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

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.