{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T04:10:30Z","timestamp":1778818230216,"version":"3.51.4"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T00:00:00Z","timestamp":1707868800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T00:00:00Z","timestamp":1707868800000},"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":["Hypertens Res"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstracts<\/jats:title><jats:p>Insufficient blood pressure control among patients with hypertension without elevated risk is a global concern, suggesting the need for treatment optimization. However, the potential harm of excessive blood pressure lowering among these patients is understudied. This study addressed this evidence gap by using nationally representative public health insurer database covering 30 million working-age population. Patients who were continuously using antihypertensive drugs with 10-year cardiovascular risk &lt;10% were identified. They were categorized by on-treatment systolic and diastolic blood pressures. The primary outcome was a composite of myocardial infarction, stroke, heart failure hospitalization, and peripheral artery disease. Of 920,533 participants (mean age, 57.3 years; female, 48.3%; mean follow-up, 2.75 years), the adjusted hazard ratios for systolic blood pressure of &lt;110, 110\u2013119, 120\u2013129 (reference), 130\u2013139, 140\u2013149, 150\u2013159, and \u2265160\u2009mmHg were 1.05 (95% confidence interval: 0.99\u20131.12), 0.97 (0.93\u20131.02), 1 (reference), 1.05 (1.01\u20131.09), 1.15 (1.11\u20131.20), 1.30 (1.23\u20131.37), and 1.76 (1.66\u20131.86), respectively; and for diastolic blood pressure of &lt;60, 60\u201369, 70\u201379 (reference), 80\u201389, 90\u201399, and \u2265100\u2009mmHg were 1.25 (1.14\u20131.38), 0.99 (0.95\u20131.04), 1 (reference), 1.00 (0.96\u20131.03), 1.13 (1.09\u20131.18), and 1.66 (1.58\u20131.76), respectively. Among low-risk patients with hypertension, diastolic blood pressure &lt;60\u2009mmHg was associated with increased cardiovascular events, while systolic blood pressure &lt;110\u2009mmHg was not. Compared to previous investigations in high-risk patients, the potential harm of excessive blood pressure lowering was less pronounced in low-risk patients with hypertension.<\/jats:p>","DOI":"10.1038\/s41440-024-01593-y","type":"journal-article","created":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T05:02:27Z","timestamp":1707886947000},"page":"1546-1554","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Low on-treatment blood pressure and cardiovascular events in patients without elevated risk: a nationwide cohort study"],"prefix":"10.1038","volume":"47","author":[{"given":"Yuichiro","family":"Mori","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsushi","family":"Mizuno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shingo","family":"Fukuma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,2,14]]},"reference":[{"key":"1593_CR1","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1016\/S0140-6736(20)30752-2","volume":"396","author":"CJL Murray","year":"2020","unstructured":"Murray CJL, Aravkin AY, Zheng P, Abbafati C, Abbas KM, Abbasi-Kangevari M, et al. Global burden of 87 risk factors in 204 countries and territories, 1990\u20132019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396:1223\u201349.","journal-title":"Lancet"},{"key":"1593_CR2","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1016\/S0140-6736(21)01330-1","volume":"398","author":"B Zhou","year":"2021","unstructured":"Zhou B, Carrillo-Larco RM, Danaei G, Riley LM, Paciorek CJ, Stevens GA, et al. Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants. Lancet. 2021;398:957\u201380.","journal-title":"Lancet"},{"key":"1593_CR3","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1161\/HYPERTENSIONAHA.118.11609","volume":"72","author":"JA Lamprea-Montealegre","year":"2018","unstructured":"Lamprea-Montealegre JA, Zelnick LR, Hall YN, Bansal N, de Boer IH. Prevalence of hypertension and cardiovascular risk according to blood pressure thresholds used for diagnosis. Hypertension. 2018;72:602\u20139.","journal-title":"Hypertension"},{"key":"1593_CR4","doi-asserted-by":"publisher","first-page":"S49","DOI":"10.1161\/01.cir.0000437741.48606.98","volume":"129","author":"DC Goff Jr","year":"2014","unstructured":"Goff DC Jr, Lloyd-Jones DM, Bennett G, Coady S, D\u2019Agostino RB, Gibbons R, et al. 2013 ACC\/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology\/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129:S49\u201373.","journal-title":"Circulation"},{"key":"1593_CR5","doi-asserted-by":"publisher","first-page":"e0248471","DOI":"10.1371\/journal.pone.0248471","volume":"16","author":"T De Backer","year":"2021","unstructured":"De Backer T, Van Nieuwenhuyse B, De Bacquer D. Antihypertensive treatment in a general uncontrolled hypertensive population in Belgium and Luxembourg in primary care: therapeutic inertia and treatment simplification. the SIMPLIFY study. PLoS One. 2021;16:e0248471.","journal-title":"PLoS One"},{"key":"1593_CR6","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1161\/HYPERTENSIONAHA.113.01922","volume":"63","author":"G Mancia","year":"2014","unstructured":"Mancia G, Grassi G. Aggressive blood pressure lowering is dangerous: the J-Curve. Hypertension. 2014;63:29\u201336.","journal-title":"Hypertension"},{"key":"1593_CR7","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1161\/HYPERTENSIONAHA.113.01018","volume":"63","author":"P Verdecchia","year":"2014","unstructured":"Verdecchia P, Angeli F, Mazzotta G, Garofoli M, Reboldi G. Aggressive blood pressure lowering is dangerous: the J-Curve. Hypertension. 2014;63:37\u201340.","journal-title":"Hypertension"},{"key":"1593_CR8","doi-asserted-by":"publisher","first-page":"2142","DOI":"10.1016\/S0140-6736(16)31326-5","volume":"388","author":"E Vidal-Petiot","year":"2016","unstructured":"Vidal-Petiot E, Ford I, Greenlaw N, Ferrari R, Fox KM, Tardif JC, et al. Cardiovascular event rates and mortality according to achieved systolic and diastolic blood pressure in patients with stable coronary artery disease: an international cohort study. Lancet. 2016;388:2142\u201352.","journal-title":"Lancet"},{"key":"1593_CR9","doi-asserted-by":"publisher","first-page":"2226","DOI":"10.1016\/S0140-6736(17)30754-7","volume":"389","author":"M B\u00f6hm","year":"2017","unstructured":"B\u00f6hm M, Schumacher H, Teo KK, Lonn EM, Mahfoud F, Mann JFE, et al. Achieved blood pressure and cardiovascular outcomes in high-risk patients: results from ONTARGET and TRANSCEND trials. Lancet. 2017;389:2226\u201337.","journal-title":"Lancet"},{"key":"1593_CR10","doi-asserted-by":"publisher","first-page":"3021","DOI":"10.1093\/eurheartj\/ehy339","volume":"39","author":"B Williams","year":"2018","unstructured":"Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. 2018 ESC\/ESH guidelines for the management of arterial hypertension. Eur Heart J. 2018;39:3021\u2013104.","journal-title":"Eur Heart J"},{"key":"1593_CR11","first-page":"e13","volume":"71","author":"PK Whelton","year":"2018","unstructured":"Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC\/AHA\/AAPA\/ABC\/ACPM\/AGS\/APhA\/ASH\/ASPC\/NMA\/PCNA Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13\u2013115.","journal-title":"Hypertension"},{"key":"1593_CR12","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1136\/bmj.39335.541782.AD","volume":"335","author":"E von Elm","year":"2007","unstructured":"von Elm E, Altman DG, Egger M, Pocock SJ, G\u00f8tzsche PC, Vandenbroucke JP, et al. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. BMJ. 2007;335:806\u20138.","journal-title":"BMJ"},{"key":"1593_CR13","unstructured":"Health and Global Policy Institute. 3.1 Japan\u2019s Health Insurance System [Internet]. Japan Health Policy NOW. Available from: https:\/\/japanhpn.org\/en\/section-3-1\/. Accessed 14 Jan 2022."},{"key":"1593_CR14","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.1001\/jamainternmed.2020.4334","volume":"180","author":"S Fukuma","year":"2020","unstructured":"Fukuma S, Iizuka T, Ikenoue T, Tsugawa Y. Association of the National Health Guidance Intervention for obesity and cardiovascular risks with health outcomes among Japanese men. JAMA Intern Med. 2020;180:1630\u20137.","journal-title":"JAMA Intern Med"},{"key":"1593_CR15","doi-asserted-by":"publisher","first-page":"308","DOI":"10.5551\/jat.42010","volume":"25","author":"K Tsushita","year":"2018","unstructured":"Tsushita K, Hosler AS, Miura K, Ito Y, Fukuda T, Kitamura A, et al. Rationale and descriptive analysis of specific health guidance: the Nationwide Lifestyle Intervention Program targeting metabolic syndrome in Japan. J Atheroscler Thromb. 2018;25:308\u201322.","journal-title":"J Atheroscler Thromb"},{"key":"1593_CR16","doi-asserted-by":"publisher","first-page":"e0286317","DOI":"10.1371\/journal.pone.0286317","volume":"18","author":"Y Mori","year":"2023","unstructured":"Mori Y, Matsushita K, Inoue K, Fukuma S. Patterns and predictors of adherence to follow-up health guidance invitations in a general health check-up program in Japan: a cohort study with an employer-sponsored insurer database. PLoS One. 2023;18:e0286317.","journal-title":"PLoS One"},{"key":"1593_CR17","unstructured":"The Japanese Ministry of Health Labour and Welfare. Annual report on the implementation of general health check-up program by Japan Health Insurance Association, 2020 (Japanese) [Internet]. 2022. Available from: https:\/\/www.mhlw.go.jp\/content\/12400000\/000944760.xlsx. Accessed 11 Nov 2022."},{"key":"1593_CR18","doi-asserted-by":"publisher","first-page":"1575","DOI":"10.1056\/NEJMoa1001286","volume":"362","author":"GW Evans","year":"2010","unstructured":"Evans GW, Byington RP, Goff DC,Jr, Grimm RH, Jr, Cutler JA.ACCORD Study Group et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010;362:1575\u201385.","journal-title":"N Engl J Med"},{"key":"1593_CR19","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1016\/S0140-6736(15)00805-3","volume":"387","author":"X Xie","year":"2016","unstructured":"Xie X, Atkins E, Lv J, Bennett A, Neal B, Ninomiya T, et al. Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: updated systematic review and meta-analysis. Lancet. 2016;387:435\u201343.","journal-title":"Lancet"},{"key":"1593_CR20","doi-asserted-by":"publisher","first-page":"S13","DOI":"10.2337\/dc18-S002","volume":"41","author":"American Diabetes Association.","year":"2018","unstructured":"American Diabetes Association. Classification and diagnosis of diabetes: standards of medical care in diabetes-2018. Diabetes Care. 2018;41:S13\u201327.","journal-title":"Diabetes Care"},{"key":"1593_CR21","doi-asserted-by":"publisher","first-page":"1827","DOI":"10.1016\/j.jacc.2009.05.073","volume":"54","author":"FH Messerli","year":"2009","unstructured":"Messerli FH, Panjrath GS. The J-curve between blood pressure and coronary artery disease or essential hypertension: exactly how essential? J Am Coll Cardiol. 2009;54:1827\u201334.","journal-title":"J Am Coll Cardiol"},{"key":"1593_CR22","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1001\/jama.1991.03460040065031","volume":"265","author":"L Farnett","year":"1991","unstructured":"Farnett L, Mulrow CD, Linn WD, Lucey CR, Tuley MR. The J-curve phenomenon and the treatment of hypertension: is there a point beyond which pressure reduction is dangerous? JAMA. 1991;265:489\u201395.","journal-title":"JAMA"},{"key":"1593_CR23","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1038\/hr.2012.165","volume":"36","author":"F Angeli","year":"2013","unstructured":"Angeli F, Reboldi G, Verdecchia P. Hypertension and the J-curve phenomenon: implications for tight blood pressure control. Hypertens Res. 2013;36:109\u201311.","journal-title":"Hypertens Res"},{"key":"1593_CR24","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1161\/HYPERTENSIONAHA.119.12787","volume":"74","author":"S Lip","year":"2019","unstructured":"Lip S, Tan LE, Jeemon P, McCallum L, Dominiczak AF, Padmanabhan S. Diastolic blood pressure J-curve phenomenon in a tertiary-care hypertension clinic. Hypertension. 2019;74:767\u201375.","journal-title":"Hypertension"},{"key":"1593_CR25","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1161\/01.CIR.100.4.354","volume":"100","author":"SS Franklin","year":"1999","unstructured":"Franklin SS, Khan SA, Wong ND, Larson MG, Levy D. Is pulse pressure useful in predicting risk for coronary heart disease? The Framingham heart study. Circulation. 1999;100:354\u201360.","journal-title":"Circulation"},{"key":"1593_CR26","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1161\/HYPERTENSIONAHA.113.01275","volume":"62","author":"SS Franklin","year":"2013","unstructured":"Franklin SS, Thijs L, Hansen TW, O\u2019Brien E, Staessen JA. White-coat hypertension: new insights from recent studies. Hypertension. 2013;62:982\u20137.","journal-title":"Hypertension"},{"key":"1593_CR27","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1161\/HYPERTENSIONAHA.116.07257","volume":"67","author":"SE Kjeldsen","year":"2016","unstructured":"Kjeldsen SE, Lund-Johansen P, Nilsson PM, Mancia G. Unattended blood pressure measurements in the systolic blood pressure intervention trial: implications for entry and achieved blood pressure values compared with other trials. Hypertension. 2016;67:808\u201312.","journal-title":"Hypertension"},{"key":"1593_CR28","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1038\/s41440-022-00994-1","volume":"46","author":"S Hoshide","year":"2023","unstructured":"Hoshide S, Yamamoto K, Katsurada K, Yano Y, Nishiyama A, Wang J-G, et al. Agreement regarding overcoming hypertension in the Asian Hypertension Society Network 2022. Hypertens Res. 2023;46:3\u20138.","journal-title":"Hypertens Res"}],"container-title":["Hypertension Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41440-024-01593-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41440-024-01593-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41440-024-01593-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T23:03:08Z","timestamp":1717542188000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41440-024-01593-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,14]]},"references-count":28,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["1593"],"URL":"https:\/\/doi.org\/10.1038\/s41440-024-01593-y","relation":{},"ISSN":["0916-9636","1348-4214"],"issn-type":[{"value":"0916-9636","type":"print"},{"value":"1348-4214","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,14]]},"assertion":[{"value":"31 July 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 January 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 January 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 February 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}