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...

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).

Hyperglycemia is a frequent condition in patients with acute coronary syndromes (ACS). Hyperglycemia during ACS is caused by an inflammatory and adrenergic response to ischemic stress, when catecholamines are released and glycogenolysis induced. Although the involved pathophysiological mechanisms have not yet been fully elucidated, it is believed that hyperglycemia is associated with an increase in free fat acids (which induce cardiac arrhythmias), insulin resistance, chemical inactivation of nitric oxide and the production of oxygen reactive species (with consequent microvascular and endothelial dysfunction), a prothrombotic state, and vascular inflammation. It is also related to myocardial metabolic disorders, leading to thrombosis, extension of the damaged area, reduced collateral circulation, and ischemic preconditioning. In the last few years, several observational studies demonstrated that hyperglycemia in ACS is a powerful predictor of survival, increasing the risk of immediate and long-term complications in patients both with and without previously known diabetes mellitus. Glucose management strategies in ACS may improve outcomes in patients with hyperglycemia, perhaps by reducing inflammatory and clotting mediators, by improving endothelial function and fibrinolysis and by reducing infarct size. Recent clinical trials of insulin in ACS have resulted in varying levels of benefit, but the clinical benefit of an aggressive treatment with insulin is yet unproved.

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Aliskiren is an orally active direct renin inhibitor which inhibits the synthesis of angiotensin I by linking to active renin on a deep cleft of its molecular structure, the site of hydrolysis of the Leu10-Val11 bond of angiotensinogen. At variance with angiotensin-converting enzyme (ACE) inhibitors, aliskiren eliminates the main substrate for the 'escape' phenomenon (synthesis of angiotensin II from angiotensin I through alternative enzymatic pathways). The possibility that the antihypertensive effect of aliskiren differs from that of ACE inhibitors needs to be proved in specifically designed clinical trials. Over the past 2 years, three studies have been published which directly compared aliskiren with ramipril, in patients with hypertension. We made a pooled analysis of these studies. In order to avoid interference with additional drugs, analysis was restricted to trial periods when the two drugs were given as monotherapy. In each individual study, systolic blood pressure (BP) was slightly lower with aliskiren. Overall, systolic BP was lower with aliskiren than with ramipril (weighted mean difference between the treatments 1.84 mmHg; fixed effect model; p < 0.0001; and 1.87 mmHg; random effect model; p = 0.0055). The standardized mean difference between the treatments was 2.58 (fixed effect model; p < 0.0001) and 2.92 (random effect model; p = 0.0017) in favor of aliskiren. Compared with ramipril, aliskiren may have induced a more complete 'upstream' inhibition of the renin-angiotensin-aldosterone system, with consequent greater suppression of angiotensin II. Another potential explanation may be the longer terminal elimination halflife of aliskiren (about 40 hours) compared with ramiprilat (13-17 hours). These data provide further evidence that aliskiren monotherapy provides a sustained BP reduction over the 24 hours.