Giovanni Mazzotta

Day-Night Dip and Early-Morning Surge in Blood Pressure in Hypertension Prognostic Implications

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 (r=0.564; P<0.0001) and the preawakening (r=0.554; P<0.0001) 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 (⩽19.5 mm Hg; quartile 1) and preawakening (⩽9.5 mm Hg; quartile 1) BP surge was associated with an excess risk of events (hazard ratio, 1.66 [95% CI, 1.14–2.42]; P=0.009; hazard ratio, 1.71 [95% CI, 1.12–2.71]; P=0.013). 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.

Dysphagia following Stroke

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.

Plasma cytokine levels in patients with obstructive sleep apnea syndrome: a preliminary study

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.

Headache characteristics in obstructive sleep apnea syndrome and insomnia

Objectives –  To determine headache characteristics in the obstructive sleep apnea syndrome (OSAS) and in insomnia.

The renin angiotensin system in the development of cardiovascular disease: role of aliskiren in risk reduction

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.

Home Blood Pressure Measurements Will Not Replace 24-Hour Ambulatory Blood Pressure Monitoring

According to Herodotos, during the month of August in the year 480 BC, a few hundred elite soldiers from Sparta, led by their king Leonida, fiercely fought at the pass of Thermopylae against an overwhelming Persian army led by Serse. Almost all of the Spartans died. The huge discrepancy between the 2 armies at the Thermopylae pass might resemble in some way the discrepancy in the number of outcome-based studies with home blood pressure (BP) and 24-hour ambulatory BP (ABP; Table 1). View this table: Table 1. Longitudinal Event-Based Studies From Independent Groups Addressing the Prognostic Value of Ambulatory and Home BPs It is out of the question that home BP is a highly valuable clinical tool,1 and its use is constantly growing in United States2 and elsewhere. However, it is also out of the question that, compared with home BP, ABP received over the past 2 or 3 decades a greater bulk of data3 supporting its use to refine risk stratification and, in general, the management of the hypertensive patient. Although both home BP and ABP provide a better prediction of organ damage and the risk of cardiovascular complications when compared with office BP,1–3 each of the 2 techniques has inherent advantages and disadvantages that make them complementary more than alternative. Table 2, partially modified by a recent position paper of the American Society of Hypertension,2 synthesizes the main features of both. The present review holds the position that 24-hour ABP should not be replaced by home BP because of its unequivocal superiority under several diagnostic and prognostic aspects. Home BP and 24-hour ABP should possibly be considered as complementary techniques, to be used with the precise aim of exploiting the best that each technique can provide. View this table: Table 2. Comparison of Home and ABP After the …

The voltage of R wave in lead aVL improves risk stratification in hypertensive patients without ECG left ventricular hypertrophy.

Objectives We tested the hypothesis that the voltages of QRS on ECG improve risk stratification in hypertensive patients without left ventricular hypertrophy on ECG. Methods and results We studied 2042 initially untreated patients with hypertension (mean age 49 years, 46% women) without left ventricular hypertrophy on ECG and no history of cardiovascular disease. At entry, all patients underwent diagnostic tests, including 24-h ambulatory blood pressure monitoring and echocardiography. Among the different ECG voltages, the R wave in lead aVL showed the closest association with left ventricle (LV) mass (r = 0.31; P < 0.001), followed by the R wave in D1 (r = 0.25) and the S wave in V3 (r = 0.22). Patients were followed up for a mean of 7.7 years (range 1–22 years), and treatment was tailored individually. During follow-up, there were 188 major cardiovascular events. The relationship between LV voltage and outcome was assessed using a Cox model with adjustment for age, sex, diabetes, smoking, total cholesterol, serum creatinine, LV mass on echocardiography and average 24-h ambulatory blood pressure. A 0.1 mV higher R wave voltage in lead aVL was associated with a 9% higher risk of cardiovascular disease (95% confidence interval = 0.04–0.15%; P < 0.001). Other ECG voltages and minor repolarization changes were not related to clinical outcome. Conclusion Our results show for the first time that the voltage of the R wave in lead aVL improves cardiovascular risk stratification in hypertensive patients without left ventricular hypertrophy on ECG. Its prognostic value is independent of LV mass on echocardiography and 24-h ambulatory blood pressure.

Influence of blood pressure reduction on composite cardiovascular endpoints in clinical trials.

Background The use of a composite cardiovascular endpoint (CCEP) is frequent in clinical trials. However, the relation between the reduction in blood pressure (BP) and the risk of CCEP is poorly known. Methods We conducted a meta-analysis of trials, which compared different BP-lowering agents with placebo or active treatments in patients with hypertension or composite features of high cardiovascular risk. The outcome measure was a triple (myocardial infarction, stroke and cardiovascular death) or quadruple (those mentioned above and congestive heart failure) CCEP. Results Thirty trials fulfilled the inclusion criteria, for a total of 221 024 patients. Experimental treatments reduced the risk of CCEP by 9% (P < 0.0001). In a multivariable meta-regression analysis, for each 5-mmHg reduction in SBP, there was a 13% less risk of CCEP (95% confidence interval 8–19, P = 0.001) and, for each 2-mmHg reduction in DBP, there was a 12% less risk of CCEP (95% confidence interval 7–16, P = 0.001). Use of triple or quadruple CCEP (P = 0.150), its definition as primary or nonprimary endpoint (P = 0.305) and use of placebo or active control as comparators (P = 0.552) did not influence the estimates. A different BP reduction of at least 4.6 mmHg in SBP or at least 2.2 mmHg in DBP was required to achieve a 95% prediction interval entirely lying below the unity. Conclusion BP reduction is important to reduce the risk of CCEP in clinical trials. A significant difference between two treatment groups in the risk of CCEP may be anticipated for a SBP/DBP reduction differing by 4.6/2.2 mmHg or more.

Different cytokine levels in thrombolysis patients as predictors for clinical outcome

Thrombolytic therapy not always improves clinical outcome in ischemic stroke patients. This could cause lymphomonocyte accumulation in the infarcted brain area. These produce an excessive amount of proinflammatory cytokines, such as IL‐1beta, IL‐6 and TNF‐alfa. The aim of our study was to determine ILs levels in fibrinolytic therapy treated patients, compared with healthy controls and to evaluate if the varying levels can predictors of neurological outcome. Eighteen patients underwent thrombolytic treatment with t‐PA within 3 h. Plasma levels of IL‐1beta, IL‐6, TNF‐alfa and IL‐10 were determined by ELISA method before and within 24 h after t‐PA infusion and compared with controls. Significantly higher levels of IL‐1beta and Il‐6 emerged in stroke patients before treatment compared with the control group (P < 0.05 and 0.04, respectively). Slightly higher plasma levels of TNF‐alfa and lower plasma levels of IL‐10 were also found at base line in stroke patients. After thrombolytic treatment no significant variations were observed in the levels of TNF‐alfa and IL‐6, whereas a trend toward lower values for IL‐1beta and higher levels for IL‐10 was observed. Positive correlations among the values of IL‐6, TNF‐alfa and National Institute of Health Stroke Scale (NIHSS) at discharges were observed. A similar correlation with modified Rankin scale score at 3 month was found. Pre‐treatment cytokine status seems to influence pre‐and long‐term clinical outcome. Therefore an investigation into the possible predictor of cytokines seem worthy.

Executive dysfunction in children affected by obstructive sleep apnea syndrome: an observational study

Introduction The role of sleep in cognitive processes can be considered clear and well established. Different reports have disclosed the association between sleep and cognition in adults and in children, as well as the impact of disturbed sleep on various aspects of neuropsychological functioning and behavior in children and adolescents. Behavioral and cognitive dysfunctions can also be considered as related to alterations in the executive functions (EF) system. In particular, the EF concept refers to self-regulatory cognitive processes that are associated with monitoring and controlling both thought and goal directed behaviors. The aim of the present study is to assess the impact of the obstructive sleep apnea syndrome (OSAS) on EF in a large sample of school aged children. Materials and methods The study population comprised 79 children (51 males and 28 females) aged 7–12 years (mean 9.14 ± 2.36 years) with OSAS and 92 healthy children (63 males and 29 females, mean age 9.08 ± 2.44 years). To identify the severity of OSAS, an overnight respiratory evaluation was performed. All subjects filled out the Italian version of the Modified Card Sorting Test to screen EFs. Moreover, to check the degree of subjective perceived daytime sleepiness, all subjects were administered the Pediatric Daytime Sleepiness Scale (PDSS). Results No significant differences between the two study groups were found for age (P = 0.871), gender (P = 0.704), z-score of body mass index (P = 0.656), total intelligence quotient (P = 0.358), and PDSS scores (P = 0.232). The OSAS children showed a significantly higher rate of total errors (P < 0.001), perseverative errors (P < 0.001), nonperseverative errors (P < 0.001), percentage of total errors (P < 0.001), percentage of perseverative errors (P < 0.001), and percentage of nonperseverative errors (P < 0.001). On the other hand, OSAS children showed a significant reduction in the number of completed categories (P = 0.036), total correct sorts (P = 0.001), and categorizing efficiency (P < 0.001). The Pearson’s correlation analysis revealed a significant positive relationship between all error parameters and apnea-hypopnea index, oxygen desaturation index, and percentage of mean desaturation of O2 with a specular negative relationship between the error parameters and the mean oxygen saturation values, such as a significant negative relationship between apnea-hypopnea index, oxygen desaturation index, percent of mean desaturation of O2, and the number of completed categories. Conclusion Our study identified differences in the executive functioning of children affected by OSAS and is the first to identify a correlation between alteration in respiratory nocturnal parameters and EF that has not yet been reported in developmental age. These findings can be considered as the strength and novelty of the present report in a large pediatric population.