Maurizio Fisicaro

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.

MMP-9 Microsatellite Polymorphism and Susceptibility to Carotid Arteries Atherosclerosis

Objective—The aims of this study were to compare a microsatellite polymorphism (PM) of matrix metalloproteinase (MMP)-9 in patients with carotid atherosclerosis and control population, and to assess the relationship between this PM and plaque structure. Methods and Results—One hundred fifty patients referring to vascular diagnostic centers for suspected carotid atherosclerosis (at ultrasound examination: 110 positive, 40 negative) and controls (n=110) have been genotyped for MMP-9 PM. After controlling for risk factors, allelic and genotype frequencies were significantly different among the groups, with significant prevalence of long microsatellites in patients with carotid atherosclerosis. Long microsatellites (settled as 22 to 27 repeats) were associated with carotid atherosclerosis (odds ratio [OR], 5.2; 95% confidence interval [CI], 2.9 to 9.2), compared with controls; an independent case control study on patients with coronary atherosclerosis confirmed such result. Binary logistic regression showed that hypertension, long microsatellites in MMP-9 PM and smoking habits were variables accounting for the difference between ultrasound-positive patients and controls. Long microsatellites were also associated to plaques with thin fibrous cap and echolucent core (OR, 13.1; 95% CI, 1.6 to 100). These alleles were slightly more represented in female patients (&khgr;2 test=0.019; OR, 2.7; 95% CI, 1.2 to 6) but not associated with other risk factors. Plasma MMP-9 levels were related neither to MMP-9 PM nor to plaque type, and were related to gender and extension of atherosclerosis in carotid arteries. Conclusions—The number of repeats (≥22 CA) in the microsatellite of MMP-9 promoter, but not MMP-9 plasma levels, is associated to carotid atherosclerosis and particularly to plaques with a thin fibrous cap.

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 β-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.

Tolerability and efficacy of combination therapy with simvastatin plus gemfibrozil in type IIb refractory familial combined hyperlipidemia

Abstract Type IIb hyperlipidemia due to familial combined hyperlipidemia (FCH) is a common lipid metabolism disorder associated with a high incidence of coronary heart disease. Simvastatin and gemfibrozil are two drugs commonly used to treat this lipid abnormality. However, monotherapy with these drugs often fails to reduce serum cholesterol and triglycerides to optimal levels. In this study the tolerability and efficacy of combined simvastatin plus gemfibrozil therapy was investigated over 18 months in 20 patients (15 men and five women, ages 42 to 71 years) at high risk for atherosclerosis affected by type IIb FCH. Patients were selected because they did not respond satisfactorily to monotherapy with simvastatin or gemfibrozil, taken for at least 6 months with no side effects, namely laboratory test alterations or subjective complaints. The administration protocol was designed as a three-phase open study. In the first phase (8 weeks) patients were assigned to take 10 mg/day simvastatin plus 600 mg/day gemfibrozil; in the second phase (4 months) variable doses of simvastatin [10 to 20 mg/day, depending on the decrease in low-density lipoprotein (LDL) cholesterol] and gemfibrozil (600 to 1200 mg/day, depending on serum triglyceride values) were prescribed. In the follow-up period (phase 3) optimum therapy was maintained. No patient dropped out of the study, and no side effects were recorded. Serum creatine phosphokinase remained within the normal range, as did other hematochemical tolerability parameters. At the end of the follow-up, total (TC) and LDL cholesterol dropped by 35% (from 334 ± 38 mg/dl to 218 ± 27 mg/dl, P P P P P

Clinical profile and outcome of patients with rheumatoid arthritis and abnormally high aortic stiffness

Objectives Ascending aorta has an increased stiffness (AoSI) in rheumatoid arthritis (RA) patients due to their chronic inflammatory status. We assessed prevalence and factors associated with increased AoSI and its prognostic role in a large cohort of RA patients. Methods We prospectively analysed 226 RA patients without overt cardiac disease compared with 226 non-RA patients matched for cardiovascular risk factors (non-RA controls). Abnormally high AoSI was diagnosed if AoSI > 6.07% (95th percentile of the AoSI detected in our reference healthy population). AoSI was assessed at the level of the aortic root by two-dimensional guided M-mode evaluation as part of a thorough echocardiography performed in all patients. Results AoSI was significantly higher in the RA patients than non-RA controls (6.3 ± 4.5% vs. 4.6 ± 3.5%, p < 0.001); it was related to older age, higher systolic blood pressure and RA disease. Predictors of AoSI in RA patients were older age, higher systolic blood pressure and the non-prescription of non-steroidal anti-inflammatory drug and/or immunomodulatory/anti-cytotoxic agents. Abnormally high AoSI was diagnosed in 41% RA patients and 21% non-RA controls (p < 0.001). The RA phenotype with abnormally high AoSI was a > 60 years old subject with systolic blood pressure > 129 mmHg, mitral annular calcification who was not receiving non-steroidal anti-inflammatory drug. By multivariate Cox regression analysis abnormally high AoSI independently predicted death or all-cause hospitalization (hazard ratio 2.85 (95% confidence interval 1.03–7.85)) at 12-month follow-up. Conclusions Increased AoSI is common, can be predicted by an ordinary clinical assessment and is a strong predictor of adverse clinical outcome at mid-term follow-up in patients with RA.

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.

Radial pseudoaneurysm after a puncture for blood gas analysis.

Radial pseudoaneurysm (PA) is a rare complication of the transradial approach for the arterial catheterization.