Intima-media thickness after pravastatin stabilizes also in patients with moderate to no reduction in LDL-cholesterol levels: the carotid atherosclerosis Italian ultrasound study.

The Carotid Atherosclerosis Italian Ultrasound study (CAIUS), a multicenter, double-blind clinical trial, performed in 305 asymptomatic, moderately hypercholesterolemic patients, clearly demonstrated beneficial effects of pravastatin on the carotid intima-media thickness (IMT) progression. The database of the CAIUS study was examined in order to investigate the presence of a relationship, if any, between the activity of pravastatin on IMT progression rate and its hypocholesterolemic effect. Quantitative B-mode ultrasound imaging was used to quantify the individual mean maximum IMT progression rate in 3 years. In the overall group of patients (placebo and pravastatin) covariance analysis showed that while the variable 'treatment' (0 = placebo, 1 = pravastatin) was significantly related to the reduction of IMT progression (F= 6.6, P = 0.01), the IMT progression did not correlate with the extent of LDL-C lowering (F= 0.00, P = 0.98). To further investigate this issue. the pravastatin treated group was stratified into quartiles of LDL-C reduction. In contrast to what was observed in the placebo group, in which a positive mean IMT progression rate was observed, independent of the extent of LDL-C reduction, no IMT progressionwas observed in any subgroup treated with pravastatin. No significant difference was found among quartiles and no trend could be identified. In conclusion, the effect of pravastatin treatment on carotid IMT progression rate is beneficial; however the CAIUS study demonstrated that lowering LDL-C by itself, does not explain the variability of beneficial changes in IMT.

Polymorphism of the apolipoprotein E gene and early carotid atherosclerosis defined by ultrasonography in asymptomatic adults.

Clinical and autoptical studies have suggested a predisposing role of the allele E4 of apolipoprotein E (apoE) in the development of atherosclerosis and cardiovascular disease. To investigate the possible contribution of apoE allele polymorphism to the carotid intima-media thickness (IMT) as assessed by ultrasound, we studied 260 asymptomatic nondiabetic subjects (121 men, 139 women; mean +/- SD age, 53 +/- 7 years), randomly selected from the population register of the inhabitants of Trieste, Italy. B-mode ultrasound was used to quantify the maximum IMT at 12 sites on the near and far wall of the common, bifurcation, and internal carotid arteries. ApoE genotypes were determined from amplified apoE sequences by restriction isotyping. The frequencies of E2, E3, and E4 alleles were 0.073, 0.827, and 0.100, respectively. As expected, subjects with E4 allele had the highest levels of total serum cholesterol and LDL cholesterol, subjects with E2 allele had the lowest levels, and those with E3 genotype had intermediate levels. The echographic measurements of carotid IMT showed increasing values from E2 to E4 carriers. After adjustment for total and LDL cholesterol serum levels, triglycerides, ratio of LDL to HDL cholesterol, age, sex, and body mass index, ANCOVA showed that the common carotid IMT was significantly greater (P = .029) in subjects with E4 allele compared with E3 carriers. Our data confirm the influence of apoE4 on cholesterol levels and clearly show that apoE genotype affects carotid atherosclerosis in its early stages in middle-aged asymptomatic subjects.

Fibromuscular dysplasia. A case report with multivessel vascular involvement.

A case of multivessel fibromuscular dysplasia involving the cervico-cephalic arteries, the right renal artery and the iliac arteries is reported. It was associated with reversible bilateral internal carotid arteries and vertebral arteries dissection, left thalamic infarct, right hemorrhagic cerebellar infarct, renovascular hypertension and intermittent claudication of the right lower limb. This report indicates that fibromuscular dysplasia is a systemic angiopathy. Renovascular hypertension may foster the appearance of complication such as dissection of the arteries affected by fibromuscular dysplasia. In the case investigated the dissection of cervico-cephalic arteries was followed by spontaneous healing and a favourable neurological outcome whereas at the iliac arteries a rapid deterioration was observed.

Carotid atherosclerosis: echographic patterns versus histological findings.

The study was carried out on 25 whole carotid arteries explanted from a corpse and perfused at constant pressure to reproduce the conditions of an in vivo examination as much as possible. Out of 5 samples with intimal thickening detected by echo, fibrosis of the tunica media was observed by the pathologist in 4 and microcalcification in 1. In 4 vessels with soft plaques at echo scanning, a wide necrotic area (2 cases), slack connective tissue (1 case) and cystic lesions (1 case) were observed. Hard lesions with (5 cases) or without (2 cases) a cone of shadow at echo evaluation corresponded to fibrous (2 cases) or fibrocalcific (3 cases) plaques. The histological study of the two echo-diagnosed thrombi showed an intermediate echographic pattern and the main feature of the non-occluding thrombus was the absence of a lumen-lesion interface. Mixed plaques were diagnosed at echo in 9 arteries and the correspondent histological aspect was a typical atheromatous lesion in all cases. Thus, the comparison of the ultrasound image with the histological findings proved the reliability of echography in the detection of atheromatous lesions with an excellent agreement between the results at the 2 examinations. Since the type of carotid lesions has an impact upon clinical events these results might support the use of vascular ultrasound images in clinical applications.

Early carotid atherosclerosis in asymptomatic adults with primary moderate hypercholesterolemia: a case-control study.

It has been shown that severe hypercholesterolemia is associated with carotid atherosclerosis but it is unclear whether this is true for moderate hypercholesterolemia. The aim of the study was to determine the prevalence of ultrasound detectable extent and severity of carotid intima-media thicknesses in 143 asymptomatic (79 males, 64 females, age range 45-64 years) primary moderate hypercholesterolemic patients (serum LDL cholesterol range 160-190 mg/dl). This group was compared with 143 asymptomatic normolipidemic subjects (serum LDL cholesterol < or = 130 mg/dl and serum triglycerides < 200 mg/dl) matched for age, sex and other cardiovascular risk factors. The maximum intima-media thickness (IMT) was measured using B-mode ultrasonography at 12 sites on the near and the far wall of the common, bifurcation and internal carotid arteries. The mean-maximum IMT at the 12 sites was compared in cases and controls. Moreover, the prevalence of intima-media thickening (i.e. at least one of the 12 sites with an IMT equal to or greater than 1.0 mm but less than 1.3) and plaques (i.e. at least one of the 12 sites with an IMT equal to or greater than 1.3 mm) was considered in the two groups. The mean-maximum intima-media thickness was 0.97 +/- 0.12 mm in hypercholesterolemic patients and 0.93 +/- 0.05 mm in controls (P < 0.0001). Intima-media thickening and plaques were detected in 76% of hypercholesterolemics vs. 57% of controls (P < 0.0002). Gender did not influence these differences.(ABSTRACT TRUNCATED AT 250 WORDS)

Lipoprotein(a) serum concentration in familial combined hyperlipidemia.

The lipoprotein(a) (Lp(a) concentrations in serum were measured by an ELISA technique in 53 subjects affected by familial combined hyperlipidemia (FCHL) and in 347 healthy individuals. Lp(a) geometric means did not differ significantly between the two groups despite the different distributions. In hyperlipidemic subjects, the distribution was markedly shifted to the right (median 17 mg/dl) while in controls it was highly skewed to the left (median = 11 mg/dl). In FCHL, Lp(a) serum levels did not differ between patients with or without coronary heart disease (CHD). It was concluded that, differently from familial hypercholesterolemia (FH), in FCHL Lp(a) may not be elevated in comparison with an adequate control population.

Treatment of intermittent claudication with antiplatelet agents.

In a double-blind study, 296 patients with intermittent claudication (Fontaine stage II) were treated with 250 mg ticlopidine twice daily, 500 mg aspirin every third day plus 75 mg dipyridamole three times daily, or 300 mg xanthinol nicotinate three times daily for 6 months. Ticlopidine and aspirin/dipyridamole, but not xanthinol nicotinate, improved platelet aggregation, reduced beta-thromboglobulin, platelet factor IV and fibrinopeptide A concentrations, and increased antithrombin III concentrations and red blood cell filterability. No changes in lipid profiles, platelet count or fibrinogen were recorded following any treatment. The doppler systolic blood pressure ratio was improved in patients treated with ticlopidine or aspirin/dipyridamole, but not with xanthinol nicotinate. It is concluded that antiplatelet treatment is useful for the treatment of limb arteriopathy.