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.

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.

C-reactive protein and myocardial infarction during percutaneous coronary intervention.

OBJECTIVE: To evaluate the prognostic information of preprocedural C-reactive protein (CRP) levels in serum to predict myocardial infarction during percutaneous coronary interventions (PCI). DESIGN: Prospective study. SETTING: University hospital. PATIENTS: A total of 400 consecutive patients with normal serum troponin T levels (0.05 microg L-1. RESULTS: Eighty-three patients (21%) experienced a myocardial infarction during PCI. The median value of CRP before the procedure was 1.83 (0.12-99.7) mg L-1. No difference was seen in CRP levels before PCI between patients without or with myocardial infarction during PCI. Multivariate analysis identified stent implantation (OR 2.68, 95% CI 1.18-7.28, P = 0.03), procedure time (OR 2.15, 95% CI 1.28-3.67, P < 0.005) and complications during the procedure (OR 3.62, 95% CI 1.72-7.58, P < 0.001) as independent predictors of myocardial infarction during PCI. CONCLUSION: Increased CRP levels in serum before PCI were not associated with myocardial infarction during the procedure. Furthermore, patients with an expected long procedure and a high probability of stent implantation have an increased risk of developing myocardial infarction during PCI. This finding may be useful to help the operator to decide the antithrombotic regime before, during and after the procedure and the need for observation after the procedure.

Classification of left main coronary obstruction--feasibility of surgical angioplasty and survival after coronary artery bypass surgery.

Angiographies of 384 patients who had coronary artery bypass surgery because of left main coronary artery (LMCA) obstruction during 1970-1989 were reviewed by analysing the pathology, feasibility of surgical angioplasty and survival. Complete LMCA occlusion was found in 2%, proximal ostial stenosis in 9%, mid-shaft stenosis in 24%, circular stenosis in 25% and distal bifurcation stenosis in 40% of the patients. Patients with an ostial stenosis were younger, more often women with less coronary artery disease and less calcified obstructions. Surgical angioplasty could have been an option in 22% of the patients. Early mortality was higher in patients with (4.7%) than in those without (1.9%) LMCA obstruction. The relative risk (RR) of early death was 1.9 (95% CL 1.1-3.5) after adjustment for patient characteristics. Similarly, the RR at 10 years was 1.3 (95% CL 1.0-1.6). LMCA obstruction was associated with an early and long-term increased mortality after surgery compared to patients without LMCA obstruction.

Significant predictors of poor prognosis in women aged

OBJECTIVES: The aim of this study was to evaluate the importance of different clinical parameters predicting long-term cardiac prognosis in younger women with an acute coronary event. DESIGN: The Stockholm Female Coronary Risk Study is a follow-up study in women 2.0 mmol L-1 (HR 2.46, 95% CI 1.06-5.54). AMI as index event and diabetes mellitus were the most significant predictors in a multivariate statistical model. Diabetes mellitus was the strongest predictor when the analysis was repeated in the total patient cohort, integrating patients that did not participate in the extended investigations. CONCLUSION: Women aged

Visual grading of emphysema severity in candidates for lung volume reduction surgery. Comparison between HRCT, spiral CT and "density-masked" images.

PURPOSE: To investigate which of three types of CT imaging yielded the best results in estimating the degree of emphysema in patients undergoing evaluation for lung volume reduction surgery (LVRS), whether there was any difference in this regard between the cranial and caudal part of the lung, and whether the degree of emphysema had an impact on the estimation. MATERIAL AND METHODS: Four radiologists visually classified different degrees of emphysema on three different types of CT images into four groups. The degree of emphysema was calculated by a computer. The three types of images were as follows: HRCT images (2-mm slice thickness); spiral CT images (10-mm slice thickness); and density-masked images (spiral CT images printed with pixels below -960 HU, depicted in white). RESULTS: The conventionally presented images from HRCT and spiral CT yielded the same results (60% respective 62% correct classifications) in assessing the degree of emphysema irrespective of localisation. Significantly improved results were obtained when the spiral CT images were presented as density-masked images (74%). CONCLUSION: There was no difference between HRCT and spiral CT in assessing the degree of emphysema in candidates for LVRS. Improvement can be achieved by the use of density-masked images.

Visual classification of emphysema heterogeneity compared with objective measurements: HRCT vs spiral CT in candidates for lung volume reduction surgery.

The aim of this study was to investigate whether spiral CT is superior to high-resolution computed tomography (HRCT) in evaluating the radiological morphology of emphysema, and whether the combination of both CT techniques improves the evaluation in patients undergoing lung volume reduction surgery (LVRS). The material consisted of HRCT (with 2-mm slice thickness) and spiral CT (with 10-mm slice thickness) of 94 candidates for LVRS. Selected image pairs from these examinations were evaluated. Each image pair consisted of one image from the cranial part of the lung and one image from the caudal part. The degree of emphysema in the two images was calculated by computer. The difference between the images determined the degree of heterogeneity. Five classes of heterogeneity were defined. The study was performed by visual classification of 95 image pairs (spiral CT) and 95 image pairs (HRCT) into one of five different classes of emphysema heterogeneity. This visual classification was compared with the computer-based classification. Spiral CT was superior to HRCT with 47% correct classifications of emphysema heterogeneity compared with 40% for HRCT-based classification ( p<0.05). The combination of the techniques did not improve the evaluation (42%). Spiral CT is superior to HRCT in determining heterogeneity of emphysema visually, and should be included in the pre-operative CT evaluation of LVRS candidates.

Thin-section CT vs spiral CT in candidates for lung volume reduction surgery: a comparison based on radiologists' subjective preferences.

The aim of this study was to investigate whether high-resolution (HRCT) or spiral CT was preferred in evaluating severe emphysema in patients undergoing lung volume reduction surgery (LVRS), whether there is any difference in this regard between the cranial and caudal part of the lung, and whether the degree of emphysema has an impact on the radiologists' preference. The study was performed by letting four radiologists compare images obtained with the two techniques (film pairs) and decide which technique they preferred or if the techniques were considered as equal in evaluating emphysema. In evaluation of 188 film pairs, the HRCT images were preferred in 56 %, spiral CT in 19 % and the techniques considered as equal in 25 %. Spiral CT images were preferred more often in the caudal part of the lung and in more advanced emphysema compared with the HRCT images. The study confirms our clinical assumption that use of both CT techniques are valuable in evaluating advanced emphysema and there may be technical as well as histopathological reasons for this.

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.

Clinical importance of risk factors and exercise testing for prediction of significant coronary artery stenosis in women recovering from unstable coronary artery disease: the Stockholm Female Coronary Risk Study.

BACKGROUND: The objectives of this study were to investigate the relation between coronary risk factors, exercise testing parameters, and the presence of angiographically significant coronary artery disease (CAD) (> or =50% luminal stenosis) in female patients previously hospitalized for an acute CAD event. METHODS AND RESULTS: All women younger than age 66 years in the greater Stockholm area in Sweden who were hospitalized for acute coronary syndromes during a 3-year period were recruited. Besides collection of clinical parameters, coronary angiography and a symptom-limited exercise test were performed in 228 patients 3 to 6 months after the index hospitalization. The mean age was 56 +/- 7 years. Angiographically nonsignificant CAD (stenosis <50%) was verified in 37% of the patients; significant CAD was found in 63%. The clinical parameters that showed the strongest relation with the presence of significant CAD after adjusting for age were history of myocardial infarction (odds ratio [OR] 4.91, 95% confidence interval [CI] 2.35 to 7.49), history of diabetes mellitus (OR 3.83, 95% CI 1.63 to 14.31), serum high-density lipoprotein cholesterol <1.4 mmol/L (OR 2.11, 95% CI 1. 20 to 3.72), and waist-to-hip ratio >0.85 (OR 1.78, 95% CI 1.02 to 3. 10). A low exercise capacity and associated low change of rate-pressure product from rest to peak exercise were the only exercise testing parameters that were significantly related to angiographically verified significant CAD (<90% of the predicted maximal work capacity adjusted for age and weight, OR 1.91, 95% CI 1. 04 to 3.50). CONCLUSIONS: In female patients recovering from unstable CAD, exercise capacity was the only exercise testing parameter of value in the prediction of significant CAD. The consideration of certain clinical characteristics and coronary risk factors offer better or complementary information when deciding on further coronary assessment.

Social relations and extent and severity of coronary artery disease. The Stockholm Female Coronary Risk Study.

AIMS: Social relations have been repeatedly linked to coronary heart disease in men, even after careful control for standard risk factors. Women have rarely been studied and results have not been conclusive. We investigated the role of social support in the severity and extent of coronary artery disease in women. METHODS AND RESULTS: One hundred and thirty-one women, aged 30 to 65 years, who were hospitalized for an acute coronary event and were included in the Stockholm Female Coronary Risk Study, were examined with computer assisted quantitative coronary angiography. Angiographic measures included presence of stenosis greater than 50% in at least one coronary artery (severity) and the number of stenoses greater than 20% within the coronary tree (extent). Social factors included two measures of social support, which were previously shown to predict coronary disease in prospective studies of men. After adjustment for age, lack of social support was associated with both measures of coronary artery disease. With further adjustment for smoking, education, menopausal status, hypertension, high density lipoprotein and body mass index, the risk ratio for stenosis greater than 50% in women with poor as compared to those with strong social support was 2.5 (95% confidence interval 1.2 to 5.3; P=0.003). Also, women with poor social support had more stenoses obstructing at least 20% of the coronary lumen with multivariate adjustment, but the difference from women with strong support was only of borderline significance (P=0.09). CONCLUSION: The findings suggest that lack of social support contributes to the severity of coronary artery disease in women, independent of standard risk factors.

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.

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.

Retardation of coronary atherosclerosis: the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) and other angiographic trials.

A large number of both primary and secondary preventive trials suggest that treatment of elevated plasma lipids may reduce the frequency of coronary heart disease (CHD) events. Meta-analyses indicate that for every 10% reduction of cholesterol, CHD mortality is lowered by 13% and all-cause mortality by 10%. Experience from several angiographic trials also suggests that coronary atherosclerosis can be retarded, and in some instances limited regression induced, by low-density lipoprotein (LDL)-cholesterol reduction and/or high-density lipoprotein (HDL)-cholesterol elevation. Coronary angiographic studies have shown that although the effects on retardation/regression of altherogenic lesions have been small, with luminal diameter changes of around 0.10 mm, the effects on clinical events were more substantial, with reductions of the order of 50%. There is also evidence that it is the mild and moderate lesions that are of particular concern with respect to the occurrence of clinical coronary events. The progression of atherosclerosis and the occurrence of coronary events are probably not exclusively dependent on a lowering of LDL-cholesterol concentrations. Analyses from the Monitored Atherosclerosis Regression Study (MARS), the Cholesterol Lowering Atherosclerotic Study (CLAS), and the Programs on the Surgical Control of the Hyperlipidaemias (POSCH) indicate that triglyceride-rich lipoproteins may also be of importance for the progression of mild/moderate lesions in subjects treated with cholesterol-lowering regimens. Recently, the results of the 5-year Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) demonstrated that bezafibrate significantly retarded the progression of coronary atheroma and coronary events in young male survivors of myocardial infarction, as assessed by changes in minimum lumen diameter. This positive outcome is most likely due to the beneficial treatment effects on the levels of serum triglycerides (-31%), plasma fibrinogen (-12%), and HDL cholesterol (+9%). The results of the BECAIT on progression of coronary atherosclerosis are comparable with those of two recent angiographic trials with HMG-CoA reductase inhibitors, the Multicenter Anti-Atheroma Study (MAAS), and the Regression Growth Evaluation Statin Study (REGRESS), despite different lipid and metabolic effects. BECAIT is the first controlled angiographic study to show that a fibrate can significantly retard the progression of coronary atherosclerosis. The exact mechanisms by which this occurs remain to be elucidated. However, the results of BECAIT illustrate the importance of factors other than LDL cholesterol in the progression of coronary atherosclerosis.

Antithrombin III supplementation for patients undergoing PTCA for unstable angina pectoris. A controlled randomized double-blind pilot study.

BACKGROUND: Thrombin activation may be a higher risk for complications and restenosis after percutaneous transluminal coronary angioplasty in unstable patients than in patients with stable angina pectoris. The effects of heparin may be partly counteracted by a decrease in antithrombin (III). The primary objectives of this study were to evaluate whether a subnormal antithrombin level was associated with a hypercoagulable state and to evaluate the effects of antithrombin supplementation, before and after percutaneous transluminal coronary angioplasty, on biochemical signs of coagulation activation. Secondary objectives were to evaluate acute complications and restenosis rate at 3 months. METHODS: In a double-blind pilot study, 50 patients with unstable angina, with ongoing heparin infusion and with subnormal antithrombin levels (< 85%) were randomized to receive antithrombin supplementation or placebo. Treatment targeted to an antithrombin level of 120% was started with a 2h intravenous infusion before the percutaneous transluminal coronary angioplasty and was repeated, if there were further subnormal values, every 12th hour for 48 h. RESULTS: Angiographic success was 20/25 in the antithrombin group and 21/25 in the placebo group (ns). Abrupt closure occurred in two and one patients in the two groups, respectively. Activation of coagulation measured as elevations of prothrombin fragment 1+2, thrombin-antithrombin complexes and fibrin D-dimer was seen 2 days after the procedure. Baseline levels of fibrin D-dimer were 68 +/- 69 micrograms.l-1 in the antithrombin group vs 71 +/- 46 micrograms.l-1 in the placebo group (ns). Two days after percutaneous transluminal coronary angioplasty the levels increased to 135 +/- 103 vs 242 +/- 150 micrograms.l-1, respectively (P < 0.05 between the groups). Restenosis at 3 months occurred in 4/20 antithrombin patients and in 8/21 placebo patients (ns). CONCLUSIONS: In unstable angina patients with heparin treatment and subnormal antithrombin levels, anti-thrombin supplementation resulted in less activation of coagulation and a tendency towards less restenosis.

Lipoprotein(a) as a determinant of coronary heart disease in young women.

BACKGROUND: Lipoprotein(a) [Lp(a)] appears to be a risk factor for coronary heart disease (CHD) in men. The role of Lp(a) in women, however, is less clear. METHODS AND RESULTS: We examined the ability of Lp(a) to predict CHD in a population-based case-control study of women 65 years of age or younger who lived in the greater Stockholm area. Subjects were all patients hospitalized for an acute CHD event between February 1991 and February 1994. Control subjects were randomly selected from the city census and were matched to patients by age and catchment area. Lp(a) was measured 3 months after hospitalization by use of an immunoturbidometric method (Incstar) calibrated to the Northwest Lipid Research Laboratories (coefficient of variation was < 9%). Of the 292 consecutive patients, 110 (37%) were hospitalized for an acute myocardial infarction, and 182 were hospitalized (63%) for angina pectoris. The mean age for both patients and control subjects was 56 +/- 7 years. Of participants, 74 patients (25%) and 84 control subjects (29%) were premenopausal. The distributions of Lp(a) were highly skewed in both patients and control subjects, with a range from 0.001 to 1.14 g/L. Age-adjusted odds ratio for CHD in the highest versus the lowest quartile of Lp(a) was 2.3 (95% confidence interval [CI], 1.4 to 3.7). After adjustment for age, smoking, education, body mass index, systolic blood pressure, total cholesterol, triglycerides, and HDL, the odds ratio was 2.9 (95% CI, 1.6 to 5.0). The odds ratios were similar when myocardial infarction and angina patients were compared with their respective control subjects. The odds ratios were 5.1 (95% CI, 1.4 to 18.4) and 2.4 (95% CI, 1.3 to 4.5) in premenopausal and postmenopausal women, respectively. CONCLUSIONS: These results suggest that Lp(a) is a determinant of CHD in both premenopausal and postmenopausal women.

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.

Angiographic assessment of effects of bezafibrate on progression of coronary artery disease in young male postinfarction patients.

BACKGROUND: Bezafibrate has effects on lipid metabolism and haemostatic function. We undertook a double-blind, placebo-controlled intervention trial, the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT), to establish whether bezafibrate (200 mg three times daily) could retard or prevent the progression of atherosclerotic lesions in dyslipidaemic male survivors of myocardial infarction who were younger than 45 years at the time of the event. METHODS: 92 patients completed an initial 3-month period of dietary intervention and were randomly assigned to treatment with bezafibrate or placebo. Dietary intervention continued throughout the trial. Coronary angiography was done at baseline and after 2 and 5 years. 81 patients (42 bezafibrate treated and 39 placebo treated) who underwent baseline angiography and at least one post-treatment angiogram were included in the efficacy analysis. The primary endpoint was change in mean minimum lumen diameter. FINDINGS: The mean minimum lumen diameter decreased from baseline to the last angiographic assessment (2 or 5 years) by 0.06 mm (95% CI 0.15 reduction to 0.01 increase) in the bezafibrate group and by 0.17 mm (0.33 reduction to 0.09 increase) in the placebo group. The treatment effect was therefore 0.13 mm (95% CI 0.10 to 0.15; p=0.049). Parallel treatment effects, although not statistically significant, were observed for the secondary angiographic endpoints (mean segment diameter 0.02 mm [0.01-0.04] and percentage stenosis -3.41% [-4.00 to -2.98]). The cumulative coronary event rate was significantly lower among bezafibrate-treated than among placebo-treated patients (three vs 11 patients; p=0.02). There were significant treatment effects of bezafibrate for serum concentrations of cholesterol (-9%; p<0.001), very-low-density-lipoprotein (VLDL) cholesterol (-35%; p<0.001), serum triglycerides (-31%; p<0.001), VLDL triglycerides (-37%; p<0.001), and plasma fibrinogen (-12%; p=0.001), whereas low-density (LDL) cholesterol concentrations did not change. High density lipoprotein (HDL) cholesterol increased significantly with bezafibrate (9%; p=0.02). INTERPRETATION: The results show that bezfibrate improves dyslipidaemia, lowers plasma fibrinogen, slows the progression of focal coronary atherosclerosis, and reduces coronary events in young survivors of myocardial infarction.

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.