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.
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.
Background: Elevated apoB-containing lipoproteins (=remnants+LDLs [low-density lipoproteins]) are a major risk factor for atherosclerotic cardiovascular disease, including peripheral artery disease (PAD) and myocardial infarction. We tested the hypothesis that remnants and LDL both explain part of the increased risk of PAD conferred by elevated apoB-containing lipoproteins. For comparison, we also studied the risk of chronic limb-threatening ischemia and myocardial infarction.
View Article and Find Full Text PDFBackground: Low levels of high-density lipoprotein (HDL) cholesterol have been associated with higher rates and severity of infection. Alterations in inflammatory mediators and infection are associated with alterations in HDL cholesterol. It is unknown whether the association between HDL and infection is present for all particle sizes, and whether the observed associations are confounded by IL-6 signalling.
View Article and Find Full Text PDFAims/hypothesis: Elevated remnant cholesterol is observationally and causally associated with increased risk of atherosclerotic cardiovascular disease (ASCVD) in the general population. This association is not well studied in individuals with diabetes, who are often included in clinical trials of remnant cholesterol-lowering therapy. We tested the hypothesis that elevated remnant cholesterol is associated with increased risk of ASCVD in individuals with diabetes.
View Article and Find Full Text PDFCurr Atheroscler Rep
November 2023
Purpose Of Review: Recent large clinical trials have failed to show that triglyceride-rich lipoprotein-lowering therapies decrease the risk of atherosclerotic cardiovascular disease (ASCVD). In this review, we reconcile these findings with evidence showing that elevated levels of triglyceride-rich lipoproteins and the cholesterol they contain, remnant cholesterol, cause ASCVD alongside low-density lipoprotein (LDL) cholesterol.
Recent Findings: Results from observational epidemiology, genetic epidemiology, and randomized controlled trials indicate that lowering of remnant cholesterol and LDL cholesterol decrease ASCVD risk by a similar magnitude per 1 mmol/L (39 mg/dL) lower non-high-density lipoprotein cholesterol (remnant cholesterol+LDL cholesterol).
Purpose Of Review: Inflammation is gaining attention as a target for prevention of atherosclerotic cardiovascular disease (ASCVD). The purpose of this review is to compare the evidence for inflammation with the evidence for low-density lipoprotein (LDL) cholesterol in ASCVD.
Recent Findings: Evidence from human genetic studies and randomized controlled trials implicate the inflammatory pathway from the inflammasome through interleukin (IL)-1 to IL-6 as a cause of ASCVD.
Aims: Cholesterol carried in triglyceride-rich lipoproteins, also called remnant cholesterol, is being increasingly acknowledged as an important causal risk factor for atherosclerosis. Elevated remnant cholesterol, marked by elevated plasma triglycerides, is associated causally with an increased risk of atherosclerotic cardiovascular disease. The association with cause-specific mortality is, however, unclear.
View Article and Find Full Text PDFAims: Low levels of HDL cholesterol have been associated with increased risk of infectious disease morbidity and mortality. Nuclear magnetic resonance (NMR) spectroscopy permits the measurement of HDL particle count and allows further subclassification according to particle size. We tested the hypothesis that low number of different HDL subfractions is associated with increased infectious disease morbidity and mortality.
View Article and Find Full Text PDFThe myeloproliferative neoplasms are associated with chronic kidney disease but whether clonal haematopoiesis of indeterminate potential (CHIP) is associated with impaired kidney function is unknown. In the Danish General Suburban Population Study (N = 19 958) from 2010 to 2013, 645 individuals were positive for JAK2V617F (N = 613) or CALR (N = 32) mutations. Mutation-positive individuals without haematological malignancy were defined as having CHIP (N = 629).
View Article and Find Full Text PDFAims: The atherogenic potential of cholesterol in triglyceride-rich lipoproteins, also called remnant cholesterol, is being increasingly acknowledged. Elevated remnant cholesterol is associated with increased risk of myocardial infarction and ischaemic stroke. We tested the hypothesis that elevated remnant cholesterol is also associated with increased risk of peripheral artery disease (PAD).
View Article and Find Full Text PDFSmoking has been associated with opposing risks of ulcerative colitis and Crohn's disease. Whether these observational associations reflect actual causal associations, confounding, or reverse causation is unclear. Using a Mendelian randomization approach, we tested the hypothesis that smoking protects against ulcerative colitis and is a cause of Crohn's disease.
View Article and Find Full Text PDFTransplant Cell Ther
September 2021
Metabolic syndrome (MetS) is a growing concern in survivors of pediatric hematopoietic stem cell transplantation (HSCT), but little is known about the underlying mechanisms. This study aimed to determine the prevalence and clinical presentation of MetS in male long-term survivors of pediatric HSCT and to investigate predisposing factors, including low-grade inflammation, altered fat distribution, and low testosterone levels. We included 98 survivors age 19 to 47 years at a median follow-up of 18 years (range, 8 to 35 years) after pediatric HSCT.
View Article and Find Full Text PDFArterioscler Thromb Vasc Biol
February 2021
Objective: Animal studies suggest that HDL (high-density lipoprotein) regulates proliferation and differentiation of hematopoietic stem cells. Using a Mendelian randomization approach, we tested the hypothesis that low HDL cholesterol is associated with high white blood cell counts. Approach and Results: We included 107 952 individuals aged 20 to 100 years from the Copenhagen General Population Study with information on HDL cholesterol, white blood cell counts, and 9 genetic variants associated with HDL cholesterol.
View Article and Find Full Text PDFBackground: Increasing evidence suggests that high-density lipoprotein (HDL) may play a role in cancer development. We tested the hypothesis that low HDL levels are associated with increased risk of cancer.
Methods: Individuals from two population-based cohorts, the Copenhagen General Population Study (2003-2015, N = 107 341), and the Copenhagen City Heart Study (1991-1994, N = 9387) were followed prospectively until end of 2016 to assess low plasma HDL cholesterol and apolipoprotein A1 as risk factors for cancer using Cox proportional hazard regression.
Background: Whether inflammation is independently associated with development of V617F mutation and myeloproliferative neoplasm is not clear. We tested the hypothesis that a loss-of-function polymorphism in (marked by rs4537545) reduces risk of V617F mutation and myeloproliferative neoplasm in a Mendelian randomization study.
Methods: We genotyped 107,969 Danes from the Copenhagen General Population Study for the rs4537545 genotype, where the T-allele is associated with impaired interleukin-6 receptor signaling and reduced inflammation.
Background: High cardiovascular comorbidity contributes to excess mortality in patients with myeloproliferative neoplasm, while less is known about respiratory comorbidity and mortality. We tested the hypothesis that individuals with myeloproliferative neoplasm have increased risk of pneumonia and respiratory mortality.
Methods: Of 249 294 invited individuals aged ≥20 from the Danish general population from 2003-2015, 107 900 participated and were included in the Copenhagen General Population Study (response-rate: 43%).
Meta-analyses and Mendelian randomization (MR) may clarify the associations of smoking, blood cells and myeloproliferative neoplasms (MPN). We investigated the association of smoking with blood cells in the Danish General Suburban Population Study (GESUS, n = 11 083), by meta-analyses (including GESUS) of 92 studies (n = 531 741) and MR of smoking variant CHRNA3 (rs1051730[A]) in UK Biobank, and with MPN in a meta-analysis of six studies (n (total/cases):1 425 529/2187), totalling 2 307 745 participants. In the meta-analysis the random-effects standardized mean difference (SMD) in current smokers versus non-smokers was 0·82 (0·75-0·89, P = 2·0 * 10 ) for leukocytes, 0·09 (-0·02 to 0·21, P = 0·12) for erythrocytes, 0·53 (0·42-0·64, P = 8·0 * 10 ) for haematocrit, 0·42 (0·34-0·51, P = 7·1 * 10 ) for haemoglobin, 0·19 (0·08-0·31, P = 1·2 * 10 ) for mean corpuscular haemoglobin (MCH), 0·29 (0·19-0·39, P = 1·6 * 10 ) for mean corpuscular volume (MCV), and 0·04 (-0·04 to 0·13, P = 0·34) for platelets with trends for ever/ex-/current smokers, light/heavy smokers and female/male smokers.
View Article and Find Full Text PDFObjective- Whether tobacco smoking causally affects white and red blood cells and thrombocyte counts is unknown. Using a Mendelian randomization approach, we tested the hypothesis that smoking causes increases in these blood cell indices. Approach and Results- We included 104 607 white Danes aged 20 to 100 years from the Copenhagen General Population Study with information on blood cell indices, smoking habits, and CHRNA3 (alpha 3 nicotinic cholinergic receptor) rs1051730 genotype, where the T allele causes higher tobacco consumption; 41 759 were former smokers and 17 852 current smokers.
View Article and Find Full Text PDFThis study investigated the in-season effect of intensified training comparing the efficacy of duration-matched intense intermittent exercise training with sprint interval training in increasing intermittent running performance, sprint ability, and muscle content of proteins related to ion handling and metabolism in football players. After the first two weeks in the season, 22 sub-elite football players completed either 10 weeks of intense intermittent training using the 10-20-30 training concept (10-20-30, n = 12) or sprint interval training (SIT, n = 10; work/rest ratio: 6-s/54-s) three times weekly, with a ~20% reduction in weekly training time. Before and after the intervention, players performed a Yo-Yo intermittent recovery test level 1 (Yo-Yo IR1) and a 30-m sprint test.
View Article and Find Full Text PDFAims: The JAK2 V617F mutation is highly recurrent in many of the myeloproliferative neoplasms, a molecular variant that can be easily detected using sensitive and minimally invasive techniques. Given the ease of JAK2 V617F testing, this test may be improperly requested for the purposes of patient 'screening' and to optimise laboratory resource utilisation, it behooves clinicians and laboratorians to perform JAK2 V617F testing only when most appropriate.
Methods: To assist with the screening of patients being considered for JAK2 V617F testing, we developed a clinical decision rule, "JAK2-tree", which can be easily applied to basic CBC parameters (haemoglobin, platelet and white blood cell counts).
Background: Former studies on smoking as a risk factor for Philadelphia-negative myeloproliferative neoplasms (MPNs) have mainly been carried out in women's cohorts and studies with various definitions of MPNs. Herein, we conducted a cohort study with register-based follow-up of a general population from Denmark, to validate and substantiate prior observations.
Methods: In the Danish Health Examination Survey cohort, we used the Cox proportional-hazards model adjusted for age, sex, body mass index, and level of education, to calculate hazard ratios (HRs), to investigate, whether daily smokers or occasional/ex-smokers had an increased risk of MPNs compared to never-smokers.
The aim of the study was to determine the impact of an interdisciplinary exercise-based rehabilitation intervention on fatigue and quality of life (QOL) in patients with Philadelphia-negative myeloproliferative neoplasms (MPNs). At the Danish Knowledge Centre for Rehabilitation and Palliative Care, a 5-day interdisciplinary exercise-based rehabilitation intervention was carried out on 48 patients with MPN. It was followed by 12 weeks of self-exercising prior to follow-up.
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