Including Intima-media Thickness Research Articles

Role of ADAR2-mediated innate immune responses in vascular inflammation and atherosclerosis

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Deutsche Forschungsgemeinschaft (DFG) Background Adenosine-to-inosine (A-to-I) RNA editing is an epitranscriptional regulator of RNA metabolism, catalyzed by the adenosine deaminases acting on RNA-1/-2 (ADAR1/2). Whether ADAR2 play a role in atherosclerotic processes remains elusive. Aim We examined the role of ADAR2 in vascular endothelial cell (EC) immunomodulatory responses and its biological relevance in murine and human atherosclerosis. Methods The role of ADAR2 in atherosclerosis was determined in a double ADAR2 and ApoE knockout mice fed with Western diet for 20 weeks. Three mouse genetic models (global and inducible vascular endothelial cell (iEC)-restricted ADAR2 and IL6ST knockout) were used to determine the role of ADAR2 in IL-6-related innate immunity. Expression levels of ADAR2 were measured in peripheral blood mononuclear cells derived from 533 individuals at risk for atherosclerotic vascular disease. Structural vascular measurements were used, including intima-media thickness (IMT), carotid wall maximum thickness (maxWT), and the number of atheromatous plaques by carotid and femoral artery ultrasonography as surrogate markers of subclinical arterial disease. Study participants were followed for major adverse cardiovascular events (MACE). Results Genetic ablation of ADAR2 resulted in a reduction of atherosclerotic plaque burden and necrotic core in the aorta and brachiocephalic trunk as well as reduced leukocyte infiltration in atherosclerotic plaques without affecting cholesterol levels in mice. Blood analysis revealed decreased pro-inflammatory cytokine levels including IL-6 after treatment of ADAR2/APOE KO mice compared to littermate control mice. Intravital imaging of IL-6-inflamed vascular endothelium showed that rolling and adhesion of leukocyte subsets to vascular wall were impaired by 2-fold in ADAR2-/- or iEC-ADAR2-/- KO mice. In vivo and ex vivo histological examination revealed that endothelial ADAR2 controls endothelial vascular adhesion molecule expression induced by gp130 signaling. ADAR2-deficient transcriptome revealed a selective upregulation of a conserved group of miRNAs targeting the IL6ST mRNA. Multilayered rescue studies including miR-inhibitors restored IL6ST levels after ADAR2 deficiency. In humans, increased ADAR2 expression was independently associated with the presence of CAD, higher C-reactive protein and mean carotid IMT after adjustment for traditional risk factors. Increased ADAR2 at baseline was prospectively associated with accelerated progression of subclinical atherosclerosis reflected by the increased number of carotid plaques at follow-up (OR=3.74, P<0.05). Finally, high ADAR2 levels were independently associated with higher MACE incidence across a median follow-up period of 54 months. Conclusion Posttranscriptional control of vascular inflammation by ADAR2 is integral for the development and progression of atherosclerosis in mice and humans. Our findings suggest that ADAR2 may serve as a promising therapeutic target for atherosclerosis.Role of ADAR2 in atherosclerosis

The gut microbiome in subclinical atherosclerosis: a population-based multiphenotype analysis

Abstract Objectives An altered microbiota, which can be described quantitatively, has been identified as playing a pivotal role in host vascular physiology, and it may contribute to various diseases. The aim of this study was to better understand the role of the gut microbiota in vascular physiology in a subclinical elderly population, and to investigate how lifestyle affects the composition of host gut microbiota to further impact the pathogenesis of vascular diseases. Methods We performed a population-based faecal metagenomic study over 569 elderly asymptomatic subclinical individuals in rural China. An association network was built based on clinical measurements and detailed epidemiologic questionnaires, including blood chemistry, arterial stiffness, carotid ultrasonography, and metagenomic datasets. Results By analyzing the breadth, depth and impact of each node of the association network, we found carotid arterial atherosclerosis indices, including intima-media thickness (IMT), were essential in the network, and were significantly associated with living habits, socio-economic status, and diet. Using mediation analysis, we found that higher frequency of eating fresh fruits and vegetables, and more exercise significantly reduced carotid atherosclerosis in terms of IMT, peak systolic velocity and end-diastolic velocity values through the mediation of Alistepes, Oligella and Prevotella. Gut microbes explained 16.5% of the mediation effect of lifestyle on the pathogenesis of carotid atherosclerosis. After adjustment, Faecalicatena [odds ratio (OR) = 0.12 ∼0.65] was shown to be protective against the formation of carotid atherosclerosis, independently, while Libanicoccus (OR = 1.46 ∼4.20 ) was associated with increased carotid arterial IMT. KEGG/KO Kyoto Encyclopedia of Genes and Genomes/ KEGG Orthology (KEGG/KO) analyses revealed a loss of anti-inflammation function in IMT subjects. Conclusion Our study revealed a Chinese population–wide phenotype–metagenomic association network and a mediation effect of gut microbiota on carotid artery atherosclerosis, hinting at potential therapeutic and preventive uses for microbiota in vascular diseases.

Monitoring the Effects of Hypolipidemic Treatment in Children with Familial Hypercholesterolemia in Poland.

Familial hypercholesterolemia (FH) is the most common monogenic autosomal dominant disorder. FH results in an increased cardiovascular mortality rate. However, cardiovascular risk control factors enable the avoidance of approximately 80% of strokes and cardiovascular diseases. Therefore, early detection and implementation of lipid-lowering treatment is essential. In the present study, 57 pediatric patients aged 9.57 ± 3.26 years with FH were enrolled in the study. Researchers checked the lipid profile and performed the ultrasound imaging including intima-media thickness (IMT) measurement and echo (e)-tracking in the study group. Patients were treated with a low-cholesterol diet solely or along with pharmacological treatment with statins. Subsequently, patients were monitored for 12 months. The positive results of dietary treatment were observed in 40 patients. The efficacy of 12 months of nutritional therapy along with pharmacological treatment was reported in 27 patients. We observed a significant decrease in the carotid beta index stiffness and an insignificant decrease in the IMT in the group of patients treated with statins. The obtained data show that statin therapy in children with FH allow for the reduction of the degree of atherosclerotic vessel changes.

P4492Peripheral blood mononuclear cell expression of the stabilizing RNA-binding protein HuR is associated with incidence and extent of human atherosclerotic cardiovascular disease

Abstract Background Human Antigen R (HuR) is a stabilizing RNA-binding protein that regulates the expression of several pro-inflammatory molecules. However, its regulation in human atherosclerotic cardiovascular disease remains unknown. Purpose To determine the association of peripheral blood mononuclear cell HuR expression with established markers of increased cardiovascular risk and atherosclerosis burden in patients with subclinical or clinically overt coronary artery disease (CAD). Methods HuR mRNA expression was measured in peripheral blood mononuclear cells derived from 289 patients with stable CAD or acute myocardial infarction (AMI) and 373 individuals without clinically overt cardiovascular disease (CVD). Structural and functional vascular measurements including intima-media thickness (IMT) and number of atheromatous plaques by carotid and femoral artery ultrasonophaphy, markers of arterial wave reflections by pulse wave analysis and pulse wave velocity were used as surrogate markers of subclinical CVD. The number of angiographically confirmed diseased coronary arteries (>50% stenosis) was used to assess the extent of CAD. Results HuR mRNA expression was significantly increased in patients with CAD (both stable and AMI) compared to controls (p=0.039). Subgroup analysis revealed that STEMI patients (n=107) had increased levels of HuR expression compared to NSTEMI (n=49, p=0.03). Among patients with stable CAD (n=133), high HuR expression was independently associated with the number of diseased coronary arteries (OR=1.35 for 1-SD increase in HuR, 95% CI 1.07–1.72, p=0.012), as well as with reduced ejection fraction (EF<45%, OR=1.32 per 1-SD increase, 95% CI 1.05–1.85, p=0.024). Among individuals without CVD, high HuR was associated with lower HDL levels (adjusted beta=-5.2 mg/dl for highest versus lowest quartile, p=0.03) and higher diastolic blood pressure (adjusted beta=3.6 mmHg, p=0.007), while, after adjustment for traditional cardiovascular risk factors, HuR levels in individuals without CVD were independently associated with increased IMT in the common carotid artery (mean increase 6.2% for highest versus lowest quartile, p=0.019). Conclusion HuR expression is associated with early subclinical arterial disease in individuals without clinically overt CVD and with the presence and severity of cardiac and vascular dysfunction in patients with clinically overt CAD. These findings imply a clinical role of the HuR pathway in cardiovascular disease and warrant further investigation.

Evaluation of atherosclerostic characteristics in senior citizens from the Ximen community of Haishu district by ultrasonography.

Background: The carotid artery is one of the means used to predict cardiovascular and cerebrovascular disease risk in the elderly. Methods: 1057 senior citizens older than 60 years from Ximen community of Haishu district, had their carotid arteries examined by ultrasound examination with parameters including intima-media thickness (IMT), presence of plaque, the plaque thickness, peal systolic velocity (PSV), resistance index (RI) and the level of narrowing of bilateral internal carotid arteries. Results: Except for IMT_(LICA), IMT_(RCCA), IMT_(RICA), PSV_(LCCA) and PSV_(RCCA), all ultrasound parameters were significantly different among different age groups (p ＜ 0.05). Comparing between sex within the same age group, except for IMT_(RCCA), PSV_(LCCA), RI_(LICA), PSV_(RCCA), PSV_(RICA) and RI_(RICA), other ultrasound parameters were found to be significantly different in the 60-70 year-old group (p ＜ 0.05); with the exception of PSV_(LICA), RI_(LICA), PSV_(RICA), RI_(RICA), the feature of the plaque on the left carotid arteries, other ultrasound parameters were significantly different in the ≥ 70-80 year-old group (p ＜ 0.05); except for IMT_(RICA) and RI_(LCCA), no other ultrasound parameters were significantly different in the ≥ 80 year-old group (p ＞ 0.05). Conclusion: Ultrasound screening has significant predictive and preventative value for cardiovascular and cerebrovascular diseases such as atherosclerosis. Early detection of these diseases will significantly improve patient outcomes in clinical practice.

Ultrasonic assessment of liver stiffness and carotid artery elasticity in patients with chronic viral hepatitis

BackgroundThis study investigated the relationship between liver stiffness and carotid artery elasticity in patients with chronic viral hepatitis. We used an acoustic radiation force impulse (ARFI) technique to measure stiffness, and a radio frequency (RF) vascular quantitative ultrasound technique to measure changes in common carotid artery elasticity and vascular function.MethodsTwo-hundred seventeen patients with chronic viral hepatitis caused by either hepatitis B virus (HBV) or hepatitis C virus (HCV) were enrolled. We divided the patients into two groups, one comprising 147 patients with chronic hepatitis B (CHB) (98 men and 49 women, average age 46.5 ± 12.2 years) and another comprising 70 patients with chronic hepatitis C (CHC) (47 men and 23 women, average age 47.6 ± 12.1 years). Additionally, 64 healthy age- and sex-matched participants (43 men and 21 women, average age 47.8 ± 5.1 years) were selected as the control group. The ARFI technique was used to measure liver stiffness and the RF ultrasound technique was used to measure carotid artery elasticity parameters including intima-media thickness (IMT), pulse wave velocity (PWV), arterial wall dilation coefficient (DC), compliance coefficient (CC), sclerosis indices α and β, and augmentation index (Aix). Clinical indicators, liver stiffness, and carotid artery elasticity parameters were observed and compared between the different age groups to investigate the correlation between carotid artery elasticity parameters and liver stiffness.ResultsThe ARFI values for the CHB and CHC groups were significantly higher than those for the control group (1.84 ± 0.52 vs. 1.04 ± 0.11 m/s; 1.86 ± 0.37 vs. 1.04 ± 0.11 m/s, respectively; P < 0.001). When compared to the control group, both CHB and CHC groups showed an IMT of the same order, but had significantly higher elasticity parameters, such as α and β, as well as lower DC and CC values (P < 0.001). The PWV of the CHC group was significantly higher than that of the control group (7.98 ± 1.42 vs. 6.09 ± 0.90 m/s, P < 0.001). In the CHB group, all parameters including ARFI, IMT, PWV, DC, CC, α and β, were significantly different between the two age groups (P < 0.05). Within the CHC group, all parameters including IMT, PWV, DC, α and β, were significantly different between the two age groups (P < 0.05), except for ARFI, wherein the difference was not statistically significant. The correlation analysis and stepwise multiple linear regression analysis indicated that for patients with CHB, age was an independent predictor of common carotid artery IMT (R2 = 0.468, F = 54.635, and P < 0.001). For patients with CHC, age and blood sugar were independent predictors of common carotid artery IMT (R2 = 0.465, F = 29.118, and P < 0.001).ConclusionAlthough based on ARFI and RF ultrasound, the carotid artery IMT in patients with CHB and CHC was not significantly higher than that in the control group, their functional elasticity parameters had already changed. This finding serves as a useful reference for the clinical diagnosis of vascular diseases in patients with viral hepatitis.Trial registrationClinicalTrials: ChiCTR1800015859 25/04/2018.

Association of body flexibility and carotid atherosclerosis in Japanese middle-aged men: a cross-sectional study

ObjectiveThis study examined the associations of body flexibility with carotid arterial remodelling, including intima–media thickness (IMT) and plaque formation in middle-aged men.MethodsThe subjects of this cross-sectional study included 1354 Japanese...

Association of serum vitamin D and parathyroid hormone with subclinical atherosclerotic phenotypes: The Dong-gu Study.

BackgroundAlthough previous studies reported an association between serum vitamin D and parathyroid hormone (PTH) with carotid atherosclerosis or arterial stiffness, these were inconsistent. We examined the independent association between serum vitamin D and PTH with multiple subclinical markers of atherosclerosis.MethodsA total of 8,217 subjects who participated in the Dong-gu Study in Korea were included in the final analysis. The carotid artery structure, including intima-media thickness (IMT), plaques, and luminal diameter, was evaluated using a high-resolution B-mode ultrasound. The brachial-ankle pulse wave velocity (baPWV) was determined using an automatic waveform analysis device, and the mean of the left and right baPWV was used.ResultsThe PTH concentration was positively associated with carotid luminal diameter and baPWV, but not with carotid IMT and plaques. The mean carotid luminal diameter of individuals with PTH levels in the second, third, and fourth quartiles was significantly larger compared with those in the first quartile (P-trend < 0.01). The mean baPWV of individuals with PTH levels in the fourth quartile was significantly greater than those with PTH levels in the first quartile (P-trend = 0.01). However, there was no significant association between vitamin D and any atherosclerotic phenotypes, including carotid IMT, plaques, luminal diameter, and baPWV.ConclusionThis suggests that PTH might affect the development of atherosclerosis by altering vascular compliance.

Carotid Atherosclerosis and Electrocardiographic Left Ventricular Hypertrophy in the General Population: The Namwon Study.

This study aimed to investigate the relationship between carotid atherosclerosis and left ventricular hypertrophy on electrocardiogram (ECG-LVH) on adults living in the community. A total of 9,266 adults who participated in the Namwon Study were included in this analysis. Carotid atherosclerosis, including intima-media thickness (IMT) and plaques, were assessed using high-resolution B-mode ultrasound. ECG-LVH was determined using the Sokolow-Lyon voltage (SokV) and Cornell voltage (CorV) criteria. The prevalence of ECG-LVH was 12.7% using the SokV criteria and 9.7% using the CorV criteria. After full adjustment, compared to the lowest quartile of common carotid artery IMT (CCA-IMT), the odds ratios and 95% confidence intervals for ECG-LVH of the carotid IMT quartiles 2, 3, and 4 increased linearly as follows: 1.54 (1.24-1.90), 1.62 (1.31-2.02), and 1.91 (1.54-2.38), respectively, for the SokV criteria (p<0.001); and 1.33 (1.05-1.68), 1.41 (1.11-1.78), and 1.48 (1.16-1.88), respectively, for the CorV criteria (p=0.003). Positive associations between the carotid bulb IMT (CB-IMT) quartiles and the ECG-LVH were also observed, although the magnitudes of association between CB-IMT and ECG-LVH were slightly lower than those of CCA-IMT. However, no significant association between carotid plaques and ECG-LVH as defined by the SokV or CorV criteria was found. The present study demonstrated that increased carotid IMT, but not carotid plaques, is significantly associated with LVH defined by various ECG criteria in a large population.

Abdominal fat distribution and carotid atherosclerosis in a general population: a semi-automated method using magnetic resonance imaging.

Available evidence suggests functional differences in visceral and subcutaneous fat. We investigated the association between quantitative measures of central adiposity with indicators of carotid atherosclerosis including intima-media thickness (IMT) and plaque in a general population using a semi-automated method on magnetic resonance imaging (MRI) data. In this cross-sectional study 200 subjects (52% female), aged 50-77years, were randomly selected from Golestan Cohort Study. Participants underwent ultrasound examination of carotid arteries and abdominal MRI. Segmentation and calculation of visceral (VFA) and subcutaneous fat area (SFA) were performed on three levels using semi-automated software. Various conventional anthropometric indices were also measured. Among 191 enrolled subjects, 77 (40%) participants had IMT≥0.8mm. Carotid plaques were detected in 86 (44%) subjects. In separate multivariate analysis models, unlike SFA and other anthropometric indices, the last tertile of VFA values was associated with at least threefold excess risk for IMT≥0.8mm (OR 3.8, 95% CI 1.36-6.94, p=0.02). There was no significant difference between mean values of categorized obesity indices in subjects with and without plaque, while participants in the highest tertile of VFA values were demonstrated to have higher risk of more than one plaque (OR 4.57, 95% CI 1.03-20.11, p=0.034). A higher amount of visceral fat, measured by a semi-automated technique using MRI, is associated with increased IMT and having more than one carotid plaque in a general population, while subcutaneous fat measures are poor indicators for identifying carotid atherosclerosis.

Serum androgen concentrations and subclinical measures of cardiovascular disease in men and women

ObjectivesMost of the observed associations of androgens and sex hormone-binding globulin (SHBG) with subclinical cardiovascular disease (CVD) stem from selected study samples with immunoassay-based hormone measurements. Thus, we used a large population-based sample with total testosterone (TT) and androstenedione (ASD) concentrations measured by liquid chromatography-tandem mass spectrometry. DesignData of 2140 individuals (mean age: 60,8 years) from the cohort Study of Health in Pomerania were assessed at baseline and 5-year follow-up. MethodsMultivariable regression models were implemented to assess cross-sectional and longitudinal associations of TT, free testosterone (fT), ASD, SHBG and dehydroepiandrosterone-sulphate (DHEAS) with measures of subclinical CVD including intima media thickness (IMT), carotid plaques, left ventricular mass (LVM), fractional shortening (FS), relative wall thickness (RWT), and left ventricular geometry. ResultsCross-sectional analyses yielded an association of TT with IMT in women (β-coefficient per log unit increase: 0.02; 95% CI: 0.007; 0.45) and ASD with FS in both sexes (men: β-coefficient: −2.94; 95% CI: −4.75; −1.12; women: β-coefficient: 1.64; 95% CI: 0.55; 2.73). In longitudinal analyses, DHEAS was positively associated with FS change (β-coefficient: 2.34; 95% CI: -0.59; 4.08). In women, SHBG was positively associated with incident plaques (Q1 vs. Q3 (Ref.): β-coefficient: 1.35; 95% CI: 1.04; 1.74). In both sexes, longitudinal analyses showed no consistent association of TT with subclinical CVD. ConclusionsDespite several sex-specific associations of androgens and SHBG with subclinical CVD, the present representative study for the age group ≥45 years among men and women from the general population detected no consistent associations in longitudinal analyses.

HbA1c is significantly associated with arterial stiffness but not with carotid atherosclerosis in a community-based population without type 2 diabetes: The Dong-gu study

ObjectivesWe examined the associations between HbA1c levels and various atherosclerotic vascular parameters among adults without diabetes from the general population. MethodsA total of 6500 community-dwelling adults, who were free of type 2 diabetes and ≥50 years of age, were included. High-resolution B-mode ultrasound was used to evaluate carotid artery structure, including intima-media thickness (IMT), plaque, and luminal diameter. Brachial-ankle pulse wave velocity (baPWV), which is a useful indicator of systemic arterial stiffness, was determined using an automatic waveform analysis device. ResultsNo significant associations were observed between HbA1c, carotid IMT, plaque, or luminal diameter in a fully adjusted model. However, the odds ratio (95% confidence interval) for high baPWV (defined as the highest quartile) increased by 1.43 (1.19–1.71) per 1% HbA1c increase after adjusting for conventional risk factors in a multivariate logistic regression analysis. In addition, HbA1c was independently associated with baPWV in a multivariate linear regression analysis. ConclusionsHigh-normal HbA1c level was independently associated with arterial stiffness, but not with carotid atherosclerotic parameters, in the general population without diabetes. Our results suggest that the functional atherosclerotic process may already be accelerated according to HbA1c level, even at a level below the diagnostic threshold for diabetes.

The ARTICO study: identification of patients at high risk of vascular recurrence after a first non-cardioembolic stroke.

BackgroundAbout 20% of patients with a first ischaemic stroke will experience a new vascular event within the first year. The atherosclerotic burden, an indicator of the extension of atherosclerosis in a patient, has been associated with the risk of new cardiovascular events in the general population. However, no predictive models reliably identify groups at a high risk of recurrence. The ARTICO study prospectively analysed the predictive value for the risk of recurrence of specific atherosclerotic markers.MethodsThe multicentre ARTICO study included 620 consecutive independent patients older than 60 years suffering from a first non-cardioembolic stroke. We analysed classical stroke risk factors; duplex study of supraaortic trunk including intima-media thickness (IMT) measurement; quantification of internal carotid (ICA) stenosis; number, morphology and surface characteristics of carotid plaques; ankle brachial index (ABI); and the presence of microalbuminuria. Patients were followed up at 6 and 12 months after inclusion. The primary end-point was death or major cardiovascular events.ResultsAny vascular event or death at 12 months occurred in 78 (13.8%) patients. In 40 (7.1%) of these the vascular event was a stroke recurrence. Weight, history of diabetes mellitus, history of symptomatic PAD, ABI <0.9 and significant ICA stenosis (>50%) were associated with a higher risk of vascular events on follow-up in the bivariate analysis.In the final Cox regression analysis, body mass index (BMI), systolic blood pressure, history of diabetes mellitus, symptomatic PAD (HR, 2.76; 95% CI, 1.10–6.95; p=0.03), and particularly patients with both ICA stenosis >50% and PAD (HR 4.52; 95% CI, 2.14-9.53; p<0.001) were independently associated with an increased risk of vascular events. Neither isolated ICA stenosis >50% nor isolated abnormal ABI remained associated with an increased risk of recurrence in comparison with the whole population.ConclusionsSymptomatic PAD identifies a high risk group of vascular recurrence after a first non-cardioembolic stroke. The associated increased risk was particularly high in patients with both ICA stenosis and either symptomatic or asymptomatic PAD. Neither asymptomatic PAD alone nor isolated ICA stenosis >50% were associated with an increased risk of recurrence in this particularly high-risk group of non-cardioembolic stroke.Electronic supplementary materialThe online version of this article (doi:10.1186/s12883-015-0278-4) contains supplementary material, which is available to authorized users.

Leukotriene haplotype × diet interaction on carotid artery hypertrophy and atherosclerosis in American Indians: The Strong Heart Family Study

Gene × diet interaction plays an important role in atherosclerosis, an inflammatory disorder. Leukotrienes are the most potent inflammatory mediators, and genetic variants encoding leukotriene genes have been implicated in atherosclerosis. This study tests nutrigenetic interaction of a previously defined leukotriene haplotype on carotid artery hypertrophy and atherosclerosis in American Indians. This study included 3402 American Indians participating in the Strong Heart Family Study (SHFS). Carotid artery measurements, including intima-media thickness (IMT), vascular mass, and plaque, were assessed using ultrasound. Eleven tagSNPs in the leukotriene A4 hydrolase (LTA4H) gene were genotyped in all subjects. Main haplotype effect and haplotype × diet interaction were examined by generalized estimating equation, adjusting for known risk factors. There was no significant main effect of haplotype or diet on any of the carotid artery measures. However, a previously defined LTA4H haplotype, called HapE, significantly interacted with dietary intake of n-3 and n-6 fatty acids on both IMT (P(HapE × n3) = 0.018, P(HapE × n6) = 0.040) and vascular mass (P(HapE × n3) = 0.012, P(HapE × n6) = 0.018), but not plaque. The direction of this nutrigenetic interaction on IMT was consistent with that reported in a recent study of Caucasian twins. Dietary intake of polyunsaturated fatty acids significantly modifies the effect of a leukotriene haplotype on carotid artery hypertrophy but not atherosclerosis in American Indians, independent of established cardiovascular risk factors. Replication of nutrigenetic interaction in two distinct ethnic groups suggests the robustness and generalizability of our findings to diverse populations.

Intima–media thickness correlates with features of metabolic syndrome in young people with a clinical diagnosis of familial hypercholesterolaemia

Familial hypercholesterolaemia (FH) is a monogenic lipid metabolism disorder characterised by markedly elevated serum low-density lipoprotein (LDL) cholesterol level due to a mutation in the LDL receptor gene. Clinical features of FH include premature atherosclerosis and coronary artery disease. To explore associations between noninvasive markers of atherosclerosis including intima-media thickness (IMT) and pulse wave velocity (PWV) and blood lipids, blood pressure (BP) and obesity in a group of young patients with FH. Study population included 36 patients aged < 35 years with the diagnosis of FH based on the Simon Broome Register criteria, and their 49 relatives who comprised the control group free of FH. Mean IMT values were higher in FH patients than controls (0.60 ± 0.19 vs. 0.53 ± 0.07 mm, respectively, p < 0.05).Mean body mass index (BMI) and waist circumference were similar in patients and controls. The prevalence of carotid atherosclerotic plaques was significantly higher among FH patients (n = 6) than in controls (n = 1) (21.4% vs. 2.6%, p = 0.012). Arterial hypertension was present in 27.8% of patients with FH and 16.3% of subjects in the control group. Systolic blood pressure (SBP) in FH patients correlated significantly with age (r = 0.35), BMI (r = 0.48) and waist circumference (r = 0.47), and diastolic blood pressure (DBP) correlated with BMI (r = 0.42) and waist circumference (r = 0.41). PWV correlated significantly with age (r = 0.44), SBP (r = 0.63) and DBP (r = 0.52). We did not find any correlations between IMT and serum lipids, BP or obesity indices in FH patients. Our findings show a higher rate of arterial hypertension in young FH patients compared to their relatives free of FH, with significant associations between BP and indices of obesity and arterial stiffness. Intensive lipid lowering and antihypertensive therapy along with a reduction in central fat may be considered a mandatory treatment strategy in young FH patients to prevent atherosclerosis and increased arterial stiffness.

FRI0427 Tumor necrosis factor blocking agents inhibit the progression of preclinical atherosclerosis in patients with ankylosing spondylitis

BackgroundAnkylosing spondylitis (AS) is associated with an increased cardiovascular (CV) risk that might be due to the chronic underlying inflammatory process, but is still unknown whether treatment with TNF inhibitors...

A vascular approach to mild amnestic cognitive impairment: a pilot study

Mild cognitive impairment (MCI) is a subtle memory disorder not matching criteria for dementia. There is evidence for vascular comorbidity in several types of dementia. We hypothesized that neurovascular workup would detect a high degree of vascular disease in patients with MCI. In cooperation with our memory clinic, patients with amnestic MCI were referred to our department for neurovascular investigation. The workup encompassed ultrasound examination with carotid duplex including Intima-Media-Thickness (IMT) measurement, and transcranial Doppler (TCD) including one-hour microemboli monitoring, cerebrovascular reactivity measurement and Bubble test. Cerebral MRI for the evaluation of vascular and white-matter lesions, brain atrophy, hippocampal volumes, and amyloid angiopathy was performed. Ten patients were included. Vascular risk factors were present in six patients. Four patients had atherosclerotic lesions, three classified as mild, and one as moderate carotid stenosis. IMT > 1 mm was found in two patients, with a maximum IMT of 1.11 mm. None of the patients with acceptable bone window had intracranial stenosis in TCD. Vasoreactivity was pathologically low in one patient. Permanent right-left shunt was found in three patients, of which one showed spontaneous cerebral microembolism. Hippocampal volume reduction and cortical atrophy were found in four patients. Chronic ischemic changes in MRI were present in one patient, and three patients had subcortical infarctions. Cortical infarctions, microbleeds, or amyloid angiopathy were not found. Pure amnestic MCI is probably less associated with cerebrovascular disease and may be more consistent with evolving Alzheimer's disease. However, vascular risk factors are common in these patients.

Chemokine CXC Ligand 16 serum concentration but not A181V genotype is associated with atherosclerotic stroke

Serum chemokine CXC Ligand 16 (CXCL16) concentration is associated with atherosclerosis and CXCL16 expression may be influenced by the polymorphism, A181V. We established whether serum CXCL16 concentration or the A181V genotype is more strongly associated with atherosclerotic stroke and its associated risk factor, carotid atherosclerosis. PCR-RFLP was used to genotype 244 atherosclerotic stroke patients (AS group), 153 stroke-free controls (patient controls) and 167 healthy controls. Serum CXCL16 concentration was determined for a subset of patients (n=135) and all controls. The same subset of patients was then examined using ultrasound to evaluate their carotid atherosclerotic lesions, including intima-media thickness (IMT), plaque stability and carotid plaque area (CPA). Compared with the patient controls and healthy controls, serum CXCL16 concentration was significantly increased in the AS group (P<0.05, and 0.01). It was also strongly associated with increased IMT, vulnerable plaque and increased CPA (P<0.05, <0.001, and <0.01). However, the CXCL16 A181V genotype distribution and allele frequencies showed no differences between AS and control groups, nor did it influence serum CXCL16 concentration. Serum CXCL16 concentration is significantly associated with atherosclerotic stroke and carotid atherosclerosis, suggesting that this biochemical test may be useful to identify patients at increased risk of atherosclerosis.

The combined use of brachial artery flow-mediated dilatation and carotid artery intima-media thickness measurements may be a method to determine vasculogenic erectile dysfunction

The aim of this study was to investigate the relationship between penile color Doppler sonography (CDS) findings and sonographic endothelial parameters in patients with erectile dysfunction (ED), including intima-media thickness (IMT) of common carotid arteries (CCA) and flow-mediated dilatation (FMD) of brachial artery. Fifty-six ED patients were included in the study. Penile CDS, IMT of CCA and FMD of brachial artery were performed in all patients. According to penile CDS findings, 27 (48%) patients had non-vasculogenic and 29 (52%) patients had vasculogenic ED. Among 29 patients, 17 (30%) patients had cavernous veno-occlusive disease (CVOD) and 12 (22%) patients had arterial/combined insufficiency (AI). Median (interquartile range) FMD values of non-vasculogenic ED, CVOD and AI were 12.50 (6.54)%, 12.82 (7.41)% and 6.25 (7.17)%, respectively. FMD was found to be impaired significantly in AI group when compared to the other groups. FMD values of CVOD group were lower when compared to non-vasculogenic group, but the difference was not statistically significant. IMT values of vasculogenic ED patients were higher than non-vasculogenic ED patients (P<0.05). Although IMT values were higher in AI group when compared to CVOD, the difference was not statistically significant. The combined use of IMT and FMD established the diagnosis of vasculogenic ED with 100% sensitivity and 59.2% specificity. The positive predictive value was 72%, negative predictive value 100% and accuracy 80%. The combined use of brachial artery FMD and carotid arteries IMT measurements may be suggested as an alternative method to evaluate vasculogenic ED.

The Female Advantage in Cardiovascular Disease: Do Vascular Beds Contribute Equally?

The female advantage in coronary heart disease occurrence is not completely understood. To characterize gender differences in cardiovascular disease by vascular site, the authors compared degrees of coronary, carotid, peripheral, and aortic atherosclerosis in men and women aged>or=55 years from the population-based Rotterdam Study (Rotterdam, the Netherlands). Data were collected between 1997 and 2000. A subset of 2,013 participants had data on both coronary calcification and one or more measures of extracoronary atherosclerosis, including intima-media thickness (IMT), carotid plaques, ankle-arm index (AAI), and aortic calcification. The multivariable-adjusted male:female odds ratios for calcium score>1,000 were 7.8 (95% confidence interval (CI): 3.2, 19.3), 5.4 (95% CI: 2.8, 10.2), and 3.0 (95% CI: 1.7, 5.2) in the lowest, middle, and highest age tertiles, respectively. For IMT>1.0 mm, severe carotid plaques, AAI<0.90, and severe aortic calcification, ratios did not decline with age. Overall multivariable-adjusted male:female odds ratios for these measures were 2.9 (95% CI: 2.0, 4.1), 2.0 (95% CI: 1.4, 2.8), 0.9 (95% CI: 0.7, 1.3), and 1.0 (95% CI: 0.8, 1.5), respectively. The authors conclude that the gender difference in atherosclerosis is larger in the coronary vessels than in other vascular beds. Remarkably, it is absent in the aorta and the lower-extremity vessels. Factors causing this site-specific gender difference require further investigation.