Treatment effects on serum lipoprotein lipids, apolipoproteins and low density lipoprotein particle size and relationships of lipoprotein variables to progression of coronary artery disease in the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT).

OBJECTIVES: To investigate the mechanisms by which bezafibrate retarded the progression of coronary lesions in the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT), we examined the relationships of on-trial lipoproteins and lipoprotein subfractions to the angiographic outcome measurements. BACKGROUND: BECAIT, the first double-blind, placebo-controlled, randomized serial angiographic trial of a fibrate compound, showed that progression of focal coronary atherosclerosis in young survivors of myocardial infarction could be retarded by bezafibrate treatment. METHODS: A total of 92 dyslipoproteinemic men who had survived a first myocardial infarction before the age of 45 years were randomly assigned to treatment for 5 years with bezafibrate (200 mg three times daily) or placebo; 81 patients underwent baseline and at least one post-treatment coronary angiography. RESULTS: In addition to the decrease in very low density lipoprotein (VLDL) cholesterol (-53%) and triglyceride (-46%) and plasma apolipoprotein (apo) B (-9%) levels, bezafibrate treatment resulted in a significant increase in high density lipoprotein-3 (HDL3) cholesterol (+9%) level and a shift in the low density lipoprotein (LDL) subclass distribution toward larger particle species (peak particle diameter +032 nm). The on-trial HDL3 cholesterol and plasma apo B concentrations were found to be independent predictors of the changes in mean minimum lumen diameter (r=-0.23, p < 0.05), and percent (%) stenosis (r = 0.30, p < 0.01), respectively. Decreases in small dense LDL and/or VLDL lipid concentrations were unrelated to disease progression. CONCLUSIONS: Our results suggest that the effect of bezafibrate on progression of focal coronary atherosclerosis could be at least partly attributed to a rise in HDL3 cholesterol and a decrease in the total number of apo B-containing lipoproteins.

Effect of bezafibrate treatment over five years on coronary plaques causing 20% to 50% diameter narrowing (The Bezafibrate Coronary Atherosclerosis Intervention Trial [BECAIT]).

Recent reports indicate that most coronary events originate from plaques causing <50% diameter stenosis. A subgroup analysis of the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) data was undertaken to determine the effects of bezafibrate in relation to baseline narrowing. BECAIT included 92 male postacute myocardial infarction patients <45 years of age. Each received double-blind treatment with bezafibrate (200 mg 3 times daily) or placebo for 5 years, together with a low-fat diet. Coronary angiography was performed at baseline and after 2 and 5 years. The mean minimum lumen diameter of lesions causing 20% to <50% diameter stenosis at baseline did not narrow over 5 years in the bezafibrate group and decreased by 0.15 mm in the placebo group (p <0.05). In segments with > or =50% diameter stenosis at baseline, no change was seen in either of the 2 groups. In the analysis including only segments with 20% to <50% stenosis at baseline, coronary events were seen in 7 of 40 patients with a progression in minimum lumen diameter of more than the median value and in 3 of 41 patients with a change less than the median value. Thus, bezafibrate had a preferential effect in slowing the progression of narrowings causing <50% stenosis at baseline in young men followed up for a 5-year period after acute myocardial infarction.

Intracoronary ultrasound measurements in women with myocardial infarction without significant coronary lesions.

METHODS: Morphologic characteristics of coronary arteries in eight women with myocardial infarction and angiographically normal or not significantly stenosed vessels were investigated with intracoronary ultrasound. The infarct-related vessel was assessed by three-dimensional volumetric analysis and compared with a control vessel from a noninfarcted area. RESULTS: Atherosclerosis was found in all infarct-related arteries. The plaques were predominantly soft, eccentric, poorly calcified, and with little lipid pools or none at all. Although the average area and thickness of plaques and cross-sectional narrowing of the infarct-related arteries were greater than those of control arteries, there were no pathognomonic characteristics of plaques in the infarct-related vessels. CONCLUSION: The possibility that atherosclerosis is the main etiologic factor for myocardial infarction can not be excluded even for women without an angiographically obvious coronary stenosis in the infarct-related vessels.

Malignant mesothelioma in Turkish immigrants residing in Sweden.

Mesothelioma is a rare neoplasm in the general population, but it is strongly associated with previous asbestos exposure. The endemic occurrence of this disease in two villages in central Turkey has raised the question of whether the inhalation of naturally occurring zeolite dust may also be a factor in the development of mesothelioma. During the past few years a large portion of the inhabitants of one of the two villages of concern has immigrated to Sweden. This report presents three cases of malignant pleural mesothelioma and the results of a chest radiographic survey among these immigrants. Mineralogical analysis of lung tissue specimens from two of the cases revealed the presence of both zeolite and asbestos minerals and therefore suggested a synergistic effect involving both types of minerals. The importance of close medical surveillance of this high-risk population is emphasized, as is the possibility that similar cases appear in other countries because of increased migration.

Physical activity and exercise performance predict long-term prognosis in middle-aged women surviving acute coronary syndrome.

AIM: To evaluate the importance of exercise testing (ET) parameters and leisure time physical activity in predicting long-term prognosis in middle-aged women hospitalized for acute coronary syndrome (ACS). METHODS AND RESULTS: Women aged <66 years recently hospitalized for ACS in the Greater Stockholm area in Sweden were recruited. All underwent baseline clinical examinations including ET and then were followed up for 9 years. Nonparticipation in ET had a hazard ratio of 4.26 (95% confidence interval 2.02-8.95) for total mortality and 3.03 (1.03-8.91) for cardiovascular mortality. All ET parameters were significantly different between survivors than nonsurvivors, except for chest pain and ST-segment depression during ET. Sedentary lifestyle and ET parameters were related to total mortality and cardiovascular mortality in a multivariate analysis adjusting for potential confounders. Predictors of total mortality were sedentary lifestyle 2.94 (1.31-6.62), exercise time 1.75 (1.07-2.87) and inadequate haemodynamic responses: low increase in pulse rate 2.04 (1.16-3.60) and systolic blood pressure (SBP) 1.88 (1.19-2.95) from rest to peak exercise. Parameters that predicted cardiovascular mortality were sedentary lifestyle 3.15 (1.13-8.74) and poor increase in SBP 2.76 (1.30-5.86) from rest to peak exercise. The relation of sedentary lifestyle to survival was substantially weakened when exercise parameters were added to the multivariate analysis model. CONCLUSION: In female patients <66 years surviving ACS, important independent predictors of long-term all-cause mortality were sedentary lifestyle, low physical fitness and inadequate pulse rate and SBP increase during exercise. Predictors of cardiovascular mortality were sedentary lifestyle and inadequate blood pressure response during exercise.

Psychosocial stress and atherosclerosis: family and work stress accelerate progression of coronary disease in women. The Stockholm Female Coronary Angiography Study.

OBJECTIVE: To examine the impact of psychosocial stress, experienced in the family and work life, on the progression of coronary atherosclerosis in women cardiac patients. DESIGN: Longitudinal follow-up study. The mean luminal diameter change over 3 years was averaged over 10 predefined coronary segments, representing the entire coronary tree. Stress in family life was measured by using the Stockholm Marital Stress Scale and that of work life by the demand-control questionnaire. SUBJECTS: Amongst patients enrolled in the Stockholm Female Coronary Angiography Study, 80 women were evaluated for stress exposure and coronary atherosclerosis progression using serial quantitative coronary angiography. RESULTS: Multi-variable-controlled mixed models anova analyses revealed that women with high stress from either family or work had significant disease progression over 3 years, whereas those with low stress had only slight progression. In women who were free of stress from either family or work life, i.e. they were satisfied with both of these life domains, the coronary artery changes had regressed. Their mean coronary luminal diameter increased by 0.22 mm (95% CI: 0.10; 0.35 mm) when compared with women who experienced stress from both sources, whose luminal diameter decreased by 0.20 mm (95% CI: -0.14; -0.25). These associations were independent of baseline luminal diameter and standard cardiovascular risk factors, including age smoking, hypertension and HDL at baseline. CONCLUSIONS: Stress from family or work life may accelerate coronary disease processes in women, whereas relative protection may be obtained from a satisfactory job and a happy marriage.

Validation of a new system in quantitative coronary arteriography.

PURPOSE: To validate ANCOR, a new system in quantitative coronary arteriography (QCA). MATERIAL AND METHODS: The validation procedure was performed by comparing the calibration factors of catheters filled with saline solution or contrast medium, and by measuring precision-drilled lumens in a test phantom filled with contrast medium. The results were compared with a well established and validated system, CMS. RESULTS: The calibration test showed that the calibration factors in the saline and contrast-medium catheters differed only a few percent when catheters with diameters of 2.0-2.67 mm were used. The phantom test showed that both systems overestimated smaller and larger diameters than these. The best results for both systems were achieved in the middle-diameter range. CONCLUSION: The ANCOR and CMS systems gave comparable results in catheter calibrations and phantom tests.

Thallium-201 single photon emission computed tomography in patients with symptoms of heart disease and non-significant coronary artery lesions.

Polar presentations of coronary angiograms and myocardial 201Tl SPECT were compared in 44 patients without significant coronary artery disease (less than 50% stenosis at angiography). Regions of reduced isotope activity (defects) were present in 18 patients (41%). Nine of these had angiographic and/or clinical evidence of non-coronary heart disease, such as documented or suspected myocardial infarction, dilated cardiomyopathy or other myocardial diseases. Such defects could be caused by impaired small vessel blood flow, abnormalities in cell membrane transport or relative differences in left ventricular wall thickness. In 9 patients defects were probably due to attenuation artifacts. Defects in patients with heart diseases were significantly larger than in those without obvious disease. The information content in coronary angiography and 201Tl SPECT overlap but are not congruent. Coronary angiography describes morphology of large coronary vessels, whereas 201Tl SPECT contains information of large and small vessel perfusion as well as membrane transport of 201Tl ions.

Thallium tomography in the detection of myocardial perfusion defects.

Tomographic 201-Tl scintigrams (SPECT) were compared with conventional planar images (PLAN) in 100 consecutive patients with ischaemic heart disease (IHD). Agreement was obtained in 78/100 and disagreement in 7/100. In 15 patients the results were equivocal. The sensitivity of PLAN and SPECT was studied in 35 patients with IHD and angina pectoris who were also examined with coronary angiography. SPECT had a sensitivity of 88 per cent compared with 84 per cent for PLAN. SPECT was better in matching perfusion defects to coronary stenoses in this small patient group.

Coronary angiography and thallium-201 single photon emission computed tomography in single vessel coronary artery disease.

Polar presentations of selective coronary angiography and myocardial 201T1 SPECT were compared in 49 patients with single vessel disease. Twenty-six lesions were located in LAD, 8 in LCX and 15 in RCA. Perfusion defects were found within the supply area of 44 stenotic and 20 non-stenotic arteries. 201T1 SPECT detected coronary disease in 45 patients (92%) and the obstructed artery in 44 (90%). Single vessel disease was correctly indicated in 28 patients (57%) where the perfusion defects did not extend significantly outside the area supplied by the stenotic artery. Extensive perfusion defects could be explained by 'collateral steal', myocardial disease, LV aneurysm or spasm in 9 patients (18%). The absence of perfusion defect related to the stenotic artery could be explained by a moderate degree of stenosis or well developed collateral vessels in 5 patients (10%). Proximal LAD lesions resulted in larger perfusion defects than distal.

Cross-sectional area of the thigh muscle in man measured by computed tomography.

Nine subjects with different training background were studied by means of muscle biopsy from musculus vastus lateralis. The cross-cut area of the different muscle fibre types was measured. By the use of a soft tissue X-ray technique, computed tomography, a cross-sectional picture of the thigh was produced at the same level as the biopsy was taken. The total cross-cut area of the vastus lateralis muscle was measured from this picture. This technique to measure a cross-cut muscle area from an X-ray picture was evaluated and found to be accurate and reproducible. The mean fibre area was highly correlated (r = 0.91; P less than 0.001) to the cross-cut area of the vastus lateralis muscle. The total number of fibres in the vastus lateralis muscle was estimated. It was concluded that the cross-sectional area of the thigh muscle can be accurately determined by means of computed tomography. The larger cross-sectional area of the vastus lateralis muscle in well trained subjects was primarily explained by a larger cross-sectional area of the fibre, while the total number of fibres in the vastus lateralis muscle seemed to be fairly equal among the subjects.

Coronary angiography and thallium-201 single photon emission computed tomography in multiple vessel coronary artery disease.

Polar presentations of selective coronary angiography and myocardial 201Tl SPECT were compared in 141 patients with multiple vessel disease, 80 with 3-vessel disease, 34 with 2-vessel disease and 27 post-bypass patients. Perfusion defects were present in 125/141 patients (89%) and were located within the area supplied by 194/359 stenotic arteries (54%) and 9 non-stenotic arteries. The type and extent of disease was correctly indicated by 201Tl SPECT in 16/80 patients (20%) with 3-vessel disease, 5/34 patients (15%) with 2-vessel disease and 8/27 post-bypass patients (30%). Perfusion defects indicated the artery with the most severe lesion in 107/125 patients (86%). False negative isotope studies were present in 15 patients (11%).

Early and late efficacy of three types of transvenous atrial leads.

Experience with three transvenous atrial leads, representing different principles, is presented. The types were screw-in (Vitatron Helifix-12), J-lead (Intermedics Lifeline 483-01) and straight-tined (Medtronic 6961). The study comprised insertion of 86 leads (30 Helifix, 40 Lifeline, 16 Medtronic) in 76 patients. Atrial fibrillation occurred during insertion in two patients, and in two others stable electrode positioning in the right atrial appendage was not achieved. Stable position and acceptable intracardiac P-waves were obtained in all the other patients (in 5 after change to another type of lead). Atrial triggered ventricular pacing was used in 34 cases and atrial pacing was used in 38. The P-wave amplitude at insertion was significantly less with Helifix than with Lifeline or Medtronic. The stimulation thresholds (range 0.25-2.5 V) did not differ significantly between the electrodes. Dislodgement of the electrode occurred during the first week in seven cases (5 Lifeline, 2 Helifix), but no late dislodgement occurred. The mean follow-up was 14 months (range 1-31). All three atrial leads offer acceptable function with regard to electro-physiological properties and electrode stability.

Exercise and redistribution thallium-201 myocardial scintigraphy: changes in distribution qualitatively unaffected by previous infarction.

Eighteen patients with stable exertional angina pectoris were investigated by thallium-201 (201Tl) exercise and redistribution single photon emission computed tomography (SPECT) after coronary angiography. Eight of the patients had a previous myocardial infarct. Six patients had single-, eight double- and four triple-vessel disease. An exercise SPECT was acquired 10 min after the administration of isotope, injected 1-2 min before the termination of a symptom-limited exercise test. A redistribution SPECT was recorded 3 h later. 201Tl activity per pixel was compared between the exercise and redistribution SPECT in relative and absolute terms. For each patient there was a good correlation between activity per pixel in the redistribution SPECT and the corresponding pixels in the exercise SPECT (mean correlation coefficient 0.86 +/- 0.08), irrespective of the extent of coronary artery disease or presence of a previous infarction in the pixel region. Relative wash-out correlated to the degree of coronary artery stenosis (r = 0.48), but did not differ between infarcted and non-infarcted myocardial regions. A similar relationship was documented for pixels with visual 'refill' in the redistribution SPECT. This implies that most of the information in the redistribution SPECT was present already in the exercise SPECT. Thus, qualitative information of a similar kind is obtained from images acquired immediately after exercise and after 3-4 h of redistribution.

Polar presentation of coronary angiography and thallium-201 single photon emission computed tomography. A method for comparing anatomic and pathologic findings in coronary angiography with isotope distribution in thallium-201 myocardial SPECT.

Individual results of coronary angiography were compared with tomographic myocardial scintigraphy (SPECT) in 99 patients. Coronary angiography findings were transferred to polar maps. Borders between arteries were assigned angles in a coordinate system constructed as a compass-rose. Areas perfused by different arteries were described by sectors. Findings were visually compared with the perfusion defects in a polar presentation of thallium-201 SPECT also described by angles. The mean values and SD for the angles representing arterial borders and perfusion defects were presented. The left ventricular myocardium was perfused by 3 coronary arteries in 92/99 patients. Dominant left artery was present in 7/99 patients; 79 perfusion defects were related to 118 arterial sectors 84 per cent had totally or partially matched stenotic arteries. Inter-individual differences in distribution of coronary arteries influence the localization of perfusion defects in myocardial SPECT and can be estimated with this polar presentation method.

Prospective clinical and radiologic study of zeolite-exposed Turkish immigrants in Sweden.

Ninety-four persons from the village of Karain, Turkey, now residing in Stockholm, were investigated clinically and radiologically. In this village, environmental exposure to erionite, a fibrous zeolite, occurs, and there is an extremely high risk of mesothelioma among the villagers. Since an earlier investigation of the cohort in 1980, another 4 young persons have fallen ill with malignant mesothelioma in this group, where the incidence thus approaches 1%/year and is the most common cause of death. Solitary pleural plaques were found in 6%, thickening of the interlobar pleura in 4% and other radiologic signs of affection of the pleura in 2%. Thickening of the interlobar fissures were observed in 1 patient as the first sign of mesothelioma which has remained asymptomatic until 1 year later. The comparatively low incidence of pleural lesions in the cohort is probably due to the low mean age (36 years). Further follow-up could give clues to the pathogenesis of malignant mesothelioma.

A roentgenological study of the small intestine after different intestinal bypass operations for treatment of morbid obesity.

Twenty-nine patients who had undergone four different types of jejunoileal bypass for obesity were examined roentgenologically after ingestion of barium contrast. Functional intestinal length, blind loop reflux and speed of contrast through the small intestine were recorded. Weight loss was not correlated to any of the mentioned parameters or to operative method. Length of functioning intestine increased and speed of contrast decreased with time after surgery.

Secondary preventive potential of lipid-lowering drugs. The Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT).

Current experience from coronary angiographic trials using different treatment regimens such as lifestyle changes, resins, nicotinic acid and statins, shows that progression of atheroma can be retarded, and that regression can sometimes be induced, by a marked lowering of LDL-cholesterol. Young post-myocardial infarction patients, however, usually exhibit a multiplicity of metabolic risk factors with dyslipidaemias, predominantly hypertriglyceridaemia, and disturbances of glucose-insulin homeostasis and of the haemostatic system. These factors, together coupled with coronary angiographic data showing that the degree of dyslipidaemia is related to the extent and degree of coronary atherosclerosis, and the fact that rapid progression of coronary atherosclerosis was foreseen in this group of patients, resulted in the initiation of the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) in 1985. BECAIT was a 5-year, double-blind, placebo-controlled study of bezafibrate (200 mg three times daily) and dietary intervention in dyslipidaemic male survivors of myocardial infarction below 45 years of age. The angiographic analysis included 81 patients (42 bezafibrate and 39 placebo) who underwent baseline and at least one post-treatment angiogram, at 2 and 5 years. Changes in mean minimum lumen diameter indicated that there was 0.13 mm less (95% Cl: 0.10; 0.15) disease progression in focal lesions in the bezafibrate group than in the placebo group (P = 0.049). Parallel, but non-statistically significant, treatment effects were observed for mean segment diameter and percent stenosis. Three patients treated with bezafibrate and 11 patients in the placebo group suffered coronary events during the course of the trial (P = 0.02 logrank test). The angiographic effects of bezafibrate were accompanied by statistically significant reductions in serum cholesterol and triglycerides. Furthermore, plasma fibrinogen levels were significantly reduced and HDL-cholesterol concentration increased but there was no net change in LDL-cholesterol. These findings show that bezafibrate slowed the progression of focal coronary atherosclerosis to a degree that is comparable to that achieved with the statins in angiographic trials such as MAAS and REGRESS. Bezafibrate also reduced the occurrence of coronary events in young post-infarction victims. Like BECAIT, analyses of data from the NHLBI type II study, CLAS, POSCH and MARS provide evidence for the role of triglyceride-rich lipoproteins in the progression of coronary artery disease. Retardation of progression of atherosclerosis and a reduction in coronary events is, therefore, possible without reducing LDL-cholesterol.