Abstract-We investigated the relationship between the day-night blood pressure (BP) dip and the early morning BP surge in an cohort of 3012 initially untreated subjects with essential hypertension. The day-night reduction in systolic BP showed a direct association with the sleep trough (rϭ0.564; PϽ0.0001) and the preawakening (rϭ0.554; PϽ0.0001) systolic BP surge. Over a mean follow-up period of 8.44 years, 268 subjects developed a major cardiovascular event (composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and heart failure requiring hospitalization) and 220 subjects died. In a Cox model, after adjustment for predictive covariates, including age, sex, diabetes mellitus, cigarette smoking, total cholesterol, left ventricular hypertrophy on ECG, estimated glomerular filtration rate, and average 24-hour systolic BP, a blunted sleep trough (Յ19.5 mm Hg; quartile 1) and preawakening (Յ9.5 mm Hg; quartile 1) BP surge was associated with an excess risk of events (hazard ratio, 1.66 [95% CI, 1.14 -2.42]; Pϭ0.009; hazard ratio, 1.71 [95% CI, 1.12-2.71]; Pϭ0.013). After adjustment for the same covariates, neither the dipping pattern nor the measures of early morning BP surge were independent predictors of mortality. In conclusion, in initially untreated subjects with hypertension, a blunted day-night BP dip was associated with a blunted morning BP surge and vice versa. In these subjects, a blunted morning BP surge was an independent predictor of cardiovascular events, whereas an excessive BP surge did not portend an increased risk of events. (Hypertension. 2012;60:34-42.)Key Words: hypertension Ⅲ dippers Ⅲ nondippers Ⅲ blood pressure monitoring Ⅲ sleep Ⅲ morning blood pressure surge Ⅲ ambulatory blood pressure O ccurrence of major cardiovascular complications, including myocardial infarction (MI), 1 stroke, 2 and sudden cardiac death, 3 peaks in the early morning hours, typically in the first 4 to 6 hours after awakening. Therefore, the hypothesis has been raised that the extent of blood pressure (BP) surge in the early morning may be associated with the risk of cardiovascular complications. This hypothesis is potentially relevant because it might imply the possibility that reducing the early morning rise in BP may lower the risk of major events that occur in the early morning. By using 24-hour ambulatory BP (ABP) monitoring in cohorts of hypertensive patients 4-6 or randomized samples from the general population, 7,8 several investigators examined the association between the morning BP surge and the subsequent outcome, but results were not univocal. On the other hand, many studies showed that the risk of cardiovascular disease directly increases with nighttime BP and a blunted BP dip from day to night. 6,[9][10][11][12] The adverse prognostic impact of a blunted or reversed diurnal BP rhythm seems difficult to reconcile with the hypothesis that an excessive rise in BP from the nighttime period to the early morning is also predictive of a worse outcome. None of the studies that addresse...

Background: Dysphagia is common after stroke. We aimed to study the prognosis of dysphagia (assessed clinically) over the first 3 months after acute stroke and to determine whether specific neurovascular-anatomical sites were associated with swallowing dysfunction. Methods: We prospectively examined consecutive patients with acute first-ever stroke. The assessment of dysphagia was made using standardized clinical methods. The arterial territories involved were determined on CT/MRI. All patients were followed up for 3 months. Results: 34.7% of 406 patients had dysphagia. Dysphagia was more frequent in patients with hemorrhagic stroke (31/63 vs. 110/343; p = 0.01). In patients with ischemic stroke, the involvement of the arterial territory of the total middle cerebral artery was more frequently associated with dysphagia (28.2 vs. 2.2%; p < 0.0001). Multivariate analysis revealed that stroke mortality and disability were independently associated with dysphagia (p < 0.0001). Conclusions: The frequency of dysphagia was relatively high. Regarding anatomical-clinical correlation, the most important factor was the size rather than the location of the lesion. Dysphagia assessed clinically was a significant variable predicting death and disability at 90 days.

Summary The levels of some pro‐ and anti‐inflammatory cytokines [interleukin (IL)‐1β, tumor necrosis factor (TNF)‐α, IL‐6, IL‐10, and transforming growth factor (TGF)‐β], were measured by enzyme‐linked immunosorbent assay (ELISA) method in the plasma of patients affected by obstructive sleep apnea syndrome (OSAS) at 22:00 hours before polysomnographic recording and immediately after the first obstructive apnea causing an SaO2 below 85%. Significantly higher levels of TNF‐α were found in OSAS patients assessed before polysomnography compared with the control group (P < 0.01). A slight but significant increase in the plasma levels of IL‐6 was also present (P < 0.05). Conversely, a significant decrease in the plasma levels of IL‐10 was evident at baseline in OSAS patients (P < 0.04). No significant difference emerged between the mean values of IL‐1α and TGF‐β between OSAS patients and controls. The present data support a prevailing activation of the Th1‐type cytokine pattern in OSAS patients, which is not associated with the severity and duration of OSAS. This can have important consequences for the outcome of OSAS patients, especially with regard to the increased risk for developing atherosclerosis and cardiovascular and cerebrovascular diseases. Immediately after the first obstructive apnea causing an SaO2 <85%, a significant variation was observed in the plasma levels of TNF‐α in OSAS patients compared with those measured before the beginning of polysomnographic recording (P < 0.001). The role played by this further increase in TNF‐α levels after the obstructive apnea in OSAS patients remains to be established in the light of the pathogenic mechanisms of this sleep disorder.

An association has been shown between plasma renin activity (PRA) and the risk of cardiovascular disease. There is also evidence that angiotensin II exerts detrimental effects on progression and instabilization of atherosclerotic plaque. The renin-angiotensin system (RAS) can be inhibited through inhibition of angiotensin I (Ang I) generation from angiotensinogen by direct renin inhibitors, inhibition of angiotensin II (Ang II) generation from angiotensin I by angiotensin-converting enzyme inhibitors and finally by direct inhibition of the action of Ang II receptor level. Aliskiren, the first direct renin inhibitor to reach the market, is a low-molecular-weight, orally active, hydrophilic nonpeptide. Aliskiren blocks Ang I generation, while plasma renin concentration increases because the drugs blocks the negative feed-back exerted by Ang II on renin synthesis. Because of its long pharmacological half-life, aliskiren is suitable for once-daily administration. Its through-to-peak ratio approximates 98% for the 300 mg/day dose. Because of its mechanism of action, aliskiren might offer the additional opportunity to inhibit progression of atherosclerosis at tissue level. Hypertension is an approved indication for this drug, which is also promising for the treatment of heart failure. The efficacy of this drug in reducing major clinical events is being tested in large ongoing clinical trials.

Atrial fibrillation (AF) confers an increased risk of mortality in patients hospitalized for acute myocardial infarction (AMI). However, it is unclear whether new-onset and preexisting AF portend a different risk. We extracted data from studies that evaluated in-hospital mortality in patients with AMI and included information on cardiac rhythm. Overall, the risk of mortality was higher in patients with AF than in those in sinus rhythm (OR 2.00, 95 % CI: 1.93-2.08; P < 0.0001). Compared with patients who remained in sinus rhythm, the risk of death was increased in patients with new AF certain (sinus rhythm on admission, new AF during hospitalization, and history of no evidence of prior AF; OR 3.38, 95 % CI: 2.98-3.83; P < 0.0001), new AF uncertain (sinus rhythm on admission, AF during hospitalization, but no clear information about previous history of AF; OR 1.90, 95 % CI:1.83-1.98; P < 0.0001), and permanent AF (AF before and during hospitalization; OR 2.01, 95 % CI:1.70-2.38;P < 0.0001). In a meta-regression analysis, the risk of death was 87 % higher in patients with new AF certain than in those with permanent AF (P = 0.013) or AF uncertain (P = 0.003), and not dissimilar in patients with new AF uncertain and permanent AF (P = 0.706).

Headache is a common finding in both OSAS and insomnia patients. Because morning headache seems to be more specific for OSAS than insomnia, and in OSAS its occurrence seems to be associated with disease severity, we hypothesize the involvement of certain pathogenic mechanisms associated with OSAS.

The present study confirms previous findings of an increase in calcitonin gene-related peptide in internal jugular venous blood of migraine without aura patients during attacks. The transient increase in the levels of IL-8 concurs with the results of recent experimental research showing a calcitonin gene-related peptide-induced activation of IL-8 gene expression, but not RANTES and MCP-1, via the transcriptional factor AP-2, which mediates transduction in response to cyclic adenosine monophosphate. Although IL-8 is transiently increased during migraine attacks, an accumulation of leukocytes secondary to neurogenic inflammation is unlikely, as it is for other inflammatory events, because they are self limiting. Other events, including nitric oxide production, may contribute to counteract meningeal transvascular leukocyte migration during migraine attacks, as suggested by the model of sterile inflammation.

In conclusion, this study demonstrates that this new approach, proposed in the Appendix (A1.1), appears easy to apply and should improve the diagnostic standard of ICHD-II in young patients too.