Identifying Familial Hypercholesterolemia Using a Blood Donor Screening Program With More Than 1 Million Volunteer Donors.

Importance: Familial hypercholesterolemia is an autosomal-dominant disorder that often causes premature coronary artery disease. Unfortunately, familial hypercholesterolemia remains largely undiagnosed.

Objective: To estimate the prevalence of familial hypercholesterolemia in a population of blood donors.

Antithrombotic treatment gap among patients with atrial fibrillation and type 2 diabetes.

Background: We investigated the use of different antithrombotic therapies at baseline among patients with a history of atrial fibrillation (AF), type 2 diabetes, and established atherosclerotic cardiovascular disease (ASCVD) enrolled in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS).

Methods: TECOS participants with a history of AF were stratified by CHADS-VASc score and their antithrombotic use evaluated. Cox proportional hazards models were employed to explore possible associations between history of AF and prespecified clinical outcomes after adjusting for key baseline characteristics.

The pericyte microenvironment during vascular development.

Vascular pericytes provide critical contributions to the formation and integrity of the blood vessel wall within the microcirculation. Pericytes maintain vascular stability and homeostasis by promoting endothelial cell junctions and depositing extracellular matrix (ECM) components within the vascular basement membrane, among other vital functions. As their importance in sustaining microvessel health within various tissues and organs continues to emerge, so does their role in a number of pathological conditions including cancer, diabetic retinopathy, and neurological disorders.

Age at Diagnosis of Type 2 Diabetes Mellitus and Associations With Cardiovascular and Mortality Risks.

Background: Risk of cardiovascular disease (CVD) and mortality for patients with versus without type 2 diabetes mellitus (T2DM) appears to vary by the age at T2DM diagnosis, but few population studies have analyzed mortality and CVD outcomes associations across the full age range.

Methods: With use of the Swedish National Diabetes Registry, everyone with T2DM registered in the Registry between 1998 and 2012 was included. Controls were randomly selected from the general population matched for age, sex, and county.

Dapagliflozin and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus and Previous Myocardial Infarction.

Background: Sodium glucose transporter-2 inhibitors reduce the risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus and a history of atherosclerotic cardiovascular disease. Because of their baseline risk, patients with previous myocardial infarction (MI) may derive even greater benefit from sodium glucose transporter-2 inhibitor therapy.

Methods: DECLARE-TIMI 58 (Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58) randomized 17 160 patients with type 2 diabetes mellitus and either established atherosclerotic cardiovascular disease (n=6974) or multiple risk factors (n=10 186) to dapagliflozin versus placebo.

Effect of Dapagliflozin on Heart Failure and Mortality in Type 2 Diabetes Mellitus.

Background: In DECLARE-TIMI 58 (Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58), the sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the composite end point of cardiovascular death/hospitalization for heart failure (HHF) in a broad population of patients with type 2 diabetes mellitus. However, the impact of baseline left ventricular ejection fraction (EF) on the clinical benefit of sodium-glucose cotransporter 2 inhibition is unknown.

Methods: In the DECLARE-TIMI 58 trial, baseline heart failure (HF) status was collected from all patients, and EF was collected when available.

Cardiovascular safety and lower severe hypoglycaemia of insulin degludec versus insulin glargine U100 in patients with type 2 diabetes aged 65 years or older: Results from DEVOTE (DEVOTE 7).

Aims: The aim of this study was to describe the risks of cardiovascular (CV) events and severe hypoglycaemia with insulin degludec (degludec) vs insulin glargine 100 units/mL (glargine U100) in patients with type 2 diabetes (T2D) aged 65 years or older.

Materials And Methods: A total of 7637 patients in the DEVOTE trial, a treat-to-target, randomized, double-blind trial evaluating the CV safety of degludec vs glargine U100, were divided into three age groups (50-64 years, n = 3682; 65-74 years, n = 3136; ≥75 years, n = 819). Outcomes by overall age group and randomized treatment differences were analysed for major adverse cardiovascular events (MACE), all-cause mortality, severe hypoglycaemia and serious adverse events (SAEs).

Relative Prognostic Importance and Optimal Levels of Risk Factors for Mortality and Cardiovascular Outcomes in Type 1 Diabetes Mellitus.

Background: The strength of association and optimal levels for risk factors related to excess risk of death and cardiovascular outcomes in type 1 diabetes mellitus have been sparsely studied.

Methods: In a national observational cohort study from the Swedish National Diabetes Register from 1998 to 2014, we assessed relative prognostic importance of 17 risk factors for death and cardiovascular outcomes in individuals with type 1 diabetes mellitus. We used Cox regression and machine learning analyses.

Lower rates of cardiovascular events and mortality associated with liraglutide use in patients treated with basal insulin: A DEVOTE subanalysis (DEVOTE 10).

Aim: To compare the associations between concomitant liraglutide use versus no liraglutide use and the risk of major adverse cardiovascular events (MACE) and all-cause mortality among patients receiving basal insulin (either insulin degludec [degludec] or insulin glargine 100 units/mL [glargine U100]) in the Trial Comparing Cardiovascular Safety of Insulin Degludec versus Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events (DEVOTE).

Materials And Methods: Patients with type 2 diabetes and high cardiovascular risk were randomized 1:1 to degludec or glargine U100. Hazard ratios for MACE/mortality were calculated using a Cox regression model adjusted for treatment and time-varying liraglutide use at any time during the trial, without interaction.

Comparison of the Effects of Glucagon-Like Peptide Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors for Prevention of Major Adverse Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus.

Background: Glucagon-like peptide 1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) have emerged as 2 new classes of antihyperglycemic agents that also reduce cardiovascular risk. The relative benefits in patients with and without established atherosclerotic cardiovascular disease for different outcomes with these classes of drugs remain undefined.

Methods: We performed a systematic review and trial-level meta-analysis of GLP1-RA and SGLT2i cardiovascular outcomes trials using the PubMed and EMBASE databases (Excerpta Medica Database).

Prevalence of cerebral palsy, intellectual disability, hearing loss, and blindness, National Health Interview Survey, 2009-2016.

Background: Developmental disabilities are present in a significant proportion of US children. Surveillance of developmental disabilities is crucial for monitoring population trends, guiding research into risk factors, and informing resource allocation.

Objective/hypothesis: We examined overall prevalence, prevalence by demographic characteristics, and trends over time for cerebral palsy (CP), intellectual disability (ID), moderate to severe hearing loss (MSHL), and blindness.

FDA guidance on antihyperglyacemic therapies for type 2 diabetes: One decade later.

In 2008, the US Food and Drug Administration (FDA) issued a guidance to industry statement concerning evaluation of the cardiovascular (CV) safety of new antihyperglycaemic therapies for type 2 diabetes. Fifteen CV outcome trials assessing three novel classes of antihyperglycaemic therapies, DPP-4 inhibitors, GLP-1 receptor agonists and SGLT-2 inhibitors, were completed by the end of 2018 and several others are ongoing. In addition, one comparative insulin trial also has been completed.

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders. They are heritable and etiologically related behaviors that have been resistant to gene discovery efforts. In sample sizes up to 1.

Expression of novel long noncoding RNAs defines virus-specific effector and memory CD8 T cells.

In response to viral infection, CD8 T cells undergo expansion and differentiate into distinct classes of effector cells. After clearance of the virus, a small population of long-lived memory cells persists. Comprehensive studies have defined the protein-coding transcriptional changes associated with this process.

Empagliflozin Reduced Mortality and Hospitalization for Heart Failure Across the Spectrum of Cardiovascular Risk in the EMPA-REG OUTCOME Trial.

Background: In the EMPA-REG OUTCOME trial (BI 10773 [Empagliflozin] Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) in patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease, in comparison with placebo, empagliflozin reduced the risks of 3-point major adverse cardiovascular events (3-point MACE), cardiovascular and all-cause death, and hospitalization for heart failure. We investigated whether these effects varied across the spectrum of baseline cardiovascular risk.

Methods: Cardiovascular death, all-cause mortality, 3-point MACE, and hospitalization for heart failure in the pooled empagliflozin and placebo groups were analyzed in subgroups by prior myocardial infarction and stroke at baseline, and by estimated baseline cardiovascular risk based on the 10-point TIMI (Thrombolysis In Myocardial Infarction) Risk Score for Secondary Prevention.

Lorcaserin and Renal Outcomes in Obese and Overweight Patients in the CAMELLIA-TIMI 61 Trial.

Background: Obesity is thought to increase renal hyperfiltration, thereby increasing albuminuria and the progression of renal disease. The effect of pharmacologically mediated weight loss on renal outcomes is not well-described. Lorcaserin, a selective serotonin 2C receptor agonist that promotes appetite suppression, led to sustained weight loss without any increased risk for major adverse cardiovascular (CV) events in the CAMELLIA-TIMI 61 trial (Cardiovascular and Metabolic Effects of Lorcaserin in Overweight and Obese Patients-Thrombolysis in Myocardial Infarction 61).

Linagliptin Effects on Heart Failure and Related Outcomes in Individuals With Type 2 Diabetes Mellitus at High Cardiovascular and Renal Risk in CARMELINA.

Background: Individuals with type 2 diabetes mellitus are at increased risk for heart failure (HF), particularly those with coexisting atherosclerotic cardiovascular disease and/or kidney disease. Some but not all dipeptidyl peptidase-4 inhibitors have been associated with increased HF risk. We performed secondary analyses of HF and related outcomes with the dipeptidyl peptidase-4 inhibitor linagliptin versus placebo in CARMELINA (The Cardiovascular and Renal Microvascular Outcome Study With Linagliptin), a cardiovascular outcomes trial that enrolled participants with type 2 diabetes mellitus and atherosclerotic cardiovascular disease and/or kidney disease.

Long-Term Association of Low-Density Lipoprotein Cholesterol With Cardiovascular Mortality in Individuals at Low 10-Year Risk of Atherosclerotic Cardiovascular Disease.

Background: The associations of low-density lipoprotein cholesterol (LDL-C) with cardiovascular disease (CVD) and coronary heart disease mortality in an exclusively low estimated 10-year risk group are not well delineated. We sought to determine the long-term associations of various LDL-C and non-high-density lipoprotein cholesterol (HDL-C) thresholds and CVD and coronary heart disease mortality in a large, low 10-year risk cohort.

Methods: The study sample included participants of the CCLS (Cooper Center Longitudinal Study) without a history of CVD or diabetes mellitus and defined as low risk (<7.

Fasiglifam-Induced Liver Injury in Patients With Type 2 Diabetes: Results of a Randomized Controlled Cardiovascular Outcomes Safety Trial.

Objective: To evaluate the cardiovascular (CV) safety of fasiglifam, a first-in-man G-protein-coupled receptor 40 (GPR40) agonist, in patients with type 2 diabetes.

Research Design And Methods: A phase 3 multicenter randomized double-blind placebo-controlled two-arm trial was intended to randomize 5,000 participants with type 2 diabetes at high CV risk to fasiglifam or placebo. The primary objective of the trial was to rule out an upper noninferiority bound >1.

SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials.

Background: The magnitude of effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on specific cardiovascular and renal outcomes and whether heterogeneity is based on key baseline characteristics remains undefined.

Methods: We did a systematic review and meta-analysis of randomised, placebo-controlled, cardiovascular outcome trials of SGLT2i in patients with type 2 diabetes. We searched PubMed and Embase for trials published up to Sept 24, 2018.

Heart Failure Epidemiology in Patients With Diabetes Mellitus Without Coronary Heart Disease.

Background: Epidemiology of patients with comorbid heart failure (HF) and diabetes mellitus (DM) without coronary heart disease (CHD) is not well described.

Methods And Results: We assessed HF incidence and outcomes in 2896 participants of the Health ABC Study (age 74.0 ± 3.

Effect of Linagliptin vs Placebo on Major Cardiovascular Events in Adults With Type 2 Diabetes and High Cardiovascular and Renal Risk: The CARMELINA Randomized Clinical Trial.

Importance: Type 2 diabetes is associated with increased cardiovascular (CV) risk. Prior trials have demonstrated CV safety of 3 dipeptidyl peptidase 4 (DPP-4) inhibitors but have included limited numbers of patients with high CV risk and chronic kidney disease.

Objective: To evaluate the effect of linagliptin, a selective DPP-4 inhibitor, on CV outcomes and kidney outcomes in patients with type 2 diabetes at high risk of CV and kidney events.