{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T16:54:35Z","timestamp":1788454475574,"version":"build-2803163510"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T00:00:00Z","timestamp":1634169600000},"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:p><jats:bold>Background:<\/jats:bold> Heterogeneous mechanisms may contribute to the occurrence of mitral annular calcification (MAC), however, little is known about the sex differences in MAC and the clinical implications of these differences. This study aimed to investigate clinical and imaging differences of MAC according to sex.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> In total, 537 patients (221 men) with MAC were identified by transthoracic echocardiography at a single center from January 2012 to June 2016. Moderate-to-severe MAC was defined as calcification extent \u2265120\u00b0 of the mitral annulus. Significant functional mitral stenosis (MS) was defined as a transmitral mean diastolic pressure gradient \u22655 mmHg.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Women more frequently had moderate-to-severe MAC and concomitant mitral regurgitation than men; however, significant functional MS was comparable between sexes. In the logistic regression analysis, old age, uncontrolled hypertension, end-stage renal disease (ESRD), and obstructive hypertrophic cardiomyopathy were significantly associated with moderate-to-severe MAC in women, whereas ESRD and moderate-to-severe aortic stenosis were in men. In the Cox regression analysis, significant functional MS was associated with all-cause death in both sexes, although an independent association was found in only women.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Women had more extended MAC than men. Significant functional MS was independently associated with unfavorable clinical outcomes in patients with MAC, which was more pronounced in women than in men.<\/jats:p>","DOI":"10.3389\/fcvm.2021.736040","type":"journal-article","created":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T05:14:00Z","timestamp":1634188440000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Sex Differences in Mitral Annular Calcification and the Clinical Implications"],"prefix":"10.3389","volume":"8","author":[{"given":"Jiwon","family":"Seo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeonju","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iksung","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geu-Ru","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Won","family":"Ha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi Young","family":"Shim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1016\/0002-8703(84)90840-8","article-title":"Mitral annular calcification: clinical, pathophysiology, and echocardiographic review","volume":"107","author":"Nestico","year":"1984","journal-title":"Am Heart J."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1492","DOI":"10.1161\/01.CIR.0000058168.26163.BC","article-title":"Mitral annular calcification predicts cardiovascular morbidity and mortality: the Framingham Heart Study","volume":"107","author":"Fox","year":"2003","journal-title":"Circulation."},{"key":"B3","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1016\/j.jcmg.2008.07.006","article-title":"Impact of mitral annular calcification on cardiovascular events in a multiethnic community: the Northern Manhattan Study","volume":"1","author":"Kohsaka","year":"2008","journal-title":"JACC Cardiovasc Imaging."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e0227753","DOI":"10.1371\/journal.pone.0227753","article-title":"Morphological and functional characteristics of mitral annular calcification and their relationship to stroke","volume":"15","author":"Kim","year":"2020","journal-title":"PLoS One."},{"key":"B5","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1016\/j.atherosclerosis.2010.08.072","article-title":"Relationships of mitral annular calcification to cardiovascular risk factors: the Multi-Ethnic Study of Atherosclerosis (MESA)","volume":"213","author":"Kanjanauthai","year":"2010","journal-title":"Atherosclerosis."},{"key":"B6","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1016\/0002-9149(86)90045-7","article-title":"The senile cardiac calcification syndrome","volume":"58","author":"Roberts","year":"1986","journal-title":"Am J Cardiol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1136\/hrt.78.5.472","article-title":"Cardiac valve calcification: characteristics of patients with calcification of the mitral annulus or aortic valve","volume":"78","author":"Boon","year":"1997","journal-title":"Heart."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1934","DOI":"10.1016\/j.jacc.2015.08.872","article-title":"Mitral annulus calcification","volume":"66","author":"Abramowitz","year":"2015","journal-title":"J Am Coll Cardiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1016\/S0002-9149(83)80181-7","article-title":"Morphologic features of the normal and abnormal mitral valve","volume":"51","author":"Roberts","year":"1983","journal-title":"Am J Cardiol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1016\/j.ahj.2013.08.015","article-title":"Risk factors associated with the incidence and progression of mitral annulus calcification: the multi-ethnic study of atherosclerosis","volume":"166","author":"Elmariah","year":"2013","journal-title":"Am Heart J."},{"key":"B11","doi-asserted-by":"publisher","first-page":"e008513","DOI":"10.1161\/CIRCIMAGING.118.008513","article-title":"Disease activity in mitral annular calcification","volume":"12","author":"Massera","year":"2019","journal-title":"Circ Cardiovasc Imaging."},{"key":"B12","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1093\/ehjci\/jev014","article-title":"Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging","volume":"16","author":"Lang","year":"2015","journal-title":"Eur Heart J Cardiovasc Imaging."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2533","DOI":"10.1161\/01.STR.0000190005.09442.ad","article-title":"Mitral annular calcification, aortic valve sclerosis, and incident stroke in adults free of clinical cardiovascular disease: the Strong Heart Study","volume":"36","author":"Kizer","year":"2005","journal-title":"Stroke."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1542","DOI":"10.1093\/eurheartj\/ehn172","article-title":"Association of mitral annular calcification and aortic valve morphology: a substudy of the aortic stenosis progression observation measuring effects of rosuvastatin (ASTRONOMER) study","volume":"29","author":"Jassal","year":"2008","journal-title":"Eur Heart J."},{"key":"B15","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1093\/ejechocard\/jen179","article-title":"Non-rheumatic annular mitral stenosis: prevalence and characteristics","volume":"10","author":"Akram","year":"2009","journal-title":"Eur J Echocardiogr."},{"key":"B16","doi-asserted-by":"publisher","first-page":"e72","DOI":"10.1161\/CIR.0000000000000932","article-title":"2020 ACC\/AHA guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines","volume":"143","author":"Otto","year":"2021","journal-title":"Circulation."},{"key":"B17","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1056\/NEJM199208063270602","article-title":"Mitral annular calcification and the risk of stroke in an elderly cohort","volume":"327","author":"Benjamin","year":"1992","journal-title":"N Engl J Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.atherosclerosis.2003.12.018","article-title":"Mitral annular calcification is a predictor for incident atrial fibrillation","volume":"173","author":"Fox","year":"2004","journal-title":"Atherosclerosis."},{"key":"B19","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1093\/ehjci\/jex093","article-title":"Mitral annular calcification progression and the risk of atrial fibrillation: results from MESA","volume":"19","author":"O'Neal","year":"2018","journal-title":"Eur Heart J Cardiovasc Imaging."},{"key":"B20","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1093\/europace\/euu265","article-title":"Mitral annular calcification and incident atrial fibrillation in the Multi-Ethnic Study of Atherosclerosis","volume":"17","author":"O'Neal","year":"2015","journal-title":"Europace."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1161\/CIRCRESAHA.120.315930","article-title":"Sex as a biological variable in atherosclerosis","volume":"126","author":"Man","year":"2020","journal-title":"Circ Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1801","DOI":"10.1056\/NEJM199906103402306","article-title":"The protective effects of estrogen on the cardiovascular system","volume":"340","author":"Mendelsohn","year":"1999","journal-title":"N Engl J Med."},{"key":"B23","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1253\/jcj.57.14","article-title":"The influence of severe bone loss on mitral annular calcification in postmenopausal osteoporosis of elderly Japanese women","volume":"57","author":"Sugihara","year":"1993","journal-title":"Jpn Circ J."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1926","DOI":"10.1161\/01.ATV.20.8.1926","article-title":"Progression of aortic calcification is associated with metacarpal bone loss during menopause: a population-based longitudinal study","volume":"20","author":"Hak","year":"2000","journal-title":"Arterioscler Thromb Vasc Biol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1161\/01.CIR.86.4.1099","article-title":"Sex-associated differences in left ventricular function in aortic stenosis of the elderly","volume":"86","author":"Carroll","year":"1992","journal-title":"Circulation."},{"key":"B26","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1016\/0002-9149(93)90678-6","article-title":"Sex differences in cardiac adaptation to isolated systolic hypertension","volume":"72","author":"Krumholz","year":"1993","journal-title":"Am J Cardiol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1016\/j.jcmg.2016.09.001","article-title":"Severe mitral annular calcification: multimodality imaging for therapeutic strategies and interventions","volume":"9","author":"Eleid","year":"2016","journal-title":"JACC Cardiovasc Imaging."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1594","DOI":"10.1161\/CIRCULATIONAHA.115.020185","article-title":"Degenerative mitral stenosis: unmet need for percutaneous interventions","volume":"133","author":"Sud","year":"2016","journal-title":"Circulation."},{"key":"B29","unstructured":"Progression of degenerative mitral stenosis: insights from a cohort of 254 patients70712\n            TyagiG\n            DangP\n            PascaI\n            PatelR\n            PaiRG\n          25790617J Heart Valve Dis.232014"},{"key":"B30","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1016\/j.echo.2015.12.012","article-title":"Survival in patients with degenerative mitral stenosis: results from a large retrospective cohort study","volume":"29","author":"Pasca","year":"2016","journal-title":"J Am Soc Echocardiogr."},{"key":"B31","doi-asserted-by":"publisher","first-page":"4321","DOI":"10.1093\/eurheartj\/ehaa819","article-title":"Prognostic importance of the transmitral pressure gradient in mitral annular calcification with associated mitral valve dysfunction","volume":"41","author":"Bertrand","year":"2020","journal-title":"Eur Heart J."}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2021.736040\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T05:14:36Z","timestamp":1634188476000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2021.736040\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,14]]},"references-count":31,"alternative-id":["10.3389\/fcvm.2021.736040"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2021.736040","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,14]]},"article-number":"736040"}}