{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T21:30:30Z","timestamp":1785447030506,"version":"3.56.0"},"reference-count":35,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T00:00:00Z","timestamp":1740614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"AMC Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background and Aims: Elevated lipoprotein(a) [Lp(a)] and familial hypercholesterolemia (FH) are both inherited dyslipidemias that are independently associated with cardiovascular disease. Surrogate markers to assess signs of atherosclerosis, such as arterial stiffness, might be useful to evaluate the cardiovascular risk in young patients. The aim of this study is to evaluate the contribution of Lp(a) to arterial stiffness, as measured by carotid pulse wave velocity (cPWV) in young adults with FH. Methods: For this cross-sectional study, 214 children with FH who participated in a randomized controlled trial between 1997 and 1999 on the efficacy and safety of pravastatin were eligible. After 20 years, these patients were invited for a hospital visit, including cPWV assessment (by 4D flow MRI) and Lp(a) measurement. Linear mixed-effects models were used to evaluate the association between Lp(a) and cPWV. Results: We included 143 patients (mean [standard deviation] age: 31.8 [3.2] years) from 108 families. Median (interquartile range) cPWV was 1.62 (1.31\u20132.06) m\/s. Both the unadjusted (\u00df = \u22120.0014 m\/s per 1 mg\/dL increase in Lp(a), 95% CI: \u22120.0052 to 0.0023, p = 0.455) and adjusted model (\u00df = \u22120.0005 m\/s per 1 mg\/dL increase in Lp(a), 95% CI: \u22120.0042 to 0.0032, p = 0.785) showed no significant association between Lp(a) and cPWV. Conclusions: Our findings indicate that Lp(a) levels are not associated with carotid arterial stiffness in young adults with FH. Possibly, High Lp(a) might cause atherosclerosis by mechanisms beyond arterial stiffness in young adults. Other surrogate markers of early signs of atherosclerosis may be more suitable to evaluate the Lp(a)-mediated contribution to atherosclerosis in young FH patients.<\/jats:p>","DOI":"10.3390\/jcm14051611","type":"journal-article","created":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T05:13:58Z","timestamp":1740633238000},"page":"1611","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Association Between Lipoprotein(a) and Arterial Stiffness in Young Adults with Familial Hypercholesterolemia"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9911-2456","authenticated-orcid":false,"given":"Sibbeliene E.","family":"van den Bosch","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Amsterdam University Medical Center, Location AMC, 1105 AZ Amsterdam, The Netherlands"},{"name":"Department of Epidemiology and Data Science, Amsterdam University Medical Center, Location AMC, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam Cardiovascular Sciences Research Institute, Diabetes & Metabolism, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lotte M. de","family":"Boer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Amsterdam University Medical Center, Location AMC, 1105 AZ Amsterdam, The Netherlands"},{"name":"Department of Epidemiology and Data Science, Amsterdam University Medical Center, Location AMC, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam Cardiovascular Sciences Research Institute, Diabetes & Metabolism, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alma","family":"Revers","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Data Science, Amsterdam University Medical Center, Location AMC, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7922-3615","authenticated-orcid":false,"given":"Eric M.","family":"Schrauben","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, location AMC, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pim van","family":"Ooij","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, location AMC, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aart J.","family":"Nederveen","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, location AMC, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willemijn E.","family":"Corpeleijn","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Amsterdam University Medical Center, Location AMC, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam Cardiovascular Sciences Research Institute, Diabetes & Metabolism, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2018-4532","authenticated-orcid":false,"given":"John J.P.","family":"Kastelein","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine, Amsterdam University Medical Center, location AMC, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6223-5671","authenticated-orcid":false,"given":"Albert","family":"Wiegman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Amsterdam University Medical Center, Location AMC, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam Cardiovascular Sciences Research Institute, Diabetes & Metabolism, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9243-0037","authenticated-orcid":false,"given":"Barbara A.","family":"Hutten","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Data Science, Amsterdam University Medical Center, Location AMC, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam Cardiovascular Sciences Research Institute, Diabetes & Metabolism, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1982","DOI":"10.1016\/j.jacc.2014.01.063","article-title":"Lipoprotein(a) levels in familial hypercholesterolemia: An important predictor of cardiovascular disease independent of the type of LDL receptor mutation","volume":"63","author":"Alonso","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1002\/clc.22880","article-title":"Elevated lipoprotein(a) and familial hypercholesterolemia in the coronary care unit: Between Scylla and Charybdis","volume":"41","author":"Ellis","year":"2018","journal-title":"Clin. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1016\/j.jacc.2018.12.037","article-title":"Value of Measuring Lipoprotein(a) During Cascade Testing for Familial Hypercholesterolemia","volume":"73","author":"Ellis","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/S2213-8587(16)30042-0","article-title":"High lipoprotein(a) as a possible cause of clinical familial hypercholesterolaemia: A prospective cohort study","volume":"4","author":"Langsted","year":"2016","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/S2213-8587(23)00156-0","article-title":"Lipoprotein(a) and carotid intima-media thickness in children with familial hypercholesterolaemia in the Netherlands: A 20-year follow-up study","volume":"11","author":"Wiegman","year":"2023","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Kim, H.L., and Kim, S.H. (2019). Pulse Wave Velocity in Atherosclerosis. Front. Cardiovasc. Med., 6.","DOI":"10.3389\/fcvm.2019.00041"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1161\/HYPERTENSIONAHA.120.15336","article-title":"Aortic Pulse Wave Velocity Predicts Cardiovascular Events and Mortality in Patients Undergoing Coronary Angiography: A Comparison of Invasive Measurements and Noninvasive Estimates","volume":"77","author":"Hametner","year":"2021","journal-title":"Hypertension"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1586\/14779072.5.1.69","article-title":"MRI of atherosclerosis: Diagnosis and monitoring therapy","volume":"5","author":"Kramer","year":"2007","journal-title":"Expert. Rev. Cardiovasc. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1093\/ajh\/hpab178","article-title":"Clinical Applications Measuring Arterial Stiffness: An Expert Consensus for the Application of Cardio-Ankle Vascular Index","volume":"35","author":"Budoff","year":"2022","journal-title":"Am. J. Hypertens."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1002\/jmri.22856","article-title":"Analysis of pulse wave velocity in the thoracic aorta by flow-sensitive four-dimensional MRI: Reproducibility and correlation with characteristics in patients with aortic atherosclerosis","volume":"35","author":"Markl","year":"2012","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1002\/jmri.24900","article-title":"Fast 4D flow MRI intracranial segmentation and quantification in tortuous arteries","volume":"42","author":"Schrauben","year":"2015","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Simistiras, A., Georgiopoulos, G., Delialis, D., Mavraganis, G., Oikonomou, E., Maneta, E., Loutos, C., Evangelou, E., and Stamatelopoulos, K. (2024). Association of Lipoprotein(a) with arterial stiffness: A Mendelian randomization study. Eur. J. Clin. Investig., 54.","DOI":"10.1111\/eci.14168"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1001\/jama.292.3.331","article-title":"Efficacy and safety of statin therapy in children with familial hypercholesterolemia: A randomized controlled trial","volume":"292","author":"Wiegman","year":"2004","journal-title":"JAMA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1056\/NEJMoa1816454","article-title":"20-Year Follow-up of Statins in Children with Familial Hypercholesterolemia","volume":"381","author":"Luirink","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1093\/clinchem\/18.6.499","article-title":"Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge","volume":"18","author":"Friedewald","year":"1972","journal-title":"Clin. Chem."},{"key":"ref_16","unstructured":"Schrauben, E. (2024, August 01). Amsterdam UMC FlowProcessingTool. Available online: https:\/\/github.com\/schrau24\/FlowProcessing\/tree\/afterfifteen."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Bargiotas, I., Mousseaux, E., Yu, W.C., Venkatesh, B.A., Bollache, E., de Cesare, A., Lima, J.A., Redheuil, A., and Kachenoura, N. (2015). Estimation of aortic pulse wave transit time in cardiovascular magnetic resonance using complex wavelet cross-spectrum analysis. J. Cardiovasc. Magn. Reson., 17.","DOI":"10.1186\/s12968-015-0164-7"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2844","DOI":"10.1093\/eurheartj\/ehq386","article-title":"Lipoprotein(a) as a cardiovascular risk factor: Current status","volume":"31","author":"Nordestgaard","year":"2010","journal-title":"Eur. Heart J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.5114\/aoms.2019.89450","article-title":"Pulse wave velocity as a measure of arterial stiffness in patients with familial hypercholesterolemia: A systematic review and meta-analysis","volume":"15","author":"Reiner","year":"2019","journal-title":"Arch. Med. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1007\/s00246-018-1927-3","article-title":"Lipoprotein (a): Examination of Cardiovascular Risk in a Pediatric Referral Population","volume":"39","author":"Qayum","year":"2018","journal-title":"Pediatr. Cardiol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Yang, P.T., Tang, L., Guo, H.R., He, Y.M., Qin, Y.X., Yan, L., Li, Z.X., Guo, Y.Z., and Wang, J.G. (J. Atheroscler. Thromb., 2024). Prevalence of Lipoprotein(a) Measurement and its Association with Arteriosclerosis in Asymptomatic Individuals in China, J. Atheroscler. Thromb., online ahead of print.","DOI":"10.5551\/jat.65214"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1159\/000438733","article-title":"Lipoprotein(a) and Arterial Stiffness Parameters","volume":"3","author":"Sorokin","year":"2015","journal-title":"Pulse"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.cca.2006.05.018","article-title":"Lipoprotein (a) as a determinant of arterial stiffness in elderly patients with type 2 diabetes mellitus","volume":"373","author":"Wakabayashi","year":"2006","journal-title":"Clin. Chim. Acta"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Brosolo, G., Da Porto, A., Bulfone, L., Vacca, A., Bertin, N., Colussi, G., Cavarape, A., Sechi, L.A., and Catena, C. (2021). Plasma Lipoprotein(a) Levels as Determinants of Arterial Stiffening in Hypertension. Biomedicines, 9.","DOI":"10.3390\/biomedicines9111510"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Huang, P.Y., Hsu, B.G., Lin, Y.L., Tang, C.C., Liou, H.H., and Tsai, J.P. (2024). Serum Lipoprotein(a) Levels as a Predictor of Aortic Stiffness in Patients on Long-Term Peritoneal Dialysis. Med. Sci. Monit., 30.","DOI":"10.12659\/MSM.944348"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2282","DOI":"10.1093\/eurheartj\/ehy165","article-title":"Arterial stiffening is a heritable trait associated with arterial dilation but not wall thickening: A longitudinal study in the twins UK cohort","volume":"39","author":"Cecelja","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.atherosclerosis.2022.04.015","article-title":"Lipoprotein(a) and cardiovascular and valvular diseases: A genetic epidemiological perspective","volume":"349","author":"Arsenault","year":"2022","journal-title":"Atherosclerosis"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.jacl.2022.10.004","article-title":"Lipoprotein(a) and inflammation- pathophysiological links and clinical implications for cardiovascular disease","volume":"17","author":"Simantiris","year":"2023","journal-title":"J. Clin. Lipidol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s00380-012-0265-2","article-title":"Oxidized lipoprotein(a) and cardio-ankle vascular index (CAVI) in hypertensive subjects","volume":"28","author":"Kotani","year":"2013","journal-title":"Heart Vessel."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"410","DOI":"10.5551\/jat.No224","article-title":"Association of serum oxidized lipoprotein(a) concentration with coronary artery disease: Potential role of oxidized lipoprotein(a) in the vasucular wall","volume":"16","author":"Morishita","year":"2009","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1172\/JCI116983","article-title":"Impairment of endothelium-dependent dilation is an early event in children with familial hypercholesterolemia and is related to the lipoprotein(a) level","volume":"93","author":"Sorensen","year":"1994","journal-title":"J. Clin. Investig."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.jpeds.2014.12.051","article-title":"High lipoprotein(a) concentrations are associated with impaired endothelial function in children","volume":"166","author":"Lapinleimu","year":"2015","journal-title":"J. Pediatr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1097\/HJH.0b013e32835b051b","article-title":"Aortic pulse wave velocity results depend on which carotid artery is used for the measurements","volume":"31","author":"Dzeko","year":"2013","journal-title":"J. Hypertens."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Piechocki, M., Przew\u0142ocki, T., Pieni\u0105\u017cek, P., Trystu\u0142a, M., Podolec, J., and Kab\u0142ak-Ziembicka, A. (2024). A Non-Coronary, Peripheral Arterial Atherosclerotic Disease (Carotid, Renal, Lower Limb) in Elderly Patients\u2014A Review: Part I\u2014Epidemiology, Risk Factors, and Atherosclerosis-Related Diversities in Elderly Patients. J. Clin. Med., 13.","DOI":"10.3390\/jcm13051471"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3925","DOI":"10.1093\/eurheartj\/ehac361","article-title":"Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: A European Atherosclerosis Society consensus statement","volume":"43","author":"Kronenberg","year":"2022","journal-title":"Eur. Heart J."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/5\/1611\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:43:20Z","timestamp":1760028200000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/5\/1611"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,27]]},"references-count":35,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["jcm14051611"],"URL":"https:\/\/doi.org\/10.3390\/jcm14051611","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,27]]}}}