Measure Of Early Atherosclerosis Research Articles

Coronary tortuosity relation with carotid intima-media thickness, coronary artery disease risk factors, and diastolic dysfunction: is it a marker of early atherosclerosis?

BackgroundCoronary tortuosity (C-Tor) is a common finding in coronary angiography (CAG). There are conflicting data about its link to atherosclerosis: one study found a negative relationship with coronary artery disease (CAD), although it had been linked to age and hypertension (HTN), which are CAD risk factors. Carotid intima-media thickness (C-IMT) is a measure of early atherosclerosis and a surrogate for CAD, diastolic dysfunction is also associated with CAD risk factors. In this retrospective case-control study, we investigated the relationship between C-Tor, C-IMT, diastolic dysfunction, and the other risk factors in patients undergoing CAG in a tertiary hospital between July 2017 and June 2018, after excluding patients with significant CAD. C-Tor was defined as the presence of ≥ 3 bends (≥ 45°) along the trunk of at least one main coronary artery in CAG.ResultsAfter excluding 663 patients due to exclusion criteria, 30 patients with C-Tor were compared with age and gender-matched controls. HTN was significantly more common in the C-Tor group (86.7% vs. 30%, p < 0.002); other clinical characteristics were similar. The C-IMT was abnormal in the C-Tor group only (p: 0.007). The diastolic dysfunction parameters differed between the two groups: the E/A ratio was < 1 in the C-Tor group and > 1 in the normal group (p: < 0.001); the E velocity and deceleration time were significantly lower in the C-Tor group (p: 0.001 and < 0.001 respectively); the E/E′ ratio, A, and A′ velocities were significantly higher (p: 0.005, < 0.001, < 0.001 respectively); while the S′ velocity was similar in the 2 groups (p: 0.078). The C-Tor group had higher total cholesterol and LDL (p: 0.003 and 0.006 respectively). All C-Tor patients undergoing stress tests had positive results. The only independent C-Tor predictors in a regression analysis were HTN, total cholesterol, A-wave velocity, and deceleration time (DT) (odds ratio: 14.7, 1.03, 1.15, and 0.95, all p: < 0.05). A-wave velocity had the best area under the curve, sensitivity, and specificity for C-Tor prediction (0.88, 73.3%, and 96.7% respectively) followed by DT (0.86, 66.67%, and 96.6% respectively).ConclusionC-Tor is associated with increased C-IMT, HTN, hyperlipidemia, and left ventricular diastolic dysfunction; all contributing to an ongoing atherosclerotic process. A-wave velocity and DT were independent predictors of C-Tor. C-Tor may cause microvascular ischemia that merits further investigation.

Association of pulse wave velocity and intima-media thickness with cardiovascular risk factors in young adults.

Pulse wave velocity (PWV), a measure of arterial stiffness, and intima‐media thickening (IMT), a measure of early atherosclerosis, are intermediate markers of cardiovascular disease which are predictive of cardiovascular events. Traditionally, both were thought to result from accumulative exposure to traditional cardiovascular risk factors. However, their association with risk factors in young adults in low‐income settings is unknown. We sought to investigate the association between PWV and IMT with traditional cardiovascular risk factors in the Andhra Pradesh Children and Parents Study cohort from Southern India. Male and female adults (N = 1440) aged between 20 and 24 years underwent measures of PWV and IMT. Exposure variables included smoking, body mass index (BMI), mean arterial pressure (MAP), glucose, homeostatic model assessment of insulin resistance (HOMA‐IR), total cholesterol, high‐density lipoprotein cholesterol (HDL‐cholesterol), and triglycerides. Association between outcome and exposure variables was assessed using linear regression analysis. Average values for PWV and IMT were 5.9 ± 0.6 m/s and 0.5 ± 0.1 mm. In univariable analysis, PWV associated with MAP, BMI, smoking, total cholesterol, glucose, and HOMA‐IR and IMT associated with MAP, BMI, tobacco use, and HDL‐cholesterol. In multivariable analysis, PWV remained strongly positively associated with MAP increasing by 0.5 m/s (P < .001) for a 10 mm Hg increase in MAP (R 2 = .37). In contrast, IMT negatively associated with HDL‐cholesterol (β = −.10; P = .012, R 2 = .02). There was weak evidence that PWV and IMT positively associated with BMI. In young adults from Southern India, PWV positively associated with blood pressure and IMT negatively associated with HDL‐cholesterol. This suggests separate etiologies for atherosclerosis and arterial stiffening in young adults.

Segmentation of Intima Media Complex ofCommon Carotid Artery

Atherosclerosis is a disease of blood vessels caused by the formation of plaques in artery walls. Its diagnosis is one of the most important medical examinations for the prevention of cardiovascular events, like myocardial infarction and stroke. The segmentation of the intima-media complex (IMC) of the common carotid artery (CCA) wall is important for the evaluation of the intima media thickness (IMT) on B-mode ultrasound (US) images. IMT is considered an important marker in the evaluation of the risk for the development of atherosclerosis. Carotid intima media thickness (IMT), which is the distance between the lumen-intima and the media-adventitia interfaces, is a measure of early atherosclerosis. segmentation algorithm is based on active contours and active contours without edges and provides information to achieve accurate segmentation. The level set formulation by Chan and Vese model provides a segmentation of the CCA US images into different distinct regions, one of which corresponds to the carotid wall region below the lumen and includes the far wall IMC.

Plasma copeptin levels are inversely associated with intima-media-thickness in men: the population-based KORA F4 study

BackgroundElevated plasma preprovasopressin (copeptin) levels are associated with cardiovascular complications as well as with an increased risk for type 2 diabetes (T2D). Here, we studied, whether plasma copeptin is related to carotid intima-media thickness (IMT), a measure of early atherosclerosis, and may thus be one explanation for the high cardiovascular risk in T2D.MethodsPlasma concentrations of copeptin and IMT of the common carotid artery were determined in 1275 participants of the population-based KORA F4 study. We used linear regression models to investigate associations between copeptin levels and IMT.ResultsIn the whole study group, copeptin levels were not significantly associated with IMT after adjustment for age and sex. Copeptin and IMT were significantly inversely associated after multivariable adjustment in the total cohort (β = -0.020 mm, 95% CI: -0.037 mm; -0.003 mm), in men (β = -0.035 mm, 95% CI: -0.061 mm; -0.009 mm) and in study participants with prediabetes (β = -0.041 mm, 95% CI: -0.078 mm; -0.005 mm) comparing quartile 4 vs quartile 1. The negative association of copeptin and IMT in men was present after adjustment for age alone. In women and patients with T2D, copeptin was not significantly associated with IMT.ConclusionsPlasma copeptin was not associated with an increased IMT in our study cohort. In contrast, copeptin levels were related to a lower IMT in men and subjects with prediabetes, suggesting that elevated copeptin concentrations do not exert proatherogenic effects on carotid arteries.

Hyperlipidemia, oxidative stress, and intima media thickness in children with chronic kidney disease

The roles of dyslipidemia and oxidative stress in the early phases of atherosclerosis were tested in children with chronic kidney disease (CKD). Intima media thickness of common carotid arteries (cIMT) is used as a measure of early atherosclerosis. Fifty-two pediatric CKD patients were enrolled in the study (10 with chronic renal failure [CRF], 22 with a renal transplant [RT], 20 with chronic hemodialysis (cHD) patients, and 36 healthy children (control group, CG). Lipid status, oxidative stress, and paraoxonase 1 (PON1) status were assessed. cIMT was measured by ultrasound, adjusted for age and sex, and presented as standard deviation scores (SDS). Children with CKD had disturbed lipid content, which was most pronounced in cHD children, with higher free cholesterol and triglycerides compared with healthy children. Oxidative stress was markedly increased (malodialdehyde [MDA, μmol/L]: CRF 1.50 ± 0.26, RT 1.55 ± 0.40, cHD 1.77 ± 0.34, CG 0.97 ± 0.33, p < 0.001) and antioxidative defense was compromised (superoxide dismutase [SOD, U/L]: CG 120 ± 21, CRF 84 ± 25, RT 93 ± 12, cHD 119 ± 37, p < 0.001). Multiple linear regression analysis showed that a model that included disease duration, blood pressure, urea, lipid, and oxidative status parameters accounted for more than 90% of the variability of cIMT-SDS. Early atherosclerosis in CKD children is caused, at least in part, by dyslipidemia and oxidative stress. Monitoring of vessel wall changes, along with assessment of oxidative stress status and high density lipoprotein (HDL) functionality is necessary to ensure better therapeutic strategies for delaying atherosclerotic changes in their asymptomatic phase.

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.)

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.

Markers of Systemic Bacterial Exposure in Periodontal Disease and Cardiovascular Disease Risk: A Systematic Review and Meta‐Analysis

Recent meta-analyses reported a weak association between periodontal disease (PD) on clinical examination and cardiovascular disease (CVD). Systemic bacterial exposure from periodontitis, which correlates poorly with the clinical examination, has been proposed as the more biologically pertinent risk factor. The purpose of this study was to review and analyze the association between PD with elevated systemic bacterial exposure and CVD. We searched in the PubMed, Cochrane Controlled Trials Register, EMBASE, and SCOPUS databases for all literature examining PD and CVD. From 10 selected publications, we extracted 12 cohort (N = 5) and cross-sectional (N = 7) studies and included 11 of these in a meta-analysis. With stratified analyses, this resulted in 14 analyses of coronary heart disease (CHD; N = 7), stroke (N = 4), and carotid intima-medial thickening (CIMT; N = 3) as a measure of early atherosclerosis. Systemic bacterial exposure was measured by periodontal bacterial burden (N = 1), periodontitis-specific serology (N = 12), or C-reactive protein (N = 1). Periodontal disease with elevated markers of systemic bacterial exposure was associated strongly with CHD compared to subjects without PD, with a summary odds ratio of 1.75 (95% confidence interval (CI): 1.32 to 2.34; P <0.001). This group was not associated with CVD events or with stroke but was associated with a significant increase in mean CIMT (0.03 mm; 95% CI: 0.02 to 0.04). Periodontal disease with elevated bacterial exposure is associated with CHD events and early atherogenesis (CIMT), suggesting that the level of systemic bacterial exposure from periodontitis is the biologically pertinent exposure with regard to atherosclerotic risk.

Inflammatory gene load is associated with enhanced inflammation and early carotid atherosclerosis in smokers.

Smoking acts as a pro-inflammatory stimulus. Inflammation may provide a key mechanism by which smoking causes atherosclerosis. If so, then the degree to which an individual mounts an inflammatory response is likely to influence atherosclerosis severity. This study examined the impact of inflammatory gene polymorphisms and gene-smoking interactions on common carotid artery intima-media thickness (IMT), a measure of early atherosclerosis. In a community population (n=1000), mean IMT was determined using ultrasound. This population was genotyped for 6 polymorphisms in 4 inflammatory genes: IL-6-174, IL-6-572, and IL-6-597; IL-1-beta-31; IL-1 receptor antagonist VNTR and CD14-159. Serum IL-6 levels were measured in the first 500 subjects. Genotypes/haplotypes associated with higher IL-6 levels were designated "inflammatory haplotypes." A gene load score was calculated, in which 2 represented individuals homozygous for > or =2 inflammatory genotypes/haplotypes and 0 was homozygous for none. Increasing gene load of inflammatory genotypes was associated with a linear increase in serum IL-6 levels (P=0.018) and increased carotid artery IMT (P=0.003). There was a significant interaction between gene load and smoking status on carotid IMT (P for interaction=0.002). Specifically, in smokers, carriers of inflammatory haplotypes had significantly increased age- and sex-adjusted IMT (IL-6-174C/IL-6-572G/IL-6-597A, P=0.005; IL-1-beta-31T/IL-1RN*2,P=0.04; CD14-159CC, P=0.028). These findings support the hypothesis that inflammation and cytokine responses provide a key mechanism by which smoking causes atherogenesis. Secondly, they highlight the importance of gene-environment, and gene-gene-environment interactions in the pathogenesis of atherosclerosis.

Automated intima-media thickness: the Los Angeles atherosclerosis study

Common carotid artery (CCA) intima-media thickness (IMT) from B-mode ultrasound is a widely used measure of early atherosclerosis. This study evaluated within- and between-sonographer reproducibility of automated edge-tracking IMT using a low-cost mobile scanner. B-mode images of the left and right CCA were acquired on two occasions (interval of 2–14 days) by two sonographers for 38 subjects, aged 31–75 y. Reproduciblity error was measured as the mean absolute difference (MAD ± SEM) and the standard deviation of differences (SDΔ) between repeated measurements. Within-sonographer (MAD = 0.027 ± 0.006 mm; SDΔ = 0.044 mm) and between-sonographer errors (MAD = 0.041 ± 0.008 mm; SDΔ = 0.064) in IMT (mean = 0.74, SD = 0.14) of a single artery were small compared to those of other protocols. Combined averaging across both body positions and arteries reduced intersonographer MAD by 47% (MAD = 0.022 ± 0.003 mm; SDΔ = 0.029 mm). These data demonstrate that the proposed IMT protocol reduces reproducibility error by more than 50% relative to several protocols used in other major studies.

No association between serum ferritin and asymptomatic carotid atherosclerosis. The Atherosclerosis Risk in Communities (ARIC) Study.

A possible association between body iron stores, measured as serum ferritin, and carotid arterial intima-media thickening was investigated in the Atherosclerosis Risk in Communities Study during 1990-1992 using a matched case-control design. For a 143-micrograms/liter greater serum ferritin concentration (the interquartile range), the odds ratio for cases with carotid intima-media thickening versus controls was 1.12 (95% confidence interval 0.97-1.30). However, there was no association (odds ratio = 1.00) after adjusting for major cardiovascular risk factors. This analysis of carotid arterial intima-media thickening, a measure of early atherosclerosis, in relation to serum ferritin does not support the hypothesis that increased body iron stores increase the risk of atherosclerotic cardiovascular disease.

Effect of Cholesterol-Lowering Medications on Progression of Mild Atherosclerotic Lesions of the Carotid Arteries and on the Risk of Stroke

The Asymptomatic Carotid Artery Progression Study (ACAPS) compared the usefulness of lovastatin alone or in combination with warfarin in the prevention of 3-year progression of mean maximum intimal-medial thickness (IMT), which is a measure of early atherosclerosis. The factorally designed, placebo-controlled study enrolled 919 men and women aged 40–79 who had moderately elevated low-density-lipoprotein (LDL) cholesterol and a single maximum IMT of 1.5–3.5 mm in the carotid arteries. Lovastatin significantly reduced LDL cholesterol. The mean maximum IMT declined at an annual rate of 0.009 mm among those persons taking lovastatin while the mean maximum IMT increased by 0.006 mm in the controls (p = 0.001). In addition, deaths and the combined frequency of coronary deaths, nonfatal myocardial infarctions and strokes were significantly lowered among the lovastatin-treated groups. Only 5 strokes (3 hemorrhages) were detected in the study; all occurred among those persons who were receiving lovastatin placebo. Our study suggests that early administration of lipid-lowering drugs halts the progression of early atherosclerosis in the carotid artery. In turn, such early primary preventive treatment may lessen the risk of important ischemic vascular events including stroke.

Ultrasound-determined intima-media thickness and atherosclerosis. Direct and indirect validation.

To evaluate ultrasonographically determined intima-media thickness as a measure of early atherosclerosis, three studies were performed. Ultrasound measurements of intima-media thickness in the carotid artery were directly validated by comparing the same thickness measured by light microscopy. The values were closely correlated (r = .82, P < .001). Intima-media thickness determined by light microscopy was consistently smaller than that determined by ultrasound, probably due to shrinkage during histological preparation. As an indirect validation, mean intima-media thickness was calculated in three large groups of patients with no plaque (n = 224), one plaque (n = 105), and one circumferential or two or more plaques (n = 54) in the carotid bifurcation. Intima-media thickness increased significantly with increasing plaque score, indicating that diffuse intima-media thickening is more pronounced with more severe atherosclerosis. The intima-media thickness also increased with increasing multifactorial cardiovascular risk, reflecting a positive relation between signs of early atherosclerosis and the burden of known risk factors for the disease. Our studies support earlier findings that have found that ultrasonographically determined intima-media thickness is a valid way to study early atherosclerosis.