Atherosclerosis plus最新文献

{"title":"Real-world data lipid profiles in one million colombian adults: The LiPAC million person study","authors":"Claudia C. Colmenares-Mejía ,&nbsp;Marcela Godoy-Corredor ,&nbsp;Esteban Morales-Mendoza ,&nbsp;Diego Alejandro Pinto-Pinzón ,&nbsp;José Medardo Rozo-Vanstrahlen ,&nbsp;Jairo Acuña-Olmos ,&nbsp;Liliana Hilarión-Gaitán ,&nbsp;María del Pilar Suarez-Ramos ,&nbsp;Diego Alberto Ruiz-Amaya ,&nbsp;Fredy Rolando Salazar-Heredia ,&nbsp;Johana Vargas-Rodríguez ,&nbsp;Mario A. Isaza-Ruget","doi":"10.1016/j.athplu.2024.11.001","DOIUrl":"10.1016/j.athplu.2024.11.001","url":null,"abstract":"<div><h3>Background and aims</h3><div>Lipid profile results are of clinical interest for assessing the presence of dyslipidemia and the risk of cardiovascular disease. This study aimed to characterize lipid profile parameters in a large adult population from different regions of Colombia.</div></div><div><h3>Methods</h3><div>Cross-sectional study. Adults with a complete lipid profile [TC, c-HDL, non-c-HDL, c-LDL, Triglycerides] from a national reference laboratory between 2018 and 2022 were included. Lipid profile levels are reported as medians and adjusted means and are also presented according to different guideline thresholds. Mixed dyslipidemia frequencies are also reported.</div></div><div><h3>Results</h3><div>1,030,195 subjects were included, with a median age of 49 years (IQR 36–61 years); 59.8 % were females. Adjusted mean value for TC was 188.1 mg/dl (CI95 % 188.0–188.2), 110.1 mg/dl (CI95 % 110.0–110.1) for c-LDL, 45.9 mg/dl (CI95 % 45.9–46.0) for c-HDL, 139.1 mg/dl (CI95 % 139.0–139.2) for non-c-HDL and 129.5 mg/dl (CI95 % 129.4–129.6) for triglycerides. The most frequent single dyslipidemia was c-HDL &lt;40 mg/dL (n = 86,725, 8.4 %), and the most common mixed dyslipidemia was TC ≥ 200 mg/dL + c-LDL &gt;130 mg/dL (n = 138,366, 17.0 %). Elevated c-LDL (≥130 mg/dL) was found in 32.4 % of the population, while c-LDL levels ≥190 mg/dL were observed in 2.0 % (n = 21,045). Triglyceride levels ≥500 mg/dL were identified in 0.3 % (n = 3103).</div></div><div><h3>Conclusion</h3><div>This large study on lipid markers from a selected sample of Colombian adults’ highlights variations in dyslipidemia by gender, age, and region. The findings emphasize the need for targeted interventions to reduce cardiovascular risk. Identifying high-risk groups is essential to improving outcomes in developing countries.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"58 ","pages":"Pages 51-58"},"PeriodicalIF":1.4,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142703592","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":"A collaborative effort across Africa to investigate risk factors and outcomes of premature acute coronary syndrome: Protocol for the EAS Lipid Registry of Africa (LIPRA)","authors":"Ashraf Reda ,&nbsp;Alexander R.M. Lyons ,&nbsp;Alberto Zambon ,&nbsp;Ahmed Bendary ,&nbsp;Mutaz Al-Khnifsawi ,&nbsp;Habib Gamra ,&nbsp;David Marais ,&nbsp;Okechukwu S. Ogah ,&nbsp;Tigist Seleshi ,&nbsp;Ahmed A.A. Suliman ,&nbsp;Julius C. Mwita ,&nbsp;Albertino Damasceno ,&nbsp;Anastase Dzudie ,&nbsp;Atef Elbahry ,&nbsp;Elsayed Farag ,&nbsp;Chala Fekadu ,&nbsp;Lilian Mbau ,&nbsp;Mohammed Mujahed ,&nbsp;Rosemary P. Minja ,&nbsp;Bernard Samia ,&nbsp;Alexandros Tselepis","doi":"10.1016/j.athplu.2024.10.002","DOIUrl":"10.1016/j.athplu.2024.10.002","url":null,"abstract":"<div><div>Data on acute coronary syndrome (ACS) is lacking in Africa where cases of premature ACS seem to be on the rise. Africa would benefit from an epidemiological assessment of premature ACS to determine its risk factors and management in this demographic to inform guidelines and practice. The European Atherosclerosis Society recognised this urgency and formed a growing network across 11 African countries to create the Lipid Registry of Africa (EAS-LIPRA). This article is based on the EAS-LIPRA protocol and presents the aims, concept and methodological considerations, and the operations and collaborative governance structure of this project. EAS-LIPRA aims to report risk factors and outcomes of premature ACS in Africa to further understand its prevalence and management via collating and pooling multinational prospective data on premature ACS across multiple sites in Africa into a standardised registry. Data will be stratified into subgroups based on country-level income as defined by the World Bank, and within country residence of urban versus rural areas. Valid statistical procedures will be employed to compare and observe trends in the pooled data based on demographics, clinical and laboratory variables, and disparities in its management. Being the first multinational lipid registry in Africa, it is envisaged that the network will expand to other African countries and sites yet to participate, facilitate other epidemiological studies in preventive cardiology, and set a precedent for other developing countries and regions.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"58 ","pages":"Pages 46-50"},"PeriodicalIF":1.4,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142552686","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":"Adherence to the Healthy Nordic Food Index is associated with reduced plasma levels of inflammatory markers in patients with heterozygous familial hypercholesterolemia","authors":"Eirin B. Løvheim ,&nbsp;Kjetil Retterstøl ,&nbsp;Ingunn Narverud ,&nbsp;Martin P. Bogsrud ,&nbsp;Bente Halvorsen ,&nbsp;Thor Ueland ,&nbsp;Pål Aukrust ,&nbsp;Kirsten B. Holven","doi":"10.1016/j.athplu.2024.10.003","DOIUrl":"10.1016/j.athplu.2024.10.003","url":null,"abstract":"<div><h3>Background and aims</h3><div>Familial hypercholesterolemia (FH) is an inherited disease associated with hypercholesterolemia, and dietary treatment is part of the treatment. We aimed to assess the dietary pattern in relation to the Healthy Nordic Food Index (HNFI) in adults with and without heterozygous FH (HeFH), and to examine the associations between dietary quality and biomarkers related to cardiovascular disease in adults with HeFH.</div></div><div><h3>Methods</h3><div>We included 205 adults (≥18 years) with HeFH who received follow-up at the Lipid Clinic in Oslo and compared them to controls (n = 228). Dietary intake was assessed using a food frequency questionnaire and dietary quality was assessed using the HNFI. Blood samples were analysed for levels of blood lipids, plasma fatty acids (FAs), and markers of inflammation and platelet activation.</div></div><div><h3>Results</h3><div>The HeFH patients (median 60 years; 50.2 % female; 25.9 % in secondary prevention) had lower intake of total and saturated fat compared to controls (32.6 energy percent (E%) vs. 34.9 E%, and 9.6 E% vs 12.0 E%, respectively; p &lt; 0.001 for both). In the HeFH patients, increasing dietary quality was associated with increased plasma levels of the n-3 polyunsaturated FAs (PUFAs) eicosapentaenoic acid and docosahexaenoic acid, and the n-6 PUFA linoleic acid, and lower plasma levels of the inflammatory cytokines Tumor Necrosis Factor and interleukin-6, and of the platelet-derived inflammatory cytokines Platelet Factor 4 and Neutrophil-Activating Peptide-2.</div></div><div><h3>Conclusion</h3><div>Norwegian patients with HeFH followed up at a Lipid Clinic eat healthier than controls. Adherence to a healthy dietary pattern is associated with higher plasma levels of n-3 and n-6 PUFA, and lower levels of inflammatory markers, including platelet markers. This may suggest that adherence to an overall healthy dietary pattern might be beneficial for HeFH patients independent of the cholesterol-lowering effect of the diet.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"58 ","pages":"Pages 38-45"},"PeriodicalIF":1.4,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142552685","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":"Efficacy and safety of lipid-lowering therapies in combination with or without statin to reduce the cardiovascular risk: A systematic review of randomised controlled trials","authors":"Gabriella Iannuzzo ,&nbsp;Geetank Kamboj ,&nbsp;Parinita Barman ,&nbsp;Shirish Dongare ,&nbsp;Shantanu Jawla","doi":"10.1016/j.athplu.2024.10.001","DOIUrl":"10.1016/j.athplu.2024.10.001","url":null,"abstract":"<div><h3>Background and aims</h3><div>Cardiovascular diseases (CVD) pose a significant global health burden. Lowering low-density lipoprotein-cholesterol is the primary therapeutic aim for preventing primary and secondary CVD events. While statins are the standard treatments, their limitations, such as side effects and intolerance in certain patient groups, necessitate exploration of alternative lipid-lowering therapies (LLTs). We systematically reviewed randomised controlled trials (RCTs) evaluating cardiovascular outcomes associated with non-statin LLTs (bempedoic acid, alirocumab, evolocumab, ezetimibe, and inclisiran) in adults with CVD or high cardiovascular risk.</div></div><div><h3>Methods</h3><div>EMBASE, Medline, Cochrane Library, and clinical trial registries were systematically searched for eligible studies, from inception until February 08, 2023. Two reviewers independently screened the studies, with discrepancies resolved by a third reviewer. Data extraction and validation were conducted, and the risk of bias was assessed using the Cochrane Risk-of-Bias tool-2 for RCTs.</div></div><div><h3>Results</h3><div>The search strategy yielded 2104 citations. Post screening for eligibility, nine unique trials/studies (84 publications) were identified. Among these, one trial each was identified for bempedoic acid and alirocumab, three for evolocumab, and four for ezetimibe. No published literature documenting the cardiovascular outcomes of inclisiran was identified. Only one trial (CLEAR Outcomes) included statin-intolerant patients at baseline. Most studies evaluated a 3-component, 4-component, or 5-component major adverse cardiovascular events composite as an outcome along with individual components. The quality of the included trials was found to be fair-to-good.</div></div><div><h3>Conclusions</h3><div>The systematic review findings emphasise the significance of considering non-statin LLTs as viable treatment options for individuals with CVD or high cardiovascular risk who cannot tolerate or achieve optimal lipid control with statin therapy alone.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"58 ","pages":"Pages 24-37"},"PeriodicalIF":1.4,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142532846","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) and the atherosclerotic burden – Should we wait for clinical trial evidence before taking action?","authors":"Isabella Fichtner ,&nbsp;Chiara Macchi ,&nbsp;Alessandra Stefania Rizzuto ,&nbsp;Stefano Carugo ,&nbsp;Alberto Corsini ,&nbsp;Massimiliano Ruscica","doi":"10.1016/j.athplu.2024.09.004","DOIUrl":"10.1016/j.athplu.2024.09.004","url":null,"abstract":"<div><div>The fact that lipoprotein(a) levels should be regarded as a causal residual risk factor in the atherosclerotic cardiovascular diseases (ASCVD) is now a no-brainer. This review article aims to summarize the latest evidence supporting the causal role of lipoprotein(a) in ASCVD and the potential strategies to reduce the lipoprotein(a) burden until clinical trial results are available. Epidemiological and genetic data demonstrate the causal link between lipoprotein(a) and increased ASCVD risk. That being said, a specific question comes to mind: “must we wait for outcome trials in order to take action?”. Given that lipoprotein(a) levels predict incident ASCVD in both primary and secondary prevention contexts, with a linear risk gradient across its distribution, measuring lipoprotein(a) can unequivocally help identify patients who may later benefit from specific lipoprotein(a)-lowering therapies. This understanding has led various National Societies to recommend dosing lipoprotein(a) in high-risk individuals and to support the recommendation of measuring lipoprotein(a) levels at least once in every adult for risk stratification.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"58 ","pages":"Pages 16-23"},"PeriodicalIF":1.4,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142421783","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":"Coronary artery calcification score and 19 biomarkers on cardiovascular events; a 10-year follow-up DanRisk substudy","authors":"Mie Schæffer ,&nbsp;Jeppe Holm Rasmussen ,&nbsp;Maise Høigaard Fredgart ,&nbsp;Selma Hasific ,&nbsp;Frederikke Nørregaard Jakobsen ,&nbsp;Flemming Hald Steffensen ,&nbsp;Jess Lambrechtsen ,&nbsp;Niels Peter Rønnow Sand ,&nbsp;Lars Melholt Rasmussen ,&nbsp;Axel CP. Diederichsen","doi":"10.1016/j.athplu.2024.09.003","DOIUrl":"10.1016/j.athplu.2024.09.003","url":null,"abstract":"<div><h3>Aim</h3><div>The SCORE2 algorithm is recommended to estimate risk of cardiovascular disease (CVD). Coronary artery calcification (CAC) score is expensive but improves the risk prediction. This study aims to determine and compare the additive value of CAC-score and 19 biomarkers in risk prediction.</div></div><div><h3>Methods</h3><div>Traditional cardiovascular (CV) risk factors, CAC-score, and a wide range of biomarkers (including lipids, calcium-phosphate metabolism, troponin, inflammation, kidney function and ankle brachial index (ABI)) were collected from 1211 randomly selected middle-aged men and women in this multicenter prospective cohort in 2009–2010. 10-year follow-up data on CV-events were obtained via the Danish Health Registries. CV-event was defined as stroke, myocardial infarction, hospitalization for heart failure, coronary artery revascularization or death from CVD. The association between SCORE2, CAC-score, biomarkers, and CV-events was assessed using cox proportional hazard rates (HR) and compared using AUC-calculation of ROC-curves. Finally, net reclassification improvement (NRI) was calculated.</div></div><div><h3>Results</h3><div>92 participants had CV-events. Adjusted for risk factors, CAC-score was significantly associated with events (adjusted HR 1.9 (95%CI:1.1; 3.3), 3.6 (95%CI:1.9; 6.8), and 5. (95%CI:2.6; 10.3) for CAC-score 1–99, CAC-score 100–399 and CAC-score ≥400, respectively. HR for the highest quartile of CRP was 2.3 (95%CI:1.2; 4.5), while none of the remaining biomarkers improved HR. Adjusted for SCORE2, the CAC-score improved AUC (AUC_CAC: 0.72, AUC_SCORE2: 0.67, <em>p&lt;</em>0.01). A combination of selected biomarkers (total cholesterol, low-density lipoprotein, phosphate, troponin, CRP, and creatinine) borderline improved AUC (AUC_{Biomarkers + SCORE2}: 0.71, AUC_SCORE2: 0.67, <em>p=</em>0.06). NRI for CAC score was 63 % (<em>p&lt;</em>0.0001).</div></div><div><h3>Conclusion</h3><div>CAC-score improved prediction of CV-events, however the selected biomarkers did not.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"58 ","pages":"Pages 9-15"},"PeriodicalIF":1.4,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142327729","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":"Eligibility for marine omega-3 fatty acid supplementation after acute coronary syndromes","authors":"Cédric Follonier ,&nbsp;Gabriel Rabassa ,&nbsp;Mattia Branca ,&nbsp;David Carballo ,&nbsp;Konstantinos Koskinas ,&nbsp;Dik Heg ,&nbsp;David Nanchen ,&nbsp;Lorenz Räber ,&nbsp;Roland Klingenberg ,&nbsp;Moa Lina Haller ,&nbsp;Sebastian Carballo ,&nbsp;Stephan Windecker ,&nbsp;Christian M. Matter ,&nbsp;Nicolas Rodondi ,&nbsp;François Mach ,&nbsp;Baris Gencer","doi":"10.1016/j.athplu.2024.09.002","DOIUrl":"10.1016/j.athplu.2024.09.002","url":null,"abstract":"<div><h3>Background and aims</h3><p>The 2019 European Society of Cardiology guidelines for the management of dyslipidemia consider the use of high-dose marine omega-3 fatty acid (FA) eicosapentaenoic acid (EPA) supplementation (icosapent ethyl 2 × 2g/day) to lower residual cardiovascular risk in high-risk patients with hypertriglyceridemia. This study aimed to assess the eligibility for omega-3 FA-EPA supplementation in patients with acute coronary syndromes (ACS).</p></div><div><h3>Methods</h3><p>In a prospective Swiss cohort of patients hospitalized for ACS, eligibility for marine omega-3 FA-EPA, defined as plasma triglyceride levels ranging from 1.5 to 5.6 mmol/l, was assessed at baseline and one-year follow-up and compared across subgroups. Lipid-lowering therapy intensification with statin and ezetimibe was modelled to simulate a hypothetical systematic treatment and its effect on omega-3 FA-EPA supplementation eligibility.</p></div><div><h3>Results</h3><p>Of 2643 patients, 98 % were prescribed statin therapy at discharge, including 62 % at a high-intensity regimen; 93 % maintained it after one year, including 53 % at a high-intensity regimen. The use of ezetimibe was 3 % at discharge and 7 % at one year. Eligibility was observed in 32 % (32 % men, 29 % women) one year post-ACS. After modelling systematic treatment with statins, ezetimibe, and both, eligibility decreased to 31 %, 25 % and 24 %, respectively. Eligibility was higher in individuals aged &lt;70 (34 vs 25 %), smokers (38 vs 28 %), diabetics (46 vs 29 %), hypertensive (35 vs 29 %), and obese patients (46 vs 22 % for normal weight), all with p-values &lt;0.001.</p></div><div><h3>Conclusion</h3><p>In a contemporary Swiss cohort of patients with ACS, up to 32 % would be eligible for omega-3 FA-EPA supplementation one year after ACS, highlighting an opportunity to mitigate residual cardiovascular risk in patients with ACS and hypertriglyceridemia.</p></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"58 ","pages":"Pages 1-8"},"PeriodicalIF":1.4,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667089524000439/pdfft?md5=140a849556d7934c58fbe2caf2c9759a&pid=1-s2.0-S2667089524000439-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142270704","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":"Clinical Service Quality and Unmet Needs in Homozygous Familial Hypercholesterolaemia Patients: Insights from UK Tertiary Centres","authors":"Heleen A. Hussein ,&nbsp;Haya Haso ,&nbsp;Bilal Bashir ,&nbsp;Raabya Pasha ,&nbsp;Anoushka Kamath ,&nbsp;Maryam Ferdousi ,&nbsp;Handrean Soran ,&nbsp;Mariamma Baptist ,&nbsp;Kirsty Nicholson","doi":"10.1016/j.athplu.2024.08.022","DOIUrl":"10.1016/j.athplu.2024.08.022","url":null,"abstract":"","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"57 ","pages":"Page 5"},"PeriodicalIF":1.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142416448","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":"Total Circulating PCSK9 Positively Correlates with Age and Free Circulating PCSK9 Positively Correlated with Body Mass Index in Healthy Volunteers","authors":"Anoushka Kamath ,&nbsp;Maryam Ferdousi ,&nbsp;Bilal Bashir ,&nbsp;Raabya Pasha ,&nbsp;Handrean Soran","doi":"10.1016/j.athplu.2024.08.006","DOIUrl":"10.1016/j.athplu.2024.08.006","url":null,"abstract":"","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"57 ","pages":"Page 8"},"PeriodicalIF":1.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423451","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 pro-atherogenic enzyme PAPP-A is active in eluates from human carotid and femoral atherosclerotic plaques","authors":"Mette Faurholdt Gude ,&nbsp;Rikke Hjortebjerg ,&nbsp;Mette Bjerre ,&nbsp;Anne Kathrine Nissen Pedersen ,&nbsp;Claus Oxvig ,&nbsp;Lars Melholt Rasmussen ,&nbsp;Jan Frystyk ,&nbsp;Lasse Steffensen","doi":"10.1016/j.athplu.2024.09.001","DOIUrl":"10.1016/j.athplu.2024.09.001","url":null,"abstract":"<div><h3>Background</h3><p>Pregnancy-associated plasma protein-A (PAPP-A) regulates bioavailability of insulin-like growth factor 1 (IGF1) in various tissues by proteolytic cleavage of a subset of IGF-binding proteins (IGFBPs). Pre-clinical studies have established a role of PAPP-A in atherosclerosis and proposed that targeting the proteolytic activity of PAPP-A has therapeutic value.</p><p>This study aimed to investigate whether human atherosclerotic plaques contain proteolytically active PAPP-A, a prerequisite for further considering PAPP-A as a therapeutic target in patients.</p></div><div><h3>Methods</h3><p>We obtained carotid (<em>n</em> = 9) and femoral (<em>n</em> = 11) atherosclerotic plaques from patients undergoing vascular surgery and incubated freshly harvested plaque tissue in culture media for 24 h. Subsequently, conditioned media were assayed for PAPP-A, STC2, IGFBP4, and IGF1 using immunoassays. Enzymatic activity of PAPP-A was assessed by its ability to process recombinant IGFBP4-IGF1 complexes - a specific substrate of PAPP-A - by Western blotting.</p></div><div><h3>Results</h3><p>PAPP-A and STC2 were detectable in conditioned media from both carotid and femoral plaques, with higher STC2 concentrations in eluates from carotid plaque incubations (<em>p</em> = 0.02). IGFBP4 and IGF1 were undetectable. Conditioned media from all 20 plaques exhibited PAPP-A proteolytic activity. However, no correlation between PAPP-A concentration and its proteolytic activity was observed, whereas the PAPP-A: STC2 molar ratio correlated with PAPP-A activity (R² = 0.25, <em>p</em> = 0.03).</p></div><div><h3>Conclusion</h3><p>This study provides evidence for the presence of enzymatically active PAPP-A in atherosclerotic plaques and underscores the need for further investigating potential beneficial effects associated with targeting PAPP-A in atherosclerotic cardiovascular disease.</p></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"57 ","pages":"Pages 30-36"},"PeriodicalIF":1.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667089524000415/pdfft?md5=f8b0f80011afbf4438f5553d4df43beb&pid=1-s2.0-S2667089524000415-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142163577","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}