{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T02:46:39Z","timestamp":1790304399675,"version":"4.1.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T00:00:00Z","timestamp":1685404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870255"],"award-info":[{"award-number":["81870255"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of the Zhejiang Province","doi-asserted-by":"publisher","award":["LY21H020001"],"award-info":[{"award-number":["LY21H020001"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005315","name":"Natural Science Foundation of Ningbo Municipality","doi-asserted-by":"publisher","award":["2021J296"],"award-info":[{"award-number":["2021J296"]}],"id":[{"id":"10.13039\/501100005315","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Observational studies have suggested that irritability is associated with a higher risk of cardiovascular disease (CVD). However, the potential causal association is not clear. Therefore, we used Mendelian randomization (MR) analysis to assess the causal association of irritability with CVD risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A two-sample MR analysis was performed to confirm the causal association of irritability with the risk of several common CVDs. The exposure data were derived from the UK biobank involving 90,282 cases and 232,386 controls, and outcome data were collected from the published genome-wide association studies (GWAS) and FinnGen database. Inverse-variance weighted (IVW), MR-Egger, and weighted median methods were performed to assess the causal association. Furthermore, the mediating effect of smoking, insomnia, and depressed affect was explored by using a two-step MR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The MR analysis indicated that genetically predicted irritability increased the risk of CVD, including coronary artery disease (CAD) (Odds ratio, OR: 2.989; 95% confidence interval, CI: 1.521\u20135.874,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001), myocardial infarction (MI) (OR: 2.329, 95% CI: 1.145\u20134.737,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.020), coronary angioplasty (OR: 5.989, 95% CI: 1.696\u201321.153,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.005), atrial fibrillation (AF) (OR: 4.646, 95% CI: 1.268\u201317.026,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.02), hypertensive heart disease (HHD) (OR: 8.203; 95% CI: 1.614\u201341.698,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.011), non-ischemic cardiomyopathy (NIC) (OR: 5.186; 95% CI: 1.994\u201313.487,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001), heart failure (HF) (OR: 2.253; 95% CI: 1.327\u20133.828,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.003), stroke (OR: 2.334; 95% CI: 1.270\u20134.292,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.006), ischemic stroke (IS) (OR: 2.249; 95% CI: 1.156\u20134.374,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.017), and ischemic stroke of large-artery atherosclerosis ISla (OR: 14.326; 95% CI: 2.750\u201374.540,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002). The analysis also indicated that smoking, insomnia, and depressed affect play an important role in the process of irritability leading to cardiovascular disease.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings support the first genetic evidence of the causality of genetically predicted irritability with the risk of developing into CVDs. Our results deliver a viewpoint that more early active interventions to manage an individual's anger and related unhealthy lifestyle habits are needed to prevent the occurrence of adverse cardiovascular events.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcvm.2023.1174329","type":"journal-article","created":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T05:54:35Z","timestamp":1685598875000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["A causal relationship between irritability and cardiovascular diseases: a Mendelian randomization study"],"prefix":"10.3389","volume":"10","author":[{"given":"Dihui","family":"Cai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongfei","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanna","family":"Ba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangfang","family":"Lian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,5,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2980","DOI":"10.1016\/j.jacc.2020.11.021","article-title":"The global burden of cardiovascular diseases and risks: a compass for global action","volume":"76","author":"Roth","year":"2020","journal-title":"J Am Coll Cardiol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e596","DOI":"10.1161\/cir.0000000000000678","article-title":"2019 Acc\/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology\/American Heart Association Task Force on clinical practice guidelines","volume":"140","author":"Arnett","year":"2019","journal-title":"Circulation"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e153","DOI":"10.1161\/cir.0000000000001052","article-title":"Heart disease and stroke statistics \u2013 2022 update: a report from the American Heart Association","volume":"145","author":"Tsao","year":"2022","journal-title":"Circulation"},{"key":"B4","doi-asserted-by":"publisher","first-page":"e104","DOI":"10.1161\/cir.0000000000000756","article-title":"Recommendations for cardiovascular health and disease surveillance for 2030 and beyond: a policy statement from the American Heart Association","volume":"141","author":"Roger","year":"2020","journal-title":"Circulation"},{"key":"B5","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1097\/00006842-199801000-00017","article-title":"Neuroendocrine, cardiovascular, and emotional responses of hostile men: the role of interpersonal challenge","volume":"60","author":"Suarez","year":"1998","journal-title":"Psychosom Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1016\/j.jad.2021.08.063","article-title":"Association between affective temperaments and severe coronary artery disease","volume":"295","author":"Vecsey-Nagy","year":"2021","journal-title":"J Affect Disord"},{"key":"B7","doi-asserted-by":"publisher","first-page":"2090","DOI":"10.1161\/01.cir.94.9.2090","article-title":"A prospective study of anger and coronary heart disease. 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