Femoral Plaques Research Articles

Additional prognostic value of physical examination, exercise testing, and arterial ultrasonography for coronary risk assessment in primary prevention

The choice of noninvasive tests used in primary prevention of cardiovascular diseases must be based on medical evidence. The aim of this study was to assess the additional prognostic value, over conventional risk factors, of physical examination, exercise testing, and arterial ultrasonography, in predicting a first coronary event. A prospective cohort study was conducted between 1996 and 2004 (n = 2,709), with follow-up in 2006 (response rate 96.6%). Participants had no history or symptoms of cardiovascular disease and had a standardized physical examination, a cardiac exercise testing, and carotid and femoral ultrasonography at baseline. Incident cases of definite coronary events were recorded during follow-up. Over the Framingham risk score, femoral bruit, positive exercise test, intima-media thickness >0.63 mm, and a femoral plaque provided significant additional information to the prediction model. The addition of the exercise test to the traditional risk factors, then the intima-media thickness and lastly the presence of femoral plaques, produces incremental increases in the area under the receiver operating characteristic curve (0.73-0.78, P = .02) and about a 50% increase in the positive predictive value (15.8%-31.4%), with no effect on the negative predictive value (96.4%-96.9%). Physical examination, exercise testing, and arterial ultrasonography provide incremental information on the risk of coronary event in asymptomatic adults. Exercise testing and femoral ultrasonography also improve the accuracy of the risk stratification.

Atheromatous Plaques: Quantitative Analysis of the Echogenicity of Different Layers

Echographic studies of the composition of atheromatous plaque make use of the median gray level, which provides an overall measure of echogenicity. We propose adding an additional dimension to this approach by dividing the lesion into layers and generating a curve that shows the variation in echolucency with depth. Femoral and carotid plaque in asymptomatic patients was investigated using both the median gray level and new layer Interobserver variability was assessed for both Three risk factors were studied: age, gender and smoking status. Differences in echogenicity-depth curves between different groups were assessed using two-way ANOVA. The two methods gave similar results for the mean echogenicity of carotid and femoral plaque. Echogenicity increased as a function of depth (r=0.96; P< .001). With the median gray level method, none of the risk factors produced a change in echogenicity. However, with the layer method, the echogenicity of femoral plaque was found to increase with age (P< .001), though gender had no effect. Moreover, the echogenicity of superficial layers was less in smokers than nonsmokers (P< .01). In carotid plaque, echogenicity increased with age (P< .01) and was higher in men (P< .01). The echogenicity of deep plaque was greater in smokers than nonsmokers (P< .05). The reproducibility of the two methods was similar. The layer method was more effective than the median gray level method for identifying the effect of age, sex and smoking status on the echogenicity of atheromatous plaque.

Carotid and femoral plaques are distinct entities

Carotid and femoral plaques are distinct entities

Systemic telomere length and preclinical atherosclerosis: the Asklepios Study

Peripheral blood leucocyte (PBL) telomere length (TL) is a systemic ageing biomarker and has been proposed to be an independent predictor of cardiovascular disease (CVD). We aimed at providing an explanation for this association by the evaluation of the biomarker value of PBL-TL in preclinical atherosclerosis. Peripheral blood leucocyte telomere length was assessed by telomere restriction fragment analysis in 2509 volunteers free from established CVD, aged approximately 35-55 years old, from the Asklepios Study cohort. Intima-media thickness (IMT) and plaque presence were determined by ultrasonography in both left and right carotid and femoral arteries. Peripheral blood leucocyte telomere length was not a significant independent determinant of IMT (P > 0.3) or plaque presence (P > 0.05), in either artery or either sex. In women but not in men, PBL-TL was a weak determinant of combined (carotid or femoral) plaque presence, adjusted for other risk factors (women: P = 0.03, men: P > 0.4). However, even in women presenting plaques, PBL-TL was still longer than in men. Since systemic TL is not a substantial underlying determinant of preclinical atherosclerosis, the association between CVD and TL cannot be explained by the fact that subjects with shorter inherited TL are predisposed to atherosclerosis.

A009 Importance of tweak-CD163 system in peripheral artery disease

CD163 is a macrophage receptor of haptoglogin/ haemoglobin complexes responsible for clearance of hemogloin. It has been recently suggested to be a potential scavenger receptor for TWEAK (Tumor necrosis factor-like weak inducer of apoptosis). TWEAK levels were reported to be decreased in carotid atherosclerosis. Our hypothesis is that decreased circulating TWEAK could be paralleled by an increased presence of CD163-expressing macrophage in atherosclerotic plaques. Since peripheral artery disease (PAD) is an important manifestation of systemic atherosclerosis, we have assessed the levels of circulating TWEAK-CD163 in PAD. Patients with PAD (n=184) had lower TWEAK (169.2±8.3 vs 211.9±15.4 pg/mL; p<0.05) and higher sCD163 (408.1±14.5 vs 317.4±8.4 ng/mL; p<0.05) plasma concentration than age-matched controls (n=330). After stratification according to the severity of disease, we observed that TWEAK/sCD163 ratio was significantly decreased in those patients with higher degree of disease (0.39±0.06 vs 0.66±0.08, p<0.05) relative to the other groups. Analysis of conditioned medium obtained from cultured human atherosclerotic femoral plaque samples (n=38) and healthy aortas (n=14) revealed that higher amount of sCD163 was released by the atherosclerotic tissue, whereas TWEAK presented the opposite trend. Our results suggest that CD163/TWEAK plasma ratio could be a potential biomarker of clinical peripheral artery disease. We can hypothesized that decreased levels of circulating TWEAK observed in atherosclerosis may be the result of a trapping by plaque macrophages through their CD163.

Carotid Atherosclerosis in Ischemic Cerebrovascular Patients

BackgroundCerebral emboli resulting from atherosclerosis at the carotid bifurcation is a major cause of ischemic stroke. A convenient and prompt evaluation is necessary for secondary prevention and treatment.MethodsIn this study, one hundred and thirty eight patients with cerebral ischemic events were enrolled; 100 patients with nonischemic cerebral diseases were enrolled as controls. Noninvasive ultrasound was used to measure the atherosclerotic plaques and intima-media thickness (IMT) of carotid and femoral artery.ResultsOur results showed that patients in study group had higher incidence and severity of carotid and femoral plaques, and higher mean intima-media thickness (IMT) at both the carotid and femoral sites compared with that of controls (p < 0.01). Carotid atherosclerosis were highly prone to have instability plaques in study group(p < 0.001).ConclusionsThis cross-sectional study showed that, the prevalence of carotid atherosclerosis and the unstable plaques were higher in cerebral ischemic patients.KeywordsCarotid artery; Atherosclerosis; Intima-media thickness; Cerebral ischemic stroke

ADAM8 and its single nucleotide polymorphism 2662 T/G are associated with advanced atherosclerosis and fatal myocardial infarction: Tampere vascular study

Objective. Previously, we scanned all 23,000 human genes for differential expression between normal and atherosclerotic tissues and found the involvement of ADAM8.Methods. We investigated the expression of ADAM8 mRNA and protein level in human atherosclerotic tissues and non-atherosclerotic internal thoracic arteries as well as the association of ADAM8 2662 T/G single nucleotide polymorphism (SNP) with the extent of coronary atherosclerosis and with the risk of fatal myocardial infarction.Results. ADAM8 mRNA was up-regulated in carotid, aortic, and femoral atherosclerotic plaques (n=24) when compared with non-atherosclerotic arteries. ADAM8 protein expression was increased in advanced atherosclerotic plaques as compared to control vessels wherein it was localized to macrophages and smooth muscle cells The G allele carriers of the ADAM8 2662 T/G SNP had significantly larger areas of fibrotic, calcified, and complicated plaques in coronary arteries (P=0.027, P=0.011, and P=0.011, respectively) and significantly higher occurrence of myocardial infarction (MI) (P=0.004) and fatal pre-hospital MI (P=0.003) than did the TT homozygotes.Conclusion. ADAM8 is a promising candidate to be involved in atherosclerosis, and its 2662 T/G allelic variant significantly associates with advanced atherosclerotic lesion areas and MI.

Echolucent femoral plaques entail higher risk of echolucent carotid plaques and a more severe inflammatory profile in peripheral arterial disease

Plaque instability is recognized as a multivessel phenomenon related to inflammation. This study examined if the morphology of femoral plaques was related to that of carotid plaques. The echogenicity of femoral and carotid plaques of 102 patients with peripheral artery disease (PAD) was studied and classified as echolucent or echorich according to the gray-scale median (GSM) value, which was 53.6 for femoral plaques and 55.2 for carotid plaques. Serum C-reactive protein (CRP) levels and neutrophil count were also measured. Echolucent carotid plaques were more frequent in patients with echolucent than in those with echorich femoral plaques (55.8% vs 32.0%; P < .01). At multivariate analysis, femoral GSM lower than the median was the only significant predictor of echolucent carotid plaques (odds ratio [OR], 3.87; 95% confidence interval [CI], 1.53-9.83). Patients with echolucent femoral plaques had higher serum CRP levels (P < .01) and a higher neutrophil count (P = .029) than patients with echorich femoral plaques. However, univariate analysis showed that neutrophil count (OR, 3.48; 95% CI, 1.23-9.85) but not hs-CRP was associated with echolucent carotid plaques. At multivariate analysis, neutrophil count exceeding the median remained associated with echolucent carotid plaques (OR, 5.71; 95% CI, 1.37-23.85), whereas the association between femoral and carotid echolucency was attenuated (OR, 3.75; 95% CI, 0.98-4.43). In PAD, the presence of echolucent femoral plaques is associated with a greater prevalence of echolucent carotid plaques, probably as a consequence of a more pronounced inflammatory profile. This confirms and extends the finding that plaque echolucency is a multivessel phenomenon. Prospective studies are needed to assess whether carotid screening in PAD patients might contribute to improving clinical decision-making.

Ecografía femoral en la evaluación de la aterosclerosis preclínica. Distribución de valores del grosor íntima-media y frecuencia de placas de ateroma en una cohorte comunitaria española

High-resolution B-mode ultrasound measurements of intima-media thickness (IMT) and plaque presence are useful to assess preclinical atherosclerosis. Normal carotid IMT values, but not normal femoral IMT values, have been reported in Spanish subjects. Our aim was to define the normality data of femoral ultrasound by sex and age. We studied 192 healthy subjects from a community cohort, 85 men and 107 women (mean age: 49 years; range: 20-81 years). We sonographically determined mean and maximum IMT in the far wall of the common femoral artery, plaque occurrence, and maximum plaque height. Reference values for femoral IMT, expressed as 25th, 50th, and 75th percentiles by sex and 5 age groups, were obtained. The 50th percentiles of mean IMT ranged from 0.50 to 1.04 mm in men in the age groups < or = 35 years and > or = 65 years, respectively. For women, corresponding IMT values ranged from 0.40 to 0.53 mm. IMT was positively related to age in both men (r = 0.44; p < 0.001) and women (r = 0.23; p = 0.019). From the regression equations of IMT versus age, the estimated yearly increase in IMT was 0.016 mm in men and 0.008 mm in women. More than 50% of men aged > or = 55 years and women aged > or = 65 years had plaques. Both IMT and plaque frequency are associated with age in men and women. Femoral IMT values in a Spanish community cohort are lower than those reported for geographical areas with higher cardiovascular risk, such as the Northern European countries and the US.

Abstract 951: Femoral Plaques Confound the Association of Circulating Oxidized Low-density Lipoprotein with Carotid Atherosclerosis in a General Population Aged 35–55 Years (Asklepios Study).

Objective. Previously reported associations of oxidized low-density lipoprotein (OxLDL) with non-invasive measures of atherosclerosis were inconsistent. Moreover oxLDL was not an independent predictor of future cardiovascular endpoints in models adjusting for lipid markers (total and HDL-cholesterol). Therefore, in the Asklepios Study cohort of 2524 asymptomatic subjects aged 35–55 years, we evaluated the multiple-adjusted association between circulating OxLDL and subclinical atherosclerosis in the carotid and femoral arteries (ultrasound based definitions). Methods and results. Participants (mean age 45 years, 51.5% females) underwent a clinical examination, ultrasound protocol for determination of intima-media thickness (IMT) and plaques (Mannheim criteria) in the left and right carotid and femoral arteries, blood analysis for OxLDL (mAb-4E6) and other risk markers. They all completed a lifestyle variables study questionnaire. OxLDL concentrations were highest in subjects with femoral plaques (n=658). In the group of subjects with carotid plaques (n=476), elevated OxLDL concentrations were related to concomitant femoral plaques detected in 54% of these subjects. Stepwise multiple regression for oxLDL comprizing classical covariates demonstrated that non-HDL-cholesterol (beta 0.41), HDL-cholesterol (beta −0.34), femoral artery plaque (beta 8.97), ln(triglycerides) (beta 4.89), and gender (beta 2.79) were significant (p &lt; 0.05) determinants. Full models including all appropriate anthropometric, hemodynamic, biochemical, and lifestyle variables confirmed that femoral plaques are independently related to OxLDL. Similar analyses demonstrated that femoral IMT, carotid IMT, or carotid plaques were not independently associated with OxLDL. Conclusion. Circulating OxLDL is independently associated with femoral plaque and not with carotid artery wall damage.

Compliance of the aorta in two diseases affecting vascular elasticity, familial hypercholesterolemia and diabetes: a MRI study

Arterial elasticity changes in familial hypercholesterolemia (FH) and diabetes mellitus (DM) with different but overlapping mechanisms. We compared aortic elasticity between 19 FH patients with the same mutation, 18 type 2 DM patients, and 30 controls, all aged 48 to 64. They underwent aortic magnetic resonance imaging, risk-factor assessment, and carotid and femoral ultrasound measurements. All patients were on adequate cardiovascular medication including statins and had established coronary heart disease (CHD). FH patients had longer-duration CHD (13.3 +/- 7.7 years) than did DM patients (5.0 +/- 3.1). Aortic compliance in the descending thoracic (DM 0.38 +/- 0.14 vs control 0.53 +/- 0.19, P = 0.032) and abdominal aorta (DM 0.45 +/- 0.20 vs control 0.66 +/- 0.25, P = 0.011) was lower in DM patients than in controls, whereas no significant difference existed between FH patients and controls. Carotid and femoral intima-media thickness was greater in FH and DM patients than in controls with no difference between patient groups. Carotid or femoral plaques appeared in 15 (79%) FH and in 10 (56%) DM patients. One control had a femoral plaque. Five FH patients showed stenosis, occlusion or both in carotid arteries. In our opinion, DM patients' lower compliance reflect mainly arterial media affecting arteriosclerosis, while FH patients' plaque status and longer duration of CHD suggest more advanced atherosclerosis. The FH patients may therefore be at increased risk for atherothrombotic events. However, due to small patient material, larger confirmatory studies are needed.

Femoral Plaques Confound the Association of Circulating Oxidized Low-Density Lipoprotein With Carotid Atherosclerosis in a General Population Aged 35 to 55 Years

Reported associations of oxidized low-density lipoprotein (oxLDL) with noninvasive measures of atherosclerosis are inconsistent. In the Asklepios Study cohort of asymptomatic subjects aged 35 to 55 years, we evaluated the relationship of circulating oxLDL with subclinical atherosclerosis in the carotid and femoral arteries. Participants (n=2524, 51.5% females) completed a study questionnaire and underwent a clinical examination, blood analysis of oxLDL (mAb-4E6) and other risk markers, and ultrasound examination of intima-media thickness (IMT) and plaques in the left and right carotid and femoral arteries. oxLDL concentrations were highest in subjects with femoral plaques (n=658). In the group of subjects with carotid plaques (n=476), elevated oxLDL concentrations are related to concomitant femoral plaques detected in 54% of these subjects. Multivariate regression analyses (including anthropometric, hemodynamic, biochemical, and lifestyle variables) showed that femoral plaques are independently related to oxLDL whereas femoral IMT, carotid IMT, or carotid plaques were not independently associated with oxLDL. Circulating oxLDL is independently associated with femoral plaque and not with carotid artery wall damage.

Baseline ICAM-1 and VCAM-1 are Increased in Initially Healthy Middle-Aged Men who Develop Cardiovascular Disease during 6.6 Years of Follow-Up

The objective of the present study was to investigate if there was a difference in baseline serum concentrations of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) between groups with and without cardiovascular events during a mean follow-up of 6.6 years in a group of initially healthy 58-year-old men. A further aim was to examine if high serum concentrations of ICAM-1 and VCAM-1 were associated with carotid and femoral artery plaque occurrence, separately. Men with cardiovascular events during follow-up had higher median serum ICAM-I and VCAM-I than those without events (P < .05). The median of serum ICAM-I and VCAM-1 in the event group was used as the cutoff level, and in those with ICAM-1 and VCAM-1 above the cutoff value, there was an increased risk of having a plaque in the femoral artery (OR = 2.8, 95% CI = 1.8-4.3; and OR = 1.6, 95% CI = 1.1-2.5, respectively).

FEMORAL ATHEROSCLEROSIS IN HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA. INFLUENCE OF THE GENETIC DEFECT

Objective—The purpose of this study was to assess femoral atherosclerosis by ultrasound in patients with molecularly defined heterozygous familial hypercholesterolemia (FH) in comparison with matched control subjects and in relation to mutational class in the LDL receptor and apolipoprotein B (APOB) genes. Methods and Results—Femoral intima-media thickness (IMT) and plaque were evaluated in 146 FH patients carrying null alleles (n48), defective-receptor alleles (n62), undetermined-function alleles (n25), or APOB defects (n11) and in 193 healthy subjects. Twenty-three patients had coronary heart disease (CHD). The frequency of both tendon xanthomas and CHD was 2-fold higher and average LDL cholesterol was 30 mg/dL higher in null-allele genotype compared with receptor-defective mutations. All femoral measurements were increased in FH patients versus controls (P0.001), and null-allele mutations showed higher age-, sex-, and LDL cholesterol-adjusted maximum IMT than receptor-defective or APOB defects (P for trend, 0.001). By multivariate analysis, independent associations of mean IMT, a measure of early atherosclerosis, were age, LDL cholesterol, sex, and systolic blood pressure. Age, null-allele genotype, sex, and smoking explained 42% of the variability of maximum IMT, a measure of advanced atherosclerosis. Conclusions—FH patients have increased femoral IMT in relation to mutational class. The findings support the usefulness of genetic testing in FH beyond securing the diagnosis. (Arterioscler Thromb Vasc Biol. 2008;28:000-000.)

Circulating matrix metalloproteinase 9 levels in relation to sampling methods, femoral and carotid atherosclerosis

To examine whether circulating levels of matrix metalloproteinase 9 (MMP-9) were associated with ultrasound-assessed intima-media thickness (IMT) and echolucent plaques in the carotid and femoral arteries. To examine preanalytical sources of variability in MMP-9 concentrations related to sampling procedures. Plasma and serum MMP-9 levels were compared with ultrasound assessed measures of femoral and carotid atherosclerosis, in a cross-sectional study of 61-year-old men (n = 473). Preanalytical sources of variability in MMP-9 levels were examined in 10 healthy subjects. Main outcome measures were circulating levels of MMP-9 in serum and plasma, IMT of the carotid and femoral arteries, and plaque status based on size and echolucency. Research unit at university hospital. Plasma concentrations of total and active MMP-9 were associated with femoral artery IMT independently of traditional cardiovascular risk factors, and were higher in subjects with moderate to large femoral plaques. Plasma MMP-9 concentration was higher in men with echolucent femoral plaques (P = 0.006) compared with subjects without femoral plaques. No similar associations were found for carotid plaques. MMP-9 concentrations were higher in serum than in plasma, and higher when sampling was performed with Vacutainer than with syringe. MMP-9 levels in serum were more strongly associated with peripheral neutrophil count compared with MMP-9 levels in plasma. Plasma MMP-9 levels were associated with atherosclerosis in the femoral artery, and total MMP-9 concentration was higher in men with echolucent femoral plaques. The choice of sample material and sampling method affect the measurements of circulating MMP-9 levels.

Associations of Insulin-Like Growth Factor (IGF)-I, IGF-II, IGF Binding Protein (IGFBP)-2 and IGFBP-3 with Ultrasound Measures of Atherosclerosis and Plaque Stability in an Older Adult Population

Circulating IGF-I is inversely associated with ischemic heart disease incidence. Whether this association relates to alterations in plaque growth or stability, and the role of IGF-II and the major binding proteins [IGF binding protein (IGFBP)-2 and -3], is unclear. Our objective was to test the hypothesis that circulating IGF-I is inversely, and IGF-II is positively, associated with subclinical atherosclerosis and plaque stability. This was a cross-sectional analysis based on 310 participants in the United Kingdom-based Boyd Orr cohort who were aged 63-82 yr. Cohort members from Aberdeen, Bristol, Dundee, Wisbech, and London were invited to clinics for fasted venepuncture and arterial ultrasound examination. Arterial intima-media thickness, arterial plaque prevalence, and computerized assessment of plaque echogenicity (a measure of stability), undertaken using the gray scale median, were calculated. In total, 269 of 310 (86.8%) participants had at least one carotid or femoral plaque. In models controlling for IGFBP-3, there was a 44% (95% confidence interval 12-64%) reduction in the odds of any plaque and a 28% lower (0-48%) odds of echolucent (unstable) plaques per sd increase in IGF-I. IGFBP-3 was positively associated with plaque instability (odds ratio: 1.38; 0.99-1.93). IGF-II was positively associated (0.05-mm increase per sd; 95% confidence interval 0.01-0.09), and IGFBP-2 was inversely associated, with carotid bifurcation intima-media thickness. Neither IGF-II nor IGFBP-2 was associated with plaque prevalence or echogenicity. High-circulating IGF-I levels may promote arterial plaque stability. IGF-II and IGFBP-2 do not appear to play a role in plaque development or stability.

Associations of IGF-I, IGF-II, IGFBP-2 and IGFBP-3 with ultrasound measures of atherosclerosis and plaque stability in an older adult population.

Context: Circulating IGF-I is inversely associated with ischemic heart disease incidence. Whether this association relates to alterations in plaque growth or stability, and the role of IGF-II and the major binding proteins [IGF binding protein (IGFBP)-2 and -3], is unclear. Objective: Our objective was to test the hypothesis that circulating IGF-I is inversely, and IGF-II is positively, associated with subclinical atherosclerosis and plaque stability. Design, Setting, and Participants: This was a cross-sectional analysis based on 310 participants in the United Kingdom-based Boyd Orr cohort who were aged 63-82 yr. Cohort members from Aberdeen, Bristol, Dundee, Wisbech, and London were invited to clinics for fasted venepuncture and arterial ultrasound examination. Main Outcomes: Arterial intima-media thickness, arterial plaque prevalence, and computerized assessment of plaque echogenicity (a measure of stability), undertaken using the gray scale median, were calculated. Results: In total, 269 of 310 (86.8%) participants had at least one carotid or femoral plaque. In models controlling for IGFBP-3, there was a 44% (95% confidence interval 12-64%) reduction in the odds of any plaque and a 28% lower (0-48%) odds of echolucent (unstable) plaques per sd increase in IGF-I. IGFBP-3 was positively associated with plaque instability (odds ratio: 1.38; 0.99-1.93). IGF-II was positively associated (0.05-mm increase per sd; 95% confidence interval 0.01-0.09), and IGFBP-2 was inversely associated, with carotid bifurcation intima-media thickness. Neither IGF-II nor IGFBP-2 was associated with plaque prevalence or echogenicity. Conclusion: High-circulating IGF-I levels may promote arterial plaque stability. IGF-II and IGFBP-2 do not appear to play a role in plaque development or stability.

Expression of sterol regulatory element-binding transcription factor (SREBF) 2 and SREBF cleavage-activating protein (SCAP) in human atheroma and the association of their allelic variants with sudden cardiac death

BackgroundDisturbed cellular cholesterol homeostasis may lead to accumulation of cholesterol in human atheroma plaques. Cellular cholesterol homeostasis is controlled by the sterol regulatory element-binding transcription factor 2 (SREBF-2) and the SREBF cleavage-activating protein (SCAP). We investigated whole genome expression in a series of human atherosclerotic samples from different vascular territories and studied whether the non-synonymous coding variants in the interacting domains of two genes, SREBF-2 1784G>C (rs2228314) and SCAP 2386A>G, are related to the progression of coronary atherosclerosis and the risk of pre-hospital sudden cardiac death (SCD).MethodsWhole genome expression profiling was completed in twenty vascular samples from carotid, aortic and femoral atherosclerotic plaques and six control samples from internal mammary arteries. Three hundred sudden pre-hospital deaths of middle-aged (33–69 years) Caucasian Finnish men were subjected to detailed autopsy in the Helsinki Sudden Death Study. Coronary narrowing and areas of coronary wall covered with fatty streaks or fibrotic, calcified or complicated lesions were measured and related to the SREBF-2 and SCAP genotypes.ResultsWhole genome expression profiling showed a significant (p = 0.02) down-regulation of SREBF-2 in atherosclerotic carotid plaques (types IV-V), but not in the aorta or femoral arteries (p = NS for both), as compared with the histologically confirmed non-atherosclerotic tissues. In logistic regression analysis, a significant interaction between the SREBF-2 1784G>C and the SCAP 2386A>G genotype was observed on the risk of SCD (p = 0.046). Men with the SREBF-2 C allele and the SCAP G allele had a significantly increased risk of SCD (OR 2.68, 95% CI 1.07–6.71), compared to SCAP AA homologous subjects carrying the SREBF-2 C allele. Furthermore, similar trends for having complicated lesions and for the occurrence of thrombosis were found, although the results were not statistically significant.ConclusionThe results suggest that the allelic variants (SREBF-2 1784G>C and SCAP 2386A>G) in the cholesterol homeostasis regulating SREBF-SCAP pathway may contribute to SCD in early middle-aged men.

Femoral Atherosclerosis In Heterozygous Familial Hypercholesterolemia

The purpose of this study was to assess femoral atherosclerosis by ultrasound in patients with molecularly defined heterozygous familial hypercholesterolemia (FH) in comparison with matched control subjects and in relation to mutational class in the LDL receptor and apolipoprotein B (APOB) genes. Femoral intima-media thickness (IMT) and plaque were evaluated in 146 FH patients carrying null alleles (n=48), defective-receptor alleles (n=62), undetermined-function alleles (n=25), or APOB defects (n=11) and in 193 healthy subjects. Twenty-three patients had coronary heart disease (CHD). The frequency of both tendon xanthomas and CHD was approximately 2-fold higher and average LDL cholesterol was 30 mg/dL higher in null-allele genotype compared with receptor-defective mutations. All femoral measurements were increased in FH patients versus controls (P<0.001), and null-allele mutations showed higher age-, sex-, and LDL cholesterol-adjusted maximum IMT than receptor-defective or APOB defects (P for trend, 0.001). By multivariate analysis, independent associations of mean IMT, a measure of early atherosclerosis, were age, LDL cholesterol, sex, and systolic blood pressure. Age, null-allele genotype, sex, and smoking explained 42% of the variability of maximum IMT, a measure of advanced atherosclerosis. FH patients have increased femoral IMT in relation to mutational class. The findings support the usefulness of genetic testing in FH beyond securing the diagnosis.

Accuracy of the screening physical examination to identify subclinical atherosclerosis and peripheral arterial disease in asymptomatic subjects

This study assessed the accuracy of the screening vascular physical examination for predicting asymptomatic peripheral arterial disease (PAD) or subclinical atherosclerosis in asymptomatic and apparently healthy subjects. A standardized physical examination and a carotid and femoral ultrasonography were administered to 2736 men and women aged 20 to 90 years old, with no personal history of cardiovascular disease (CVD) and no complaint of neurologic, coronary, or lower limb symptom. We assessed the accuracy of auscultation for bruits and pulse palpation for identifying the presence of significant carotid stenosis, carotid plaque, femoral plaque, and ankle-brachial index (ABI) <0.9 at ultrasonography. The presence of a femoral bruit provided information on the presence of both an ABI <0.9 (positive likelihood ratio [+LR], 2.90; 95% confidence interval [CI], 1.63 to 5.16) and a femoral plaque (+LR, 3.23; 95% CI, 2.22 to 4.71), and this information was independent from the cardiovascular risk factors. The absence of both pedal pulses also provided additional information, beyond risk factors, on the presence of an ABI <0.9 (+LR, 3.57; 95% CI, 1.93 to 6.60). The presence of a carotid bruit did not affect the likelihood of carotid stenosis, plaque, or intima-media thickness above the median. Unlike carotid auscultation, pulse palpation and auscultation for femoral bruits provided valuable information on the presence of asymptomatic PAD and underlying atherosclerosis in apparently healthy subjects.