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.

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Obstructive sleep apnea (OSA) has been increasingly linked to cardiovascular disease, endothelial dysfunction, and oxidative stress, generated by repetitive nocturnal hypoxemia and reperfusion. Circulating free nitrotyrosine has been reported as a novel biomarker of nitric oxide (NO)-induced oxidative/nitrosative stress. Nitrosative stress has been implicated as a possible mechanism for development of cardiovascular diseases. We tested the hypothesis that repetitive severe hypoxemia resulting from OSA would increase NO-mediated oxidative stress. We studied 10 men with newly diagnosed moderate to severe OSA who were free of other diseases, had never been treated for OSA, and were taking no medications. Nitrotyrosine measurements, performed by liquid chromatography-tandem mass spectrometry, were made before and after untreated apneic sleep. We compared free nitrotyrosine levels in these patients with those obtained at similar times in 10 healthy male control subjects without OSA, with similar age and body mass index. Evening baseline nitrotyrosine levels were similar before sleep in the control and OSA groups [0.16 Ϯ 0.01 and 0.15 Ϯ 0.01 ng/ml, respectively, P ϭ not significant (NS)]. Neither normal nor disturbed apneic sleep led to significant changes of plasma nitrotyrosine (morning levels: control group 0.14 Ϯ 0.01 ng/ml; OSA group 0.15 Ϯ 0.01 ng/ml, P ϭ NS). OSA was not accompanied by increased circulating free nitrotyrosine either at baseline or after sleep. This observation suggests that repetitive hypoxemia during OSA does not result in increased NO-mediated oxidative/nitrosative stress in otherwise healthy subjects with OSA. nitric oxide; cardiovascular diseases OBSTRUCTIVE SLEEP APNEA (OSA) has been linked to increased prevalence of cardiovascular and cerebrovascular morbidity (43). OSA is characterized by repetitive episodes of apnea and hypopnea that lead to surges in arterial blood pressure and increased sympathetic nerve activity (37, 45). More recently, OSA has also been associated with inflammation (35, 39, 44), endothelial dysfunction (19, 22) and increased oxidative stress (6,9,23,32), generated by repetitive nocturnal hypoxemia and reoxygenation. However, the mechanisms for increased cardiovascular disease in OSA are not fully understood.Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are the most important free radicals in the human body causing increased oxidative/nitrosative stress and tissue injury under pathological conditions (20, 31). Emerging evidence suggests that ROS are involved in the development and progression of a wide range of cardiovascular diseases (1,14,27,30). Recent studies also indicate that RNS may likewise contribute to cardiovascular disease, including vascular inflammation, endothelial dysfunction, coronary artherosclerosis, hypertension, and heart failure (2,3,7,15,36,41). OSA has been strongly linked to oxidative stress (6, 9, 23, 32); however, the effects of OSA on RNS have not been evaluated.Peroxynitrite (ONNO Ϫ ) and other RNS are generated by t...

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The addition of simvastatin to enalapril in hypertensive patients with average cholesterol levels improves parameters of diastolic function independently of changes in blood pressure or cholesterol.

A 46-year-old man with bicuspid aortic valve and severe calcific aortic stenosis was submitted to aortic valve replacement with a stented bioprosthesis. He developed Staphylococcus epidermidis prosthetic valve endocarditis a month later, presenting in the emergency room with acute myocardial infarction. The mechanism of myocardial ischemia was a large aortic root abscess causing left main extrinsic compression. He was urgently taken to the operating room, and an aortic root replacement with cryopreserved homograft was performed, associated with autologous pericardium patch closure of aortic to right atrium fistula and coronary artery bypass grafting of the left anterior descending. After a difficult postoperative period with multiple problems, he was eventually discharged home. At 36-month follow-up, he is asymptomatic with no recurrent infection, and the left main coronary artery is widely patent on control chest computed tomography.