{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T13:15:22Z","timestamp":1783689322647,"version":"3.55.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>\n                    Homocysteine (HCY) has been implicated in cardiovascular disease through adverse effects on vascular endothelium, oxidative stress, and thrombogenic pathways. Saudi Arabia has a young population and an increasing burden of cardiovascular disease, yet regional data on HCY and B-vitamin profiles in premature acute coronary syndrome (ACS) remain limited. This single-center cross-sectional exploratory study evaluated serum HCY, vitamins B12, B6, B1, and folate levels in 80 patients with premature ACS at King Fahd Military Medical Complex (KFMMC), Dhahran, Saudi Arabia. Premature ACS was defined as ACS occurring in men aged &amp;lt;=55 years and women aged &amp;lt;=65 years. Clinical, laboratory, electrocardiographic, echocardiographic, angiographic, and SYNTAX score II 2020 data were collected. Spearman correlation showed a weak but statistically significant inverse association between HCY and folate (rho = \u22120.254,\n                    <jats:italic>p<\/jats:italic>\n                    = 0.040; approximate R2 = 0.065), whereas correlations between HCY and vitamins B12, B1, and B6 were not statistically significant. Most patients had low SYNTAX score categories, and exploratory ordinal regression suggested associations between selected biomarkers\/clinical variables and SYNTAX score category; however, these findings should be interpreted cautiously because of the small sample size, absence of a control group, and risk of model instability. The study provides preliminary descriptive data on HCY and B-vitamin status among Saudi patients with premature ACS and highlights the need for larger, controlled, multicenter studies incorporating dietary assessment and genetic determinants such as MTHFR polymorphisms.\n                  <\/jats:p>","DOI":"10.3389\/fmed.2026.1847202","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T12:27:36Z","timestamp":1783686456000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Role of homocysteine, vitamins B12, B6, B1, and folate in Saudi patients with premature acute coronary syndrome"],"prefix":"10.3389","volume":"13","author":[{"given":"Khalid","family":"Alfaraidy","sequence":"first","affiliation":[{"name":"Department of Cardiology, King Fahad Military Medical Complex, Ministry of Defense Health Services","place":["Dhahran, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayman","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Cardiology, King Fahad Military Medical Complex, Ministry of Defense Health Services","place":["Dhahran, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Woodman","sequence":"additional","affiliation":[{"name":"Department of Scientific Research, King Fahad Military Medical Complex, Ministry of Defense Health Services","place":["Dhahran, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rehab","family":"Al-Ansari","sequence":"additional","affiliation":[{"name":"Adult Hematology Unit, Department of Internal Medicine, King Fahad Military Medical Complex, Ministry of Defense Health Services","place":["Dhahran, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasser A.","family":"Al Malki","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory, King Fahad Military Medical Complex, Ministry of Defense Health Services","place":["Dhahran, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatimah S.","family":"Alayidh","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory, King Fahad Military Medical Complex, Ministry of Defense Health Services","place":["Dhahran, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaser","family":"Alnaam","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, Prince Sultan Military College of Health Sciences","place":["Dammam, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulrahman","family":"Al Husil","sequence":"additional","affiliation":[{"name":"Department of Cardiology, King Fahad Military Medical Complex, Ministry of Defense Health Services","place":["Dhahran, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed I.","family":"Amin","sequence":"additional","affiliation":[{"name":"Department of Cardiology, King Fahad Military Medical Complex, Ministry of Defense Health Services","place":["Dhahran, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masniwati","family":"Sigem","sequence":"additional","affiliation":[{"name":"Department of Cardiology, King Fahad Military Medical Complex, Ministry of Defense Health Services","place":["Dhahran, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousef M.","family":"Hawsawi","sequence":"additional","affiliation":[{"name":"Research Center, King Faisal Specialist Hospital and Research Center","place":["Jeddah, Saudi Arabia"]},{"name":"Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lamiaa H.","family":"Al-Jamea","sequence":"additional","affiliation":[{"name":"Department of Academic Affairs and Training, King Fahad Military Medical Complex, Ministry of Defense Health Services","place":["Dhahran, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e56","DOI":"10.1161\/CIR.0000000000000659","article-title":"Heart disease and stroke statistics-2019 update: a report from the American heart association","volume":"139","author":"Benjamin","year":"2019","journal-title":"Circulation."},{"key":"B2","doi-asserted-by":"publisher","first-page":"228","DOI":"10.12688\/f1000research.74926.1","article-title":"Risk factors for premature coronary artery disease (PCAD) in adults: a systematic review protocol","volume":"10","author":"Khoja","year":"2021","journal-title":"F1000Res"},{"key":"B3","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1186\/s12872-015-0145-7","article-title":"Prevalence and risk factors of premature coronary artery disease in patients undergoing coronary angiography in Kurdistan, Iraq","volume":"15","author":"Mohammad","year":"2015","journal-title":"BMC Cardiovasc Disord."},{"key":"B4","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/j.ihj.2022.08.003","article-title":"Premature coronary artery disease, risk factors, clinical presentation, angiography and interventions: hospital based registry","volume":"74","author":"Sharma","year":"2022","journal-title":"Indian Heart J."},{"key":"B5","doi-asserted-by":"publisher","first-page":"473","DOI":"10.2147\/VHRM.S33305","article-title":"Disparity in risk factor pattern in premature versus late-onset coronary artery disease: a survey of 15,381 patients","volume":"8","author":"Reibis","year":"2012","journal-title":"Vasc Health Risk Manag."},{"key":"B6","doi-asserted-by":"publisher","first-page":"51","DOI":"10.5681\/jcvtr.2014.010","article-title":"Non-modifiable factors of coronary artery stenosis in late onset patients with coronary artery disease in Southern Iranian population","volume":"6","author":"Tabei","year":"2014","journal-title":"J Cardiovasc Thorac Res."},{"key":"B7","first-page":"103","article-title":"Association of major modifiable risk factors among patients with coronary artery disease\u2013a retrospective analysis","volume":"52","author":"Achari","year":"2004","journal-title":"J Assoc Physicians India."},{"key":"B8","first-page":"541","volume":"54","author":"Lutteri","year":"1999","journal-title":"Rev Med Liege."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1179807","DOI":"10.3389\/fnut.2023.1179807","article-title":"Homocysteine-a retrospective and prospective appraisal","volume":"10","author":"McCaddon","year":"2023","journal-title":"Front Nutr."},{"key":"B10","doi-asserted-by":"publisher","first-page":"144767","DOI":"10.1016\/j.gene.2020.144767","article-title":"Study the association of transmembrane serine protease 6 gene polymorphisms with iron deficiency status in Saudi Arabia","volume":"751","author":"Al-Amer","year":"2020","journal-title":"Gene."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.exphem.2018.07.007","article-title":"Philadelphia-like acute lymphoblastic leukemia: diagnostic dilemma and management perspectives","volume":"67","author":"Kotb","year":"2018","journal-title":"Exp Hematol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.3390\/cancers15041012","article-title":"Antiapoptotic gene genotype and allele variations and the risk of lymphoma","volume":"15","author":"Al-Amer","year":"2023","journal-title":"Cancers."},{"key":"B13","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1373\/clinchem.2003.021634","article-title":"Facts and recommendations about total homocysteine determinations: an expert opinion","volume":"50","author":"Refsum","year":"2004","journal-title":"Clin Chem."},{"key":"B14","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1186\/s12939-021-01510-6","article-title":"Socioeconomic determinants and inequalities in the prevalence of non-communicable diseases in Saudi Arabia","volume":"20","author":"Al-Hanawi","year":"2021","journal-title":"Int J Equity Health."},{"key":"B15","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1186\/s12872-024-03845-8","article-title":"A national perspective on cardiovascular diseases in Saudi Arabia","volume":"24","author":"Alqahtani","year":"2024","journal-title":"BMC Cardiovasc Disord."},{"key":"B16","doi-asserted-by":"publisher","first-page":"12727","DOI":"10.1038\/s41598-024-62970-8","article-title":"Identifying risk factors and mortality rate of premature coronary artery disease in young Saudi population","volume":"14","author":"Al-Khlaiwi","year":"2024","journal-title":"Sci Rep."},{"key":"B17","doi-asserted-by":"publisher","first-page":"2449051","DOI":"10.1080\/20523211.2024.2449051","article-title":"Transforming healthcare: Saudi Arabia's vision 2030 healthcare model","volume":"18","author":"Suleiman","year":"2025","journal-title":"J Pharm Policy Pract"},{"key":"B18","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1016\/j.thromres.2008.08.021","article-title":"High prevalence of hyperhomocysteinemia in young population of North India - a potential risk factor for coronary artery disease?","volume":"123","author":"Kumar","year":"2009","journal-title":"Thromb Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.ajem.2010.10.011","article-title":"Killip classification in patients with acute coronary syndrome: insight from a multicenter registry","volume":"30","author":"El-Menyar","year":"2012","journal-title":"Am J Emerg Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1016\/S0002-9149(01)01457-6","article-title":"Predictive value of the Killip classification in patients undergoing primary percutaneous coronary intervention for acute myocardial infarction","volume":"87","author":"DeGeare","year":"2001","journal-title":"Am J Cardiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1957","DOI":"10.1093\/eurheartj\/eht529","article-title":"Reperfusion therapy for ST elevation acute myocardial infarction 2010\/2011: current status in 37 ESC countries","volume":"35","author":"Kristensen","year":"2014","journal-title":"Eur Heart J"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1038\/s41598-024-51192-7","article-title":"Impacts of the SYNTAX score I, II and SYNTAX score II 2020 on left main revascularization","volume":"14","author":"Sung","year":"2024","journal-title":"Sci Rep."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1016\/S0140-6736(20)32114-0","article-title":"Redevelopment and validation of the SYNTAX score II to individualise decision making between percutaneous and surgical revascularisation in patients with complex coronary artery disease: secondary analysis of the multicentre randomised controlled SYNTAXES trial with external cohort validation","volume":"396","author":"Takahashi","year":"2020","journal-title":"Lancet."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.1016\/S0895-4356(96)00236-3","article-title":"Simulation study of the number of events per variable in logistic regression analysis","volume":"49","author":"Peduzzi","year":"1996","journal-title":"J Clin Epidemiol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"2455","DOI":"10.1177\/0962280218784726","article-title":"Sample size for binary logistic prediction models: beyond events per variable criteria","volume":"28","author":"van Smeden","year":"2019","journal-title":"Stat Methods Med Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.15537\/1658-3175.2534","article-title":"Coronary artery disease in Saudi Arabia","volume":"25","author":"Al-Nozha","year":"2004","journal-title":"Saudi Med J."},{"key":"B27","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1056\/NEJM199909023411001","article-title":"The effect of spironolactone on morbidity and mortality in patients with severe heart failure","volume":"341","author":"Pitt","year":"1999","journal-title":"N Engl J Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1056\/NEJMoa1009492","article-title":"Eplerenone in patients with systolic heart failure and mild symptoms","volume":"364","author":"Zannad","year":"2011","journal-title":"N Engl J Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1186\/s12872-024-03832-z","article-title":"Acute coronary syndrome patterns in the young: risk factor profile and in-hospital outcomes in a tertiary referral hospital in Kenya","volume":"24","author":"Kassam","year":"2024","journal-title":"BMC Cardiovasc Disord."},{"key":"B30","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.amjcard.2021.05.011","article-title":"Gender differences in premature coronary artery disease (from the national data from the NHANES database)","volume":"153","author":"Krittanawong","year":"2021","journal-title":"Am J Cardiol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1016\/S0002-9343(03)00051-2","article-title":"Influence of the menstrual cycle on the timing of acute coronary events in premenopausal women","volume":"114","author":"Hamelin","year":"2003","journal-title":"Am J Med."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1213","DOI":"10.1186\/s12889-020-09298-w","article-title":"Demographic, behavioral, and cardiovascular disease risk factors in the Saudi population: results from the prospective urban rural epidemiology study (PURE-Saudi)","volume":"20","author":"Alhabib","year":"2020","journal-title":"BMC Public Health."},{"key":"B33","doi-asserted-by":"publisher","first-page":"148","DOI":"10.37616\/2212-5043.1336","article-title":"Cardiovascular disease in Saudi Arabia: facts and the way forward","volume":"35","author":"Tash","year":"2023","journal-title":"J Saudi Heart Assoc."},{"key":"B34","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1186\/s12889-023-15834-1","article-title":"High prevalence of lack of knowledge and unhealthy lifestyle practices regarding premature coronary artery disease and its risk factors among the Saudi population","volume":"23","author":"Al-Khlaiwi","year":"2023","journal-title":"BMC Public Health."},{"key":"B35","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/j.jsha.2017.03.004","article-title":"Cardiovascular risk factors burden in Saudi Arabia: the Africa middle east cardiovascular epidemiological (ACE) study","volume":"29","author":"Ahmed","year":"2017","journal-title":"J Saudi Heart Assoc."},{"key":"B36","doi-asserted-by":"publisher","first-page":"49","DOI":"10.5539\/gjhs.v8n3p49","article-title":"Quality of life for Saudi patients with heart failure: a cross-sectional correlational study","volume":"8","author":"AbuRuz","year":"2015","journal-title":"Glob J Health Sci."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1847202\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T12:27:37Z","timestamp":1783686457000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1847202\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,10]]},"references-count":36,"alternative-id":["10.3389\/fmed.2026.1847202"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1847202","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,10]]},"article-number":"1847202"}}