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

Consistency and accuracy of the Medical Subject Headings® thesaurus for electronic indexing and retrieval of chronobiologic references

none1The aim of this study was to investigate the reliability of the National Library of Medicine (NLM)'s Medical Subject Headings((R)) (MeSH) thesaurus for electronic indexing and retrieval of published chronobiologic papers. A sample set of 228 recent chronobiologic references was downloaded from the MEDLINE((R))'s database together with all MeSH entries associated with them. The following descriptors were analyzed among the headings of obvious chronobiologic relevance: chronobiology, chronobiology disorders, biological clocks, circadian rhythm, chronotherapy, drug administration schedule, periodicity, seasons, sleep disorders/circadian rhythm, and time factors. A comparison was made between the number of references identified by each heading and the number of articles actually pertinent to the same heading (as ascertained after reading each article of the sample set). This made possible an assessment of consistency (retrieved number not less than actual number) and accuracy (retrieved number not greater than actual number) of the usage of each MeSH entry. By reading each article, it was also possible to identify common chronobiologic concepts not yet associated with specific MeSH headings. In the preselected set of chronobiologic references, seasons identified all articles pertinent to seasonal variations and rhythms. However, chronobiology disorders missed 97.6% of its pertinent articles; periodicity, 95.2%; chronobiology, 87.7%; chronotherapy, 70%; time factors, 62.3%; and sleep disorders/circadian rhythm, 47.4%. Drug administration schedule missed 40% of the chronotherapeutic articles and identified 15% of the chronopharmacologic articles; biological clocks missed 24.1% of its pertinent articles and wrongly identified 8.3% of the retrieved articles; and circadian rhythm missed 2.7% of all circadian studies and wrongly identified 8.2% of the articles it retrieved. When used to search chronobiologic articles in the entire MEDLINE database, drug administration schedule, seasons, and time factors appeared to lack sufficient specificity to produce accurate results. Some common chronobiologic concepts were found not to be associated with any specific MeSH heading, namely, chronoepidemiology, chronopharmacology, chronotoxicology, chronotype, entrainment, and masking. For common chronobiologic concepts and definitions, the use of available MeSH headings appears to often yield inconsistent and inaccurate results; moreover, the MeSH thesaurus remains incomplete.openF. PortaluppiPortaluppi, Francesc

Time-dependent structure and control of arterial blood pressure - Closing remarks

Arterial blood pressure is under a complex neuro-endocrine regulation. The homeostatic vision of such regulation is largely incomplete and needs to be revised according to its temporal structure. The contributions reported here shed new light in this respect

Chronobiology and chronotherapy of ischemic heart disease

none2The occurrence of the clinical manifestations of ischemic heart disease (IHD)--myocardial ischemia and angina pectoris, acute myocardial infarction, and sudden cardiac death--is unevenly distributed during the 24 h with greater than expected events during the initial hours of the daily activity span and in the late afternoon or early evening. Such temporal patterns result from circadian rhythms in pathophysiological mechanisms plus cyclic environmental stressors that trigger ischemic events. Both the pharmacokinetics (PK) and pharmacodynamics (PD) of many, though not all, anti-ischemic oral nitrate, calcium channel blocker, and beta-adrenoceptor antagonist medications have been shown to be influenced by the circadian time of their administration. The requirement for preventive and therapeutic interventions varies predictably during the 24 h, and thus therapeutic strategies should also be tailored accordingly to optimize outcomes. During the past decade, two first generation calcium channel blocker chronotherapies have been developed, trialed, and marketed in North America for the improved treatment of IHD. Nonetheless, there has been relatively little investigation of the administration-time (circadian rhythm) dependencies of the PK and PD of conventional anti-ischemic medications, and there has been little progress in the development of new generation IHD chronotherapies. Available epidemiologic, pharmacologic, and clinico-therapeutic evidence demonstrates how the chronobiologic approach to IHD can contribute new insight and opportunities to improve drug design and drug delivery to enhance therapeutic outcomes.openF. Portaluppi; B. LemmerPortaluppi, Francesco; B., Lemme

Perspectives on the chronotherapy of hypertension based on the results of the MAPEC study

Appreciation of chronotherapy in hypertension continues to lag, despite clear demonstrations by many studies of (i) clinically relevant dosing-time differences of the beneficial and adverse effects of most blood pressure (BP) medications and (ii) significant association between reduced sleep-time BP decline of non-dippers and their heightened risk of cardiovascular disease (CVD). The Syst-Eur and HOPE outcome trials showed evening administration of nitrendipine and ramipril in these respective studies impacts sleep-time BP, converting the 24-h BP pattern to a more dipper one and in the HOPE study decreasing CVD risk. The CONVINCE study intended to compare BP control and CVD protection afforded by conventional β-blocker and diuretic medications versus a special drug-delivery verapamil formulation as a bedtime hypertension chronotherapy; however, the trial was terminated prematurely, not based on inadequate performance of the chronotherapy but on a corporate business decision. The just completed MAPEC study is the first trial specifically designed to prospectively test the hypothesis that bedtime administration of ≥1 conventional medications exerts better BP control and CVD risk reduction than the traditional approach of scheduling all medications in the morning. The results of this 5.6-yr median follow-up study establish that bedtime chronotherapy more effectively improves BP control, better decreases prevalence of non-dipping, and, most importantly, best reduces CVD morbidity and mortality. This chronotherapeutic approach to hypertension is justified by the fact that BP is usually lowest at night as is sodium excretion, but when sodium intake is excessive or its daytime excretion hampered, nocturnal BP is adjusted higher, to a level required for compensation overnight, via the pressure/natriuresis mechanism, resulting in non-dipping 24-h BP patterning. In diurnally active persons, the entire circadian BP pattern may be reset to a lower mean level and to a "more normal" day-night variation, simply by enhancing natriuresis during the night-the time-of-day when it can be most effective. A modification as simple and inexpensive as switching ≥1 hypertension medications from morning to evening may be all that is needed to normalize nighttime BP, exerting an effect exactly like sodium restriction. Current clinical concepts such as "normotensive non-dipper" (with higher CVD risk than a hypertensive dipper), broad recommendation of pharmacotherapy with exclusively high "smoothness index" medications (without attention to individual patient needs defined by the features of the 24-h BP pattern), and reliance upon static daytime diagnostic BP thresholds based solely on single office cuff assessment necessitate urgent reconsideration

Time-Dependent Structure and Control of Arterial Blood Pressure

none2Time-Dependent Structure and Control of Arterial Blood Pressure: Proceedings of a conference held in Ferrara, Italy, September 10-12, 1995.noneF. Portaluppi; M.H. SmolenskyPortaluppi, Francesco; M. H., Smolensk

Circadian rhythmic and environmental determinants of 24-hour blood pressure regulation in normal and hypertensive conditions

none2The biology of human beings is not constant during the 24 hours, menstrual cycle, and year as inferred by the concept of homeostasis. Instead, most of life's functions vary predictably and often dramatically over these and other time periods. Circadian rhythms, in particular, are of great importance to clinical medicine in general (565) and to CV medicine in particular. In this chapter, we discussed in great detail the 24-hour patterns of BP, HR and other CV hemodynamics in normal and hypertensive states. These patterns arise from circadian rhythms in neuroendocrine and other functions plus day-night differences in physical activity, mental strain, and posture. In hypertensive patients at risk to CV events, the staging of the peak and trough of these critical circadian rhythms gives rise to an increased vulnerability to angina, myocardial infarct, sudden cardiac death, and stroke in the morning when environmental triggers of CV events tend to be most intense. Not only does the vulnerability to myocardial infarct vary during the 24 hours, but so does its clinical course (566). Symptom onset between 6.00h and noon is associated with greatest infarct size, whereas an onset time between midnight and 6.00h is associated with significantly lower risk of circulatory arrests from ventricular arrhythmias (567). Moreover, the circadian-time-dependent occurrence of myocardial infarction is likely to affect the success of thrombolysis, which has been shown to be less in patients who have a morning onset (568). Finally, the body’s biological time structure can also exert significant influence on the pharmacokinetics and effects of antihypertensive and other medications used to treat hypertensive and other CV conditions. This will be discussed in depth in another chapter of this volume. Nonetheless, the prominent circadian patterns in BP, myocardial oxygen demand, coagulation and CV events bring to fore the concept of chronotherapeutics — medications which proportion their concentration during the 24 hours in synchrony with day-night differences in the biological requirement for therapy. In the United States two verapamil chronotherapies are now approved by the Food and Drug Administration. One is approved for the treatment of angina pectoris and both are approved for the treatment of hypertension. These chronotherapies have been shown to be effective in attenuating the rapid rise of BP in morning and elevated level during daytime activity without inducing super-dipping of BP during sleep. Nonetheless, it is not yet known whether they afford primary protection against CV morbidity and morality in the long term. The answer to this question must await the completion of the CONVINCE trial that entails the comparison of conventional equal-interval, equal-dose, ß-blocker and diuretic therapy versus verapamil chronotherapy dosed once daily in the evening (569).openF. Portaluppi; M.H. SmolenskyPortaluppi, Francesco; M. H., Smolensk

Biodisponibilità e digitale

Messa a punto delle problematiche relative alla biodisponibilità della digitale e alle sue conseguenze clinico-terapeutich

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 one's 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