Benedetta Boari

Circadian Variation in Stroke Onset: Identical Temporal Pattern in Ischemic and Hemorrhagic Events

Stroke is the culmination of a heterogeneous group of cerebrovascular diseases that is manifested as ischemia or hemorrhage of one or more blood vessels of the brain. The occurrence of many acute cardiovascular events—such as myocardial infarction, sudden cardiac death, pulmonary embolism, critical limb ischemia, and aortic aneurysm rupture—exhibits prominent 24 h patterning, with a major morning peak and secondary early evening peak. The incidence of stroke exhibits the same 24 h pattern. Although ischemic and hemorrhagic strokes are different entities and are characterized by different pathophysiological mechanisms, they share an identical double‐peak 24 h pattern. A constellation of endogenous circadian rhythms and exogenous cyclic factors are involved. The staging of the circadian rhythms in vascular tone, coagulative balance, and blood pressure plus temporal patterns in posture, physical activity, emotional stress, and medication effects play central and/or triggering roles. Features of the circadian rhythm of blood pressure, in terms of their chronic and acute effects on cerebral vessels, and of coagulation are especially important. Clinical medicine has been most concerned with the prevention of stroke in the morning, when population‐based studies show it is of greatest risk during the 24 h; however, improved protection of at‐risk patients against stroke in the early evening, the second most vulnerable time of cerebrovascular accidents, has received relatively little attention thus far.

Oxidative Stress in Essential Hypertension

A major cause for endothelial dysfunction in essential hypertension is decreased availability of nitric oxide (NO). Impairment in NO bioavailability is likely to be the consequence of multiple mechanisms affecting NO synthesis as well as NO breakdown. An alteration in the redox balance in endothelial cells leads to increased superoxide anion production and oxidative stress. This in turn not only exerts negative effects on vascular tone, but is also able to activate important mechanisms (such as platelet activity, leukocyte adhesion, vascular smooth muscle cell proliferation and expression of adhesion molecules) with an established central role in the pathogenesis of hypertensive target organ damage. As a consequence, a drug therapy able to restore NO availability in essential hypertensive patients would probably exert additional benefits, as compared to blood pressure lowering per se, in terms of prevention of target organ damage and improved prognosis of these patients. Unfortunately, as of today only the antagonists of the renin-angiotensin system and the calcium-channel blockers have shown some ability in this respect, whereas no longitudinal intervention study has been undertaken, so far, to prove that the restoration of NO bioavailability through an antihypertensive treatment may confer additional prognostic advantage to essential hypertensive patients.

Impact of Time to Treatment on Mortality After Prehospital Fibrinolysis or Primary Angioplasty

To the Editor: We read with interest the article by Steg et al,1 which reported that prehospital thrombolysis may be preferable to primary percutaneous coronary intervention (PCI) for patients treated within the first 2 hours after symptoms begin. A recent study,2 however, reported the superiority of primary angioplasty over fibrinolysis for patients needing transportation that takes 2 hours or less. In all studies, time-dependency of reperfusion success is usually evaluated in terms of time from symptom onset, not from time of symptom onset. It is not the same to have a myocardial infarction in the morning or in the evening. In morning hours, from 6 am to …

Seasonal variation in occurrence of pulmonary embolism: analysis of the database of the Emilia-Romagna region, Italy.

Seasonal variation in the occurrence of cardiovascular and cerebrovascular events, including pulmonary embolism (PE), has been reported; however, recent large‐scale, population‐based studies conducted in the United States did not confirm such seasonality. The aim of this large‐scale population study was to determine whether a temporal pattern in the occurrence of PE exists. The analysis considered all consecutive cases of PE in the database of all hospital admissions of the Emilia Romagna region in Italy at the Center for Health Statistics between January 1998 and December 2005. PE cases were first grouped according to season of occurrence, and the data were analyzed by the χ2 test for goodness of fit. Then, inferential chronobiologic (cosinor and partial Fourier) analysis was applied to monthly data, and the best‐fitting curve for the annual variation was derived. The total sample consisted of 19,245 patients (8,143 male, mean age 71.6±14.1 yrs; 11,102 female, mean age 76.1±13.7 yrs). Of these, 2,484 were <65 yrs, 5,443 were between 65 and 74, and 11,318 were ≥75 yrs. There were 4,486 (23.3%) fatal‐case outcomes. PE occurred least frequently in spring (n=4,442 or 23.1%) and most frequent in winter (n=5,236 or 27.2%, goodness of fit χ2=75.75, p<0.001). Similar results were obtained for subgroups formed by gender, age, fatal/non‐fatal outcome, presence/absence of major underlying co‐morbid conditions, and specific risk factors. Inferential chronobiological analysis identified a significant annual pattern in PE, with the peak between November and December for the total sample of cases (p<0.001), males (p<0.001), females (p=0.002), fatal and non‐fatal cases (p<0.001 for both), and subgroups formed by age (<65 yrs, p=0.012; 65–74 yrs, p<0.001; ≥75 yrs, p=0.012). This pattern was independent of the presence/absence of hypertension (p=0.003 and p<0.001, respectively), pulmonary disease (p<0.001 and p<0.001, respectively), stroke (p<0.001 and p=0.004, respectively), neoplasms (p=0.005 and p=0.001, respectively), heart failure (p=0.022 and p<0.001, respectively), and deep vein thrombosis (p=0.002 and p<0.001, respectively). However, only a non‐statistically significant trend was found for subgroups formed by cases of diabetes mellitus, infections, renal failure, and trauma.

Seasonal Variation in Onset of Myocardial Infarction—A 7‐year single‐center study in Italy

Like many other serious acute cardiovascular and cerebrovascular events, acute myocardial infarction (AMI) shows seasonal variation, being most frequent in the winter. We sought to investigate whether age, gender, and hypertension influence this pattern. We studied 4014 (2259 male and 1755 female) consecutive patients with AMI presenting to St. Anna Hospital of Ferrara, Italy between January 1998 and December 2004. Some 1131 (28.2%) of the AMI occurred in persons <65 yrs of age, and 2883 (71.8%) in those ≥65 yrs of age. AMI was over‐represented in males (82% in the <65 yr group vs. 56.6% in the ≥65 yr group (χ2=13.99; p<0.001). Hypertension had been previously documented in 964 (24%) of the cases. There were 691 (17.2%) fatal case outcomes; fatal outcomes were significantly higher among the 3054 normotensive (n=614 or 20.1%) than the 964 hypertensive cases (n=77 or 8%; χ2=74.94, p<0.001). AMIs were most frequent in the winter (n=1076 or 26.8% of all the events) and least in the summer (n=924 or 23.0% of all the events; χ2=12.36, p=0.007). The greatest number of AMIs occurred in December (n=379 or 9.44%), and the lowest number in September (n=293 or 7.3%; χ2=11.1, p=0.001). Inferential chronobiological (Cosinor) analysis identified a significant annual pattern in AMI in those ≥65 yrs of age, with a peak between December and February—January for the total sample (p<0.005), January for the sample of males (p=0.014), February for fatal infarctions (p=0.017), and December for non‐fatal infarctions (p=0.006). No such temporal variations were detected in any of these categories in those <65 yrs of age. The annual pattern in AMI was also verified by Cosinor analysis in the following hypertensive subgroups: hypertensive males (n=552: January, p=0.014), non‐fatal infarctions in hypertensive patients (n=887: January, p=0.018), and elderly normotensives (n=1556: November, p=0.007).

Seasonal Variation in Onset of Pulmonary Embolism is Independent of Patients' Underlying Risk Comorbid Conditions

As for many cardiovascular events, pulmonary embolism (PE) is not randomly distributed over time, but shows rhythmic patterns. The purpose of this study was to investigate whether such temporal pattern of occurrence varied in subgroups of patients according to different risk comorbid conditions. All cases of PE observed at the Hospital of Ferrara, Italy, from 1998 to 2001, were considered. After determination of the day of onset, the population was grouped by gender and the most common underlying risk comorbid conditions, e.g., deep vein thrombosis (DVT), neoplasms, cardiomyopathies, traumas/surgical operations, diabetes mellitus, pulmonary diseases, hypertension, cerebrovascular diseases, heart failure, hematologic diseases. For statistical analysis, chi-square test for goodness of fit and partial Fourier series were used. A total of 784 cases (mean age 71 ± 14 years) were included. Frequency of onset was higher in winter for total population (p=0.002), men (p=0.004), DVT (p=0.001), pulmonary disease (p=0.008), cardiomyopathies (p=0.011), and major traumas/surgical operations (p=0.049). Chronobiologic analysis identified a winter peak for total population (p=0.008), men (p<O.OOl), DVT (p=0.006), pulmonary diseases (p=0.017), and hypertension (p=0.026). This study confirms the winter peak of PE and provides evidence that it is not influenced by the underlying clinical conditions, but probably by endogenous variations.

Does Circadian and Seasonal Variation in Occurrence of Acute Aortic Dissection Influence in‐Hospital Outcomes?

The risk of acute aortic dissection (AAD) exhibits chronobiological variations with peak onset in the morning and in winter. However, it is not known whether the time of day or season of the year of the AAD affects clinical outcomes. We studied 1,032 patients enrolled in the International Registry of Acute Aortic Dissection from January 1997 to December 2001. For circadian and seasonal analysis, the time and date of symptom onset were available for 741 and 1,007 patients, respectively, and were grouped into four 6 h periods (morning, afternoon, evening, and night) and four seasons (winter, spring, summer, and autumn). The χ2 test for goodness of fit was used to evaluate non‐uniformity of the time of day and time of year for critical in‐hospital clinical events, including death. While highest incidence of AAD occurred in the morning and winter, clinical events (including mortality) were similar during the four different periods of the 24 h (χ2=1.9, p=0.60) and seasonal (χ2=1.2, p=0.75) periods.

The Winter Peak in the Occurrence of Acute Aortic Dissection is Independent of Climate

We recently reported the existence of a higher risk of acute aortic dissection (AAD) during the winter months. However, it is not known whether this winter peak is affected by climate. To address this issue, we evaluated data from 969 AAD patients who were enrolled at various sites around the globe and who were participating in the International Registry of Acute Aortic Dissection (IRAD). We found a significant (p=0.001; χ2 test) difference in the number of AAD events occurring during the different seasons of the year, with highest incidence in winter (28.4%) and lowest incidence in summer (19.9%). Furthermore, the winter peak was evident in both cold and temperate climate settings, suggesting that the relative change in temperature, rather than absolute temperature, and/or endogenous annual rhythms are critical mechanistic factors.

Discharge diagnosis and comorbidity profile in hospitalized older patients with dementia.

The aim of this study was to investigate the principal discharge diagnosis and related comorbidity in hospitalized older patients affected by dementia.

Circadian and Seasonal Variation of Migraine Attacks in Children

Object.—To investigate the rhythmicity of migraine episodes without aura in a pediatric population.