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Introduction: Serum lipid profiles play a crucial role in diagnosing and evaluating cardiovascular diseases. However, the presence of paraprotein can lead to inaccurate dyslipidemia results on automated analyzers., Case Report: A 65-year-old woman whose combined concentrations of HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) consistently surpassed her total serum cholesterol levels over a period of three months presented with unusual lipid component detection. Further analysis revealed the presence of a monoclonal paraprotein, identified as an IgMλ band, with a concentration of 28.0 g/L. The patient was subsequently diagnosed with Waldenström macroglobulinemia. The use of abnormal reaction kinetic curves and the β quantification method, along with an alternative method that did not suffer from interference, revealed that the monoclonal paraprotein interfered with the measurements of HDL-C, LDL-C, apolipoprotein A-I (apoA-I), and apolipoprotein B (apoB) when using the Roche detection system. This interference led to spurious elevated HDL-C concentrations and falsely decreased apoA-I and apoB concentrations, while the LDL-C results were minimally affected. Although diluting the sample normalized the HDL-C and LDL-C measurements, the interference with the apoA-I and apoB assays persisted. No other common biochemical tests were interfered with this paraprotein., Conclusion: Caution is advised when using a homogenous method for direct measurement of HDL-C and LDL-C in patients with monoclonal paraprotein. Techniques to recognize and eliminate this interference are available. However, immunoturbidimetric detection of apoA-I and apoB levels is also susceptible to this interference, which is not readily removable., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: There is a growing burden of non-obese people with diabetes mellitus (DM). However, their cardiovascular risk (CV), especially in the presence of cardiovascular-kidney-metabolic (CKM) comorbidities is poorly characterised. The aim of this study was to analyse the risk of major CV adverse events in people with DM according to the presence of obesity and comorbidities (hypertension, chronic kidney disease, and dyslipidaemia)., Methods: We analysed persons who were enrolled in the prospective Silesia Diabetes Heart Project (NCT05626413). Individuals were divided into 6 categories according to the presence of different clinical risk factors (obesity and CKM comorbidities): (i) Group 1: non-obese with 0 CKM comorbidities; (ii) Group 2: non-obese with 1-2 CKM comorbidities; (iii) Group 3: non-obese with 3 CKM comorbidities (non-obese "extremely unhealthy"); (iv) Group 4: obese with 0 CKM comorbidities; (v) Group 5: obese with 1-2 CKM comorbidities; and (vi) Group 6: obese with 3 CKM comorbidities (obese "extremely unhealthy"). The primary outcome was a composite of CV death, myocardial infarction (MI), new onset of heart failure (HF), and ischemic stroke., Results: 2105 people with DM were included [median age 60 (IQR 45-70), 48.8% females]. Both Group 1 and Group 6 were associated with a higher risk of events of the primary composite outcome (aHR 4.50, 95% CI 1.20-16.88; and aHR 3.78, 95% CI 1.06-13.47, respectively). On interaction analysis, in "extremely unhealthy" persons the impact of CKM comorbidities in determining the risk of adverse events was consistent in obese and non-obese ones (P int =0.824), but more pronounced in individuals aged < 65 years compared to older adults (P int = 0.028)., Conclusion: Both non-obese and obese people with DM and 3 associated CKM comorbidities represent an "extremely unhealthy" phenotype which are at the highest risk of CV adverse events. These results highlight the importance of risk stratification of people with DM for risk factor management utilising an interdisciplinary approach., (© 2024. The Author(s).)

Aim: The guidelines recommend statins to prevent cardiovascular events in patients with type 2 diabetes (T2D) however, the importance of baseline LDL-Cholesterol (LDL-C) levels remains controversial. This study aimed to determine the association of statin use in T2D patients with major adverse cardiovascular events (MACE) and all-cause mortality and whether this association differs by baseline LDL-C levels., Data Synthesis: Medline, Embase, and Web of Science were systematically searched from inception until January 2022. Observational studies in patients with T2D comparing statin users vs non-users, with reports of the baseline LDL-C levels, were included. Random-effects meta-analysis and meta-regression were performed to estimate the overall effect on the risk of all-cause mortality and MACE (a composite of myocardial infarction, heart failure, stroke, and revascularization events) and the modification in the association by baseline LDL-C levels. We categorized studies according to their baseline LDL-C levels into 1) <100 mg/dl (2.59 mmol/l), 2) 100-130 mg/dl (2.59-3.37 mmol/l) and 3) >130 mg/dl (3.37 mmol/l) categories. A total of 9 cohort studies (n = 403,411 individuals) fulfilled our criteria. The follow-up duration ranged from 1.7 to 8 years. The overall combined estimate showed that statin therapy was associated with a significantly lower risk of MACE (Hazard Ratio (HR): 0.70 [95% CI 0.59 to 0.83], Absolute risk reduction percentage (ARR%): 3.19% [95%CI 0.88 to 5.50%) and all-cause mortality (HR: 0.60 [95% CI 0.46 to 0.79], ARR%: 5.23% [95% CI 2.18 to 8.28%), but varied, albeit not statistically significant, by baseline LDL-C levels. Studies with baseline LDL-C levels higher than 130 mg/dl had the greatest reduction of MACE (HR: 0.58 [95% CI 0.37 to 0.90]) and all-cause mortality risk (HR: 0.51 [95% CI [ 0.29 to 0.90]). The HRs of MACE in studies with LDL-C levels of 100-130 mg/dl and <100 mg/dl categories were respectively (0.70 [95% CI 0.59 to 0.83]) and (0.83 [95% CI [0.68 to 1.00]); and that of all-cause mortality were respectively (0.62 [95% CI 0.38 to 1.01]) and (0.67 [95% CI [0.44 to 1.02]). Statin use changes the HRs of MACE (0.99 [95%CI, 0.98 to 0.99]; P = 0.04) and all-cause mortality (0.99 [95% CI 0.98 to 1.01]; P = 0.8) per each mg/dl increase in baseline LDL-C level in meta-regression analyses., Conclusion: Statin therapy in patients with T2D was associated with reduced risk of MACE and all-cause mortality. Significant differences across studies with different baseline LDL-C levels were not observed., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Conflict of interest: M.S. reports serving as a consultant or research support (or both) from CiVi, Resverlogix, Lexicon, Baxter, Esperion, Amarin, New Amsterdam, Tourmaline, Sanofi, and Regeneron Pharmaceuticals, Inc. E.R.: No disclosures. P.G.S. reports grants, personal fees, and non-financial support from Sanofi; grants and personal fees from Amarin, Servier, and Bayer; personal fees from Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Idorsia, Pfizer, and Novartis. J.W.J. receives research grants from The Netherlands Heart Foundation, the Interuniversity Cardiology Institute of The Netherlands, and the European Commission Seventh Framework Programme; and research support from Amgen, Astellas, AstraZeneca, Daiichi Sankyo, Lilly, Merck-Schering-Plough, Novartis, Pfizer, Roche, and Sanofi. M.Sc. is an employee of Roche and may hold shares in the company. D.L.B. discloses the following relationships: Advisory Board: Angiowave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, and Stasys; Board of Directors: Angiowave (stock options), Boston VA Research Institute, Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock), Society of Cardiovascular Patient Care, TobeSoft; Chair: Inaugural Chair, American Heart Association Quality Oversight Committee; Consultant: Broadview Ventures, Hims; Data Monitoring Committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute; Rutgers University (for the NIH-funded MINT Trial); Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today's Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees), Wiley (steering committee); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women's Hospital who assigned to Lexicon; neither I nor Brigham and Women's Hospital receive any income from this patent); Research Funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, 89Bio; Royalties: Elsevier (Editor, Braunwald's Heart Disease); Site Co-Investigator: Author contributions Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, Vascular Solut.

Aims: This study aims to compare the preventive effect of low- or moderate-statin with ezetimibe combination therapy and high-intensity statin monotherapy on cardiovascular disease (CVD) and all-cause death in a real-world setting., Methods and Results: Using the Korean National Health Insurance Service datasets, two cohorts comparing high-intensity statin monotherapy with low- or moderate-intensity statin and ezetimibe combination were constructed by 1:1 propensity score matching procedure. Primary outcome was a composite of myocardial infarction (MI), stroke, and all-cause death. Secondary outcome was an individual event. The study population was followed from baseline until the date of events, or the last health check-ups, whichever came first. Compared to high-intensity statin monotherapy, moderate-intensity statin with ezetimibe combination significantly reduced the risk of composite outcome [hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.77-0.92, P < 0.001] as well as individual MI (HR 0.81, 95% CI 0.71-0.94, P = 0.005) and stroke (HR 0.78, 95% CI 0.65-0.93, P = 0.005), but not all-cause death. Low-intensity statin with ezetimibe also significantly reduced the risk of the composite outcomes (HR 0.80, 95% CI 0.66-0.97, P = 0.024) compared to high-intensity statin monotherapy, but the risk of individual outcome did not differ between two groups. Statin and ezetimibe combination demonstrated consistent effect across various subgroups., Conclusion: Among people without pre-existing CVD, moderate-intensity statin with ezetimibe combination was superior to high-intensity statin monotherapy in preventing composite outcomes as well as each of MI and stroke. In contrast, low-intensity statin with ezetimibe combination reduced the risk of composite but not individual outcomes., Competing Interests: Conflict of interest: J.E.J. reports research support from Kyung Hee University which is her institution. Y.-C.H. research funding from Celltrion Pharm Inc. However, the authors declare that they have no competing financial interests or personal relationships that could influence the work reported in this article., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: Assessment of residual cardiovascular risk in statin-treated patients with atherosclerotic cardiovascular disease (ASCVD) is pivotal for optimizing secondary preventive therapies. This study investigates if non-high-density lipoprotein cholesterol (non-HDL-C) is associated with residual ASCVD risk in statin-treated ischaemic heart disease (IHD) patients with and without diabetes., Methods and Results: Using the Western Denmark Heart Registry, we identified statin-treated patients with IHD examined by coronary angiography (CAG) from 2011 to 2020. Non-HDL-C was assessed within 1 year after CAG. Outcomes were ASCVD (myocardial infarction, ischaemic stroke, and cardiovascular death) and all-cause death. Cox regression analyses obtained hazard ratios (HRs) adjusted for age, sex, smoking, and hypertension. A total of 42 057 patients were included: 8196 patients with diabetes and 33 861 without diabetes. During the median 4.6 years of follow-up, event rates per 1000 person-years of ASCVD were 28.8 (27.1-30.5) and 17.2 (16.5-17.8) among patients with and without diabetes. In patients with diabetes, the adjusted HRs of ASCVD as compared with non-HDL-C < 25th percentile were 1.0 (0.9-1.2), 1.3 (1.1-1.6), and 1.6 (1.2-2.1) for patients in the 25th-74th, 75th-94th, and ≥95th percentiles. In patients without diabetes, the corresponding adjusted HRs were 1.1 (0.9-1.1), 1.2 (1.1-1.4), and 1.7 (1.4-2.0). Results were consistent across sex, age, clinical presentation, and low-density lipoprotein cholesterol strata., Conclusion: In statin-treated IHD patients with and without diabetes, non-HDL-C, especially above the 75th percentile, is associated with residual cardiovascular risk. These results have implications for secondary prevention, targeting patients who may benefit most from intensified preventive therapy., Competing Interests: Conflict of interest: M.K.H. has received a research grant from the Novo Nordisk Foundation (grant number NNF22OC0074083). M.B.M. has achieved lecture fees from Novo Nordisk, AstraZeneca, Amarin, Sanofi, and Amgen. K.K.W.O. is supported by a grant from the Danish Cardiovascular Academy funded by the Danish Heart Association and Novo Nordisk. P.G.T.: none. RWT: the Department of Clinical Epidemiology, Aarhus University, receives funding for other studies in the form of institutional research grants to (and administered by) Aarhus University. None of these studies has any relation to the present study. M.M. is supported by a grant from the Novo Nordisk Foundation (grant number NNF22OC0074083), has received lecture and/or advisory board fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, and Novo Nordisk, has received research grants from Philips, Bayer, and Novo Nordisk, has received a travel grant from Novo Nordisk, has ongoing institutional research contracts with Janssen, Novo Nordisk, and Philips, and is a minor shareholder in Novo Nordisk, Eli Lilly and Company, and Verve Therapeutics., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. 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.)

Competing Interests: Conflict of interest: none declared.

Background: Evidence from cohort studies indicates a bidirectional relationship between periodontal disease and type 2 diabetes (T2D), but the underlying mechanisms remain unknown. In this study, we aimed to (1) identify saliva, plasma, and multifluid metabolomic signatures associated with periodontal disease and (2) determine if these signatures predict T2D progression and cardiometabolic biomarkers at year 3., Methods and Results: We included participants from the SOALS (San Juan Overweight Adult Longitudinal Study) (n=911). Metabolites from saliva (k=635) and plasma (k=1051) were quantified using liquid chromatography-mass spectrometry. We applied elastic net regression with 10-fold cross-validation to identify baseline metabolomic signatures of periodontal disease. Multivariable Cox proportional hazards regression and linear regression were used to evaluate the association with T2D progression and biomarker concentrations. Metabolomic profiles included highly weighted metabolites related to lysine and pyrimidine metabolism. Periodontal disease or its 3 metabolomic signatures were not associated with T2D progression in 3 years. Prospectively, 1-SD increments in the multifluid and saliva metabolomic signatures were associated with higher low-density lipoprotein (multifluid: 12.9±5.70, P =0.02; saliva: 13.3±5.11, P =0.009). A 1-SD increment in the plasma metabolomic signature was also associated with Homeostatic Model Assessment for Insulin Resistance (2.67±1.14, P =0.02) and triglyceride (0.52±0.18, P =0.002)., Conclusions: Although metabolomic signatures of periodontal disease could not predict T2D progression, they were associated with low-density lipoprotein, triglyceride, and Homeostatic Model Assessment for Insulin Resistance levels at year 3.

Atherosclerotic cardiovascular disease (ASCVD) is a significant health challenge, and apolipoprotein B (ApoB)-containing lipoproteins are increasingly recognized as central to its progression. Initially labelled as the "low-density lipoprotein hypothesis," our understanding of the etiology of ASCVD has evolved into the "ApoB principle," which highlights the causal and consistent role of all ApoB lipoproteins in ASCVD development. We review the large body of data from genetic studies, to epidemiologic studies, to clinical trials that support this foundational principle. We also provide an overview of the recommendations from guideline committees across the globe on dyslipidemia management and compare these with recent Canadian guidelines. With a few key differences, recent guidelines worldwide provide largely concordant recommendations for diagnosing and managing dyslipidemia with general consensus regarding the need for optimal control of low-density lipoprotein cholesterol and ApoB-containing lipoproteins to prevent cardiovascular events and improve patient care., (Copyright © 2024. Published by Elsevier Inc.)

Aim: We aimed to evaluate the impact of a multicomponent healthcare intervention, primarily designed to improve glycemic control, on blood pressure and lipids in individuals with poorly controlled type 2 diabetes mellitus (T2DM) in the Catalonian primary care setting METHODS: A cluster, non-randomized, controlled pragmatic trial was conducted across 11 primary care centers. The intervention group (N=225) received a comprehensive, patient-centered approach, including a dedicated monographic consultation to address therapeutic inertia. The control group (N=181) mirrored the intervention group but lacked the monographic consultation. Secondary endpoints included lipid and blood pressure control assessed at baseline and after a 12-month follow-up., Results: 245 participants completed the study over 12 months. We found no differences in the reduction of lipid laboratory parameters between the groups at the final visit. However, no significant differences were found between the groups for other lipids or the proportion of participants achieving lipid target values. Likewise, no differences were noted between the groups for blood pressure, its target control, and treatment at the final visit. Various clinical factors such as age, sex, diabetes duration, HbA1c levels, BMI, and macrovascular complications among the participants were associated with achieving lipid and blood pressure targets at the final visit., Conclusion: The pragmatic multicomponent intervention proposed in the INTEGRA study, showed that including a component designed to reduce clinical inertia in the management of glycemia did not demonstrate benefits in improving lipids and blood pressure in patients with poorly controlled T2DM., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The funders had no role in the design of the study, in the collection, analysis, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results. M.M.-C. has received advisory and or speaking fees from Astra-Zeneca, Bayer, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, Novo Nordisk, and Sanofi; he has received research grants to the institution from Astra-Zeneca, GSK, Lilly, MSD, Novartis, Novo Nordisk, and Sanofi. J. F.-N. has received advisory and or speaking fees from Astra-Zeneca, Ascensia, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, Novo Nordisk, and Sanofi; he has received research grants to the in-stitution from Astra-Zeneca, GSK, Lilly, MSD, Novartis, Novo Nordisk, Sanofi, and Boehringer. D.M. has received advisory and/or speaking fees from AB Biotics, Amgen, Almirall, Ferrer, Gilead, Menarini, MSD, Novo Nordisk and Sanofi. A.M has received advisory and or speaking fees from Astra-Zeneca, Boehringer Ingelheim, Lilly, MSD, Novo Nordisk, and Sanofi; he has received research grants to the institution from Sanofi. M.G, A.B., E.R. and B.V. have no conflict of interest to declare., (Copyright © 2024 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Background: This study evaluates insulin resistance prevalence in young females without diabetes, assessing risk factors and adiposity indices for early detection of cardiometabolic disorders. Methods: A cross-sectional study was conducted, involving 282 females aged 18-35 years from suburban and rural areas of Sri Lanka. Anthropometric measurements [height, weight, waist circumference (WC)] were obtained and biochemical parameters [fasting glucose, insulin, insulin resistance (IR), total cholesterol, high-density lipoproteins, (HDL), low-density lipoproteins, triglycerides] were measured. The anthropometric and biochemical data were compared between the groups of normal weight controls and overweight/obese cases, as well as between females with or without IR. Results: The prevalence of IR in controls and cases were 48.6% and 57.1%, respectively. Both groups had mean Homeostasis Model Assessment-IR values greater than the normal cutoff value of 2.5. Females with IR showed higher prevalence of dyslipidemia than those without IR. Compared to the controls (2.81%), the prevalence of metabolic syndrome (MetS) was substantially greater among cases (46.42%). Both groups showed a statistically significant association between IR and MetS, but the association was considerably stronger in cases [ r  = 0.616, odds ratio (OR) >8] than in controls ( r  = 0.175, OR >1). Controls exhibited lower HDL levels, hypertriglyceridemia, and elevated IR levels ( P  < 0.05), and their ORs for acquiring MetS were >2, <1, and >3, respectively. Importantly, overweight/obese cases exhibited a significant association ( P  < 0.05) with all the MetS risk variables. Visceral adiposity index (VAI) proves to be a precise measurement for identifying IR and cardiovascular disease (CVD) among young females ( Z  = -3.651), surpassing the accuracy of other indices. Body mass index, body round index, a body shape index, and WC were also reliable measurements to assess IR and the risk of CVD ( P  < 0.05). Conclusion: The study underscores the importance of assessing IR in nondiabetic young females to identify early cardiometabolic risks. VAI emerges as a precise measurement for identifying IR and CVD risk, surpassing the accuracy of other indices.

Underutilization of lipid-lowering therapy (LLT) and failure to attain guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals are important quality gaps in cardiovascular risk optimization, especially among patients with atherosclerotic cardiovascular disease (ASCVD). Large database analyses demonstrate an unmet need for improved LDL-C measurement, and that nearly 75% of patients with ASCVD have an LDL-C level above guideline-recommended levels, and greater than 50% are not treated with statins or ezetimibe. Proposed solutions for overcoming these obstacles to optimal lipid management include provider- and patient-facing educational interventions, health information technology strategies, implementation of incentive-based care, advocacy efforts, and systems-based process innovations. While individual interventions may not be enough to overcome the totality of barriers to optimal LLT, comprehensive multifaceted approaches that address barriers at the provider, patient, and healthcare delivery level are likely to offer the greatest likelihood of success and improved patient outcomes., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Abstract: In vitro investigations have established metformin's capacity to downregulate proprotein convertase subtilisin/kexin type 9 (PCSK9) expression, suggesting a potential beneficial effect on atherogenic lipoprotein particles when combined with metformin therapy. Our objective was to assess whether metformin could mitigate statin-induced adverse effects on PCSK9, thereby improving lipid profiles in patients with coronary artery disease (CAD) but without diabetes. Employing an open-label, placebo-controlled, randomized trial, we randomized patients with CAD but without diabetes into CLA (cholesterol-lowering agents alone: atorvastatin ± ezetimibe, n = 38) and Met + CLA groups (metformin plus CLA, n = 33) in a 1:1 ratio. The primary end point was the therapeutic impact of 1-month metformin combination treatment on low-density lipoprotein cholesterol (LDL-C) and PCSK9 levels. Baseline LDL-C and PCSK9 levels were 76.18 mg·dL -1 and 80.54 ng·mL -1 , respectively. After 1 month, metformin significantly reduced LDL-C (-20.81%, P < 0.001), enabling 72% of patients to attain guideline-recommended LDL-C goals. Noteworthy reductions in PCSK9 levels (-15.03%, P < 0.001) were observed. Moreover, Met + CLA markedly reduced LDL particle number more than CLA alone (-10.65% vs. 1.45%, P = 0.009), primarily due to diminished small-dense LDL particle count. Mechanistically, our study demonstrated metformin's inhibition of statin-induced PCSK9 expression in human hepatocellular cells. In summary, a 1-month metformin combination regimen reduced LDL-C levels in patients with CAD but without diabetes by inhibiting PCSK9 expression., Trial Registration: Chinese Clinical Trial Registry identifier: ChiCTR1900026925 (26/10/2019)., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: To identify peri- and post-menopausal women at risk of non-communicable diseases in rural India and to assess their prevalence amongst these groups via the use of artificial intelligence., Settings and Design: An observational study conducted by the Indian Menopause Society in collaboration with the Government of Maharashtra. The study included rural women residents of three villages in the Latur district of Maharashtra, India., Materials and Methods: Accredited social health activist workers identified 400 peri- and post-menopausal women aged 45-60 years. Specific symptoms able to predict the presence of a non-communicable disease were identified through the use of artificial intelligence., Statistical Analysis Used: Descriptive statistics and predictive network charts analysis., Results: The mean age of 316 women included in the analysis was 50.4 years and the majority of them were illiterate (68 %). The prevalence of dyslipidaemia, osteopenia, diabetes mellitus, obesity and hypertension were 58 %, 50 %, 25 %, 25 %, and 20 % respectively. None of their symptoms or laboratory reports could be significantly correlated directly with any of these non-communicable diseases. Hence, we used a cluster of symptoms to suggest the presence of hypertension, diabetes mellitus, osteoporosis and hypothyroidism via predictive network analysis charts., Conclusions: Screening of at-risk women can be done using an artificial intelligence-based screening tool for early diagnosis, timely referral and treatment of non-communicable diseases with the support of community health workers., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Various factors have been described in the literature to explain the tendency of an individual to undergo medical screenings. This study aimed to assess the association between the level of knowledge about dyslipidaemia and the frequency of lipid testing, as well as the potential impact of predisposing, enabling, and need factors on the uptake of blood lipid screening. This study was a cross-sectional survey involving 314 participants who were Malaysian residents of Taman Selatan, Klang, aged 30 and above. The study utilized a 42-item paper-based bilingual questionnaire to evaluate the predisposing, enabling, and need factors that could potentially influence the practice of lipid testing. Out of the 314 residents approached, 271 responded to the questionnaire yielding a response rate of 86.31%. The median knowledge score was 5 out of 17. Lower monthly income (OR = 3.225, 95% CI = 0.255 to 2.141), higher number of comorbidities (OR = 2.724, 95% CI = 0.037 to 2.013), higher total knowledge score (OR = 1.334, 95% CI = 0.063 to 0.512) and respondent's belief and attitude (OR = 0.813, 95% CI = -2.033 to -0.539), were found to be significantly associated with the frequency of lipid testing. In conclusion, the knowledge level regarding dyslipidaemia was below average and associated with a lower tendency to undergo frequent lipid testing. There is a need for innovative health awareness such as active educational campaigns in various settings of the community. Further qualitative studies that explore the understanding of the publics', and antecedents of their, lipid screening behaviour are required. Appropriate communication by healthcare providers should be encouraged during patient consultations for higher impact., Competing Interests: The authors have no conflicts of interest to declare for this study., (Copyright: © 2024 Paramalingam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: High-intensity statin therapy is currently recommended initial guideline therapy in ACS treatment. However, only a minority of patients are achieving LDL-C attainment goal at 6 months. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are on recommended guideline therapy post-ACS if LDL-C goal attainment is not achieved after high-intensity statin (4-6 weeks) and after the addition of ezetimibe if guideline goal attainment is not achieved after an additional 4-6 weeks. Thus, it has been recommended that PCSK9 inhibitors be considered earlier post-ACS. However, the efficacy of early PCSK9 inhibitors initiation in ACS patients remains uncertain., Methods: This systematic review and meta-analysis was conducted following PRISMA guidelines. Randomized controlled trials (RCTs) and observational studies involving ACS patients who received PCSK9 inhibitors within 48 h of hospitalization were included. Common and random effects models were used to evaluate the pooled effect of early PCSK9 inhibitor administration. Nine RCTs and three cohort studies were included., Results: Early PCSK9 inhibitor administration reduced the incidence of MI, ACS hospitalization, and revascularization at 6-18 months post-ACS. Although there was a drift towards reduced stroke, all-cause mortality, and cardiovascular death, no statistically significant reduction was observed. Additionally, PCSK9 inhibitors significantly enhanced lipid control at 4-12 weeks after index hospitalization., Conclusion: Early PCSK9 inhibitors initiation in ACS patients reduces MACE and improves lipid profiles. While the results propose promising benefits in terms of stroke and mortality, further research with longer follow-up is required for more decisive evidence., (© 2024. The Author(s).)

Infrared spectroscopy is a powerful technique for probing the molecular profiles of complex biofluids, offering a promising avenue for high-throughput in vitro diagnostics. While several studies showcased its potential in detecting health conditions, a large-scale analysis of a naturally heterogeneous potential patient population has not been attempted. Using a population-based cohort, here we analyze 5,184 blood plasma samples from 3,169 individuals using Fourier transform infrared (FTIR) spectroscopy. Applying a multi-task classification to distinguish between dyslipidemia, hypertension, prediabetes, type 2 diabetes, and healthy states, we find that the approach can accurately single out healthy individuals and characterize chronic multimorbid states. We further identify the capacity to forecast the development of metabolic syndrome years in advance of onset. Dataset-independent testing confirms the robustness of infrared signatures against variations in sample handling, storage time, and measurement regimes. This study provides the framework that establishes infrared molecular fingerprinting as an efficient modality for populational health diagnostics., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The ODYSSEY OUTCOMES trial, comprising over 47 000 patient-years of placebo-controlled observation, demonstrated important reductions in the risk of recurrent ischaemic cardiovascular events with the monoclonal antibody to proprotein convertase subtilisin/kexin type 9 alirocumab, as well as lower all-cause death. These benefits were observed in the context of substantial and persistent lowering of low-density lipoprotein cholesterol with alirocumab compared with that achieved with placebo. The safety profile of alirocumab was indistinguishable from matching placebo except for a ∼1.7% absolute increase in local injection site reactions. Further, the safety of alirocumab compared with placebo was evident in vulnerable groups identified before randomization, such as the elderly and those with diabetes mellitus, previous ischaemic stroke, or chronic kidney disease. The frequency of adverse events and laboratory-based abnormalities was generally similar to that in placebo-treated patients. Thus, alirocumab appears to be a safe and effective lipid-modifying treatment over a duration of at least 5 years., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: Dyslipidemia is one of the causes of coronary heart disease (CAD), and apolipoprotein E (APOE) gene polymorphism affects lipid levels. However, the relationship between APOE gene polymorphisms and premature CAD (PCAD, male CAD patients with ≤ 55 years old and female with ≤ 65 years old) risk had different results in different studies. The aim of this study was to assess this relationship and to further evaluate the relationship between APOE gene polymorphisms and PCAD risk in the Hakka population., Methods: This study retrospectively analyzed 301 PCAD patients and 402 age matched controls without CAD. The APOE rs429358 and rs7412 polymorphisms were genotyped by polymerase chain reaction (PCR) -chip technique. The distribution of APOE genotypes and alleles between the case group and the control group was compared. The relationship between APOE genotypes and PCAD risk was obtained by logistic regression analysis., Results: The frequency of the APOE ɛ3/ɛ4 genotype (18.9% vs. 10.2%, p = 0.001) and ε4 allele (11.1% vs. 7.0%, p = 0.007) was higher in the PCAD patients than that in controls, respectively. PCAD patients with ɛ2 allele had higher TG level than those with ɛ3 allele, and controls carried ɛ2 allele had higher HDL-C level and lower LDL-C level than those carried ɛ3 allele. Regression logistic analysis showed that BMI ≥ 24.0 kg/m 2 (BMI ≥ 24.0 kg/m 2 vs. BMI 18.5-23.9 kg/m 2 , OR: 1.763, 95% CI: 1.235-2.516, p = 0.002), history of smoking (Yes vs. No, OR: 5.098, 95% CI: 2.910-8.930, p < 0.001), ɛ3/ɛ4 genotype (ɛ3/ɛ4 vs. ɛ3/ɛ3, OR: 2.203, 95% CI: 1.363-3.559, p = 0.001), ε4 allele (ε4 vs. ε3, OR: 2.125, 95% CI: 1.333-3.389, p = 0.002), and TC level (OR: 1.397, 95% CI: 1.023-1.910, p = 0.036) were associated with PCAD., Conclusions: In summary, BMI ≥ 24.0 kg/m 2 , history of smoking, APOE ɛ3/ɛ4 genotype, and TC level were independent risk factors for PCAD. It means that young individuals who are overweight, have a history of smoking, and carried APOE ɛ3/ɛ4 genotype had increased risk of PCAD., (© 2024. The Author(s).)

Background: The coexistence of multiple standard modifiable risk factors (SMuRFs),classical and novel risk factors (RFs) for atherosclerotic cardiovascular disease (ASCVD) is common in the Middle East (ME). There is a paucity of data on the coexistence of these RFs in ME young women., Aim: Comparing the prevalence and the statistical patterns of the SMuRFs, classical and novel RFs in target population., Methods: In this case-control (1:2) study, consecutive young women aged 18-50 years were enrolled in 12 centers (July 2021 to October 2023). Prevalence and coexistence of 19 RFs were compared between cases with ASCVD and their controls. The RFs included SMuRFs (hypertension, type 2 diabetes, dyslipidemia, and cigarette smoking), other classical RF (obesity, family history of premature ASCVD, and physical inactivity), novel RFs and social determinants of health (health insurance, place of residence, depression, and level of education)., Results: The study included 627 subjects; 209 had ASCVD (median age 46 years, IQR 49-42 years) and 418 controls (median age 45 years, IQR 48-41 years). The presence of 1-2 RFs; (ASCVD: 63.2%, Control: 54.1%, p=0.037) and 3-4 RFs; (ASCVD: 27.8%, Control: 3.3%, p < 0.001) SMuRFs was more prevalent in women with ASCVD. Similarly, the presence of 4-5 RFs; (ASCVD: 40.7%, Control: 14.6%, p<0.001), and 6-7 (ASCVD: 10.5%, Control: 1%, p < 0.001). The classical RF were also significantly common in these women. The distribution of multiple novel RF was not statistically significant across both groups. Finally, regarding the socioeconomic RFs in women with ASCVDs, the presence of 1-2 RFs (ASCVD: 59.8%, Control: 76.1%, p < 0.001) was significantly less common while the presence of 3-4 RFs (ASCVD: 39.2%, Control: 21.8%, p < 0.001) was vastly more common., Conclusion: An elevated rate of coexistence of classical RF in the case group, mainly socioeconomic and SMuRFs. By managing them primary and secondary ASCVDs prevention attained., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Al-Shudifat et al.)

Background: Dyslipoproteinemia often involves simultaneous derangements of multiple lipid traits. We aimed to evaluate the phenotypic and genetic characteristics of combined lipid disturbances in a general population-based cohort., Methods: Among UK Biobank participants without prevalent coronary artery disease, we used blood lipid and apolipoprotein B concentrations to ascribe individuals into 1 of 6 reproducible and mutually exclusive dyslipoproteinemia subtypes. Incident coronary artery disease risk was estimated for each subtype using Cox proportional hazards models. Phenome-wide analyses and genome-wide association studies were performed for each subtype, followed by in silico causal gene prioritization and heritability analyses. Additionally, the prevalence of disruptive variants in causal genes for Mendelian lipid disorders was assessed using whole-exome sequence data., Results: Among 450 636 UK Biobank participants: 63 (0.01%) had chylomicronemia; 40 005 (8.9%) had hypercholesterolemia; 94 785 (21.0%) had combined hyperlipidemia; 13 998 (3.1%) had remnant hypercholesterolemia; 110 389 (24.5%) had hypertriglyceridemia; and 49 (0.01%) had mixed hypertriglyceridemia and hypercholesterolemia. Over a median (interquartile range) follow-up of 11.1 (10.4-11.8) years, incident coronary artery disease risk varied across subtypes, with combined hyperlipidemia exhibiting the largest hazard (hazard ratio, 1.92 [95% CI, 1.84-2.01]; P =2×10 -16 ), even when accounting for non-HDL-C (hazard ratio, 1.45 [95% CI, 1.30-1.60]; P =2.6×10 -12 ). Genome-wide association studies revealed 250 loci significantly associated with dyslipoproteinemia subtypes, of which 72 (28.8%) were not detected in prior single lipid trait genome-wide association studies. Mendelian lipid variant carriers were rare (2.0%) among individuals with dyslipoproteinemia, but polygenic heritability was high, ranging from 23% for remnant hypercholesterolemia to 54% for combined hyperlipidemia., Conclusions: Simultaneous assessment of multiple lipid derangements revealed nuanced differences in coronary artery disease risk and genetic architectures across dyslipoproteinemia subtypes. These findings highlight the importance of looking beyond single lipid traits to better understand combined lipid and lipoprotein phenotypes and implications for disease risk., Competing Interests: P. Natarajan reports research grants from Allelica, Amgen, Apple, Boston Scientific, Genentech/ Roche, and Novartis, personal fees from Allelica, Apple, AstraZeneca, Blackstone Life Sciences, Creative Education Concepts, CRISPR Therapeutics, Eli Lilly & Co, Foresite Labs, Genentech/ Roche, GV, HeartFlow, Magnet Biomedicine, Merck, and Novartis, scientific advisory board membership of Esperion Therapeutics, Preciseli, and TenSixteen Bio, scientific co-founder of TenSixteen Bio, equity in MyOme, Preciseli, and TenSixteen Bio, and spousal employment at Vertex Pharmaceuticals, all unrelated to the resent work. The other authors report no conflicts.

Background: The abnormal low-density protein cholesterol (LDL-C) level in the development of atherosclerosis is often comorbid in individuals with type 2 diabetes mellitus(T2DM). This study aimed to investigate the aggravating effect of abnormal LDL-C levels on coronary artery plaques assessed by coronary computed tomography angiography (CCTA) in T2DM., Materials and Methods: This study collected 3439 T2DM patients from September 2011 to February 2022. Comparative analysis of differences in coronary plaque characteristics was performed for the patients between the normal LDL-C level group and the abnormal LDL-C level group. Factors with P < 0.1 in the univariable linear regression analyses were included in the multivariable linear stepwise regression., Results: A total of 2820 eligible T2DM patients were included and identified as the normal LDL-C level group (n = 973) and the abnormal LDL-C level group (n = 1847). Compared with the normal LDL-C level group, both on a per-patient basis and per-segment basis, patients with abnormal LDL-C level showed more calcified plaques, partially calcified plaques, low attenuation plaques, positive remodellings, and spotty calcifications. Multivessel obstructive disease (MVD), nonobstructive stenosis (NOS), obstructive stenosis (OS), plaque involvement degree (PID), segment stenosis score (SSS), and segment involvement scores (SIS) were likely higher in the abnormal LDL-C level group than that in the normal LDL-C level group (P < 0.001). In multivariable linear stepwise regression, the abnormal LDL-C level was validated as an independent positive correlation with high-risk coronary plaques and the degree and extent of stenosis caused by plaques (low attenuation plaque: β = 0.116; positive remodelling: β = 0.138; spotty calcification: β = 0.091; NOS: β = 0.427; OS: β = 0.659: SIS: β = 1.114; SSS: β = 2.987; PID: β = 2.716, all P value < 0.001)., Conclusions: Abnormal LDL-C levels aggravate atherosclerotic cardiovascular disease (ASCVD) in patients with T2DM. Clinical attention deserves to be caught by the tailored identification of cardiovascular risk categories in T2DM individuals and the achievement of the corresponding LDL-C treatment goal., (© 2024. The Author(s).)

Background: Statin effects extend beyond low-density lipoprotein cholesterol reduction, potentially modulating the metabolism of bioactive lipids (BALs), crucial for biological signaling and inflammation. These bioactive metabolites may serve as metabolic footprints, helping uncover underlying processes linked to pleiotropic effects of statins and yielding a better understanding of their cardioprotective properties. This study aimed to investigate the impact of high-intensity statin therapy versus placebo on plasma BALs in the JUPITER trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin; NCT00239681), a randomized primary prevention trial involving individuals with low-density lipoprotein cholesterol <130 mg/dL and high-sensitivity C-reactive protein ≥2 mg/L., Methods: Using a nontargeted mass spectrometry approach, over 11 000 lipid features were assayed from baseline and 1-year plasma samples from cardiovascular disease noncases from 2 nonoverlapping nested substudies: JUPITER discovery (n=589) and JUPITER validation (n=409). The effect of randomized allocation of rosuvastatin 20 mg versus placebo on BALs was examined by fitting a linear regression with delta values (∆=year 1-baseline) adjusted for age and baseline levels of each feature. Significant associations in discovery were analyzed in the validation cohort. Multiple comparisons were adjusted using 2-stage overall false discovery rate., Results: We identified 610 lipid features associated with statin randomization with significant replication (overall false discovery rate, <0.05), including 26 with annotations. Statin therapy significantly increased levels of 276 features, including BALs with anti-inflammatory activity and arterial vasodilation properties. Concurrently, 334 features were significantly lowered by statin therapy, including arachidonic acid and proinflammatory and proplatelet aggregation BALs. By contrast, statin therapy reduced an eicosapentaenoic acid-derived hydroxyeicosapentaenoic acid metabolite, which may be related to impaired glucose metabolism. Additionally, we observed sex-related differences in 6 lipid metabolites and 6 unknown features., Conclusions: Statin allocation was significantly associated with upregulation of BALs with anti-inflammatory, antiplatelet aggregation and antioxidant properties and downregulation of BALs with proinflammatory and proplatelet aggregation activity, supporting the pleiotropic effects of statins beyond low-density lipoprotein cholesterol reduction., Competing Interests: Disclosures The parent JUPITER trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) was funded by AstraZeneca (Wilmington, DE), which had no role in the current study. Quest Diagnostics and LabCorp (LipoScience) conducted assays at no additional charges. O.V. Demler received support from Kowa, not related to the current work. S. Mora has served as a consultant to Pfizer for work outside the current study. M. Jain is the founder and chief executive officer of Sapient, a private organization specialized in biotechnology research for biomarker profiling. P.M. Ridker received past investigator-initiated research grant support from AstraZeneca to conduct the JUPITER trial; has current investigator-initiated research grant support from Novartis, Novo Nordisk, Kowa, Amarin, Pfizer, Esperion, National Heart, Lung, and Blood Institute, Bristol Myers Squibb, and Operation Warp Speed; served as a consultant to Novartis, Flame, Agepha, Ardelyx, AstraZeneca, Janssen, Civi Biopharm, GlaxoSmithKline, SOCAR, Novo Nordisk, Health Outlook, Montai Health, Eli Lilly, New Amsterdam, Boehringer-Ingelheim, RTI, Cytokinetics, Horizon Therapeutics, and Cardio Therapeutics; has minority shareholder equity positions in Uppton, Bitteroot Bio, and Angiowave; received nonmonetary research support from the Pfizer Bristol Myers Squibb Alliance and from Quidel, Inc, to conduct federally funded COVID-19 research; and receives compensation for service on the Peter Munk Advisory Board (University of Toronto), the Leducq Foundation, Paris FR, and the Baim Institute (Boston, MA). None of these conflicts relate to the current article. The other authors report no conflicts.

Introduction: Ethnic and gender differences in plasma lipid composition have been widely reported among the general population, but there are scarce data on athletes., Aim: To assess ethnic and gender differences in lipid profile across a large cohort of Olympic athletes practicing different sport disciplines METHODS: We enrolled 1165 Olympic athletes divided into power, endurance, and mixed disciplines according to European Society of Cardiology classification. Sixty-two (5.3%) were Afro-Caribbean. Body composition and fat mass percentage were measured. Blood samples were collected and lipid profile was investigated., Results: Compared to Caucasians, Afro-Caribbeans had better lipid profile characterized by lower LDL (90 ± 25 mg/dL vs. 97.1 ± 26.2 mg/dL, p = 0.032) lower LDL/HDL ratio (1.39 ± 0.5 vs. 1.58 ± 0.6, p = 0.012), lower non-HDL-cholesterol (102.5 ± 27.4 mg/dL vs. 111.5 ± 28.5 mg/dL, p = 0.015) and lower TC/HDL (2.59 ± 0.6 vs. 2.82 ± 0.7, p = 0.010). Female Afro-Caribbeans showed lower TG/HDL ratio (p = 0.045) and TC/HDL ratio (p = 0.028), due to higher HDL (p = 0.005) compared to male Afro-Caribbeans. In Caucasian athletes, females showed even more evident differences with lower TC, LDL, and higher HDL with subsequent lower ratios compared to men. Moreover, endurance Caucasian athletes had lower LDL (p = 0.003) and TG (p = 0.017) plasmatic levels and higher HDL levels compared to non-endurance Caucasian athletes (p< 0.0001) CONCLUSIONS: Ethnicity and gender have a significant influence on plasmatic lipid balance in elite athletes and Afro-Caribbeans have favorable lipid profiles compared to Caucasians. Moreover, endurance sports, particularly in Caucasian athletes, are associated with better lipid profile compared to other type of sports., (© 2024. The Author(s).)

Background/aims: Statins are common lipid-lowering agents used in dyslipidemia. However, they increase serum creatinine phosphokinase (CPK) levels. Currently, there are no studies on the effect of thyroid-stimulating hormone (TSH) levels on CPK levels after statin administration. Therefore, this study aimed to investigate CPK level alterations after statin administration according to TSH quartiles in participants with euthyroidism., Methods: This retrospective analysis included 25,047 patients with euthyroidism. CPK levels were measured before and 6 months after statin administration. Normal TSH levels were divided into four quartiles, and the CPK levels and proportions of patients with normal CPK levels after statin administration for each TSH quartile were evaluated., Results: The baseline CPK level was significantly higher in the lowest TSH quartile (Q1) compared to the other quartiles but decreased after statin administration. Thus, the difference between the CPK levels and the other quartile groups was not significant. The proportion of patients with normal CPK levels was also significantly lowest in Q1 before statin administration; however, no significant difference was noted in the ratio among each group after statin administration. These findings were consistent with the findings of the analysis according to statin intensity., Conclusion: In patients in the lowest TSH quartile of the normal TSH range, the CPK level decreased, and the proportion of normal CPK levels increased significantly after statin administration. However, similar changes were not observed in other TSH quartiles. Therefore, further studies are required to mechanistically confirm these conclusions.

Background: Atherosclerotic cardiovascular disease (ASCVD) is the most common cause of death in Europe. Although the 2019 European Society of Cardiology/European Atherosclerosis Society Guidelines for the management of dyslipidaemias claim a target low-density lipoprotein cholesterol (LDL-C) value of <55 mg/dL for very high-risk patients by use of lipid-lowering therapy (LLT) and lifestyle adaptations, the target level achievement is not satisfactory. We examined LLT use in ASCVD patients exceeding LDL-C target levels at admission and its adaptations at discharge., Methods and Results: Between January 2017 and February 2020, 1091 patients with LDL-C >100 mg/dL and ASCVD defined as diagnosis of angina pectoris (AP, n = 179), acute myocardial infarction (AMI, n = 317), chronic ischemic heart disease (CHD, n = 195), or peripheral artery disease (PAD, n = 400) were extracted from hospital records. LLT use on admission and discharge as well as recommendations on lifestyle and nutrition were analysed. On admission, 51% of the patients were not taking LLT. At discharge, 91% were prescribed statins and 87% were advised on lifestyle adaptation and/or pharmacological treatment. High-intensity statin use at discharge was present in 63% of the AP-group, 92% of the AMI-group, 62% of the CHD-group and 71% of the PAD-group. Ezetimibe was present in 16% and proprotein convertase subtilisin/kexin 9 inhibitors (PCSK9i) in 1%. However, of those on high-intensity statin, 25% remained on insufficient statin dosage., Conclusion: Switch to high-intensity statins and use of ezetimibe and PCSK9i was low in chronic ASCVD patients. Even though statin intake was high in high-risk patients, target levels were still not reached., Competing Interests: Declaration of competing interest CE has received travel support from Abbott outside the submitted work. HR has received speaker honoraria from NeoVasc, Corvia, BMS, MedUpdate, StremedUp, NephroUpdate, and Pfizer. He has acted as a consultant for BMS, Pfizer and Pluristem receiving in part also financial compensations for this work. He has received research grants from the German Federal Ministry for Education and Research (BMBF). His division within the University Hospital of Muenster has taken or is still taking part in multicentre trials of BARD, Bayer, BIOTRONIK, Novartis, and Pluristem receiving patient fees and financial compensation for these efforts. All honoraria, research grants, fees and financial compensations were received outside the submitted work. NM reports speaker honoraria from BARD and Bayer Vital GmbH, outside the submitted work. TJB was supported by a grant from BMBF (HiGHmed 01ZZ1802V). KG has worked as advisory board member for Amgen, Novartis and Daiichi-Sankyo and received honoraria from Amgen, Bayer Vital, Daiichi-Sankyo, Novartis, Sanofi Aventis and Amarin, all outside the submitted work. All other authors have nothing to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Detecting dyslipidemia early is important because atherosclerosis originates in childhood and early treatment can improve outcomes. In 2022, the Canadian Cardiovascular Society (CCS) and Canadian Pediatric Cardiology Association (CPCA) published a clinical practice update to detect, evaluate, and manage pediatric dyslipidemia. However, guidance on its translation into clinical laboratories is lacking. The Canadian Society of Clinical Chemists Working Group on Reference Interval Harmonization Lipid Team aims to assist guideline implementation and promote harmonized pediatric lipid reporting across Canada. The 2022 CCS/CPCA clinical practice update, 2011 National Heart, Lung, and Blood Institute integrated guidelines, and new data analysis (Canadian pediatric reference values from the Canadian Laboratory Initiative on Pediatric Reference Intervals [CALIPER] and retrospective patient data from large community laboratories) were incorporated to develop 5 key recommendations. These include recommendations to: (1) offer nonfasting and fasting lipid testing; (2) offer a lipid panel including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and triglycerides, with apolipoprotein B and lipoprotein(a) available as individually orderable tests; (3) flag total cholesterol, LDL-C, and non-HDL-C results ≥ 95th percentile, and HDL-C results < 10th percentile, as recommended by CCS/CPCA/National Heart, Lung, and Blood Institute and validated by CALIPER, and flag apolipoprotein B and nonfasting triglyceride results ≥ 95th percentile on the basis of CALIPER, and do not flag Lp(a) results but mention the adult cutoff in the interpretive comments; (4) implement interpretive comments listed in the current report; and (5) implement the National Institutes of Health LDL-C equation. The Canadian Society of Clinical Chemists Working Group on Reference Interval Harmonization Lipid Team will support clinical laboratories to implement these recommendations using knowledge translation strategies. Harmonizing pediatric lipid reporting across Canadian clinical laboratories will optimize clinical decision-making and improve cardiovascular risk management in youth., (Copyright © 2024 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Introduction: A new cardiovascular risk (CVR) calculator that incorporates Lipoprotein(a) [Lp(a)] levels has recently been designed., Aims: To estimate CVR using the new score and to identify the reduction in low-density lipoprotein cholesterol (LDL-C) or systolic blood pressure (SBP) necessary to balance the risk attributable to Lp(a)., Methods: CVR throughout life and at 10 years was estimated with the new score in patients in primary prevention, both considering and not considering the value of Lp(a). When the estimated risk considering Lp(a) levels exceeded the baseline risk, the reduction in LDL-C levels or SBP necessary to balance the risk attributable to Lp(a) was calculated., Results: In total, 671 patients (mean age 54.2 years, 47.2% women) were included. Globally, 22.7% of the population had high Lp(a) values (> 50 mg/dL or > 125 nmol/L). When calculating CVR throughout life and considering the Lp(a) value, the global risk increased in 66.7% of cases (median 19.3%). Similar results were observed when we assessed the 10-year risk. The risk associated with Lp(a) could be completely compensated by decreasing LDL-C (average 21 mg/dL) or SBP (average 6.3 mmHg) in 79.2% and 74.7% of cases, respectively., Conclusion: When calculating the CVR with the new score, two-thirds and one-third of the population were bidirectionally recategorized as 'up' or 'down,' respectively. The decrease in LDL-C or SBP mitigated the increased risk caused by Lp(a) levels across a substantial proportion of patients., (© 2024. The Author(s).)

Background and Aims: Sodium glucose co-transporter 2 (SGLT2)-inhibitors were developed as glucose-lowering drugs. Surprisingly, SGLT2-inhibitors also reduced risk of cardiovascular disease. The impact of SGLT2-inhibitors on lipids and lipoproteins is unclear, but an effect might contribute to the observed lower cardiovascular risk. We conducted a meta-analysis to examine this, overall and by dose, ethnicity, and drug type., Methods: PubMed, EMBASE and Web of Science were searched for randomized controlled trials examining all available SGLT2-inhibitors. Studies with available lipid measurements were included. Quantitative data synthesis was performed using random and fixed effects models., Results: We identified 60 randomized trials, including 147,130 individuals. Overall, using random effects models, SGLT2-inhibitor treatment increased total cholesterol by 0.09 mmol/L (95% CI: 0.06, 0.13), low-density lipoprotein (LDL) cholesterol by 0.08 mmol/L (0.05, 0.10), and high-density lipoprotein (HDL) cholesterol by 0.06 mmol/L (0.05, 0.07), while it reduced triglycerides by 0.10 mmol/L (0.06, 0.14). Fixed effects estimates were similar but with smaller effect sizes for HDL cholesterol and triglycerides. For higher SGLT2-inhibitor doses, there was a nominally higher non-significant effect on lipids and lipoproteins. In Asian compared to non-Asian populations, a slightly larger increase in HDL cholesterol and a decrease in triglycerides were observed, but with similar results for total and LDL cholesterol. Treatment effects on lipids and lipoproteins were generally robust across different SGLT2-inhibitor drugs., Conclusion: In meta-analyses, SGLT2-inhibition increased total, LDL, and HDL cholesterol and decreased triglycerides. Effect sizes varied slightly by drug dose and ethnicity but were generally robust by drug type., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Børge Nordestgaard reports consultancies with Novo Nordisk. The other authors have no disclosures., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Atherosclerotic cardiovascular disease (ASCVD) is accelerated in people with diabetes. Dyslipidemia, hyperglycemia, oxidative stress, and inflammation play a role via a variety of mechanisms operative in the artery wall. In addition, some unique features predispose people with type 1 diabetes to accelerated atherosclerosis. Various organizations have created guidelines that provide advice regarding screening, risk assessment, and roadmaps for treatment to prevent ASCVD in diabetes. Management of dyslipidemia, especially with statins, has proven to be of immense benefit in the prevention of clinical CVD. However, since many patients fail to attain the low levels of low-density lipoproteins (LDL) recommended in these guidelines, supplemental therapy, such as the addition of ezetimibe, bempedoic acid or PCSK9 inhibitors, is often required to reach LDL goals. As a result, the upfront use of combination therapies, particularly a statin plus ezetimibe, is a rational initial approach. The addition to statins of drugs that specifically lower triglyceride levels has not proven beneficial, although the addition of icosapent-ethyl has been shown to be of value, likely by mechanisms independent of triglyceride lowering. Newer treatments in development, including apoC-III and ANGPTL3 inhibitors, seem promising in further reducing apoB-containing lipoproteins., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Atherosclerotic cardiovascular disease (ASCVD) represents the primary cause of mortality among patients with Type 2 Diabetes Mellitus (T2DM). In this population, High-Density Lipoprotein (HDL) particles exhibit abnormalities in number, composition, and function, culminating in diminished anti-atherosclerotic capabilities despite normal HDL cholesterol (HDL-C) concentrations. Hyperglycemic conditions contribute to these alterations in HDL kinetics, composition, and function, causing T2DM patients' HDL particles to exhibit decreased concentrations of diverse lipid species and proteins. Treatment of hyperglycemia has the potential to correct abnormal HDL particle attributes in T2DM; however, pharmacological interventions, including metformin and thiazolidinediones, yield inconsistent outcomes with respect to HDL-C concentrations and functionality. Despite numerous attempts with diverse drugs, pharmacologically augmenting HDL-C levels has not resulted in clinical benefits in mitigating ASCVD risk. In contrast, reducing Low Density Lipoprotein cholesterol (LDL-C) via statins and ezetimibe has demonstrated significant efficacy in curtailing CVD risk among T2DM individuals. Promising results have been observed in animal models and early-phase trials utilizing recombinant HDL and Lecitin Cholesterol Acyl Transferase (LCAT) -enhancing agents, but the evaluation of their efficacy and safety in large-scale clinical trials is ongoing. While aberrant HDL metabolism constitutes a prevalent aspect of dyslipidemia in T2DM, HDL cholesterol concentrations and composition no longer offer valuable insights for informing therapeutic decisions. Nevertheless, HDL metabolism remains a critical research area in T2DM, necessitating further investigation to elucidate the role of HDL particles in the development of diabetes-associated complications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background and Aims: Half of dyslipidemic patients sometimes discontinue statin medication. It is unclear if blood atherogenic risk increases right after statin discontinuation or if there is a lingering protective effect. We sought to determine if a legacy effect prevented blood lipid increases during the first stages of statin cessation., Methods and Results: Atherogenic blood lipid profile was measured in 10 overweight (BMI 31 ± 3 kg m -2 ) middle-aged males (62 ± 7 years old), statin users, while fasted and postprandially. Trials were conducted before (i.e., Day 0) and after 4, 7, 15, and 30 days of statin withdrawal and 20 days after statins reloading (Day 50). Four days after statin discontinuation, blood fasting LDL-c, total cholesterol (CHOL), and triglyceride (TG) concentrations increased by 30%, 18%, and 17%, respectively (P < 0.05). The increases in LDL-c, CHOL, and TG peaked after 7-15 days at 79%, 48%, and 34% of basal levels (P < 0.001), respectively. There were no significant correlations between the increases in blood lipids and the dose or years under statin treatment (P = 0.156-0.575). Twenty days after resuming statins, blood LDL-c (2.79 ± 1.06 vs 2.20 ± 0.50 mmol L -1 ; P = 0.568), CHOL (4.85 ± 1.41 vs 4.25 ± 0.83 mmol L -1 ; P = 0.747), and TG (1.47 ± 0.60 vs 1.50 ± 0.68 mmol L -1 ; P = 0.782), returned to basal levels., Conclusions: Our data does not support a statin lingering/legacy effect in blood lipids since they dangerously increased after only 4 days of statin withdrawal in every patient, regardless of dose and years under treatment. Reloading statins restored blood lipids, evidencing a reproducible biological effect at the whole-body level., Competing Interests: Declaration of competing interest The authors have no conflicts of interest. ClinicalTrials.gov identifier: NCT04477590. The authors state that the results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Aims: We aimed to explore the association between remnant cholesterol (RC) level and risks of all-cause and cardiovascular deaths among American diabetic adults., Methods and Results: The data of 4,095 diabetic participants from the National Health and Nutrition Examination Survey (1999-2018) were included for analysis. Deaths were ascertained till December 31, 2019. RC level associated with death was assessed on a continuous scale with restricted cubic splines and by pre-defined quartile groups with Cox regression analysis. After a median follow-up of 6.9 years, 1,060 all-cause and 289 cardiovascular deaths occurred. Association between RC and death was U-shaped, and RC level correlated with the lowest risks of both all-cause and cardiovascular deaths was 0.85 mmol/L. After adjusting for confounders, compared with Quartile 3 (0.66-0.93 mmol/L), hazard ratios for all-cause deaths were 1.43 (95%CI 1.18-1.72, P = 0.0002) in Quartile 1 (≤0.47 mmol/L), 1.20 (95%CI 1.00-1.44, P = 0.05) in Quartile 2 (0.47-0.66 mmol/L), and 1.25 (95%CI 1.05-1.49, P = 0.02) in Quartile 4 (>0.93 mmol/L). Higher risk was also observed for cardiovascular deaths in Quartile 1 (HR 1.66, 95%CI 1.15-2.41, P = 0.007), Quartile 2 (HR 1.39, 95%CI 0.97-2.00, P = 0.08), and Quartile 4 (HR 1.54, 95% CI 1.08-2.19, P = 0.02), as compared with Quartile 3., Conclusion: In US adults with diabetes, low and high levels of RC were associated with increased risks of all-cause and cardiovascular deaths, and the lowest risk was observed at RC level of 0.85 mmol/L. These findings suggested that maintaining appropriate RC level may help reduce risk of death in diabetic patients., Competing Interests: Declaration of competing interest There are no conflicts of interest to report., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Dyslipidemia is an important risk factor for cardiovascular morbidity and mortality. Although low-density lipoprotein (LDL) is primarily responsible, the importance of triglyceride (TG) and high-density lipoprotein (HDL) has also been recognized. The present study investigated the effect of the atherogenic index of plasma (AIP), in which atherogenic and protective lipoproteins were evaluated together, on the initial flow in patients with ST elevation myocardial infarction. AIP was calculated as log(TG/HDL-cholesterol). Patients included in the study (n = 1535) were divided into Thrombolysis in Myocardial Infarction (TIMI) flow grade 0 and >0. AIP was found to be significantly different between 2 groups (.55 ± .23 vs .67 ± .21; P < .001). AIP was an independent predictor for pre-intervention TIMI flow (Odds Ratio: 2.778). A moderate correlation was found between TIMI frame count measurements, calculated in patients with TIMI 2-3, and AIP (Pearson correlation coefficient: .63, P < .001). In the receiver operating characteristic analysis, AIP showed the highest area under curve (AUC) compared with other lipid parameters for predicting vascular patency. The AUC of AIP was .634, the cut-off value was .59, and the sensitivity and specificity were 67.6% and 68.4%, respectively ( P < .001). In conclusion, AIP was found to be an important marker affecting pre-percutaneous coronary intervention TIMI flow., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Glucokinase (GK) plays a key role in glucose metabolism. In the liver, GK is regulated by GK regulatory protein (GKRP) with nuclear sequestration at low plasma glucose level. Some GK activators (GKAs) disrupt GK-GKRP interaction which increases hepatic cytoplasmic GK level. Excess hepatic GK activity may exceed the capacity of glycogen synthesis with excess triglyceride formation. It remains uncertain whether hypertriglyceridemia associated with some GKAs in previous clinical trials was due to direct GK activation or impaired GK-GKRP interaction., Methods: Using publicly available genome-wide association study summary statistics, we selected independent genetic variants of GCKR and GCK associated with fasting plasma glucose (FPG) as instrumental variables, to mimic the effects of impaired GK-GKRP interaction and direct GK activation, respectively. We applied two-sample Mendelian Randomization (MR) framework to assess their causal associations with lipid-related traits, risks of metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiovascular diseases. We verified these findings in one-sample MR analysis using individual-level statistics from the Hong Kong Diabetes Register (HKDR)., Results: Genetically-proxied impaired GK-GKRP interaction increased plasma triglycerides, low-density lipoprotein cholesterol and apolipoprotein B levels with increased odds ratio (OR) of 14.6 (95% CI 4.57-46.4) per 1 mmol/L lower FPG for MASLD and OR of 2.92 (95% CI 1.78-4.81) for coronary artery disease (CAD). Genetically-proxied GK activation was associated with decreased risk of CAD (OR 0.69, 95% CI 0.54-0.88) and not with dyslipidemia. One-sample MR validation in HKDR showed consistent results., Conclusions: Impaired GK-GKRP interaction, rather than direct GK activation, may worsen lipid profiles and increase risks of MASLD and CAD. Development of future GKAs should avoid interfering with GK-GKRP interaction., (© 2024. The Author(s).)

Objective: To investigate the association between cumulative exposure to low-density lipoprotein cholesterol (LDL-C) and carotid intima-media thickness (IMT) in the young adulthood population., Methods: Young adult subject (18-45 year old) from the Kailuan Study group who participated in the same period of follow-up and received carotid artery ultrasound were selected as the observation subjects. Among them, 3651 cases met the inclusion criteria, which required that carotid artery color ultrasound examinations be completed from 2010 to 2016, with complete IMT measurements, LDL-C data collected at least twice before carotid ultrasound, and participants' age to be ≤ 45 years at the time of carotid artery color ultrasound examination. Linear regression was used to analyze the correlation between time-weighted average (TWA) to LDL-C cumulative exposure and IMT the young population. Logistic regression was used to analyze the effects of different TWA groups on IMT thickening. Considering that the use of anti hypertensive drugs and lipid-lowering drugs may affect TWA LDL-C, this study excluded people taking antihypertensive drugs and lipid-lowering drugs, and conducted a repeat analysis of the main results., Results: There was a positive correlation between TWA LDL-C and IMT, with IMT increasing by 0.017 mm when TWA LDL-C increased by 1 mmol/L * year. The TWA LDL-C in the highest group was identified as a risk factor for IMT thickening, with odds ratio (OR) values of 1.812(1.027 ~ 3.200) in the T3 group. After excluding patients taking antihypertensive drugs and lipid-lowering drugs, the results still showed that the T3 group with the highest TWA LDL-C was a risk factor for IMT thickening, with an OR value of 1.850(0.988-3.464), P for trend is 0.043., Conclusion: This cohort study revealed that TWA LDL-C is positively correlated with IMT in young adulthood for risk stratification, and control LDL-C levels at an earlier age may reduce the lifetime risk of developing atherosclerotic disease., Trial Registration: ChiCTR-TNC-11001489., (© 2024. The Author(s).)

Background: Circulating atherogenic index of plasma (AIP) levels has been proposed as a novel biomarker for dyslipidemia and as a predictor of insulin resistance (IR) risk. However, the association between AIP and the incidence of new-onset stroke, particularly in individuals with varying glucose metabolism status, remains ambiguous., Methods: A total of 8727 participants aged 45 years or older without a history of stroke from the China Health and Retirement Longitudinal Study (CHARLS) were included in this study. The AIP was calculated using the formula log [Triglyceride (mg/dL) / High-density lipoprotein cholesterol (mg/dL)]. Participants were divided into four groups based on their baseline AIP levels: Q1 (AIP ≤ 0.122), Q2 (0.122 < AIP ≤ 0.329), Q3 (0.329 < AIP ≤ 0.562), and Q4 (AIP > 0.562). The primary endpoint was the occurrence of new-onset stroke events. The Kaplan-Meier curves, multivariate Cox proportional hazard models, and Restricted cubic spline analysis were applied to explore the association between baseline AIP levels and the risk of developing a stroke among individuals with varying glycemic metabolic states., Results: During an average follow-up of 8.72 years, 734 participants (8.4%) had a first stroke event. The risk for stroke increased with each increasing quartile of baseline AIP levels. Kaplan-Meier curve analysis revealed a significant difference in stroke occurrence among the AIP groups in all participants, as well as in those with prediabetes mellitus (Pre-DM) and diabetes mellitus (DM) (all P values < 0.05). After adjusting for potential confounders, the risk of stroke was significantly higher in the Q2, Q3, and Q4 groups than in the Q1 group in all participants. The respective hazard ratios (95% confidence interval) for stroke in the Q2, Q3, and Q4 groups were 1.34 (1.05-1.71), 1.52 (1.19-1.93), and 1.84 (1.45-2.34). Furthermore, high levels of AIP were found to be linked to an increased risk of stroke in both pre-diabetic and diabetic participants across all three Cox models. However, this association was not observed in participants with normal glucose regulation (NGR) (p > 0.05). Restricted cubic spline analysis also demonstrated that higher baseline AIP levels were associated with higher hazard ratios for stroke in all participants and those with glucose metabolism disorders., Conclusions: An increase in baseline AIP levels was significantly associated with the risk of stroke in middle-aged and elderly individuals, and exhibited distinct characteristics depending on the individual's glucose metabolism status., (© 2024. The Author(s).)

Background: A phase 3 trial was conducted to evaluate the efficacy and safety of ongericimab, a monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9, as an add-on treatment to optimized lipid-lowering therapy in Chinese patients with primary hypercholesterolemia and mixed dyslipidemia., Methods and Results: A total of 806 patients who were receiving stable and optimized lipid-lowering therapy but did not achieve their low-density lipoprotein cholesterol (LDL-C) targets were enrolled and randomly assigned in a 2:1:2:1 ratio to receive either ongericimab 150 mg or matching placebo every 2 weeks, or ongericimab 300 mg or matching placebo every 4 weeks for 52 weeks. Efficacy and safety were evaluated in 802 patients who received at least 1 dose of ongericimab or placebo. The primary end point was the percentage change in LDL-C from baseline to week 24. Our findings demonstrated that the least-squares mean difference of percentage change in LDL-C from baseline to week 24 was -67.7% (95% CI, -72.5% to -63.0%; P <0.0001) in the ongericimab 150 mg every 2 weeks group compared with the placebo every 2 weeks group, and -61.2% (95% CI, -67.1% to -55.2%; P <0.0001) in the ongericimab 300 mg every 4 weeks group compared with the placebo every 4 weeks group. These reductions were sustained up to week 52. Furthermore, treatment with ongericimab favorably altered other lipid parameters. A similar incidence of adverse events was observed in the ongericimab and placebo groups., Conclusions: Ongericimab, as an add-on treatment to optimized lipid-lowering therapy, significantly reduced LDL-C and was well-tolerated in Chinese patients with primary hyperlipidemia and mixed dyslipidemia who did not achieve their LDL-C targets., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04781114.

Aims: Elevated small dense LDL cholesterol (sd-LDL-C) increases atherosclerotic cardiovascular disease (CVD) risk. Although coronary artery calcification (CAC) is widely used for predicting CVD events, few studies have examined the relationship between sd-LDL-C and CAC., Methods and Results: This study included 4672 individuals with directly measured baseline sd-LDL-C and CAC from the Multi-Ethnic Study of Atherosclerosis [mean (standard deviation) age: 61.9 (10.4) years; 52.5% women; 47.3% with baseline CAC (mean score >0)]. We used multi-variable general linear models and restricted cubic splines with the goodness of fit testing to evaluate the association of sd-LDL-C with the presence of CAC. Odds ratios [OR (95% confidence interval)] were adjusted for demographics and cardiovascular risk factors, including estimated total LDL-C. Higher quartiles of sd-LDL-C were associated with the presence of CAC, even after accounting for total LDL-C. Compared with the lowest quartile of sd-LDL-C, participants in Quartiles 2, 3, and 4 had higher odds for the presence of baseline CAC [Quartile 2 OR: 1.24 (1.00, 1.53); Quartile 3 OR: 1.51 (1.19, 1.93); and Quartile 4 OR 1.59 (1.17, 2.16)]. Splines suggested a quadratic curvilinear relationship of continuous sd-LDL-C with CAC after adjustment for demographics and CVD risk factors (quadratic vs. first-order sd-LDL-C terms likelihood ratio test: P = 0.015), but not after accounting for total LDL-C (quadratic vs. first-order terms: P = 0.156)., Conclusion: In a large, multi-ethnic sample without known CVD, higher sd-LDL-C was associated with the presence of CAC, above and beyond total LDL-C. Whether selective direct measurement of sd-LDL-C is indicated to refine cardiovascular risk assessment in primary prevention warrants further investigation., Competing Interests: Conflict of interest: M.D.S. has participated in scientific advisory boards with the following entities: Amgen, Agepha, Ionis, Novartis, Precision BioScience, Novo Nordisk, and New Amsterdam; and has served as a consultant for Ionis, Novartis, Regeneron, Aidoc, Kaneka, and Shanghai Pharma Biotherapeutics. C.L.S. has received honoraria from the National Institutes of Health for service on grant review panels. All other authors have nothing to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This article briefly discusses the risk factors for the development of lower extremity artery disease, namely smoking, diabetes mellitus, hyperlipidemia/dyslipidemia and hypertension. Each of these risk factors will be discussed in detail in forthcoming articles of the journal.

Studies have shown that fasting during Ramadan has different effects on circulating levels of several biochemical markers. This study aims to conduct a comprehensive evaluation of studies related to the effect of fasting in the holy month of Ramadan on lipid profile, uric acid, and HbA1c in CKD patients. Studies were systematically searched and collected from three databases (PubMed, Scopus, and Web of Science). After screening, the quality and risk of bias assessment of the selected articles were evaluated. Study heterogeneity was assessed using the Cochrane test and I² statistic. In case of any heterogeneity random effects model with the inverse-variance method was applied. All analyses were performed using STATA software version 16. Four observational studies were included in this study. The results of this meta-analysis were that cholesterol (Weighted mean differences (WMD):0.21 with 95% CI:-0.09-0.51 (P-value=:0.18)), LDL (WMD:0.06 with 95% CI -0.24-0.36 (P-value:0.69)), triglyceride (WMD:0.05 with 95% CI:-0.25-0.35 (P-value:0.73)) had not-significant increase. Uric acid (WMD: -0.11 with 95% CI: -0.42-0.21 (P-value:0.51)) and HbA1c (WMD: -0.22 with 95% CI: -0.79-0.36 (P-value: 0.46)) show a non-significant decrease. The results of the analyses did not report significant changes in the lipid profile, uric acid, and HbA1c in CKD patients after Ramadan fasting., Competing Interests: Declaration of Competing Interest The authors have not disclosed any competing interests., (Copyright © 2024 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Background: Statins are lipid-lowering drugs with favorable anti-inflammatory effects. This study aimed to explore different statin-based lipid-lowering strategies to reduce high-sensitivity C-reactive protein (hs-CRP)., Hypothesis: The hypothesis is that different statin-based lipid-lowering strategies might reduce hs-CRP., Methods: This retrospective study included 3653 patients who underwent percutaneous coronary intervention (PCI). Three statin-based lipid-lowering strategies were investigated, including different types of statins (atorvastatin vs. rosuvastatin), statin combined with ezetimibe therapy (vs. without), and intensive statin therapy (vs. regular). The hs-CRP levels and blood lipid indicators were measured at baseline and after 1-month lipid-lowering therapy. Multivariable linear regression analysis and structural equation mode analysis were conducted to verify the association between different lipid-lowering strategies, Δhs-CRP (%) and ΔLDL-C (%)., Results: Totally, 3653 patients were enrolled with an average age of 63.81 years. Multivariable linear regression demonstrated that statin combined with ezetimibe therapy was significantly associated with decreased Δhs-CRP (%) (β = -0.253, 95% CI: [-0.501 to -0.005], p = 0.045). The increased ΔLDL-C (%) was an independent predictor of elevated levels of Δhs-CRP (%) (β = 0.487, 95% CI: [0.15-0.824], p = 0.005). Furthermore, structural equation model analysis proved that statin combined with ezetimibe therapy (β = -0.300, p < 0.001) and intensive statin therapy (β = -0.032, p = 0.043) had an indirect negative effect on Δhs-CRP via ΔLDL-C., Conclusions: Compared with routine statin use, statin combined with ezetimibe therapy and intensive statin therapy could further reduce hs-CRP levels., (© 2024 The Author(s). Clinical Cardiology published by Wiley Periodicals LLC.)

Background and Aims: Proper prescription and high adherence to intensive lipid lowering drugs (LLD) in patients with coronary heart disease (CHD) are crucial and strongly recommended. The aim of this study is to investigate long-term treatment patterns and adherence to LLD following hospitalization for a CHD event., Methods: Patients admitted to two Norwegian hospitals with a CHD event from 2011 to 2014 (N = 1094) attended clinical examination and completed a questionnaire, median 16 months later. Clinical data were linked to pharmacy dispensing data from 2010 to 2020. The proportions using high-intensity statin therapy (atorvastatin 40/80 mg or rosuvastatin 20/40 mg) and non-statin LLD after the CHD event were assessed. Adherence was evaluated by proportion of days covered (PDC) and gaps in treatment., Results: Median age at hospitalization was 63 (IQR 12) years, 21 % were female. Altogether, 1054 patients (96 %) were discharged with a statin prescription, while treatment was dispensed in 85 % within the following 90 days. During median 8 (SD 2.5) years follow-up, the proportion using high-intensity statin therapy ranged 62-68 %, whereas the use of ezetimibe increased from 4 to 26 %. PDC <0.8 was found in 22 % of statin users and 26 % of ezetimibe users. The proportions with a treatment gap exceeding 180 days were 22 % for statins and 28 % for ezetimibe. Smoking at hospitalization and negative affectivity were significantly associated with reduced statin adherence, regardless of adherence measure., Conclusions: In this long-term follow-up of patients with CHD, less than 70 % used high-intensity statin therapy with only small changes over time, and only 25 % used additional treatment with ezetimibe. We identified factors associated with reduced statin adherence that may be target for interventions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:IE and CB are affiliated with Oslo Economics and have completed consultancy assignments outside the submitted work for several public and private institutions in recent years. HS is affiliated with Steno Diabetes Center Aarhus and has received consultancy fees from Novartis, Arla Foods AMBA, Bristol-Myers Squibb, Pfizer and Neumirna outside the submitted work. EH, ES and TD reports no conflicts of interest. SH has received lecture fees from Sanofi, Novartis, and Pfizer outside the submitted work. JM received lecture fees from Sanofi, Novartis, Boehringer Ingelheim, and Bayer outside the submitted work., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Mobile health technology's impact on cardiovascular risk factor control is not fully understood. This study evaluates the association between interaction with a mobile health application and change in cardiovascular risk factors., Methods and Results: Participants with hypertension with or without dyslipidemia enrolled in a workplace-deployed mobile health application-based cardiovascular risk self-management program between January 2018 and December 2022. Retrospective evaluation explored the influence of application engagement on change in blood pressure (BP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and weight. Multiple regression analyses examined the influence of guideline-based, nonpharmacological lifestyle-based digital coaching on outcomes adjusting for confounders. Of 102 475 participants, 49.1% were women. Median age was 53 (interquartile range, 43-61) years, BP was 134 (interquartile range, 124-144)/84 (interquartile range, 78-91) mm Hg, TC was 183 (interquartile range, 155-212) mg/dL, LDL-C was 106 (82-131) mg/dL, and body mass index was 30 (26-35) kg/m 2 . At 2 years, participants with baseline systolic BP ≥140 mm Hg reduced systolic BP by 18.6 (SEM, 0.3) mm Hg. At follow up, participants with baseline TC ≥240 mg/dL reduced TC by 65.7 (SEM, 4.6) mg/dL, participants with baseline LDL-C≥160 mg/dL reduced LDL-C by 66.6 (SEM, 6.2) mg/dL, and participants with baseline body mass index ≥30 kg/m 2 lost 12.0 (SEM, 0.3) pounds, or 5.1% of body weight. Interaction with digital coaching was associated with greater reduction in all outcomes., Conclusions: A mobile health application-based cardiovascular risk self-management program was associated with favorable reductions in BP, TC, LDL-C, and weight, highlighting the potential use of this technology in comprehensive cardiovascular risk factor control.

Aims: Most studies of treatment adherence after acute coronary syndrome (ACS) are based on prescribed drugs and lack long-term follow-up or consecutive data on risk factor control. We studied the long-term treatment adherence, risk factor control, and its association to recurrent ACS and death., Methods and Results: We retrospectively included 3765 patients (mean age 75 years, 40% women) with incident ACS from 1 January 2006 until 31 December 2010 from the Swedish Primary Care Cardiovascular Database of Skaraborg. All patients were followed until 31 December 2014 or death. We recorded blood pressure (BP), low-density lipoprotein cholesterol (LDL-C), recurrent ACS, and death. We used data on dispensed drugs to calculate the proportion of days covered for secondary prevention medications. Cox regressions were used to analyse the association of achieved BP and LDL-C to recurrent ACS and death. The median follow-up time was 4.8 years. The proportion of patients that reached BP of <140/90 mm Hg was 58% at Year 1 and 66% at Year 8. 65% of the patients reached LDL-C of <2.5 mmol/L at Year 1 and 56% at Year 8; however, adherence to statins varied from 43% to 60%. Only 62% of the patients had yearly measured BP, and only 28% yearly measured LDL-C. Systolic BP was not associated with a higher risk of recurrent ACS or death. Low-density lipoprotein cholesterol of 3.0 mmol/L was associated with a higher risk of recurrent ACS {hazard ratio [HR] 1.19 [95% confidence interval (CI) 1.00-1.40]} and death HR [1.26 (95% CI 1.08-1.47)] compared with an LDL-C of 1.8 mmol/L., Conclusion: This observational long-term real-world study demonstrates low drug adherence and potential for improvement of risk factors after ACS. Furthermore, the study confirms that uncontrolled LDL-C is associated with adverse outcome even in this older population., Competing Interests: Conflict of interest: S.B. reports research grants from Astra Zeneca and personal fees from Amarin, Amgen, Astra Zeneca, Sanofi, and Novo Nordisk. T.K. report research grants to Karolinska Institutet from Medtronic and ReCor Medical. These companies do not have access to the data and do not have the right to review manuscripts before publication., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The 2013 ACC/AHA Guideline was a paradigm shift in lipid management and identified the four statin-benefit groups. Many have studied the guideline's potential impact, but few have investigated its potential long-term impact on MACE. Furthermore, most studies also ignored the confounding effect from the earlier release of generic atorvastatin in Dec 2011., Methods: To evaluate the potential (long-term) impact of the 2013 ACC/AHA Guideline release in Nov 2013 in the U.S., we investigated the association of the 2013 ACC/AHA Guideline with the trend changes in 5-Year MACE survival and three other statin-related outcomes (statin use, optimal statin use, and statin adherence) while controlling for generic atorvastatin availability using interrupted time series analysis, called the Chow's test. Specifically, we conducted a retrospective study using U.S. nationwide de-identified claims and electronic health records from Optum Labs Database Warehouse (OLDW) to follow the trends of 5-Year MACE survival and statin-related outcomes among four statin-benefit groups that were identified in the 2013 ACC/AHA Guideline. Then, Chow's test was used to discern trend changes between generic atorvastatin availability and guideline potential impact., Results: 197,021 patients were included (ASCVD: 19,060; High-LDL: 33,907; Diabetes: 138,159; High-ASCVD-Risk: 5,895). After the guideline release, the long-term trend (slope) of 5-Year MACE Survival for the Diabetes group improved significantly (P = 0.002). Optimal statin use for the ASCVD group also showed immediate improvement (intercept) and long-term positive changes (slope) after the release (P < 0.001). Statin uses did not have significant trend changes and statin adherence remained unchanged in all statin-benefit groups. Although no other statistically significant trend changes were found, overall positive trend change or no changes were observed after the 2013 ACC/AHA Guideline release., Conclusions: The 2013 ACA/AHA Guideline release is associated with trend improvements in the long-term MACE Survival for Diabetes group and optimal statin use for ASCVD group. These significant associations might indicate a potential positive long-term impact of the 2013 ACA/AHA Guideline on better health outcomes for primary prevention groups and an immediate potential impact on statin prescribing behaviors in higher-at-risk groups. However, further investigation is required to confirm the causal effect of the 2013 ACA/AHA Guideline., (© 2024. The Author(s).)