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.

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. 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. 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. 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.

Hirsch L ，Shechter A ，Feinberg MS ，Koren-Morag N ，Shechter M ... -  《-》

Usefulness of brachial artery flow-mediated dilation to predict long-term cardiovascular events in subjects without heart disease.

Endothelial dysfunction is considered an important prognostic factor in atherosclerosis. To determine the long-term association of brachial artery flow-mediated dilation (FMD) and adverse cardiovascular (CV) events in healthy subjects, we prospectively assessed brachial FMD in 618 consecutive healthy subjects with no apparent heart disease, 387 men (63%), and mean age 54 ± 11 years. After overnight fasting and discontinuation of all medications for ≥12 hours, FMD was assessed using high-resolution linear array ultrasound. Subjects were divided into 2 groups: FMD ≤11.3% (n = 309) and >11.3% (n = 309), where 11.3% is the median FMD, and were comparable regarding CV risk factors, lipoproteins, fasting glucose, C-reactive protein, concomitant medications, and Framingham 10-year risk score. In a mean clinical follow-up of 4.6 ± 1.8 years, the composite CV events (all-cause mortality, nonfatal myocardial infarction, hospitalization for heart failure or angina pectoris, stroke, coronary artery bypass grafting, and percutaneous coronary interventions) were significantly more common in subjects with FMD ≤11.3% rather than >11.3% (15.2% vs 1.2%, p = 0.0001, respectively). Univariate analysis demonstrated that the median FMD significantly predicted CV events (odds ratio 2.78, 95% CI 1.35 to 5.71, p <0.001). Multivariate analysis, controlling for traditional CV risk factors, demonstrated that median FMD was the best independent predictor of long-term CV adverse events (odds ratio 2.93, 95% CI 1.28 to 6.68, p <0.001). In conclusion, brachial artery median FMD independently predicts long-term adverse CV events in healthy subjects with no apparent heart disease in addition to those derived from traditional risk factor assessment.

Shechter M ，Shechter A ，Koren-Morag N ，Feinberg MS ，Hiersch L ... -  《-》

Long-term association of brachial artery flow-mediated vasodilation and cardiovascular events in middle-aged subjects with no apparent heart disease.

Shechter M ，Issachar A ，Marai I ，Koren-Morag N ，Freinark D ，Shahar Y ，Shechter A ，Feinberg MS ... -  《-》

The association of endothelial dysfunction and cardiovascular events in healthy subjects and patients with cardiovascular disease.

Shechter M ，Marai I ，Marai S ，Sherer Y ，Sela BA ，Feinberg MS ，Rubinstein A ，Shoenfeld Y ... -  《ISRAEL MEDICAL ASSOCIATION JOURNAL》

Early morning attenuation of endothelial function in healthy humans.

Otto ME ，Svatikova A ，Barretto RB ，Santos S ，Hoffmann M ，Khandheria B ，Somers V ... -  《-》