Meta-analysis of epigenome-wide association studies of carotid intima-media thickness

Common carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta?=??0.0264, p value?=?3.5?×?10^–8) in the discovery panel and was replicated in replication panel (beta?=??0.07, p value?=?0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value?=?1.4?×?10^–13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.

     

Are serum TSH levels associated with oxidized low‐density lipoprotein? Results from the Study of Health in Pomerania

Objective Oxidized LDL (oxLDL) is involved in the pathogenesis of atherosclerosis. Thus, it is important to investigate putative risk factors for increased oxLDL. Evidence suggests that, compared to euthyroid individuals, LDL‐cholesterol (LDL‐C) levels are lower in individuals with overt hyperthyroidism. Whereas oxidization of LDL‐C into oxLDL is increased in overt hyper‐ and hypothyroidism, it has not been investigated whether subclinical thyroid dysfunction impacts on oxLDL levels in general. We have analysed the association between serum thyrotrophin (TSH) levels and oxLDL in a population‐based study. Design, Patients and Measurements Of the 4308 individuals enrolled in the Study of Health in Pomerania, data from 3519 individuals were analysed (680 missing the oxLDL variable). oxLDL was measured by the oxLDL competitive ELISA on a BEP 2000. Multivariable linear regression models were performed to assess the association between serum TSH and oxLDL levels. Results TSH was positively associated with oxLDL in a curvilinear fashion with increasing serum TSH levels. Subgroup analyses revealed a significant association only in the group of individuals >60 years. Additionally, serum TSH levels were not associated with the ratio of oxLDL to LDL (β = ?0·04; 95% CI = ?0·08, 0·01; P = 0·084). Conclusions We demonstrate an association between serum TSH and oxLDL levels especially in the range of subclinical thyroid disease. Our study suggests that serum TSH levels affect LDL‐C production or clearance rather than the LDL‐C oxidation processes.     

Three-dimensional transcranial color-coded sonography for the examination of the arteries of the circle of Willis.

Because examinations of the intracranial vessels using conventional transcranial color-coded sonography (TCCS) lack spatial orientation and reproducibility, development of a three-dimensional (3-D) imaging technique is required. Three patients with middle cerebral artery (MCA) stenosis, three with suspected intracranial aneurysm, two with vascular malformation, and one healthy volunteer were investigated by 3-D TCCS using a magnetic spatial positioning sensor mounted on the transducer for simultaneous recording of the probe coordinates to create a volumetric data set. Three-dimensional transcranial color-coded sonography enabled good visualization of intracranial aneurysms and MCA stenoses. However, it failed to detect morphological details in vascular malformations. In conclusion, 3-D TCCS is a promising technique that opens new perspectives in depicting intracranial vessels and provides volume measurement of intracranial aneurysms.     

Volumetric Assessment of Plaque Progression With 3-Dimensional Ultrasonography Under Statin Therapy

BACKGROUND AND PURPOSE: Lowering of serum cholesterol levels with HMG-CoA reductase inhibitors (statins) slowed the progression of atherosclerosis in the carotid arteries in several clinical trials using carotid artery intima media thickness as primary outcome measure. Whereas conventional ultrasonography is limited to thin 2-dimensional image planes, 3-dimensional (3D) ultrasonography provides quantitative measurement of the entire carotid artery plaque volume. This study aims to assess the feasibility of 3D ultrasonography to monitor plaque progression in hypercholesterolemic patients. METHODS: The authors prospectively assessed the progression of 31 carotid artery plaques over 15.1 +/- 4.5 months in a study of 23 patients (6 women, 17 men; mean age = 61.7 +/- 7.5 years) with hypercholesterolemia under therapy with HMG-CoA reductase inhibitors. All patients were maintained on a lipid-lowering diet. Sixteen patients were additionally treated with statins. Quantitative measurements of carotid artery plaque volumes were performed after 3D reconstruction of exactly parallel transverse duplex ultrasound scans (slice distance = 0.1 mm) into volumetric 3D data sets and segmentation of voxels representing the carotid artery plaque. RESULTS: Within the treatment group, plaques were significantly less frequently progressive if they had a hypoechoic echogenicity (11%, n = 9 vs 64%, n = 14; P = .016) or if baseline serum cholesterol levels were above 8.0 mmol/L (9%, n = 11 vs 75%, n = 12; P = .002). CONCLUSION: Three-dimensional ultrasonography extends the measurement of the arterial wall thickness to the 3D volume of an entire atherosclerotic plaque including analysis of its morphology and configuration. However, further clinical trials with an adequate sample size to achieve sufficient statistical power are necessary to assess the effect of statin therapy on plaque progression.     

Prevalence of carotid artery stenosis in Taiwanese patients with one ischemic stroke

PURPOSE: Ethnic differences in the distribution of atherosclerosis in the brain-supplying vessels are well described. However, only scarce data exist on the prevalence of extracranial carotid artery stenosis in Taiwanese patients who have had a single ischemic stroke. METHODS: Color-coded duplex sonography was used to evaluate the carotid arteries in a hospital-based study on 276 consecutive first-time Taiwanese stroke patients. Significant atherosclerotic lesions of the internal carotid arteries (ICA) were defined as a stenosis of more than 50% or an occlusion. RESULTS: The prevalence of significant carotid lesions was 6% (35/552) in the entire cohort and 8% (17/224) in patients with hemispheric strokes. Among patients with large-artery atheroscleroses, according to criteria of the Trial of Org 10172 in Acute Stroke Treatment, only 27% had significant extracranial ICA disease whereas 69% had intracranial vessel stenoses. Older patients tended to have more severe ICA lesions, while other risk factors were not correlated with carotid stenosis. CONCLUSION: The prevalence of more than 50% ICA stenosis was low in Taiwanese patients with first hemispheric ischemic strokes, indicating that it is not a major cause of ischemic stroke in this population.     

Hemodynamic Effects of Innominate Artery Occlusive Disease on Anterior Cerebral Artery

Stenoses of the innominate artery (IA) may affect flow conditions in the carotid arteries. However, alternating flow in ipsilateral anterior cerebral artery (ACA) due to IA stenosis is extremely rare. A 49-year-old woman who was evaluated for symptomatic cerebrovascular disease presented with right latent subclavian and right carotid system steal. Transcranial Doppler examination displayed systolic deceleration wave-forms in the right terminal internal carotid artery and alternating flow in the right ACA. Magnetic resonance angiography demonstrated tight stenosis of the right IA. For a thorough study of the hemodynamic effects of IA stenosis, a combination of duplex and transcranial Doppler examination is required.     

Extracranial Internal Carotid Artery Occlusion: The Role of Common Carotid Artery Volume Flow

BACKGROUND AND PURPOSE: Quantitative measurement of blood flow volume in the common carotid artery (CCA) is now possible using the color velocity imaging quantification (CVI-Q) ultrasound technique. The aim of this study was to evaluate the cerebral hemodynamic effects of unilateral internal carotid artery (ICA) occlusion on CCA blood flow volumes (FVs) using CVI-Q. METHODS: Records of ultrasound studies in our neurosonology laboratory were retrospectively reviewed to identify patients with unilateral ICA occlusions who at a minimum received both a routine color duplex carotid ultrasound examination and quantitative measurement of FV in the CCA, bilaterally, using the CVI-Q method. A total of 71 patients met criteria and were included in the cohort. A side to side comparison was performed for FV, peak systolic velocities (PSV), end-diastolic velocities (EDV), and resistance indices (RIs) in the CCA. Results correlated with any other available data such as flow direction in the ophthalmic artery and the presence of intracranial collateralization. RESULTS: The FV, PSV, and EDV were significantly reduced, and the RI was significantly increased in the CCA on the side of the occlusion. A subgroup analysis in patients who also had an examination of the ophthalmic (n = 61) and the intracranial arteries of the Circle of Willis (n = 50), showed significantly higher FV in the CCA on the side of the occlusion if there was also reversed flow in the ophthalmic artery on the side of the occlusion (344 +/- 144 ml/min versus 169 +/- 53 ml/min). CONCLUSION: Quantitative FV measurement using CVI-Q ultrasound can identify clear alterations in volume flow, collateral pathways, and cerebral hemodynamics in patients with unilateral ICA occlusion. It is a complementary tool, providing additional objective information about the cerebral hemodynamic effects of ICA occlusion that goes beyond what is available using routine flow velocity data.