Remnant Cholesterol: Quantification, Concentrations by Sex and Age, and Risk of Ischemic Heart Disease.

Background: Observational and genetic causal studies have shown an association between high concentrations of remnant cholesterol and increased risk of ischemic heart disease. However, findings from randomized intervention trials that reduced plasma triglycerides, a surrogate marker of remnant cholesterol, have been conflicting. The exact mechanisms by which remnant cholesterol contributes to atherosclerosis and, ultimately, ischemic heart disease remain incompletely understood.

Healthcare utilization associated with obesity management in Ontario, Canada.

This study aimed to describe the characteristics, healthcare resources utilized and costs incurred by adults receiving publicly funded obesity care in Ontario, Canada. People living with obesity who first visited Wharton Medical Clinic, a weight and diabetes management clinic in Ontario, between 2015 and 2018 were identified. Pseudoanonymized data were linked to administrative databases to understand healthcare utilization and costs borne by the public payer over 3 years.

Efficacy and safety of once-weekly semaglutide 2·4 mg versus placebo in people with obesity and prediabetes (STEP 10): a randomised, double-blind, placebo-controlled, multicentre phase 3 trial.

Background: There are currently limited data regarding the effect of semaglutide 2·4 mg in individuals with obesity and prediabetes in clinical trials. We aimed to assess the efficacy and safety of semaglutide 2·4 mg for weight management and glycaemic control in participants with obesity and prediabetes.

Methods: STEP 10 was a randomised, double-blind, parallel-group, phase 3 trial done across 30 trial sites in Canada, Denmark, Finland, Spain, and the UK and included participants aged 18 years or older with a BMI of 30 kg/m or higher and prediabetes according to UK National Institute for Health and Care Excellence criteria (defined as having at least one of the following at screening: HbA of 6·0-6·4% [42-47 mmol/mol] or fasting plasma glucose [FPG] of 5·5-6·9 mmol/L).

Obesity, Cardiorenal Comorbidities, and Risk of Hospitalization in Patients With Heart Failure With Preserved Ejection Fraction.

Objective: To compare clinical features of patients with obesity-related heart failure (HF) with preserved ejection fraction (HFpEF) with those of patients with similar body mass index (BMI) but no HF and to examine the association between degree of obesity and risk for hospitalizations.

Methods: This was a retrospective analysis of 22,750 adults from a large US electronic health care data set (January 1, 2012, through July 31, 2019), including 4975 with HFpEF. Baseline characteristics were compared between patients with HFpEF and a control group matched on BMI, age, sex, and year of BMI record.

Hypertriglyceridemia-Associated Pancreatitis: New Concepts and Potential Mechanisms.

Background: Triglycerides are a major source of energy, while high plasma triglycerides are a risk factor for various diseases and premature death. Severely elevated plasma triglycerides are a well-established cause of acute pancreatitis with high mortality, likely due to the presence of elevated levels of chylomicrons and large very low-density lipoproteins in plasma. As markedly elevated levels of these very large lipoproteins are not generally found in mild to moderate hypertriglyceridemia, this was previously not regarded as a cause or marker of increased risk of acute pancreatitis.

Association between body mass index, weight loss and the chance of pregnancy in women with polycystic ovary syndrome and overweight or obesity: a retrospective cohort study in the UK.

Study Question: What are the associations between baseline BMI (Study 1) and change in body weight (Study 2) with the likelihood of pregnancy in women with polycystic ovary syndrome (PCOS).

Summary Answer: In women with PCOS, higher baseline BMI was associated with a lower chance of pregnancy; however, weight loss was associated with an increased chance of pregnancy versus maintaining a stable weight or gaining weight.

What Is Known Already: Two studies in large cohorts of Danish women with the intention to become pregnant showed a decline in fecundability ratios with higher BMI.

Elevated LDL Triglycerides and Atherosclerotic Risk.

Background: It is unclear whether elevated low-density lipoprotein (LDL) triglycerides are associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD).

Objectives: This study tested the hypothesis that elevated LDL triglycerides are associated with an increased risk of ASCVD and of each ASCVD component individually.

Methods: The study investigators used the Copenhagen General Population Study, which measured LDL triglycerides in 38,081 individuals with a direct automated assay (direct LDL triglycerides) and in another 30,208 individuals with nuclear magnetic resonance (NMR) spectroscopy (NMR LDL triglycerides).

Small Dense Low-Density Lipoprotein Cholesterol and Ischemic Stroke.

Objective: For decades, it has been suggested that small dense low-density lipoprotein (sdLDL) may be particularly atherogenic. High levels of sdLDL are associated with an increased risk of ischemic heart disease; however, the association of sdLDL with ischemic stroke has not been explored in a large prospective study on the general population. We tested the hypothesis that high sdLDL cholesterol levels are associated with an increased risk of ischemic stroke.

Changes in Glucose Metabolism and Glycemic Status With Once-Weekly Subcutaneous Semaglutide 2.4 mg Among Participants With Prediabetes in the STEP Program.

Objective: This analysis of 3,375 adults with overweight/obesity across the Semaglutide Treatment Effect in People with obesity (STEP) 1, 3, and 4 trials evaluated whether more participants with prediabetes had normoglycemia after 68 weeks' treatment with once-weekly semaglutide 2.4 mg plus lifestyle intervention versus placebo and assessed changes in glucose metabolism in participants with prediabetes.

Research Design And Methods: STEP 1, 3, and 4 were phase 3, 68-week, randomized, placebo-controlled, multinational trials; STEP 4 had a 20-week semaglutide run-in and 48-week randomized period.

Low and high pancreatic amylase is associated with pancreatic cancer and chronic pancreatitis.

Incidences of pancreatic cancer and acute and chronic pancreatitis are rising globally, and often no curative treatment is available at the time of diagnosis. We tested the hypothesis that low and high plasma concentrations of pancreatic amylase are associated with increased risk of pancreatic cancer, acute pancreatitis, and chronic pancreatitis in the general population. We included 101,765 individuals (55% women) aged 20-100 years from the Copenhagen General Population Study with baseline measurements of plasma pancreatic amylase.

Directly measured vs. calculated remnant cholesterol identifies additional overlooked individuals in the general population at higher risk of myocardial infarction.

Aims: We tested the hypothesis that high directly measured remnant cholesterol is associated with increased risk of ischaemic heart disease (IHD) and myocardial infarction (MI) in the general population. We also explored whether directly measured vs. calculated remnant cholesterol is superior in identifying individuals at increased risk.

VLDL Cholesterol Accounts for One-Half of the Risk of Myocardial Infarction Associated With apoB-Containing Lipoproteins.

Background: Plasma apolipoprotein B (apoB) is a composite measure of all apoB-containing lipoproteins causing atherosclerotic cardiovascular disease; however, it is unclear which fraction of risk is explained by cholesterol and triglycerides, respectively, in very low-density lipoproteins (VLDLs).

Objectives: The authors tested the hypothesis that VLDL cholesterol and triglycerides each explain part of the myocardial infarction risk from apoB-containing lipoproteins.

Methods: Nested within 109,751 individuals from the Copenhagen General Population Study, the authors examined 25,480 subjects free of lipid-lowering therapy and myocardial infarction at study entry.

Novel Insights From Human Studies on the Role of High-Density Lipoprotein in Mortality and Noncardiovascular Disease.

The vast majority of research about HDL (high-density lipoprotein) has for decades revolved around the possible role of HDL in atherosclerosis and its therapeutic potential within cardiovascular disease prevention; however, failures with therapies aimed at increasing HDL cholesterol has left questions as to what the role and function of HDL in human health and disease is. Recent observational studies have further shown that extreme high HDL cholesterol is associated with high mortality leading to speculations that HDL could in some instances be harmful. In addition, evidence from observational, and to a lesser extent genetic studies has emerged indicating that HDL might be associated with the development of other major noncardiovascular diseases, such as infectious disease, autoimmune disease, cancer, type 2 diabetes, kidney disease, and lung disease.

Genetic Variants Associated With Increased Plasma Levels of Triglycerides, via Effects on the Lipoprotein Lipase Pathway, Increase Risk of Acute Pancreatitis.

Background & Aims: Almost one third of adults in the West have increased plasma levels of triglycerides. Even mild to moderate hypertriglyceridemia (2-10 mmol/L or 177-886 mg/dL) is associated with an increased risk of acute pancreatitis. However, it is not clear whether hypertriglyceridemia is a cause or result of acute pancreatitis.

Worldwide Prevalence of Familial Hypercholesterolemia: Meta-Analyses of 11 Million Subjects.

Background: Despite the greater prevalence of familial hypercholesterolemia (FH) in subjects with ischemic heart disease (IHD), premature IHD, and severe hypercholesterolemia (low-density lipoprotein ≥190 mg/dl), overall prevalence estimates are not available.

Objectives: The aim of this study was to provide worldwide estimates of FH prevalence in subjects with IHD, premature IHD, and severe hypercholesterolemia compared with those in the general population.

Methods: In this systematic review and meta-analyses, Embase, PubMed, and the Web of Science were searched until June 3, 2019, for peer-reviewed papers and conference abstracts reporting heterozygous FH prevalence in nonfounder populations, revealing 104 studies eligible for inclusion.

Low High-Density Lipoprotein Cholesterol to Monitor Long-Term Average Increased Triglycerides.

Context: Increased triglyceride-rich remnants represent a causal risk factor for ischemic cardiovascular disease.

Objective: We tested the hypothesis that low high-density lipoprotein (HDL) cholesterol can be used to monitor long-term high triglycerides/remnant cholesterol, just as high hemoglobin A1c (HbA1c) can be used to monitor long-term high glucose levels.

Design, Setting, Participants, And Interventions: We studied cross-sectionally 108 731 individuals, dynamically 1313 individuals with lipid measurement at 10 repeated visits, short-term 305 individuals during a fat load, and long-term 10 479 individuals with 2 lipid measurements 10 years apart.

Body Mass Index, Triglycerides, and Risk of Acute Pancreatitis: A Population-Based Study of 118 000 Individuals.

Objective: The incidence of acute pancreatitis is rising worldwide and currently no curative treatment exists. Clarification of preventable risk factors is important for the reduction of morbidity and mortality from acute pancreatitis. In this study, we tested the hypothesis that the risk of acute pancreatitis associated with body mass index (BMI) is partly mediated through elevated triglycerides.

Lipoprotein(a)-Lowering by 50 mg/dL (105 nmol/L) May Be Needed to Reduce Cardiovascular Disease 20% in Secondary Prevention: A Population-Based Study.

Objective: High Lp(a) (lipoprotein[a]) cause cardiovascular disease (CVD) in a primary prevention setting; however, it is debated whether high Lp(a) lead to recurrent CVD events. We tested the latter hypothesis and estimated the Lp(a)-lowering needed for 5 years to reduce CVD events in a secondary prevention setting. Approach and Results: From the CGPS (Copenhagen General Population Study; 2003-2015) of 58 527 individuals with measurements of Lp(a), 2527 aged 20 to 79 with a history of CVD were studied.

Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A third of nonfasting plasma cholesterol is in remnant lipoproteins: Lipoprotein subclass profiling in 9293 individuals.

Background And Aims: Increased concentrations of calculated remnant cholesterol in triglyceride-rich lipoproteins are observationally and genetically, causally associated with increased risk of ischemic heart disease; however, when measured directly, the fraction of plasma cholesterol present in remnant particles is unclear. We tested the hypothesis that a major fraction of plasma cholesterol is present in remnant lipoproteins in individuals in the general population.

Methods: We examined 9293 individuals from the Copenhagen General Population Study using nuclear magnetic resonance spectroscopy measurements of total cholesterol, free- and esterified cholesterol, triglycerides, phospholipids, and particle concentration.

How To Identify Familial Premature Myocardial Infarction: Comparing Approaches To Identify Familial Hypercholesterolemia.

Context: How best to identify families with premature myocardial infarction is unclear.

Objective: We compared approaches to identify familial premature myocardial infarction in the general population using different familial hypercholesterolemia (FH) criteria and low-density lipoprotein (LDL) cholesterol cut-points.

Design And Setting: Clinical and mutation criteria for FH and LDL cholesterol cut-points were applied for identification of familial premature myocardial infarction in 106,732 individuals from the Copenhagen General Population Study.

Low HDL Cholesterol and High Risk of Autoimmune Disease: Two Population-Based Cohort Studies Including 117341 Individuals.

Background: HDL is quantitatively the most important lipoprotein in most species and mechanistic evidence points toward a role for HDL in normal immune function. We tested the hypothesis that concentrations of HDL cholesterol are associated with risk of autoimmune disease.

Methods: From 2 studies of the general population-the Copenhagen General Population Study and the Copenhagen City Heart study-we included 107954 and 9387 individuals with baseline measurements of HDL cholesterol.

Remnant cholesterol and risk of ischemic stroke in 112,512 individuals from the general population.

Objective: High remnant cholesterol concentrations are associated with high risk of ischemic heart disease, but whether this is also the case for ischemic stroke is unknown. We tested the hypothesis that high remnant cholesterol concentrations are associated with increased risk of ischemic stroke in the general population.

Methods: A total of 102,964 individuals from the Copenhagen General Population Study with information on remnant cholesterol at baseline in 2003-2015 were included in a prospective, observational association study.