Background-Cardiovascular events such as myocardial infarction, sudden death, and stroke have a peak incidence in the early hours after waking. The mechanisms involved in this circadian variation are not clear. Endothelial dysfunction is associated with increased risk for cardiovascular events. We tested the hypothesis that endothelial function is reduced in the early morning, around the time of waking, compared with measurements obtained both before sleep and later in the day in healthy humans. Methods and Results-We studied 30 subjects (19 men, 11 women; mean age, 41.6 years). All participants underwent polysomnography to exclude obstructive sleep apnea or other sleep disorders. Brachial artery flow-mediated endothelium-dependent vasodilation (FMD) and endothelium-independent dilation (non-FMD) were measured on 3 different occasions: before subjects went to sleep (9 PM), the next morning immediately after waking (6 AM), and during the late morning 5 hours after waking (11 AM). All subjects had normal sleep with good sleep efficiency of 84Ϯ2%. Compared with before sleep, FMD decreased markedly in the early morning after waking and recovered by late morning (9 PM, 7.5Ϯ1%; 6 AM, 4.4Ϯ0.7%; 11 AM, 7.7Ϯ1%; Pϭ0.02). Non-FMD was similar for the 3 periods of observation (9 PM, 17.3Ϯ1.6%; 6 AM, 17.2Ϯ1.3%; 11 AM, 18.5Ϯ1.7%). Conclusions-FMD is blunted in the early morning in healthy subjects. Decreased endothelial function in the early morning may have implications for our understanding of the morning peak in cardiac and vascular events. (Circulation.

Background-C-reactive protein (CRP) is synthesized from the liver and is regulated by cytokines, especially interleukin-6. Leptin, the adipocyte-derived protein product of the ob gene, is related to amount of body fat. The long form of the leptin receptor resembles cytokine receptors, which include the interleukin-6 receptor. Both leptin and CRP may be increased in women, in obesity, and in inflammation, and both have been linked to cardiovascular pathophysiological processes and increased cardiovascular risk. We tested the hypothesis that leptin is associated with CRP levels independently of the influences of gender, body mass index (BMI), waist-to-hip ratio, and other variables. Methods and Results-We studied 100 healthy volunteers (48 men, and 52 women). For all subjects, leptin was independently associated with CRP after adjustment for age, gender, BMI, waist-to-hip ratio, smoking, and alcohol consumption (Fϭ12.39, Pϭ0.0007). There was a strong and significant positive relationship between leptin and CRP in both women (Rϭ0.61, PϽ0.0001) and men (Rϭ0.55, PϽ0.0001) considered separately. The association between leptin and CRP was significant even after adjustment for age, BMI, waist-to-hip ratio, smoking, and alcohol consumption in women (Fϭ7.13, Pϭ0.01) and men (Fϭ5.69, Pϭ0.02). When only subjects with BMI Ͻ25 kg/m 2 were considered (nϭ47), CRP was not linked to BMI (Rϭ0.02, Pϭ0.96), but a significant association between leptin and CRP was still evident (Rϭ0.55, PϽ0.0001). Conclusions-Leptin

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Otherwise healthy OSA patients, without any other co-morbidities, do not manifest evidence for higher oxidative stress and lipid peroxidation. Thus, oxidative stress and lipid peroxidation do not appear to be key mediators of increased cardiovascular disease in OSA patients.

Goal Sleep apnea affects over half of acute ischemic stroke patients and is associated with poor stroke outcomes. This pilot study assessed the feasibility of a randomized, sham-controlled continuous positive airway pressure trial in acute ischemic stroke patients. Methods Subjects identified to have sleep apnea based on an apnea-hypopnea index ≥ 5 on overnight polysomnography or portable respiratory monitoring within 7 days of stroke symptom onset were randomized to receive active or sham continuous positive airway pressure for 3 months. Objective usage was ascertained by compliance data cards. Subjects, treating physicians, and outcome assessors were masked to intervention allocation. Findings Among 87 consented subjects, 74 were able to complete sleep apnea screening, 54 (73%) of whom had sleep apnea; 32 agreed to randomization. Of the 15 who commenced active titration, 11 (73%) took the device home, and 8 (53%) completed the 3 month follow-up. Of the 17 subjects who commenced sham titration, 11 (65%) took the sham device home and completed the 3 month follow-up. The median cumulative usage hours over the 90 days were similar in the active group (53 hours (IQR: 22, 173)) and the sham group (74 hours (17, 94)) and blinding to condition was successfully maintained. Conclusion This first-ever, randomized, sham-controlled trial of continuous positive airway pressure in patients with recent stroke and sleep apnea showed that sham treatment can be an effective placebo.

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WOLK, ROBERT, ANNA SVATIKOVA, CHRISTY A.

Oral snuff tobacco increases heart rate, blood pressure, and epinephrine. Despite the increase in blood pressure, there is no decrease in either MSNA or peripheral vascular resistance. Smokeless tobacco is a powerful autonomic and hemodynamic stimulus. Catecholamine release from the adrenal medulla likely contributes to this response.