Atherosclerosis plus最新文献

{"title":"Lomitapide in paediatric patients with homozygous familial hypercholesterolaemia (HoFH) – Analysis of patient-level LDL-C reduction, fat-soluble vitamins, lipoproteins and patient maturation from the APH-19 study","authors":"Luis Masana , Alberto Zambon , Claus Peter Schmitt , Christina Taylan , Joenna Driemeyer , Hofit Cohen , Paola Sabrina Buonuomo , Abdullah Alashwal , Mohammed Al-Dubayee , José Luis Diaz-Diaz , Faouzi Maatouk , Sergio Martinez-Hervas , Brian Mangal , Naji Kholaif , Sandra Löwe , Zsuzsanna Tamas ∗","doi":"10.1016/j.athplu.2024.08.020","DOIUrl":"10.1016/j.athplu.2024.08.020","url":null,"abstract":"","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"57 ","pages":"Page 4"},"PeriodicalIF":1.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extreme founder effect associated with hyperglycemia and hyperlipidemia on the island of NIAS/Indonesia","authors":"Ingo Kennerknecht ,&nbsp;Johannes M. Hämmerle ,&nbsp;Manfred Fobker ,&nbsp;Jerzy-Roch Nofer","doi":"10.1016/j.athplu.2024.07.002","DOIUrl":"10.1016/j.athplu.2024.07.002","url":null,"abstract":"<div><p>The island of Nias/Indonesia shows an extremely reduced genetic diversity indicating a strong founder effect. As a consequence, the prevalence of some disease genes should significantly differ among populations depending on the gene pool passed on to the founder population and their successive expansion as it has already been documented for several monogenic diseases. Results of the current study based on routine laboratory blood examination give rise to the notion that this might also hold true for polygenic disorders. We observed very high prevalence of hyperglycemia (non-fasting glucose above 200 mg/dL in 14 % Nias population compared to 1.5 % in the population of the neighboring island of Sumatra) accompanied by hypertriglyceridemia, high non-HDL-cholesterol, and low HDL-cholesterol levels. These findings suggest that the Nias population may be disproportionally affected by prediabetes and type 2 diabetes mellitus. By contrast, laboratory parameters potentially indicative of other polygenic disorders such as total plasma cholesterol, electrolytes, creatinine, urea, and uric acid were comparable between the inhabitants of Nias and Sumatra islands. To our knowledge this is the first study suggesting that the extremely strong genetic bottleneck seen in the Nias population translates into the widespread metabolic disease with potentially deleterious influence on public health.</p></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"57 ","pages":"Pages 26-29"},"PeriodicalIF":1.4,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667089524000178/pdfft?md5=308d0b8c2f1c0734c601c409bf9639ac&pid=1-s2.0-S2667089524000178-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141846605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of very low Lipoprotein(a) levels with risks of new-onset diabetes and non-alcoholic liver disease","authors":"Ming Wai Yeung ,&nbsp;M. Abdullah Said ,&nbsp;Yordi J. van de Vegte ,&nbsp;Niek Verweij ,&nbsp;Robin P.F. Dullaart ,&nbsp;Pim van der Harst","doi":"10.1016/j.athplu.2024.07.001","DOIUrl":"https://doi.org/10.1016/j.athplu.2024.07.001","url":null,"abstract":"<div><h3>Background and aims</h3><p>We aimed to study the association of very low serum Lipoprotein(a) [Lp(a)] concentrations with new-onset type 2 diabetes (T2D) and non-alcoholic liver disease (NAFLD) in the context of statin usage in the UK Biobank, a large prospective population cohort.</p></div><div><h3>Methods</h3><p>Using an extended biomarker dataset, we identified 47,362 participants with very low Lp(a) concentrations (&lt;3.8 nmol/L) from a total of 451,479 participants. With a median follow-up of 12.3 years, we assessed the risk of new-onset cardiometabolic diseases in participants stratified by statin usage with Cox proportional hazards models. We performed two-sample Mendelian randomization MR analyses to test causal relationship between genetically predicted Lp(a) and T2D and NAFLD.</p></div><div><h3>Results</h3><p>Taking the participants with Lp(a) within reportable range as the reference group, the hazard ratios (HR) for T2D were 1.07 (95 % confidence interval, CI 1.01–1.13) and for NAFLD 1.30 (95 % CI 1.20–1.41) respectively for participants with very low Lp(a) (&lt;3.8 nmol/L). The risk for new-onset T2D was higher in participants using statins (adjusted HR 1.15; 95 % CI 1.05–1.27). The risk estimates for new-onset NAFLD were comparable in the analysis stratified by statin use. There was no evidence for causal links between genetically predicted Lp(a) and T2D nor NAFLD in two-sample MR analyses.</p></div><div><h3>Conclusions</h3><p>Very low Lp(a) was associated with higher risks of T2D and NAFLD in a prospective analysis of the UK Biobank. The association with T2D was influenced by lipid lowering medication usage. MR analyses did not support causality for these inverse associations.</p></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"57 ","pages":"Pages 19-25"},"PeriodicalIF":1.4,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667089524000166/pdfft?md5=c3a6777b13986ebec4c5e9321f64810d&pid=1-s2.0-S2667089524000166-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141607836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipoprotein(a) in children and adolescents with genetically confirmed familial hypercholesterolemia followed up at a specialized lipid clinic","authors":"Anja K. Johansen ,&nbsp;Martin P. Bogsrud ,&nbsp;Magne Thoresen ,&nbsp;Jacob J. Christensen ,&nbsp;Ingunn Narverud ,&nbsp;Gisle Langslet ,&nbsp;Tone Svilaas ,&nbsp;Kjetil Retterstøl ,&nbsp;Kirsten B. Holven","doi":"10.1016/j.athplu.2024.06.002","DOIUrl":"https://doi.org/10.1016/j.athplu.2024.06.002","url":null,"abstract":"<div><h3>Background and aim</h3><p>Many children with an FH mutation also exhibit elevated lipoprotein(a) levels, which is an independent risk factor for atherosclerotic cardiovascular disease. Studies have reported higher levels of lipoprotein(a) in adult and middle-aged women than men. There is limited knowledge on the concentration and change of lipoprotein(a) levels in children with genetic FH, and therefore we investigated sex-differences in lipoprotein(a) level and change in lipoprotein(a) in girls and boys with genetically confirmed FH.</p></div><div><h3>Methods</h3><p>Medical records were reviewed retrospectively in 438 subjects with heterozygous FH that started follow-up below the age of 19 years at the Lipid Clinic, Oslo University Hospital in Norway, and of these we included 386 subjects with at least one Lp(a) measurement.</p></div><div><h3>Results</h3><p>Mean (SD) age at baseline was 13.8 (7.3) years and the age was similar between sexes. Girls had a higher lipoprotein(a) level than boys at baseline: median (25–75 percentile) 223 (108–487) vs. 154 (78–360) mg/L, respectively (<em>p</em> &lt; 0.01). From baseline to follow-up measurement (mean [SD] 8.9 [6.1] years apart), the mean (95 % CI) absolute and percentage change in Lp(a) level in girls was 151.4 (54.9–247.8) mg/L and 44.8 (16.4–73.1) %, respectively, and in boys it was 66.8 (22.9–110.8) mg/L and 50.5 (8.8–92.3) %, respectively (both p &gt; 0.05).</p></div><div><h3>Conclusions</h3><p>We found an increase in Lp(a) levels in children with genetic FH with age, and higher levels in girls than boys, which could impact risk assessment and future ASCVD. Further research is needed to elucidate whether subjects with FH could benefit from lipoprotein(<em>a</em>)-lowering therapies that are under current investigations.</p></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"57 ","pages":"Pages 13-18"},"PeriodicalIF":1.4,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667089524000154/pdfft?md5=15f96828203462a10735210142d91fb5&pid=1-s2.0-S2667089524000154-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141478933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NAD+ metabolism and therapeutic strategies in cardiovascular diseases","authors":"Chongxu Shi ,&nbsp;Zhaozhi Wen ,&nbsp;Yihang Yang ,&nbsp;Linsheng Shi ,&nbsp;Dong Liu","doi":"10.1016/j.athplu.2024.06.001","DOIUrl":"https://doi.org/10.1016/j.athplu.2024.06.001","url":null,"abstract":"<div><p>Nicotinamide adenine dinucleotide (NAD+) is a central and pleiotropic metabolite involved in cellular energy metabolism, cell signaling, DNA repair, and protein modifications. Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Metabolic stress and aging directly affect the cardiovascular system. Compelling data suggest that NAD + levels decrease with age, obesity, and hypertension, which are all notable risk factors for CVD. In addition, the therapeutic elevation of NAD + levels reduces chronic low-grade inflammation, reactivates autophagy and mitochondrial biogenesis, and enhances oxidative metabolism in vascular cells of humans and rodents with vascular disorders. In preclinical models, NAD + boosting can also expand the health span, prevent metabolic syndrome, and decrease blood pressure. Moreover, NAD + storage by genetic, pharmacological, or natural dietary NAD + -increasing strategies has recently been shown to be effective in improving the pathophysiology of cardiac and vascular health in different animal models, and human health. Here, we review and discuss NAD + -related mechanisms pivotal for vascular health and summarize recent experimental evidence in NAD + research directly related to vascular disease, including atherosclerosis, and coronary artery disease. Finally, we comparatively assess distinct NAD + precursors for their clinical efficacy and the efficiency of NAD + elevation in the treatment of major CVD. These findings may provide ideas for new therapeutic strategies to prevent and treat CVD in the clinic.</p></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"57 ","pages":"Pages 1-12"},"PeriodicalIF":1.6,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667089524000142/pdfft?md5=5c934b362462e68508d9d5357b0a38dc&pid=1-s2.0-S2667089524000142-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141313913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trends in cardiovascular disease among Inuit in Greenland from 1994 to 2021","authors":"Hjalte Erichsen Larsen ,&nbsp;Uka Wilhjelm Geisler ,&nbsp;Finn Gustafsson ,&nbsp;Michael Lynge Pedersen ,&nbsp;Marit Eika Jørgensen","doi":"10.1016/j.athplu.2024.04.002","DOIUrl":"10.1016/j.athplu.2024.04.002","url":null,"abstract":"<div><h3>Background and aims</h3><p>Cardiovascular disease (CVD) poses significant health challenges globally. While substantial data exists for most populations, the Arctic Inuit's CVD incidence rates remain understudied. This research aimed to change this by estimating CVD incidence and mortality rates in Greenland from 1994 to 2021.</p></div><div><h3>Methods</h3><p>Using nationwide registers, a retrospective observational study was conducted, focusing on individuals born in Greenland to Greenlandic-born parents. Data were sourced from the Greenlandic Hospital Discharge Register and the nationwide electronic medical record.</p></div><div><h3>Results</h3><p>A total of 65,824 individuals were included. the age- and sex-specific incidence rates (IR) of ischemic heart disease, stroke, and heart failure (HF) declined from 1994 to 2021, with the most substantial decline observed for HF among women. Conversely, the IR of atrial fibrillation/flutter increased in both men and women, while the IR of myocardial infarction rose among men. The IR for stroke was particularly elevated compared to other CVD subgroups. Mortality rates for those diagnosed with CVD were 2.4 times higher than those without. Men exhibited a 40 % elevated mortality risk relative to women.</p></div><div><h3>Conclusion</h3><p>The study provides pivotal insights into CVD trends within the Arctic Inuit population, highlighting both positive developments and areas of concern. Given the increasing elderly demographic in Greenland, proactive health strategies are crucial. Emphasizing primary prevention and addressing specific CVD risks, particularly the elevated stroke IR, is imperative for future public health efforts.</p></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"56 ","pages":"Pages 12-20"},"PeriodicalIF":1.6,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667089524000129/pdfft?md5=9d4d7793df96d29ba2f3fbeec3cb849c&pid=1-s2.0-S2667089524000129-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140763717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carotid intimamedia thickness in patients with severe hypertriglyceridemia","authors":"Maud Ahmad ,&nbsp;Brooke A. Kennedy ,&nbsp;Surim Son ,&nbsp;Adam D. McIntyre ,&nbsp;Julieta Lazarte ,&nbsp;Jian Wang ,&nbsp;Robert A. Hegele","doi":"10.1016/j.athplu.2024.04.001","DOIUrl":"https://doi.org/10.1016/j.athplu.2024.04.001","url":null,"abstract":"<div><h3>Background and aims</h3><p>Severe hypertriglyceridemia (HTG), defined as plasma triglyceride (TG) concentration &gt; 10 mmol/L, is relatively uncommon, and its implications for atherosclerotic cardiovascular disease (ASCVD) risk remain somewhat unclear. We evaluated the association between severe HTG and carotid intima-media thickness (IMT), a marker for ASCVD.</p></div><div><h3>Methods</h3><p>We studied three clinical cohorts: 88 patients with severe HTG (mean TG level 20.6 mmol/L), 271 patients with familial hypercholesterolemia (FH) as a contrast group, and 70 normolipidemic controls. Carotid IMT was measured using standardized ultrasound imaging. Statistical analysis was conducted using one-way analysis of variance (ANOVA) to compare mean IMT values, analysis of covariance (ANCOVA) to adjust for confounding variables, specifically age and sex, as well as Spearman pairwise correlation analysis between variables.</p></div><div><h3>Results</h3><p>Unadjusted mean carotid IMT was greater in severe HTG and FH groups compared to controls, however, this was no longer significant for severe HTG after adjustment for age and sex. In contrast, adjusted carotid IMT remained significantly different between the FH and control groups.</p></div><div><h3>Conclusions</h3><p>Our findings suggest that extreme TG elevations in severe HTG patients are not significantly associated with carotid IMT, in contrast to the increased IMT seen in FH patients. These findings add perspective to the complex relationship between severe HTG and ASCVD risk.</p></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"56 ","pages":"Pages 7-11"},"PeriodicalIF":1.6,"publicationDate":"2024-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667089524000117/pdfft?md5=66e95fac89487f72c0bb4e8c1d754e6b&pid=1-s2.0-S2667089524000117-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140650951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucagon-like Peptide-1 analogues and delipidation of coronary atheroma in statin-treated type 2 diabetic patients with coronary artery disease: The prespecified sub-analysis of the OPTIMAL randomized clinical trial","authors":"Yu Kataoka ,&nbsp;Satoshi Kitahara ,&nbsp;Sayaka Funabashi ,&nbsp;Hisashi Makino ,&nbsp;Masaki Matsubara ,&nbsp;Miki Matsuo ,&nbsp;Yoko Omura-Ohata ,&nbsp;Ryo Koezuka ,&nbsp;Mayu Tochiya ,&nbsp;Tamiko Tamanaha ,&nbsp;Tsutomu Tomita ,&nbsp;Kyoko Honda-Kohmo ,&nbsp;Michio Noguchi ,&nbsp;Kota Murai ,&nbsp;Kenichiro Sawada ,&nbsp;Takamasa Iwai ,&nbsp;Hideo Matama ,&nbsp;Satoshi Honda ,&nbsp;Masashi Fujino ,&nbsp;Kazuhiro Nakao ,&nbsp;Teruo Noguchi","doi":"10.1016/j.athplu.2024.03.001","DOIUrl":"https://doi.org/10.1016/j.athplu.2024.03.001","url":null,"abstract":"<div><h3>Background and aims</h3><p>Randomized clinical trials have demonstrated the ability of glucagon-like peptide-1 analogues (GLP-1RAs) to reduce atherosclerotic cardiovascular disease events in patients with type 2 diabetes (T2D). How GLP-1RAs modulate diabetic atherosclerosis remains to be determined yet.</p></div><div><h3>Methods</h3><p>The OPTIMAL study was a prospective randomized controlled study to compare the efficacy of 48-week continuous glucose monitoring- and HbA1c-guided glycemic control on near infrared spectroscopty (NIRS)/intravascular ultrasound (IVUS)-derived plaque measures in 94 statin-treated patients with T2D (jRCT1052180152, UMIN000036721). Of these, 78 patients with evaluable serial NIRS/IVUS images were analyzed to compare plaque measures between those treated with (n = 16) and without GLP-1RAs (n = 72).</p></div><div><h3>Results</h3><p>All patients received a statin, and on-treatment LDL-C levels were similar between the groups (66.9 ± 11.6 vs. 68.1 ± 23.2 mg/dL, p = 0.84). Patients receiving GLP-1RAs demonstrated a greater reduction of HbA1c [-1.0 (-1.4 to −0.5) vs. −0.4 (-0.6 to −0.2)%, p = 0.02] and were less likely to demonstrate a glucose level &gt;180 mg/dL [-7.5 (-14.9 to −0.1) vs. 1.1 (-2.0 - 4.2)%, p = 0.04], accompanied by a significant decrease in remnant cholesterol levels [-3.8 (-6.3 to −1.3) vs. −0.1 (-0.8 - 1.1)mg/dL, p = 0.008]. On NIRS/IVUS imaging analysis, the change in percent atheroma volume did not differ between the groups (−0.9 ± 0.25 vs. −0.2 ± 0.2%, p = 0.23). However, GLP-1RA treated patients demonstrated a greater frequency of maxLCBI_4mm regression (85.6 ± 0.1 vs. 42.0 ± 0.6%, p = 0.01). Multivariate analysis demonstrated that the GLP-1RA use was independently associated with maxLCBI_4mm regression (odds ratio = 4.41, 95%CI = 1.19–16.30, p = 0.02).</p></div><div><h3>Conclusions</h3><p>In statin-treated patients with T2D and CAD, GLP-1RAs produced favourable changes in lipidic plaque materials, consistent with its stabilization.</p></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"56 ","pages":"Pages 1-6"},"PeriodicalIF":1.6,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667089524000099/pdfft?md5=62075046dc5f7ac01d5b74dc5d82f5dd&pid=1-s2.0-S2667089524000099-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140350741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment intensification with bempedoic acid to achieve LDL-C goal in patients with ASCVD: A simulation model using a real-world patient cohort in the US","authors":"Kristen Migliaccio-Walle ,&nbsp;David Elsea ,&nbsp;Anand Gupta ,&nbsp;Evelyn Sarnes ,&nbsp;Kristel Griffith ,&nbsp;Rajshree Pandey ,&nbsp;Kristin Gillard","doi":"10.1016/j.athplu.2024.01.006","DOIUrl":"https://doi.org/10.1016/j.athplu.2024.01.006","url":null,"abstract":"<div><h3>Background and aims</h3><p>Guidelines recommend that high-risk patients with atherosclerotic cardiovascular disease (ASCVD) be treated with maximally tolerated statins to lower low-density lipoprotein cholesterol (LDL-C) levels and reduce the risk of major adverse cardiovascular events. In patients whose LDL-C remains elevated, non-statin adjunct therapies, including ezetimibe (EZE), bempedoic acid (BA), and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are recommended.</p></div><div><h3>Methods</h3><p>The impact of BA and EZE in a fixed-dose combination (FDC) on LDL-C goal attainment was evaluated using a simulation model developed for a United States cohort of high-risk adults with ASCVD. Treatment was simulated for 73,056 patients not at goal (LDL-C &gt;70 mg/dL), comparing BA + EZE (FDC), EZE only, and no oral adjunct therapy (NOAT). The addition of PCSK9 inibitors was assumed after 1 year in patients not at LDL-C goal. Treatment efficacy was estimated from clinical trials. Patient-level outcomes were predicted over a 10-year horizon accounting for treatment discontinuation and general mortality.</p></div><div><h3>Results</h3><p>Baseline mean age of the cohort was 67 years, most were White (79%) and male (56%). A majority had established coronary artery disease (75%), 48% had diabetes, and mean LDL-C was 103.0 mg/dL. After 1 year, 79% of patients achieved LDL-C goal (mean, 61.1 mg/dL) with BA + EZE (FDC) compared to 58% and 42% with EZE (71.7 mg/dL) and NOAT (78.4 mg/dL), respectively.</p></div><div><h3>Conclusions</h3><p>This simulation shows that adding BA + EZE (FDC) to maximally tolerated statins would result in more patients achieving LDL-C goal than adding EZE alone or NOAT.</p></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"55 ","pages":"Pages 98-105"},"PeriodicalIF":1.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667089524000075/pdfft?md5=9b906d47b10a988b17c20a7f84fb806a&pid=1-s2.0-S2667089524000075-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140290445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of hydroxychloroquine on cholesterol synthesis depends on the profile of cholesterol metabolism. A controlled clinical study","authors":"Piia Simonen ,&nbsp;Lotta Ulander ,&nbsp;Kari K. Eklund ,&nbsp;Mikko Niemi ,&nbsp;Janne T. Backman ,&nbsp;Helena Gylling ,&nbsp;Juha Sinisalo ,&nbsp;OXI pilot trial","doi":"10.1016/j.athplu.2024.02.002","DOIUrl":"https://doi.org/10.1016/j.athplu.2024.02.002","url":null,"abstract":"<div><h3>Background and aims</h3><p>Hydroxychloroquine (HCQ) has a variable effect on cholesterol synthesis. To clarify this, we assessed the effect of HCQ on the cholesterol-synthesis pathway in individuals with low and high cholesterol absorption efficiency.</p></div><div><h3>Method</h3><p>A total of 53 acute myocardial infarction patients with a constant statin dose randomized to receive HCQ or placebo for six months in a double-blind manner, were classified further into low (n = 26) and high (n = 27) cholesterol absorbers based on the median baseline serum cholestanol level. Serum lipids and biomarkers of cholesterol synthesis (squalene, lanosterol, zymostenol, desmosterol, and lathosterol) and absorption efficiency (sitosterol and cholestanol), were measured at baseline and one-, six-, and 12-month follow-up visits.</p></div><div><h3>Results</h3><p>In low cholesterol absorbers, serum cholesterol concentration and cholesterol synthesis and absorption biomarkers did not differ between the HCQ and placebo groups. At one month, high cholesterol absorbers with HCQ had lower serum cholesterol concentration and serum lanosterol to cholesterol ratio in comparison to the placebo group (HCQ 3.18 ± 0.62 vs. placebo 3.71 ± 0.65, p = 0.042, and HCQ 10.4 ± 2.55 vs. placebo 13.1 ± 2.36, p = 0.008, respectively). At 12 months, serum desmosterol to cholesterol ratio was lower in HCQ users (HCQ 47.1 ± 7.08 vs. placebo 59.0 ± 13.1, p = 0.011).</p></div><div><h3>Conclusions</h3><p>HCQ affects the cholesterol-synthesis pathway in high cholesterol absorbers. It reduces serum lanosterol and desmosterol ratios and consequently serum cholesterol concentration possibly by inhibiting the activity of lanosterol synthase as described earlier in <em>vitro</em> studies.</p></div><div><h3>Trial registration</h3><p>ClinicalTrials.gov Identifier: NCT02648464.</p></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"55 ","pages":"Pages 93-97"},"PeriodicalIF":1.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667089524000087/pdfft?md5=334b6cd36a8b60f9eb21b4e6208cec38&pid=1-s2.0-S2667089524000087-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140052435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}