Biomedical subjects

M G Bond

Publications and source records attributed to M G Bond.

At least 37 records · Page 2Linked to original sources

PubMed1996

Final outcome results of the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS). A randomized controlled trial.

OBJECTIVE: To compare the rate of progression of mean maximum intimal-medial thickness (IMT) in carotid arteries, using quantitative B-mode ultrasound imaging, during antihypertensive therapy with isradipine vs hydrochlorothiazide. DESIGN: Randomized, double-blind, positive-controlled trial. SETTING: Nine medical center clinics. POPULATION: A total of 883 patients with baseline mean +/- SD systolic and diastolic blood pressure (SBP and DBP, respectively) of 149.7 +/- 16.6 and 96.5 +/- 5.1 mm Hg, age of 58.5 +/- 8.5 years, and maximum IMT of 1.17 +/- 0.20 mm. INTERVENTIONS: Twice daily doses of isradipine (2.5-5.0 mg) or hydrochlorothiazide (12.5-25 mg). MAIN OUTCOME MEASURE (PRIMARY END POINT): Rate of progression of mean maximum IMT in 12 carotid focal points over 3 years. RESULTS: There was no difference in the rate of progression of mean maximum IMT between isradipine and hydrochlorothiazide over 3 years (P=.68). There was a higher incidence of major vascular events (eg, myocardial infarction, stroke, congestive heart failure, angina, and sudden death) in isradipine (n=25; 5.65%) vs hydrochlorothiazide (n=14; 3.17%) (P=.07), and a significant increase in nonmajor vascular events and procedures (eg, transient ischemic attack, dysrhythmia, aortic valve replacement, and femoral popliteal bypass graft) in isradipine (n=40; 9.05%) vs hydrochlorothiazide (n=23; 5.22%) (P=.02). At 6 months, mean DBP decreased by 13.0 mm Hg in both groups, and mean SBP decreased by 19.5 mm Hg in hydrochlorothiazide and 16.0 mm Hg in isradipine (P=.002); the difference in SBP between the 2 groups persisted throughout the study but did not explain the increased incidence of vascular events in patients treated with isradipine. CONCLUSION: The rate of progression of mean maximum IMT in carotid arteries, the surrogate end point in this study, did not differ between the 2 treatment groups. The increased incidence of vascular events in patients receiving isradipine compared with hydrochlorothiazide is of concern and should be studied further.

Aged↗

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↗

PubMed1996

Apolipoprotein E polymorphism is associated with segment-specific extracranial carotid artery intima-media thickening.

BACKGROUND AND PURPOSE: Apolipoprotein E (apoE) polymorphism affects plasma cholesterol and may influence risk of atherosclerosis. We investigated the association of apoE with carotid artery wall thickening (an index of atherosclerosis) in individuals with and without coronary artery disease (CAD). METHODS: ApoE phenotypes were resolved in 260 individuals equally represented by angiographically determined CAD case subjects and disease-free control subjects. Carotid artery intima-media thickening (IMT) was evaluated by B-mode ultrasound. Associations of apoE (E2, E3, or E4) with risk factors and IMT were evaluated in general linear models adjusted for age, sex, and CAD status with and without other traditional risk factors. RESULTS: Total cholesterol (TC) and LDL cholesterol were associated with apoE isoforms. Mean TC and LDL cholesterol were lower in E2 (n = 33) carriers than E3 (n = 155) and E4 (n = 66) carriers (each P < .001). IMT also varied by apoE. E2 carriers had less common carotid IMT than E3 and E4 carriers (P < .01), while internal carotid IMT was less in E2 and E3 carriers than in E4 carriers (P < .02). Bifurcation IMT was not associated with apoE (P = .24). ApoE polymorphism remained associated with common (P < .01) and internal (P < .04) IMT, and the association of apoE with mean IMT of all sites reached significance (P < .04) after adjustment for age, sex, CAD status, TC, LDL cholesterol, HDL cholesterol, triglycerides, diabetes, hypertension, and smoking. CONCLUSIONS: ApoE polymorphism is associated with segment specific carotid IMT. The association of apoE with carotid IMT was statistically independent of apoE-associated variation in LDL cholesterol levels.

Aged↗

PubMed1996

Ultrasound protocol and quality control procedures in the European Lacidipine Study on Atherosclerosis (ELSA).

The European Lacidipine Study on Atherosclerosis (ELSA) is a multinational interventional clinical trial aimed at determining the antiatherosclerotic effects of Lacidipine, a calcium antagonist, when compared to atenolol, a beta-blocker, on the carotid arteries of 2300 cardiovascular asymptomatic patients with moderately high blood pressure. Quantitative B-mode ultrasound imaging is being used to measure the intima-media thickness of a standardized section of the carotid arteries including the distal common, bifurcation, and proximal internal carotids. Prospective investigations of large samples of population using ultrasonographic endpoints rely heavily on the precision and reproducibility of the method. Therefore, specific quality control protocols are required to determine and monitor cross-sectional and longitudinal stability of the measurement reproducibility. In ELSA, the ultrasound methodology was specifically designed to include a set of procedures to quality control the critical components of measurement variation including instrumentation, and ultrasound operators, i.e. sonographers and readers. The ELSA clinical trial will provide the largest set of prospective quality control data on the use of quantitative B-mode ultrasound imaging.

Arteriosclerosis↗

PubMed1995

Pravastatin, Lipids, and Atherosclerosis in the Carotid Arteries (PLAC-II).

The Pravastatin, Lipids, and Atherosclerosis in the Carotid Arteries trial (PLAC-II) was initiated in 1987 and was the first double-blind, randomized clinical trial with progression of early extracranial carotid atherosclerosis as an outcome variable. We randomized 151 coronary patients to placebo or pravastatin and treated them for 3 years. B-mode ultrasound quantification of carotid artery intimal-medial thickness (IMT) was obtained at baseline and sequentially during this period. The primary outcome was the change in the mean of the maximum IMT measurements over time. Effects on individual carotid artery segments (common, bifurcation, internal carotid artery) and on clinical events were also investigated. During follow-up, plasma concentrations of total cholesterol were lower in pravastatin-treated patients compared with those of placebo-treated patients (4.81 vs 6.08 mmol/liter [186 vs 235 mg/dl]) as were concentrations of low density lipoprotein (LDL) cholesterol (3.10 vs 4.29 mmol/liter [120 vs 167 mg/dl]). Plasma concentrations of high density lipoprotein2 (HDL2) cholesterol were higher in pravastatin-treated patients than in placebo-treated patients (0.16 vs 0.14 mmol/liter [6.1 vs 5.5 mg/dl]). Active treatment resulted in a nonsignificant 12% reduction in progression of the mean-maximum IMT (from 0.068 mm/yr placebo to 0.059 mm/yr pravastatin) and a statistically significant 35% reduction in IMT progression in the common carotid (p = 0.03). Active treatment was also associated with a 60% reduction of nonfatal myocardial infarction plus death caused by coronary artery disease (p = 0.09), a 61% reduction of any fatal event plus any nonfatal myocardial infarction (p = 0.04), and an 80% reduction of fatal plus any nonfatal myocardial infarction (p = 0.03).

Anticholesteremic Agents↗

PubMed1995

Association of coronary disease with segment-specific intimal-medial thickening of the extracranial carotid artery.

BACKGROUND: Several investigators have evaluated relations between risk factors and intimal-medial thickness (IMT) of the extracranial carotid arteries and between IMT and clinical cardiovascular disease. Different indexes of IMT have been used as referents. We compared the strength of association of various IMT measurements with coronary artery disease as measured at coronary angiography. METHODS AND RESULTS: We quantified the mean of the IMT for 12 sites of the extracranial carotid arteries (common carotid, bifurcation, internal carotid, near and far walls, and left and right sides [mean aggregate]) as well as for various combinations of sites (eg, segment-specific means, far walls only, maximum of any site) in 270 patients with or free of coronary artery disease. Models including age and all the indexes of IMT identified the mean aggregate as the only variable independently associated with the status of coronary atherosclerosis for the group as a whole. Next most strongly correlated was the mean common plus bifurcation. When classification algorithms were tested for ability to correctly classify case patients and control subjects, the mean bifurcation, mean common plus bifurcation, and mean aggregate were most strongly related to case-control status; however, the predictive power of the mean common was also strong. CONCLUSIONS: These data support use of the mean aggregate extracranial carotid IMT for correlation with the status of coronary atherosclerosis; however, the data also support use of the mean common plus bifurcation, since there is little increase in predictive power of the mean aggregate over this index. Use of the common carotid alone is also justifiable and may be preferable for certain analyses.

Age Factors↗

PubMed1995

Pravastatin, Lipids, and Atherosclerosis in the Carotid Arteries (PLAC-II)

We randomized 151 coronary patients to placebo or pravastatin and treated them for 3 years. B-mode ultrasound quantification of carotid artery intimal-medial thickness (IMT) was obtained at baseline and sequentially during this period. The primary outcome was the change in the mean of the maximal IMT measurements across time. Effects on individual carotid artery segments (common, bifurcation, and internal carotid) and on clinical events were also investigated. Plasma concentrations of total cholesterol were lower with active treatment than with placebo (4.80 vs 6.07 mmol/L [186 vs 235 mg/dl], respectively) as were concentrations of low-density lipoprotein cholesterol (3.11 vs 4.30 mmol/L [120 vs 167 mg/dl], respectively). Plasma concentrations of high-density lipoprotein2 cholesterol were higher with active treatment (0.16 vs 0.14 mmol/L [6.1 vs 5.5 mg/dl], respectively). Active treatment resulted in a nonsignificant 12% reduction in progression of the mean-maximum IMT (from 0.068 to 0.059 mm/year) and a statistically significant 35% reduction in IMT progression in the common carotid. Active treatment was also associated with a reduction in fatal and nonfatal coronary events [corrected] (p = 0.09) and of any fatal event plus nonfatal myocardial infarction (p = 0.04).

Arteriosclerosis↗

PubMed1995

Postprandial lipoprotein responses in hypertriglyceridemic subjects with and without cardiovascular disease.

Three groups of age- and weight-matched men (aged 40 to 70 years) without diabetes were studied: controls (n = 10), plasma triglycerides (TG) less than 180 mg/dL and no cardiovascular disease (CVD); HTG-CVD (n = 11), hypertriglyceridemic (HTG) (TG > 240 mg/dL) without CVD; and HTG+CVD (n = 10), HTG (TG > 240 mg/dL) with documented CVD. HTG+CVD subjects had higher fasting and post-oral glucose tolerance test insulin levels than the other two groups, respectively. Very-low-density lipoprotein (VLDL)+chylomicrons (CMs), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and three high-density lipoprotein (HDL) subfractions (HDL-L, HDL-M, and HDL-D, from least to most dense) were isolated by gradient ultracentrifugation. Fasting lipoproteins were similar in HTG groups, except for higher VLDL lipid to apolipoprotein (apo) B ratios (P < .04) in the HTG+CVD group. Subjects were fed a high-fat mixed meal, and lipoprotein composition was determined at 3, 6, 9, and 12 hours postprandially. Postprandial responses of the core lipids (TG and cholesterol esters [CE]) in all of the lipoprotein subfractions were similar in the two HTG groups at each time point. However, both controls and HTG-CVD subjects had increases in HDL-M phospholipid (PL) at 9 and 12 hours with no change in HDL-D PL. The HTG+CVD group, on the other hand, had no increase in HDL-M PL and had a substantial reduction in HDL-D PL. These changes resulted in significant increases in HDL-M and HDL-D PL to apo A-I ratios in both controls and HTG-CVD subjects between 6 and 12 hours, whereas there was no increase seen in the HTG+CVD group. The HTG-CVD group also had a significantly greater increase in the VLDL+CM PL to apo B ratio (P = .038) at 3 hours than the HTG+CVD group. This diminished amount of surface lipid per VLDL particle may account for the late decrease in the HDL-D PL to apo A-I ratio seen in HTG+CVD patients. There were no other postprandial lipid or apolipoprotein differences between the two HTG groups. We conclude therefore that the major postprandial lipoprotein abnormality in these HTG+CVD patients was a failure to increase the PL content per particle in VLDL+CM, HDL-M, and HDL-D. This abnormality could prevent the usual increase in reverse cholesterol transport seen in postprandial plasma and therefore contribute to their increased incidence of CVD. The greater insulin resistance seen in these patients also appears to contribute significantly to their CVD.

Adult↗

PubMed1995

Bone marrow infiltration by a parietal lobe grade III oligodendroglioma.

We report a patient with oligodendroglioma metastases 1 year after tumour debulking and postoperative radiotherapy to the parietal lobe primary. This treatment controlled the patient's tumour locally. Distant recurrence was manifest by back pain, weight loss and malaise. The serum alkaline phosphatase was raised and a bone scan showed generalized increased uptake. Bone marrow trephine revealed infiltration by oligodendroglioma. Bone marrow infiltration by gliomas is very rare. If the trephine had not been performed it might have been assumed that he had a disseminated second primary tumour.

Bone Marrow Neoplasms↗

PubMed1995

Differential distribution of 70-kD heat shock protein in atherosclerosis. Its potential role in arterial SMC survival.

Smooth muscle cell death may contribute to necrotic plaque rupture and subsequent thromboembolus. Stress-induced synthesis of heat-shock proteins (HSPs) normally protects cells from death, but vascular HSPs may become insufficient as cytotoxicity increases in advanced plaques. To determine whether vascular HSP content is altered near necrosis, we compared 70-kD HSP (HSP70) distribution between fibrotic and necrotic plagues in immunostained carotid endarterectomy specimens. Average levels of HSP70 immunoreactivity were compared by video densitometry between fibrotic and necrotic plaques or between their underlying media. Both necrotic plaques and their underlying media contained significantly more HSP70 staining than did fibrotic tissues. To test whether cellular HSP70 correlated with resistance to toxicity in vitro, aortic smooth muscle cells (aSMCs) were heat shocked to induce endogenous HSPs or given 2 to 50 micrograms/mL purified HSP70. Cells were then serum deprived or exposed to 12 to 96 mumol/L cholestanetriol (C3ol) or 25-hydroxycholesterol, and survival was determined. Cellular HSP70 content was assayed by immunoblotting, and protein synthesis was monitored by 35S radiolabeling. Serum deprivation inhibited general protein synthesis but induced HSP70; C3ol exposure inhibited both overall protein and HSP70 synthesis, including post-heat shock. Induction of endogenous HSPs or 10 micrograms/mL exogenous HSP70 improved viability of serum-deprived cells (P < .05 and P < .01, respectively), while only exogenous HSP70 protected against C3ol (P < .002). The results suggest that insufficient HSP70 accumulates in aSMCs residing near necrosis to protect against plaque toxicity; aSMC death might then occur, allowing resident macrophages to degrade and destabilize the matrix, leading to rupture.

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

Potential modification of plaque behavior through the European lacidipine study on atherosclerosis.

The European Lacidipine Study on Atherosclerosis (ELSA) has been designed to compare the effects of two antihypertensive agents, the calcium antagonist lacidipine and the beta-blocker atenolol, on the development of atherosclerosis in hypertensive patients stratified according to the presence of carotid plaques, or the presence or absence of carotid artery intima-media thickening. ELSA is a multinational, multicenter, randomized, double-blind, parallel group study that is to be conducted over a 5-year period. Recruitment and treatment will take place at 23 referral centers in seven countries. A total cohort of 3,660 patients, aged between 45 and 75 years, with diastolic blood pressure 95-115 mm Hg and systolic blood pressure < or = 210 mm Hg at enrollment, will be stratified into three groups according to a B-mode ultrasound analysis of the carotid wall morphology. After a 1-month placebo run-in period, patients will be randomized to receive either lacidipine (4-6 mg once daily) or atenolol (50-100 mg once daily). Nonresponders will be treated with hydrochlorothiazide (12.5 mg, eventually titrated to 25 mg if required), on an open basis. During the course of the study, patients will be monitored by carotid ultrasound assessment and ambulatory blood pressure monitoring. The results of this study should further understanding of the pathobiology of atherosclerosis, and its development and prevention.

Adrenergic beta-Antagonists↗

PubMed1994

Relationship of intraabdominal fat as measured by magnetic resonance imaging to postprandial lipemia in middle-aged subjects.

Adipose distribution has been associated with coronary artery disease and its risk factors. We previously described an association between postprandial triglyceride response (pptg response) to a standard high-fat meal and extracranial carotid atherosclerosis. This study was designed to evaluate the association between intraabdominal fat and pptg response. Twenty-nine subjects were recalled for determination of intraabdominal fat by magnetic resonance imaging (MRI). Fat was quantified according to an inversion recovery protocol previously validated and the cross-sectional area of intraabdominal fat at the umbilicus was analyzed as an independent variable. We observed a strong independent correlation between intraabdominal fat and pptg response to a fatty meal (r = 0.521, P < 0.05). Baseline triglyceride was also independently correlated with postprandial triglycerides (r = 0.631, P < 0.05). In univariate analysis, intraabdominal fat was correlated with age, sex, body mass index (BMI), waist-to-hip ratio (WHR), and dietary saturated fatty acids. The association with age and BMI persisted in multivariate analyses.

Abdomen↗

PubMed1994

Association of risk factors and body iron status to carotid atherosclerosis in middle-aged eastern Finnish men.

High body iron stores have been proposed as a risk factor for advanced atherosclerosis. We investigated the prevalence of early atherosclerotic changes, and their relation to conventional CHD risk factors and body iron status. A cross-sectional study was carried out in 206 men aged 50 to 60 years (6% random population sample). Intima-media thickness (IMT) of the carotid artery was evaluated with high-resolution B-mode ultrasonography. Statistical analyses were performed separately for men with and without cardiovascular disease (CVD). Among all the study participants, 6.6% had IMT > 1.3 mm in the common carotid artery, whereas 53.8% had IMT > 1.5 mm in the carotid bifurcation. Respective values were 4.8% and 46.8% for those without CVD, and 8.5% and 62.2% for those with CVD. Mean IMT in the carotid bifurcation, the predilection site for atherosclerosis, was 1.85 mm (95% CI 1.72; 1.98) in the men with CVD, as compared to 1.65 mm (95% CI 1.56; 1.73) in the men free of CVD. Serum LDL cholesterol (beta = 0.26), saturated fat intake (beta = 0.20), blood haemoglobin (beta = -0.29), systolic blood pressure (beta = 0.21) and smoking (beta = 0.19), jointly explained 23% of the variance in the carotid bifurcation IMT in the men without CVD. Neither serum ferritin, transferrin nor dietary iron levels were associated with carotid bifurcation atherosclerosis. On the other hand, in the men with CVD, age (beta = 0.34) and physical activity (beta = -0.25) jointly explained 16.5% of the IMT variance in the carotid bifurcation.(ABSTRACT TRUNCATED AT 250 WORDS)

Carotid Stenosis↗

PubMed1994

Associations of lipoprotein cholesterols, apolipoproteins A-I and B, and triglycerides with carotid atherosclerosis and coronary heart disease. The Atherosclerosis Risk in Communities (ARIC) Study.

Previous research shows generally greater proportional elevation in apolipoprotein B (apoB) levels than in low-density lipoprotein cholesterol (LDL-C) in coronary heart disease (CHD) case subjects compared with control subjects. The Atherosclerosis Risk in Communities study provided general populations of 7261 men and women free of cardiovascular symptoms for evaluating the associations between intima-media thickening in extracranial carotid arteries measured using ultrasound imaging and fasting plasma LDL-C, high-density lipoprotein cholesterol (HDL-C), apoB, apolipoprotein A-I (apoA-I), triglycerides, and HDL density subfractions. A CHD group was selected for comparison. Lipid factors show approximately linear associations with carotid thickness: positive for LDL-C and plasma apoB and negative for HDL-C and apoA-I levels. Apolipoproteins and HDL density subfractions did not contribute to the association after accounting for LDL-C and HDL-C. Compared with control subjects, persons whose carotid thickness exceeded 0.9 mm had greater proportional elevations in LDL-C than in apoB, whereas HDL-C reductions were small. CHD case subjects showed greater proportional elevations of apoB than LDL-C. Although the lipid profiles associated with asymptomatic carotid wall thickening and stenotic coronary disease are similar, the differences found suggest that LDL-C is the most important lipid factor in earlier stages of atherogenesis, whereas the metabolism of triglyceride-rich lipoproteins and its effects on LDL and HDL may be more relevant to later atherothrombotic processes.

Apolipoprotein A-I↗

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

Carotid plaque associations among hypertensive patients.

OBJECTIVE: To assess the relationship between cardiovascular risk factors and carotid plaque. DESIGN: Hypertensive patients were screened for randomization into the Multicenter Isradipine Diuretic Atherosclerosis Study, a trial intended to determine if blood pressure control by isradipine as compared with hydrochlorothiazide will blunt the progression of carotid plaque (intima plus media thickness, 1.3 to 3.5 mm) in patients with serum cholesterol levels of less than 6.85 mmol/L (265 mg/dL) without insulin-dependent diabetes mellitus or estrogen therapy. Demographics of those who underwent B-mode ultrasound evaluations at common, bifurcation, and internal carotid artery sites to detect plaque were assessed from a southern and a northern site. SETTING: Participants were from ambulatory outpatient clinics associated with medical schools. PATIENTS: The initial screening included 1823 hypertensive volunteer patients who were between 40 and 83 years of age who had a diastolic pressure of 90 to 114 mm Hg (or < 90 mm Hg with treatment). OUTCOME MEASURES: Complete data were collected on the variables of age, cholesterol, cigarette smoking, race, gender, and the presence of carotid plaque in 1126 patients. RESULTS: All variables were significantly associated with carotid plaque (intima plus media thickness, > or = 1.3 mm). The adjusted percentage with plaque was 66.4% +/- 3.4% for blacks and 70.1% +/- 2.3% for whites at the southern site and 42.7% +/- 4.5% for blacks and 61.3% +/- 3.2% for whites at the northern site. The rate of plaque was 75.8% among cigarette smokers, despite a mildly elevated cholesterol level. CONCLUSIONS: Although these 1126 cases do not constitute a random sample of patients, these data suggest that there may be regional differences in racial tendencies toward plaque among blacks.

Aged↗

PubMed1993

Atherosclerosis alters the localization of HSP70 in human and macaque aortas.

Evidence suggests an important role for heat shock proteins (HSPs) in the evolution of atherosclerotic necrotic cores. The present study compared normal-appearing and atherosclerotic aortas obtained from control and diet-induced atherosclerotic cynomolgus macaques and from human autopsies, with respect to the localization and content of 70-kDa HSPs (HSP70). The distribution pattern of HSP70 was determined by immunostaining tissue sections with anti-HSP70 monoclonal antibody against both constitutive and inducible isoforms. Changes in HSP70 staining with developing atherosclerosis were quantitated using video morphometry. Total aortic HSP70 content was evaluated by Western blotting tissue homogenates. In both macaque and human aortas, HSP70 staining was homogeneous in normal-appearing regions, but developed a heterogeneous pattern in the presence of atherosclerosis. Immunostaining for three other HSPs (90, 65, and 28 kDa) confirmed the change as HSP-specific. Video morphometry indicated a significant positive association between severity of atherosclerosis and altered patterns of HSP70 staining. However, Western blots detected no difference in total HSP70 content of either human or macaque aortas with plaque progression. The data suggest HSP70 localization changes in aortas during atherosclerosis evolution without affecting overall aortic HSP70 content. Such changes in HSP70 localization may reflect differences in the cellular response and resistance to cytotoxic conditions present within the plaque, which could influence the expansion of necrotic cores.

Animals↗