{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T08:20:26Z","timestamp":1793089226297,"version":"4.5.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2011,1,18]]},"abstract":"<jats:sec>\n                    <jats:title>Background\u2014<\/jats:title>\n                    <jats:p>Biomarkers of atherosclerosis may refine clinical decision making in individuals at risk of cardiovascular disease. The purpose of the study was to determine the prognostic significance of endothelial function and other vascular markers in apparently healthy men.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results\u2014<\/jats:title>\n                    <jats:p>\n                      The cohort consisted of 1574 men (age, 49.4 years) free of vascular disease. Measurements included flow-mediated dilation and its microvascular stimulus, hyperemic velocity, carotid intima-media thickness, and C-reactive protein. Cox proportional hazard models evaluated the relationship between vascular markers, Framingham risk score, and time to a first composite cardiovascular end point of vascular death, revascularization, myocardial infarction, angina, and stroke. Subjects had low median Framingham risk score (7.9%). Cardiovascular events occurred in 71 subjects (111 events) over a mean follow-up of 7.2\u00b11.7 years. Flow-mediated dilation was not associated with subsequent cardiovascular events (hazard ratio, 0.92;\n                      <jats:italic>P<\/jats:italic>\n                      =0.54). Both hyperemic velocity (hazard ratio, 0.70; 95% confidence interval, 0.54 to 0.90;\n                      <jats:italic>P<\/jats:italic>\n                      =0.006) and carotid intima-media thickness (hazard ratio, 1.45; confidence interval, 1.15 to 1.83;\n                      <jats:italic>P<\/jats:italic>\n                      =0.002) but not C-reactive protein (\n                      <jats:italic>P<\/jats:italic>\n                      =0.35) were related to events in a multivariable analysis that included Framingham risk score (per unit SD). Furthermore, the addition of hyperemic velocity to Framingham risk score resulted in a net clinical reclassification improvement of 28.7% (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.001) after 5 years of follow-up in the intermediate-risk group. Overall net reclassification improvement for hyperemic velocity was 6.9% (\n                      <jats:italic>P<\/jats:italic>\n                      =0.24).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\u2014<\/jats:title>\n                    <jats:p>In men, hyperemic velocity, the stimulus for flow-mediated dilation, but not flow-mediated dilation itself was a significant risk marker for adverse cardiovascular outcomes. The prognostic value was additive to traditional risk factors and carotid intima-media thickness. Hyperemic velocity, a newly described marker of microvascular function, is a novel tool that may improve risk stratification of lower-risk healthy men.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.110.953653","type":"journal-article","created":{"date-parts":[[2011,1,3]],"date-time":"2011-01-03T23:11:40Z","timestamp":1294096300000},"page":"163-169","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":353,"title":["Microvascular Function Predicts Cardiovascular Events in Primary Prevention"],"prefix":"10.1161","volume":"123","author":[{"given":"Todd J.","family":"Anderson","sequence":"first","affiliation":[{"name":"From the Department of Cardiac Sciences and Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, AB (T.J.A., F.C., H.C., K.H., M.F.); Calgary Health Research, Alberta Health Services, Calgary, AB (M.S.R.); Department of Medicine, Dalhousie University, Halifax, NS (L.M.T.); Department of Medicine, McGill University, Montreal, QC (J.B.); Department of Surgery, University of Toronto, Toronto, ON (S.V.); and Population Health Research Institute and Department of Medicine, McMaster..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francois","family":"Charbonneau","sequence":"additional","affiliation":[{"name":"From the Department of Cardiac Sciences and Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, AB (T.J.A., F.C., H.C., K.H., M.F.); Calgary Health Research, Alberta Health Services, Calgary, AB (M.S.R.); Department of Medicine, Dalhousie University, Halifax, NS (L.M.T.); Department of Medicine, McGill University, Montreal, QC (J.B.); Department of Surgery, University of Toronto, Toronto, ON (S.V.); and Population Health Research Institute and Department of Medicine, McMaster..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence M.","family":"Title","sequence":"additional","affiliation":[{"name":"From the Department of Cardiac Sciences and Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, AB (T.J.A., F.C., H.C., K.H., M.F.); Calgary Health Research, Alberta Health Services, Calgary, AB (M.S.R.); Department of Medicine, Dalhousie University, Halifax, NS (L.M.T.); Department of Medicine, McGill University, Montreal, QC (J.B.); Department of Surgery, University of Toronto, Toronto, ON (S.V.); and Population Health Research Institute and Department of Medicine, McMaster..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Buithieu","sequence":"additional","affiliation":[{"name":"From the Department of Cardiac Sciences and Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, AB (T.J.A., F.C., H.C., K.H., M.F.); Calgary Health Research, Alberta Health Services, Calgary, AB (M.S.R.); Department of Medicine, Dalhousie University, Halifax, NS (L.M.T.); Department of Medicine, McGill University, Montreal, QC (J.B.); Department of Surgery, University of Toronto, Toronto, ON (S.V.); and Population Health Research Institute and Department of Medicine, McMaster..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Sarah","family":"Rose","sequence":"additional","affiliation":[{"name":"From the Department of Cardiac Sciences and Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, AB (T.J.A., F.C., H.C., K.H., M.F.); Calgary Health Research, Alberta Health Services, Calgary, AB (M.S.R.); Department of Medicine, Dalhousie University, Halifax, NS (L.M.T.); Department of Medicine, McGill University, Montreal, QC (J.B.); Department of Surgery, University of Toronto, Toronto, ON (S.V.); and Population Health Research Institute and Department of Medicine, McMaster..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Conradson","sequence":"additional","affiliation":[{"name":"From the Department of Cardiac Sciences and Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, AB (T.J.A., F.C., H.C., K.H., M.F.); Calgary Health Research, Alberta Health Services, Calgary, AB (M.S.R.); Department of Medicine, Dalhousie University, Halifax, NS (L.M.T.); Department of Medicine, McGill University, Montreal, QC (J.B.); Department of Surgery, University of Toronto, Toronto, ON (S.V.); and Population Health Research Institute and Department of Medicine, McMaster..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy","family":"Hildebrand","sequence":"additional","affiliation":[{"name":"From the Department of Cardiac Sciences and Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, AB (T.J.A., F.C., H.C., K.H., M.F.); Calgary Health Research, Alberta Health Services, Calgary, AB (M.S.R.); Department of Medicine, Dalhousie University, Halifax, NS (L.M.T.); Department of Medicine, McGill University, Montreal, QC (J.B.); Department of Surgery, University of Toronto, Toronto, ON (S.V.); and Population Health Research Institute and Department of Medicine, McMaster..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marinda","family":"Fung","sequence":"additional","affiliation":[{"name":"From the Department of Cardiac Sciences and Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, AB (T.J.A., F.C., H.C., K.H., M.F.); Calgary Health Research, Alberta Health Services, Calgary, AB (M.S.R.); Department of Medicine, Dalhousie University, Halifax, NS (L.M.T.); Department of Medicine, McGill University, Montreal, QC (J.B.); Department of Surgery, University of Toronto, Toronto, ON (S.V.); and Population Health Research Institute and Department of Medicine, McMaster..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subodh","family":"Verma","sequence":"additional","affiliation":[{"name":"From the Department of Cardiac Sciences and Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, AB (T.J.A., F.C., H.C., K.H., M.F.); Calgary Health Research, Alberta Health Services, Calgary, AB (M.S.R.); Department of Medicine, Dalhousie University, Halifax, NS (L.M.T.); Department of Medicine, McGill University, Montreal, QC (J.B.); Department of Surgery, University of Toronto, Toronto, ON (S.V.); and Population Health Research Institute and Department of Medicine, McMaster..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva M.","family":"Lonn","sequence":"additional","affiliation":[{"name":"From the Department of Cardiac Sciences and Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, AB (T.J.A., F.C., H.C., K.H., M.F.); Calgary Health Research, Alberta Health Services, Calgary, AB (M.S.R.); Department of Medicine, Dalhousie University, Halifax, NS (L.M.T.); Department of Medicine, McGill University, Montreal, QC (J.B.); Department of Surgery, University of Toronto, Toronto, ON (S.V.); and Population Health Research Institute and Department of Medicine, McMaster..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/288373a0"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(92)93147-F"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.106.678276"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ehj.2004.06.039"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.0000137305.77635.68"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2009.01.376"},{"key":"e_1_3_4_8_2","first-page":"61","article-title":"The fate of endothelial function testing: rationale and design of the Firefighters and Their Endothelium (FATE) study","volume":"19","author":"Anderson TJ","year":"2003","unstructured":"Anderson TJ, Roberts AC, Hildebrand K, Conradson HE, Jones C, Bridge P, Edworthy S, Lonn E, Verma S, Charbonneau F. 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