title: Microvascular function predicts cardiovascular events in primary prevention: long-term results from the Firefighters and Their Endothelium (FATE) study.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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±1.7 years. Flow-mediated dilation was not associated with subsequent cardiovascular events (hazard ratio, 0.92; P=0.54). Both hyperemic velocity (hazard ratio, 0.70; 95% confidence interval, 0.54 to 0.90; P=0.006) and carotid intima-media thickness (hazard ratio, 1.45; confidence interval, 1.15 to 1.83; P=0.002) but not C-reactive protein (P=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% (P<0.001) after 5 years of follow-up in the intermediate-risk group. Overall net reclassification improvement for hyperemic velocity was 6.9% (P=0.24).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardiac Sciences and Libin Cardiovascular Institute of Alberta, University of Calgary, 1403-29th St. NW, Calgary, AB, Canada. todd.anderson@albertahealthservices.ca
authors.forename: Todd J
authors.initials: TJ
authors.lastname: Anderson
authors.forename: Francois
authors.initials: F
authors.lastname: Charbonneau
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Title
authors.forename: Jean
authors.initials: J
authors.lastname: Buithieu
authors.forename: M Sarah
authors.initials: MS
authors.lastname: Rose
authors.forename: Heather
authors.initials: H
authors.lastname: Conradson
authors.forename: Kathy
authors.initials: K
authors.lastname: Hildebrand
authors.forename: Marinda
authors.initials: M
authors.lastname: Fung
authors.forename: Subodh
authors.initials: S
authors.lastname: Verma
authors.forename: Eva M
authors.initials: EM
authors.lastname: Lonn
mesh_terms: D000328:Adult; D001783:Blood Flow Velocity / Q000502:physiology; D001916:Brachial Artery / Q000502:physiology; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000503:physiopathology / Q000517:prevention & control*; D015331:Cohort Studies; D004730:Endothelium, Vascular / Q000502:physiology*; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D055806:Microvessels / Q000502:physiology*; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012307:Risk Factors; D017539:Tunica Intima / Q000000981:diagnostic imaging; D017540:Tunica Media / Q000000981:diagnostic imaging; D014463:Ultrasonography
chemical_list: D002097:C-Reactive Protein