title: The impact of early compared to late morning hours on brachial endothelial function and long-term cardiovascular events in healthy subjects with no apparent coronary heart disease.
abstract: BACKGROUND
  Adverse cardiovascular events (CVE) tend to peak during early morning post-waking hours. Our objective was to explore a possible correlation between early and late morning hours and flow-mediated dilation (FMD), and whether early morning FMD reduction contributes to a circadian pattern of cardiac and vascular vulnerability.
  
  
  METHODS
  Brachial FMD was prospectively assessed in 268 consecutive healthy subjects, 169 (63%) men, mean age 53 ± 11 years, without any concomitant medications. Following an overnight fast, FMD and endothelium-independent nitroglycerin-mediated vasodilation were assessed using high-resolution ultrasound. All subjects were followed up by phone every 6 months for combined CVE, which included all-cause mortality, myocardial infarction, hospitalization for heart failure or angina pectoris, stroke, coronary artery bypass grafting and percutaneous coronary interventions.
  
  
  RESULTS
  The cohort was divided into Group A with FMD performed immediately post-waking, between 6:00 and 10:00 am [n=151 (56%) subjects], and Group B after 10:00 am [n=117 (46%) subjects]. Although both groups were comparable regarding baseline brachial artery diameter and the prevalence of risk factors, FMD was significantly lower in Group A compared with Group B subjects (10.4 ± 3.4% vs. 13.5 ± 3.5%, p=0.007, respectively). In a mean follow-up of 45 ± 21 months, the composite CVEs were significantly more common in subjects with ≤(n=128) vs. >(n=140) the median FMD of 11.3% [18/128 (14.1%) vs. 1/140 (0.7%), p=0.007, respectively]. Furthermore, FMD independently predicted long-term adverse CVE.
  
  
  CONCLUSIONS
  FMD is blunted in early compared to late morning post-waking hours, and independently predicts long-term adverse CVE in healthy subjects with no apparent heart disease.
authors.affiliation: Leviev Heart Center, Chaim Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Liran
authors.initials: L
authors.lastname: Hirsch
authors.forename: Alon
authors.initials: A
authors.lastname: Shechter
authors.forename: Micha S
authors.initials: MS
authors.lastname: Feinberg
authors.forename: Nira
authors.initials: N
authors.lastname: Koren-Morag
authors.forename: Michael
authors.initials: M
authors.lastname: Shechter
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001783:Blood Flow Velocity / Q000502:physiology; D001916:Brachial Artery / Q000000981:diagnostic imaging* / Q000502:physiology; D002318:Cardiovascular Diseases / Q000000981:diagnostic imaging* / Q000503:physiopathology; D002940:Circadian Rhythm / Q000502:physiology; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging* / Q000502:physiology; D005260:Female; D006304:Health Status; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors; D014463:Ultrasonography; D055815:Young Adult