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A Hamsten

Publications and source records attributed to A Hamsten.

At least 109 records · Page 6Linked to original sources
PubMed1998

A common functional polymorphism in the promoter region of the microsomal triglyceride transfer protein gene influences plasma LDL levels.

Microsomal triglyceride transfer protein (MTP) is required for the assembly and cellular secretion of apolipoprotein B (apoB) -containing lipoproteins from the liver and intestine. The secretion pattern of apoB-containing lipoproteins is likely to influence the VLDL and LDL levels in plasma. By initial opportunistic screening for polymorphic sites in the regulatory region of the MTP gene by gene sequencing in 20 healthy male subjects, a common functional G/T polymorphism was detected 493 bp upstream from the transcriptional start point. There was differential binding of unique nuclear proteins at this site, as shown by electrophoretic mobility shift assay. The G variant seemed to bind two or three nuclear proteins that do not bind to the T variant. Expression studies with minimal promoter constructs linked to the chloramphenicol acetyltransferase reporter and transfected into HepG2 cells revealed marked enhancement of transcriptional activity with the T variant. The prevalence of the MTP promoter genotypes was investigated in a group of 184 healthy, middle-aged white men; the frequency of homozygosity for the MTP -493 T variant was .06 and the allele frequency of MTP -493T was .25 in the population. These homozygous subjects had a 22% lower LDL cholesterol concentration than did heterozygotes or subjects homozygous for the MTP -493 G variant (2.9+/-0.6 versus 3.7+/-0.8 mmol/L, P<.05). Analysis of apoB and triglyceride contents in VLDL subfractions revealed a markedly changed balance within the VLDL population. Subjects homozygous for the MTP -493 T variant had fewer but more lipid-rich VLDL particles, thereby arguing for an effect of MTP expression on the hepatic secretion of triglyceride-rich, apoB-containing lipoproteins. This common genetic variation of the MTP promoter is likely to have important implications for cardiovascular disease.

Adult↗
PubMed1998

Platelet activity in vivo in hyperlipoproteinemia--importance of combined hyperlipidemia.

Platelet hyperactivity in vitro is found in patients with isolated hypercholesterolemia. It is, however, less well established if platelet activity in vivo is enhanced, and if there are differences between various types of hyperlipoproteinemia. Platelet function in vivo was studied at rest and during mental stress in men with isolated hypercholesterolemia (phenotype IIa; n = 21) or combined hyperlipidemia (phenotype IIb; n = 29), and age-matched normolipidemic controls (n = 41). The urinary excretion of 11-dehydrothromboxane B2 was elevated in patients compared to controls (IIa, p <0.05; IIb, p <0.001), and higher in type IIb than in IIa patients (p <0.05). Platelet secretion, assessed as plasma beta-thromboglobulin levels, was higher in type IIb patients compared to controls (p <0.01) and type IIa patients (p <0.05) during mental stress. The urinary excretion of beta-thromboglobulin was also elevated in type IIb patients compared to controls (p <0.05). Platelet aggregability at rest, as measured by filtragometry ex vivo was, however, reduced in both patient groups compared to controls (p <0.05). No correlations were found between plasma lipoprotein levels and markers of platelet function in vivo. Type IIb patients had higher plasma fibrinogen levels and higher leukocyte counts than controls (p <0.05 and p <0.001) and type IIa patients (p <0.05 and p = 0.06). Thromboxane excretion was positively related to fibrinogen levels and leukocyte counts (p <0.01 for both). Preliminary data regarding serum TNF-alpha also indicated an elevation of this inflammatory cytokine in type IIb patients (p <0.05 vs controls). In conclusion, thromboxane generation and platelet secretion in vivo are enhanced in patients with hypercholesterolemia, and particularly so among patients with concomitant elevation of plasma triglycerides. The mechanism is unknown, but inflammatory mediators may be involved. The present findings are of interest in relation to the role of triglycerides in coronary artery disease.

Adult↗
PubMed1998

Transient triglyceridemia in healthy normolipidemic men increases cellular processing of large very low density lipoproteins by fibroblasts in vitro.

Exaggerated and prolonged postprandial triglyceridemia is a characteristic of patients with precocious coronary heart disease. Although large very low density lipoprotein (VLDL) particles accumulate during alimentary lipemia, the biological properties of the postprandial VLDL remain unknown. In the present study, an intravenous infusion of a chylomicron-like emulsion was given to healthy normolipidemic men to examine the effects of transient triglyceridemia in vivo on compositional and cell biological characteristics of VLDL. The postinfusion large(Svedberg flotation rate (Sf) (60-400) VLDL was found to have increased capacity to inhibit low density lipoprotein (LDL) binding to the LDL-receptor and a greater ability to suppress the 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity of cultured fibroblasts compared to VLDL isolated from fasting plasma. These alterations in cellular interactions were accompanied by increases in the number of apolipoprotein (apo) E, C-I, and C-III molecules per large VLDL particle and loss of apoC-II, compositional changes similar to those observed after an oral fat load. The increase in number of apoE molecules per large VLDL particle correlated positively and significantly with the increase in the capacity of large VLDL to inhibit LDL binding to the LDL receptor (r = 0.76, P = 0.01, n = 10). In contrast, the composition of the small (Sf 20-60) VLDL particles did not change significantly, nor was the LDL receptor-mediated processing of these particles altered consistently. These observations indicate that large VLDL particles that accumulate during alimentary lipemia undergo compositional changes that render them more prone to cellular binding and uptake.

Adult↗
PubMed1998

Differences in apolipoprotein and lipid composition between human chylomicron remnants and very low density lipoproteins isolated from fasting and postprandial plasma.

Triglyceride-rich lipoproteins (TRLs) that are modified during alimentary lipemia and their remnants are indicated to play an important role in the development of atherosclerosis. Although recent studies in transgenic and gene knock-out animal models have shed new light on the function of different apolipoproteins (apos) in the metabolism of TRLs and on their respective role in atherogenesis in these models, little is known about the compositional properties of human chylomicron remnants and very low density lipoprotein (VLDL). To address this issue, apos E, C-I, C-II, and C-III and lipids (triglycerides, phospholipids and cholesterol) were measured in Svedberg flotation rate (Sf) 60-400 and Sf 20-60 subfractions of VLDL and chylomicron remnants isolated from fasting and postprandial plasma samples in ten normotriglyceridemic men. VLDL was separated from chylomicron remnants by immunoaffinity chromatography using monoclonal antibodies (4G3 and 5E11) recognizing apoB-100 but not apoB-48 epitopes. The triglyceride, cholesterol and apoC-II contents of large (Sf 60-400) chylomicron remnants were significantly higher compared with large VLDL particles, while the small (Sf 20-60) chylomicron remnants contained significantly more apoC-II molecules but fewer apoC-I molecules than small VLDL. Whereas the apoC-III contents of large chylomicrons decreased, the apoC-III contents of large VLDL increased postprandially. The cholesterol to triglyceride ratio of large VLDL particles increased transiently by 50% in response to the oral fat load, whereas the cholesterol to triglyceride ratio of large chylomicron remnant particles and small TRL remnants increased 50-100% throughout the entire postprandial period. The specific alterations of the apolipoprotein and lipid composition of chylomicron remnants and VLDL particles observed during alimentary lipemia are likely to target these lipoprotein species differently to metabolic routes and to confer both endogenous and exogenous remnant lipoprotein roles in atherogenesis.

Adult↗
PubMed1998

Coagulation factor V (Arg506-->Gln) mutation and early saphenous vein graft occlusion after coronary artery bypass grafting.

The factor V (Arg506-->Gln) mutation confers an increased risk of deep vein thrombosis, whereas its role in saphenous vein graft closure after coronary artery bypass grafting (CABG) remains unclear. This study examined the anticoagulant response to activated protein C (APC ratio) in relation to the surgical trauma and the significance of the factor V Leiden mutation in determining postoperative thrombin generation and fibrin formation and the risk of early vein graft occlusion. A total of 108 men undergoing elective CABG for exertional angina pectoris (mean age 61.1 +/- 8.7 years) were examined. The patency of saphenous vein grafts was studied at routine reangiography three months after CABG. Of 100 patients who underwent reangiography, 23 had one or more occluded vein grafts at reangiography. Heterozygosity for the factor V (Arg506-->Gln) mutation tended to be associated with early saphenous vein graft occlusion (5/11 carriers vs. 18/89 non-carriers with graft occlusion, chi2 = 3.52, p = 0.06), whereas pre- and postoperative APC ratios did not. Pre- and postoperative determinations of prothrombin fragment 1+2, thrombin-antithrombin complexes and soluble fibrin levels did not differ between patients with and without the mutation. Early saphenous vein graft occlusion after CABG could tentatively be added to deep vein thrombosis as a vascular complication that can be attributed to the factor V (Arg506-->Gln) mutation.

Aged↗
PubMed1997

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.

Adult↗
PubMed1997

The way ahead in the management of unstable coronary artery disease.

Recent knowledge of the composition of coronary plaques is briefly reviewed, including factors that are considered to be responsible for the provocation of instability. Based on this information, possibilities for the early detection of threatening instability and measures to prevent destabilization of coronary plaques and to counteract thrombus formation are discussed.

Collagen↗
PubMed1997

Mortality prediction in diabetic patients with myocardial infarction: experiences from the DIGAMI study.

OBJECTIVES: We analysed predictors of 1-year mortality following acute myocardial infarction in patients with diabetes mellitus by applying uni- and multivariate statistics on the DIGAMI cohort. BACKGROUND: Diabetic patients with acute myocardial infarction have a poor prognosis. This may depend on a poor metabolic control, a hypothesis that was tested in DIGAMI, a prospective randomised study. In this trial institution of immediate intensive insulin treatment reduced 1-year mortality by 30%. METHODS: We recruited 620 diabetic patients with acute myocardial infarction, 314 of whom served as controls, while the remaining 306 patients were treated with an acute insulin-glucose infusion followed by multidose subcutaneous insulin. RESULTS: Age, previous myocardial damage, duration of the diabetes and previous insulin therapy were significantly related to 1-year mortality, while conventional risk factors lacked independent prognostic weight. Female sex was not linked to mortality when controlling for the confounding effects of other predictors. One of the strongest predictors of a fatal outcome, in particular during the hospital phase, was blood glucose at hospital admission. Beta-blockade appeared to exert a striking, independent secondary-preventive effect. CONCLUSIONS: It seems that good metabolic control and not conventional risk factors is of major importance for diabetic patients sustaining acute myocardial infarction. Also treatment with beta-blockade seems to be of special importance in this category of patients.

Adrenergic beta-Antagonists↗
PubMed1997

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.

Bezafibrate↗
PubMed1997

Alterations of VLDL composition during alimentary lipemia.

Apoliprotein (apo) B-100-containing very low density lipoprotein (VLDL) particles secreted from the liver accumulate in plasma during alimentary lipemia. To determine whether changes of VLDL composition occur in the postprandial state that may render these lipoproteins more atherogenic, apoE, C-I, C-II, and C-III, and lipids (triglycerides, phospholipids, and cholesterol) were measured in Svedberg flotation (Sf) 60-400 (large) and Sf 20-60 (small) VLDL before and after an oral fat load. Ten normotriglyceridemic (NTG) and three hypertriglyceridemic (HTG) healthy men were given a fat-rich mixed meal (1,000 kCal with 60.2 E% from fat). Triglyceride-rich lipoproteins were isolated by density gradient ultracentrifugation from plasma samples obtained before (fasting) and at 2-h intervals after the meal. VLDL was then separated from chylomicrons and their remnants by immunoaffinity chromatography using monoclonal antibodies 4G3 and 5E11, recognizing apoB-100, but not apoB-48 epitopes. Large and small VLDL isolated from the NTG group were enriched with apoE and C-I, and cholesterol, but depleted of apoC-II in the postprandial state, whereas the apoC-III, triglyceride, and phospholipid contents were essentially unchanged. The compositional changes of VLDL in HTG subjects were similar but more pronounced compared with NTG subjects. We conclude that postprandial lipemia in healthy men induces transient compositional alterations of VLDL that link these lipoprotein species to the formation of atherosclerosis.

Adult↗
PubMed1997

Chylomicron/chylomicron remnant turnover in humans: evidence for margination of chylomicrons and poor conversion of larger to smaller chylomicron remnants.

The size of cholesterol-rich lipoprotein particles is a strong determinant of whether they may be deposited in the arterial wall and by this become potentially atherogenic. This study deals with the in vivo transformation of larger-sized chylomicrons and chylomicron remnants to smaller-sized remnants. Twelve healthy men aged 22 to 45 years were given a fatty meal to which retinyl palmitate (RP) had been added. Plasmapheresis was performed 4 1/2 h after meal intake to isolate approximately 400 ml plasma. The RP-rich plasma was re-injected to the subject 24 h later. The RP content was determined in whole plasma and in Svedberg flotation rate fractions (Sf) > 400, Sf 60-400 and Sf 20-60. A compartmental model was developed for the kinetic analysis. Lipoprotein fractions showed minimal signs of aggregation, thus arguing for well-preserved postprandial lipoproteins. Approximately a fourth [23% (4-68%)] of the RP-containing lipoproteins in the Sf > 400 pool was converted to smaller species (Sf 60-400). Conversion of material from the Sf 60-400 to the Sf 20-60 fraction could not be detected. In a second study a large bolus dose of a triglyceride emulsion (Intralipid) was injected to subjects shortly after the RP-labeled plasma to investigate the endothelial binding of the chylomicron/chylomicron remnants. RP material in the Sf > 400 fraction rapidly returned to plasma, arguing for margination of chylomicrons, whereas the corresponding effect was minimal in the Sf 60-400 and Sf 20-60 fractions. The formation of small chylomicron remnants from the larger chylomicron/chylomicron remnant species is limited and large chylomicron/chylomicron remnants are not evenly distributed in plasma, rather they show signs of being marginated to the vascular endothelium.

Adolescent↗
PubMed1996

Progression of coronary atherosclerosis is associated with a common genetic variant of the human stromelysin-1 promoter which results in reduced gene expression.

There is a common polymorphism in the promoter sequence of the human stromelysin-1 gene, with one allele having a run of six adenosines (6A) and the other five adenosines (5A). We have previously reported, in a 3-year follow-up study of patients with coronary atherosclerosis, that those patients who are homozygous for the 6A allele show a more rapid progression of the disease. In this study, we have investigated whether the 5A/6A promoter polymorphism plays a role in the regulation of stromelysin-1 gene expression. In transient transfection experiments, a stromelysin-1 promoter construct with 6A at the polymorphic site was found to express less of the chloramphenicol acetyltransferase reporter gene than a construct containing 5A. Electrophoretic mobility shift assay and DNase I footprinting revealed the interaction of one or more nuclear protein(s) with the DNA sequence at the 5A/6A polymorphic site. The binding of one of the nucleoprotein factors was more readily detectable with an oligonucleotide probe corresponding to the 6A allele as compared with a probe corresponding to the 5A allele. Replacing the core binding sequence with a random DNA sequence abolished the interaction between the nuclear protein(s) and the probe and also increased reporter gene expression in transiently transfected cells. Thus, the common 5A/6A polymorphism of the human stromelysin-1 promoter appears to play an important role in regulating stromelysin-1 gene expression and may be involved in the progression of coronary heart disease.

Alleles↗
PubMed1996

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.

Adult↗
PubMed1996

High-density lipoprotein: relations to metabolic parameters and severity of coronary artery disease.

The regulation of plasma high-density lipoprotein (HDL) cholesterol level by the joint influence of plasma lipoprotein lipids, lipoprotein lipase (LPL), hepatic lipase (HL), cholesteryl ester transfer protein (CETP), oral glucose tolerance, and postload plasma insulin and proinsulin levels was investigated in young postinfarction patients and healthy population-based control subjects. In addition, the association between HDL cholesterol and the number and severity of coronary stenoses previously reported in this cohort of young postinfarction patients was further investigated by analyzing the determinants and angiographic relations of HDL subclasses measured by gradient gel electrophoresis. The following parameters showed significant univariate relations with HDL cholesterol level in the patient group: very-low-density lipoprotein (VLDL) cholesterol and triglyceride, low-density lipoprotein (LDL) triglyceride, and postload plasma insulin concentrations, preheparin plasma LPL mass, and postheparin plasma HL activity. In the control group, significant correlations with HDL cholesterol concentration in addition to those noted among the patients were found for body mass index (BMI), LDL cholesterol level, postload plasma intact proinsulin concentration, and LPL activity in postheparin plasma. In contrast to the patients, no significant relations were noted for postload plasma insulin level and preheparin plasma LPL mass. Multiple stepwise regression analysis showed that 42% of the variability of HDL cholesterol in the patients could be accounted for by VLDL cholesterol concentration (29%), LDL triglyceride level (7%), and postheparin plasma HL activity (8%), whereas the corresponding figure in controls was 35% (VLDL cholesterol concentration [9%] and postheparin plasma HL activity [26%]. The strength of the relationships of HDL cholesterol and HDL subclasses to the coronary stenosis score was similar and statistically significant (r = .25 to .36). When the metabolic parameters that correlated with HDL cholesterol and HDL subclass concentrations in univariate analysis were used as covariates, all relations to the coronary stenosis score disappeared. This clearly indicates that the influence of triglyceride-rich lipoproteins and lipolytic enzymes needs to be considered when assessing the association between HDL cholesterol and coronary artery disease (CAD).

Adult↗
PubMed1996

Apolipoprotein B-48.

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Apolipoprotein B-100↗
PubMed1996

Inverse relation between the concentration of low-density-lipoprotein vitamin E and severity of coronary artery disease.

Oxidation of low-density lipoprotein (LDL) is believed to play an important role in atherogenesis, and antioxidant vitamins are thought to protect against coronary artery disease (CAD). We investigated whether the vitamin E concentrations in serum and LDL were associated with the severity of CAD as assessed by a semiquantitative scoring system in which coronary angiograms are analyzed for the number and size of distinct stenotic lesions (global stenosis score). The study group consisted of 64 consecutive male survivors of myocardial infarction aged < 45 y. Lipid-adjusted serum and LDL vitamin E concentrations were significantly lower in the patients than in 35 age-matched male control subjects, whereas the absolute serum and LDL vitamin E concentrations did not differ significantly. No associations were found between the serum concentration or lipid-adjusted serum values of vitamin E and the stenosis score. In contrast, significant inverse correlation was found between the LDL vitamin E concentration, whether adjusted to the lipid (r=-0.477,P<0.001) or protein (r=-0.375, P<0.01) content of LDL, and the global coronary stenosis score. We conclude that a low LDL vitamin E concentration might play a role in the development of stenoses in coronary arteries and may contribute to clinically manifest CAD.

Adult↗
PubMed1996

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.

Adult↗