Sex and Circadian Periodicity of Cardiovascular Diseases: Are Women Sufficiently Represented in Chronobiological Studies?

Women are often excluded/underrepresented in clinical trials; sometimes, the number of men/women participants or separate analysis by sex are not reported. A robust body of evidence demonstrated that several life-threatening acute cardiovascular diseases, for example, acute myocardial infarction, sudden cardiac death, cardiac arrest, rupture or dissection of aortic aneurysms, and stroke, exhibit a circadian periodicity with a morning peak. An analysis of 20 years of chronobiologic studies (44% of them, accounting for 85% of total cases, with separate analysis by sex) confirmed that morning hours are a critical time of onset of acute cardiovascular diseases in men and women.

Marital Status, Cardiovascular Diseases, and Cardiovascular Risk Factors: A Review of the Evidence.

BACKGROUND: There is evidence showing that marital status (MS) and marital disruption (i.e., separation, divorce, and being widowed) are associated with poor physical health outcomes, including for all-cause mortality. We checked for the available evidence on the association between MS and cardiovascular (CV) diseases, outcomes, and CV risk factors. METHODS: A search across the PubMed database of all articles, including the term "marital status" in their title, was performed. All articles were then manually checked for the presence of the following terms or topic: CV diseases, acute myocardial infarction, acute coronary syndrome, coronary artery disease, cardiac arrest, heart failure, heart diseases, and CV mortality. Moreover, other search terms were: CV risk factors, hypertension, cholesterol, obesity, smoking, alcohol, fitness and/or physical activity, and health. Systematic reviews, meta-analyses, controlled trials, cohort studies, and case-control studies were potentially considered pertinent for inclusion. Case reports, comments, discussion letters, abstracts of scientific conferences, articles in other than English language, and conference abstracts or proceedings were excluded. RESULTS: In total, 817 references containing the title words "marital status" were found. After elimination of articles dealing with other topics, 70 records were considered pertinent. Twenty-two were eliminated for several reasons, such as old articles, no abstract, full text unavailable, other than English language, comments, and letters. Out of the remaining 48 articles, 13 were suitable for the discussion, and 35 (accounting for 1,245,967 subjects) were included in this study. CONCLUSIONS: Most studies showed better outcomes for married persons, and men who were single generally had the poorest results. Moreover, being married was associated with lower risk factors and better health status, even in the presence of many confounding effects.

Chronobiology of Takotsubo Syndrome and Myocardial Infarction: Analogies and Differences.

Several pathophysiologic factors, not harmful if taken alone, are capable of triggering unfavorable events when presenting together within the same temporal window (chronorisk), and the occurrence of many cardiovascular events is not evenly distributed in time. Both acute myocardial infarction and takotsubo syndrome seem to exhibit a temporal preference in their onset, characterized by variations according to time of day, day of the week, and month of the year, although with both analogies and differences.

Chronotype, gender and general health.

BACKGROUND: Light-dark alternation has always been the strongest external circadian "zeitgeber" for humans. Due to its growing technological preference, our society is quickly transforming toward a progressive "eveningness" (E), with consequences on personal circadian preference (chronotype), depending on gender as well. The aim of this study was to review the available evidence of possible relationships between chronotype and gender, with relevance on disturbances that could negatively impact general health, including daily life aspects. METHODS: Electronic searches of the published literature were performed in the databases MEDLINE and Web of Science, by using the Medical Subject Heading (MeSH), when available, or other specific keywords. RESULTS: Results were grouped into four general areas, i.e. (a) "General and Cardiovascular Issues", (b) "Psychological and Psychopathological Issues", (c) "Sleep and Sleep-Related Issues" and (d) "School and School-Related Issues". (a) E is associated with unhealthy and dietary habits, smoking and alcohol drinking (in younger subjects) and, in adults, with diabetes and metabolic syndrome; (b) E is associated with impulsivity and anger, depression, anxiety disorders and nightmares (especially in women), risk taking behavior, use of alcohol, coffee and stimulants, psychopathology and personality traits; (c) E has been associated, especially in young subjects, with later bedtime and wake-up time, irregular sleep-wake schedule, subjective poor sleep, school performance and motivation, health-related quality of life; (d) E was associated with lowest mood and lower overall grade point average (especially for women). CONCLUSIONS: Eveningness may impact general health, either physical or mental, sleep, school results and achievements, especially in younger age and in women. The role of family support is crucial, and parents should be deeply informed that abuse of technological devices during night hours may lead to the immature adjustment function of children's endogenous circadian pacemakers.

The crucial factor of hospital readmissions: a retrospective cohort study of patients evaluated in the emergency department and admitted to the department of medicine of a general hospital in Italy.

BACKGROUND: Early hospital readmissions, defined as rehospitalization within 30 days from a previous discharge, represent an economic and social burden for public health management. As data about early readmission in Italy are scarce, we aimed to relate the phenomenon of 30-day readmission to factors identified at the time of emergency department (ED) visits in subjects admitted to medical wards of a general hospital in Italy. METHODS: We performed a retrospective 30-month observational study, evaluating all patients admitted to the Department of Medicine of the Hospital of Ferrara, Italy. Our study compared early and late readmission: patients were evaluated on the basis of the ED admission diagnosis and classified differently on the basis of a concordant or discordant readmission diagnosis in respect to the diagnosis of a first hospitalization. RESULTS: Out of 13,237 patients admitted during the study period, 3,631 (27.4%) were readmitted; of those, 656 were 30-day rehospitalizations (5% of total admissions). Early rehospitalization occurred 12 days (median) later than previous discharge. The most frequent causes of rehospitalization were cardiovascular disease (CVD) in 29.3% and pulmonary disease (PD) in 29.7% of cases. Patients admitted with the same diagnosis were younger, had lower length of stay (LOS) and higher prevalence of CVD, PD and cancer. Age, CVD and PD were independently associated with 30-day readmission with concordant diagnosis and kidney disease with 30-day rehospitalization with a discordant diagnosis. CONCLUSIONS: Comorbid patients are at higher risk for 30-day readmission. Reduction of LOS, especially in elderly subjects, could increase early rehospitalization rates.

Takotsubo cardiomyopathy and acute infectious diseases: a mini-review of case reports.

Takotsubo cardiomyopathy (TTC), also defined as "stress cardiomyopathy," is characterized by a systolic dysfunction localized in the apical and medial left ventricles. Takotsubo cardiomyopathy is more prevalent in females and it is usually related to an event triggered by physical or emotional stress. We systematically explored PubMed and Embase medical information source to identify case reports showing association between infection and TTC. For each kind of infection, we collected a set of data, including pathogen, site of infection, clinical outcome, patient age and sex, and author and year of publication. We found 26 articles dealing with 27 case reports (74% women). The mean age was 61.4 ± 13.7 years and bacterial infections were more frequent (n = 23, 85.2%). In 14 cases, there was a culture-based definition of the bacterial strain: gram+ in 8 cases (57.1%) and gram- in 6 cases (42.9%). Clinical outcome was always favorable.

Heart and lung, a dangerous liaison-Tako-tsubo cardiomyopathy and respiratory diseases: A systematic review.

AIM: To investigate the possible association between Tako-tsubo cardiomyopathy (TTC)-a reversible clinical condition mimicking an acute myocardial infarction characterized by multifactorial pathophysiologic mechanisms- and respiratory system diseases. METHODS: We systematically searched PubMed and EMBASE medical information sources, to identify the different triggering causes, limiting our search to articles in English. The search keywords were: "tako-tsubo cardiomyopathy", "takotsubo", "takotsubo cardiomyopathy", "broken heart syndrome", "stress-induced cardiomyopathy", "apical ballooning syndrome", and "ampulla cardiomyopathy in combination with respiratory diseases, lung, pulmonary disease. For each kind of disease, we registered: author, year and country of study, patient sex, age, concurring situation, and outcome. RESULTS: Out of a total of 1725 articles found, we selected 37 papers reporting a total of 38 patients. As expected, most patients were women (81.6%), mean age was 65 ± 10 years. Outcome was favorable in 100% of cases, and all the patients have been discharged uneventfully in a few days. CONCLUSION: An association between respiratory diseases and TTC is likely to exist. Patients with severe respiratory diseases, due to the high dosages of ß2-agonists used or to the need of invasive procedures, are highly exposed to the risk of developing TTC.

Association between in-hospital mortality and renal dysfunction in 186,219 patients hospitalized for acute stroke in the Emilia-Romagna region of Italy.

Using a regional Italian database, we evaluated the relationship between renal dysfunction and in-hospital mortality (IHM) in patients with acute stroke (ischemic/hemorrhagic). Patients were classified on the basis of renal damage: without renal dysfunction, with chronic kidney disease (CKD), and with end-stage renal disease (ESRD). Of a total of 186,219 patients with a first episode of stroke, 1626 (0.9%) had CKD and 819 (0.4%) had ESRD. Stroke-related IHM (total cases) was independently associated with CKD, ESRD, atrial fibrillation (AF), age, and Charlson comorbidity index (CCI). In patients with ischemic stroke (n=154,026), IHM remained independently associated with CKD, ESRD, AF, and CCI. In patients with hemorrhagic stroke (n=32,189), variables that were independently associated with IHM were CKD, ESRD, and AF. Renal dysfunction is associated with IHM related to stroke, both ischemic and hemorrhagic, with even higher odds ratios than those of other established risk factors, such as age, comorbidities, and AF.

Seasonal variation of platelets in a cohort of Italian blood donors: a preliminary report.

BACKGROUND: Since available data are not univocal, the aim of this study was to explore the existence of a seasonal variation in platelet count. METHODS: The study was based on the database of the Italian Association of Blood Volunteers (AVIS), section of Ferrara, Italy, 2001-2010. Hematological data (170,238 exams referring to 16,422 donors) were categorized into seasonal and monthly intervals, and conventional and chronobiological analyses were applied. RESULTS: Platelets and plateletcrit were significantly higher in winter-autumn, with a main peak in December-February (average +3.4% and +4.6%, respectively, P <0.001 for both). CONCLUSIONS: Although seasonal variations have been reported for several acute cardiovascular diseases, it is extremely unlikely that such a slight increase in platelet count in winter alone may be considered as a risk factor.

Chronobiology in aortic diseases - "is this really a random phenomenon?".

Although acute aortic rupture or dissection is relatively uncommon, it ranks in third position among necropsy-confirmed causes of out-of-hospital sudden death in the general population. Similar to other acute cardiovascular events (e.g., acute myocardial infarction, sudden death, stroke, and pulmonary embolism) there is a growing body of evidence regarding temporal patterns in onset, characterized by circadian, seasonal and weekly variations for aortic aneurysms. On one hand, it is possible that these cardiovascular diseases share common underlying pathophysiologic mechanisms, e.g., increase in blood pressure, heart rate, sympathetic activity, basal vascular tone, vasoconstrictive hormones, and prothrombotic tendency. On the other hand, the possibility exists that the connecting link is an internal disruption (dyssynchrony) of some molecular mechanisms intrinsic to the peripheral biological clock (that of cardiomyocyte is the most widely investigated). Such disruption may contribute to cardiovascular disease and biological rhythms - an intriguing hypothesis for future research.

Breaking heart: chronobiologic insights into takotsubo cardiomyopathy.

A considerable amount of evidence has shown that the major acute cardiovascular diseases, ie, myocardial infarction, sudden cardiac death, stroke, pulmonary embolism, and rupture or dissection of aortic aneurysms do not occur randomly in time, but exhibit specific temporal patterns in their onset, according to time of day, month or season, and day of the week. This contributes to the definition of "chronorisk", where several factors, not harmful if taken alone, are capable of triggering unfavorable events when presenting all together within the same temporal window. This article reviews the actual knowledge about time of onset of takotsubo cardiomyopathy.