53 research outputs found
Clinical response to probucol in hypercholesterolemia: peculiar sensitivity of different subpopulations
No full textThe effectiveness of probucol therapy in group of 140 hypercholesterolemic patients who had been treated with probucol for at least six months, up to two years, was investigated in this study. The responses, in terms of individual percentage reduction of plasma LDL-C levels, have been evaluated trying to assess the sensitivity of specific subgroups of patients and their response to treatment. Clinical data and plasma lipid/lipoprotein levels were determined at baseline, at the sixth month and then at the end of 2 years. To identify and characterize subpopulation showing different sensitivity to the probucol treatment, the effectiveness of probucol therapy was related to the sex hormonal status and major lipid or non lipid parameters. Response to probucol was evaluated after stratification of patients by sex, tertiles of HDL-C levels (at baseline) and pre-/post-menopausal status in women. After six months plasma LDL-C levels was reduced of 7.0%. Stratifying patients into tertiles of HDL-C levels, the LDL-C response after six months of treatment was about 8.30% in the higher tertile group, vs a 6.5% of the lower. However in all patients who have been treated and followed for 2 years, the maximum LDL-C reduction was achieved at the end of the second year (11.6%
A new method for the non-invasive assessment of forearm arterial compliance in human subjects: impaired arterial compliance in hypercholesterolemia
No full textA new plethysmographic method that allows the non-invasive assessment of forearm arterial compliance (FAC) was developed. A study was carried out in order to demonstrate its feasibility, reproducibility and capacity to detect changes induced by nitrates or by muscarinic stimuli. Moreover, it has been investigated whether the proposed method was sensitive enough to detect differences in FAC between normo- and hypercholesterolemic subjects. Simultaneous recordings of forearm pulse volume and blood pressure (BP) over the whole cardiac cycle are used to establish the pulse volume-BP relationship. Due to the not uniform structural composition of the arterial media this relationship is non-linear. Thus, compliance can be defined only in terms of a given BP. In order to compute the non-linear compliance and to account for the BP dependence, FAC was measured on-line by computing the ratio of dV/dP, and the area under the FAC/BP curve (FAC(AUC)) was determined in a standard range of blood pressures (70-130 mmHg). The method is highly reproducible; indeed, the FAC(AUC) values obtained from 16 subjects with two independent observations were highly significantly correlated (r=0.91; p<0.0001, C.V.=15.2%). The method is also highly sensitive to nitrate and muscarinic stimuli. The results show a reduced FAC(AUC) in hypercholesterolemics vs controls [2.28±0.8x10E-3 vs 4.12±1.06x10E-3 (ml/100ml forearm/mmHg)•mmHg; p=0.0001]. In conclusion, this new plethysmographic method, allows the non-invasive assessment of the forearm arterial compliance and provides a potentially useful tool to detect and monitor in vivo, without stimulating arterial dilatation e.g. by acetylcholine infusion, the functional arterial changes in subjects with major risk factors for arterial disease as well as the effects of dietary/drug treatments
Non-invasive assessment of unstimulated forearm arterial compliance in human subjects. Impaired vasoreactivity in hypercholesterolaemia
No full textA study was carried out in order to determine the feasibility and reproducibility of a direct plethysmographic assessment of unstimulated forearm arterial compliance (FAC) in hypercholesterolaemic and normocholesterolaemic subjects. Simultaneous recordings of forearm pulse volume and blood pressure over the whole cardiac cycle are used to establish the pulse volume-blood pressure relationship. FAC was measured on-line by computing the ratio of dV/dP. The area under the curve (FAC(AUC)) of FAC/blood-pressure curve was determined in a standard range of blood pressure (70-130 mmHg). The method was validated by demonstrating its capacity to detect changes in FAC(AUC) induced by nitrate and by muscarinic stimuli. The results show a reduced FAC(AUC) in hypercholesterolaemic patients vs. controls (2.28 +/- 0.8 x 10(-3) vs. 4.12 +/- 1.06 x 10(-3) (mL 100 mL-1 forearm mmHg-1) mmHg; P = 0.0001). The method appears to be highly sensitive to nitrate and muscarinic stimuli. The new technique provides a potentially useful tool to detect and monitor in vivo, without stimulating arterial dilatation, e.g. by acetylcholine infusion, the functional arterial changes in subjects with a major risk factor for arterial disease as well as the effects of dietary/drug treatments
Cardiovascular determinants of QT interval duration in dysplipidemic patients in primary prevention in two genders
No full textAim: The aim was to investigate the relationship between rate corrected QT intervals in dyslipidemic patients in primary prevention (males vs. females) with the other major cardiovascular risk factors (age, SBP, DBP,BMI, LDL-C, HDL-C). Methods: 183 males and 222 females were investigated. Heart rate (HR) and QT intervals were measured automatically from resting ECGs. Six methods (Bazett, Fridericia, Hodges, Nomogram-Karjalainen, Rautaharju and Sagie-Framingham,) were used to correct the QT interval for HR. Exclusion criteria were: left or right bundle branch block, atrial fibrillation and use of medications affecting the QT intervals. Crude correlations (Spearman rank) between QT or QTcs with cardiovascular risk factors were examined. Linear regression analyses were performed to evaluate predominant determinants of QT. Results: In males statistically significant (p< 0.05 for Bazett and p< 0.01 for the other QTcs) crude correlations were found between QT or QTcs (B F,H, K, R and S-F) and age r=0.216 (corrected: 0.166-0.226-0.224-0.225-0.207-0.221).In females crude correlations were significant (p< 0.05) between QTcs (F, H, K) and age (r=0.139-0.150-0.137). We observed gender differences in the relationship betweenQT or QTcs with SBP. We found positive correlations in males for QTcs (B F,H, K, R and S-F) with SBP ( r=0.274-0.224-0.195-0.233-0.246-0.246; p< 0.01).Negative correlations were found in females (QT r= -0.190; p< 0.01 and QTc (H) r= -0.143;p< 0.05). In males after multiple linear regression analyses, age was the strongest predictor of QT (B= 0.062;p< 0.05), whereas SBP was the best determinant of QTc (Rautaharju B=0.343;p< 0.05). In females, age and SBP were significant independent variables for QT (B=0.612;-0.631;p< 0.01). Conclusions: QT measurements may provide additional diagnostic and prognostic information in dyslipidemic patients in primary prevention. However, the effect of cardiovascular risk factors seems to differ between males and females on QT interval duration
LIPOPROTEIN STRUCTURE IN MALE-SUBJECTS DURING IN-VIVO LIPOLYSIS - EFFECT OF AN ANTI-LIPOLYTIC TREATMENT WITH ACIPIMOX
No full textPlasma free fatty acid (FFA) levels were raised in healthy volunteers by the administration of a fatty meal and epinephrine infusion (0.15 mg/kg per min), to test the hypothesis that enhanced lipolysis might lead to changes in lipoprotein distribution and to the formation of lipoprotein complexes, also impairing the interconversion of high density lipoproteins (HDL). The study was carried out in double-blind conditions in volunteers pre-treated with either placebo or with acipimox, a nicotinic acid analogue with a long- lasting activity. Lipolysis was effectively induced; the treatment with acipimox prevented the rise of free fatty acids (FFA), and it also blunted the triglyceride (TG) increase occurring during the test. Whereas the mean low density lipoprotein (LDL) particle size did not change, the HDL particle distribution showed a progressive shift to smaller particles, both after placebo and after acipimox, the changes in size being maximal 3-7 h after the meal. Evaluation of HDL interconversion in plasma samples incubated at 37°C for 6 h showed the expected accumulation of HDL(2a) particles, with a parallel decrease of HDL(3a); however, this conversion was not affected by the presence of elevated FFA levels and no difference was noted in subjects taking either placebo or acipimox. These clinical data fail to confirm the hypothesis that enhanced lipolysis may lead to dramatic changes in plasma lipoprotein distribution and/or in aggregation or fusion of lipoprotein particles, as reported from in vitro experiments. This study, however, successfully achieved a useful model of exaggerated lipolysis and confirmed the important activity of a low dose nicotinic acid analogue in inhibiting lipolysis
Effect of plasma cholesterol reduction by pravastatin on the functional properties of forearm arteries in hypercholesterolemic patients
No full textSince functional properties in the vasculature of hypercholesterolemic subjects are impaired, a six-month pravastatin treatment (20 mg/die) was tested in an open design, on the impaired unstimulated forearm arterial compliance (Un-FAC(AUC)) of 14 asymptomatic type IIa familial hypercholesterolemic patients. In order to evaluate whether FAC(AUC) changes might be related to the extent of cholesterol reduction achieved, this evaluation was carried out in five severely hypercholesterolemic patients, undergoing LDL-apheresis
Omacor in familial combined hyperlipidemia: effects on lipids and low density lipoprotein subclasses
No full textElevations of plasma cholesterol and/or triglycerides, and the prevalence of small, dense LDL particles remarkably increase coronary risk in patients with familial combined hyperlipidemia (FCHL). A total of 14 FCHL patients were studied, to investigate the ability of Omacor, a drug containing the n-3 fatty acids eicosapentaenoic and docosahexaenoic acid (EPA and DHA), to favorably correct plasma lipid/lipoprotein levels and LDL particle distribution. The patients received four capsules daily of Omacor (providing 3.4 g EPA+DHA per day) or placebo for 8 weeks in a randomized, double-blind, cross-over study. Omacor significantly lowered plasma triglycerides and VLDL-cholesterol levels, by 27 and 18%, respectively. Total cholesterol did not change but LDL-cholesterol and apolipoprotein B (apoB) concentrations increased by 21 and 6%. As expected, LDL particles were small (diameter=24.9±0.3 nm) and apoB-rich (LDL-cholesterol/apoB ratio=1.27±0.26) in the selected subjects. After Omacor treatment LDL became enriched in cholesterol (LDL-cholesterol/apoB ratio=1.40±0.17), mainly cholesteryl esters, indicating accumulation in plasma of more buoyant and core enriched LDL particles. Indeed, the separation of LDL subclasses by rate zonal ultracentrifugation showed an increase of the plasma concentration of IDL and of the more buoyant, fast floating LDL-1 and LDL-2 subclasses after Omacor, with a parallel decrease in the concentration of the denser, slow floating LDL-3 subclass. However, the average LDL size did not change after Omacor (25.0±0.3 nm). The resistance of the small LDL pattern to drug-induced modifications implies that a maximal lipid-lowering effect must be achieved to reduce coronary risk in FCHL patients. Copyright (C) 2000 Elsevier Science Ireland Ltd
Iron-ovotransferrin preparation does not interfere with ciprofloxacin absorption
No full textIron supplements can interfere with the bioavailability of a number of drugs, including thyroxine, tetracycline derivatives, penicillamine, methyldopa, levodopa, carbidopa, ciprofloxacin, and the newer fluoroquinolones. A new iron formulation was tested in which iron ions are bound to ovotransferrin, a protein that shares more than an 80% similarity with the sequence of human transferrin and apparently is less likely than the commonly used iron salts to reduce drug absorption. Ciprofloxacin was taken as a model drug, of wide use and restricted range of therapeutic levels, and its absorption was evaluated after the administration of the iron-ovotransferrin complex versus an iron-gluconate formulation in healthy volunteers. At variance with the iron gluconate formulation, which led to a reduction of about 50% of peak serum ciprofloxacin levels (Cmax; 1.0 +/- 0.2 versus 2.4 +/- 0.3 micrograms/ml; p < 0.01) and of the area under the serum concentration-time curve from time 0 to infinity [AUC(0 - infinity); 10.1 +/- 1.1 versus 18.3 +/- 1.0 mg.L-1.hr; p < 0.01], the iron-ovotransferrin complex caused only modest, non significant changes in absorption with a minimal reduction of the AUC[0 - infinity) (17.3 +/- 1.0 versus 18.3 +/- 1.0 mg.L-1.hr; difference not significant) and a nonsignificant decrease in the Cmax (2.2 +/- 0.3 versus 2.4 +/- 0.3 microgram/ml; difference not significant). Iron was also well absorbed from the formulation in the presence of a fatty meal. The very common drug interactions with oral iron preparations can be effectively prevented by the use of the iron-ovotransferrin complex interacting to a minimal extent with a sensitive drug with a reduced margin of efficacy, such as ciprofloxacin
Common carotid intima-media thickness measurement. A method to improve accuracy and precision
No full textBACKGROUND AND PURPOSE:
High-resolution ultrasonographic imaging is a noninvasive method that allows estimation of the thickness of the intima-media complex in human carotid arteries. The determination of intima-media thickness involves several steps, each of which may introduce an error that influences the reproducibility of the method. In the present study, apart from the general reproducibility of the determination of intima-media thickness, the error introduced by each step was evaluated.
METHODS:
B-mode scans were performed on 14 randomly selected patients. The common carotid arteries were examined in anterior, lateral, and posterior planes, with a standard methodology and by a new method, making use of external reference points.
RESULTS:
The error in general reproducibility in determination of the subject's mean intima-media thickness was 5.9%. This parameter was also evaluated in a paired manner after dividing the whole artery into sectors; with this protocol, the percent error in general reproducibility was 15%. The main source of variability in the evaluation of common carotid intima-media thickness was found to lie in the operator's subjectivity in the choice of the carotid sector to be processed (percent error, 10.27%). A method was therefore designed that used external reference points, resulting in reduction of this error by 38.2%.
CONCLUSIONS:
While the mean intima-media thickness might be considered a reproducible parameter to evaluate differences between populations exposed to diverse risk factors, evolutional or therapy-induced changes in the individual may be better monitored on defined carotid sectors. This may be achieved with a high reproducibility by use of the proposed method based on external reference points
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