{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T20:09:25Z","timestamp":1762459765628,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2019,10,8]],"date-time":"2019-10-08T00:00:00Z","timestamp":1570492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003443","name":"Ministry of Education and Science of the Russian Federation","doi-asserted-by":"publisher","award":["0546-2015-0011"],"award-info":[{"award-number":["0546-2015-0011"]}],"id":[{"id":"10.13039\/501100003443","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Despite the fact that an association of osteopoenia\/osteoporosis with elevated risk of coronary artery calcification (CAC) and coronary atherosclerosis (CA) is well-established, it remains unclear whether bone turnover markers can be employed in long-term prognostication of such patients. Here we measured serum calcium, phosphate, calcitonin, parathyroid hormone (PTH), osteoprotegerin, osteocalcin, osteopontin, alkaline phosphatase and its bone isoenzyme, subsequently correlating them with an adverse cardiovascular outcome after 3 years of follow-up. The extent of brachiocephalic artery stenosis, CA, or CAC, as well as prevalence of osteopoenia\/osteoporosis before the coronary artery bypass graft (CABG) surgery, did not differ between outcome groups, suggesting that subtle molecular mechanisms might be involved in determining the outcome rather than clinical or subclinical disease. After stepwise logistic regression, serum osteocalcin &gt; 26.8 ng\/mL and PTH &gt; 49.1 pg\/mL were independent predictors of an adverse outcome. Serum ionised calcium correlated with multivessel coronary artery disease; moreover, patients with severe CA (SYNTAX score &gt; 21) had higher serum ionised calcium than those with mild CA. Likewise, serum alkaline phosphatase was associated with severe CA and CAC (Agatston score &gt; 400). In conclusion, serum PTH, osteocalcin, and alkaline phosphatase are associated with an adverse cardiovascular outcome 3 years after CABG surgery regardless of osteopoenia\/osteoporosis, coronary\/peripheral atherosclerosis, and CAC.<\/jats:p>","DOI":"10.3390\/diagnostics9040143","type":"journal-article","created":{"date-parts":[[2019,10,8]],"date-time":"2019-10-08T09:00:38Z","timestamp":1570525238000},"page":"143","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Increased Serum Parathyroid Hormone, Osteocalcin and Alkaline Phosphatase Are Associated with a Long-Term Adverse Cardiovascular Outcome after Coronary Artery Bypass Graft Surgery"],"prefix":"10.3390","volume":"9","author":[{"given":"Olga","family":"Barbarash","sequence":"first","affiliation":[{"name":"Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo 650002, Russia"},{"name":"Department of Cardiology and Cardiovascular Surgery, Kemerovo State Medical University, Kemerovo 650056, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikhail","family":"Zykov","sequence":"additional","affiliation":[{"name":"Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo 650002, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vasiliy","family":"Kashtalap","sequence":"additional","affiliation":[{"name":"Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo 650002, Russia"},{"name":"Department of Cardiology and Cardiovascular Surgery, Kemerovo State Medical University, Kemerovo 650056, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oksana","family":"Hryachkova","sequence":"additional","affiliation":[{"name":"Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo 650002, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7573-0636","authenticated-orcid":false,"given":"Alexandr","family":"Kokov","sequence":"additional","affiliation":[{"name":"Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo 650002, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga","family":"Gruzdeva","sequence":"additional","affiliation":[{"name":"Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo 650002, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina","family":"Shibanova","sequence":"additional","affiliation":[{"name":"Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo 650002, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anton","family":"Kutikhin","sequence":"additional","affiliation":[{"name":"Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo 650002, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1016\/j.jacc.2018.11.053","article-title":"PCI and CABG for Treating Stable Coronary Artery Disease: JACC Review Topic of the Week","volume":"73","author":"Doenst","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e002708","DOI":"10.1161\/CIRCOUTCOMES.116.002708","article-title":"Thirty-Year Mortality After Coronary Artery Bypass Graft Surgery: A Danish Nationwide Population-Based Cohort Study","volume":"10","author":"Adelborg","year":"2017","journal-title":"Circ. Cardiovasc. Qual. Outcomes"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1177\/0218492317692465","article-title":"Minimally invasive coronary artery bypass grafting: A systematic review","volume":"25","author":"Kikuchi","year":"2017","journal-title":"Asian Cardiovasc. Thorac. Ann."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e003742","DOI":"10.1161\/CIRCIMAGING.115.003742","article-title":"Long-Term Prognosis After Coronary Artery Calcium Scoring Among Low-Intermediate Risk Women and Men","volume":"9","author":"Kelkar","year":"2016","journal-title":"Circ. Cardiovasc Imaging"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"654","DOI":"10.2215\/CJN.07450714","article-title":"Vascular calcification in patients with nondialysis CKD over 3 years","volume":"10","author":"Molina","year":"2015","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1001\/jamacardio.2017.0363","article-title":"CRIC Investigators. Coronary Artery Calcification and Risk of Cardiovascular Disease and Death Among Patients With Chronic Kidney Disease","volume":"2","author":"Chen","year":"2017","journal-title":"JAMA Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"582","DOI":"10.21037\/jtd.2017.02.84","article-title":"Higher coronary artery calcification score is associated with adverse prognosis in patients with stable angina pectoris","volume":"9","author":"Wang","year":"2017","journal-title":"J. Thorac. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.atherosclerosis.2017.01.029","article-title":"Calcification of the splenic, iliac, and breast arteries and risk of all-cause and cardiovascular mortality","volume":"259","author":"Hendriks","year":"2017","journal-title":"Atherosclerosis"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.1016\/j.amjcard.2013.07.038","article-title":"Impact of the severity of coronary artery calcification on clinical events in patients undergoing coronary artery bypass grafting (from the Acute Catheterization and Urgent Intervention Triage Strategy Trial)","volume":"112","author":"Ertelt","year":"2013","journal-title":"Am. J. Cardiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1002\/jbmr.2530","article-title":"QCT Volumetric Bone Mineral Density and Vascular and Valvular Calcification: The Framingham Study","volume":"30","author":"Chan","year":"2015","journal-title":"J. Bone Miner. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.hlc.2016.02.002","article-title":"Decreased Cathepsin K Plasma Level may Reflect an Association of Osteopoenia\/Osteoporosis with Coronary Atherosclerosis and Coronary Artery Calcification in Male Patients with Stable Angina","volume":"25","author":"Barbarash","year":"2016","journal-title":"Heart Lung Circ."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Task Force Members, Montalescot, G., Sechtem, U., Achenbach, S., Andreotti, F., Arden, C., Budaj, A., Bugiardini, R., Crea, F., and Cuisset, T. (2013). 2013 ESC guidelines on the management of stable coronary artery disease: The Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur. Heart J., 34, 2949\u20133003.","DOI":"10.1093\/eurheartj\/eht296"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1093\/eurjhf\/hfs105","article-title":"ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC","volume":"14","author":"McMurray","year":"2012","journal-title":"Eur. J. Heart Fail."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1093\/eurheartj\/eht151","article-title":"2013 ESH\/ESC guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC)","volume":"34","author":"Mancia","year":"2013","journal-title":"Eur. Heart J."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Authors\/Task Force Members, Ryd\u00e9n, L., Grant, P.J., Anker, S.D., Berne, C., Cosentino, F., Danchin, N., Deaton, C., Escaned, J., and Hammes, H.P. (2013). ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: The Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD). Eur. Heart J., 34, 3035\u20133087.","DOI":"10.1093\/eurheartj\/eht108"},{"key":"ref_16","unstructured":"National Clinical Guideline Centre (UK) (2014). Obesity: Identification, Assessment and Management of Overweight and Obesity in Children. Young People and Adults: Partial Update of CG43, National Institute for Health and Care Excellence."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.jocd.2013.08.004","article-title":"Executive summary of the 2013 International Society for Clinical Densitometry Position Development Conference on bone densitometry","volume":"16","author":"Schousboe","year":"2013","journal-title":"J. Clin. Densitom."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1053\/j.ajkd.2008.11.029","article-title":"Plasma parathyroid hormone level and prevalent cardiovascular disease in CKD stages 3 and 4: An analysis from the Kidney Early Evaluation Program (KEEP)","volume":"53","author":"Bhuriya","year":"2009","journal-title":"Am. J. Kidney Dis."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Chartsrisak, K., Vipattawat, K., Assanatham, M., Nongnuch, A., Ingsathit, A., Domrongkitchaiporn, S., Sumethkul, V., and Distha-Banchong, S. (2013). Mineral metabolism and outcomes in chronic kidney disease stage 2-4 patients. BMC Nephrol., 14.","DOI":"10.1186\/1471-2369-14-14"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1097\/01.hjr.0000114706.27531.01","article-title":"Serum parathyroid hormone levels predict coronary heart disease: The Troms\u00f8 Study","volume":"11","author":"Kamycheva","year":"2004","journal-title":"Eur. J. Cardiovasc. Prev. Rehabil."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s00395-008-0774-4","article-title":"Ischemic injury activates PTHrP and PTH1R expression in human ventricular cardiomyocytes","volume":"104","author":"Monego","year":"2009","journal-title":"Basic Res. Cardiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2054","DOI":"10.1016\/j.ehj.2003.09.010","article-title":"Parathyroid hormone and left ventricular hypertrophy","volume":"24","author":"Saleh","year":"2003","journal-title":"Eur. Heart J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1681\/ASN.V961018","article-title":"Myocyte\/capillary mismatch in the heart of uremic patients","volume":"9","author":"Amann","year":"1998","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"S80","DOI":"10.1046\/j.1523-1755.63.s84.1.x","article-title":"Morphology of the heart and arteries in renal failure","volume":"84","author":"Tyralla","year":"2003","journal-title":"Kidney Int. Suppl."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/ki.2010.392","article-title":"Risk stratification for cardiac death in hemodialysis patients without obstructive coronary artery disease","volume":"79","author":"Nishimura","year":"2011","journal-title":"Kidney Int."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.2337\/dc06-2438","article-title":"Parathyroid hormone levels and the prevalence of metabolic syndrome in community-dwelling older adults","volume":"30","author":"Reis","year":"2007","journal-title":"Diabetes Care"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1161\/01.STR.0000078371.00577.76","article-title":"Possible role of parathyroid hormone-related protein as a proinflammatory cytokine in atherosclerosis","volume":"34","author":"Ortego","year":"2003","journal-title":"Stroke"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1097\/MCA.0000000000000089","article-title":"The association of serum parathyroid hormone and severity of coronary artery diseases","volume":"25","author":"Shekarkhar","year":"2014","journal-title":"Coron. Artery Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"601","DOI":"10.3892\/br.2016.761","article-title":"Correlation between serum parathyroid hormone levels and coronary artery calcification in patients without renal failure","volume":"5","author":"Wu","year":"2016","journal-title":"Biomed. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Tacey, A., Qaradakhi, T., Brennan-Speranza, T., Hayes, A., Zulli, A., and Levinger, I. (2018). Potential Role for Osteocalcin in the Development of Atherosclerosis and Blood Vessel Disease. Nutrients, 10.","DOI":"10.3390\/nu10101426"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1007\/s00198-011-1586-1","article-title":"Associations of total osteocalcin with all-cause and cardiovascular mortality in older men. The Health In Men Study","volume":"23","author":"Yeap","year":"2012","journal-title":"Osteoporos. Int."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1530\/EJE-13-1044","article-title":"Plasma osteocalcin levels as a predictor of cardiovascular disease in older men and women: A population-based cohort study","volume":"171","author":"Holvik","year":"2014","journal-title":"Eur. J. Endocrinol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/1440-1681.12853","article-title":"Association of serum osteocalcin levels with major adverse cardiovascular events: A 4.4-year retrospective cohort study","volume":"45","author":"Zhang","year":"2018","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1253\/circj.CJ-16-1288","article-title":"Preoperative Serum Alkaline Phosphatase and Clinical Outcome of Off-Pump Coronary Artery Bypass Surgery","volume":"81","author":"Kim","year":"2017","journal-title":"Circ. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1093\/eurheartj\/ehs419","article-title":"Serum alkaline phosphatase is a predictor of mortality.; myocardial infarction, or stent thrombosis after implantation of coronary drug-eluting stent","volume":"34","author":"Park","year":"2013","journal-title":"Eur. Heart J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1111\/eci.12752","article-title":"Alkaline phosphatase and prognosis in patients with coronary artery disease","volume":"47","author":"Ndrepepa","year":"2017","journal-title":"Eur. J. Clin. Investg."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Oh, P.C., Lee, K., Kim, T.H., Moon, J., Park, H.W., Jang, H.J., Park, S.D., Kwon, S.W., Suh, J., and Kang, W.C. (2017). Prognostic impact of alkaline phosphatase measured at time of presentation in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0171914"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/9\/4\/143\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:28:14Z","timestamp":1760189294000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/9\/4\/143"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,8]]},"references-count":37,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["diagnostics9040143"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics9040143","relation":{},"ISSN":["2075-4418"],"issn-type":[{"type":"electronic","value":"2075-4418"}],"subject":[],"published":{"date-parts":[[2019,10,8]]}}}