Autoantibodies against the endothelial receptor of protein C are associated with acute myocardial infarction in young women.

BACKGROUND: Acute myocardial infarction (AMI) is rare among young women. The search for unknown risk factors is warranted. Endothelial protein C receptor (EPCR) is largely present at the endothelial surface of large arteries. No studies about association of anti-EPCR autoantibodies (anti-EPCR) with AMI are available. METHODS: Plasma IgA, IgM and IgG anti-EPCR levels were measured by enzyme-linked immunosorbent assay in 165 women younger than 45 years who survived a first AMI and 165 healthy women, matched by age and geographical origin. RESULTS: Using the 90th percentile of IgA anti-EPCR in the control group, IgA anti-EPCR were independently associated with AMI after adjustment for cardiovascular risk factors (OR 5.1; 95% CI 1.7-15.6; P = 0.004). The risk apparently conferred by IgA anti-EPCR increased dose-dependently (P for trend =0.0002). IgM anti-EPCR were less consistently associated with AMI: a significant increase in the risk was found when women above the 90th percentile were compared with those in the lowest quartile (OR 3.6; 95% CI 1.2-11.5; P = 0.03). IgG anti-EPCR were similar in patients and controls. A total of 145 patients underwent coronary arteriography. IgA or IgM anti-EPCR were not different among patients with different degrees of atherosclerotic lesion (anova, P = 0.77 and 0.24, respectively). CONCLUSIONS: High levels of IgA and, to a lesser extent, IgM anti-EPCR, are associated with AMI in young women.

[The diagnostic and therapeutic procedures in pulmonary embolism: a survey in the Veneto Region]. / Iter diagnostici e terapeutici nell'embolia polmonare: inchiesta nella Regione Veneto.

BACKGROUND: Pulmonary embolism is one of the most frequent cardiopulmonary diseases, but it is often under- or misdiagnosed. In order to address this issue and to identify flow charts that are commonly used in pulmonary embolism diagnosis and treatment, 191 clinical wards of internal medicine, cardiology, geriatrics, pneumology and intensive care units, located in the Veneto Region, were surveyed. METHODS: An anonymous questionnaire was mailed to each ward in order to collect clinical diagnostic information on all pulmonary embolisms which occurred during 1993. Among the returned questionnaires, 114 (59.6%) had usable information for the analysis. RESULTS: The vast majority of participating centers reported in 1993 less than 10 pulmonary embolism events. No significant differences were observed between internal medicine, geriatrics, pneumology wards and intensive care units. The reported events, however, were slightly higher in the divisions of cardiology with an annual average of 12 events per center. First level diagnostic procedures, such as ECG, chest X-ray and arterial blood gas analysis were chosen and performed in all patients. Interestingly, Doppler echocardiography, which is often not included in official guidelines for pulmonary embolism diagnosis, was performed in 56% of the participating centers. On the contrary, ventilation-perfusion lung scanning, which is considered highly predictive in many diagnostic algorithms, was underutilized (35% perfusion scan, 20% ventilation scan). This underuse was probably due to technical and organizational difficulties. Pulmonary angiography, the most accurate procedure for the diagnosis of pulmonary embolism, was performed in 28% of the patients. During the acute phase, intravenous heparin was commonly used; 91% of patients received the infusion continuously, 4% intermittently. Thrombolysis was performed in 25% of the patients. The preferred drugs were recombinant tissue-plasminogen activator (67%), followed by urokinase (20%) and streptokinase (13%). To start thrombolytic therapy, 20% of the interviewed clinicians considered sufficient the evidence of clinical manifestations of pulmonary embolism confirmed by echocardiographic data. At discharge, prescription of oral anticoagulant drugs was common (78%) for at least 6 months (47%). Standardized procedures for the diagnosis and treatment of pulmonary embolism were already implemented in 13% of the participating centers. CONCLUSIONS: These data suggest a common effort to define unanimous conventional protocols in the management of pulmonary embolism. It should be underlined, however, that a particular attention to the clinical manifestations and a productive collaboration among clinicians with different expertise are required to improve the diagnosis and treatment of pulmonary embolism.

Pulmonary hypertension associated with human immunodeficiency virus infection. Report of two cases and review of the literature.

Recent reports have suggested a possible association between HIV-1 infection and "idiopathic" pulmonary hypertension (PH), but the pathogenetic role of the viral agent has not been fully defined yet. We report the cases of two white males positive for human immunodeficiency virus type 1 (HIV-1) who presented with clinical and hemodynamic diagnosis of pulmonary hypertension. They were heterosexual, non-hemophiliac, heroin abusers with no signs of clinical AIDS. Neither one of the patients had opportunistic lung infections or any other cause of secondary pulmonary hypertension. In one case, peculiar clinical and electrocardiographic features of PH were associated with signs of thrombotic thrombocytopenic purpura (TTP). The association between PH and HIV-1 infection might be explained by a severe alteration of pulmonary endothelial cell homeostasis secondary to HIV-1 viral infection.

Target organ damage and ambulatory blood pressure in stage I hypertension. The Hypertension and Ambulatory Recording Venetia Study.

According to recent international guidelines the decision on whether to treat young subjects during the early phase of hypertension should be based not only on their office blood pressure but also on their ambulatory blood pressure and whether target organ damage has occurred. Few data on the prevalence of hypertensive complications in young subjects with mild hypertension are available. In the Hypertension and Ambulatory Recording Venetia Study (HARVEST), a multicenter trial conducted in northeast Italy, the percentage of young borderline-to-mild hypertensive subjects with echocardiographic left ventricular hypertrophy was 4.5% and the percentage with concentric remodeling was 4%. Clear differences in cardiac size and geometric adjustment to ambulatory systolic pressure between the two sexes were found. The impact of blood pressure on the walls of the left ventricle and on the left ventricular mass was remarkable in women but weak in men. The assessment of left ventricular systolic function confirmed that many young mild hypertensive subjects have an increased ejective performance. The left ventricular contractility evaluated by midwall measurement was, however, found to be depressed in 9.2% of the HARVEST participants. Their left ventricular diastolic function was similar to that of 50 normotensive controls. The prevalence of microalbuminuria [albumin excretion rate (AER) > 30 mg/24 h) was 6.1%, only slightly higher than that found by other authors among normotensive subjects and much lower than that observed among patients with more severe hypertension. For our stage I hypertensives, however, the AER was correlated to the 24 h blood pressure with high statistical significance, whereas we found no relationship between the AER and left ventricular mass index either for all of the subjects taken together or for the men and women considered separately. The results suggest that renal and cardiac involvement do not occur in parallel during the initial phase of hypertension.

[Bolus thrombolysis in pulmonary embolism. Review of experimental and clinical data]. / La trombolisi in bolo nell'embolia polmonare. Rassegna di dati sperimentali e clinici.

Although heparin is the primary drug used to treat pulmonary embolism, its limits include poor prevention of recurrence, and slow and delayed normalization of hemodynamic parameters. Over the past decades, thrombolysis has proved to be the most rapid and effective therapy to normalize hemodynamic parameters and angiographic and scintigraphic indexes of obstruction. Studies conducted up to the present have not, however, demonstrated a significant advantage over heparin with respect to mortality. Moreover, thrombolytic drugs carry a greater risk of hemorrhage than heparin. Various experimental studies have demonstrated that the short-term administration of recombinant tissue plasminogen activator (rt-PA) is more effective and decreases risk of hemorrhage. To our knowledge, only a few uncontrolled clinical studies on bolus thrombolysis with urokinase have been done. Studies comparing a 0.6 mg/Kg bolus of intravenous rt-PA versus the infusion of 100 mg over 2 hours have given conflicting results. Of these, some have demonstrated that bolus administration is safer and more effective while others have provided nearly overlapping results regarding safety and the reduction of pulmonary resistances. One study reports higher mortality in a group receiving 0.6 mg/Kg bolus rt-PA. Until these questions are clarified, administration of thrombolytics in the following doses is advised: streptokinase bolus 250,000 U over 30 min + 100,000 U/hour for 24 hours; urokinase bolus 4400 U/Kg for 10 min + 4400 U/Kg/hour for 12-24 hours; rt-PA 100 mg for 2 hours.

Follow up after spontaneous coronary artery dissection: a report of five cases.

Five cases of spontaneous coronary artery dissection (SCAD) are reported, three in women and two in men (mean age 44 years; range 28-65), all of whom suffered a myocardial infarction. Common risk factors for coronary artery disease were present in the two men; in the female group one patient was taking an oral contraceptive, one was in the postpartum period, and the third was a smoker. Only the three women received intravenous alteplase and their ejection fraction was normal; both men had impaired left ventricular function. Two patients had SCAD of the left anterior descending coronary artery and three of the right coronary artery. Only the two men had angiographic features of coronary atherosclerotic involvement. No patients required surgical revascularisation or percutaneous transluminal coronary angioplasty. At a mean follow up of 27 months (range 6 to 40) all patients were alive and all but one were asymptomatic.

Response to orthostatic stress predicts office-daytime blood pressure difference, but not nocturnal blood pressure fall in mild essential hypertensives: results of the harvest trial.

1. The aim of the present study was to evaluate whether postural blood pressure (BP) change could predict office-day-time BP disparity and the nocturnal BP fall in young, mild essential hypertensives. We investigated 411 males aged between 18 and 45 years with never treated borderline to mild hypertension. BP was measured three times after a 5 min rest in the supine position and thereafter three times after 2 min of standing. The mean of six BP measurements obtained during two visits in the lying position was defined as office BP. 2. Twenty-four hour ambulatory BP monitoring was performed with either the A&D TM-2420 model 7 or the ICR Spacelabs 90207. BP values were averaged for day- and night-time periods. The nocturnal BP fall was defined as the difference between the average day- and night-time BP. 3. The standing-lying difference was significantly inversely correlated with the office-daytime difference for both systolic blood pressure (SBP) (r = -0.34, P < 0.001) and diastolic blood pressure (DBP) (r = -0.24, P < 0.001). These correlations did not change when the obese subjects (body mass index > 30 kg/m2) were excluded from the analysis. No significant correlation between standing-lying difference and nocturnal BP fall was found. 4. Our results indicate that white coat hypertension assessed as the office-daytime BP disparity is partially related (in a negative fashion) to the BP reaction to standing. The postural BP change does not predict nocturnal BP fall in young, mild essential hypertensives.

Ambulatory blood pressure in mild hypertensive women taking oral contraceptives. A case-control study.

The aim of the present study was to compare the ambulatory blood pressure levels in mild (stage 1) hypertensive women using oral contraceptives and respective values in nonusers of oral contraceptives with similar office blood pressure. The study group consisted of 24 mild hypertensive patients taking low dosage estrogen-progestogen oral contraceptives. Seventy women of similar age and body mass index who had never used oral contraceptives served as a control group. Both daytime and nighttime systolic blood pressure values were significantly higher in oral contraceptive users. There was an average 8.3 mm Hg difference (95% confidence interval, 3.0 to 13.7 mm Hg; P = .003) for the daytime and 6.1 mm Hg difference (95% confidence interval, 0.4 to 11.8 mm Hg; P = .04) for the nighttime. No significant differences in ambulatory diastolic blood pressure between the two groups were found. These data provide evidence that hypertensive oral contraceptive users with the same office blood pressure as that in hypertensive noncontraceptive users have a significantly higher ambulatory systolic blood pressure. Our results support the opinion that alternative methods of contraception should be considered for hypertensive women in place of oral contraceptives.

[Alcohol consumption, arterial pressure and metabolic parameters in a population of borderline hypertension subjects. The results of the HARVEST Multicenter Study. Hypertension and Ambulatory Recording Venetia Study]. / Consumo di alcol, pressione arteriosa e parametri metabolici in una popolazione di soggetti con ipertensione borderline. Risultati dello Studio Policentrico HARVEST.

In 544 borderline to mild hypertensive subjects (mean age 33.5 +/- 8.6 years) participating in the HARVEST trial the relationship between alcohol consumption, blood pressure levels and several clinical parameters was examined. Subjects were divided into 3 groups according to whether they did not drink (Group 1, n = 171) or their daily alcohol intake was < 50 g (Group 2, n = 184) or > 50 g (Group 3, n = 54). In the 409 men alcohol consumption was related to age (p < 0.0001), body weight (p < 0.05) and coffee consumption (p < 0.0001). Group 3 drinkers were also more sedentary than the 2 other groups (p < 0.05). Both office (p < 0.001) and 24-hour (p < 0.001) diastolic blood pressure were greater in the drinkers than in the non drinkers, while no difference was observed in systolic blood pressure. Twenty-four-hour heart rate was higher in Group 3, but urinary catecholamines were similar in the 3 groups of men. Blood glucose (p < 0.001), total cholesterol (p = 0.001) and triglyceride (p < 0.005) were related to alcohol consumption, while HDL-cholesterol was not different in the 3 groups. Albumin excretion rate and uricemia were also unrelated to alcohol intake. In the 135 women a similar alcohol-related trend was observed for office diastolic blood pressure and for the metabolic parameters. In conclusion, the results of the present study confirm the association between alcohol consumption and blood pressure levels, which was apparent also within a population of borderline to mild hypertensive subjects and stress the role of alcohol in determining an abnormality of the metabolic parameters.

Sudden cardiac arrest in a teenager as first manifestation of Takayasu's disease.

A 14-year-old girl was rescued from a sudden cardiac arrest at school. Aortography disclosed mild aortic root dilation with aortic valve incompetence and subocclusion of coronary ostia and left common carotid artery. An emergency aortocoronary bypass operation was undertaken, but the patient did not recover from cardiopulmonary bypass. Postmortem disclosed massive myocardial infarction. The microscopic feature of arterial involvement was consistent with giant cell Takayasu's arteritis. The abrupt clinical presentation in this teenager with coronary ostial subocclusion is very unusual.

PAIMS 2: alteplase combined with heparin versus heparin in the treatment of acute pulmonary embolism. Plasminogen activator Italian multicenter study 2.

BACKGROUND: The effect of alteplase versus heparin in pulmonary embolism has not been studied extensively with serial pulmonary angiograms. OBJECTIVES: The aim of this randomized, open trial was to evaluate the efficacy and safety of alteplase followed by heparin, versus heparin alone, in 36 patients with angiographically documented pulmonary embolism. METHODS: Twenty patients were allocated randomly to a 2-h infusion of alteplase (10 mg bolus, then 90 mg over 2 h) followed by heparin; the other 16 patients were given intravenous heparin at a continuous infusion rate of 1,750 IU/h. RESULTS: The vascular obstruction, assessed by the Miller index at pulmonary angiography, decreased significantly in alteplase-treated patients (p less than 0.01) from a baseline of 28.3 +/- 2.9 to a value of 24.8 +/- 5.2 2 h after the start of infusion; in the heparin group there was no change (from 25.3 +/- 5.3 to 25.2 +/- 5.4). Mean pulmonary artery pressure decreased significantly from a baseline of 30.2 +/- 7.8 mm Hg to 21.4 +/- 6.7 in the alteplase group and increased in the heparin group (from 22.3 +/- 10.5 to 24.8 +/- 11.2 mm Hg). For a subset of patients, lung scans were performed at baseline and on days 7 and 30. There were no differences between the two groups in the follow-up lung scans, but there were significant decreases from the baseline values. Bleeding occurred in 14 of 20 alteplase-treated patients and in 6 of 16 in the heparin group (p = NS). There were three major bleeding episodes in the alteplase group and two in the heparin group. Two patients died after fibrinolysis (one of acute renal failure after cardiac tamponade and one of cardiac arrest after cerebral hemorrhage) and one patient in the heparin group died of recurrent pulmonary embolism. CONCLUSIONS: Alteplase resulted in a greater and faster improvement of the angiographic and hemodynamic variables compared with heparin. However, the high frequency of bleeding observed with alteplase in this trial suggests that patients should be carefully selected before thrombolytic therapy is given.

[Treatment of unstable angina with dipyridamole combined with low doses of aspirin. A multicenter pilot double-blind controlled study]. / Trattamento dell'angina instabile con dipiridamolo associato a basse dosi di aspirina. Studio multicentrico pilota in doppio-cieco controllato.

In order to assess the usefulness of a combination of low-dose aspirin (25 mg b.i.d.) with dipyridamole (200 mg b.i.d.) in the prevention of major coronary events in patients with acute unstable angina, we performed a prospective, double-blind, placebo-controlled study involving 88 consecutive patients admitted to three Hospital Departments of Cardiology. The patients entered the study as soon as possible after hospital admission, and were treated and followed up to one year. There was no appreciable difference in side effects and adverse reactions between the treatment and control group. The incidence of cardiac death and/or nonfatal myocardial infarction during the whole period of observation was 14% (6/44) in the treatment group and 25% (11/44) in the placebo group by "intention-to-treat" analysis; 16% (4/25) and 32% (10/31), respectively, by "drug-efficacy" analysis (p = 0.21 by Fisher's exact test, non significant difference). However, when considering the only events occurred in the first month (2/44 in the treatment group and 9/44 in the placebo group, amounting to 4.5 and 20 percent, respectively), the combination of dipyridamole with low-dose aspirin reached a statistically significant protective effect (p = 0.04). The results of this pilot study provide strong evidence for a beneficial effect of the regimen tested in patients with acute unstable angina, at least in the first weeks of treatment, while at the same time suggesting a safe alternative for patients with contraindications to higher doses of aspirin.

[Peripartum cardiomyopathy: clinical, echocardiographic and biopsy aspects]. / Cardiomiopatia peripartum. Aspetti clinici, ecocardiografici e bioptici.

In order to characterize the features of peripartum cardiomyopathy, clinical, echocardiographic and right ventricular endomyocardial bioptic data obtained from 6 patients (pts) (age range: 34.1 +/- 5.5. yrs) who fulfilled peripartum cardiomyopathy diagnostic criteria, were analyzed. Five of these pts had clinical and non-invasive studies for a mean period of 41.6 +/- 59.6 months. All but one were multiparous. Five developed heart failure one month before delivery. Three patients had active myocarditis at endomyocardial biopsy and were treated with immunosuppressive therapy. At follow-up, 3 pts improved by two or three grades of the NYHA functional classification. All 3 showed a reduction in the left ventricular end diastolic diameter (from 3.9 +/- 0.4 to 3.4 +/- 0.3 cm/m2) and a normalization of the shortening fraction in 2 (from 15 to 36% and from 13 to 46% respectively) at echocardiography. These two patients had active myocarditis at the first endomyocardial biopsy. At follow-up, all 3 pts with active myocarditis showed histological evidence of healed myocarditis. In conclusion, peripartum cardiomyopathy is characterized by a high incidence of active myocarditis and improvement seems more frequent in this subgroup of pts.

[Post-infarct rupture of the interventricular septum. 2-dimensional, continuous Doppler, pulsed and color-coded echocardiographic evaluation]. / Rottura post-infartuale del setto interventricolare. Valutazione ecocardiografica bidimensionale, Doppler continuo, pulsato e con codice di colori.

Rupture of the interventricular septum is an infrequent but always serious complication of acute myocardial infarction. It requires accurate timely diagnosis to decide the proper treatment and eventual surgical intervention. Echo-color-Doppler-cardiography appears to have such diagnostic capacities. In a total of 403 pts, with acute myocardial infarction we found 7 pts (1.7%) with suspected interventricular septum rupture; 5 with infero-posterior infarction and 2 with an anterior one. In 4 pts shock and death occurred rapidly, 2 pts were submitted to angiography and then to surgery with a good outcome, 1 pt died immediately after surgical repair. Echocardiographic findings were: 1) by 2-D (7 pts), direct visualization of septal rupture in 5/7, all with infero-posterior infarctions; 2) by pulsed wave Doppler (5 pts), detection of a typical systolic turbulence on the right septum in 5/5 pts, 3 with infero-posterior myocardial infarction, 2 with an anterior one; 3) by color Doppler (3 pts), detection of a "mosaic" color-jet expanding into the right ventricle in 3/3 pts, 2 with an anterior and 1 with an infero-posterior myocardial infarction. This technique immediately located two small ruptures which had not been easily detected by pulsed Doppler alone. In conclusion, echocolordopplercardiography appears to be a reliable method for the detection of ventricular septal rupture after myocardial infarction in so timely and accurately a manner as to rule out more aggressive procedures, angiography and surgery.