial to increase outcome expectations and exercise among breast cancer survivors.

Aim: The aim of this study was to test the feasibility and fidelity of an intervention, Moving On, aimed to increase outcome expectations OEs (i.e. what one expects to obtain or avoid as a result of a behaviour) and exercise among breast cancer survivors.

Perinatal western-type diet and associated gestational weight gain alter postpartum maternal mood.

Introduction: The role of perinatal diet in postpartum maternal mood disorders, including depression and anxiety, remains unclear. We investigated whether perinatal consumption of a Western-type diet (high in fat and branched-chain amino acids [BCAA]) and associated gestational weight gain (GWG) cause serotonin dysregulation in the central nervous system (CNS), resulting in postpartum depression and anxiety (PPD/A).

Methods: Mouse dams were fed one of four diets (high-fat/high BCAA, low-fat/high BCAA, high-fat, and low-fat) prior to mating and throughout gestation and lactation.