Marco Pala

Dipper and Non-Dipper Blood Pressure 24-Hour Patterns: Circadian Rhythm–Dependent Physiologic and Pathophysiologic Mechanisms

Neuroendocrine mechanisms are major determinants of the normal 24-h blood pressure (BP) pattern. At the central level, integration of the major driving factors of this temporal variability is mediated by circadian rhythms of monoaminergic systems in conjunction with those of the hypothalamic-pituitary-adrenal, hypothalamic-pituitary-thyroid, opioid, renin-angiotensin-aldosterone, plus endothelial systems and specific vasoactive peptides. Humoral secretions are typically episodic, coupled either to sleep and/or the circadian endogenous (suprachiasmatic nucleus) central pacemaker clock, but exhibiting also weekly, monthly, seasonal, and annual periodicities. Sleep induction and arousal are influenced also by many hormones and chemical substances that exhibit 24-h variation, e.g., arginine vasopressin, vasoactive intestinal peptide, melatonin, somatotropin, insulin, steroids, serotonin, corticotropin-releasing factor, adrenocorticotropic hormone, thyrotropin-releasing hormone, endogenous opioids, and prostaglandin E2, all with established effects on the cardiovascular system. As a consequence, physical, mental, and pathologic stimuli that activate or inhibit neuroendocrine effectors of biological rhythmicity may also interfere with, or modify, the temporal BP structure. Moreover, immediate adjustment to exogenous components/environment demands by BP rhythms is modulated by the circadian-time-dependent responsiveness of biological oscillators and their neuroendocrine effectors. This knowledge contributes to a better understanding of the pathophysiology of abnormalities of the 24-h BP pattern and level and their correction through circadian rhythm-based chronotherapeutic strategies. (Author correspondence: prf@unife.it)

Pulmonary Hypertension in Dialysis Patients: A Cross-Sectional Italian Study

Introduction. Pulmonary hypertension (PHT) is an independent predictor of mortality. The aim of this study was to relate pulmonary arterial pressure (PAP) to the cardiovascular status of dialysis patients. Methods. 27 peritoneal dialysis (PD) and 29 haemodialysis (HD) patients (60 ± 13 years, 37 males, dialysis vintage was 40 ± 48 months) had PAP measured by echocardiography. Clinical and laboratory data of the patients were recorded. Results. PHT (PAP > 35 mmHg) was detected in 22 patients (39%; PAP 42 ± 6 mmHg) and was diagnosed in 18.5% of PD patients and 58.6% of HD patients (P = .0021). The group of subjects with PH had higher dialysis vintage (63 ± 60 versus 27 ± 32 months, P = .016), interdialytic weight gain (2.1 ± 1 versus 1.3 ± 0.9 Kg, P = .016), lower diastolic blood pressure (73 ± 12 versus 80 ± 8 mmHg, P = .01) and ejection fraction (54 ± 13 versus 60 ± 7%, P = .021) than the patients with normal PAP. PAP was correlated positively with diastolic left ventricular volume (r = 0.32, P = .013) and negatively with ejection fraction (r = −0.54, P < .0001). PHT was independently associated with dialysis vintage (OR 1.022, 95% CI 1.002–1.041, P = .029) and diastolic blood pressure (OR 0.861, 95% CI 0.766–0.967, P = .011). Conclusions. PHT is frequent in dialysis patients, it appears to be a late complication of HD treatment, mainly related to cardiac performance and cardiovascular disease history.

Twenty-Four-Hour Patterns in Occurrence and Pathophysiology of Acute Cardiovascular Events and Ischemic Heart Disease

The scientific literature clearly establishes the occurrence of cardiovascular (CV) accidents and myocardial ischemic episodes is unevenly distributed during the 24 h. Such temporal patterns result from corresponding temporal variation in pathophysiologic mechanisms and cyclic environmental triggers that elicit the onset of clinical events. Moreover, both the pharmacokinetics and pharmacodynamics of many, though not all, CV medications have been shown to be influenced by the circadian time of their administration, even though further studies are necessary to better clarify the mechanisms of such influence on different drug classes, drug molecules, and pharmaceutical preparations. Twenty-four-hour rhythmic organization of CV functions is such that defense mechanisms against acute events are incapable of providing the same degree of protection during the day and night. Instead, temporal gates of excessive susceptibility exist, particularly in the morning and to a lesser extent evening (in diurnally active persons), to aggressive mechanisms through which overt clinical manifestations may be triggered. When peak levels of critical physiologic variables, such as blood pressure (BP), heart rate (HR), rate pressure product (systolic BP × HR, surrogate measure of myocardial oxygen demand), sympathetic activation, and plasma levels of endogenous vasoconstricting substances, are aligned together at the same circadian time, the risk of acute events becomes significantly elevated such that even relatively minor and usually harmless physical and mental stress and environmental phenomena can precipitate dramatic life-threatening clinical manifestations. Hence, the delivery of CV medications needs to be synchronized in time, i.e., circadian time, in proportion to need as determined by established temporal patterns in risk of CV events, and in a manner that averts or minimizes undesired side effects. (Author correspondence: prf@unife.it)

Seasonal and Weekly Patterns of Occurrence of Acute Cardiovascular Diseases: Does a Gender Difference Exist?

BACKGROUND Cardiovascular (CV) disease is the leading cause of death in women. It is known that acute CV events exhibit temporal patterns of onset, that is, seasonal and weekly. We aimed to verify whether such patterns show differences by gender. METHODS We analyzed cumulative data from our previous studies dealing with hospital admissions for CV events, such as acute myocardial infarction (AMI), stroke, transient ischemic attack (TIA), aortic diseases (AD), and pulmonary embolism (PE), in the region Emilia-Romagna (RER) of Italy (ICDM9-CM codes, years 1998?2006). Total population and subgroups by gender (percentage of monthly and daily events) were tested for uniformity with the chi-square test, and a chronobiologic method was applied to monthly percentage of data for seasonal rhythmic analysis. RESULTS Season: We considered 130,693 patients (45.1% women): 64,191 AMI, 43,642 TIA, 4,615 AD, 19,425 PE. The monthly and seasonal distribution showed respective peaks in January and in winter, with no differences by gender. Day-of-week: We considered 168,921 patients (45.6% women): 64,191 AMI, 56,453 stroke, 43,642 TIA, 4,615 AD. The weekly distribution showed a peak on Monday, with no differences by gender. A multivariate regression logistic analysis, including in the model either major CV risk factors (hypertension, dyslipidemia, diabetes mellitus) and subgroups by age, did not find any difference in the temporal distribution of events in women and men. CONCLUSIONS The seasonal and day-of-week distribution of occurrence of CV events seems to be independent of gender.

Cocaine and Acute Vascular Diseases

Cocaine is one of the most widely used drugs of abuse. Chest pain is the most common side effect requiring emergency visits after cocaine use. Vasoconstriction and platelet activation are the main effects of cocaine in the vasculature. In this brief review, we consider the most important clinical effects of cocaine abuse on the heart, brain and kidney. Symptoms related to cocaine toxicity such as myocardial infarction, congestive heart failure, arrhythmias, aortic dissection, stroke, renal failure, are similar to the clinical picture of atherosclerotic vascular damage, even if the age of cocaine abusers is usually in the second and third decades. Clinicians (especially emergency department physicians) should consider substance abuse among the differential diagnosis of chest pain in young people.

Estimation of renal function in patients with eating disorders

BACKGROUND Renal function could be evaluated with different equations such as Cockcroft-Gault formula (C-G), Mayo Clinic Quadratic (MAYO) and four MDRD variables. Clinical application of different formulae in conditions with severe energy restriction or in obese subjects is still a matter of investigation. METHOD Renal function of 55 anorexia nervosa (AN) and 44 bulimia nervosa (BN) patients was evaluated with C-G formula for creatinine clearance calculation, and glomerular filtration rate (GFR) was estimated with MAYO and MDRD equations. RESULTS BN group was older and had higher weight, body mass index (BMI), body surface area than AN subjects; however, their mean BMI was in the normal range. AN group had better renal function than BN one when it was evaluated with MAYO and MDRD; on the contrary, it was worse when it was calculated with C-G. The results obtained from the three formulae were poorly correlated and Bland-Altman analysis confirmed that the results of the three formulae were not in agreement. DISCUSSION C-G is inaccurate when it is applied to obese or cachectic subjects. MDRD underestimates renal function in normal-high GFR. MAYO seems to be a good alternative to the other equations leading to correct classification of patients; therefore, it should be used to diagnose eating disorder subjects as renal insufficient.

Outcomes of weekend versus weekday admission for acute aortic dissection or rupture: A retrospective study on the Italian National Hospital Database

rupture: A retrospective study on the Italian National Hospital Database M. Gallerani ⁎, S. Volpato , B. Boari , M. Pala , A. De Giorgi , F. Fabbian , V. Gasbarro , E. Bossone , K.A. Eagle , F. Carle , R. Manfredini h a Department of Internal Medicine, Hospital of Ferrara, Italy b Section of Internal Medicine, Gerontology and Clinical Nutrition, University of Ferrara, Italy c Clinica Medica, Department of Medical Sciences, University of Ferrara, Italy d Vascular Surgery Unit, University of Ferrara, Italy e Cardiology Division, Cava de Tirreni and Amalfi Coast Hospital, University of Salerno, Italy f University of Michigan Cardiovascular Center, Ann Arbor, MI, USA g Interdepartmental Center for Biostatistical Epidemiology and Medical Informatics, Politecnica University of Marche, Italy h Clinica Medica, Department of Medical Sciences and Vascular Diseases Center, University of Ferrara, Italy

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

BackgroundEarly 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.MethodsWe 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.ResultsOut 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.ConclusionsComorbid patients are at higher risk for 30-day readmission. Reduction of LOS, especially in elderly subjects, could increase early rehospitalization rates.

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.

Clinical features of cardio-renal syndrome in a cohort of consecutive patients admitted to an internal medicine ward.

Introduction: Cardiorenal syndrome (CRS) is a disorder of the heart and kidney whereby interactions between the 2 organs can occur. We recorded the clinical features of CRS in patients consecutively admitted to an Internal Medicine ward. Patients and Methods: We retrospectively analyzed the anthropometric, history, clinical, biochemical and treatment characteristics in 438 out of 2,998 subjects (14.6%) admitted to our unit (from June 2007 to December 2009), diagnosed with CRS, according to Acute Dialysis Quality Initiative (ADQI) recommendations. Estimated glomerular filtration (eGFR) was calculated using several equations: MDRD (Modification of Diet in Renal Disease; 2 variations GFRMDRD186, GFRMDRD175), Mayo, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Cockroft-Gault. Results: Mean age was 80±8 years, 222 (50.6%) were males, 321 (73.2%) were smokers, 229 (52.2%) were diabetic, 207 (47.2%) had a history of acute myocardial infarction, 167 (38.1%) had angina, 135 (30.8%) were affected by cerebrovascular disease, 339 (77.3%) had peripheral arterial disease. CRS was type 1 in 211 cases (48.2%), type 2 in 96 (21.9%), type 3 in 88 (20.1%), type 4 in 29 (6.6%) and type 5 in 14 (3.2%). eGFR, calculated by different formulae, ranged between 31 and 36 ml/min/1.73 m2. GFR was lower in CRS type 3 than in the other types, and the values ranged between 24 and 27 ml/min/1.73 m2. Mean hospital length-of-stay (LOS) was 9.8±6.3 days. Diuretics were the most prescribed medication (78.7%); only 5 patients underwent haemodialysis. Conclusions: CRS is common, especially in the elderly. CRS Type 1 was the prevalent subset and patients had stage 3-4 renal insufficiency. Results obtained from the GFR equations were similar although the Mayo equation tended to overestimate the eGFR.