Biomedical subjects

P Rubba

Publications and source records attributed to P Rubba.

At least 37 records · Page 2Linked to original sources

PubMed1999

Stiffness of the aortic wall in hypercholesterolemic children.

Arterial stiffness may be an indicator of early vascular changes signaling the development of vascular disease, while hypercholesterolemia is a well-recognized promoter of atherogenesis. It has been shown that hypercholesterolemic children have a thicker intima-media in the carotid artery than children with normal cholesterol. The aim of this study was to assess the stiffness of the abdominal aorta in children with hypercholesterolemia. Noninvasive imaging evaluation of the aorta was performed in 85 outpatient children (age, 3 to 14 years) with and without high cholesterol levels ((and) 247 mg/dL [6.4 mmol/L], respectively). Ultrasound imaging of the abdominal aorta that allowed diameter measurements was available in 67 children. Using an image-processing workstation, the maximum and minimum internal diameter of the aorta was measured, and the following indices of elastic properties of the abdominal aorta were derived: arterial strain, pressure-strain elastic modulus, and stiffness. No statistical difference for aortic strain, stiffness, and elastic modulus was found in normocholesterolemic compared with hypercholesterolemic children. The effect of age on the elastic modulus was different in the two groups: in normal children, the elastic modulus increased linearly with age (y = -0.020+0.003 x age [months], P<.001), while the high-cholesterol group had a weak increase in this parameter with age (y = 0.118+0.0009 x age, P = .051). The slope of the regression equations (elastic modulus vage) was significantly different in the two groups (t = 2.45, P = .017). The behavior of arterial stiffness with respect to age was similar, y = 0.677+0.018 x age (P = .002) in normocholesterolemic children and y = 2.06+0.00198 x age (P = .66) in hypercholesterolemic children. The slope of the regression equations (stiffness v. age) was significantly different in the two groups (t = 2.37, P = .021). The present study demonstrates an influence of hypercholesterolemia on age-related modification in the elastic properties of the aorta. A remodeling of the aortic wall in hypercholesterolemic children (cholesterolemia >247 mg/dL) could explain the different age-dependent increase in aortic elastic modulus and stiffness.

Adolescent↗

PubMed1999

Cholesterol-lowering and vascular reactivity in relation to coronary heart disease.

Despite the strong evidence that cholesterol-lowering treatment is effective in the primary and secondary prevention of coronary heart disease, there is a great discrepancy between the results relating to prognosis and the ability of this treatment to induce regression of coronary atheromatous plaques. Since hypercholesterolemia causes a dysfunction in vascular reactivity, improvement can also be ascribed to restoration of vascular relaxation capacity. This conclusion is supported by a wealth of clinical and experimental evidence.

Anticholesteremic Agents↗

PubMed1998

Low circulating folate and vitamin B6 concentrations: risk factors for stroke, peripheral vascular disease, and coronary artery disease. European COMAC Group.

BACKGROUND: A high plasma homocysteine concentration is a risk factor for atherosclerosis, and circulating concentrations of homocysteine are related to levels of folate and vitamin B6. This study was performed to explore the interrelationships between homocysteine, B vitamins, and vascular diseases and to evaluate the role of these vitamins as risk factors for atherosclerosis. METHODS: In a multicenter case-control study in Europe, 750 patients with documented vascular disease and 800 control subjects frequency-matched for age and sex were compared. Plasma levels of total homocysteine (before and after methionine loading) were determined, as were those of red cell folate, vitamin B12, and vitamin B6. RESULTS: In a conditional logistic regression model, homocysteine concentrations greater than the 80th percentile for control subjects either fasting (12.1 micromol/L) or after a methionine load (38.0 micromol/L) were associated with an elevated risk of vascular disease independent of all traditional risk factors. In addition, concentrations of red cell folate below the lowest 10th percentile (<513 nmol/L) and concentrations of vitamin B6 below the lowest 20th percentile (<23.3 nmol/L) for control subjects were also associated with increased risk. This risk was independent of conventional risk factors and for folate was explained in part by increased homocysteine levels. In contrast, the relationship between vitamin B6 and atherosclerosis was independent of homocysteine levels both before and after methionine loading. CONCLUSIONS: Lower levels of folate and vitamin B6 confer an increased risk of atherosclerosis. Clinical trials are now required to evaluate the effect of treatment with these vitamins in the primary and secondary prevention of vascular diseases.

Adult↗

PubMed1997

Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project.

CONTEXT: Elevated plasma homocysteine is a known risk factor for atherosclerotic vascular disease, but the strength of the relationship and the interaction of plasma homocysteine with other risk factors are unclear. OBJECTIVE: To establish the magnitude of the vascular disease risk associated with an increased plasma homocysteine level and to examine interaction effects between elevated plasma homocysteine level and conventional risk factors. DESIGN: Case-control study. SETTING: Nineteen centers in 9 European countries. PATIENTS: A total of 750 cases of atherosclerotic vascular disease (cardiac, cerebral, and peripheral) and 800 controls of both sexes younger than 60 years. MEASUREMENTS: Plasma total homocysteine was measured while subjects were fasting and after a standardized methionine-loading test, which involves the administration of 100 mg of methionine per kilogram and stresses the metabolic pathway responsible for the irreversible degradation of homocysteine. Plasma cobalamin, pyridoxal 5'-phosphate, red blood cell folate, serum cholesterol, smoking, and blood pressure were also measured. RESULTS: The relative risk for vascular disease in the top fifth compared with the bottom four fifths of the control fasting total homocysteine distribution was 2.2 (95% confidence interval, 1.6-2.9). Methionine loading identified an additional 27% of at-risk cases. A dose-response effect was noted between total homocysteine level and risk. The risk was similar to and independent of that of other risk factors, but interaction effects were noted between homocysteine and these risk factors; for both sexes combined, an increased fasting homocysteine level showed a more than multiplicative effect on risk in smokers and in hypertensive subjects. Red blood cell folate, cobalamin, and pyridoxal phosphate, all of which modulate homocysteine metabolism, were inversely related to total homocysteine levels. Compared with nonusers of vitamin supplements, the small number of subjects taking such vitamins appeared to have a substantially lower risk of vascular disease, a proportion of which was attributable to lower plasma homocysteine levels. CONCLUSIONS: An increased plasma total homocysteine level confers an independent risk of vascular disease similar to that of smoking or hyperlipidemia. It powerfully increases the risk associated with smoking and hypertension. It is time to undertake randomized controlled trials of the effect of vitamins that reduce plasma homocysteine levels on vascular disease risk.

Adult↗

PubMed1996

Effects of short-term reduction in serum cholesterol with simvastatin in patients with stable angina pectoris and mild to moderate hypercholesterolemia.

To evaluate the effects of short-term cholesterol-lowering treatment on myocardial effort ischemia, 22 patients with stable effort ischemia and mild to moderate hypercholesterolemia (low density lipoprotein [LDL] cholesterol 160 to 220 mg/dl) were randomly allocated at baseline (TO) in 2 groups. Group A included 12 patients treated with simvastatin 10 mg bid; group B included 10 patients treated with placebo. All patients underwent a treadmill electrocardiography (ECG) test; total cholesterol, HDL and LDL cholesterol, triglycerides, plasma, and blood viscosity were measured. All tests were repeated after 4 and 12 weeks. For 18 of the same patients (11 taking simvastatin, 7 receiving placebo), forearm strain-gouge plethysmography was performed at baseline and after 4 weeks, both at rest and during reactive hyperemia. At 4 and 12 weeks, group A showed a significant reduction in total cholesterol (p <0.05) and LDL (p <0.05), with unchanged HDL, triglycerides, blood, and plasma viscosity. Effort was unmodified, ST-segment depression at peak effort and ischemic threshold were significantly improved after 4 and 12 weeks (all p <0.05) with unchanged heart rate x systolic blood pressure product. A significant increase in the excess flow response to reactive hyperemia was detected in group A (p <0.03); group B showed no changes in hematochemical and ergometric parameters. These data suggest that cholesterol-lowering treatment is associated with an improvement in myocardial effort ischemia; this might be explained by a more pronounced increase of coronary blood flow and capacity of vasodilation in response to effort.

Analysis of Variance↗

PubMed1996

Pravastatin reduces carotid intima-media thickness progression in an asymptomatic hypercholesterolemic mediterranean population: the Carotid Atherosclerosis Italian Ultrasound Study.

PURPOSE: The Carotid Atherosclerosis Italian Ultrasound Study (CAIUS) was performed to test the effects of lipid lowering on the progression of carotid intima-media thickness (IMT) in 305 asymptomatic patients from a Mediterranean country. PATIENTS AND METHODS: Eligibility included hypercholesterolemia (baseline means: low-density lipoprotein [LDL] = 4.68 mmol/L, high-density lipoprotein [HDL] = 1.37 mmol/L), and at least one 1.3 < IMT < 3.5 mm in the carotid arteries. Patients (mean age 55 years, 53% male) were assigned to pravastatin (40 mg/day, n = 151) or placebo (n not equal to 154). Ultrasound imaging was used to quantify IMT at baseline, and semiannually thereafter for up to 3 years. The mean of the 12 maximum IMTs (MMaxIMT), was calculated for each patient visit, and used to determine each patient's longitudinal progression slope. The intention-to-treat group difference in the MMaxIMT progression was chosen a priori as the primary end point. RESULTS: Five serious cardiovascular events (1 fatal myocardial infarction), and 7 drop-outs for cancer were registered. In the pravastatin group, LDL decreased -0.22 after 3 months versus -0.01 in the placebo group, and remained substantially unchanged afterward (-0.23 versus +0.01 at 36 months, respectively). Progression of the MMaxIMT was 0.009 +/- 0.0027 versus -0.0043 +/- 0.0028 mm/year (mean +/- SE, P < 0.0007) in the placebo and pravastatin groups, respectively. IMT progression slopes diverged after 6 months of treatment. CONCLUSIONS: Pravastatin stops the progression of carotid IMT in asymptomatic, moderately hypercholesterolemic men and women. This finding extends the beneficial effects of cholesterol lowering to the primary prevention of atherosclerosis in a population with relatively low cardiovascular event rates, and suggests that this benefit is mediated by specific morphological effects on early stages of plaque development.

Anticholesteremic Agents↗

PubMed1995

Lipid-lowering treatment: effects on endothelial dysfunction.

An association has been demonstrated between the extent of atherosclerotic involvement and vasodilatory capacity in coronary and cerebral circulation. Impairment of endothelium-dependent relaxation is inversely related to HDL concentrations in plasma. Angiographic studies in humans have shown improved vasodilation capacity of the coronary arteries after lipid-lowering treatment.

Animals↗

PubMed1995

Ultrasonographic correlates of carotid atherosclerosis in transient ischemic attack and stroke.

BACKGROUND AND PURPOSE: Atherosclerotic plaques in extracranial carotid arteries, particularly in the bifurcation of the common carotid and internal carotid arteries, may cause transient cerebral ischemia and stroke by lumen stenosis or plaque-related thromboembolism. B-mode ultrasound imaging has the capability of providing information on plaque thickness, characteristics, and location in carotid arteries. METHODS: A retrospective analysis of 242 stroke and 336 transient ischemic attack (TIA) patients, recruited for the B-Scan Ultrasound Imaging Assessment Program, was performed to determine the ultrasonographic correlates of carotid atherosclerosis and acute cerebral ischemia. A matched case-control study design was used to compare brain hemispheres with ischemic lesions ("cases") to unaffected contralateral hemispheres ("controls") with regard to the presence and characteristics of carotid artery plaques. RESULTS: The first set of analyses examined the association between the presence of carotid plaques ipsilateral to the brain lesion and the occurrence of stroke or TIA and showed an association with recent episodes of TIA and stroke (odds ratio [OR], 1.6; P = .03) but not with past episodes. In a subset (n = 232) of patients with plaques in both carotid arteries and recent cerebral ischemic events, stroke was associated with ipsilateral carotid artery occlusion (P = .02). Lumen measurements at the site of the minimum residual lumen (MRL) diameter showed a significant association between a narrower lumen diameter in the carotid artery ipsilateral to case hemisphere and stroke (difference, 1.0 mm; P = .0003). TIA patients showed an association between both hypoechoic carotid plaques (OR, 3.0; P = .005) and the presence of longitudinal lesion motion (OR, 3.0; P = .02) with ipsilateral brain involvement. Plaque thickness at the MRL was positively correlated with both ipsilateral TIA (ipsilateral side, 4.4 +/- 0.15 mm; contralateral side, 3.9 +/- 0.16 mm; P = .007) and stroke (ipsilateral side, 4.2 +/- 0.23 mm; contralateral side, 3.3 +/- 0.21 mm; P = .0006). CONCLUSIONS: These data demonstrate significant relationships between carotid artery ultrasound plaque characteristics and ischemic cerebrovascular events. These findings encourage further prospective studies in asymptomatic subjects focused on echographic carotid plaque characteristics as predictors of subsequent TIA or stroke.

Aged↗

PubMed1995

Antioxidants in the Mediterranean diet.

It has been suggested that antioxidant vitamins or other antioxidants might inhibit the oxidation of low density lipoproteins into a particularly atherogenic form and preserve endothelial function. Antioxidants in the Mediterranean diet have been evaluated in relation to cardiovascular disease protection in this area. Observational epidemiologic data obtained from case-control, cohort or cross-cultural studies have consistently suggested that persons, such as those living in the Mediterranean area, who consume large amounts of antioxidant vitamins have a lower than average risk of cardiovascular disease. In another cross-cultural comparison, dietary intake, antioxidant status and plasma lipid peroxidation were compared in healthy young persons in Naples (Southern Italy) who consumed typical regional foods, and in Bristol (UK). The Naples group consumed more tomatoes and tomato juice, a higher proportion of monounsaturated fatty acids (from olive oil) and had a higher level of lipid antioxidant vitamin E (P = 0.005) and of beta carotene (P < 0.001) than the Bristol group. The intake of vitamin C, fresh fruit and vegetables, plasma vitamin A, serum selenium and copper levels did not differ. Several indices of plasma lipid peroxidation were significantly lower in the Naples group: conjugated dienes (P < 0.001), diene conjugation index (P = 0.019), lipid peroxides (P < 0.001). Dietary habits leading to relatively low levels of oxidized lipoproteins might contribute to the lower risk of coronary artery disease in Southern Italy.

Antioxidants↗

PubMed1994

Extracoronary atherosclerosis and genetic variants of apolipoprotein AI-CIII cluster in myocardial infarction survivors from southern Italy.

The relationships between some genetic markers, as evaluated by DNA analysis, and ultrasound evidence of extracoronary athero-sclerosis, as detected by ultrasound methods, were evaluated in 39 myocardial infarction survivors of middle age and in 40 healthy controls of comparable age. Coronary heart disease (CHD) patients showed higher levels of triglycerides (P = 0.01) and greater number of exsmokers (P = 0.004). Carotid stenoses (> 15%) were detected in ten CHD patients and in two controls; iliac stenoses (> 15%) or abnormal ankle/arm ratio (< 0.97) were found in ten CHD patients and in one control; the scores of vascular disease severity in the myocardial infarction survivors were higher (Mann-Whitney test) than in controls (P < 0.01). Molecular genetic analysis of SstI restriction fragment length polymorphism (RFLP) of the apolipoprotein (apo) AI-CIII cluster and of the apo B gene demonstrated a higher frequency of the S2 allele (SstI RFLP) in coronary patients than in controls (P = 0.04) and no significant differences in the frequencies of XbaI RFLP of the apo B gene between patients and controls. The relative risk of myocardial infarction associated with an abnormal vascular score (> 8) or with the presence of the rare allele S2 (SstI apo AI-CIII polymorphism) was estimated by odds ratios. The lower 95% limits of odds ratios were above 1 (indicating significant increase in the relative risk of myocardial infarction) both in the case of vascular score and that of SstI RFLP. These associations were independent of one another and of triglyceride levels. SstI RFLP association with CHD disappeared after adjustment for smoking habits.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoprotein A-I↗

PubMed1994

Prevalence of plaques and stenoses detectable by echo-Doppler examination in the femoral arteries of an elderly population.

Using echo-Doppler evaluation, we assessed the prevalence of possible atherosclerotic lesions in the common femoral arteries (n = 478) and superficial femoral arteries (n = 478) in 239 subjects (age range 65-94 years) living in retirement houses in Seattle. Ankle pressure was measured with a pneumatic cuff and a continuous wave Doppler. There were 68 individuals with an ankle arm index less than 0.97 and 39 of these with a index below 0.90. An echo-Doppler examination was performed with an Advanced Technologies Laboratories Mark 600 Duplex Scanner. We found 167 (34.9%) common femoral arteries affected by non-stenosing plaque while 19 arteries (4%) had stenosis or occlusion. In addition, 178 (37.2%) superficial femoral arteries showed non-stenosing plaques. The subjects with common femoral disease were 27 (11.3%), those with evidence of superficial femoral artery disease were 48 (20.1%), and those affected by disease in both sites were 84 (35.1%). There were 80 people (33.5%) with no ultrasound evidence of femoral artery disease. We found that the presence and severity of disease increased progressively in the decades 65-74, 75-84 and 85-94. We also demonstrated a positive association between major cardiovascular risk factors and ultrasound evidence of peripheral disease. The prevalence of femoral artery disease in an apparently healthy population was relatively high, although stenoses in most instances were not severe.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

PubMed1994

A comparison of antioxidant status and free radical peroxidation of plasma lipoproteins in healthy young persons from Naples and Bristol.

Ischaemic heart disease mortality is much lower in Southern Italy than in the U.K. and this is not entirely explained by differences in classical risk factors. Differences in antioxidant intake, affecting free radical peroxidation of plasma lipoproteins, may be relevant. Therefore, dietary intake, antioxidant status and plasma lipid peroxidation were compared in healthy young persons eating typical regional diets from Naples (22) and Bristol (26). The Naples group consumed more fresh tomatoes, more fat as monounsaturates (from olive oil) and had higher plasma levels of the lipid antioxidants vitamin E (mean (SD; 95% CI) 29.1 (4.5; 26.8 to 31.3) vs 25.1 (3.86; 23.4 to 26.8) mumol.l-1, P = 0.005) and beta-carotene (4.74 (1.2; 4.14 to 5.34) vs 2.85 (0.8; 2.5 to 3.2) mumol.l-1, P < 0.001). Intakes of vitamin C, total uncooked fruit and vegetables, plasma vitamin A, serum selenium and copper levels were similar. All indices of plasma lipid peroxidation were significantly lower in the Naples group: conjugated dienes (median (interquartile range; non-parametric 95% CI)) 29 (21.5-39.9; 24 to 36.7) vs 41.5 (37-48.5; 38 to 44.5) mumol.l-1, P < 0.001; diene conjugation index 1.38 (1.02-1.55; 1.06 to 1.49) x 10(-2) vs 1.57 (1.43-1.74; 1.44 to 1.71) x 10(-2), P = 0.019; lipid peroxides (geometric mean (95% CI) 1.24 (1.12 to 1.37) vs 4.58 (3.84 to 5.46) mumol.l-1, P < 0.001.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Increased intima-media thickness of the common carotid artery in hypercholesterolemic children.

Common carotid intima-media thickness was measured by B-mode ultrasound imaging in 46 children (mean age, 7.4 years) with serum cholesterol > or = 6.4 mmol/L (mean, 8.25 mmol/L) and in 48 children (mean age, 6.4 years) with serum cholesterol < 6.4 mmol/L (mean, 4.60 mmol/L). Maximum thickness was significantly higher in hypercholesterolemic children than in control children (0.50 versus 0.47 mm, P = .007). Subgroup analysis showed that only in children > 6.2 years old (the median of all the children's ages) was maximum thickness significantly higher in hypercholesterolemic children than in control children (0.51 versus 0.48 mm, P = .014). The odds ratio (OR) of common carotid intima-media thickening (maximum thickness of the far wall higher than the 95th percentile of the control group, 0.51 mm) between patients and control subjects was statistically significant both in univariate analysis (OR, 6.39; 95% confidence interval, 1.19 to 32.3; P = .025) and after age (OR, 5.96; 95% confidence interval, 1.09 to 32.4; P = .039) and sex (OR, 7.54; 95% confidence interval, 1.38 to 41.2; P = .020) were controlled for. Children > 6 years old with serum cholesterol > or = 6.4 mmol/L show increased thickness of the common carotid intima-media.

Adolescent↗

PubMed1994

Premature carotid atherosclerosis: does it occur in both familial hypercholesterolemia and homocystinuria? Ultrasound assessment of arterial intima-media thickness and blood flow velocity.

BACKGROUND AND PURPOSE: Homocystinuria due to cystathionine beta-synthase deficiency and familial hypercholesterolemia are inherited disorders of metabolism that are associated with premature development of cardiovascular disease. This study addresses the possibility that different patterns of carotid wall damage and cerebral blood flow hemodynamics are present in these two metabolic diseases. METHODS: Twelve patients with homocystinuria due to cystathionine beta-synthase deficiency (mean age, 24 years), 10 patients with homozygous familial hypercholesterolemia (mean age, 26 years), and 11 healthy control subjects (mean age, 26 years) underwent a vascular examination by noninvasive methods. B-mode ultrasound imaging was used to obtain measurements of intima-media thickness of common carotid, bifurcation, and internal carotid arteries as an index of atherosclerosis. Cerebral blood flow velocity was estimated from vascular examination of the middle cerebral artery by transcranial Doppler. Systolic, diastolic, and mean velocities were measured. Pulsatility index, a possible indicator of vascular resistance in the cerebral circulation, was also calculated. RESULTS: Mean maximum intima-media thickness was 1.4 mm in patients with familial hypercholesterolemia, 0.6 mm in patients with homocystinuria, and 0.6 mm in control subjects. The difference between hypercholesterolemic and homocystinuric patients or control subjects was statistically significant (P < .001). Diastolic blood flow velocities were significantly reduced in the middle cerebral arteries of hypercholesterolemic patients compared with homocystinuric patients or control subjects (P < .05), whereas systolic or mean velocities did not differ. The pulsatility index, a possible indicator of vascular resistance in the cerebral circulation, was significantly higher in hypercholesterolemic patients compared with homocystinuric patients or healthy control subjects (P < .01). A direct relation was demonstrated between pulsatility index of the middle cerebral artery and mean maximum intima-media thickness of carotid arteries on the same side (P < .001). CONCLUSIONS: Familial hypercholesterolemia is responsible for diffuse and focal thickening of carotid arteries and possibly also for hyperlipidemic endothelial dysfunction extending to small resistance arteries and leading to a disturbed cerebral blood flow. Patients with homocystinuria due to homozygosis for cystathionine beta-synthase deficiency seldom have plaques in their carotid arteries. They are similar to healthy control subjects with regard to both intima-media thickness and blood flow velocity in the middle cerebral artery. Therefore, it is unlikely that typical atherosclerotic lesions precede thrombotic events in homocystinuria. However, it is possible that arterial dilatations caused by medial damage lead to thrombosis in homocystinuric patients.

Adolescent↗

PubMed1993

Lowering blood lipids to treat atherosclerosis: vascular tone, plaques, events, and mortality.

Hypercholesterolemia has been associated with an increase in vascular tone, mainly because of an impairment of endothelium-dependent relaxation. This endothelial dysfunction occurs before any definite atherosclerotic lesion is demonstrated. In both animal models and humans the correction of hypercholesterolemia has been associated with hemodynamic improvement. Several controlled trials have demonstrated that long-term treatment with cholesterol-lowering drugs is effective in blocking progression and in some cases in inducing regression of angiographically detected arterial lesions. Arteriographies produce a negative image of the arterial lumen but do not provide sufficient information on vessel wall status. Noninvasive B-mode ultrasound has allowed a direct visualization of the arterial wall in superficial vascular districts, such as the carotid bifurcation. Wall and lesion measures are increasingly used as end points for clinical trials of antiatherosclerotic drugs. In secondary prevention, cholesterol reduction is associated with a lower incidence of coronary heart disease, although the cholesterol reduction should be at least 8-9% to have an impact on total mortality.

Adult↗

PubMed1993

Treating mild hypercholesterolemia in the absence of overt cardiovascular disease: if, when, and why?

Cohort data define a range of cholesterol concentrations (160-200 mg/dl), which is desirable in terms of public health. Cholesterol-lowering treatment leading to a serum cholesterol in this range is favorable for coronary heart disease prevention and safe in terms of noncardiovascular mortality. In individuals with moderate cholesterol elevation and without other coronary risk factors, the physician should encourage a healthy lifestyle and give prudent nutritional advice. Detection of asymptomatic cardiovascular disease by noninvasive methods might be used to identify individuals with mild hypercholesterolemia, but nevertheless at high risk for ischemic accidents. The aim of lipid-lowering treatment is to improve life expectancy through reduction of a major cause of premature death.

Coronary Disease↗

PubMed1993

Noninvasive ultrasound techniques versus angiography for monitoring drug-induced changes of the arterial walls.

Even though angiographic studies contribute to understanding the process of atherosclerosis progression/regression in humans, they have several important limitations. The number of participants in all the studies is small and those who accept the invasive vascular investigation are highly selected patients, in most instances in an advanced stage of cardiovascular disease. Furthermore, arteriography provides the image of the vessel lumen but no information on the vessel wall. Noninvasive methods can describe the characteristics of the arteries with regard to morphology (intima-media thickness, surface irregularities, areas of calcification) and the hemodynamic correlates of vascular lesions. No single methodology describes all aspects of the disease process. However, B-mode ultrasound imaging gives information on the vessel wall, whereas Doppler mainly describes the hemodynamic consequences of arterial disease. Before any noninvasive methodology can be adopted for a clinical trial, extensive validation data (preferably using pathology rather than angiography as a "gold standard"), and accurate information on reproducibility and on inter-, intraobserver variability, should be available. Also, quantitative details on the natural history of the disease and on the potential of intervention, as evaluated by the specific methodology to be used, should be known.

Angiography↗

PubMed1993

Cerebral blood flow velocity and systemic vascular resistance after acute reduction of low-density lipoprotein in familial hypercholesterolemia.

BACKGROUND AND PURPOSE: Low-density lipoprotein apheresis is currently used for the treatment of familial hypercholesterolemia, an inherited disorder of metabolism associated with premature development of cardiovascular disease. We wanted to evaluate cerebral blood flow velocity, cardiac output, and systemic vascular resistance in patients with familial hypercholesterolemia before and after low-density lipoprotein apheresis. METHODS: Ten patients (age range, 14 to 46 years; 4 males, 6 females) with familial hypercholesterolemia (8 homozygotes, 2 heterozygotes) and 10 healthy control subjects of comparable age and sex distribution participated in the study. Low-density lipoprotein apheresis by dextran sulfate was performed in 8 patients (7 homozygotes, 1 heterozygote). Six patients (4 homozygotes, 2 heterozygotes) underwent a procedure of extracorporeal erythrocyte filtration with the same extracorporeal volume as for low-density lipoprotein apheresis, but with the exclusion of the passage of plasma through the dextran sulfate column. Cerebral blood flow velocity (transcranial Doppler), cardiac output, and systemic vascular resistance (electric bioimpedance cardiography) were determined by noninvasive techniques before and 1 day and 7 days after low-density lipoprotein apheresis or extracorporeal erythrocyte filtration. Plasma and blood viscosities were measured at the same time. RESULTS: Before apheresis, mean and diastolic cerebral flow velocities were abnormally low in hypercholesterolemic patients (P < .01 and P < .02 vs healthy control subjects, respectively). After apheresis, low-density lipoprotein cholesterol was lowered by 40% to 60% from baseline, and cerebral blood flow velocities (mean, systolic, and diastolic velocities) were increased (P < .01). Cardiac output, systemic vascular resistance, and viscosity values were not significantly modified. Extracorporeal erythrocyte filtration (without passage of plasma through the dextran sulfate column) did not modify serum lipids, hemodynamic parameters, or viscosity values. CONCLUSIONS: Low-density lipoprotein apheresis produces potentially useful hemodynamic effects. They are not adequately explained by changes in blood viscosity alone and might reflect a restoration of endothelium-mediated vasodilation, which is inhibited by high concentrations of low-density lipoprotein.

Adolescent↗