The influence of atorvastatin on walking performance in peripheral arterial disease.

BACKGROUND: Recently it has been shown that statins can improve walking distance in patients with peripheral arterial disease. We examined whether statins used in moderate dosages with the aim of reaching the target levels for hypercholesterolemia could improve walking performance in patients with peripheral arterial disease. PATIENTS AND METHODS: 37 patients with hypercholesterolemia (LDL cholesterol = 3.46 +/- 0.13 mmol/l), who had previously not been treated by statins, were randomized in a double-blind study to a group receiving either atorvastatin at 20 mg/day (N = 20) or placebo (N = 17). All patients had stable intermittent claudication (Fontaine class IIa or IIb). At baseline, after one and three months the pain-free walking distance was measured in all patients. RESULTS: After 3 months patients in the treated group had reached target cholesterol values (LDL cholesterol = 2,34 +/- 0.9 mmol/l), whereas no significant change in lipids was observed in the control group. The ankle-brachial pressure index (ABPI) did not change significantly in either group. After 3 months the pain-free walking distance was increased significantly (p < 0.001), but similarly in both groups (at entry: 56 (53-108) m vs 53 (53-106) m; after 3 months: 79 (53-108) m vs 106 (66-159) m, for the treated and placebo group, respectively). Therefore this effect had to be attributed to regular exercise and not to statin use. CONCLUSIONS: Our results show that routine treatment with statin (atorvastatin 20 mg/day), which is effective in reducing the level of cholesterol, does not produce an improvement in walking performance in patients with peripheral arterial disease.

Endothelial dysfunction in post-myocardial infarction patients with various expressions of risk factors.

It has not been established yet whether patients who suffer myocardial infaction (MI) in the absence of classic risk factors also have endothelial dysfunction (ED), as has been shown for patients with risk factors, and if so, to what extent it is manifested. Young male patients in the stable phase after MI were included in the study. At the time of MI, 20 patients had high and 21 patients low expression of risk factors. The control group consisted of 35 healthy age-matched males. ED was estimated by ultrasound measurement of the endothelium-dependent dilation of the brachial artery, induced by the reactive hyperemia test. Compared to the control group, the level of endothelium-dependent vasodilation was significantly reduced in both groups of patients (controls: 9.1% +/- 5.6%; patients with high risk: 5.5% +/- 5.1%; patients with low risk: 5.6 +/- 3.5 %; ANOVA, p<.01). There was no difference between both groups of patients. These results showed that ED is not associated or due only to classic risk factors. It appears that ED may occur and precede development of atherosclerosis in the absence of classic risk factors. These novel findings can have important clinical implications.

Flow-mediated dilatation and intima-media thickness in patients with lacunar infarctions.

OBJECTIVES: To evaluate systemic endothelial function and atherosclerotic changes in patients with lacunar infarctions (LI) we examined flow-mediated dilatation (FMD) and intima-media thickness (IMT) and compared them to patients with similar risk factors (SR) and healthy controls. METHODS: FMD and IMT were investigated in patients with LI (20 patients, aged 60.9 +/- 7.3 years), 21 age- and gender-matched patients with SR and 21 healthy controls. RESULTS: FMD was more impaired in patients with LI (0.4% +/- 5.0%) compared to patients with SR (3.8% +/- 4.8%) and healthy controls (7.9% +/- 6.0%) (P < or = 0.01), whereas IMT was similarly thickened in both groups of patients. CONCLUSIONS: We found that patients with LI have a diminished FMD, but a similar IMT, compared to patients with SR. Our results reveal that for a given level of atherosclerosis patients with LI have additional endothelial impairment.

Both cerivastatin and fenofibrate improve arterial vasoreactivity in patients with combined hyperlipidaemia.

OBJECTIVES: The aim of this study was to compare the effects of cerivastatin and fenofibrate on endothelium dependent and independent arterial dilation. DESIGN: In a prospective, double blind study, 38 overweight, nonsmoking, males aged between 40 and 60 years with combined hyperlipidaemia were randomized and, after 6 weeks run-in phase with American Heart Association step I diet treatment, submitted to 12 weeks' treatment either with fenofibrate (250 mg daily) or cerivastatin. Cerivastatin was given in a daily dose of 0.2 mg for 6 weeks and was increased to 0.4 mg daily, if the LDL-C did not decrease below 3.0 mmol x L(-1). Flow-mediated (endothelium-dependent) dilation (FMD) and nitroglycerin-induced (endothelium-independent) [gliceryltrinitrate (GTN)] dilation of brachial artery were measured using high resolution ultrasound. RESULTS: The FMD increased from 3.4 +/- 3.3 to 9.3 +/- 2.4% (P < 0.001) in the cerivastatin group, and from 3.3 +/- 2.8 to 6.5 +/- 3.1% (P < 0.001) in the fenofibrate group, the improvement being significantly better after cerivastatin (P=0.006). GTN increased from 11.5 +/- 4.1 to 16.2 +/- 3.5% (P < 0.01) and from 11.1 +/- 2.5 to 16.0 +/- 2.9% (P < 0.01), respectively, with no difference between the groups. Cerivastatin reduced total cholesterol by 24%, LDL-cholesterol by 31%, triglycerides by 24%, ox-LDL by 29% and increased HDL-cholesterol by 5%, whilst, after fenofibrate, these changes were -15, -13, -41, -17 and 18%, respectively. Only the decrease of LDL-C turned out to be an independent predictor the FMD improvement. The improvement in GTN-induced dilation did not correlate with the changes in blood lipids. CONCLUSIONS: Both cerivastatin and fenofibrate lead to an improvement of endothelium-dependent and endothelium-independent dilation of brachial artery in overweight patients with combined hyperlipidaemia and no other atherosclerotic risk factors. The effects on FMD were greater in subjects receiving cerivastatin than in subjects receiving fenofibrate, but the effects on GTN were equal in both groups.

Fibrinolytic parameters and insulin resistance in young survivors of myocardial infarction with heterozygous familial hypercholesterolemia.

A characteristic feature of patients with heterozygous familial hypercholesterolemia (FH) is the premature occurrence of coronary artery disease because of elevated LDL cholesterol levels. Hyperinsulinemia and insulin resistance, important characteristics of the cardiovascular dysmetabolic syndrome (CDS), were found to be associated with coronary artery disease in FH subjects, as in the general population. We investigated whether hypofibrinolysis, as part of CDS, is independently associated with symptomatic coronary artery disease in these high-risk patients. Clinical examination (body mass index, waist circumference, blood pressure) and blood analysis (plasma tissue plasminogen activator (t-PA) antigen, plasminogen activator inhibitor (PAI-1) antigen and activity, fibrinogen, serum lipids and lipoproteins, fasting glucose and insulin) were carried out in 39 male patients with heterozygous FH (aged 46.6 +/- 8.8 years). Insulin resistance was calculated using the homeostasis model assessment (HOMA) mathematical model. Thirteen of the patients had suffered a myocardial infarction (MI) 5 to 8 years ago (aged 47.8 +/- 6.1 years) and 26 were free of coronary artery disease (aged 45.9 +/- 9.9 years). There was no difference in total and LDL cholesterol between the two groups. Patients with previous myocardial infarction had significantly higher levels of insulin, insulin resistance, triglycerides, t-PA antigen, PAI-1 antigen and activity, and significantly lower values of HDL cholesterol. Other widely recognised risk factors for coronary artery disease, such as smoking, systolic and diastolic blood pressure, obesity and age, did not differ significantly between the groups. In the logistic regression model, PAI-1 antigen, as a marker of hypofibrinolysis, emerged as an independent risk factor for the occurrence of myocardial infarction (odds ratio 1.55; p = 0.02). In summary our results suggest that the impairment of fibrinolytic activity resulting from elevated levels of PAI-1 antigen and activity and t-PA antigen is an independent variable in CDS associated with the premature occurrence of myocardial infarction in male patients with FH.