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

BackgroundAdverse 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. MethodsBrachial FMD was prospectively assessed in 268 consecutive healthy subjects, 169 (63%) men, mean age 53±11years, 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 6months 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. ResultsThe cohort was divided into Group A with FMD performed immediately post-waking, between 6:00 and 10:00am [n=151 (56%) subjects], and Group B after 10:00am [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±21months, 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. ConclusionsFMD 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.