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tools are needed to identify heart failure (HF) risk earlier in its course. We evaluated the association of multidimensional cardiopulmonary exercise testing (CPET) phenotypes with subclinical risk markers and predicted long-term HF risk in a large community-based cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We studied 2532 Framingham Heart Study participants [age 53 \u00b1 9 years, 52% women, body mass index (BMI) 28.0 \u00b1 5.3 kg\/m2, peak oxygen uptake (VO2) 21.1 \u00b1 5.9 kg\/m2 in women, 26.4 \u00b1 6.7 kg\/m2 in men] who underwent maximum effort CPET and were not taking atrioventricular nodal blocking agents. Higher peak VO2 was associated with a lower estimated HF risk score (Spearman correlation r: \u22120.60 in men and \u22120.55 in women, P &amp;lt; 0.0001), with an observed overlap of estimated risk across peak VO2 categories. Hierarchical clustering of 26 separate CPET phenotypes (values residualized on age, sex, and BMI to provide uniformity across these variables) identified three clusters with distinct exercise physiologies: Cluster 1\u2014impaired oxygen kinetics; Cluster 2\u2014impaired vascular; and Cluster 3\u2014favourable exercise response. These clusters were similar in age, sex distribution, and BMI but displayed distinct associations with relevant subclinical phenotypes [Cluster 1\u2014higher subcutaneous and visceral fat and lower pulmonary function; Cluster 2\u2014higher carotid-femoral pulse wave velocity (CFPWV); and Cluster 3\u2014lower CFPWV, C-reactive protein, fat volumes, and higher lung function; all false discovery rate &amp;lt; 5%]. Cluster membership provided incremental variance explained (adjusted R2 increment of 0.10 in women and men, P &amp;lt; 0.0001 for both) when compared with peak VO2 alone in association with predicted HF risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Integrated CPET response patterns identify physiologically relevant profiles with distinct associations to subclinical phenotypes that are largely independent of standard risk factor-based assessment, which may suggest alternate pathways for prevention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.14797","type":"journal-article","created":{"date-parts":[[2024,6,29]],"date-time":"2024-06-29T01:44:37Z","timestamp":1719625477000},"page":"3279-3289","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Clusters of Multidimensional Exercise Response Patterns and Estimated Heart Failure Risk in the Framingham Heart Study"],"prefix":"10.1093","volume":"11","author":[{"given":"Patricia E.","family":"Miller","sequence":"first","affiliation":[{"name":"Department of Biostatistics, Boston University School of Public Health , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya","family":"Gajjar","sequence":"additional","affiliation":[{"name":"Section of Cardiovascular Medicine, Department of Medicine, Boston University School of Medicine , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary F.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Cardiovascular Engineering, Inc. , Norwood, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadiya S.","family":"Khan","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine and Preventive Medicine, Northwestern University Feinberg School of Medicine , Chicago, IL ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramachandran S.","family":"Vasan","sequence":"additional","affiliation":[{"name":"Boston University's and NHLBI's Framingham Heart Study , Framingham, MA ,","place":["USA"]},{"name":"University of Texas School of Public Health San Antonio , San Antonio, TX ,","place":["USA"]},{"name":"Department of Medicine, University of Texas Health Science Center , San Antonio, TX ,","place":["USA"]},{"name":"Department of Population Health Sciences, University of Texas Health Science Center , San Antonio, TX ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin G.","family":"Larson","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Boston University School of Public Health , Boston, MA ,","place":["USA"]},{"name":"Boston University's and NHLBI's Framingham Heart Study , Framingham, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory D.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Cardiovascular Research Center, and Pulmonary Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi V.","family":"Shah","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Vanderbilt Translational and Clinical Research Center, Vanderbilt University Medical Center , Nashville, TN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6993-9396","authenticated-orcid":false,"given":"Matthew","family":"Nayor","sequence":"additional","affiliation":[{"name":"Section of Cardiovascular Medicine, Department of Medicine, Boston University School of Medicine , Boston, MA ,","place":["USA"]},{"name":"Boston University's and NHLBI's Framingham Heart Study , Framingham, MA ,","place":["USA"]},{"name":"Section of Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine , 72 E Concord Street, Suite L-516, Boston, MA, 02118 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,6,28]]},"reference":[{"key":"2026012113142087200_ehf214797-bib-0001","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.1002\/ejhf.2946","article-title":"Heart failure diagnosis in the general community\u2014Who, how and when? 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