Carmelo Fersini

Undiagnosed sleep-disordered breathing among male nondippers with essential hypertension.

Objective A blunting of the nocturnal fall in arterial blood pressure is found in a minority of patients (nondippers) with essential hypertension. We tested whether sleep-disordered breathing (snoring and apnea or hypopnea) might explain such a finding for male patients, among whom its prevalence is much higher. Setting and patients We studied 100 new cases of hypertension in men, observed consecutively by a local group of general practitioners and diagnosed essential hypertensives in a referral clinic. By using 24 h ambulatory blood pressure monitoring with a SpaceLabs 90207 device, 15 patients were classified initially nondippers (daytime ambulatory blood pressure ≥ 136/87 mmHg; night-time decrease by < 10% of the daytime mean), but only 11 were confirmed to be nondippers by continuous blood pressure monitoring with a Finapres device. Ten dippers matched by age, body mass index and mean 24 h blood pressure were used as controls. Main outcome measures Parameters of nocturnal polysomnography. Results During polysomnography, the nondippers exhibited a blunting of the sleep-related fall in blood pressure and an increased variability in blood pressure associated with sleep-disordered breathing (heavy snoring for all, with an apnea or hypopnea index > 10 in 10 cases). Six of the control patients breathed normally and four snored nonapneically. There was a normal fall in nocturnal blood pressure in all 10 cases. Conclusions The nondipper condition appears to be associated with undiagnosed apneic snoring for an unselected population of previously untreated male subjects with a diagnosis of essential hypertension. Ambulatory blood pressure monitoring of such patients is of limited diagnostic value.

Chronobiological aspects of acute cerebrovascular diseases

The study was aimed at further investigating the circadian and circannual patterns of stroke onset. Study design and type of participants: 977 strokes (475 in men and 502 in women) concerning 926 subjects (457 men and 469 women) admitted to Ferrara Hospital in two calendar years (1990–1991), were prospectively investigated. The strokes were classified as based on cerebral infarction (CI), transient ischemic attack (TIA) and cerebral hemorrhage (CH: subarachnoid and intracerebral hemorrhage). Two statistical models of analysis were used. The assessment of circadian and circannual periodicity was performed utilizing the single cosinor method. A separate analysis was performed after distribution of events into 6‐hour intervals, and chi‐square test for fit was applied to the number of observed versus expected cases. The majority of strokes occurred in the morning between 7 a.m. and noon (35% of cases) and the hypothesis of a uniform distribution of the time onset was rejected on the basis of the chi‐square for all subtypes of stroke. A circadian rhythm was found for CI and TIA with acrophase at the 11.56 and 12.41 respectively. Also a circannual periodicity was found for CI with a prevalent peak in October. The spectral analysis detected a circadian cycle for CH having a period of 4 h, and a circannual cycle for TIA with a period of 4 months. This study confirms that stroke is a high‐chronorisk disease, with specific circadian and circannual rhythms. This is very important for a better understanding and control of the underlying factors and in terms of prevention.

Chronobiological Patterns of Onset of Acute Cerebrovascular Diseases

There is a considerable amount of data indicating that several major unfavorable cerebrovascular events are not randomly distributed over time, but show a peculiar distribution along the day, the week, and the months of the year. The authors review the available evidence on the chronobiological (circadian, weekly, and seasonal) patterns of onset of acute cerebrovascular diseases and variations in their possible triggering mechanisms. The existence of a peculiar chronobiological pattern in the onset of acute cerebrovascular disease, characterized by both circadian (morning and evening occurrence), circaseptan (last and first days of the week), and circannual (especially in winter) is confirmed, although differences depending on biological (gender, age), pathological (diabetes, hypertension, smoke, alcohol), cultural, social, and environmental factors exist. A deeper knowledge of the underlying pathophysiologic mechanisms could provide more effective insights for both preventive strategies and optimization of therapeutic approach.

Time-Dependent Effect of Isradipine on the Nocturnal Hypertension in Chronic Renal Failure

Nocturnal hypertension is frequently observed in chronic renal failure and contributes to the risk of target organ damages. We assessed whether antihypertensive therapy may restore a nocturnal blood pressure (BP) fall in this condition. A sustained-release oral formulation (SRO) of isradipine was used, and the possible differences in the response to morning nu evening dosing were also investigated. Sixteen hypertensive patients with chronic renal failure due to parenchymal kidney disease were studied after 2 weeks of single-blind placebo runin. According to the double-blind, randomized, cross-over design, they received 5 mg isradipine SRO at 08:00, or at 20:00 for 4 weeks, separated by a single-blind placebo period of 2 weeks. A 24-h BP monitoring at 10-min intervals was carried out at the end of each treatment using a SpaceLabs 90207 instrument. Under placebo, blunt BP profiles were observed, whereas HR showed a mean nocturnal fall of 17.4%, which remained unaltered after isradipine. Both isradipine treatments were equally effective in reducing the mean 24-h BP levels. However, the evening regimen showed a more pronounced effect during the night. The mean nocturnal fall in systolic/diastolic BP represented 4.8/8.7% and 7.5/10.9% of the corresponding daytime mean after morning and evening dosing, respectively. Only the evening administration reset the normal synchronization of the 24-h BP and HR profiles. Our findings demonstrate that antihypertensive treatment may restore a nocturnal BP fall in renal patients. An evening regimen of isradipine SRO seems more apt than a morning regimen to obtain this therapeutic goal.

From a static to a dynamic concept of risk: the circadian epidemiology of cardiovascular events.

A growing body of evidence substantiates that the occurrence of cardiovascular events in unevenly distributed in time, especially during the 24 h. These temporal patterns are indicative of temporal variation in the (1) pathophysiological mechanisms that trigger cardiovascular events and (2) physiological status of the cardiovascular system, which combine to give rise to 24 h and other periodicities in the susceptibility to disease. The classic assumption of epidemiologic studies is constancy (or homeostasis) in ones risk to disease during the 24 h, as well as other, time domains. However, we propose a new concept, that of chronorisk since it takes into account the temporal variability in the pathophysiological mechanisms and their reciprocal temporal interactions that lead to day-night and other time-dependent patterns in cardiovascular events. This chronobiological approach, which is expected to contribute new insight into the prognostic and therapeutic assessment of cardiovascular events, is worthy of broader application in cardiovascular and other fields of medicine and warrants further investigation.

Serum cholesterol concentrations in parasuicide.

OBJECTIVE —To evaluate whether people who have committed parasuicide have low serum cholesterol concentrations. DESIGN —Results of blood tests in subjects admitted to hospital for parasuicide compared with those of a control group of non-suicidal subjects; comparison in subgroup of parasuicide subjects of two sets of blood test results (one set from admission for parasuicide and the other from admission for some other illness). SETTING —General hospital, Ferrara, Italy. SUBJECTS —331parasuicide subjects aged 44 (SD 21) years (109 with two sets of blood test results) and 331 controls. MAIN OUTCOME MEASURES —Serum cholesterol concentrations and possible association with parasuicide, considering sex, violence of method of parasuicide, and underlying psychiatric disorder. RESULTS —Lower serum cholesterol concentrations (4.96 (SD 1.16) mmol/l) were found in the parasuicide subjects than in the controls (5.43 (1.30); P < 0.001), regardless of sex and degree of violence of parasuicide method. Both men and women with two sets of blood test results had lower cholesterol concentrations after parasuicide. Linear regression analysis showed that the difference in cholesterol concentrations was significantly related to the length of time between the taking of the two sets of blood samples. CONCLUSION —The study showed low cholesterol concentrations after parasuicide. This finding agrees with previous studies, which suggest an association between low cholesterol concentration and suicide. Key messages Trials of cholesterol lowering have shown an increased mortality from violent deaths and suicide No studies of cholesterol concentrations in parasuicide subjects are available This study shows lower cholesterol concentrations in parasuicide subjects than in controls The association between low cholesterol concentration and parasuicide, however, does not allow definite conclusions to be drawn Further prospective trials are needed to focus on the possible effects of abrupt variation in cholesterol concentration on behaviour

Relationships of the Circadian Rhythms of Thrombotic, Ischemic, Hemorrhagic, and Arrhythmic Events to Blood Pressure Rhythms

Convincing evidence has recently accumulated that several unfavorable cardiovascular events show a well defined pattern in their occurrence throughout the day. Myocardial angina and infarction, sudden cardiac death, arrhythmias, fatal pulmonary thromboembolism, and ischemic and hemorrhagic cerebrovascular accidents occur more frequently in the morning, after awaking, until noon. Diurnal variations in multiple biologic functions, such as assumption of an upright posture associated with increased platelet aggregability, changes in blood clotting, fibrinolysis, and vascular tone and resistance, may be potentially active triggering factors. Moreover, variations in sympathetic tone, catecholamine secretion, and blood pressure have to be considered. The role of triggering factors and their relationships with blood pressure patterns is discussed in view of an optimized pharmacologic treatment.

Out-of-hospital sudden death referring to an emergency department☆

Over an 11-year period, autopsies were performed on 957 of 1038 nontraumatic deaths in the Emergency Department of the Central Hospital in Ferrara, Italy. Of these 957 cases, 732 (76.5%) met criteria for sudden death. In 100 (14%) of these cases, the death could be attributed to pulmonary embolism (55 cases), stroke (17), or rupture of aortic aneurysm (28). Acute myocardial infarction accounted for 403 (55%) of all sudden deaths. Severe coronary artery disease was found in 340 (84%) of these 403 deaths, with plaque fissuring or thrombi in 189 or 151 cases, respectively. Among the 229 sudden deaths for whom no immediate cause could be determined (31% of the total population), all had evidence of heart disease: 147 individuals had severe coronary artery disease, with plaque fissuring or thrombi found in 72 or 43, respectively. The remaining cases with no immediate cause of death had evidence of a cardiomyopathy (61) or valvular disease (21). We conclude that acute myocardial infarction accounts for the majority of cases of nontraumatic sudden death in our Emergency Department. Altogether, 84% of these patients had severe coronary artery disease. In approximately one-third of cases for whom no immediate cause of sudden death could be determined, all had evidence of heart disease, and about two-thirds had severe coronary artery disease.

Cricadian rhythms and the heart: Implications for chronotherapy of cardiovascular diseases

Clinical Pharmacology and Therapeutics (1994) 56, 244–247; doi:10.1038/clpt.1994.133

Dissociated 24-Hour Patterns of Somatotropin and Prolactin in Fatal Familial Insomnia

To assess the changes in the 24-hour profiles of serum somatotropin and prolactin levels during total disruption of the sleep/wake cycle sustained over several months, we studied 2 subjects affected by fatal familial insomnia, a rare disease characterized by selective thalamic degeneration that causes chronic sleep loss. Under standardized conditions and polysomnographic control, the patients underwent repeated 24-hour study sessions covering the entire clinical course of the disease. Hormones were assayed at 30-min intervals. Four healthy volunteers were used as controls. A sleep/wake cycle was always absent in fatal familial insomnia. Serum somatotropin and prolactin concentrations never exceeded the normal range of variation. The nocturnal elevation of somatotropin disappeared simultaneously with sleep loss, whereas a significant 24-hour component of variations in serum prolactin levels was present for months after total disruption of the sleep/wake cycle, with normally placed nocturnal acrophases. Complete obliteration of the 24-hour component was achieved for prolactin only in the advanced stages, through a progressive decrease in 24-hour amplitude of variation. Selective and progressive degeneration of the mediodorsal and anterior ventral nuclei of the thalamus causes an early obliteration of the 24-hour rhythm of somatotropin and a later disappearance of circadian prolactin rhythmicity.(ABSTRACT TRUNCATED AT 250 WORDS)