{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T04:26:33Z","timestamp":1786854393410,"version":"build-2736575974"},"reference-count":37,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Silesia","award":["PCN-1-178\/N\/2\/Z"],"award-info":[{"award-number":["PCN-1-178\/N\/2\/Z"]}]},{"award":["PCN-1-178\/N\/2\/Z"],"award-info":[{"award-number":["PCN-1-178\/N\/2\/Z"]}],"id":[{"id":"https:\/\/ror.org\/005k7hp45","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Pers. Med.","JPM"],"abstract":"<jats:p>Background: Familial hypercholesterolemia (FH) is associated with accelerated atherosclerosis and an increased risk of cardiovascular disease. Aims: To evaluate circulating biomarkers of inflammation and atherosclerosis in patients with clinically suspected FH stratified according to the Dutch Lipid Clinic Network (DLCN) criteria. Methods: This cross-sectional study included 80 patients (mean age, 53.4 [13.2] years; 58% women) receiving maximally tolerated lipid-lowering therapy (statins \u00b1 ezetimibe). Serum concentrations of lipoprotein-associated phospholipase A2 (Lp-PLA2), tumor necrosis factor-\u03b1 (TNF-\u03b1), apolipoprotein B (ApoB), oxidized low-density lipoprotein (oxLDL), and monocyte chemoattractant protein-1 (MCP-1) were measured. Participants were classified as definite FH (DLCN score &gt; 8; n = 45) or non-definite FH (DLCN score \u2264 8; n = 35). Biomarker concentrations were analyzed according to the above subgroups and sex. Results: Patients with definite FH had significantly higher serum Lp-PLA2 concentrations (62.2 [33.8] vs. 46.5 [19.9] ng\/mL; p = 0.03) and TNF-\u03b1 concentrations (6.94 [4.53] vs. 4.51 [2.93] pg\/mL; p = 0.02) compared to non-definite FH, whereas ApoB, oxLDL, and MCP-1 concentrations did not differ significantly between the subgroups. Women had significantly higher TNF-\u03b1 concentrations compared to men (6.57 [4.74] vs. 4.60 [2.20] pg\/mL; p = 0.04) with no differences among other cytokines. Conclusions: Patients with definite FH exhibited persistently higher circulating Lp-PLA2 and TNF-\u03b1 concentrations despite maximally tolerated lipid-lowering therapy, suggesting ongoing activation of specific inflammatory pathways. These findings support further investigation of Lp-PLA2 and TNF-\u03b1 as candidate biomarkers for cardiovascular risk assessment in FH.<\/jats:p>","DOI":"10.3390\/jpm16080429","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T08:08:29Z","timestamp":1786694909000},"page":"429","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Residual Inflammatory Potential in Patients with Treated Non-Definite and Definite Familial Hypercholesterolaemia: A Clinical Study"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2815-1087","authenticated-orcid":false,"given":"Patrycja","family":"Brz\u00f3ska-Ritter","sequence":"first","affiliation":[{"name":"Department of Cardiology, School of Health Sciences, Medical University of Silesia, 40-635 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8863-0589","authenticated-orcid":false,"given":"Piotr","family":"\u017barczy\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Cardiology, School of Health Sciences, Medical University of Silesia, 40-635 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2296-8827","authenticated-orcid":false,"given":"Maciej","family":"Haberka","sequence":"additional","affiliation":[{"name":"Department of Cardiology, School of Health Sciences, Medical University of Silesia, 40-635 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"960","DOI":"10.5603\/KP.a2018.0053","article-title":"Prevalence, diagnosis, and treatment of familial hypercholesterolaemia in outpatient practices in Poland","volume":"76","author":"Chlebus","year":"2018","journal-title":"Kardiol. Pol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"132667","DOI":"10.1016\/j.ijcard.2024.132667","article-title":"Clinical reality and challenges with familial hypercholesterolemia patients\u2019 management: 2024 results from the Regional Center for Rare Diseases Registry in Poland","volume":"419","author":"Lewek","year":"2025","journal-title":"Int. J. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"17093","DOI":"10.1038\/nrdp.2017.93","article-title":"Familial hypercholesterolaemia","volume":"3","author":"Defesche","year":"2017","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"475","DOI":"10.5603\/KP.a2019.0029","article-title":"Prevalence of familial hypercholesterolemia in patients with acute coronary syndromes","volume":"77","author":"Bobrowska","year":"2019","journal-title":"Kardiol. Pol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1080\/14779072.2023.2218087","article-title":"Lipid profile screening and ASCVD prevention","volume":"21","author":"Figorilli","year":"2023","journal-title":"Expert Rev. Cardiovasc. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1093\/eurheartj\/ehz455","article-title":"2019 ESC\/EAS Guidelines for the management of dyslipidaemias","volume":"41","author":"Mach","year":"2019","journal-title":"Eur. Heart J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3478","DOI":"10.1093\/eurheartj\/eht273","article-title":"Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population","volume":"34","author":"Nordestgaard","year":"2013","journal-title":"Eur. Heart J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S108","DOI":"10.1016\/j.ihj.2023.12.002","article-title":"Familial hypercholesterolemia","volume":"76","author":"Sawhney","year":"2024","journal-title":"Indian Heart J."},{"key":"ref_9","first-page":"89","article-title":"Atherosclerosis and inflammation","volume":"155","author":"Climent","year":"2020","journal-title":"Med. Clin."},{"key":"ref_10","first-page":"2058738419827154","article-title":"Lp-PLA2 in predicting cardiovascular events in metabolic disease patients","volume":"33","author":"Mannucci","year":"2019","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Popa-Fotea, N.M., Ferdoschi, C.E., and Micheu, M.M. (2023). Molecular and cellular mechanisms of inflammation in atherosclerosis. Front. Cardiovasc. Med., 10.","DOI":"10.3389\/fcvm.2023.1200341"},{"key":"ref_12","first-page":"164","article-title":"TNF-\u03b1 promotes early atherosclerosis by increasing transcytosis of LDL across endothelial cells","volume":"289","author":"Zhang","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1038\/nri2171","article-title":"Evolving functions of endothelial cells in inflammation","volume":"7","author":"Pober","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s11883-024-01259-7","article-title":"IL-6 and Cardiovascular Risk: A Narrative Review","volume":"27","author":"Mehta","year":"2025","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3227","DOI":"10.1093\/eurheartj\/ehab484","article-title":"2021 ESC Guidelines on cardiovascular disease prevention in clinical practice","volume":"42","author":"Visseren","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1093\/eurheartj\/ehab368","article-title":"2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure","volume":"42","author":"McDonagh","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3021","DOI":"10.1093\/eurheartj\/ehy339","article-title":"2018 ESC\/ESH Guidelines for the management of arterial hypertension","volume":"39","author":"Williams","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"28","DOI":"10.14797\/mdcvj.887","article-title":"Past, present, and future of familial hypercholesterolemia management","volume":"17","author":"Rocha","year":"2021","journal-title":"Methodist DeBakey Cardiovasc. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4043","DOI":"10.1093\/eurheartj\/ehad192","article-title":"2023 ESC Guidelines for the management of cardiovascular disease in patients with diabetes","volume":"44","author":"Marx","year":"2023","journal-title":"Eur. Heart J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.atherosclerosis.2018.08.013","article-title":"Evaluation of the performance of the Dutch Lipid Clinic Network score","volume":"277","author":"Casula","year":"2018","journal-title":"Atherosclerosis"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1093\/eurjpc\/zwae331","article-title":"Performance of LDL-C only compared to the Dutch Lipid Clinic Network score","volume":"32","author":"Ferch","year":"2025","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_22","first-page":"108","article-title":"Lipoprotein-associated phospholipase A2 activity is higher in definite familial hypercholesterolemia","volume":"272","author":"Mattina","year":"2018","journal-title":"Atherosclerosis"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.pharma.2015.09.002","article-title":"Lp-PLA2, a biomarker of vascular inflammation and vulnerability of atherosclerosis plaques","volume":"74","year":"2016","journal-title":"Ann. Pharm. Fr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/s13167-011-0063-4","article-title":"Lipoprotein-associated phospholipase A2: Role in atherosclerosis and utility as a biomarker","volume":"2","author":"Colley","year":"2011","journal-title":"EPMA J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.atherosclerosis.2014.01.022","article-title":"Subjects with familial hypercholesterolemia are characterized by an inflammatory phenotype despite long-term intensive cholesterol lowering treatment","volume":"233","author":"Holven","year":"2014","journal-title":"Atherosclerosis"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Morales-Portano, J.D., Trujillo-Cort\u00e9s, R., Roa-Mart\u00ednez, B.M., P\u00e9rez-Cabeza de Vaca, R., Garc\u00eda, S., Mondrag\u00f3n-Ter\u00e1n, P., and Su\u00e1rez-Cuenca, J.A. (2024). Expression of pro- and anti-inflammatory cytokines during anti-PCSK9 therapy in statin-resistant familial hypercholesterolemia. Front. Cardiovasc. Med., 11.","DOI":"10.3389\/fcvm.2024.1417044"},{"key":"ref_27","first-page":"49","article-title":"Sex differences in inflammation during atherosclerosis","volume":"8","author":"Fairweather","year":"2015","journal-title":"Clin. Med. Insights Cardiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"117270","DOI":"10.1016\/j.atherosclerosis.2023.117270","article-title":"Sex differences in lipids: A life course approach","volume":"384","author":"Holven","year":"2023","journal-title":"Atherosclerosis"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1093\/abbs\/gmv092","article-title":"Excess TNF \u03b1 in the blood activates monocytes with the potential to directly form cholesteryl ester laden cells","volume":"47","author":"Zhu","year":"2015","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1194\/jlr.M300448-JLR200","article-title":"Increased production of VLDL apoB-100 in subjects with familial hypercholesterolemia","volume":"45","author":"Tremblay","year":"2004","journal-title":"J. Lipid Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1042\/CS20090402","article-title":"Regulation of plasma LDL: The apoB paradigm","volume":"118","author":"Sniderman","year":"2010","journal-title":"Clin. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"107598","DOI":"10.1016\/j.intimp.2021.107598","article-title":"MCP-1: Function, regulation, and involvement in disease","volume":"101","author":"Singh","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1097\/01.fjc.0000156821.50457.32","article-title":"Effect of atorvastatin and fenofibrate treatment on monocyte chemoattractant protein-1 release","volume":"45","author":"Okopien","year":"2005","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_34","first-page":"1967","article-title":"Persistence of oxidized LDL despite intensive statin therapy in familial hypercholesterolemia","volume":"22","author":"Witteman","year":"2002","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Jiang, H., Zhou, Y., Nabavi, S.M., Sahebkar, A., Little, P.J., Xu, S., Weng, J., and Ge, J. (2022). Mechanisms of oxidized LDL mediated endothelial dysfunction. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.925923"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"27","DOI":"10.2174\/138161211795049831","article-title":"Oxidative modification of lipoproteins","volume":"17","author":"Tsimikas","year":"2011","journal-title":"Curr. Pharm. Des."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"110641","DOI":"10.1016\/j.isci.2024.110641","article-title":"Recent progress in gene therapy for familial hypercholesterolemia treatment","volume":"27","author":"Luo","year":"2024","journal-title":"iScience"}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/16\/8\/429\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T04:11:53Z","timestamp":1786853513000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/16\/8\/429"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,14]]},"references-count":37,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["jpm16080429"],"URL":"https:\/\/doi.org\/10.3390\/jpm16080429","relation":{},"ISSN":["2075-4426"],"issn-type":[{"value":"2075-4426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,14]]}}}