{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T16:07:35Z","timestamp":1790352455168,"version":"4.1.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T00:00:00Z","timestamp":1661126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,2,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Cardiovascular disease and cancer share common pathogenesis and risk factors. Coronary microvascular dysfunction (CMD), reflecting impaired coronary microvascular dilation in response to stress, is related to a higher risk of major cardiovascular events; however, its association with cancer has not been explored.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>A retrospective study on 1042 patients with non-obstructive coronary artery diseases (NOCADs) was performed. Data regarding demographic, clinical history, diagnostic coronary reactivity test, and cancer occurrence were collected. Coronary microvascular dysfunction was defined as coronary flow reserve (the ratio of hyperaemic blood flow to resting blood flow) \u22642.5. Thirty-four per cent had CMD (67.4% female and the average age was 52.4 \u00b1 12.2 years). Of 917 patients with no history of cancer, 15.5% developed cancer during follow-up [median of 9 (4, 16) years]. Kaplan\u2013Meier analysis showed that CMD patients had lower cancer-free survival compared with those without CMD (log-rank P = 0.005). Cox proportional hazard analyses showed that after adjusting for age, sex, hypertension, diabetes, smoking, and glomerular filtration rate, CMD is independently associated with cancer [hazard ratio, 1.4; 95% confidence interval (CI), 1.09\u20132.04; P = 0.04]. The rate of major adverse cardiovascular events (MACE) was significantly higher in CMD patients compared with that in non-CMD patients who had a previous history of cancer [odds ratio (OR), 2.5; 95% CI, 1\u20136.2; P = 0.04] and those with no history of cancer (OR, 1.4; 95% CI, 1.01\u20131.9; P = 0.044).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Coronary microvascular dysfunction is associated with cancer incidence in patients presenting with NOCADs. This study emphasizes follow-up in patients with CMD to evaluate the risk of MACE as well as potential malignant diseases.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/eurjpc\/zwac184","type":"journal-article","created":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T04:27:42Z","timestamp":1661142462000},"page":"209-216","source":"Crossref","is-referenced-by-count":25,"title":["Coronary microvascular dysfunction is an independent predictor of developing cancer in patients with non-obstructive coronary artery disease"],"prefix":"10.1093","volume":"30","author":[{"given":"Nazanin","family":"Rajai","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Mayo Clinic , 200 First Street SW, Rochester, MN 55902 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9669-8009","authenticated-orcid":false,"given":"Ali","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Mayo Clinic , 200 First Street SW, Rochester, MN 55902 , USA"},{"name":"Department of Internal Medicine, Saint Louis University School of Medicine , Saint Louis, MO , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takumi","family":"Toya","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Mayo Clinic , 200 First Street SW, Rochester, MN 55902 , USA"},{"name":"Division of Cardiology, National Defense Medical College , Tokorozawa, Saitama , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaskanwal D","family":"Sara","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Mayo Clinic , 200 First Street SW, Rochester, MN 55902 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joerg","family":"Herrmann","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Mayo Clinic , 200 First Street SW, Rochester, MN 55902 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilach O","family":"Lerman","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Mayo Clinic , 200 First Street SW, Rochester, MN , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9446-5313","authenticated-orcid":false,"given":"Amir","family":"Lerman","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Mayo Clinic , 200 First Street SW, Rochester, MN 55902 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,8,22]]},"reference":[{"key":"2023021416214626800_zwac184-B1","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1161\/CIRCULATIONAHA.112.001183","article-title":"Ideal cardiovascular health is inversely associated with incident cancer: the Atherosclerosis Risk In Communities study","volume":"127","author":"Rasmussen-Torvik","year":"2013","journal-title":"Circulation"},{"key":"2023021416214626800_zwac184-B2","doi-asserted-by":"crossref","DOI":"10.1177\/1179546819866445","article-title":"Cancer therapy-related cardiac dysfunction: an overview for the clinician","volume":"13","author":"Perez","year":"2019","journal-title":"Clin Med Insights Cardiol"},{"key":"2023021416214626800_zwac184-B3","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1161\/CIRCULATIONAHA.118.033603","article-title":"Linking heart failure to cancer: background evidence and research perspectives","volume":"138","author":"Bertero","year":"2018","journal-title":"Circulation"},{"key":"2023021416214626800_zwac184-B4","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1002\/ejhf.472","article-title":"Incidence of cancer in patients with chronic heart failure: a long-term follow-up study","volume":"18","author":"Banke","year":"2016","journal-title":"Eur J Heart Fail"},{"key":"2023021416214626800_zwac184-B5","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCEP.121.009947","article-title":"Coronary microvascular dysfunction and the risk of atrial fibrillation from an artificial intelligence-enabled electrocardiogram","volume":"14","author":"Ahmad","year":"2021","journal-title":"Circ Arrhythm Electrophysiol"},{"key":"2023021416214626800_zwac184-B6","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1002\/ejhf.2010","article-title":"Coronary microvascular dysfunction is associated with exertional haemodynamic abnormalities in patients with heart failure with preserved ejection fraction","volume":"23","author":"Ahmad","year":"2021","journal-title":"Eur J Heart Fail"},{"key":"2023021416214626800_zwac184-B7","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1016\/j.jcin.2015.06.017","article-title":"Prevalence of coronary microvascular dysfunction among patients with chest pain and nonobstructive coronary artery disease","volume":"8","author":"Sara","year":"2015","journal-title":"JACC Cardiovasc Interv"},{"key":"2023021416214626800_zwac184-B8","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1001\/archinternmed.2009.50","article-title":"Adverse cardiovascular outcomes in women with nonobstructive coronary artery disease: a report from the Women\u2019s Ischemia Syndrome Evaluation Study and the St James Women Take Heart Project","volume":"169","author":"Gulati","year":"2009","journal-title":"Arch Intern Med"},{"key":"2023021416214626800_zwac184-B9","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.120.017746","article-title":"Coronary microvascular endothelial dysfunction in patients with angina and nonobstructive coronary artery disease is associated with elevated serum homocysteine levels","volume":"9","author":"Ahmad","year":"2020","journal-title":"J Am Heart Assoc"},{"key":"2023021416214626800_zwac184-B10","doi-asserted-by":"crossref","first-page":"569","DOI":"10.4244\/EIJ-D-20-00853","article-title":"Prognostic impact and clinical outcomes of coronary flow reserve and hyperemic microvascular resistance","volume":"17","author":"Toya","year":"2021","journal-title":"EuroIntervention"},{"key":"2023021416214626800_zwac184-B11","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1007\/s12079-021-00611-9","article-title":"The role of vascular endothelial protein tyrosine phosphatase on nitric oxide synthase function in diabetes: from molecular biology to the clinic","volume":"15","author":"Justo","year":"2021","journal-title":"J Cell Commun Signal"},{"key":"2023021416214626800_zwac184-B12","first-page":"533","article-title":"Coronary microvascular endothelial dysfunction is an independent predictor of development of osteoporosis in postmenopausal women","volume":"10","author":"Prasad","year":"2014","journal-title":"Vasc Health Risk Manag"},{"key":"2023021416214626800_zwac184-B13","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1093\/cvr\/cvaa009","article-title":"The pathogenic role of coronary microvascular dysfunction in the setting of other cardiac or systemic conditions","volume":"116","author":"Konst","year":"2020","journal-title":"Cardiovasc Res"},{"key":"2023021416214626800_zwac184-B14","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1177\/2047487319884246","article-title":"Assessment of peripheral endothelial function predicts future risk of solid-tumor cancer","volume":"27","author":"Toya","year":"2020","journal-title":"Eur J Prev Cardiol"},{"key":"2023021416214626800_zwac184-B15","doi-asserted-by":"crossref","first-page":"104223","DOI":"10.1016\/j.mvr.2021.104223","article-title":"Use of peripheral arterial tonometry in detection of abnormal coronary flow reserve","volume":"138","author":"Gaeta","year":"2021","journal-title":"Microvasc Res"},{"key":"2023021416214626800_zwac184-B16","doi-asserted-by":"crossref","first-page":"31","DOI":"10.3390\/diagnostics7020031","article-title":"Comparison of the peripheral reactive hyperemia index with myocardial perfusion reserve by 82Rb PET\/CT in HIV-infected patients","volume":"7","author":"\u00d8rb\u00e6k","year":"2017","journal-title":"Diagnostics"},{"key":"2023021416214626800_zwac184-B17","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1093\/eurheartj\/ehp459","article-title":"Coronary microcirculatory vasodilator function in relation to risk factors among patients without obstructive coronary disease and low to intermediate Framingham score","volume":"31","author":"Rubinshtein","year":"2010","journal-title":"Eur Heart J"},{"key":"2023021416214626800_zwac184-B18","doi-asserted-by":"crossref","first-page":"2621","DOI":"10.1161\/CIRCULATIONAHA.106.641654","article-title":"Smoking is associated with epicardial coronary endothelial dysfunction and elevated white blood cell count in patients with chest pain and early coronary artery disease","volume":"115","author":"Lavi","year":"2007","journal-title":"Circulation"},{"key":"2023021416214626800_zwac184-B19","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1056\/NEJMra061889","article-title":"Coronary microvascular dysfunction","volume":"356","author":"Camici","year":"2007","journal-title":"N Engl J Med"},{"key":"2023021416214626800_zwac184-B20","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1093\/cvr\/cvz301","article-title":"Pathophysiology and diagnosis of coronary microvascular dysfunction in ST-elevation myocardial infarction","volume":"116","author":"Konijnenberg","year":"2020","journal-title":"Cardiovasc Res"},{"key":"2023021416214626800_zwac184-B21","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1093\/cvr\/cvz058","article-title":"Inflammation: a common contributor to cancer, aging, and cardiovascular diseases\u2014expanding the concept of cardio-oncology","volume":"115","author":"Libby","year":"2019","journal-title":"Cardiovasc Res"},{"key":"2023021416214626800_zwac184-B22","doi-asserted-by":"publisher","DOI":"10.1111\/jgs.17921","article-title":"AGS and NIA bench-to bedside conference summary: cancer and cardiovascular disease","author":"Mohile","year":"2022","journal-title":"J Am Geriatr Soc"},{"key":"2023021416214626800_zwac184-B23","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1056\/NEJMoa1701719","article-title":"Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease","volume":"377","author":"Jaiswal","year":"2017","journal-title":"N Engl J Med"},{"key":"2023021416214626800_zwac184-B24","doi-asserted-by":"crossref","first-page":"2625","DOI":"10.1016\/j.jacc.2018.09.042","article-title":"Coronary microvascular disease pathogenic mechanisms and therapeutic options: JACC state-of-the-art review","volume":"72","author":"Taqueti","year":"2018","journal-title":"J Am Coll Cardiol"},{"key":"2023021416214626800_zwac184-B25","doi-asserted-by":"crossref","first-page":"141","DOI":"10.5487\/TR.2014.30.3.141","article-title":"Endothelium-derived relaxing factors of small resistance arteries in hypertension","volume":"30","author":"Kang","year":"2014","journal-title":"Toxicol Res"},{"key":"2023021416214626800_zwac184-B26","doi-asserted-by":"crossref","first-page":"726539","DOI":"10.1155\/2014\/726539","article-title":"Nitric oxide synthetic pathway in patients with microvascular angina and its relations with oxidative stress","volume":"2014","author":"Porro","year":"2014","journal-title":"Oxid Med Cell Longev"},{"key":"2023021416214626800_zwac184-B27","first-page":"31","article-title":"Comparison of serum gamma-glutamyltransferase levels between patients with cardiac syndrome X and healthy asymptomatic individuals","volume":"70","author":"Demir","year":"2012","journal-title":"Kardiol Pol"},{"key":"2023021416214626800_zwac184-B28","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/0027-5107(94)90245-3","article-title":"Chronic infections and inflammatory processes as cancer risk factors: possible role of nitric oxide in carcinogenesis","volume":"305","author":"Ohshima","year":"1994","journal-title":"Mutat Res"},{"key":"2023021416214626800_zwac184-B29","first-page":"4759","article-title":"Colorectal carcinogenesis: role of oxidative stress and antioxidants","volume":"37","author":"Carini","year":"2017","journal-title":"Anticancer Res"},{"key":"2023021416214626800_zwac184-B30","first-page":"400","article-title":"Chronic inflammation and cancer: the role of the mitochondria","volume":"25","author":"Kamp","year":"2011","journal-title":"Oncology (Williston Park)"},{"key":"2023021416214626800_zwac184-B31","doi-asserted-by":"crossref","first-page":"11553","DOI":"10.1007\/s13277-016-5098-7","article-title":"Role of interleukin-6 in cancer progression and therapeutic resistance","volume":"37","author":"Kumari","year":"2016","journal-title":"Tumour Biol"},{"key":"2023021416214626800_zwac184-B32","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/nrc3611","article-title":"Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms","volume":"13","author":"Elinav","year":"2013","journal-title":"Nat Rev Cancer"},{"key":"2023021416214626800_zwac184-B33","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1016\/S0140-6736(11)61720-0","article-title":"Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials","volume":"379","author":"Rothwell","year":"2012","journal-title":"Lancet"},{"key":"2023021416214626800_zwac184-B34","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s10552-011-9881-x","article-title":"Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in cancer progression and survival: a systematic review","volume":"23","author":"Mc Menamin","year":"2012","journal-title":"Cancer Causes Control"},{"key":"2023021416214626800_zwac184-B35","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1161\/01.CIR.0000153339.27064.14","article-title":"Endothelial function: cardiac events","volume":"111","author":"Lerman","year":"2005","journal-title":"Circulation"},{"key":"2023021416214626800_zwac184-B36","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.119.014954","article-title":"Association of isolated coronary microvascular dysfunction with mortality and major adverse cardiac events: a systematic review and meta-analysis of aggregate data","volume":"9","author":"Gdowski","year":"2020","journal-title":"J Am Heart Assoc"},{"key":"2023021416214626800_zwac184-B37","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1007\/s00330-018-5895-z","article-title":"Microvascular obstruction extent predicts major adverse cardiovascular events in patients with acute myocardial infarction and preserved ejection fraction","volume":"29","author":"Galea","year":"2019","journal-title":"Eur Radiol"},{"key":"2023021416214626800_zwac184-B38","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1002\/acr.24108","article-title":"Coronary microvascular dysfunction in rheumatoid arthritis compared to diabetes mellitus and association with all-cause mortality","volume":"73","author":"Liao","year":"2021","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"2023021416214626800_zwac184-B39","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1097\/MCA.0000000000000145","article-title":"Microvascular endothelial dysfunction predicts the development of erectile dysfunction in men with coronary atherosclerosis without critical stenoses","volume":"25","author":"Reriani","year":"2014","journal-title":"Coron Artery Dis"},{"key":"2023021416214626800_zwac184-B40","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.ejim.2021.05.027","article-title":"Prognostic impact of coronary microvascular dysfunction in patients with myocardial infarction with non-obstructive coronary arteries","volume":"92","author":"Abdu","year":"2021","journal-title":"Eur J Intern Med"},{"key":"2023021416214626800_zwac184-B41","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1136\/heartjnl-2019-315909","article-title":"Coronary slow flow is associated with a worse clinical outcome in patients with Takotsubo syndrome","volume":"106","author":"Montone","year":"2020","journal-title":"Heart"},{"key":"2023021416214626800_zwac184-B42","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.transproceed.2015.12.048","article-title":"Coronary microvascular dysfunction predicts long-term outcome in simultaneous pancreas-kidney transplantation","volume":"48","author":"Tona","year":"2016","journal-title":"Transplant Proc"},{"key":"2023021416214626800_zwac184-B43","first-page":"27","article-title":"New insights on the toxicity on heart and vessels of breast cancer therapies","volume":"10","author":"Lanza","year":"2022","journal-title":"Med Sci (Basel)"},{"key":"2023021416214626800_zwac184-B44","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1097\/CM9.0000000000002054","article-title":"Immune checkpoint inhibitors-associated cardiotoxicity in immunotherapy trials on gastrointestinal cancer patients","volume":"135","author":"Li","year":"2022","journal-title":"Chin Med J (Engl)"},{"key":"2023021416214626800_zwac184-B45","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.hfc.2022.02.006","article-title":"Arrhythmic complications associated with cancer therapies","volume":"18","author":"Pothineni","year":"2022","journal-title":"Heart Fail Clin"},{"key":"2023021416214626800_zwac184-B46","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.hfc.2022.02.012","article-title":"Radiation-induced cardiac dysfunction: optimizing radiation delivery and postradiation care","volume":"18","author":"Pedersen","year":"2022","journal-title":"Heart Fail Clin"}],"container-title":["European Journal of Preventive Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/eurjpc\/advance-article-pdf\/doi\/10.1093\/eurjpc\/zwac184\/47200624\/zwac184.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurjpc\/article-pdf\/30\/3\/209\/49178843\/zwac184.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurjpc\/article-pdf\/30\/3\/209\/49178843\/zwac184.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T17:49:47Z","timestamp":1676396987000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eurjpc\/article\/30\/3\/209\/6672959"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,22]]},"references-count":46,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,8,22]]},"published-print":{"date-parts":[[2023,2,14]]}},"URL":"https:\/\/doi.org\/10.1093\/eurjpc\/zwac184","relation":{},"ISSN":["2047-4873","2047-4881"],"issn-type":[{"value":"2047-4873","type":"print"},{"value":"2047-4881","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,2,1]]},"published":{"date-parts":[[2022,8,22]]}}}