{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T17:09:03Z","timestamp":1788282543363,"version":"build-2803163510"},"reference-count":33,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Hyperhomocysteinemia (homocysteine [Hcy] \u226515 \u03bcmol\/L) is frequently observed in patients with impaired kidney function and has been associated with vascular remodeling and increased cardiovascular risk. We aimed to evaluate the relationship between Hcy, arterial stiffness, coronary artery disease (CAD), peripheral arterial disease, and biomarkers of kidney injury in patients undergoing elective coronary angiography. Methods: In this prospective observational study, 133 patients undergoing elective coronary angiography were stratified according to serum Hcy levels (Hcy &lt;15 vs. Hcy \u226515 \u03bcmol\/L). CAD severity was assessed angiographically. Arterial stiffness was evaluated using carotid\u2013femoral pulse wave velocity (cfPWV), while peripheral arterial disease was assessed using ankle\u2013brachial index (ABI). Kidney function was evaluated using serum creatinine, estimated glomerular filtration rate (eGFR), cystatin C, and urinary albumin-to-creatinine ratio (UACR). Correlation, multivariable regression, logistic regression, and receiver operating characteristic (ROC) analyses were performed. Results: Patients with hyperhomocysteinemia demonstrated significantly worse kidney function, including higher serum creatinine, cystatin C, and UACR levels, and lower eGFR (all p &lt; 0.01). Patients with elevated Hcy levels also exhibited significantly higher cfPWV values (11.4 \u00b1 3.3 vs. 9.7 \u00b1 2.1 m\/s, p &lt; 0.001). Hcy correlated positively with cystatin C, creatinine, UACR, and cfPWV, and inversely with eGFR. In multivariable linear regression analysis, Hcy remained independently associated with increased cfPWV after adjustment for age, sex, and eGFR (\u03b2 = 0.137, 95% CI 0.047\u20130.226, and p = 0.003). This association remained significant in sensitivity analyses incorporating hypertension, diabetes mellitus, LDL cholesterol, and statin therapy (\u03b2 = 0.124, 95% CI 0.032\u20130.216, and p = 0.008). No independent associations were observed between Hcy and angiographic CAD severity or ABI values. ROC analysis demonstrated modest discrimination for elevated arterial stiffness (AUC = 0.66, 95% CI 0.56\u20130.76) and good discrimination for impaired kidney function (AUC = 0.82, 95% CI 0.69\u20130.92). Conclusions: Elevated Hcy levels were independently associated with impaired kidney function and increased central arterial stiffness, but not with angiographic CAD severity or peripheral arterial disease. These findings suggest that hyperhomocysteinemia may reflect cardiorenal vascular dysfunction and diffuse vascular remodeling rather than focal obstructive atherosclerotic disease. Further studies are needed to determine its clinical utility and prognostic value.<\/jats:p>","DOI":"10.3390\/jcm15134961","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:49:23Z","timestamp":1782434963000},"page":"4961","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Association of Homocysteine with Arterial Stiffness and Kidney Injury Biomarkers in Patients with Suspected Coronary Artery Disease"],"prefix":"10.3390","volume":"15","author":[{"given":"Nejc","family":"Piko","sequence":"first","affiliation":[{"name":"Department of Dialysis, University Medical Centre Maribor, 2000 Maribor, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastjan","family":"Bevc","sequence":"additional","affiliation":[{"name":"Department of Nephrology, University Medical Centre Maribor, 2000 Maribor, Slovenia"},{"name":"Medical Faculty, University of Maribor, 2000 Maribor, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1425-4189","authenticated-orcid":false,"given":"Franjo Husam","family":"Naji","sequence":"additional","affiliation":[{"name":"Clinical Department of Cardiology and Angiology, University Medical Centre Maribor, 2000 Maribor, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7395-752X","authenticated-orcid":false,"given":"Robert","family":"Ekart","sequence":"additional","affiliation":[{"name":"Department of Dialysis, University Medical Centre Maribor, 2000 Maribor, Slovenia"},{"name":"Medical Faculty, University of Maribor, 2000 Maribor, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1111\/j.1753-4887.2000.tb01862.x","article-title":"Homocysteine: A history in progress","volume":"58","author":"Finkelstein","year":"2000","journal-title":"Nutr. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"McCaddon, A., and Miller, J.W. (2023). Homocysteine-a retrospective and prospective appraisal. Front. Nutr., 10.","DOI":"10.3389\/fnut.2023.1179807"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Tinelli, C., Di Pino, A., Ficulle, E., Marcelli, S., and Feligioni, M. (2019). Hyperhomocysteinemia as a Risk Factor and Potential Nutraceutical Target for Certain Pathologies. Front. Nutr., 6.","DOI":"10.3389\/fnut.2019.00049"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1475-2891-14-6","article-title":"Role of homocysteine in the development of cardiovascular disease","volume":"14","author":"Ganguly","year":"2015","journal-title":"Nutr. J."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Poznyak, A.V., Sadykhov, N.K., Kartuesov, A.G., Borisov, E.E., Sukhorukov, V.N., and Orekhov, A.N. (2022). Atherosclerosis Specific Features in Chronic Kidney Disease (CKD). Biomedicines, 10.","DOI":"10.3390\/biomedicines10092094"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1111\/joim.13279","article-title":"Homocysteine\u2014From disease biomarker to disease prevention","volume":"290","author":"Smith","year":"2021","journal-title":"J. Intern. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1159\/000368532","article-title":"Albuminuria is Associated with Subendocardial Viability Ratio in Chronic Kidney Disease Patients","volume":"40","author":"Ekart","year":"2015","journal-title":"Kidney Blood Press. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"305","DOI":"10.2147\/VHRM.S106534","article-title":"Detection of peripheral arterial disease with an improved automated device: Comparison of a new oscillometric device and the standard Doppler method","volume":"12","author":"Millasseau","year":"2016","journal-title":"Vasc. Health Risk Manag."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"188","DOI":"10.2174\/1874192401610010188","article-title":"Pulse Wave Analysis by Applanation Tonometry for the Measurement of Arterial Stiffness","volume":"10","author":"Doupis","year":"2016","journal-title":"Open Cardiovasc. Med. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1093\/ndt\/gfl044","article-title":"Why is homocysteine elevated in renal failure and what can be expected from homocysteine-lowering?","volume":"21","year":"2006","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1081\/JDI-120004098","article-title":"Homocysteine and vascular access thrombosis in hemodialysis patients","volume":"24","author":"Hojs","year":"2002","journal-title":"Ren. Fail."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1111\/j.1523-1755.2004.00732.x","article-title":"Association between serum homocysteine and markers of impaired kidney function in adults in the United States","volume":"66","author":"Francis","year":"2004","journal-title":"Kidney Int."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.cca.2014.02.007","article-title":"Association between homocysteine status and the risk of nephropathy in type 2 diabetes mellitus","volume":"431","author":"Mao","year":"2014","journal-title":"Clin. Chim. Acta"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/s41440-021-00780-5","article-title":"Urinary albumin-to-creatinine ratio and the risk of first stroke in Chinese hypertensive patients treated with angiotensin-converting enzyme inhibitors","volume":"45","author":"He","year":"2022","journal-title":"Hypertens. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1080\/14737159.2020.1768849","article-title":"Cystatin C as a biomarker of chronic kidney disease: Latest developments","volume":"20","author":"Benoit","year":"2020","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Shih, Y.L., Shih, C.C., and Chen, J.Y. (2022). Elevated homocysteine level as an indicator for chronic kidney disease in community-dwelling middle-aged and elderly populations in Taiwan: A community-based cross-sectional study. Front. Med., 9.","DOI":"10.3389\/fmed.2022.964101"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Shen, Z., Zhang, Z., and Zhao, W. (2022). Relationship between plasma homocysteine and chronic kidney disease in US patients with type 2 diabetes mellitus: A cross-sectional study. BMC Nephrol., 23.","DOI":"10.1186\/s12882-022-03045-6"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1159\/000486013","article-title":"Association Between Plasma Homocysteine and Microalbuminuria in Untreated Patients with Essential Hypertension: A Case-Control Study","volume":"42","author":"Kuang","year":"2017","journal-title":"Kidney Blood Press. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/s41043-023-00430-1","article-title":"Hypertension and cystatin C account for sex differences in serum homocysteine levels in acute coronary syndrome subjects with normal serum creatinine","volume":"42","author":"Shang","year":"2023","journal-title":"J. Health Popul. Nutr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1159\/000314812","article-title":"Reduced kidney function estimated by cystatin C and clinical outcomes in hypertensive patients with coronary artery disease: Association with homocysteine and other cardiovascular risk factors","volume":"33","author":"Dzielinska","year":"2010","journal-title":"Kidney Blood Press. Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Chen, Z.H., Zhu, X.T., Hu, Z.P., Ni, J.X., and Chen, H.L. (2024). Correlation of serum homocysteine and cystatin C levels with prognosis in heart failure with preserved ejection fraction patients. BMC Cardiovasc. Disord., 24.","DOI":"10.1186\/s12872-024-04253-8"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1093\/eurjpc\/zwae022","article-title":"Homocysteine, hyperhomocysteinemia, and H-type hypertension","volume":"31","author":"Wu","year":"2024","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"107702","DOI":"10.1016\/j.jdiacomp.2020.107702","article-title":"Albuminuria rather than glomerular filtration rate is associated with vascular endothelial function in patients with type 2 diabetes","volume":"34","author":"Kakutani","year":"2020","journal-title":"J. Diabetes Complicat."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Romero-Gonz\u00e1lez, G., Rodr\u00edguez-Chitiva, N., Ca\u00f1ameras, C., Pa\u00fal-Mart\u00ednez, J., Urrutia-Jou, M., Troya, M., Soler-Majoral, J., Torres, F.G., S\u00e1nchez-Bay\u00e1, M., and Calabia, J. (2024). Albuminuria, Forgotten No More: Underlining the Emerging Role in CardioRenal Crosstalk. J. Clin. Med., 13.","DOI":"10.3390\/jcm13030777"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1161\/01.ATV.21.1.74","article-title":"Serum homocysteine levels are associated with the development of (micro)albuminuria: The Hoorn study","volume":"21","author":"Jager","year":"2001","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_26","first-page":"100515","article-title":"Elevated plasma homocysteine levels are associated with impaired peripheral microvascular vasomotor response","volume":"28","author":"Toya","year":"2020","journal-title":"Int. J. Cardiol. Heart Vasc."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Yuan, D., Chu, J., Lin, H., Zhu, G., Qian, J., Yu, Y., Yao, T., Ping, F., Chen, F., and Liu, X. (2022). Mechanism of homocysteine-mediated endothelial injury and its consequences for atherosclerosis. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.1109445"},{"key":"ref_28","first-page":"32","article-title":"Association between serum homocysteine and arterial stiffness in elderly: A community-based study","volume":"11","author":"Zhang","year":"2014","journal-title":"J. Geriatr. Cardiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"9709","DOI":"10.18632\/aging.102416","article-title":"Association of homocysteine with carotid-femoral pulse wave velocity in a southern Chinese population","volume":"11","author":"Wang","year":"2019","journal-title":"Aging"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"346","DOI":"10.14744\/SEMB.2018.77864","article-title":"The Relation between Homocysteine Levels in Patients with Acute Coronary Syndrome and Grace Score","volume":"54","author":"Calim","year":"2020","journal-title":"Sisli Etfal Hastan. Tip. Bul."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Petrovic, O., Vidanovic, S., Jovanovic, I., Paunovic, I., Rakocevic, I., Milasinovic, D., Tesic, M., Boskovic, N., Dukic, D., and Ostojic, M. (2024). Does Atrial Fibrillation at Diagnosis Change Prognosis in Patients with Aortic Stenosis?. J. Clin. Med., 13.","DOI":"10.3390\/jcm13133917"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1177\/0003319708319938","article-title":"Outcomes in patients with abnormal myocardial perfusion imaging and normal coronary angiogram","volume":"60","author":"Delcour","year":"2009","journal-title":"Angiology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"313","DOI":"10.5830\/CVJA-2011-048","article-title":"Association between plasma homocysteine and myocardial SPECT abnormalities in patients referred for suspected myocardial ischaemia","volume":"23","author":"Ankrah","year":"2012","journal-title":"Cardiovasc. J. Afr."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/13\/4961\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T04:18:23Z","timestamp":1783052303000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/13\/4961"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,25]]},"references-count":33,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["jcm15134961"],"URL":"https:\/\/doi.org\/10.3390\/jcm15134961","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,25]]}}}