{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:14:50Z","timestamp":1790381690661,"version":"4.1.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T00:00:00Z","timestamp":1665360000000},"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. Cardiovasc. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Functional vitamin B12 deficiency is common in cardiovascular diseases (CVDs), such as heart failure and myocardial infarction. Methylmalonic acid (MMA) is a specific and sensitive marker of vitamin B12 deficiency. However, there are scarce data in regard to the relationship between MMA and CVDs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>In this cross-sectional study, we analyzed data of 5,313 adult participants of the National Health and Nutrition Examination Survey (NHANES) 2013\u20132014. Associations between MMA and other variables were assessed with linear regression models. Univariable and multivariable logistic regression models were employed to explore the association between MMA and CVDs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The weighted prevalence of CVDs was 8.8% in the general population of the USA. Higher MMA levels were found in participants with CVDs (<jats:italic>p<\/jats:italic> &amp;lt; 0.001). Linear regression models revealed positive associations between serum MMA level and age (<jats:italic>p<\/jats:italic> &amp;lt; 0.001), glycohemoglobin (<jats:italic>p<\/jats:italic> = 0.023), fasting glucose (<jats:italic>p<\/jats:italic> = 0.044), mean cell volume (<jats:italic>p<\/jats:italic> = 0.038), and hypertension (<jats:italic>p<\/jats:italic> = 0.003). In the multivariable logistic model adjusting for age, gender, ethnicity, smoking, hypertension, glycohemoglobin, body mass index (BMI), low-density lipoprotein-cholesterol (LDL-C), renal dysfunction and vitamin B12, serum MMA (adjusted odds ratio, 3.08; 95% confidence interval: 1.63\u20135.81, <jats:italic>p<\/jats:italic> = 0.002, per ln nmol\/L increment) was associated with CVDs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study demonstrated that elevated serum MMA levels were independently associated with the presence of CVDs and may be used to predict the occurrence of CVDs.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcvm.2022.966543","type":"journal-article","created":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T04:39:55Z","timestamp":1665376795000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Increased serum methylmalonic acid levels were associated with the presence of cardiovascular diseases"],"prefix":"10.3389","volume":"9","author":[{"given":"Xiaoya","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wudi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meixiang","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.nutres.2015.10.003","article-title":"Metabolic vitamin B12 deficiency: a missed opportunity to prevent dementia and stroke.","volume":"36","author":"Spence","year":"2016","journal-title":"Nutr Res."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/nu11020482","article-title":"Vitamin B12 in relation to oxidative stress: a systematic review.","volume":"11","author":"van de Lagemaat","year":"2019","journal-title":"Nutrients."},{"key":"B3","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1097\/MOG.0b013e3283505852","article-title":"Subclinical cobalamin deficiency.","volume":"28","author":"Carmel","year":"2012","journal-title":"Curr Opin Gastroenterol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2015","DOI":"10.1001\/jama.288.16.2015","article-title":"Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis.","volume":"288","author":"Homocysteine Studies","year":"2002","journal-title":"JAMA."},{"key":"B5","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1046\/j.1365-2257.2001.00370.x","article-title":"Homocysteine and methylmalonic acid as indicators of folate and vitamin B12 deficiency in pregnancy.","volume":"23","author":"McMullin","year":"2001","journal-title":"Clin Lab Haematol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1016\/j.biochi.2012.10.028","article-title":"Serum vitamin B12 not reflecting vitamin b12 status in patients with type 2 diabetes.","volume":"95","author":"Obeid","year":"2013","journal-title":"Biochimie."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0147843","article-title":"Methylmalonic acid and homocysteine as indicators of vitamin B-12 deficiency in cancer.","volume":"11","author":"Vashi","year":"2016","journal-title":"PLoS One."},{"key":"B8","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1016\/j.hjc.2019.10.010","article-title":"Methylmalonic acid and vitamin B12 in patients with heart failure.","volume":"61","author":"Polytarchou","year":"2020","journal-title":"Hellenic J Cardiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1016\/j.jpeds.2011.06.005","article-title":"Cardiac disease in methylmalonic acidemia.","volume":"159","author":"Prada","year":"2011","journal-title":"J Pediatr."},{"key":"B10","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1093\/oxfordjournals.aje.a008828","article-title":"Homocysteine metabolism and risk of myocardial infarction: relation with vitamins B6, B12, and folate.","volume":"143","author":"Verhoef","year":"1996","journal-title":"Am J Epidemiol."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/7043883","article-title":"The regulation and characterization of mitochondrial-derived methylmalonic acid in mitochondrial dysfunction and oxidative stress: from basic research to clinical practice.","volume":"2022","author":"Liu","year":"2022","journal-title":"Oxid Med Cell Longev."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101741","article-title":"Mitochondria-Derived methylmalonic acid, a surrogate biomarker of mitochondrial dysfunction and oxidative stress. 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