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Our objective was to identify distinct phenotypes of hypertensive individuals with potentially different cardiovascular risk profiles using data\u2010driven cluster analysis. We performed clustering, a procedure that identifies groups with similar characteristics, in 3726 individuals (mean age 59.4\u00a0years, 49% women) with grade 2 hypertension (blood pressure \u2265160\/100\u00a0mmHg or antihypertensive medication) selected from FINRISK 1997, 2002, and 2007 cohorts. We computed clusters based on eight factors associated with hypertension: mean arterial pressure, pulse pressure, non\u2010high\u2010density lipoprotein cholesterol, blood glucose, BMI, C\u2010reactive protein, estimated glomerular filtration rate, and alcohol. After that, we used Cox regression models adjusted for age and sex to assess the relative risk of cardiovascular disease (CVD) outcomes between the clusters and a reference group of 11\u00a0020 individuals. We observed two comparable clusters in both men and women. The Metabolically Challenged (MC) cluster was characterized by high blood glucose (<jats:italic>Z<\/jats:italic>\u2010score 4.4\u00a0\u00b1\u00a01.1 vs 0.2\u00a0\u00b1\u00a00.8, men; 3.5\u00a0\u00b1\u00a01.1 vs 0.0\u00a0\u00b1\u00a00.6, women) and elevated BMI (30.4\u00a0\u00b1\u00a04.1 vs 28.9\u00a0\u00b1\u00a04.3, men; 32.7\u00a0\u00b1\u00a04.9 vs 29.3\u00a0\u00b1\u00a05.5, women). Over a 10\u2010year follow\u2010up (1034 CVD events), MC had 1.6\u2010fold (95% CI 1.1\u20102.4) CVD risk compared to non\u2010MC and 2.5\u2010fold (95% CI 1.7\u20103.7) CVD risk compared to the reference group (<jats:italic>P<\/jats:italic>\u00a0\u2264\u00a0.009 for both). Using unsupervised hierarchical clustering, we found two phenotypically distinct hypertension subgroups with different risks of CVD complications. This substratification could be used to design studies that explore the differential effects of antihypertensive therapies among subgroups of hypertensive individuals.<\/jats:p>","DOI":"10.1111\/jch.13984","type":"journal-article","created":{"date-parts":[[2020,8,16]],"date-time":"2020-08-16T11:10:51Z","timestamp":1597576251000},"page":"1546-1553","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Unsupervised hierarchical clustering identifies a metabolically challenged subgroup of hypertensive individuals"],"prefix":"10.1111","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6036-889X","authenticated-orcid":false,"given":"Felix C.","family":"Vaura","sequence":"first","affiliation":[{"name":"Department of Medicine University of Turku  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7563-5324","authenticated-orcid":false,"given":"Veikko V.","family":"Salomaa","sequence":"additional","affiliation":[{"name":"Finnish Institute for Health and Welfare (THL)  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilkka M.","family":"Kantola","sequence":"additional","affiliation":[{"name":"Division of Medicine Turku University Hospital  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Risto","family":"Kaaja","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Turku  Turku Finland"},{"name":"Division of Medicine Turku University Hospital  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo","family":"Lahti","sequence":"additional","affiliation":[{"name":"Department of Future Technologies University of Turku  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7394-7487","authenticated-orcid":false,"given":"Teemu J.","family":"Niiranen","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Turku  Turku Finland"},{"name":"Finnish Institute for Health and Welfare (THL)  Helsinki Finland"},{"name":"Division of Medicine Turku University Hospital  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31679-8"},{"key":"e_1_2_8_3_1","unstructured":"World Health Organization.A global brief on hypertension: silent killer global public health crisis: World Health Day 2013;2013.https:\/\/apps.who.int\/iris\/handle\/10665\/79059. 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