Arterial stenosis and atherothrombotic events in polycythemia vera and essential thrombocythemia.

UNLABELLED: Patients with polycythemia vera (PV) and essential thrombocythemia (ET) are at risk of developing arterial and venous thromboembolic complications. Given the complex interaction between blood cells and the vessel wall, it is possible that atherogenesis may also be accelerated in these patients. We used Doppler arterial ultrasound to assess the presence of arterial stenosis in a cohort of PV and ET patients. MATERIAL AND METHODS: A total of 37 patients, 29 with PV and 8 with ET, were investigated. Aside from an extensive clinical and hematological evaluation, arterial Doppler ultrasonography was performed in all patients; in 3 patients arteriography/coronarography was also performed. RESULTS: Twenty four patients (65%) had a history of atherothrombotic events including cerebral ischemic attacks (CIA) in 12 patients, ischemic heart disease (IHD) in 10 patients and peripheral occlusive arterial disease (POAD) in 12 patients. Eight patients had multiple atherothrombotic events. Twenty five patients (67%) had other atherosclerotic risk factors such as smoking, dyslipidemia, hypertension and diabetes. Significant arterial stenosis was found in 23 patients (62.1%), including 12 patients with carotid plaques, 10 with peripheral arterial stenosis, 3 with coronary stenosis, 2 with aortic plaque and 2 with common iliac artery stenosis. In 12 patients multiple arterial stenoses were found. The presence of arterial stenosis was significantly correlated with the occurrence or thrombotic events (p = 0.0003) and was also correlated with the concomitant presence of polyglobulia and thrombocytosis. Both the thrombotic risk and the probability of stenosis detection were augmented by additional risk factors such as smoking, hypertension and dyslipidemia. DISCUSSION AND CONCLUSIONS: The high incidence of arterial thrombotic events in our PV and ET patients was associated with a high incidence of stenosis detectable by arterial ultrasound. Hyperviscosity, endothelial damage due to leukocyte activation with subsequent thrombus formation, hyperhomocysteinemia and hyperexpression of activating genes such as JAK2 and STAT5 are all features characteristic of PV and ET that may contribute, along with other risk factors, to the development and progression of atherothrombosis. Cytotoxic treatment in PV and TE may be beneficial both through its antiproliferative effect on hematopoiesis and on the atherosclerotic plaques, atherogenesis being described as a proliferative disease of the vessel wall.

Arterial compliance in hypertension and heart failure.

The purpose of this paper is to investigate the relation between the presence and degree of arterial compliance impairment and, respectively, the clinical conditions of systemic hypertension and/or heart failure. We investigated 19 patients with hypertension, without heart failure (group A), 13 patients with hypertension and heart failure class NYHA II (group B), 10 patients with coronary heart disease and heart failure class NYHA II (group C) and 7 control patients without clinically relevant cardio-vascular diseases (group D). Compliance was evaluated with a Complior device, by measuring carotid femoral and carotid-radial pulse-wave velocities (PWV). Carotid-radial PWV did not differ significantly between the various groups (10.8 +/- 2, 10.6 +/- 0.9, 9.5 +/- 1.5 and 9.9 +/- 1.6 m/s, for groups A, B, C and D, respectively). Carotid-femoral PWV, in group A hypertensive p without heart failure, was 13.1 +/- 2.9 m/s, significantly higher as compared to group C p with coronary heart disease and heart failure (10.5 +/- 2.4 m/s, p = 0.02), as well as compared to group D controls (9.8 +/- 2.6, p = 0.02). Group B p, with heart failure associated to hypertension, had a carotid-femoral PWV of 13.5 +/- 3.9 m/s, similar to the one found in group A hypertensive p without heart failure. When comparing groups B and C p with heart failure, we noted that the carotid-femoral PWV was significantly (p = 0.04) increased in hypertensive p, as compared to those with coronary heart disease. In conclusion, the results of our study confirm the impairment of arterial compliance, in hypertensive patients. The carotid-femoral, but not the carotid-radial PWV, were useful for identifying impaired compliance in these patients. Heart failure, associated to hypertension, was not accompanied by a supplemental deterioration of arterial compliance. In fact, our study could not confirm the decrease of arterial compliance, in heart failure patients, as compared to controls. This study suggests the importance of hypertension, with its structural arterial wall changes, in the genesis of arterial compliance impairment.

Apolipoproteins A1 and B levels and serum cholinesterase activity in hyperlipidemic subjects.

Serum apolipoprotein B (apo B) levels were found to be significantly (p < 0.001) higher in the 27 patients with combined hyperlipidemia (144 m./dl +/- 27.6) than in the 17 normal weight normolipidemic control subjects (92 mg/dl +/- 20.6; X +/- SD). When compared to apolipoprotein A1 (apo A1) levels obtained in controls (168.5 mg/dl +/- 28.4), hyperlipidemic subjects displayed a moderate yet significant (p < 0.02) decrease of this apolipoprotein (140 mg/dl +/- 24.2). Serum apo B levels were significantly (p < 0.001) correlated with serum cholesterol concentrations and also, to a lesser degree (p < 0.01), with serum cholinesterase activity. A highly significant correlation (p < 0.001) between apo A1 and HDL cholesterol levels was also noted. The decrease ofHDL cholesterol occurring in hyperlipidemic men (-30%) was however more accentuated than the decrease of apo A1 (-18%) suggesting an enhanced transfer of cholesterol esters from HDL to VLDL and LDL. It is considered that the determination of apolipoproteins may be useful not only for the detection of risk factors for atherosclerosis, but also for a better insight concerning the mechanisms involved in the development of an atherogenic dyslipidemia.

Primary coronary angioplasty in acute myocardial infarction excluded from thrombolysis: in-hospital and mid-term results.

The clinical, in-hospital and mid-term (14 +/- 12 months), results of primary percutaneous coronary angioplasty (PTCA) were investigated in 74 consecutive patients (pts) with acute myocardial infarction excluded from thrombolysis, of whom 9 pts with cardiogenic shock. In pts without cardiogenic shock at admission, the success rate of primary PTCA was high (92.3%) and the in-hospital mortality was low (3%). There were 89.2% asymptomatic pts during the in-hospital period. During the mid-term follow-up, pts without cardiogenic shock at admission had a mortality of only 4%, 66% of them remained asymptomatic, 24% developed angina pectoris and 6% had a new myocardial infarction. In pts with cardiogenic shock at admission to the hospital, the success rate of primary PTCA was of only 55.5% and the in-hospital mortality was high, 77.7%. In conclusion, primary PTCA in acute myocardial infarction excluded from thrombolysis is particularly useful in patients without cardiogenic shock.

Clinical and etiopathogenetic profile of heart failure in the First Medical Clinic of Cluj-Napoca. A study of 5 years.

The authors analysed the main etiopathogenetic conditions and the clinical and evolutional profile of 1586 patients with heart failure (HF), admitted to the First Medical Clinic of Cluj-Napoca between 1990 and 1994. Ischemic heart disease was found in 1,236 patients (78%), followed by chronic cor pulmonale, valvulopathies and congenital heart diseases. Among the precipitating and/or aggravating factors of HF, the most important were infections in 434 patients (33.10%), and arrhythmias, especially atrial fibrillation, in 332 patients (25.39%). In decreased order of frequency there were also failure to observe prescribed therapy, uncontrolled arterial hypertension, anemias, dyselectrolytemias, dysproteinemias. HF had a chronic evolution in 1,450 patients (91.40%), and an acute one in 136 (8.6%). In conditions of complex therapy including cardiotonics, diuretics, plus, more recently, conversion enzyme inhibitors, the clinical evolution was favourable in 1,432 patients (90.20%), which had a lower functional class on discharge from hospital.

Increased plasma factor VIII:c activity in patients with unstable angina pectoris.

Plasma factor VIII:c activity was found to be significantly (p < 0.01) higher in the 17 patients with unstable angina pectoris (201% +/- 121; x +/- SD) than in the 10 healthy control subjects (97% +/- 16). Plasma fibrinogen level was also significantly (p < 0.003) higher in patients (455 mg/dl +/- 188) than in controls (260 mg/dl +/- 35) but there was no significant correlation between these two variables within the group of patients with unstable angina. No difference could be noted between plasma antithrombin III activities in patients and in controls. It is considered that the increased factor VIII:c activity in patients with unstable angina pectoris could be subsequent to the acute phase reaction induced by cytokines and/or by an enhanced adrenergic stimulation, although the possible presence of genetically-conditioned hyperactive factor VIII:c molecules can not be excluded. Since the outcome of a ruptured plaque may also depend on the systemic thrombotic propensity at the time of rupture, the presently reported findings could be pathogenically relevant.

Partial interruption of the inferior vena cava: ten-year evolution in protocols at Grenoble University Hospital. Study of 621 patients.

An evolution in protocols regarding indications and modalities for Partial Interruption of the Inferior Vena Cava (PIIVC) on 621 patients at Grenoble University Hospital is reported and the influence of new methods in diagnosis (vascular sonography) and therapy (percutaneous filters) is assessed. This comparative study covers the intervals from 1982-1984 (Period A - 333 patients), and 1989-1991 (Period B - 288 patients). The percentage of patients with venous thromboembolic disease who underwent PIIVC clearly decreased (21.8% in period A vs. 13% in period B, p < 0.01). The incidence of what are currently miscalled "prophylactic", but are in fact adjunctive indications also diminished (115 patients in period A, or 34.5% of the PIIVC cases vs. 60 patients in period B, or 20.8% of the PIIVC cases, p < 0.05). There was a reduction in the use of Miles caval clips (59 patients or 17.7% for period A vs. 34 patients or 11.8% for period B, p < 0.05). Although there has been an increase in the use of percutaneous caval filters, the use of percutaneous filters has not lead to an increase in the real rate of PIIVC performed by an Angiology Unit with a large experience in the diagnosis and follow-up of patients with venous thromboembolic disease.

Homozygous or compound heterozygous qualitative antithrombin III deficiency.

A male patient of 24 years who had experienced thrombotic episodes since the age of 15 displayed an unusually low antithrombin III (AT III) activity measured as heparin cofactor (13% of the normal), while a similarly decreased value (16% of normal) was found in a 26 year old brother who had suffered from thrombotic events since the age of 12 years. AT III heparin cofactor activities were close to 50% of normal in the father, mother, another brother and a sister, none of whom had experienced thrombotic episodes. Since all available members of the family, including the patient, displayed near normal AT III antigen levels (73-85%) normal total progressive antithrombin activities (92-110%) as assessed by the thrombin agarose diffusion technique and normal total progressive anti-Xa activities, the propositus and his brother could be considered to be homozygotes or compound heterozygotes for a qualitative familial AT III deficiency probably caused by an abnormality of the heparin binding site. Molecular techniques would be required to elucidate the precise mutation giving rise to the deficiency.

Antithrombin III deficiency.

Data on clinical features and laboratory diagnosis of familial antithrombin deficiency, a rather heterogeneous group of disorders, are illustrated by observations on two Romanian kindreds afflicted by recurrent thrombotic episodes. In a first family, both plasma antithrombin III antigen and activity were reduced to 50% of normal, a condition characteristic for a heterozygous type I (quantitative) familial antithrombin III deficiency. In a second kindred, the two brothers who had experienced thrombotic events since they were teenagers, displayed exceedingly low AT III heparin cofactor activity (13% and 16% of the normal, respectively) while values around 50% of the normal were recorded in their parents who had not experienced thrombotic episodes. Since plasma antithrombin III antigen and total progressive antithrombin III activity were within normal limits in all the investigated members of this family it was considered that the two brothers were homozygotes or compound heterozygotes and the parents were heterozygotes for a qualitative-antithrombin III deficiency caused by an abnormality of the heparin binding site.

His-Purkinje waveforms on externally recorded averaged unfiltered electrocardiograms.

Electrocardiographic signal recorded in right unipolar leads (2V1, 3V1, V1) was amplified (up to 500,000 times) averaged (256 or 512 cardiac cycles) and finally digitally filtered, in order to record His-Purkinje (HP) activity. A group of 41 patients with sinus rhythm and PR intervals ranging between 100 and 250 ms was repeatedly investigated. Distinct and highly reproducible waveforms located in the PR segment, attributable to HP activity, were recorded on the averaged unfiltered traces in 14 patients (34%). Waveforms, with an amplitude ranging between 4 and 80 microV, were positive in 13 patients and negative in one. In one patient, with atrial tachycardia with 2:1 atrioventricular block, two positive successive deflections suggested the possibility of recording the proximal and distal His activity. Externally recorded averaged unfiltered traces could be useful for the investigation of HP activity in a relatively large proportion of patients.

Observations on the diagnostic criteria of the "nontransmural" acute myocardial infarction.

In 15 patients with acute myocardial infarction (AMI) lacking Q waves ("nontransmural"), selected from 317 patients with AMI, successively observed, diagnostic criteria and evolution were analysed. Clinical and enzymatic diagnostic criteria of the "nontransmural" AMI indicated a significant myocardial necrosis. Anginal pain was particularly recurrent. Various and variable electrocardiographic signs (ST--T changes, arrhythmias, etc.) suggested a significant, extensive, myocardial damage. Complications (heart pump failure, arrhythmias, peripheral and cerebral ischemic attacks), frequently severe, occurred in the majority of the patients. "Nontransmural" AMI occurred mainly in patients older than 60, with systemic arterial involvement. Four of the patients died (two during the acute phase); in one of them, transmural AMI, suggested by a complicating pericarditis, was confirmed by necropsy. The so-called "nontransmural" AMI proved to be an actual or potentially severe condition. Its differentiation from the "transmural" AMI on the basis of electrocardiographic criteria is artificial and unjustified.