[Hereditary hemorragic telangiectasia: the state of art]. / Teleangectasia emorragica ereditaria: stato dell'arte.

Hereditary Hemorrhagic Telangiectasia (HHT) or Rendu-Osler-Weber syndrome, is a multisystemic vascular dysplasia. The disease is transmitted as a dominant autosomic character. The Hereditary Hemorrhagic Telangiectasia is differentiated in two subclasses: (1) HHT1, which is caused by mutation of ENG gene. This gene is localized on long arm of chromosome 9: (2) HHT2, which is caused by mutation of ALK-1 gene. This gene is located on long arm of chromosome 12. These two genes codify for two receptorial proteins: the endoglin and the activin-like protein 1; these proteins belong to receptorial superfamily of TGF-beta, which is involved in vascular remodelling and angiogenesis. Clinically, the consequences of these mutations are represented by the formation of cutaneous and/or mucous telangiectases and artero-venous fistulas. In both cases histological alteration is the same: extremely ectatic venules with numerous layers of myocytes around them. Arterioles communicate with venules directly without a capillary filter. Essentially, telangiectases manifest themselves with hemorrhages, while more common consequences of fistulas are secondary to formation of shunts with a possible thromboembolism; that is particularly serious in case of pulmonary artero-venous malformations. In 2000. Shovlin published 4 diagnostic criteria (criteria of Curaçao): (1) spontaneous and recurrent epistaxis; (2) multiple telangiectases; (3) visceral artero-venous malformations; (4) familiarity for HHT. Actually there is no possibility for a genetic therapy of HHT. Therefore, the therapeutic efforts are turned to control of symptoms and to the prevention of complications.

Oxidative-stress-mediated arterial dysfunction in patients with peripheral arterial disease.

AIMS: To investigate the existence of a relationship among flow-mediated dilation (FMD), nitric oxide (NO), and oxidative stress in patients with peripheral arterial disease (PAD), and to assess if the administration of an antioxidant was able to improve arterial dilatation. METHODS AND RESULTS: We performed a cross-sectional study comparing FMD, 8-Hydroxy-2-deoxy-2-deoxyguanosine (8-OHdG), a marker of oxidative stress, and nitrite/nitrate (NOx) serum levels in a population of 25 PAD patients and 40 controls. In the second part of the study, 21 PAD patients were randomly allocated to a treatment sequence of 7 days of i.v. infusion of placebo or 6 g/day propionyl-L-carnitine (PLC) in a cross-over design. Compared with controls, patients with PAD had enhanced 8-OHdG serum levels (2.4 +/- 1.2 vs. 4.24 +/- 3.11 ng/mL; P < 0.001), reduced NOx (17.02 +/- 6.11 vs. 11.28 +/- 6.02 microM; P < 0.001), and lowered FMD (10.34 +/- 2.14 vs. 6.69 +/- 2.95; P < 0.001). PLC infusion was associated with an increase of FMD [from 6.6 +/- 0.6 to 11.1 +/- 1.2% (mean +/- SE), P = 0.004] and NOx (from 14.5 +/- 1.4 to 17.1 +/- 1.2 microM; +18%, P = 0.012) and a decrease of 8-OHdG (from 3.62 +/- 0.37 to 2.64 +/- 0.32 ng/mL; -27%, P < 0.001). No changes were observed after placebo treatment. CONCLUSION: This study shows that in PAD patients, oxidative stress is implicated in determining reduced FMD.

[Therapy of dyslipidemia in post-infarction: state of the art]. / Terapia delle dislipidemie nel post-infarto: stato dell'arte.

Between the risks factors involved in the atherogenesis LDL-cholesterol is determinant because highly associated to cardiovascular events. The primary target for the prevention of coronary diseases is a reduction of LDL-cholesterol because that reduces the cardiovascular mortality and the total mortality. The NCEP ATP III 2004 guide-lines propose as therapeutic target for the high-risk patients the reduction of plasma levels of LDL-cholesterol under 100 mg/dl and according to new trials under 70 mg/dl. The dyslipidaemia treatments are based on two approaches, i.e., the therapeutic lifestyle change and the pharmacological therapy. The available drugs are statins, fibrates, anion exchange resins, nicotinic acid. In the acute coronary syndrome patients is desirable to start immediately a therapy with statins since the hospital phase and direct the treatment to aggressive therapy. Unfortunately, the statin doses used in the most secondary prevention trials allow to get LDL-cholesterol under 100 mg/dl in the only half high-risk patients. The innovative therapeutic approach to hypercholesterolemia today is based on a double inhibition of cholesterol synthesis and absorption combining a statin with ezetimibe.

New aldosteron receptor inhibitors in heart failure.

This report summarizes the new therapeutic approaches in post-ischaemic heart failure given the important sanitary and socioeconomic impact resulting from the clinical management of this syndrome. Ventricular remodeling, causing changes to left ventricular anatomy and function, is the major cause of heart dysfunction. The physio-pathological role of the renin-angiotensin-aldosterone system has emerged from experimental studies and has been confirmed by the efficacy of ACE-inhibition. Although treatment with spironolactone (a non selective aldosterone antagonist) significantly reduces both the hospitalization and the mortality of NYHA III patients, this compound has important side effects. In this review we examine the efficacy of eplerenone, a new aldosterone receptor antagonist, with a more selective activity with respect to spironolactone. Several studies versus placebo have demonstrated that this molecule, alone or in combination with anti-hypertensive drugs, is very effective in left ventricular hypertrophy and in post-ischaemic heart failure treatment. In particular, we will consider the EPHESUS as the most important study both for the size of patient group and for the experimental plan. Finally, as regards the culture and experience of single physicians, a simple flow chart of the therapy of post-ischaemic heart failure is proposed.

Cortisol circadian rhythm and 24-hour Holter arterial pressure in OSAS patients.

Obstructive sleep apnea syndrome (OSAS) is a syndrome in which the principal symptom is apnea during sleep. Hypoxia in OSAS is a stress condition, which when prolonged in time, could alter hypothalamo-hypophysial-suprarenal control and the cortisol cicadian rhythm. We studied 28 patients with OSAS (30-60 years old), 20 female and 8 male. We calculated the OSAS class according to the Simmons classification. Twenty of the 28 patients maintained unmodified cortisol circadian rhythms, while 8 had cortisol levels more elevated in late and nocturnal hours. Holter monitoring showed arterial hypertension in 8 of the 28 patients (the same patients with cortisol circadian rhythm alteration). Our data seem to indicate that when the OSAS patients lack cortisol circadian rhythm they are having arterial hypertension.

Increased thrombin generation and circulating levels of tumour necrosis factor-alpha in patients with chronic Helicobacter pylori-positive gastritis.

BACKGROUND: Conflicting data have been reported concerning the relationship between Helicobacter pylori infection and coronary heart disease. AIM: To evaluate clotting system activation and plasma levels of tumour necrosis factor-alpha, a procoagulant cytokine, in patients with H. pylori-positive and -negative gastritis. METHODS: Three groups of patients were identified: 38 with H. pylori-positive gastritis, 18 with H. pylori-negative gastritis, and 40 H. pylori-negative controls with normal gastric mucosa. Plasma levels of prothrombin fragment 1 + 2 (F1 + 2) and tumour necrosis factor-alpha were assayed. Patients were also controlled after 2 and 6 months following standard H. pylori eradication treatment. RESULTS: At baseline, fragment 1 + 2 and tumour necrosis factor-alpha levels in H. pylori-positive patients were significantly higher than those in H. pylori-negative patients with gastritis (P < 0.05 and P < 0.01, respectively). After H. pylori eradication, fragment 1 + 2 and tumour necrosis factor-alpha levels showed a significant decrease at 2 months (P = 0.03 and P = 0.02, respectively) and a further reduction at 6 months, reaching levels observed in H. pylori-negative patients and controls. CONCLUSIONS: The increase thrombin generation rate and the correlation of plasma fragment 1 + 2 and tumour necrosis factor-alpha levels in H. pylori-positive patients suggest a role for inflammation in mediating the relationship between H. pylori infection and activation of the clotting system.

[Evaluation of C3c, C4 and C1-esterase inhibitor (C1-INH) during unstable angina]. / Valutazione del C3c, del C4 e dell'inibitore della C1q-esterasi (C1-INH) in corso di angina instabile.

BACKGROUND: The complement system plays an important role in the physiopathology of acute myocardial infarction (AMI) taking part in myocardial damage and reperfusion injury. The aim of this study is to investigate the plasmatic levels of some complement components (C3c, C4 and C1-INH) during unstable angina (C1-INH) and their different concentrations in relation to the different myocardial areas affected by ischemia. METHODS: The plasmatic levels of C1-INH, C3c and c4 in 30 patients affected by unstable angina, and those of 22 clinically healthy subjects (control group) were evaluated (Nefelometer Behering). The patients were divided into four groups according to the different myocardial area affected by ischemia (anterior, antero-lateral, lateral or inferior ischemia), RESULTS: No statistically significant differences were found in plasmatic levels of C3c, C4 and C1-INH between the group of patients and the control group. There is a statistically significant difference between the C1-INH levels of the patients with inferior ischemia and the plasmatic concentrations of the whole patients' group (p<0,01), the control group (p<0,01) and the group of patients with lateral ischemia (p<0,02). CONCLUSIONS: There seems to be a different activation of the complement system during unstable angina, in relation to the different myocardial area affected by ischemia.

Prevalence of human herpesvirus (HHV)-8 infection among carriers of cardiovascular disease.

Infectious agents, such as herpesviruses, have been hypothesized to be involved in development of atheromatous plaque. The study aim was to evaluate the possibility that HHV-8 infection could be an additional risk factor for the establishment of cardiovascular disease. HHV-8 seroprevalence was determined by immunofluorescence in a population of cardiovascular disease patients (n=50) as compared to an age- and sex-matched group of control subjects (n=47); HHV-8 genome was detected in DNA extracted from circulating PBMC and from atheromatous lesions by PCR with primers specific for the minor virus capsid gene (ORF 26). The seroprevalence of HHV-8 was significantly increased in the patients as compared to the control population, while the presence of HHV-8 genome was observed in PBMC from 2 patients and 1 control. Virus-specific DNA was found in 2 out of 4 atheromatous plaques. The higher seroprevalence in patients suffering from vascular diseases as compared to age-and sex-matched controls suggests that HHV-8 infection could be an additional risk factor for the establishment of cardiovascular disease, although the data on the persistence of viral DNA in PBMC or in the arterial lesions are too exiguous to definitively support this hypothesis. More extensive studies are needed to define the exact role of HHV-8 infection in the establishment and progression of atheromatous lesions.

ET-1 levels in cardioischemic patients undergoing atrial pacing.

Atrial pacing (AP) procedure was carried out in 11 cardioischemic patients to reproduce tachycardia-induced myocardial ischemia. Six control subjects underwent the same procedure until the maximum pacing rate was reached. During the procedure, endothelin-1 (ET-1) and plasma lactate levels were measured in the coronary sinus and in the aortic root. In all the patients, atrial pacing provoked electrocardiographic signs and metabolic evidence of myocardial ischemia and a significant decrease (p<0.001) in left ventricular ejection fraction. At AP-induced ischemia, coronary sinus (17.31 +/- 4.20 pg/mL) and arterial (9.60 +/- 3.31 pg/mL) ET-1 plasma levels were significantly different (p<0.001) in the patients. On the contrary, at maximum pacing rate, no significant difference (p=0.186) emerged between coronary sinus (9.72 +/- 1.09 pg/mL) and arterial (8.95 +/- 0.75 pg/mL) plasma ET-1 levels in the control group. These results suggest that, in cardioischemic patients, tachycardia can induce the coronary endothelium to release significant amounts of ET-1.

[Circadian variations in the onset of acute myocardial infarction]. / Variazione circadiana dell'insorgenza dell'infarto miocardico acuto.

BACKGROUND: Several studies have observed a circadian pattern in the onset of acute myocardial infarction (AMI), with a peak incidence in the morning hours. It has been suggested that different circadian rhythms may exist in various subgroups of patients. METHODS: This study sought to determine whether the circadian incidence of AMI varied by sex, age, cardiovascular risk factors, previous history of ischemic accidents, the site of AMI, and the short-term outcome. These possibilities were examined in a population of 597 consecutive patients with AMI, admitted to the coronary care unit. 548 patients have been included in the study, 442 men (80.6%) and 106 women (19.4 %); mean age 64.5 years. RESULTS: A peak incidence of AMI was found between 06.01 a.m. and 12.00 a.m. (32.4%; p<0.0002). This peak was present in patients 65 years old (33.2%; p<0.005), in men (32.5%; p<0.0002) but not in women, in smokers (32.1%; p<0.0005) and in those that did not smoke (33.0%; p<0.04), in patients with hypercholesterolemia (34.9%; p<0.006 ) and without hypercholesterolemia (31.1%; p<0.03). A circadian rhythm was absent in diabetics, hypertensives and in patients with a history of previous cardiovascular events. Regarding the site of AMI, inferior AMI showed an increased incidence between 06.01 a.m. and 12.00 a.m. (36.2%; p<0.002), while the circadian distribution of anterior AMI, as well as non-Q wave AMI, did not show this incidence. Finally, higher mortality was reported in patients with an AMI onset at night (22.3%). CONCLUSIONS: These results give further clues in understanding the external and inner factors acting in the morning hours as triggers for AMI.

Angiotensin-converting-enzyme inhibitor administration must be monitored for serum amylase and lipase in order to prevent an acute pancreatitis: a case report.

Some clinical cases published in literature show that angiotensin-converting enzyme (ACE)-inhibitor administration may cause acute pancreatitis. In this work, the authors report a case of a patient affected by hypertension. Upon admission, the authors started antihypertensive therapy using captopril, which caused an important amylase and lipase rise within 13 days. When the ACE-inhibitor therapy was stopped, a rapid decrease of the serum enzyme was observed within 3 days. The high levels of serum amylase and lipase were linked to neutrophilia but were not associated with relevant symptomatic findings or features of pancreatopathy. The absence of the usual conditions that may cause pancreatitis, such as biliary stasis, hypercalcemia, or alcohol abuse, and the rapid decrease of serum enzyme levels after drug suspension suggested an ACE-inhibitor-induced pancreatitis. This is the first clinical report of an ACE-inhibitor-induced pancreatitis in which captopril administration was found after hospitalization. The drug suspension probably prevented other complications. This case report suggests that, when ACE-inhibitor administration is started, serum amylase and lipase should be monitored in order to prevent acute pancreatitis without waiting for clinical evidence of a pancreatopathy.

Met-enkephalin levels during PTCA-induced myocardial ischemia.

Met-enkephalin (Met-enk) has been demonstrated to modulate myocardial-ischemia mechanisms via the opioid receptors, but no studies are now available on Met-enk levels in the coronary circulation. In this experience Met-enk levels were evaluated in aortic root and in coronary sinus at baseline (T0), during PTCA induced transient ischemia (T1) and during reperfusion (T2). No significant differences were found at any time. Thus, it appears that there is no Met-enk extraction from the coronary circulation during provoked myocardial ischemia and no Met-enk release from the ischemic heart.

Further evidence against the implication of active cytomegalovirus infection in vascular atherosclerotic diseases.

The possible contribution of cytomegalovirus (CMV) to pathogenetic events associated with atherosclerotic lesion establishment and progression is still controversial. We evaluated the possibility that active ongoing CMV infection could be correlated to evolution of unstable atheromatous lesion, by analyzing patients suffering from unstable angina (n=61), acute myocardial infarction (n=43), stable angina (n=26) and peripheral arteriopathy (n=22) as compared to healthy subjects (n=30). Particularly, we assessed: past exposure to CMV by evaluating anti-CMV IgG antibodies; ongoing CMV infection by evaluating anti-CMV IgM antibodies and circulating interleukin (IL)-8 in serum; and CMV DNAemia in peripheral blood mononuclear cells (PBMC). Mean IgG values were significantly increased in patients from all groups, as compared to healthy subjects. CMV-specific IgM, as well as CMV DNAemia, were undetectable in both controls and patients. Circulating IL-8, significantly elevated in a group of individuals experiencing active CMV infection, was not significantly higher in cardiovascular disease patients, as compared to control subjects. These findings confirm previous evidence from the increased exposure to CMV infection in patients with atheromatous lesions. However, they provide further evidence against a direct implication of active systemic CMV infection in the pathogenesis of cardiovascular diseases, particularly those involving plaque instability.

Primary pulmonary hypertension in HIV patients: a systematic review.

The relationship between grade of pulmonary hypertension and factors associated with human immunodeficiency virus among patients with HIV infection is poorly documented. This report documents the most extensive attempt made thus far to determine whether a relationship exists between degree of pulmonary hypertension and the following conditions: HIV risk factor, degree of immunosuppression, presence or absence of AIDS, and presence or absence of liver cirrhosis. A retrospective study involving a search of the published literature on primary pulmonary hypertension among HIV cases from 1987 to 1998, using the Medline and Aidsline databases was conducted. Patients for whom secondary causes of pulmonary hypertension could be excluded were selected, and the following information for each was recorded: age, gender, risk factors for HIV infection, HIV disease stage according to the Centers for Disease Control, previous opportunistic and neoplastic diseases, CD4+ cell count (cells/L), presence or absence of liver cirrhosis, pulmonary systolic artery pressure level, and lung pathology specimens. Information about the patient's survival time was also recorded. Seventy-six patients were judged to have primary pulmonary hypertension and were included in the study. While no correlation was found between pulmonary systolic artery pressure level and CD4+ cell counts, a statistically significant difference was found between HIV-positive patients with and without AIDS as determined by the Centers for Disease Control criteria with regard to the degree of pulmonary hypertension, expressed as pulmonary systolic artery pressure level (85.4 +/- 17 mm Hg vs 71.8 +/- 15 mm Hg, p < 0.013). Although a higher PAPS was present in HIV cirrhotic patients, a statistically significant difference was not found between degree of pulmonary hypertension and evidence of hepatic cirrhosis (85 +/- 21 mm Hg vs 73.1 +/- 15 mm Hg, p < 0.062). Patients with AIDS and primary pulmonary hypertension present a higher degree of pulmonary hypertension than non-AIDS patients. Pulmonary hypertension associated with HIV seems to be related to a cytokine-related stimulation and proliferation of endothelium. High levels of cytokines present in AIDS patients can favor pulmonary hypertension, but the role of a host response to HIV--determined by one or more HLA subtypes--is suspected to enhance high cytokine production levels.

The role of met-enkephalin in silent myocardial ischemia in diabetic patients.

Met-enkephalin plasma levels were evaluated in 20 cardioischemic diabetic patients. All the patients had ECG ischemic signs. Ten patients with diabetic autonomic neuropathy, experienced no pain during myocarial ischemia. Met-enkephalin levels in the diabetic patients with silent myiocardial ischemia were significantly lower compared to those in the symptomatic patients. This demonstrates that the absence of myocardial ischemic pain in neuropathic diabetic patients is not accounted for by met-enkephalin action.

Mitral prolapse. A heart anomaly in a clinical neuroendocrine context.

Mitral valve prolapse was identified as a separate nosological entity by Barlow in 1963. A characteristic of this cardiac anomaly is blood reflux into the left atrium during the systole owing to the lack of adhesion between valve flaps. The presence of symptoms linked to neuroendocrine dysfunctions or to the autonomic nervous system lead to the onset of the pathology known as mitral valve prolapse syndrome (MVPs). It is usually diagnosed by chance in asymptomatic patients during routine tests. MVPs includes complex alterations to the neurovegetative system and a high clinical incidence of neuropsychiatric symptoms, like anxiety and panic attacks. A neuroendocrine mechanism thought to underlie panic attacks was recently proposed based on a biological model. In general, the cardiovascular anomaly manifested by patients with MVPs could be defined in neuroendocrine-constitutional terms.

A case of chronic adrenocortical insufficiency with iatrogenic anasarca.

The decrease in active hormones that characterizes chronic adrenal insufficiency results in hypovolemia. In some patients, residual adrenal function, mineralocorticoid therapy, and concomitant heart or liver failure, or both, can paradoxically provoke edema. The case report that follows describes a patient with iatrogenically induced anasarca resulting from the unhappy confluence of usually appropriate therapy and coexisting medical conditions.

Are elevated levels of soluble ICAM-1 a marker of chronic graft disease in heart transplant recipients?

Positivity for circulating intercellular adhesion molecule-1 (ICAM-1) in heart transplant recipients has been claimed to predict the development of coronary artery disease and risk of graft failure. Soluble ICAM-1 were evaluated in 32 heart transplant recipients. Five of these patients, who had undergone transplantation several years before, were positive for soluble ICAM-1 but did not present any clinical sign of graft rejection. Furthermore, although heart graft coronary disease was diagnosed in 15 of the 32 patients, they did not show significantly higher titres of soluble ICAM-1 compared to the remaining patients. These findings suggest that major caution is necessary when considering ICAM-1 positivity as a marker of graft disease.

Influence of thrombolytic therapy on inferior acute myocardial infarction with concomitant anterior ST segment depression.

The purposes of this study were to analyze the prognostic significance of precordial ST segment depression and to determine whether thrombolytic therapy is effective for all patients with inferior acute myocardial infarction (AMI) or whether there is a different effectiveness for patients with concomitant anterior ST segment depression persisting for 24 hours or longer. Medical charts of 176 patients were studied. On the basis of ECG the patients were subclassified into three groups according to the presence, persistence, or absence of significant ST segment depression: Group 1: anterior ST segment depression persisting for less than 24 hours (45.4%); Group 2: anterior ST segment depression persisting for more than 24 hours (17.6%); Group 3: no anterior ST segment depression (37%). Age, Killip class, peak creatine kinase, hospital deaths, left ventricular ejection fraction, regional wall motion score, postinfarction angina, and ventricular/supraventricular arrhythmia of all patients were studied. Parameters of the three groups were compared: worse results were found in group 1 and the worst in group 2. This result is independent of thrombolytic therapy. Finally, the same parameters of thrombolyzed and nonthrombolyzed groups were compared: no statistically significant difference was observed. Among thrombolyzed patients the number of those with ST depression lasting more than 24 hours is lower than in nonthrombolyzed patients. It can be assumed that thrombolytic therapy in inferior AMI determines a shifting of patients from a worse prognosis group (ST segment depression persisting for more than 24 hours) to a better prognosis group (ST segment depression persisting for less than 24 hours).