{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T03:09:52Z","timestamp":1777000192228,"version":"3.51.4"},"reference-count":41,"publisher":"BMJ","issue":"7","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2017,5,8]]},"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To examine the relationship between glycated haemoglobin A1c (HbA1c) levels and the risk of cardiovascular outcomes and all-cause mortality based on data from observational studies and to determine the optimal levels of HbA1c for preventing cardiovascular events and\/or mortality in diabetic and non-diabetic populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Review methods<\/jats:title>\n                    <jats:p>We systematically searched Medline, Embase, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews and Web of Science databases, from inception to July 2016, for observational studies addressing the association of HbA1c levels with mortality and cardiovascular outcomes. Random effects models were used to compute pooled estimates of HR and respective 95% CI for all-cause mortality, cardiovascular mortality and risk of cardiovascular events, separately for people with and without diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Seventy-four published studies were included in the systematic review, but only 46 studies could be incorporated in the meta-analysis. In both diabetic and non-diabetic populations, there was an increase in the risk of all-cause mortality when HbA1c levels were over 8.0% and 6.0%, respectively. The highest all-cause mortality in people with diabetes was HbA1c above 9.0% (HR=1.69; 95%\u2009CI 1.09 to 2.66) and in those without diabetes was HbA1c above 6.0% (HR=1.74; 95%\u2009CI 1.38 to 2.20). However, both diabetic and non-diabetic populations with lower HbA1c levels (below 6.0%\u2009HR=1.57; 95%\u2009CI 1.14 to 2.17 and below 5.0%\u2009HR=1.19; 95%\u2009CI 1.04 to 1.36, respectively) had higher all-cause mortality. Similar pooled estimates were found when cardiovascular mortality was the outcome variable.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>HbA1c is a reliable risk factor of all-cause and cardiovascular mortality in both diabetics and non-diabetics. Our findings establish optimal HbA1c levels, for the lowest all-cause and cardiovascular mortality, ranging from 6.0% to 8.0% in people with diabetes and from 5.0% to 6.0% in those without diabetes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2017-015949","type":"journal-article","created":{"date-parts":[[2017,7,31]],"date-time":"2017-07-31T20:25:36Z","timestamp":1501532736000},"page":"e015949","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":171,"title":["Glycated haemoglobin A1c as a risk factor of cardiovascular outcomes and all-cause mortality in diabetic and non-diabetic populations: a systematic review and meta-analysis"],"prefix":"10.1136","volume":"7","author":[{"given":"Iv\u00e1n","family":"Cavero-Redondo","sequence":"first","affiliation":[{"name":"Universidad de Castilla\u2014La Mancha, Health and Social Research Center, Cuenca, Spain"}]},{"given":"Barbara","family":"Peleteiro","sequence":"additional","affiliation":[{"name":"EPI Unit, Instituto de Sa\u00fade P\u00fablica,Universidade do Porto, Porto, Portugal"},{"name":"Departamento de Ci\u00eancias da Sa\u00fade P\u00fablica e Forenses e Educa\u00e7\u00e3o M\u00e9dica, Faculdade de Medicina, Universidade do Porto, Porto, Portugal"}]},{"given":"Celia","family":"\u00c1lvarez-Bueno","sequence":"additional","affiliation":[{"name":"Universidad de Castilla\u2014La Mancha, Health and Social Research Center, Cuenca, Spain"}]},{"given":"Fernando","family":"Rodriguez-Artalejo","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine and Public Health, Universidad Aut\u00f3noma de Madrid\/ IdiPaz, CIBERESP, and IMDEA-Food Institute. CEI UAM+CSIC, Madrid, Spain"}]},{"given":"Vicente","family":"Mart\u00ednez-Vizca\u00edno","sequence":"additional","affiliation":[{"name":"Universidad de Castilla\u2014La Mancha, Health and Social Research Center, Cuenca, Spain"},{"name":"Universidad Aut\u00f3noma de Chile, Facultad de Ciencias de la Salud, Talca, Chile"}]}],"member":"239","published-online":{"date-parts":[[2017,7,31]]},"reference":[{"key":"2025121600470277000_7.7.e015949.1","unstructured":"Mendis S . Global status report on noncommunicable diseases. Geneva: \u00a0World Health Organization, 2014."},{"key":"2025121600470277000_7.7.e015949.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0195-668X(03)00347-6"},{"key":"2025121600470277000_7.7.e015949.3","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-S005"},{"key":"2025121600470277000_7.7.e015949.4","unstructured":"World Health Organization. Use of glycated haemoglobin (HbA1c) in the diagnosis of diabetes mellitus: abbreviated report of a WHO consultation. Geneva: WHO, 2011."},{"key":"2025121600470277000_7.7.e015949.5","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0154411","article-title":"The Accuracy of Diagnostic Methods for Diabetic Retinopathy: A Systematic Review and Meta-Analysis","volume":"11","author":"Mart\u00ednez-Vizca\u00edno","year":"2016","journal-title":"PLoS One"},{"key":"2025121600470277000_7.7.e015949.6","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.20.7.1183"},{"key":"2025121600470277000_7.7.e015949.7","doi-asserted-by":"publisher","DOI":"10.1001\/jama.297.6.611"},{"key":"2025121600470277000_7.7.e015949.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.09.001"},{"key":"2025121600470277000_7.7.e015949.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2012.11.032"},{"key":"2025121600470277000_7.7.e015949.10","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.2006.087932"},{"key":"2025121600470277000_7.7.e015949.11","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.192278"},{"key":"2025121600470277000_7.7.e015949.12","doi-asserted-by":"publisher","DOI":"10.1900\/RDS.2014.11.138"},{"key":"2025121600470277000_7.7.e015949.13","doi-asserted-by":"crossref","first-page":"24071","DOI":"10.1038\/srep24071","article-title":"HbA1c and Risks of All-Cause and Cause-Specific Death in Subjects without Known Diabetes: A Dose-Response Meta-Analysis of Prospective Cohort Studies","volume":"6","author":"Zhong","year":"2016","journal-title":"Sci Rep"},{"key":"2025121600470277000_7.7.e015949.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2009.06.005"},{"key":"2025121600470277000_7.7.e015949.15","doi-asserted-by":"publisher","DOI":"10.1001\/jama.283.15.2008"},{"key":"2025121600470277000_7.7.e015949.16","unstructured":"Higgins JPT , Green S . selecting studies and collecting data. Cochrane Handbook of Systematic Reviews of Interventions, Version 5.1.0. Cochrane Collaboration, 2011. www.\u200bcochrane-handbook.\u200borg. (updated Mar 2011)."},{"key":"2025121600470277000_7.7.e015949.17","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2016-012229","article-title":"Glycosylated haemoglobin as a predictor of cardiovascular events and mortality: a protocol for a systematic review and meta-analysis","volume":"6","author":"Cavero-Redondo","year":"2016","journal-title":"BMJ Open"},{"key":"2025121600470277000_7.7.e015949.18","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-158-4-201302190-00009"},{"key":"2025121600470277000_7.7.e015949.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.cct.2006.04.004"},{"key":"2025121600470277000_7.7.e015949.20","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1186"},{"key":"2025121600470277000_7.7.e015949.21","doi-asserted-by":"crossref","unstructured":"Peat J , Barton B , Elliott E . Statistics workbook for evidence-based health care. John Wiley & Sons 2009.","DOI":"10.1002\/9781444300499"},{"key":"2025121600470277000_7.7.e015949.22","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0258(19991030)18:20<2693::AID-SIM235>3.0.CO;2-V"},{"key":"2025121600470277000_7.7.e015949.23","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.323.7304.101"},{"key":"2025121600470277000_7.7.e015949.24","doi-asserted-by":"publisher","DOI":"10.1037\/\/0033-2909.86.3.638"},{"key":"2025121600470277000_7.7.e015949.25","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0042551","article-title":"Glycosylated hemoglobin in relationship to cardiovascular outcomes and death in patients with type 2 diabetes: a systematic review and meta-analysis","volume":"7","author":"Zhang","year":"2012","journal-title":"PLoS One"},{"key":"2025121600470277000_7.7.e015949.26","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s00592-015-0803-3","article-title":"Hypoglycemia and risk of vascular events and mortality: a systematic review and meta-analysis","volume":"53","author":"Yeh","year":"2016","journal-title":"Acta Diabetol"},{"key":"2025121600470277000_7.7.e015949.27","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.ijcard.2016.06.118","article-title":"Effects of biological age on the associations of blood pressure with cardiovascular and non-cardiovascular mortality in old age: A population-based study","volume":"220","author":"Liang","year":"2016","journal-title":"Int J Cardiol"},{"key":"2025121600470277000_7.7.e015949.28","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.5603\/KP.a2013.0148","article-title":"Age, sex, and secondary prevention of ischaemic heart disease in everyday practice","volume":"71","author":"Jankowski","year":"2013","journal-title":"Kardiol Pol"},{"key":"2025121600470277000_7.7.e015949.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.ypmed.2007.08.012"},{"key":"2025121600470277000_7.7.e015949.30","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2840-10-98"},{"key":"2025121600470277000_7.7.e015949.31","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.27.5.1047"},{"key":"2025121600470277000_7.7.e015949.32","doi-asserted-by":"publisher","DOI":"10.1161\/hc4601.099487"},{"key":"2025121600470277000_7.7.e015949.33","unstructured":"Mendis S , Puska P , Norrving B . Global atlas on cardiovascular disease prevention and control. World Health Organization 2011."},{"key":"2025121600470277000_7.7.e015949.34","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.26.11.3160"},{"key":"2025121600470277000_7.7.e015949.35","doi-asserted-by":"publisher","DOI":"10.2337\/diab.28.12.1039"},{"key":"2025121600470277000_7.7.e015949.36","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.20.7.1183"},{"key":"2025121600470277000_7.7.e015949.37","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-9033"},{"key":"2025121600470277000_7.7.e015949.38","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-S005"},{"key":"2025121600470277000_7.7.e015949.39","unstructured":"World Health Organization. Use of glycated haemoglobin (HbA1c) in the diagnosis of diabetes mellitus: abbreviated report of a WHO consultation. Geneva: WHO, 2011."},{"key":"2025121600470277000_7.7.e015949.40","doi-asserted-by":"publisher","DOI":"10.1159\/000235241"},{"key":"2025121600470277000_7.7.e015949.41","doi-asserted-by":"publisher","DOI":"10.1002\/sim.2331"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2017-015949","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T08:47:28Z","timestamp":1765874848000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2017-015949"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7]]},"references-count":41,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2017,7,31]]},"published-print":{"date-parts":[[2017,7]]}},"alternative-id":["10.1136\/bmjopen-2017-015949"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2017-015949","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7]]}}}