Search

Background: It is increasingly clear that triglyceride-rich lipoproteins are proinflammatory and cause low-grade systemic inflammation. However, it is currently unknown whether elevated plasma triglycerides are causally related to the development of psoriasis, a skin disorder driven by chronic inflammation., Objectives: To determine if elevated plasma triglycerides are associated with increased risk of psoriasis in observational and Mendelian randomization analysis., Methods: Consecutive individuals from the Copenhagen General Population Study were included. We used plasma triglycerides (n = 108 043) and a weighted triglyceride allele score (n = 92 579) on nine known triglyceride-altering genetic variants. Genetic results were replicated in 337 159 individuals from the UK Biobank. Psoriasis was defined using the International Classification of Diseases, version 10 (ICD-10) code for hospital contact in the main analyses, and prescription of topical antipsoriatics for mild psoriasis in the sensitivity analysis., Results: During a follow-up of median (range) 9.3 (0.1-15.1) years from 2003 to 2015 through 2018, 855 (1%) individuals were diagnosed with psoriasis by ICD-10 in the observational analysis and 772 (1%) in the Mendelian randomization analysis. In the observational analysis, the multivariable adjusted hazard ratio for psoriasis by ICD-10 was 1.26 [95% confidence interval (CI) 1.15-1.39] per doubling in plasma triglycerides with a corresponding causal odds ratio of incident psoriasis of 2.10 (95% CI 1.30-3.38). Causality was confirmed from data from the UK Biobank. Results were similar but slightly attenuated when we used topical antipsoriatic prescriptions for mild psoriasis., Conclusions: Elevated plasma triglycerides are associated with an increased risk of psoriasis in observational and Mendelian randomization analysis., Competing Interests: Conflicts of interest B.G.N. reports consultancies and talks sponsored by Abbott, Akcea, Amarin, Amgen, AstraZeneca, Denka, Esperion, Ionis, Kowa, Novartis, Novo Nordisk, Regeneron, Sanofi and Silence Therapeutics. There are no financial or other conflicts of interest for A.M.G., A.B.W. or S.E.B., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: The long-term pulmonary sequelae of mild coronavirus disease 2019 (COVID-19) remains unknown. In this study, we aimed to characterize lung function trajectories in individuals with mild COVID-19 from preinfection to 2 years postinfection., Methods: We reinvited participants 2 years after infection from our matched cohort study of the Copenhagen General Population who had initially been examined 5.4 months after infection. We repeated lung tests and questionnaires. Linear mixed models were used to estimate dynamics in lung volumes in individuals with COVID-19 patients versus uninfected controls over two intervals: from pre-infection to 6 months postinfection and 6 months postinfection to 2 years postinfection., Results: 52 individuals (48.6%) attended the 2-year examination at median 1.9 years (interquartile range, 1.8-2.4) after COVID-19, all with mild infection. Individuals with COVID-19 had an adjusted excess decline in forced expiratory volume in 1 second (FEV1) of 13.0 mL per year (95% confidence interval [CI], -23.5 to -2.5; P = .02) from before infection to 6 months after infection compared to uninfected controls. From 6 to 24 months after infection, they had an excess decline of 7.5 mL per year (95% CI, -25.6-9.6; P = .40). A similar pattern was observed for forced vital capacity (FVC). Participants had a mean increase in diffusing capacity for carbon monoxide (DLco) of 3.33 (SD 7.97) between the 6- and 24-month examination., Conclusions: Our results indicate that mild COVID-19 infection affects lung function at the time of infection with limited recovery 2 years after infection., Competing Interests: Potential conflicts of interest. T. B. reports grants from Pfizer, Novo Nordisk Foundation, Simonsen Foundation, and Lundbeck Foundation; grants and personal fees from GSK, Pfizer, and Gilead; and personal fees from Boehringer Ingelheim and MSD, all outside the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: The PROMINENT trial, a cardiovascular outcome trial of the triglyceride- and remnant cholesterol-lowering agent pemafibrate, has shown neutral results despite reduction in plasma triglycerides and remnant cholesterol. We tested the hypothesis that absolute mass changes in remnant cholesterol, LDL cholesterol, and apolipoprotein B explain the results of the PROMINENT trial., Methods: Among 108,431 individuals from the Copenhagen General Population Study (CGPS), those who met the key inclusion criteria of the PROMINENT trial were analyzed to mimic the trial design. Endpoint atherosclerotic cardiovascular disease (ASCVD) was cardiovascular death, myocardial infarction, ischemic stroke, and coronary revascularization as defined in PROMINENT., Results: In the PROMINENT trial, treatment with pemafibrate resulted in -7 mg/dL (-0.18 mmol/L; -18 %) change in remnant cholesterol, +10 mg/dL (+0.26 mmol/L; +12 %) LDL cholesterol, and +5 mg/dL (+0.05 g/L; +5 %) apolipoprotein B. In the CGPS mimicking PROMINENT, the estimated hazard ratios for ASCVD were 0.97 (95 % confidence interval: 0.94-0.99) for a -7 mg/dL (-0.18 mmol/L) change in remnant cholesterol, 1.04 (1.01-1.07) for a +10 mg/dL (+0.26 mmol/L) change in LDL cholesterol, and 1.02 (1.01-1.03) for a +5 mg/dL (+0.05 g/L) change in apolipoprotein B. When combining absolute changes in remnant cholesterol, LDL cholesterol, and apolipoprotein B, the estimated hazard ratio for ASCVD was 1.05 (0.96-1.14) in the CGPS mimicking PROMINENT compared to 1.03 (0.91-1.15) in the PROMINENT trial., Conclusions: Absolute mass changes in remnant cholesterol, LDL cholesterol, and apolipoprotein B can explain results of the PROMINENT trial. The 3 mg/dL (0.08 mmol/L) higher total atherogenic cholesterol together with 5 mg/dL (0.05 g/L) higher apolipoprotein B seem to explain the trend toward more ASCVD in the pemafibrate arm., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: BGN reports consultancies or talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea, Amgen, Amarin, Kowa, Denka, Novartis, Novo Nordisk, Esperion, Silence Therapeutics, Abbott, Mankind, Lilly, and Arrowhead. TD reports a consultancy by Novo Nordisk. AL reports a talk sponsored by Amarin and a consultancy by Novartis., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the contributions of low-grade inflammation measured by C-reactive protein (CRP), hyperglycaemia, and type 2 diabetes to risk of ischemic heart disease (IHD) and cardiovascular disease (CVD) death in the general population, and whether hyperglycaemia and high CRP are causally related., Research Design and Methods: Observational and bidirectional, one-sample Mendelian randomization (MR) analyses in 112,815 individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study, and bidirectional, two-sample MR with summary level data from two publicly available consortia, CHARGE and MAGIC., Results: Observationally, higher plasma CRP was associated with stepwise higher risk of IHD and CVD death, with hazard ratios and 95% confidence intervals (95%CI) of 1.50 (1.38, 1.62) and 2.44 (1.93, 3.10) in individuals with the 20% highest CRP concentrations. The corresponding hazard ratios for elevated plasma glucose were 1.10 (1.02, 1.18) and 1.22 (1.01, 1.49), respectively. Cumulative incidences of IHD and CVD death were 365% and 592% higher, respectively, in individuals with both type 2 diabetes and plasma CRP ≥ 2 mg/L compared to individuals without either. Plasma CRP and glucose were observationally associated (β-coefficient: 0.02 (0.02, 0.03), p = 3 × 10 - 20 ); however, one- and two-sample MR did not support a causal effect of CRP on glucose (-0.04 (-0.12, 0.32) and - 0.03 (-0.13, 0.06)), nor of glucose on CRP (-0.01 (-0.08, 0.07) and - 0.00 (-0.14, 0.13))., Conclusions: Elevated concentrations of plasma CRP and glucose are predictors of IHD and CVD death in the general population. We found no genetic association between CRP and glucose, or vice versa, suggesting that lowering glucose pharmacologically does not have a direct effect on low-grade inflammation., (© 2024. The Author(s).)

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., Methods: apoB, remnant cholesterol, and LDL cholesterol were measured in 93 461 individuals without statin use at baseline from the Copenhagen General Population Study (2003-2015). During up to 15 years of follow-up, 1207 had PAD, 552 had chronic limb-threatening ischemia, and 2022 had myocardial infarction in the Danish National Patient Registry. Remnant and LDL cholesterol were calculated from a standard lipid profile. Remnant and LDL particle counts were additionally measured with nuclear magnetic resonance spectroscopy in 25 347 of the individuals. Results were replicated in 302 167 individuals without statin use from the UK Biobank (2004-2010)., Results: In the Copenhagen General Population Study, multivariable adjusted hazard ratios for risk of PAD per 1 mmol/L (39 mg/dL) increment in remnant and LDL cholesterol were 1.9 (95% CI, 1.5-2.4) and 1.1 (95% CI, 1.0-1.2), respectively; corresponding results in the UK Biobank were 1.7 (95% CI, 1.4-2.1) and 0.9 (95% CI, 0.9-1.0), respectively. In the association from elevated apoB to increased risk of PAD, remnant and LDL cholesterol explained 73% (32%-100%) and 8% (0%-46%), respectively; corresponding results were 63% (30%-100%) and 0% (0%-33%) for risk of chronic limb-threatening ischemia and 41% (27%-55%) and 54% (38%-70%) for risk of myocardial infarction; results for remnant and LDL particle counts corroborated these findings., Conclusions: PAD risk conferred by elevated apoB-containing lipoproteins was explained mainly by elevated remnants, while myocardial infarction risk was explained by both elevated remnants and LDL., Competing Interests: Disclosures B.G. Nordestgaard reports consultancies and talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea, Amgen, Kowa, Denka, Amarin, Novartis, Novo Nordisk, Esperion, Abbott, Silence Therapeutics, USV, Mankind, Lilly, Arrowhead, and Marea. The other authors report no conflicts.