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Objective: The aim of this study was to investigate the relationship between triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) and the risk of cardiovascular disease (CVD) in middle-aged and elderly Chinese population. CVD has high morbidity and mortality in China, with 5.09 million CVD deaths in 2019 and a mortality rate of 364.5 cases per 100,000 people. Existing studies have focused on specific populations and lack studies on the general population., Methods: This study used data from the China Health and Aged Care Tracking Survey (CHARLS) to analyse the middle-aged and elderly population between 2011 and 2020. The exposure variable was TG/HDL-C ratio, the outcome variable was the occurrence of heart disease (including myocardial infarction, coronary heart disease, etc.), and the covariates included age, gender, education level, and body mass index. The final sample size was 4,551 participants. Weighted Cox regression models were used to assess the association between TG/HDL-C and CVD risk, and nonlinear associations and stratified analyses were performed., Results: The results demonstrated a significant association between TG/HDL-C ratios and cardiac morbidity, with a risk ratio of 0.71 (95% CI: 0.71-0.71) in the adjusted model II. Nonlinear analysis revealed a threshold effect. Within the TG/HDL-C 0.15-1.5 interval (inflection point LnTG/HDL-C 0.41), each 1-unit increase in Ln (TG/HDL-C) was associated with a 17% reduction in the risk. The inflection point was associated with a 0.83-fold reduction in the risk of CVD (95% CI: 0.75, 0.92; p = 0.0003), but beyond this point, the association was no longer significant (1.00-fold reduction in risk; 95% CI: 0.95, 1.05; p = 0.9701). In contrast, stratified analyses demonstrated that the results were more applicable to women and those younger than 65 years., Conclusion: In summary, the study found a significant inverse relationship between the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and the risk of cardiovascular disease in the middle-aged and elderly Chinese population, with a nonlinear threshold effect observed at a TG/HDL-C ratio of around 1.5., Competing Interests: Declarations Ethics approval and consent to participate This study was approved by the Biomedical Ethics Committee of Peking University (IRB00001052-11015). The study adhered to the principles of Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). All participants were thoroughly informed and signed a written informed consent form prior to enrollment, thereby agreeing to participate in the baseline and follow-up surveys. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Aims: To estimate the proportion eligible for lipid-lowering therapy (LLT) when using the systemic coronary risk estimation 2 (SCORE2) on apparently healthy individuals., Methods and Results: Individuals aged 50-64 years were randomly invited to The Swedish Cardiopulmonary Bioimage Study (n = 30 154). Participants with previous atherosclerotic cardiovascular disease (CVD), diabetes mellitus, or chronic kidney disease were excluded. The 10-year risk of CVD was estimated using the SCORE2 equation and the multicell chart. Eligibility for LLT was estimated according to the 2021 European Society of Cardiology CVD prevention guidelines. Presence of coronary atherosclerosis was determined using coronary computed tomography angiography (CCTA). Among 26 570 apparently healthy individuals, 32% had high and 4% had very high 10-year CVD risk, according to the SCORE2 equation. Among high- and very-high-risk individuals, 99% had low-density lipoprotein cholesterol levels above guideline goals making 35% of the total population eligible for LLT. Of those eligible, undergoing imaging, 38% had no signs of coronary atherosclerosis according to CCTA. Using the SCORE2 chart, 52% of the population were eligible for LLT, of which 44% had no signs of coronary atherosclerosis. In those with high or very high risk, ongoing LLT was reported in 7% and another 11% received LLT within 6 months after study participation., Conclusion: Nearly all apparently healthy individuals with high and very high CVD risk, or 35% of the total population, were eligible for LLT according to guidelines, and a large proportion had no signs of atherosclerosis. Compared with the SCORE2 equation, the SCORE2 chart resulted in more individuals being eligible for LLT., Competing Interests: Conflict of interest: A.Y. reports institutional research grant from MSD, outside the submitted work. A.R.-F. reports grants from Amarin and Bayer and payment for lectures and expert testimony from Amarin, Amgen, Astra Zeneca, Boehringer Ingelheim, Novartis, Novo Nordisk, Orion Pharma, Pfizer, and Sanofi. J.A. reports lecture fee from Boehringer Ingelheim, Astra Zeneca, MSD, Bayer, and Novartis and advisory board reimbursement from Astra Zeneca and Novartis. S.S. reports consultancy and speakers honoraria from Actelion Ltd. E.H. reports institutional research grants from Pfizer and Amgen and small personal fees from Amarin, Amgen, Astra Zeneca, Bayer, and Novo Nordisk. T.J. reports research grant funding from MSD (significant). All other authors declare no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: To assess whether implementation of the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) dyslipidaemia guidelines observed between 2020 and 2021 improved between 2021 and 2022 in the SANTORINI study., Methods and Results: Patients with high or very high cardiovascular (CV) risk were recruited across 14 European countries from March 2020 to February 2021, with 1-year prospective follow-up until May 2022. Lipid-lowering therapy (LLT) and 2019 ESC/EAS risk-based low-density lipoprotein (LDL) cholesterol (LDL-C) goal attainment (defined as <1.4 mmol/L for patients at very high CV risk and <1.8 mmol/L for patients at high CV risk) at 1-year follow-up were compared with baseline. Of 9559 patients enrolled, 9136 (2626 high risk and 6504 very high risk) had any available follow-up data, and 7210 (2033 high risk and 5173 very high risk) had baseline and follow-up LDL-C data. Lipid-lowering therapy was escalated in one-third of patients and unchanged in two-thirds. Monotherapy and combination therapy usage rose from 53.6 and 25.6% to 57.1 and 37.9%, respectively. Mean LDL-C levels decreased from 2.4 to 2.0 mmol/L. Goal attainment improved from 21.2 to 30.9%, largely driven by LLT use among those not on LLT at baseline. Goal attainment was greater with combination therapy compared with monotherapy at follow-up (39.4 vs. 25.5%)., Conclusion: Lipid-lowering therapy use and achievement of risk-based lipid goals increased over 1-year follow-up particularly when combination LLT was used. Nonetheless, most patients remained above goal; hence, strategies are needed to improve the implementation of combination LLT., Competing Interests: Conflict of interest: K.K.R. has received honoraria for consulting, lectures from Abbott Laboratories, Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim, Cargene, CRISPR, Daiichi Sankyo, Eli Lilly Company, Emendobio, Esperion, Kowa, New Amsterdam Pharma, Novartis Corporation, Nodthera, GSK, Novo Nordisk, Pfizer, Regeneron, Sanofi, SCRIBE, Silence Therapeutics, and VAXXINITY. In addition, he has received research grant support to his institution from Amgen, Daiichi Sankyo, Sanofi, Regeneron, and Ultragenyx, plus stock options from New Amsterdam Pharma, Scribe, and Pemi 31. A.L.C. received research grant support from Amryt Pharma, Menarini, Ultragenyx, and Viatris, and lecturing fees from Amarin, Amgen, Amryt Pharma, AstraZeneca, Daiichi Sankyo, Esperion, Ionis Pharmaceutical, Medscaper, Menarini, Merck, Novartis, Peervoice, Pfizer, Recordati, Regeneron, Sandoz, Sanofi, The Corpus, Ultragenyx, and Viatris. M.A. received research grant support and lecturing fees from Alfasigma, Amgen, Amryt, Daiichi Sankyo, Ionis Pharmaceuticals/Akcea Therapeutics, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi, Sobi, Viatris, and Ultragenyx. A.B., R.C., M.L., and J.S. are employees of Daiichi Sankyo. H.T. received grant support and lecturing fees from Daiichi Sankyo and participated in an advisory board run by Daiichi Sankyo. T.S. received consulting fees from Amgen, Novartis, Orion Pharma, and Valio, and lecturing fees from Amarin, Pfizer, and GSK. He is a patient on statin and ezetimibe therapy. U.L. received grant support from Daiichi Sankyo, Novartis, and Amgen and lecturing fees from Daiichi Sankyo, Novartis, Amgen, Sanofi, Boehringer, MSD, Pfizer, Lilly, and AstraZeneca. He has also been a member of advisory boards for Daiichi Sankyo, Novartis, Amgen, Sanofi, Boehringer, and MSD, in addition to donning leadership/fiduciary roles with EAS, ESC, DGK, and DACH., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: European clinical guidelines recommend that patients with atherosclerotic cardiovascular disease (ASCVD), including ischaemic heart disease (IHD), stroke, and peripheral arterial disease (PAD), are prescribed lipid lowering treatment (LLT) and treated to target low-density lipoprotein cholesterol (LDL-C) levels. This study aimed to document trends in ASCVD, including treatment, monitoring, and achievement of target LDL-C., Methods and Results: A retrospective observational population study was performed using linked healthcare data (2010-22). Over the study period, the number of patients with ASCVD increased from 181 153 to 207 747 (8882 to 9398 per 100 000). The proportion of patients prescribed LLT decreased from 75.3% in 2010 to 67.1% in 2022; high-intensity statin therapy increased from 9.4 to 25.2%, while non-high-intensity statin therapy decreased from 59.6 to 38.2%. The prescription of high-intensity statin therapy was consistently higher amongst patients with IHD (10.9% in 2010 increasing to 28.0% in 2022) than in patients with stroke (4.7-21.6%) or PAD (3.9-10.6%).The proportion of cases with documented LDL-C decreased from 58.0% in 2010 to 49.3% in 2022. Of those with documented LDL-C in 2022, 44.0% achieved LDL-C < 1.8 mmol/L, including 45.2% of those with IHD, 42.0% of those with stroke, and only 32.8% of those with PAD., Conclusion: Prescription of LLT, including high-intensity statin therapy, documentation of LDL-C, and achievement of target LDL-C levels was relatively low, especially in PAD patients. Although target achievement in 'tested patients' increased over time, the proportion of patients undergoing lipid testing declined. More rigorous lipid management requires prioritisation, especially for PAD and stroke patients., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: No data are available on early initiation of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in patients with acute coronary syndrome (ACS) in the real world. This study investigates the effects of PCSK9i started at time of ACS hospitalization on lipid control and major cardiovascular (CV) events in the real world., Methods and Results: The lipid control outcome was the percentage of patients reaching the LDL-C target of <55 mg/dL at first lipid control. The clinical outcome was the incidence of composite major CV events (all-cause death, non-fatal MI, non-fatal stroke, and ischaemia-driven revascularization) during a follow-up in relation to quartiles of LDL-C at first lipid control. We included 771 patients with ACS from the AT-TARGET-IT registry, receiving PCSK9i prescription during hospitalization or at discharge. Median LDL-C was 137 mg/dL and decreased to 43 mg/dL at first lipid control. 527 (68.3%) patients achieved LDL-C target at the first lipid control at a median time of 37 days from hospitalization; of them, 404 (76.8%) were discharged on statin plus ezetimibe background therapy. Event curves through a median follow-up of 11 months across quartiles of LDL-C showed a stepwise lower risk of 4P-MACE, 3P-MACE, all-cause mortality, and ischaemia-driven revascularization in lower quartile of LDL-C values at first lipid control (<23 mg/dL) and in patients reaching LDL-C < 55 mg/dL., Conclusion: Intensive and early lipid-lowering therapy using PCSK9i in patients with ACS (strike early-strike strong strategy) is safe and effective in clinical practice and associated with a reduction of residual CV risk., Competing Interests: Conflict of interest: none declared., (© 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.)

Aims: Women are less likely to receive lipid-lowering therapy (LLT) after acute myocardial infarction (AMI). We analysed whether this under-prescription currently persists and has an impact on long-term outcomes., Methods and Results: The FAST-MI programme consists of nationwide registries including all patients admitted for AMI ≤ 48 h from onset over a 1 month period in 2005, 2010, and 2015, with long-term follow-up. This analysis focused on high-intensity LLT (atorvastatin ≥ 40 mg or equivalent, or any combination of statin and ezetimibe) in women and men. Women accounted for 28% (N = 3547) of the 12 659 patients. At discharge, high-intensity LLT was significantly less prescribed in women [54 vs. 68% in men, P < 0.001, adjusted odds ratio (OR) 0.78(95% confidence interval (CI) 0.71-0.87)], a trend that did not improve over time: 2005, 25 vs. 35% (P = 0.14); 2010, 66 vs. 79% (P < 0.001); 2015, 67 vs. 79.5% (P = 0.001). In contrast, female sex was not associated with a lack of other recommended treatments at discharge: beta-blockers [adjusted OR 0.98(95% CI 0.88-1.10), P = 0.78], or renin-angiotensin blockers [adjusted OR 0.94(95% CI 0.85-1.03), P = 0.18]. High-intensity LLT at discharge was significantly associated with improved 5 year survival and infarct- and stroke-free survival in women [adjusted hazard ratios (HR) 0.74(95% CI 0.64-0.86), P < 0.001 and adjusted HR: 0.81(95% CI: 0.74-0.89); P < 0.001, respectively]. Similar results were found using a propensity score-matched analysis [HR for 5 year survival in women with high-intensity LLT: 0.82(95% CI 0.70-0.98), P = 0.03]., Conclusion: Women suffer from a bias regarding the prescription of high-intensity LLT after AMI, which did not attenuate between 2005 and 2015, with potential consequences on both survival and risk of cardiovascular events., Competing Interests: Conflict of interest: N.D. has received personal fees and non-financial support from Amgen, AstraZeneca, Bayer, BMS, Sanofi, personal fees from Boehringer Ingelheim, Intercept, MSD, Novo Nordisk, Pfizer, Servier, UCB Pharmaceuticals, and Vifor, all outside the submitted work. E.P. reports fees for lectures and/or consulting: Amgen, AstraZeneca, Bayer, Biotronik, BMS, Boehringer Ingelheim, Daiichi Sankyo, Lilly, MSD, The Medicine Company, Sanofi, Saint Jude Medical, Servier, Siemens. J.F. reports speaking fees for Amgen, Sanofi, Servier and MSD. F.S. reports personal fees from Amgen, AstraZeneca, Bayer, BMS, MSD, Pfizer, and Sanofi, outside the submitted work. T.S. reports grants from AstraZeneca, Daiichi Sankyo, Eli-Lilly, GSK, MSD, Novartis, Sanofi, and personal fees for board membership and/or consultancy and/or lectures from AstraZeneca, BMS, Sanofi, and Novartis. J.-L.G. reports personal fees for lectures and/or consulting: Amgen, MSD, Novartis, and Sanofi-Winthrop France., (© 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.)

Introduction: Inclisiran, an siRNA targeting hepatic PCSK9 mRNA, administered twice-yearly (after initial and 3-month doses), substantially and sustainably reduced LDL-cholesterol (LDL-C) in Phase III trials. Whether lowering LDL-C with inclisiran translates into a reduced risk of major adverse cardiovascular events (MACE) is not yet established. In-silico trials applying a disease computational model to virtual patients receiving new treatments allow to emulate large scale long-term clinical trials. The SIRIUS in-silico trial programme aims to predict the efficacy of inclisiran on CV events in individuals with established atherosclerotic cardiovascular disease (ASCVD)., Methods and Results: A knowledge-based mechanistic model of ASCVD was built, calibrated, and validated to conduct the SIRIUS programme (NCT05974345) aiming to predict the effect of inclisiran on CV outcomes. The SIRIUS Virtual Population included patients with established ASCVD (previous myocardial infarction (MI), previous ischemic stroke (IS), previous symptomatic lower limb peripheral arterial disease (PAD) defined as either intermittent claudication with ankle-brachial index <0.85, prior peripheral arterial revascularization procedure, or vascular amputation) and fasting LDL-C ≥ 70 mg/dL, despite stable (≥4 weeks) well-tolerated lipid-lowering therapies.SIRIUS is an in-silico multi-arm trial programme. It follows an idealized crossover design where each virtual patient is its own control, comparing inclisiran to (i) placebo as adjunct to high-intensity statin therapy with or without ezetimibe, (ii) ezetimibe as adjunct to high-intensity statin therapy, (iii) evolocumab as adjunct to high-intensity statin therapy and ezetimibe.The co-primary efficacy outcomes are based on the time to the first occurrence of any component of 3P-MACE (composite of CV death, nonfatal MI, or nonfatal IS) and time to occurrence of CV death over 5 years., Perspectives/conclusion: The SIRIUS in-silico trial programme will provide early insights regarding potential effect of inclisiran on MACE in ASCVD patients, several years before the availability of the results from ongoing CV outcomes trials (ORION-4 and VICTORION-2-P)., Clinical Trial Registration: Clinicaltrials.gov identifier: NCT05974345., Competing Interests: Conflict of interest: Denis Angoulvant reports having received payment or honoraria for lectures, presentations, speakers bureaus or educational events from Amgen, Alnylam, Amarin, Astra Zeneca, Boehringer, BMS, Bouchara Recordati, Pfizer, Novartis, Novo Nordisk, Organon, Sanofi, Servier, Vifor. Gabriel Steg reports the following: research grants from Amarin and Sanofi. Consulting or speaking for Amarin, Amgen, BMS and Novo-Nordisk. Clinical Trials (Steering committee, CEC, DSMB) for Amarin, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Idorsia, Janssen, Novartis, Novo-Nordisk, Pfizer, Sanofi. Senior Associate Editor at Circulation and Chief Scientific Officer of Bioquantis Guillaume Mahé reports having received payments for consulting, speaking, or educational events from Amgen, Amarin, Bayer Healthcare, BMS, Leo Pharma, Novartis, Novo Nordisk, Pfizer and Sanofi. Bertrand Cariou reports having received payments for consulting, speaking, or educational events from Amgen, Astra Zeneca, BMS, Eli Lilly, Novartis, Novo Nordisk, Sanofi, Ultragenyx. Franck Boccara reports having received payments for consulting, speaking, or educational events from Amgen, Amarin, Novartis, Novo Nordisk, Boehringer, Servier, ViiV healthcare, Gilead and Sanofi. Pierre Amarenco reports the following: grants from the French government (PHRC: RIISC-THETIS, TST-40, SPICAF trials), Pfizer and AstraZeneca (TST trial). Speaker fee from Novartis, Viatris and Sanofi. Advisory board for Novartis and Neuraltide. Steering committee for Bayer., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Obesity is a complex, diverse and multifactorial disease that has become a major public health concern in the last decades. The current classification systems relies on anthropometric measurements, such as BMI, that are unable to capture the physiopathological diversity of this disease. The aim of this study was to redefine the classification of obesity based on the different H-NMR metabolomics profiles found in individuals with obesity to better assess the risk of future development of cardiometabolic disease., Materials and Methods: Serum samples of a subset of the Di@bet.es cohort consisting of 1387 individuals with obesity were analyzed by H-NMR. A K-means algorithm was deployed to define different H-NMR metabolomics-based clusters. Then, the association of these clusters with future development of cardiometabolic disease was evaluated using different univariate and multivariate statistical approaches. Moreover, machine learning-based models were built to predict the development of future cardiometabolic disease using BMI and waist-to-hip circumference ratio measures in combination with H-NMR metabolomics., Results: Three clusters with no differences in BMI nor in waist-to-hip circumference ratio but with very different metabolomics profiles were obtained. The first cluster showed a metabolically healthy profile, whereas atherogenic dyslipidemia and hypercholesterolemia were predominant in the second and third clusters, respectively. Individuals within the cluster of atherogenic dyslipidemia were found to be at a higher risk of developing type 2 DM in a 8 years follow-up. On the other hand, individuals within the cluster of hypercholesterolemia showed a higher risk of suffering a cardiovascular event in the follow-up. The individuals with a metabolically healthy profile displayed a lower association with future cardiometabolic disease, even though some association with future development of type 2 DM was still observed. In addition, H-NMR metabolomics improved the prediction of future cardiometabolic disease in comparison with models relying on just anthropometric measures., Conclusions: This study demonstrated the benefits of using precision techniques like H-NMR to better assess the risk of obesity-derived cardiometabolic disease., (© 2024. The Author(s).)

Dyslipidaemia is a common chronic kidney disease (CKD) and contributes to excessively elevated cardiovascular mortality. The pathophysiology is complex and modified by comorbidities like the presence/absence of proteinuria, diabetes mellitus or drug treatment. This paper provides an overview of currently available treatment options. We focused on individuals with CKD and excluded those on renal replacement therapy (haemodialysis, peritoneal dialysis, or kidney transplantation). The use of statins is safe and recommended in most patients, but guidelines vary with respect to low-density lipoprotein (LDL) cholesterol goals. While no dedicated primary or secondary prevention studies are available for pro-protein convertase subtilisin/kexin type 9 inhibitors, secondary analyses of large outcome trials reveal no effect modification on endpoints by the presence of CKD. Similar data have been shown for bempedoic acid, but no definite conclusion can be drawn with respect to efficacy and safety. No outcome trials are available for inclisiran while the cholesterol lowering effects seem to be unaffected by CKD. Finally, the value of fibrates and icosapent ethyl in CKD is unclear. Lipid abnormalities contribute to the massive cardiovascular disease burden in CKD. Lowering of LDL cholesterol with statins (and most likely PCSK9 inhibitors) reduces the event rate and thus statin therapy should be initiated in almost all individuals. Other interventions (bempedoic acid, inclisiran, fibrates, or icosapent ethyl) currently need a case-by-case decision before prescription., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Backgrounds: High-intensity statin is recommended for patients undergoing percutaneous coronary intervention (PCI), and ezetimibe is recommended to be added in patients not achieving low-density lipoprotein cholesterol (LDL-C) targets. Moderate-intensity statin plus ezetimibe can reduce LDL-C levels similar to high-intensity statin. The aim of this study is to examine the long-term efficacy and safety of moderate-intensity statin plus ezetimibe as the first-line strategy compared to high-intensity statin in patients undergoing PCI., Method: Data was obtained from the Health Insurance Review and Assessment Service database of South Korea. Patients who underwent PCI from 2012 to 2017 were included. The primary efficacy endpoint was major adverse cardiac cerebrovascular events (MACCEs), a composite of all-cause death, revascularization, or ischemic stroke. The safety endpoint was new-onset diabetes mellitus (DM)., Results: A total of 45,501 patients received high-intensity statin (n = 38,340) or moderate-intensity statin plus ezetimibe (n = 7,161). Among propensity-score-matched 7,161 pairs, MACCEs occurred in 1,460 patients with high-intensity statin and 1,406 patients with moderate-intensity statin plus ezetimibe (33.8% vs. 31.9%, hazard ratio 0.96, 95% confidence interval 0.89-1.03, P = 0.27) at a median follow-up of 2.7 years. DM was newly diagnosed in 398 patients with high-intensity statin and 342 patients with moderate-intensity statin plus ezetimibe (12.5% vs. 10.7%; hazard ratio 0.84, 95% confidence interval 0.73-0.97, P = 0.02)., Conclusion: In patients undergoing PCI, moderate-intensity statin plus ezetimibe demonstrated a similar risk of MACCEs but a lower risk of new-onset DM than high-intensity statin. Early combination treatment of moderate-intensity statin and ezetimibe may be a useful and safe lipid-lowering strategy after PCI., (© 2024. The Author(s).)

Objective: Patients with symptomatic lower extremity artery disease (LEAD) should have an optimal management in terms of lipid goal [i.e. controlled LDL-cholesterol (LDLc)] and medical treatment (triple therapy with an antiplatelet agent, a statin and an angiotensin-converting enzyme inhibitor or a angiotensin-receptor antagonist). Prevalence of LEAD patients with a LDLc < 0.55 g/l is unknown. Aims of this study were to: (i) describe the prevalence of patients with a LDLc < 0.55 g/l, (ii) describe the prevalence of patients with an optimal medical treatment; (iii) compare this management between patients with a vascular surgery history and those without a vascular surgery history; and (iv) evaluate the number of patients eligible for new lipid-lowering therapies according to FOURIER and REDUCE-IT criteria., Methods: In this single-center retrospective study, prevalence is expressed as numbers and percentages. Comparison of the number of well managed patients between LEAD patients with a vascular surgery history and those without was performed. Number of patients who would be eligible for FOURIER and REDUCE-IT studies were calculated., Results: Among the LEAD patients included in the analysis (n = 225), only 12.4% (n = 28) had a LDLc < 0.55 g/L. The prevalence of patients who received the optimal medical treatment was 50.7% (n = 114). There was no statistical difference in the prevalence of patients with and without vascular surgery history achieving the LDLc goal (n = 9 (10.6%) vs. n = 19 (13.6%); p = not significant). Ninety-three patients (46.0%) would be eligible for EVOLOCUMAB treatment according to the Fourier study design whereas 17 patients (8.4%) would be eligible for treatment with ICOSAPENT ETHYL according to the REDUCE-IT study design., Conclusion: A majority of LEAD patients did not reach the LDLc goals. LEAD patients with a vascular surgery history did not experience a better management whereas they had a more consistent follow-up., (© 2024. The Author(s).)

Background: Limited observational research has explored the relationship between the non-high-density lipoprotein cholesterol (non-HDL-C) to high-density lipoprotein cholesterol (HDL-C) ratio (NHHR) and the risk of post-stroke depression (PSD). This study aims to investigate the potential associations between NHHR and PSD., Methods: A cross-sectional study was conducted using data from stroke participants aged 20 and older, sourced from the National Health and Nutrition Examination Survey (NHANES) spanning 2005 to 2018. Depression was assessed using the PHQ-9 questionnaire. The association between NHHR and PSD risk was evaluated through weighted multivariate logistic regression and restricted cubic spline (RCS) models. Subgroup and sensitivity analyses were performed to validate the findings., Results: In the continuous model, the NHHR value for the PSD group (3.23±1.84) was significantly higher than that of the non-PSD group (2.79±1.40, p=0.015). Logistic regression analysis in the fully adjusted model revealed a positive association between NHHR and PSD (OR 1.16, 95 % CI 1.03-1.30, p=0.016). Interaction tests showed no significant differences across strata (p > 0.05 for interaction). Restricted cubic spline results indicated a linear dose-response relationship between NHHR and PSD risk (P for non-linearity = 0.6). This association persisted in various subgroup analyses., Conclusion: NHHR was significantly correlated with an increased risk of PSD among U.S. adults. Further re-search on NHHR could contribute to the prevention and treatment of PSD., Competing Interests: Declaration of competing interest The authors declared that there were no potential conflicts of interest regarding this article., (Copyright © 2024. Published by Elsevier Inc.)

Background and Aim: Adequate serum vitamin D levels correlate with a more favorable lipid profile compared to deficient levels. Despite the well-established prevalence of vitamin D deficiency in children with obesity, studies investigating its influence on lipid profiles in this population are scarce. We explored the impact of vitamin D status on lipid profiles and markers of atherogenic dyslipidemia in a cohort of children and adolescents with obesity., Methods and Results: A total of 271 Caucasian children and adolescents with overweight/obesity and a control group of 54 pediatric patients with normal weight. All participants underwent outpatient visits for the assessment of clinical parameters and venous blood collection for biochemical analysis such as triglycerides (TG)/HDL-C ratio, LDL-C/HDL-C ratio, atherogenic index of plasma AIP), vitamin D level. Individuals with obesity displayed severe vitamin D deficiency (25-OH-D ≤10 ng/ml) at a higher frequency compared to those with normal weight (p = 0.03). In patients with overweight/obesity and low 25-OH-D levels show higher values of glycemia (p = 0.001), insulin resistance (HOMA-IR and TRYG p < 0.001), TG (p < 0.001), TG/HDL-C (p = 0.001), AIP (p < 0.001), SBP (p = 0.01), and DBP (p = 0.04). In normal-weight individuals with low 25-OH- D levels an increased values of glycemia (p = 0.01), insulin resistance (HOMA-IR p = 0.01 and TRYG p = 0.002), TG (p = 0.01), TG/HDL-C (p = 0.02), AIP (p = 0.01). A direct correlation between 25-OH-D levels and metabolic parameters is observed., Conclusions: A correlation between vitamin D levels and the lipid/atherosclerotic profile was recorded. Vitamin D deficiency may represent a preventable and easily treatable cardiometabolic risk factor, emphasizing the importance of early intervention and preventive measures., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interests., (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.)

Background: Older general population-based studies found an inverse association between serum HDL-cholesterol and both cardiovascular disease (CVD) events and mortality, but more recent data have suggested a U-shaped relationship. Whether this applies to type 2 diabetes is uncertain. The aim of this study was to assess the prognostic significance of serum HDL-cholesterol concentrations in representative, community-based participants from the Fremantle Diabetes Study Phase II (FDS2)., Methods: We followed 1,479 FDS2 participants with confirmed type 2 diabetes (713 females, mean age 65.6 years; 763 males, mean age 65.9 years) from entry (2008-2011) to death/end-2021. Major adverse cardiovascular events (non-fatal myocardial infarction (MI), non-fatal stroke, cardiovascular death; 3-point MACE), and all-cause mortality were ascertained from prospectively collected data and validated administrative databases. Independent associates of 3-point MACE by sex, excluding participants with prior MI/stroke, were assessed using Cox and competing risk models with sex-specific quintiles of HDL-cholesterol added to the most parsimonious models. Predictors of all-cause mortality were identified using Cox proportional hazards modelling., Results: In females, with baseline serum HDL-cholesterol quintile 2 (1.04-1.22 mmol/L) as reference, both quintiles 1 (< 1.04 mmol/L) and 5 (> 1.59 mmol/L) were significant independent predictors of 3-point MACE (P < 0.027) and all-cause death (P < 0.019) after adjustment for a full range of demographic, clinical and laboratory variables. In males, serum HDL-cholesterol quintile did not add to the most parsimonious model for 3-point MACE, but quintile 1 (< 0.90 mmol/L) was a significant predictor of death (P = 0.026 versus quintile 4 (1.15-1.31 mmol/L) as reference) after adjustment. Competing risk analyses for 3-point MACE showed similar results to the Cox models for both sexes., Conclusion: There was a significant U-shaped relationship between serum HDL-cholesterol and both 3-point MACE and all-cause death in females with type 2 diabetes after adjustment for confounders. There was no such relationship for 3-point MACE in males but a low HDL-cholesterol was associated with all-cause mortality. These data have sex-specific implications for assessment of serum lipid profiles in the clinical management of type 2 diabetes., (© 2024. The Author(s).)

Background: Glucomannan has been studied for various health benefits, but its effects on lipid profile in adults are not well understood. This meta-analysis aims to evaluate the impact of glucomannan supplementation on serum/plasma levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), Apo B1, Apo A1, APO-B/ A1 ratio, and LDL-C/ HDL-C in adults., Methods: A comprehensive search was conducted across Scopus, PubMed, Embase, and Web of Science from inception to June 2024 to identify randomized controlled trials (RCTs) assessing glucomannan supplementation on lipid profile in adults. Data were extracted and analyzed using random effects model to determine the standardized mean differences (SMDs) and 95% confidence intervals (CIs) for each biomarker., Results: Glucomannan supplementation significantly decreased TC (SMD: -3.299; 95% CI: -4.955, -1.664, P < 0.001; I 2  = 95.41%, P-heterogeneity < 0.001), LDL-C (SMD: -2.993; 95% CI: -4.958, -1.028; P = 0.006; I 2  = 95.49%, P-heterogeneity < 0.001), and Apo B1 (SMD: -2.2; 95% CI: -3.58, -0.82; P = 0.01). However, glucomannan did not alter the levels of TG (SMD: -0.119; 95% CI: -1.076, 0.837, P = 0.789; I 2  = 91.63%, P-heterogeneity < 0.001), Apo A1 (SMD: -0.48; 95% CI: -6.27, 5.32; P = 0.76), APO-B/ A1 ratio (SMD: -1.15; 95% CI: -2.91, 0.61; P = 0.11), and LDL-C/ HDL-C ratio (SMD: -2.2; 95% CI: -7.28, 2.87; P = 0.2)., Conclusions: Glucomannan supplementation has a beneficial effect on the level of TC and LDL-C., (© 2024. The Author(s).)

Aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are effective in reducing cardiovascular events, but their impact on all-cause mortality and medical utilization compared to statins is unclear. This study investigated PCSK9 inhibitor use and its impact on mortality and medical utilization vs. statins, using TriNetX database data with up to 9 years of follow-up., Methods and Results: This retrospective cohort study analysed TriNetX data spanning 1 July 2015, to 31 December 2023, including 79 194 PCSK9 inhibitor users (alirocumab, evolocumab, inclisiran) and 5 437 513 statin users with hyperlipidaemia. The primary outcomes were all-cause mortality and medical utilization, including hospital inpatient services, emergency department visits, critical care, and mechanical ventilation. Propensity score matching showed that PCSK9 inhibitor use was associated with a 28.3% lower risk of all-cause mortality [adjusted hazard ratio (aHR) 0.717, 95% confidence interval (CI): 0.673-0.763] and significant reductions in medical utilization (hospital inpatient services usage: aHR 0.692, 95% CI: 0.664-0.721; emergency department services: aHR 0.756, 95% CI: 0.726-0.788; critical care services: aHR 0.619, 95% CI: 0.578-0.664; and mechanical ventilation: aHR 0.537, 95% CI: 0.484-0.596) compared to statins. These findings were consistent across various demographics and clinical subgroups. The sensitivity analyses supported the robustness of the findings., Conclusion: PCSK9 inhibitors significantly reduced all-cause mortality and medical utilization compared to statins, suggesting their important role in dyslipidaemia management, particularly for statin-naïve or intolerant patients. Further research, including randomized controlled trials, is needed to confirm these findings and explore the underlying mechanisms., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Icosapent ethyl lowers triglycerides and significantly reduces major adverse cardiovascular events (MACE), though treatment effects may vary between individuals. This study aimed to determine the relative and absolute effects of icosapent ethyl on MACE according to baseline cardiovascular disease (CVD) risk in patients with atherosclerotic cardiovascular disease (ASCVD)., Methods and Results: Participants from the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) with ASCVD were included (n = 5785). The primary outcome was 3-point MACE, i.e. non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death. Baseline 5-year risk of MACE was estimated using the European Society of Cardiology (ESC) guideline-recommended SMART2 risk score. Modification of the relative treatment effects of icosapent ethyl by baseline risk was assessed using Cox proportional hazards models, including a treatment-by-risk interaction. Next, treatment effects were assessed stratified by quartiles of baseline risk. During a median follow-up of 4.8 years (interquartile range 3.2-5.3), MACE occurred in 361 vs. 489 patients in the icosapent ethyl vs. placebo group [95% confidence interval (CI)]; hazard ratio (HR) 0.72 (0.63-0.82), absolute risk reduction (ARR) 4.4% (2.6-6.2%), number needed to treat (NNT) 23 (16-38), and 5-year Kaplan-Meier estimated cumulative incidence reduction (CIR) 5.7% (3.5-7.9%). Icosapent ethyl significantly reduced MACE in all risk quartiles, with an HR (95% CI) of 0.62 (0.43-0.88), 0.66 (0.48-0.92), 0.69 (0.53-0.90), and 0.78 (0.63-0.96), respectively (P for treatment-by-risk interaction = 0.106). The ARR (95% CI) increased across risk quartiles, i.e. was 3.9% (1.0-6.8%), 4.3% (1.2-7.3%), 5.1% (1.4-8.7%), and 5.6% (1.3-10.0%), respectively. This translates to NNTs (95% CI) of 26 (15-98), 24 (14-84), 20 (11-70), and 18 (10-77). The 5-year CIR (95% CI) was 4.8% (1.3-8.2%), 5.0% (1.3-8.7%), 6.1% (1.7-10.5%), and 7.7% (2.3-13.2%), respectively. Consistent results were obtained for 5-point MACE, additionally including coronary revascularization and unstable angina., Conclusion: Among patients with ASCVD and elevated triglyceride levels, icosapent ethyl significantly reduces the risk of MACE irrespective of baseline CVD risk, though absolute benefits are largest for patients at the highest risk., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Examine whether the low-density lipoprotein cholesterol (LDL -C) determination method influences the rate of statin initiation for primary prevention of cardiovascular disease., Methods and Results: We conducted a register-based retrospective study in the Region of Southern Denmark. Two hospital-based laboratories in the region directly measure LDL -C whereas four laboratories calculate LDL -C using Friedewald's formula. Physicians do not choose which method is used. We included all statin-naïve patients ≥40 years with no history of cardiovascular disease, diabetes, or chronic kidney disease, who had their LDL -C determined during 2018-2019. There were 202 807 people who had LDL -C determined during the study period (median age 59 years, 44% women) of which 37% had a direct LDL -C measurement. The median reported LDL -C was 3.40 mmol/L [interquartile range (IQR) 2.90-4.00] for those with a direct measurement vs. 3.00 mmol/L (IQR 2.40-3.50) for those with calculated LDL -C. For those with direct measurement, re-calculated LDL -C (using Friedewald's formula) was 0.35 mmol/L lower than the reported direct LDL -C measurement. Among those with directly measured LDL -C, 3.6% initiated statins compared with 2.7% of those with a calculated LDL -C. Direct LDL -C measurement led to higher odds of having a statin initiated compared with calculated LDL -C (adjusted odds ratio 1.23, 95% CI 1.17-1.30); for those with triglycerides >1.7 mmol/L the adjusted odds ratio was 1.41 (95% CI 1.30-1.52)., Conclusion: Differences in the reporting of LDL -C from laboratories using different methods have a substantial influence on physician's decisions to prescribe statins., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

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.)

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.)

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.

Purpose: Many adults with atherosclerotic cardiovascular disease (ASCVD) who are recommended to take a statin, ezetimibe and/or a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) by the 2018 American Heart Association/American College of Cardiology cholesterol guideline do not receive these medications. We estimated the percentage of recurrent ASCVD events potentially prevented with guideline-recommended cholesterol-lowering therapy following a myocardial infarction (MI) hospitalization., Methods: We conducted simulations using data from US adults with government health insurance through Medicare or commercial health insurance in the MarketScan database. We used data from patients with an MI hospitalization in 2018-2019 to estimate the percentage receiving guideline-recommended therapy. We used data from patients with an MI hospitalization in 2013-2016 to estimate the 3-year cumulative incidence of recurrent ASCVD events (i.e., MI, coronary revascularization or ischemic stroke). The low-density lipoprotein cholesterol (LDL-C) reduction with guideline-recommended therapy was derived from trials of statins, ezetimibe and PCSK9i, and the associated ASCVD risk reduction was estimated from a meta-analysis by the Cholesterol-Lowering Treatment Trialists Collaboration., Results: Among 279,395 patients with an MI hospitalization in 2018-2019 (mean age 75 years, mean LDL-C 92 mg/dL), 27.3% were receiving guideline-recommended cholesterol-lowering therapy. With current cholesterol-lowering therapy use, 25.3% (95%CI: 25.2%-25.4%) of patients had an ASCVD event over 3 years. If all patients were to receive guideline-recommended therapy, 19.8% (95%CI: 19.5%-19.9%) were estimated to have an ASCVD event over 3 years, representing a 21.6% (95%CI: 20.5%-23.6%) relative risk reduction., Conclusion: Implementation of guideline-recommended cholesterol-lowering therapy could prevent a substantial percentage of recurrent ASCVD events., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Cardiovascular disease is the leading cause of death among women in the United States. Past research has highlighted the importance of the relationship between female-specific demographics and traditional risk factors. The present analysis aimed to identify the prevalence of modifiable risk factors in women attending a community cardiovascular health screening., Methods: Data collected between 2011 and 2019 were obtained from the Houston HeartReach Registry. Participants were classified as having or not having each of 4 traditional cardiometabolic risk factors: hypertension, diabetes, body mass index indicating overweight or obesity, and dyslipidemia. Differences in prevalence were compared using the Pearson χ2 test., Results: Most participants had hypertension, overweight or obesity, and dyslipidemia. Older women (≥65 years) had the highest prevalence of all cardiometabolic risk factors. Black participants had a higher prevalence of hypertension (P = .006) and a lower prevalence of dyslipidemia (P = .009) than non-Black participants. Hispanic participants had a lower prevalence of hypertension (P < .001) and a higher prevalence of overweight or obesity (P = .03) than non-Hispanic participants. Participants in the lowest household income bracket (<$25,000) were more likely to have diabetes (P = .001) and overweight or obesity (P = .004) than participants in the highest income bracket (≥$50,000). Unemployed participants had a higher prevalence of diabetes (P < .001), overweight or obesity (P = .004), and dyslipidemia (P < .001) than employed participants. Comorbidity analysis revealed clustering of multiple cardiometabolic risk factors. Moreover, risk factor hot spots were identified by zip code, which could help select future sites for targeted screening., Conclusion: The analysis found that cardiometabolic risk factor prevalence varies with demographic and socioeconomic status. Geographic areas where cardiometabolic risk factor prevalence was highest were also identified. Further participant recruitment and analysis are required to create predictive models of cardiovascular disease risk in women., (© 2024 The Authors. Published by The Texas Heart Institute®.)

Background: It remains unclear whether the association between dyslipidemia status and triglyceride-glucose (TyG) index with myocardial damage varies in the context of type 2 diabetes mellitus (T2DM). This study aimed to determine the differential effects of dyslipidemia status and TyG index on left ventricular (LV) global function and myocardial microcirculation in patients with T2DM using cardiac magnetic resonance (CMR) imaging., Methods: A total of 226 T2DM patients and 72 controls who underwent CMR examination were included. The T2DM group was further categorized into subgroups based on the presence or absence of dyslipidemia (referred to as T2DM (DysL+) and T2DM (DysL-)) or whether the TyG index exceeded 9.06. CMR-derived LV perfusion parameters, remodeling index, and global function index (GFI) were assessed and compared among groups. A multivariable linear regression model was employed to evaluate the effects of various variables on LV myocardial microcirculation, remodeling index, and GFI., Results: The LV GFI sequentially decreased in controls, T2DM (DysL-), and T2DM (DysL+) groups (p < 0.001), and was lower (p = 0.003) in T2DM with higher TyG index group than in lower TyG index group. The LV remodeling index was higher in higher TyG index group than in lower TyG index group (p = 0.002), but there was no significant difference in whether the subgroup was accompanied by dyslipidemia. Multivariable analysis revealed that the TyG index, but not dyslipidemia status, was independently associated with LV remodeling index (β coefficient[95% confidence interval], 0.152[0.025, 0.268], p = 0.007) and LV GFI (- 0.159[- 0.281, - 0.032], p = 0.014). For LV myocardial microcirculation, perfusion index, upslope, and max signal intensity sequentially decreased in controls, T2DM (DysL-), and T2DM (DysL+) groups (all p < 0.001). Dyslipidemia status independently correlated with perfusion index (- 0.147[- 0.272, - 0.024], p = 0.02) and upslope (- 0.200[- 0.320, 0.083], p = 0.001), while TyG index was independently correlated with time to maximum signal intensity (0.141[0.019, 0.257], p = 0.023)., Conclusions: Both dyslipidemia status and higher TyG index were associated with further deterioration of LV global function and myocardial microvascular function in the context of T2DM. The effects of dyslipidemia and a higher TyG index appear to be differential, which indicates that not only the amount of blood lipids and glucose but also the quality of blood lipids are therapeutic targets for preventing further myocardial damage., (© 2024. The Author(s).)

Background: Rapid progression of non-target lesions (NTLs) leads to a high incidence of NTL related cardiac events post-PCI, which accounting half of the recurrent cardiac events. It is important to identify the risk factors and establish an accurate clinical prediction model for the rapid progression of NTLs post-PCI. PCSK9 inhibitors lower LDL-c levels significantly, also show the anti-inflammation effect, and may have the potential to reduce the rapid progression of NTLs post-PCI. We tried to test this hypothesis and explore the potential mechanisms., Methods: This retrospective study included 1250 patients who underwent the first PCI and underwent repeat coronary angiography for recurrence of chest pain within 24 months. General characteristics, laboratory tests and inflammatory factors(IL-10, IL-6, IL-8, IL-1β, sIL-2R, and TNF-α) were collected. Machine learning (LASSO regression) was mainly employed to select the important characteristic risk factors for the rapid progression of NTLs post-PCI and build prediction models. Finally, mediator analysis was employed to explore the potential mechanisms by which PCSK9 inhibitors reduce the rapid progression of NTLs post-PCI., Results: There were more diabetes, less beta-blockers and PCSK9 inhibitors application, higher HbA1c, LDL-c, ApoB, TG, TC, uric acid, hs-CRP, TNF-α, IL-6, IL-8, and sIL-2R in NTL progressed group. LDL-c, hs-CRP, IL-8, and sIL-2R were characteristic risk factors for the rapid progression of NTLs post-PCI, combining LDL-c, hs-CRP, IL-8, and sIL-2R builds the optimal model for predicting the rapid progression of NTLs post-PCI (AUC = 0.632). LDL-c had a clear and incomplete mediating effect (95% CI, mediating effect: 51.56%) in the reduction of the progression of NTLs by PCSK9 inhibitors, and there was a possible mediating effect of IL-8 (90% CI), and sIL-2R (90% CI)., Conclusions: LDL-c, hs-CRP, IL-8, and sIL-2R may be the key characteristic risk factors for the rapid progression of NTLs post-PCI, and combining these parameters might predict the rapid progression of NTLs post-PCI. The application of PCSK9 inhibitors had a negative correlation with the rapid progression of NTLs. In addition to the significant LDL-c-lowering, PCSK9 inhibitors may reduce the rapid progression of NTLs by reducing local inflammation of plaque., Trial Registration: ChiCTR2200058529; Date of registration: 2022-04-10., (© 2024. The Author(s).)

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: This study aims to systematically evaluate the clinical efficacy and safety of acupuncture in combination with statin therapy compared to statin monotherapy for the treatment of dyslipidemia., Methods: A comprehensive search for relevant randomized controlled trials assessing the clinical efficacy of acupuncture and statin combination in the treatment of dyslipidemia was conducted. Databases including PubMed, EMbase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, China Biology Medicine disc, Wanfang database, and China Science and Technology Journal Database were searched up to October 27, 2023., Results: Sixteen Chinese-language studies involving a total of 1333 subjects were included for analysis. The meta-analysis revealed that the total effective rate of acupuncture combined with statin was significantly higher than that of statin alone (odds ratios = 3.32, 95% confidence intervals [CI] = 2.33 to 4.72). Furthermore, the combination of acupuncture with statin treatment resulted in a significant reduction in triglyceride levels (mean differences [MD] = -0.72 mmol/L, 95% CI = -1.05 to -0.4), total cholesterol levels (MD = -0.79 mmol/L, 95% CI = -1.07 to -0.51), low-density lipoprotein cholesterol levels (MD = -0.61 mmol/L, 95% CI = -0.95 to -0.27) and traditional Chinese medicine syndrome integral (MD = -1.32, 95% CI = -1.75 to -0.89), compared to statin treatment alone. Additionally, the high-density lipoprotein cholesterol level was higher in the combined acupuncture and statin treatment group than in the statin treatment alone group (MD = 0.44 mmol/L, 95% CI = 0.09 to 0.79). Notably, the rate of adverse reactions reported with combined acupuncture and statin treatment was lower than that with statin therapy alone., Conclusion: Our findings support the potential of acupuncture combined with statin as a viable clinical treatment option for dyslipidemia. However, it is important to note that current research on the mechanism of acupuncture for lipid-lowering has not yielded definitive results, and there are inherent biases in the conducted clinical studies., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Backgrounds and Objective: Statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, are pivotal in managing hypercholesterolemia and reducing cardiovascular risk. While rosuvastatin demonstrates superior efficacy and tolerability compared to other statins, its safety profile in elderly patients older than 75 years old with acute coronary syndrome (ACS) remains underexplored. So, the objective of this study is to evaluate the frequency of adverse reactions and investigate the efficacy of high-dose rosuvastatin on lipid profiles in elderly patients aged over 75 with ACS., Methods: In this observational study, 110 consecutive elderly ACS patients attending Modarres Hospital in Tehran, Iran, in 2019 were enrolled. The effects of high-dose rosuvastatin were assessed in elderly patients older than 75 years old by comparison of the adverse effects, lipid profile, cardiac function, and other biomarkers at the baseline and after 6 weeks of rosuvastatin therapy with a dose of 40 mg., Results: Following 6 weeks of treatment, there was a significant reduction in total cholesterol (136.2 ± 24.3 to 115.5 ± 24.0, p = 0.001) and LDL levels (72.6 ± 17.5 to 50.9 ± 18.9, p = 0.001), accompanied by a notable increase in HDL levels (38.3 ± 7.1 to 47.2 ± 7.4, p = 0.001). Cardiac function, as measured by ejection fraction (EF), significantly improved from 43.4 ± 8.8 to 48.5 ± 8.5 (p = 0.001). Adverse effects such as cramps (N = 12, p = 0.001), weakness (N = 28, p = 0.001), and anorexia (N = 12, p = 0.001) were reported but did not warrant discontinuation of therapy. Notably, no cases of jaundice were observed. Two deaths occurred due to major adverse cardiac events (MACE) during the study period, unrelated to stroke or recurrent myocardial infarction., Conclusion: Totally, high-dose rosuvastatin therapy effectively improved lipid profiles, cardiac function, and liver enzyme levels in elderly ACS patients, with manageable adverse effects. These findings underscore the importance of rosuvastatin in optimizing cardiovascular health in this vulnerable population., (© 2024. The Author(s).)

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).)

Elevated blood cholesterol and triglyceride levels induced by secondary causes are frequently observed. The identification and appropriate handling of these causes are essential for secondary dyslipidemia treatment. Major secondary causes of hypercholesterolemia and hypertriglyceridemia include an unhealthy diet, diseases and metabolic conditions affecting lipid levels, and therapeutic side effects. It is imperative to correct secondary causes prior to initiating conventional lipid-lowering therapy. Guideline-based lipid therapy can then be administered based on the subsequent lipid levels.

Background: COVID-19 restrictions prompted changes in chronic disease management and lifestyle modifications, potentially altering cardiometabolic indicators and lipid-lowering pharmacotherapy patterns. We aimed to assess lipid-lowering drug (LLD) utilization trends during COVID-19 restrictions., Methods: We obtained nationwide outpatient drug sales and prescribing data for 01.03.2018-31.12.2022 from IQVIA™ Turkey. We evaluated average monthly LLD consumption, their costs, and quarterly prescribing levels in three periods: "before restrictions" (BfR, 01.03.2018-31.03.2020), "during restrictions" (DuR, 01.04.2020-31.03.2022), and "after restrictions" (AfR, 01.04.2022-31.12.2022). Drug utilization was measured via "defined daily dose/1000 inhabitants/day" (DID) metric., Results: LLD utilization increased from 25.4 ± 3.1 DID in BfR to 36.2 ± 6.8 DID in DuR (p < 0.001), and to 42.6 ± 5.3 DID in AfR (p < 0.001 vs. BfR). Statin consumption significantly rose from 22.0 ± 3.0 DID in BfR to 31.6 ± 6.3 DID in DuR (p < 0.001), and further to 37.6 ± 4.7 DID in AfR (p < 0.01 vs. DuR). High-intensity statin consumption elevated by 115.9% in AfR compared to baseline (p < 0.001). Prescribing of LLDs decreased from 12.5 ± 0.6 DID in BfR to 7.2 ± 1.2 DID in DuR (p < 0.001), later reached 13.6 ± 3.8 DID in AfR (p < 0.001 vs. DuR), with prescribing for ongoing users following similar trend. Expenditure on LLDs increased from €8.4 m ± 0.9 m in BfR to €11.4 m ± 2.0 m in DuR (p < 0.001) and to €12.8 m ± 1.9 m in AfR (p < 0.001 vs. BfR)., Conclusions: This study revealed a surge in consumption of LLDs in Turkey following the onset of the COVID-19 pandemic. This rise might be related to practices facilitating drug access, in addition to potentially greater adherence, or the necessity for more intense pharmacotherapy due to elevated cardiovascular risk., 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 Inc. All rights reserved.)

Background: Arteriovenous fistula (AVF) failure can occur in patients undergoing hemodialysis (HD). In this study, we explored the correlation between hyperlipidemia and AVF failure in patients undergoing HD. Moreover, we compared the lipid profiles of patients with chronic kidney disease (CKD) with those of healthy people to provide a basis for lipid-lowering in patients undergoing HD., Method and Analysis: We searched PubMed, Web of Science, Embase, the Cochrane library, CNKI, CBM, the China Science Periodical Database, and the China Science and Technology Journal Database. The final search was conducted on August 31, 2021, and the search period was restricted between 2000 and August 31, 2021, without publication restrictions. All studies met the inclusion criteria, and the influences of sex, age, geographical location, diagnosis method, and publication year were excluded. The data were analyzed using the random-effects model and the fixed-effects model., Results: Twenty-eight studies were included in the meta-analysis with 121,666 patients in the CKD group and 1714 patients in the AVF failure group. Triglyceride concentration in patients with CKD was higher than in healthy subjects (MD: -31.56, 95% CI: -41.23 to -21.90, p  < 0.00001). A high total cholesterol (TC) concentration (MD: 6.97, 95% CI: 2.19-11.74, p  = 0.004) and a high low-density lipoprotein cholesterol (LDL-C) concentration (MD: 23.83, 95% CI: 18.48-29.18, p  < 0.00001) were associated with AVF failure. Furthermore, HDL-C was lower in the AVF failure group than in the AVF patency group (MD: -2.68, 95% CI: -4.60 to -0.76, p  = 0.006)., Conclusion: Our analysis indicates that the AVF failure may be related to the increase of TC/LDL-C and the decrease of HDL-C. Although current guidelines do not consider intensive lipid-lowering therapy as necessary in patients undergoing HD, our research indicates that patients with AVF undergoing HD may need regular TC/LDL-C-lowering therapy to prevent AVF failure. However, this issue still needs well designed prospective trials., 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.

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.)

Background/aims: Achieving rapid reduction of low-density lipoprotein cholesterol (LDL-C) levels below 55 mg/dL in patients with acute myocardial infarction (AMI) can be challenging with statins alone. This single-center, retrospective study aimed to assess the impact of single-dose injection of evolocumab 140 mg on LDL-C levels during the peri-percutaneous coronary intervention (PCI) period in patients with AMI., Methods: A total of 95 patients with AMI who underwent PCI were divided into the evolocumab (n = 50) and non-evolocumab (n = 45) groups., Results: The percentage change of LDL-C level at 1-3 weeks from baseline was 78.4 ± 13.4% reduction in the evolocumab group versus 45.6 ± 22.6% in the non-evolocumab group, with a mean difference of -33.5% between the groups (95% CI: -42.6 to -24.5%; p < 0.001). The achievement rate of LDL-C levels below 55 mg/dL at 1-3 weeks was significantly higher in the evolocumab group than in the non-evolocumab group (97.7% vs. 60.0%, p < 0.001)., Conclusion: Patients with AMI who received single-dose injection of evolocumab 140 mg during the peri-PCI period had a significantly greater LDL-C reduction and higher proportion of patients achieved the target LDL-C level in the early phase AMI than those who did not receive evolocumab.

Objectives: We aimed to assess secondary prevention strategies after ischaemic stroke or transient ischaemic attack (TIA)., Materials and Methods: We investigated the impact of European Stroke Organisation (ESO) Guideline recommendations for secondary prevention on recurrent events among people with non-cardioembolic ischaemic stroke or TIA. We assessed the following interventions by survival analysis or modelling impacts from clinical trial data: two blood pressure (BP) drugs compared to one drug; LDL-cholesterol target <1.8 mmol/L; and pioglitazone therapy. Outcomes were mortality, major adverse cardiovascular events (MACE) and recurrent stroke or myocardial infarction (MI)., Results: We included 4,037 people admitted between 01/12/2015 to 31/12/2018: mean (SD) age 68.6 (12.9) years; 1984 (49.1 %) female and median (IQR) follow-up 2.2 (1.5-3.1) years. Prescription of two BP drugs was associated with reduced mortality in our sample of 2238 people with hypertension (HR 0.64, 95 %CI 0.51-0.81; P<0.001). We estimate an LDL-cholesterol target <1.8 mmol/L could reduce MACE incidence from 128 to 114 events (95 %CI 103-127) in our sample of 1024 people with LDL-cholesterol 1.8 mmol/L who were not already prescribed intensive lipid-lowering therapy over median (IQR) 2.2 (1.5-2.9) years follow-up (ARR 1.38 %, NNT 73). We estimate pioglitazone therapy could reduce incidence of recurrent stroke or MI from 192 to 169 events (95 %CI 156-185) in our sample of 1587 people with diabetes or insulin resistance over median (IQR) 2.4 (1.7-3.2) years follow-up (ARR 1.45 %, NNT 69)., Conclusions: We estimate that implementing ESO guidelines in a Scottish population after ischaemic stroke or TIA would reduce mortality and recurrent cardiovascular events., Competing Interests: Declaration of competing interest AC: research grants from Pfizer; honoraria from BMS, Pfizer, AstraZeneca and Boeheringer Ingelheim; JD: speaker fees from Pfizer, BMS, Bayer, Boeringher Ingelheim, Daiichi Sankyo; research funding from Pfizer and BMS; advisory board for Medtronic. Other authors: no conflicts. AC and JD: conceived study and ethical approval. CS, SW, GK and OD: data analysis. CS and SW: first draft of manuscript. All authors: reviewed and approved final manuscript., (Copyright © 2024. Published by Elsevier Inc.)

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: 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.)

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.)

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.

Introduction: Dyslipidemia is an established risk factor for cardiovascular diseases. We aimed to review its role in the pathogenesis of lower extremity arterial disease (LEAD), as well as the effect of lipid-lowering treatment on the progression of LEAD., Evidence Acquisition: PubMed/MedLine, EMBASE and Scopus were searched between January 1990 and January 2024 for articles investigating the role of dyslipidemias and hyperlipidemias in the pathogenesis of LEAD. A separate search focused on the effects of lipid-lowering therapy on patients with LEAD., Evidence Synthesis: There is evidence that dyslipidemias play a major role in the development of LEAD. All patients with LEAD should receive intensive lipid-lowering therapy for the reduction not only of claudication symptoms and amputation rates, but also of myocardial infarction and cardiovascular event rates., Conclusions: Vascular specialists should keep in mind the pivotal role of dyslipidemia in the pathogenesis and progression of LEAD.

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.)

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.)

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.)