{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:02:41Z","timestamp":1789603361774,"version":"build-2803163510"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Cardiovasc Disord"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Metabolic disorders are increasing worldwide and are characterized by various risk factors such as abdominal obesity, insulin resistance, impaired glucose metabolism, and dyslipidemia. Observational studies suggested a bidirectional association between cardiovascular diseases and metabolic disorders and its components. However, the causal associations between them remained unclear. This study aims to investigate the causal relationship between metabolic disorders and cardiovascular disease through Mendelian randomization (MR) analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A two-sample MR analysis based on publicly available genome-wide association studies were used to infer the causality. The single-nucleotide polymorphisms with potential pleiotropy were excluded by MR-PRESSO. The effect estimates were constructed using the random-effects inverse-variance-weighted method as the primary estimate. Furthermore, MR-Egger and weighted median were also performed to detect heterogeneity and pleiotropy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Genetically predicted metabolic disorders increased the risk for coronary heart disease (OR\u2009=\u20091.77, 95% CI: 1.55\u20132.03, p\u2009&lt;\u20090.001), myocardial infarction (OR\u2009=\u20091.75, 95% CI: 1.52\u20132.03, p\u2009&lt;\u20090.001), heart failure (OR\u2009=\u20091.26, 95% CI: 1.14\u20131.39, p\u2009&lt;\u20090.001), hypertension (OR\u2009=\u20091.01, 95% CI: 1.00-1.02, p\u2009=\u20090.002), and stroke (OR\u2009=\u20091.19, 95% CI: 1.08\u20131.32, p\u2009&lt;\u20090.001). The concordance of the results of various complementary sensitivity MR methods reinforces the causal relationship further.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study provides evidence of a causal relationship between metabolic disorders and increased risk of coronary heart disease, myocardial infarction, heart failure, hypertension, and stroke. Special attention should be paid to improving metabolic disorders to reduce the development of cardiovascular diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12872-023-03567-3","type":"journal-article","created":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T01:01:51Z","timestamp":1698714111000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Metabolic disorders and risk of cardiovascular diseases: a two-sample mendelian randomization study"],"prefix":"10.1186","volume":"23","author":[{"given":"Zhe","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longyang","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqi","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihong","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,10,31]]},"reference":[{"key":"3567_CR1","doi-asserted-by":"crossref","unstructured":"Fahed G, Aoun L, Bou Zerdan M et al. Metabolic syndrome: updates on pathophysiology and management in 2021. Int J Mol Sci 2022, 23(2).","DOI":"10.3390\/ijms23020786"},{"issue":"3","key":"3567_CR2","doi-asserted-by":"publisher","first-page":"e3502","DOI":"10.1002\/dmrr.3502","volume":"38","author":"JL Silveira Rossi","year":"2022","unstructured":"Silveira Rossi JL, Barbalho SM, Reverete de Araujo R, et al. Metabolic syndrome and Cardiovascular Diseases: going beyond traditional risk factors. Diab\/Metab Res Rev. 2022;38(3):e3502.","journal-title":"Diab\/Metab Res Rev"},{"key":"3567_CR3","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.ahj.2016.04.011","volume":"177","author":"J Delgado-Lista","year":"2016","unstructured":"Delgado-Lista J, Perez-Martinez P, Garcia-Rios A, et al. CORonary Diet intervention with Olive oil and cardiovascular PREVention study (the CORDIOPREV study): Rationale, methods, and baseline characteristics: a clinical trial comparing the efficacy of a Mediterranean diet rich in olive oil versus a low-fat diet on Cardiovascular Disease in coronary patients. Am Heart J. 2016;177:42\u201350.","journal-title":"Am Heart J"},{"issue":"1","key":"3567_CR4","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1186\/s12933-020-01129-x","volume":"19","author":"EY Lee","year":"2020","unstructured":"Lee EY, Han K, Kim DH, et al. Exposure-weighted scoring for metabolic syndrome and the risk of Myocardial Infarction and Stroke: a nationwide population-based study. Cardiovasc Diabetol. 2020;19(1):153.","journal-title":"Cardiovasc Diabetol"},{"issue":"1","key":"3567_CR5","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s12933-021-01215-8","volume":"20","author":"HJ Ahn","year":"2021","unstructured":"Ahn HJ, Han KD, Choi EK, et al. Cumulative burden of metabolic syndrome and its components on the risk of atrial fibrillation: a nationwide population-based study. Cardiovasc Diabetol. 2021;20(1):20.","journal-title":"Cardiovasc Diabetol"},{"issue":"2","key":"3567_CR6","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1007\/s11906-018-0812-z","volume":"20","author":"MG Saklayen","year":"2018","unstructured":"Saklayen MG. The global epidemic of the metabolic syndrome. Curr Hypertens Rep. 2018;20(2):12.","journal-title":"Curr Hypertens Rep"},{"issue":"3","key":"3567_CR7","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1016\/j.thromres.2014.12.030","volume":"135","author":"MJ van Rooy","year":"2015","unstructured":"van Rooy MJ, Pretorius E. Metabolic syndrome, platelet activation and the development of transient ischemic Attack or thromboembolic Stroke. Thromb Res. 2015;135(3):434\u201342.","journal-title":"Thromb Res"},{"issue":"23","key":"3567_CR8","doi-asserted-by":"publisher","first-page":"e020760","DOI":"10.1161\/JAHA.121.020760","volume":"10","author":"H Iso","year":"2021","unstructured":"Iso H, Cui R, Takamoto I, et al. Risk classification for metabolic syndrome and the incidence of Cardiovascular Disease in Japan with low prevalence of obesity: a pooled analysis of 10 prospective cohort studies. J Am Heart Association. 2021;10(23):e020760.","journal-title":"J Am Heart Association"},{"issue":"1","key":"3567_CR9","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/s13073-021-00857-3","volume":"13","author":"S Rao","year":"2021","unstructured":"Rao S, Yao Y, Bauer DE. Editing GWAS: experimental approaches to dissect and exploit disease-associated genetic variation. Genome Med. 2021;13(1):41.","journal-title":"Genome Med"},{"issue":"4","key":"3567_CR10","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1002\/jrsm.1346","volume":"10","author":"J Bowden","year":"2019","unstructured":"Bowden J, Holmes MV. Meta-analysis and mendelian randomization: a review. Res Synthesis Methods. 2019;10(4):486\u201396.","journal-title":"Res Synthesis Methods"},{"issue":"1","key":"3567_CR11","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1186\/s12916-021-02188-x","volume":"19","author":"SC Larsson","year":"2021","unstructured":"Larsson SC, Burgess S. Causal role of high body mass index in multiple chronic Diseases: a systematic review and meta-analysis of mendelian randomization studies. BMC Med. 2021;19(1):320.","journal-title":"BMC Med"},{"issue":"7944","key":"3567_CR12","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1038\/s41586-022-05473-8","volume":"613","author":"MI Kurki","year":"2023","unstructured":"Kurki MI, Karjalainen J, Palta P, et al. FinnGen provides genetic insights from a well-phenotyped isolated population. Nature. 2023;613(7944):508\u201318.","journal-title":"Nature"},{"issue":"9","key":"3567_CR13","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.1038\/s41588-018-0133-9","volume":"50","author":"C Roselli","year":"2018","unstructured":"Roselli C, Chaffin MD, Weng LC, et al. Multi-ethnic genome-wide association study for atrial fibrillation. Nat Genet. 2018;50(9):1225\u201333.","journal-title":"Nat Genet"},{"issue":"10","key":"3567_CR14","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1038\/ng.3396","volume":"47","author":"M Nikpay","year":"2015","unstructured":"Nikpay M, Goel A, Won HH, et al. A comprehensive 1,000 genomes-based genome-wide association meta-analysis of coronary artery Disease. Nat Genet. 2015;47(10):1121\u201330.","journal-title":"Nat Genet"},{"issue":"1","key":"3567_CR15","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1038\/s41467-019-13690-5","volume":"11","author":"S Shah","year":"2020","unstructured":"Shah S, Henry A, Roselli C, et al. Genome-wide association and mendelian randomisation analysis provide insights into the pathogenesis of Heart Failure. Nat Commun. 2020;11(1):163.","journal-title":"Nat Commun"},{"issue":"6","key":"3567_CR16","doi-asserted-by":"publisher","first-page":"1971","DOI":"10.1161\/HYPERTENSIONAHA.120.15761","volume":"76","author":"S van Oort","year":"2020","unstructured":"van Oort S, Beulens JWJ, van Ballegooijen AJ, Grobbee DE, Larsson SC. Association of Cardiovascular Risk factors and lifestyle behaviors with Hypertension: a mendelian randomization study. Hypertens (Dallas Tex: 1979). 2020;76(6):1971\u20139.","journal-title":"Hypertens (Dallas Tex: 1979)"},{"issue":"7","key":"3567_CR17","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.1038\/s41588-019-0449-0","volume":"51","author":"R Malik","year":"2019","unstructured":"Malik R, Chauhan G, Traylor M, et al. Publisher correction: multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with Stroke and Stroke subtypes. Nat Genet. 2019;51(7):1192\u20133.","journal-title":"Nat Genet"},{"issue":"1","key":"3567_CR18","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1097\/EDE.0000000000000559","volume":"28","author":"S Burgess","year":"2017","unstructured":"Burgess S, Bowden J, Fall T, Ingelsson E, Thompson SG. Sensitivity analyses for robust causal inference from mendelian randomization analyses with multiple genetic variants. Epidemiol (Cambridge Mass). 2017;28(1):30\u201342.","journal-title":"Epidemiol (Cambridge Mass)"},{"issue":"2","key":"3567_CR19","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1093\/ije\/dyv080","volume":"44","author":"J Bowden","year":"2015","unstructured":"Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol. 2015;44(2):512\u201325.","journal-title":"Int J Epidemiol"},{"issue":"7","key":"3567_CR20","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.7150\/ijbs.7.1003","volume":"7","author":"S Braun","year":"2011","unstructured":"Braun S, Bitton-Worms K, LeRoith D. The link between the metabolic syndrome and cancer. Int J Biol Sci. 2011;7(7):1003\u201315.","journal-title":"Int J Biol Sci"},{"key":"3567_CR21","doi-asserted-by":"crossref","unstructured":"Lee HS, In S, Park T. The Homocysteine and metabolic syndrome: a mendelian randomization study. Nutrients 2021, 13(7).","DOI":"10.3390\/nu13072440"},{"issue":"1","key":"3567_CR22","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1186\/s12967-023-03920-2","volume":"21","author":"YY Liang","year":"2023","unstructured":"Liang YY, Chen J, Peng M, et al. Association between sleep duration and metabolic syndrome: linear and nonlinear mendelian randomization analyses. J Translational Med. 2023;21(1):90.","journal-title":"J Translational Med"},{"issue":"6","key":"3567_CR23","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1038\/s41575-022-00581-2","volume":"19","author":"A Metwaly","year":"2022","unstructured":"Metwaly A, Reitmeier S, Haller D. Microbiome risk profiles as biomarkers for inflammatory and metabolic disorders. Nat Reviews Gastroenterol Hepatol. 2022;19(6):383\u201397.","journal-title":"Nat Reviews Gastroenterol Hepatol"},{"key":"3567_CR24","doi-asserted-by":"publisher","first-page":"753039","DOI":"10.3389\/fendo.2021.753039","volume":"12","author":"W Zhang","year":"2021","unstructured":"Zhang W, Guo X, Chen L, et al. Ketogenic diets and Cardio-Metabolic Diseases. Front Endocrinol. 2021;12:753039.","journal-title":"Front Endocrinol"},{"issue":"5","key":"3567_CR25","doi-asserted-by":"publisher","first-page":"829","DOI":"10.2337\/diacare.25.5.829","volume":"25","author":"DW Dunstan","year":"2002","unstructured":"Dunstan DW, Zimmet PZ, Welborn TA, et al. The rising prevalence of Diabetes and impaired glucose tolerance: the Australian Diabetes, obesity and Lifestyle Study. Diabetes Care. 2002;25(5):829\u201334.","journal-title":"Diabetes Care"},{"issue":"4","key":"3567_CR26","doi-asserted-by":"publisher","first-page":"683","DOI":"10.2337\/diacare.24.4.683","volume":"24","author":"B Isomaa","year":"2001","unstructured":"Isomaa B, Almgren P, Tuomi T, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care. 2001;24(4):683\u20139.","journal-title":"Diabetes Care"},{"issue":"15","key":"3567_CR27","doi-asserted-by":"publisher","first-page":"1691","DOI":"10.1093\/eurjpc\/zwab020","volume":"28","author":"A Cittadini","year":"2021","unstructured":"Cittadini A, Salzano A, Iacoviello M, et al. Multiple hormonal and metabolic deficiency syndrome predicts outcome in Heart Failure: the T.O.S.CA. Registry. Eur J Prev Cardiol. 2021;28(15):1691\u2013700.","journal-title":"Eur J Prev Cardiol"},{"issue":"11","key":"3567_CR28","doi-asserted-by":"publisher","first-page":"e1009922","DOI":"10.1371\/journal.pgen.1009922","volume":"17","author":"Z Lin","year":"2021","unstructured":"Lin Z, Deng Y, Pan W. Combining the strengths of inverse-variance weighting and Egger regression in mendelian randomization using a mixture of regressions model. PLoS Genet. 2021;17(11):e1009922.","journal-title":"PLoS Genet"},{"issue":"1","key":"3567_CR29","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1186\/s12967-022-03407-6","volume":"20","author":"X Chen","year":"2022","unstructured":"Chen X, Hong X, Gao W, et al. Causal relationship between physical activity, leisure sedentary behaviors and COVID-19 risk: a mendelian randomization study. J Translational Med. 2022;20(1):216.","journal-title":"J Translational Med"},{"key":"3567_CR30","doi-asserted-by":"publisher","first-page":"186","DOI":"10.12688\/wellcomeopenres.15555.1","volume":"4","author":"S Burgess","year":"2019","unstructured":"Burgess S, Davey Smith G, Davies NM, et al. Guidelines for performing mendelian randomization investigations. Wellcome open Research. 2019;4:186.","journal-title":"Wellcome open Research"},{"key":"3567_CR31","doi-asserted-by":"publisher","first-page":"e26","DOI":"10.1017\/S2045796021000810","volume":"31","author":"X Sun","year":"2022","unstructured":"Sun X, Liu B, Liu S, et al. Sleep disturbance and psychiatric disorders: a bidirectional mendelian randomisation study. Epidemiol Psychiatric Sci. 2022;31:e26.","journal-title":"Epidemiol Psychiatric Sci"},{"issue":"3","key":"3567_CR32","doi-asserted-by":"publisher","first-page":"701","DOI":"10.2337\/dc21-1609","volume":"45","author":"F Cheng","year":"2022","unstructured":"Cheng F, Luk AO, Shi M, et al. Shortened leukocyte telomere length is Associated with Glycemic Progression in Type 2 Diabetes: a prospective and mendelian randomization analysis. Diabetes Care. 2022;45(3):701\u20139.","journal-title":"Diabetes Care"},{"key":"3567_CR33","doi-asserted-by":"crossref","unstructured":"Li L, Yang X. The Essential Element Manganese, Oxidative Stress, and Metabolic Diseases: Links and Interactions. Oxidative medicine and cellular longevity 2018, 2018:7580707.","DOI":"10.1155\/2018\/7580707"},{"issue":"11","key":"3567_CR34","doi-asserted-by":"publisher","first-page":"1603","DOI":"10.1016\/j.freeradbiomed.2010.09.006","volume":"49","author":"S Reuter","year":"2010","unstructured":"Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med. 2010;49(11):1603\u201316.","journal-title":"Free Radic Biol Med"},{"issue":"9","key":"3567_CR35","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1038\/s41569-022-00676-y","volume":"19","author":"J Bor\u00e9n","year":"2022","unstructured":"Bor\u00e9n J, Taskinen MR, Bj\u00f6rnson E, Packard CJ. Metabolism of triglyceride-rich lipoproteins in health and dyslipidaemia. Nat Reviews Cardiol. 2022;19(9):577\u201392.","journal-title":"Nat Reviews Cardiol"},{"issue":"23","key":"3567_CR36","doi-asserted-by":"publisher","first-page":"2254","DOI":"10.1161\/CIRCULATIONAHA.120.051937","volume":"143","author":"Y Liu","year":"2021","unstructured":"Liu Y, Luo Q, Su Z, et al. Suppression of myocardial hypoxia-inducible Factor-1\u03b1 compromises metabolic adaptation and impairs cardiac function in patients with cyanotic congenital Heart Disease during Puberty. Circulation. 2021;143(23):2254\u201372.","journal-title":"Circulation"},{"key":"3567_CR37","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.lfs.2016.02.002","volume":"148","author":"V Rani","year":"2016","unstructured":"Rani V, Deep G, Singh RK, Palle K, Yadav UC. Oxidative stress and metabolic disorders: Pathogenesis and therapeutic strategies. Life Sci. 2016;148:183\u201393.","journal-title":"Life Sci"}],"container-title":["BMC Cardiovascular Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12872-023-03567-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12872-023-03567-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12872-023-03567-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T01:02:14Z","timestamp":1698714134000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmccardiovascdisord.biomedcentral.com\/articles\/10.1186\/s12872-023-03567-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,31]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["3567"],"URL":"https:\/\/doi.org\/10.1186\/s12872-023-03567-3","relation":{},"ISSN":["1471-2261"],"issn-type":[{"value":"1471-2261","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,31]]},"assertion":[{"value":"26 February 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 October 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 October 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not Applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"Not Applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The authors declare no conflict of interest.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"529"}}