Triglyceride content increases while cholesterol content decreases in HDL and LDL+IDL fractions following normal meals: The Copenhagen General Population Study of 25,656 individuals.

BACKGROUND AND AIMS: During fat tolerance tests, plasma triglycerides increase while high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and intermediate-density lipoprotein (IDL) cholesterol decrease. However, it is unknown whether triglyceride content increases and cholesterol content decreases in HDL and LDL + IDL fractions following normal meals in the general population. Therefore, we tested the hypothesis that triglyceride content increases while cholesterol content decreases in HDL and LDL + IDL fractions following normal meals. METHODS: In this cross-sectional study, we included 25,656 individuals aged 20-100 years, all without lipid-lowering therapy at examination and selected for metabolomic profiling from the Copenhagen General Population Study. Triglyceride and cholesterol content of 14 lipoprotein fractions weas measured using nuclear magnetic resonance (NMR) spectroscopy. Time since last meal was recorded by the examiner immediately before blood sampling. RESULTS: Following normal meals in age and sex-adjusted analyses and when compared with fasting levels, plasma triglycerides were higher for up to 5-6 h, and triglyceride content was higher for up to 6-7 h in HDL fractions, for up to 6-7 h in LDL + IDL fractions, and for up to 5-6 h in very-low-density lipoprotein (VLDL) fractions. Further, plasma cholesterol was lower for up to 2-3 h, and cholesterol content was lower for up to 0-1 h in HDL fractions and for up to 4-5 h in LDL + IDL fractions, while cholesterol content was higher for up to 4-5 h in VLDL fractions. CONCLUSIONS: Following normal meals, triglyceride content increases while cholesterol content decreases in HDL and LDL + IDL fractions.

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. METHODS: This prospective study included 38,319 individuals from the Copenhagen General Population Study with fresh sample measurements of sdLDL cholesterol. Median follow-up time was 3.1 years. We observed 302 and 74 ischemic and hemorrhagic strokes from baseline in 2013 to 2017 to the end of follow-up in 2018. For comparison, we included estimates for large buoyant LDL cholesterol and total LDL cholesterol. RESULTS: Higher levels of sdLDL cholesterol were log-linearly associated with increased risk of ischemic stroke. Compared with individuals with sdLDL cholesterol in the lowest tertile (≤0.60 mmol/l; ≤23 mg/dl) the multivariable adjusted hazard ratio for ischemic stroke was 1.79 (95% confidence interval = 1.31-2.43) for the highest tertile (≥0.86 mmol/l; ≥33 mg/dl). Multivariable adjusted hazard ratios for ischemic stroke per 1 mmol/l (38.7 mg/dl) higher levels were 1.69 (1.28-2.22) for sdLDL cholesterol, 0.95 (0.78-1.16) for large buoyant LDL cholesterol, and 1.08 (0.93-1.25) for total LDL cholesterol. Hazard ratios were similar when further adjusting for body mass index (BMI) and diabetes mellitus in the biological pathway in combination with related lipids and lipoproteins. INTERPRETATION: Higher sdLDL cholesterol levels were robustly associated with increased risk of ischemic stroke. ANN NEUROL 2023;93:952-964.

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). Meta-analyses aggregated the present findings with previously reported results. RESULTS: During a median follow-up of 3.0 and 9.2 years, respectively, 872 and 5,766 individuals in the 2 cohorts received a diagnosis of ASCVD. Per 0.1 mmol/L (9 mg/dL) higher direct LDL triglycerides, HRs were 1.26 (95% CI: 1.17-1.35) for ASCVD, 1.27 (95% CI: 1.16-1.39) for ischemic heart disease, 1.28 (95% CI: 1.11-1.48) for myocardial infarction, 1.22 (95% CI: 1.08-1.38) for ischemic stroke, and 1.38 (95% CI: 1.21-1.58) for peripheral artery disease. Corresponding HRs for NMR LDL triglycerides were 1.26 (95% CI: 1.20-1.33), 1.33 (95% CI: 1.25-1.41), 1.41 (95% CI: 1.31-1.52), 1.13 (95% CI: 1.05-1.23), and 1.26 (95% CI: 1.10-1.43), respectively. The foregoing results were not entirely statistically explained by apolipoprotein B levels. In meta-analyses for the highest quartile vs the lowest quartile of LDL triglycerides, random-effects risk ratios were 1.50 (95% CI: 1.35-1.66) for ASCVD (4 studies; 71,526 individuals; 8,576 events), 1.62 (95% CI: 1.37-1.93) for ischemic heart disease (6 studies; 107,538 individuals; 9,734 events), 1.30 (95% CI: 1.13-1.49) for ischemic stroke (4 studies; 78,026 individuals; 4,273 events), and 1.53 (95% CI: 1.29-1.81) for peripheral artery disease (4 studies; 107,511 individuals; 1,848 events). CONCLUSIONS: Elevated LDL triglycerides were robustly associated with an increased risk of ASCVD and of each ASCVD component individually in 2 prospective cohort studies and in meta-analyses of previous and present studies combined.

Development and validation of a model to predict incident chronic liver disease in the general population: The CLivD score.

BACKGROUND & AIMS: Current screening strategies for chronic liver disease focus on detection of subclinical advanced liver fibrosis but cannot identify those at high future risk of severe liver disease. Our aim was to develop and validate a risk prediction model for incident chronic liver disease in the general population based on widely available factors. METHODS: Multivariable Cox regression analyses were used to develop prediction models for liver-related outcomes with and without laboratory measures (Modellab and Modelnon-lab) in 25,760 individuals aged 40-70 years. Their data were sourced from the Finnish population-based health examination surveys FINRISK 1992-2012 and Health 2000 (derivation cohort). The models were externally validated in the Whitehall II (n = 5,058) and Copenhagen City Heart Study (CCHS) (n = 3,049) cohorts. RESULTS: The absolute rate of incident liver outcomes per 100,000 person-years ranged from 53 to 144. The final prediction model included age, sex, alcohol use (drinks/week), waist-hip ratio, diabetes, and smoking, and Modellab also included gamma-glutamyltransferase values. Internally validated Wolbers' C-statistics were 0.77 for Modellab and 0.75 for Modelnon-lab, while apparent 15-year AUCs were 0.84 (95% CI 0.75-0.93) and 0.82 (95% CI 0.74-0.91). The models identified a small proportion (<2%) of the population with >10% absolute 15-year risk for liver events. Of all liver events, only 10% occurred in participants in the lowest risk category. In the validation cohorts, 15-year AUCs were 0.78 (Modellab) and 0.65 (Modelnon-lab) in the CCHS cohort, and 0.78 (Modelnon-lab) in the Whitehall II cohort. CONCLUSIONS: Based on widely available risk factors, the Chronic Liver Disease (CLivD) score can be used to predict risk of future advanced liver disease in the general population. LAY SUMMARY: Liver disease often progresses silently without symptoms and thus the diagnosis is often delayed until severe complications occur and prognosis becomes poor. In order to identify individuals in the general population who have a high risk of developing severe liver disease in the future, we developed and validated a Chronic Liver Disease (CLivD) risk prediction score, based on age, sex, alcohol use, waist-hip ratio, diabetes, and smoking, with or without measurement of the liver enzyme gamma-glutamyltransferase. The CLivD score can be used as part of health counseling, and for planning further liver investigations and follow-up.

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. All had measurements of plasma apoB (quantitating number of apoB-containing lipoproteins) and cholesterol and triglyceride content of VLDL, intermediate-density lipoproteins (IDLs), and low-density lipoproteins (LDLs). RESULTS: During a median 11 years of follow-up, 1,816 were diagnosed with myocardial infarction. Per 1-mmol/l higher levels, multivariable-adjusted hazard ratios for myocardial infarction were 2.07 (95% confidence interval [CI]: 1.81 to 2.36) for VLDL cholesterol, 1.19 (95% CI: 1.14 to 1.25) for VLDL triglycerides, 5.38 (95% CI: 3.73 to 7.75) for IDL cholesterol, and 1.86 (95% CI: 1.62 to 2.14) for LDL cholesterol. Per 1-g/l higher plasma apoB, the corresponding value was 2.21 (95% CI: 1.90 to 2.58). In a step-up Cox regression, risk factors for myocardial infarction entered by importance as VLDL cholesterol, systolic blood pressure, smoking, and IDL + LDL cholesterol, whereas VLDL triglycerides did not enter the model. VLDL cholesterol explained 50% and IDL + LDL cholesterol 29% of the risk of myocardial infarction from apoB-containing lipoproteins, whereas VLDL triglycerides did not explain risk. CONCLUSIONS: VLDL cholesterol explained one-half of the myocardial infarction risk from elevated apoB-containing lipoproteins, whereas VLDL triglycerides did not explain risk.

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. Fourteen subclasses of decreasing size and their lipid constituents were analysed: six subclasses were very low-density lipoprotein (VLDL), one intermediate-density lipoprotein (IDL), three low-density lipoprotein (LDL), and four subclasses were high-density lipoprotein (HDL). Remnant lipoproteins were VLDL and IDL combined. RESULTS: Mean nonfasting cholesterol concentration was 1.84 mmol/L (72 mg/dL) for remnants, 2.01 mmol/L (78 mg/dL) for LDL, and 1.83 mmol/L (71 mg/dL) for HDL, equivalent to remnants containing 32% of plasma total cholesterol. Of 14 lipoprotein subclasses, large LDL and IDL were the ones containing most of plasma cholesterol. The plasma concentration of remnant cholesterol was from ∼1.4 mmol/L (54 mg/dL) at age 20 to ∼1.9 mmol/L (74 mg/dL) at age 60. Corresponding values for LDL cholesterol were from ∼1.5 mmol/L (58 mg/dL) to ∼2.1 mmol/L (81 mg/dL). CONCLUSIONS: Using direct measurements, one third of total cholesterol in plasma was present in remnant lipoproteins, that is, in the triglyceride-rich lipoproteins IDL and VLDL.

Total sitting time, leisure time physical activity and risk of hospitalization due to low back pain: The Danish Health Examination Survey cohort 2007-2008.

AIMS: This study aimed to test the hypotheses that a high total sitting time and vigorous physical activity in leisure time increase the risk of low back pain and herniated lumbar disc disease. METHODS: A total of 76,438 adults answered questions regarding their total sitting time and physical activity during leisure time in the Danish Health Examination Survey 2007-2008. Information on low back pain diagnoses up to 10 September 2015 was obtained from The National Patient Register. The mean follow-up time was 7.4 years. Data were analysed using Cox regression analysis with adjustment for potential confounders. Multiple imputations were performed for missing values. RESULTS: During the follow-up period, 1796 individuals were diagnosed with low back pain, of whom 479 were diagnosed with herniated lumbar disc disease. Total sitting time was not associated with low back pain or herniated lumbar disc disease. However, moderate or vigorous physical activity, as compared to light physical activity, was associated with increased risk of low back pain (HR = 1.16, 95% CI: 1.03-1.30 and HR = 1.45, 95% CI: 1.15-1.83). Moderate, but not vigorous physical activity was associated with increased risk of herniated lumbar disc disease. CONCLUSIONS: The results suggest that total sitting time is not associated with low back pain, but moderate and vigorous physical activity is associated with increased risk of low back pain compared with light physical activity.

Hyperhidrosis Substantially Reduces Quality of Life in Children: A Retrospective Study Describing Symptoms, Consequences and Treatment with Botulinum Toxin.

Studies on children with hyperhidrosis are sparse. This retrospective study presents clinical data and quality of life, along with treatment effect and safety of botulinum toxin (BTX). Case reports from 366 children were included to capture the medical history of hyperhidrosis. The total median score of the Dermatology Life Quality Index before treatment was 11 for children aged 16-17 years and 12 for children younger than 16 years. The children described physical, psychosocial and consequence-related symptoms. More than 70% had multifocal hyperhidrosis. BTX-A and/or BTX-B were given to 323 children, 193 of whom received repeated treatments. The highest score in a 5-grade scale concerning treatment effect was reported by 176/193 children, i.e. their "sweating disappeared completely". No severe adverse events occurred. Focal and multifocal hyperhidrosis in children reduces quality of life considerably. Treatment with BTX-A and/or BTX-B has been performed with success.