Alpha-1 antitrypsin deficiency and risk of sleep apnea: a nationwide cohort study.

Objectives: α-Antitrypsin deficiency is a disease characterized by increased neutrophil elastase activity leading to tissue getting less elastic and robust. It is known that if tissue in the pharynx becomes less elastic and robust, it could contribute to obstructive sleep apnea. This paper seeks to investigate whether patients with α-antitrypsin deficiency have an increased risk of sleep apnea.

Discordance analyses comparing LDL cholesterol, Non-HDL cholesterol, and apolipoprotein B for cardiovascular risk estimation.

For decades, studies have tried to identify the cholesterol marker that best reflects risk of atherosclerotic cardiovascular disease(ASCVD). Comparing low-density-lipoprotein(LDL) cholesterol, non-high-density-lipoprotein(non-HDL) cholesterol, and apolipoprotein B(apoB) as ASCVD risk markers has been challenged by high correlation between them. Thus, discordance analyses, directly addressing disagreements between the cholesterol markers, have emerged.

Venous thromboembolism associated with severe dyspnea and asthma in 21,205 adults from the Danish population.

Background: Long-term consequences after a pulmonary embolism include lung function deficits, dyspnea, and chronic thromboembolic pulmonary hypertension. Recent studies suggest patients who experience pulmonary embolism may also be at increased risk of asthma.

Methods: We tested the hypothesis that individuals with pulmonary embolism or deep vein thrombosis (venous thromboembolism) have lower lung function, or higher risks of dyspnea and asthma using data from 21,205 random adults from the Danish General Suburban Population Study.

Cardiovascular diseases and risk of dementia in the general population.

Aims: Cardiovascular diseases (CVDs) have been linked to increased risk of dementia in observational studies, whereas genetic studies have yielded inconsistent findings. We aimed to determine whether nine CVDs are causally associated with the risk of all-cause dementia, Alzheimer's disease, and vascular dementia.

Methods: We performed time-dependent Cox regression analyses in three prospective cohorts, the Copenhagen City Heart Study (N=10,373), the Copenhagen General Population Study (N=101,582), and the UK Biobank (N=377,706), and meta-analyzed individual estimates.

Challenges in Achieving LDL Cholesterol Targets and Novel Approaches to Lipid Lowering.

Low-density lipoprotein cholesterol (LDL-C) is the preeminent target for the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD). Despite the expansive evidence supporting therapeutic reductions in LDL-C with statin therapy, many high-risk patients do not achieve guideline recommended treatment targets resulting in avoidable cardiovascular events and higher healthcare expenditures. Underutilization of effective LDL-C lowering is exacerbated by low adherence to statin therapy even among patients following an acute coronary event.

Diabetes and elevated plasma glucose in heart valve calcification and disease: the Copenhagen General Population Study.

Aim: The only treatment available for aortic valve stenosis is valve replacement, which makes it important to identify modifiable risk factors. We tested the hypotheses that diabetes and elevated plasma glucose are associated with aortic and mitral valve calcification and aortic valve stenosis, and that these associations are explained partly by elevated plasma triglycerides, hypertension, and body mass index.

Methods: In the Copenhagen General Population Study with 110,291 individuals, we evaluated risk of aortic valve stenosis and mitral valve regurgitation from health registers, and in a subset of 12,006 cardiac CT scanned individuals aortic and mitral valve calcification.

Low LDL cholesterol and risk of bacterial and viral infections: observational and Mendelian randomization studies.

Aims: Low levels of LDL cholesterol may be associated with risk of infectious disease. We tested the hypothesis that low LDL cholesterol due to genetic variation in the , , and genes and a polygenic LDL cholesterol score is associated with risk of infectious diseases in the general population.

Methods And Results: Using observational and Mendelian randomization designs, we examined associations of low plasma LDL cholesterol with risk of bacterial and viral infections in 119 805 individuals from the Copenhagen General Population Study/Copenhagen City Heart Study, 468 701 from the UK Biobank, and up to 376 773 from the FinnGen Research Project.

High remnant cholesterol and atherosclerotic cardiovascular disease in healthy women and men ages 70-100.

Aims: High remnant cholesterol has been increasingly recognized as an important risk factor for atherosclerotic cardiovascular disease (ASCVD). However, uncertainty remains regarding this association in old age. The aim of this study was to test the hypothesis that higher remnant cholesterol is associated with higher incidence of ASCVD in healthy women and men aged 70-100.

High ionized calcium in the general population and risk of primary hyperparathyroidism.

Background: Although it is generally held that in otherwise healthy individuals, primary hyperparathyroidism is the most likely cause of persistent hypercalcemia, solid research supporting this assumption is absent. We aimed to examine the relative and absolute risk of primary hyperparathyroidism associated with an incidental high ionized calcium in the general population.

Methods: We used the Danish Copenhagen General Population Study, a prospective cohort study with inclusion in 2003-2015, to investigate the association of ionized calcium on continuous and categorical scales with primary hyperparathyroidism using Cox regression and competing-risk regression.

Prevalence of obesity among adult patients with congenital heart disease: A population-based study.

Introduction: Adults with congenital heart disease (ACHD) are at increased risk of premature atherosclerotic cardiovascular disease. Obesity is an independent risk factor for a number of cardiometabolic diseases including atherosclerotic cardiovascular disease in healthy individuals; however, data on obesity in ACHD are limited. This study examined the prevalence of obesity in ACHD and the possible correlation between obesity and ACHD lesion severity.

Clinical familial hypercholesterolemia - factors influencing diagnosis and cardiovascular risk in the general population.

Background: Individuals with familial hypercholesterolemia (FH) are at high risk of developing cardiovascular disease due to high LDL cholesterol concentrations. Other cardiovascular risk factors may add to this risk.

Methods: We used Dutch Lipid Clinic Network (DLCN) criteria to diagnose FH in 106,865 individuals from the Copenhagen General Population Study.

Expanding the triglyceride range in clinical trials: therapeutic opportunities.

Background And Aims: Guidelines focus on individuals with triglycerides between 2.3 and 5.6 mmol/L (200 and 499 mg/dL).

Small Remnants versus Large Triglyceride-Rich Lipoproteins in Risk of Atherosclerotic Cardiovascular Disease.

Background: Small remnants may penetrate the arterial intima more efficiently compared to large triglyceride-rich lipoproteins (TGRL). We tested the hypothesis that the importance of remnant cholesterol for the risk of atherosclerotic cardiovascular disease (ASCVD) may depend on the size of the remnants and TGRL carrying cholesterol.

Methods: The cholesterol content of small remnants and large TGRL were measured in 25 572 individuals from the Copenhagen General Population Study (2003-2015) and in 222 721 individuals from the UK Biobank (2006-2010) using nuclear magnetic resonance spectroscopy.

Effect of empagliflozin on plasma lipids and lipoproteins in type 2 diabetes and heart failure - Empire HF and SIMPLE.

Objective: Beyond glucose-lowering, sodium-glucose co-transporter 2 (SGLT2) inhibitors have cardioprotective effects with unclear mechanisms. We examined changes in an extensive panel of plasma lipids, lipoproteins, and apolipoproteins and whether these changes were independent of weight loss, hemoglobin A1c, and hematocrit in patients treated with empagliflozin versus placebo to better understand the observed cardioprotective effects.

Methods: Post-hoc analyses of two double-blind, placebo-controlled trials, the Empire HF trial including 190 patients with heart failure and reduced ejection fraction and the SIMPLE trial including 90 patients with type 2 diabetes randomized to, respectively, 10 mg and 25 mg empagliflozin daily or placebo for 12 weeks.

VLDL triglycerides and cholesterol in non-alcoholic fatty liver disease and myocardial infarction.

Background And Aims: Myocardial infarction is a leading cause of death in individuals with non-alcoholic fatty liver disease (NAFLD). The two diseases share elevated very low-density lipoproteins (VLDL) carrying both triglycerides and cholesterol; however, in NAFLD mainly triglycerides accumulate in liver cells while in myocardial infarction mainly cholesterol accumulates in the atherosclerotic plaque. We hypothesized that VLDL triglycerides preferentially associate with risk of NAFLD, while VLDL cholesterol preferentially associates with risk of myocardial infarction.

Ages at coronary heart disease and death in familial hypercholesterolaemia: a Danish nationwide study spanning 44 years.

Background And Aims: Familial hypercholesterolaemia leads to lifelong elevated low-density lipoprotein cholesterol with increased risk of coronary heart disease and pre-mature death. It is unknown whether the prognosis for individuals with familial hypercholesterolaemia has improved over the past four decades as registration of this condition has been limited worldwide. However, in Danish nationwide registries, modified ICD coding has allowed such registration since 1978.

Overweight, obesity, and cardiovascular disease in heterozygous familial hypercholesterolaemia: the EAS FH Studies Collaboration registry.

Background And Aims: Overweight and obesity are modifiable risk factors for atherosclerotic cardiovascular disease (ASCVD) in the general population, but their prevalence in individuals with heterozygous familial hypercholesterolaemia (HeFH) and whether they confer additional risk of ASCVD independent of LDL cholesterol (LDL-C) remains unclear.

Methods: Cross-sectional analysis was conducted in 35 540 patients with HeFH across 50 countries, in the EAS FH Studies Collaboration registry. Prevalence of World Health Organization-defined body mass index categories was investigated in adults (n = 29 265) and children/adolescents (n = 6275); and their association with prevalent ASCVD.

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.

Mortality and risk of diabetes, liver disease, and heart disease in individuals with haemochromatosis C282Y homozygosity and normal concentrations of iron, transferrin saturation, or ferritin: prospective cohort study.

Objectives: To test whether haemochromatosis C282Y homozygotes have increased risk of diabetes, liver disease, and heart disease even when they have normal plasma iron, transferrin saturation, or ferritin concentrations and to test whether C282Y homozygotes with diabetes, liver disease, or heart disease have increased mortality compared with non-carriers with these diseases.

Design: Prospective cohort study.

Setting: Three Danish general population cohorts: the Copenhagen City Heart Study, the Copenhagen General Population Study, and the Danish General Suburban Population Study.

Transthyretin Tetramer Destabilization and Increased Mortality in the General Population.

Importance: Transthyretin tetramer destabilization is the rate-limiting step in the development of transthyretin cardiac amyloidosis, an underrecognized contributor to mortality in older adults.

Objective: To test the hypothesis that transthyretin tetramer destabilization is associated with all-cause and cardiovascular mortality in the general population.

Design, Setting, And Participants: In this cohort study including individuals aged 20 to 80 years, genetic data were analyzed from 2 similar prospective studies of the Danish general population, the Copenhagen City Heart Study (CCHS) and the Copenhagen General Population Study (CGPS).

One in Five Atherosclerotic Cardiovascular Disease Events in Individuals With Diabetes Attributed to Elevated Remnant Cholesterol.

Aims: Elevated remnant cholesterol (= the cholesterol carried in triglyceride-rich lipoproteins) is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and is common in individuals with diabetes. We tested the hypothesis that ASCVD in individuals with diabetes can be partly attributed to elevated remnant cholesterol.

Materials And Methods: We included 3806 individuals with diabetes identified among 107,243 individuals from the Copenhagen General Population Study and used multivariable adjusted Poisson regression to estimate the fraction of ASCVD attributable to elevated remnant cholesterol.

A PSA SNP associates with cellular function and clinical outcome in men with prostate cancer.

Genetic variation at the 19q13.3 KLK locus is linked with prostate cancer susceptibility in men. The non-synonymous KLK3 single nucleotide polymorphism (SNP), rs17632542 (c.