Intima-media Thickness Levels Research Articles

Association of blood pressure in the supine position with target organ damage in subjects over 60 years old.

ObjectiveToexplore the correlation between blood pressure in the supine position and target organ damage in subjects over 60 years of age.MethodsIn 2444 individuals, we investigated the association of systolic blood pressure (SBP) in the supine position with the target organ damage indices microalbuminuria (ALBU), brachial–ankle pulse wave velocity (baPWV), and carotid intima–media thickness (IMT). Supine hypertension (SH) is defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg. Subjects were assigned to either the SH group (1275 cases) or the non-SH group (1169 cases).ResultsThe levels of ALBU, baPWV, and IMT, as well as the percentage of participants with ALBU > 30 mg/L, baPWV ≥ 1400 cm/s, and IMT ≥ 1 mm, were significantly higher in the SH group than in the non-SH group. Multivariate logistic regression analysis showed that SH was an independent risk factor for baPWV and IMT, but the relationship with ALBU was not statistically significant after correction for confounding factors.ConclusionsSH is a risk factor for target organ damage, as expressed by the indices baPWV and IMT. The association of SH with kidney damage requires further study.

OP.2D.06] DIFFERENCES IN ENDOTHELIAL GLYCOCALYX IN RECENTLY DIAGNOSED AND UNTREATED MIDDLE-AGED HYPERTENSIVE PATIENTS REGARDING INCREASED CARDIOVASCULAR RISK

Objective: Target organ damage (TOD) evaluation in patients with arterial hypertension is necessary in order to estimate cardiovascular risk (CVR) and plan treatment. Increased carotid intima-media thickness (IMT), an index of TOD, represents the diffuse vascular atheromatosis. The integrity of endothelial glycocalyx (EG) plays a vital role in vascular permeability, inflammation and elasticity and finally to cardiovascular disease. Sideview Darkfield imaging allows for non-invasive automated estimation of EG dimensions based on the erythrocyte column distribution. We aimed to investigate any differences in EG levels in untreated patients with essential hypertension. Design and method: We studied 86 patients with newly diagnosed and never treated essential hypertension (mean age 53 + 7 years, 53 males). Increased perfusion boundary region (PBR) of the sublingual arterial microvessels (ranged from 5–25 micrometers) using Sideview Darkfield imaging (Microscan, Glycocheck) was measured as a non-invasive accurate index of reduced EG thickness. We estimated carotid intima-media thickness using carotid ultrasonography (normal levels IMT < 0.8 mm). Results: The whole population was divided in two groups regarding IMT levels, group A (IMT < 0.8 mm, n = 30, mean age 52 + 7 years, 17 males) and group B (IMT > 0.8 mm, n = 56, mean age 54 + 7 years, 36 males). Group A and B were also matched for age and sex. No differences were found within groups regarding 24 h systolic and diastolic ABPM as well as PBR 5–25, PBR 10–19 and PBR 20–25. We found that PBR 5–9 was increased in group B (1.19 + 0.1 vs. 1.13 + 0.1, p = 0.04) compared with group A. Conclusions: EG dimensions are reduced in hypertensive patients with augmented cardiovascular risk. Further studies are needed to confirm our results in a larger population and possibly establish EG measurement as a new cardiovascular risk marker.

Chitotriosidase as a novel biomarker of early atherosclerosis in hemodialysis patients.

Increasing evidence suggests that inflammation and increased macrophage activity have a central role in pathogenesis of atherosclerosis. It is shown that chitotriosidase (CHIT-1) is a marker of macrophage activity in atherosclerotic plaque, and is found associated with severity of atherosclerotic lesion. There is no data about CHIT-1 activity of hemodialysis patients in the literature. Thus, we hypothesized that in hemodialysis patients, CHIT-1 levels might be a novel biomarker in early atherosclerosis. Forty-five hemodialysis patients were included in the study (age: 61.93 ± 13.34). Intima media thickness (IMT) was evaluated with high-resolution B-mode ultrasonography. Biomarker levels were measured in serum of patients. We found positive correlation among IMT, age (R: 0.426, P: 0.004) and, CHIT-1 value (R: 0.462, P: 0.001) in spearman correlation analysis. When age, CRP, creatinine, P, Alb, CHIT-1 were chosen as measures that can effect IMT in multiple regression model, IMT level was related with CHIT-1 (Beta: 0,396, P: 0.012) and age (Beta: 0,313 P: 0,048) independently. In conclusion, this is the first report showing that serum CHIT-1 level was related independently with carotid IMT in hemodialysis patients. This biomarker might have an unknown role in the development of atherosclerosis during uremia.

RELATONSHIP BETWEEN SERUM LIPOPROTEIN-ASSOCIATED PHOSPHOLIPSAE A2 AND CAROTD INTMAMEDIA THICKNESS WITH CEREBRAL INFARCTON

Background and Purpose: Cerebral atherosclerosis is the leading cause of mechanical obstruction of blood flow that final event is cerebral infarction. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory biomarkers specific for blood vessels, is an important factor predicted extent of atherosclerosis. The study aimed to assess the association between serum Lp-PLA2 concentration with carotid intimamedia thickness (IMT). Materials andMethod: The cross – sectional study, in 37 patients who presented to Department of Cardiology - Hue University Hospital and Hue Central Hospital. Vulnerability asessment of the external carotid artery into the skull through ultrasound by measuring carotid intima-media thickness. Testing serum Lp-PLA2 concentration, lipid profile, blood glucose. Results: Group of patients with thickness of carotid IMT levels of serum Lp-PLA2 was 27.73 IU/ml higher than the group with thickness normal carotid IMT was 14.35 IU/ml; p &lt; 0.05. Total cholesterol, LDL cholestrol, triglycerid and Lp-PLA2 are the factors capable of predict the changes in size IMT; (p &lt;0.05). There is moderate correlation between Lp-PLA2 levels and carotid intima-media thickness (r = 0.47; p &lt; 0.05). Conclusion: Higher Lp-PLA2 levels is significantly associated with carotid intimamedia thickness in patients who have cerebral infarction. Key words: Stroke, atherosclerosis, inflammation, biomarker.

The relationship between homocysteine and carotid intima-media thickness in acute cerebral infarction

Objective To investigate the relationship between the different levels of homocysteine (Hcy) and carotid intima-media thickness (IMT) in acute cerebral infarction patients. Methods 140 patients with acute cerebral infarction in our hospital were included. The patients were divided into H1 group (Hcy≤10 μmol/L) and H2 group (Hcy>10 μmol/L) dependent on the level of plasma Hcy. Meanwhile, 70 healthy people were included in the study as the control group. The clinical biochemical indicators and the values of IMT were detected in the three groups. Results Compared with the control group, the level of plasma Hcy in the H1 and H2 group were increased [(8.73±1.63), (23.71±3.27) μmol/L], and there was more significant in H2 group (P<0.05). There was significant difference in IMT in three groups (P<0.05). The value of IMT increased in H2 group was much more significant compared with H1 group (P<0.05). Based on the log-transformed values of IMT as the dependent variable, multiple stepwise linear regression showed significant associations of Hcy levels variables with increased IMT (B=0.004, P<0.01). Conclusion The increased IMT level was associated with the level of plasma Hcy in patients with acute cerebral infarction. Key words: Acute cerebral infarction; Homocysteine; Carotid intima-media thickness

Circulating soluble form of LR11, a regulator of smooth muscle cell migration, is a novel marker for intima-media thickness of carotid arteries in type 2 diabetes

BackgroundSmooth muscle cell (SMC) migration from the media to the intima, a process affecting plaque stability in advanced-stage atherosclerosis, is under the control of LR11. To delineate the clinical significance of the circulating soluble form of LR11 (sLR11) in patients with type 2 diabetes (T2D), we analyzed the correlation of sLR11 levels with intima-media thickness (IMT) of carotid arteries. MethodsPlasma sLR11 levels were measured in 165 patients with T2D (mean age 56.2±10.4 y, 58.2% males, and BMI 24.6±3.6) by ELISA. Averaged IMT levels of common carotid arteries were determined by ultrasonography. ResultsCirculating sLR11 levels were 9.8±3.5ng/ml, and correlated positively with the classical atherosclerosis risk factors age, sex, systolic blood pressure, low-density lipoprotein-cholesterol (LDL-C), fasting plasma-glucose (FPG), and glycosylated hemoglobin. Multivariate linear regression analysis indicated that only FPG was associated with sLR11; sLR11 correlated positively with IMT, together with age and FPG, but less with LDL-C. Among the serum risk factors for IMT, multivariate linear regression analysis uncovered that sLR11 was independently associated with IMT. Subsequent logistic analysis revealed that FPG correlated best with IMT values at a cut-off of 0.80mm and sLR11 at a cut-off of 0.90mm, respectively, while LDL-C showed lower discriminatory power at any IMT cut-off values. ConclusionIncreased sLR11 concentrations are highly associated with increased IMT as well as with FPG in middle-aged, non-obese patients with T2D. Circulating sLR11 may be a novel marker representing the pathophysiology of intimal SMCs in patients with T2D.

Associations of Psychological Well-Being With Carotid Intima Media Thickness in African American and White Middle-Aged Women.

The present cross-sectional study aimed to a) examine associations between measures of psychological well-being, specifically life satisfaction and life engagement, and intima media thickness, a subclinical marker of atherosclerosis; b) investigate if the interaction of psychological well-being and life events correlated with intima media thickness; and c) explore these relationships across race. A sample of 485 women (38% African American and 62% white; mean [standard deviation] age = 50.2 [2.9] years) underwent ultrasonography to assess carotid artery intima media thickness (IMT). The women completed self-report measures of life satisfaction, life engagement, and life events. Average (standard deviation) IMT was 0.666 (0.10) mm. Life satisfaction showed a significant, independent, inverse relationship with IMT, after controlling for demographic, behavioral, psychological, and cardiovascular covariates (β = -0.105, p = .039), such that each 1-point higher life satisfaction score was correlated with a significant 0.008-mm lower level of mean IMT. No significant association was seen between life events and IMT (r = 0.05, p = .32), and life satisfaction did not interact with life events on IMT (β = -0.036, p = .46). No significant interaction between life satisfaction and race on IMT was observed (β = 0.068, p = .37). In contrast to life satisfaction, life engagement was not a significant correlate of IMT (r = -0.07, p = .12). Life satisfaction, a measure of psychological well-being, is an important independent correlate of subclinical atherosclerosis in middle-aged women.

The Role of Liuwei Dihuang Pills and Ginkgo Leaf Tablets in Treating Diabetic Complications.

Objective. To observe the clinical prophylactic and therapeutic efficacy of Liuwei Dihuang Pills and Ginkgo Leaf Tablets for type 2 diabetic vascular complications. Methods. It was a randomized, double-blind and placebo-controlled clinical trial. 140 outpatients with type 2 diabetes were recruited and randomly divided into the treatment group and control group. The two groups were given basic therapy (management of blood sugar, blood pressure, etc.). Additionally, the treatment group was given Liuwei Dihuang Pills and Ginkgo Leaf Tablets, while the control group was given Liuwei Dihuang Pills and Ginkgo Leaf Tablets placebos. All subjects were followed up for consecutive 36 months and observed monthly. The clinical data as urinary microalbumin to urinary creatinine ratio (Umalb/cr), carotid intima-media thickness (IMT), diabetic nephropathy (DN) and diabetic retinopathy (DR) prevalence, cardiovascular and cerebrovascular events, blood glucose, and blood pressure were collected and analyzed statistically. Results. After 36-month treatment, the Umalb/cr level and DN and DR prevalence in treatment group were all significantly lower than control group (P < 0.05). However, the IMT level and the incidence of cardiovascular and cerebrovascular events were not significantly different between the two groups (P > 0.05). Conclusions. Liuwei Dihuang Pills and Ginkgo Leaf Tablets are beneficial to diabetic microvascular complications, while the efficacy to diabetic macrovascular complications needs more observations.

A Study on Hs-CRP, Carotid Intima Media Thickness, and Lipid Profile in Children of Patients with Premature CAD

Background: This study aimed to evaluate the risk markers of Coronary Artery Disease (CAD), so that appropriate lifestyle changes can be instituted early to prevent or delay development of the disease. Objectives: This study aimed to evaluate the risk markers of CAD based on inflammation and arterial morphology; i.e., high sensitivity C-Reactive Protein (hs-CRP) and carotid artery Intima Media Thickness (IMT), in children of patients with premature CAD. Patients and Methods: This was a case-control study with predetermined end points. It was conducted on 40 subjects randomly selected from the children of premature CAD patients and 40 age- and sex-matched healthy controls. Blood levels of hs-CRP, lipid profile, and carotid IMT were assessed for all the subjects. The relationship among these parameters was evaluated by univariate and multivariate analyses using the SPSS statistical software, version 22.0 and P < 0.05 was considered as statistically significant. Results: The mean values of Total Cholesterol (TC, 139.8 ± 24 vs. 111.3 ± 14.7, P < 0.05), Triglycerides (TG, 81.8 ± 15.3 vs. 63.4 ± 10.8, P < 0.05), Low Density Lipoprotein (LDL, 85.2 ± 22.2 vs. 57.5 ± 14.1, P < 0.05), hs-CRP (1.2 ± 0.77 vs. 0.79 ± 0.27, P < 0.05) and carotid artery IMT (0.49 ± 0.09 vs. 0.422 ± 0.03, P < 0.05) were significantly higher in the cases compared to the controls. Also, both LDL/High Density Lipoprotein (HDL) and TC/HDL ratios were significantly higher in the cases compared to the controls. Moreover, a significant positive correlation was found between carotid IMT and hs-CRP. Conclusions: Children of patients with premature CAD showed a significantly higher incidence of dyslipidemia as well as significantly increased levels of the inflammation marker, hs- CRP, compared to the age- and sex-matched controls. This indicates that atherosclerosis is not only a disease of lipid deposition, but also an inflammatory process. This was further confirmed by demonstration of a significantly raised IMT.

Plasma Prekallikrein Is Associated With Carotid Intima-Media Thickness in Type 1 Diabetes.

The hypothesis that plasma prekallikrein (PK) is a risk factor for the development of vascular complications was assessed in a study using the Diabetes Control and Complications Trial (DCCT)/Epidemiology and Diabetes Interventions and Complications (EDIC) cohort of subjects with type 1 diabetes. The circulating levels of plasma PK activity were measured in the plasma of 636 subjects with type 1 diabetes (EDIC years 3-5). Common and internal carotid intima-media thickness (IMT) were measured by B-mode ultrasonography in EDIC years 1 and 6. Plasma PK levels were positively and significantly associated with BMI, hemoglobin A1c, systolic blood pressure, total cholesterol, LDL cholesterol, and triglycerides but not with age, sex, duration of diabetes, or HDL cholesterol. Univariate and multivariable statistical models after controlling for other risk factors consistently demonstrated a positive association between plasma PK and progression of internal carotid IMT. Multivariate analysis using a general linear model showed plasma PK to be significantly associated with progression of both internal and combined IMT (Wilks Λ P value of 0.005). In addition, the mean internal carotid IMT levels were higher in subjects with plasma PK levels in the highest 10th percentile compared with subjects with plasma PK levels in the lower 10th percentile (P = 0.048). These novel findings implicate plasma PK as a risk factor for vascular disease in type 1 diabetes.

Association between subclinical carotid atherosclerosis, hyperhomocysteinaemia and mild cognitive impairment.

Evidence suggests that intima-media thickness (IMT) and plasma homocysteine (Hcy) levels are associated with one another, and both appear to be related to cognitive dysfunction. However, no connection between both factors taken together and mild cognitive impairment (MCI) has been established. This study analysed potential relationships between IMT, Hcy and MCI. We included 105 patients with MCI and 76 controls with no history of vascular disease. All participants underwent laboratory analyses, a carotid ultrasound, and clinical and neuropsychological assessment. We used the Mantel-Haenszel test (MHT), ANCOVA and multiple linear regression models (MLRM) to examine any associations between IMT, Hcy and cognitive state. The MHT revealed a significant association between IMT and risk of MCI (z = 4.285, P < 0.0001). The OR for the upper quartile vs the lower quartile was 5.12 (95% CI: 2.12-12.36). MHT also showed a clear association between Hcy levels and risk of MCI (z = 3.01, P = 0.003). OR for the upper vs the lower quartile was 3.39 (95% CI: 1.41-8.12). Additionally, we found a correlation between IMT and Hcy (r = 0.162, P = 0.032). Our results suggest that there is a connection between IMT, Hcy levels and presence of amnestic MCI in a population with no history of clinically manifest atherosclerosis. Furthermore, there is also a connection between the IMT and Hcy levels themselves.

Childhood metabolic syndrome, inflammation and carotid intima-media thickness. The Aboriginal Birth Cohort Study

Background/objectivesWe evaluated whether atherosclerotic changes associated with MetS in Australian Aboriginals are reversible in childhood. In addition, we investigated whether heightened inflammation is mediating the adverse effects of MetS. MethodsThe study cohort comprised of 351 children from the Aboriginal Birth Cohort Study (a longitudinal study based in the Northern Territory of Australia) aged 9–13years at baseline examination who were followed up 6years later. MetS was defined by at least three of the following parameters within the extreme sex- and age-specific quartile: highest quartile for waist circumference, blood pressure, triglycerides, and glucose, and lowest quartile for HDL-cholesterol. Carotid intima-media thickness (IMT) and C-reactive protein (CRP) were assessed at follow-up. ResultsIndividuals with MetS at baseline or follow-up had increased carotid IMT at follow-up (mean±SEM 539±3 vs. 561±8μm, P=0.007; and 537±3 vs. 567±8μm, P<0.0001 respectively). In combined analyses from baseline and follow-up studies, those individuals with MetS only at baseline had partially improved vascular status; their IMT was not significantly increased compared to those without MetS at both time-points (534±3 vs. 550±10μm, P=0.09). At the follow-up examination, MetS status was associated with increased IMT levels only among individuals with CRP levels above the median (≥2.1mg/l) (536±5 vs. 573±9μm, P<0.0001, P for interaction 0.01). ConclusionsMetS in childhood is associated with subclinical atherosclerosis in an Australian Aboriginal population and the effects appear to be mediated by increased inflammation. The extent of atherosclerosis was partially reduced if metabolic status improved during the follow-up.

Carotid intima-media thickness is not related with clinical outcomes in young hypertensives.

IntroductionCareful observations of long- and short-term outcomes associated with carotid intima-media thickness (IMT) are relatively limited.MethodsA total of 2,972 patients (male:female = 1,960:1,012; mean age = 62 ± 12 years) who underwent carotid IMT measurements from September 2003 to March 2009 were divided into four groups. Group I (n = 271; mean age, 42 ± 7.8 years) included normotensive younger subjects (males, <45 years and females <55 years), group II (n = 992; mean age, 63 ± 9 years) included normotensive elderly subjects, group III (n = 177; mean age, 46 ± 7.8 years) was hypertensive younger subjects, and group IV (n = 1,532; mean age, 63 ± 10.2 years) was hypertensive elderly subjects. We analyzed the clinical and cardiovascular events in the younger hypertensive subjects based on IMT measurements.ResultsThe baseline characteristics of the subjects showed that carotid IMT increased in the elderly subjects and in patients with hypertension. Poor clinical outcomes, such as all-cause death and major adverse cardiac events, were related with age, not with hypertension. Among the conventional risk factors, age and the highest quartile level of right maximum carotid IMT were related with major adverse events (young: odds ratio [OR], 0.47; 95% confidence interval [CI], 0.25 to 0.9 vs. OR, 1.73; 95% CI, 1.20 to 2.49). The patients in the highest quartile of carotid IMT had worse survival outcomes than those with the lowest IMT (p = 0.03).DiscussionSubjects with hypertension had increased carotid IMT levels. Controlling hypertension and carefully evaluating carotid IMT are important to prevent cardiovascular events even in younger subjects with hypertension.

Increased carotid artery intima-media thickness and myeloperoxidase level in children with newly diagnosed juvenile idiopathic arthritis.

IntroductionJuvenile idiopathic arthritis (JIA) is a frequent childhood rheumatic disease characterized by chronic inflammation. The latter has been related to impairment of arterial functional-structural properties, atherogenesis and later cardiovascular events. The objective of this study was to examine intima-media thickness (IMT) and the parameters of arterial stiffness in children with JIA at diagnosis and their correlation with JIA subtype and markers of inflammation and atherosclerosis.MethodsThirty-nine newly diagnosed patients with JIA (26 girls; mean age, 13.2 ± 2.6 years) and 27 healthy controls (9 girls; mean age, 13.6 ± 3.4 years) were included in the study. Twelve patients had oligoarthritis, fifteen had extended oligoarthritis and twelve had rheumatoid factor–negative polyarthritis. IMT of the common carotid artery was determined by ultrasonography, carotid-femoral pulse wave velocity (cfPWV) and augmentation index adjusted to a heart rate of 75 beats/min (AIx@75) were determined by applanation tonometry. The serum levels of atherosclerosis-related biomarkers, such as asymmetric dimethylarginine (ADMA), myeloperoxidase (MPO) and adiponectin, were measured by enzyme-linked immunosorbent assay.ResultsMean IMT (0.46 ± 0.04 vs. 0.42 ± 0.04 mm; p = 0.0003) and MPO concentration (115.2 [95 % confidence interval {95 % CI}, 97.4–136.3] vs. 57.6 [95 % CI, 47.1–70.3] ng/ml; p < 0.0001) were higher in the patients with JIA than in the control subjects. The cfPWV, AIx@75 and serum ADMA and adiponectin levels did not significantly differ between the groups and JIA subtypes. Serum adiponectin level correlated negatively with AIx@75 in patients with JIA (r = −0.38; p < 0.05).ConclusionsPatients with JIA have increased mean IMT and elevated MPO levels at early stages of the disease. AIx@75 was inversely independently associated with adiponectin level in the patients, suggesting that lower adiponectin levels might influence arterial subclinical stiffening in patients with newly diagnosed JIA.

Ambient air pollution and racial/ethnic differences in carotid intima-media thickness in the Multi-Ethnic Study of Atherosclerosis (MESA)

BackgroundIn the USA, ethnic disparities in atherosclerosis persist after accounting for known risk factors. Ambient air pollution is associated with increased levels of atherosclerosis and differs in the USA by...

25OH-Vitamin D3 Levels in Obesity and Metabolic Syndrome—Unaltered in Young and not Correlated to Carotid IMT in All Ages

Contradictory results exist for levels of vitamin D measured in patients with cardiovascular disease (CVD), obesity and metabolic syndrome (MetS). To clarify this, we investigated 527 participants of the STYJOBS/ EDECTA cohort (NCT00482924), with ages between 10 and 65 years. A cross-sectional analysis of anthropometry, carotid intima media thickness (IMT), and laboratory measurements for 25OH-Vitamin D3 (vitD), glucose metabolism, ultra-sensitive C-reactive protein (US-CRP), interleukin-6 (IL-6), lipids, liver-, renal-parameters, and kynurenine to tryptophan ratio were made for a selection of persons who were either obese or of normal weight. The homeostasis model assessment insulin resistance (HOMA) was also measured. As compared to the normal weight controls, significantly decreased blood levels of vitD were found in overweight/obese adults, which were not observed in the juveniles. Nevertheless, both overweight/obese juveniles and adults had significantly increased US-CRP, IL-6, HOMA, triglyceride, and LDL-cholesterol levels, and significantly decreased HDL-cholesterol levels. Juveniles with MetS displayed unchanged levels of vitD as compared to overweight/obese juveniles without MetS. Although IMT was significantly increased in both juvenile and adult overweight/obese subjects, vitD and IMT levels were not correlated. Assuming a minimum threshold of 20 ng/ml for the establishment of "low" or "normal" vitD levels, no significant alteration in IMT, metabolic, and inflammatory markers was observed in juveniles with a low vitD-status . In conclusion, although metabolic and inflammatory symptoms of obesity are displayed in juveniles, their vitD levels are unaffected. This, together with the complete lack of association with carotid IMT in both juveniles and adults, argues against a causative role of vitD in obesity-associated vascular pathology.

Genetic association and gene-smoking interaction study of carotid intima-media thickness at five GWAS-indicated genes: The Bogalusa Heart Study

ObjectivesTo examine the associations of five GWAS-identified genes with carotid intima-media thickness (IMT) in a biracial sample from the Bogalusa Heart Study, and evaluate their participation in gene-smoking interactions. MethodsFar wall IMTs of common carotid arteries were measured using high-resolution B-mode ultrasound. Both the gene-smoking interactions and single-marker associations were evaluated by linear models of carotid IMT levels, while the gene-based analyses were assessed through the truncated product method. A Bonferroni multiple testing correction was applied. ResultsMarker rs7840785 (PINX1) was significantly associated with right carotid IMT (p=0.0003) using all participants; mean levels for the CC, TC, and TT genotypes were 0.74 (0.73 to 0.75), 0.76 (0.75 to 0.78), and 0.78 (0.75, 0.81), respectively. Similar trends were observed in blacks (p=0.0031) and whites (p=0.0118). Marker rs7844465 (ZHX2) was significantly associated with left carotid IMT in whites (p=0.0005); mean IMT levels for the GG, TG, and TT genotypes were 0.73 (0.71 to 0.74), 0.75 (0.74 to 0.77) and 0.78 (0.75 to 0.81), respectively. Marker rs6841473 (EDNRA) modified the association between smoking and left carotid IMT in blacks (p=2.79×10−5). In addition, gene-based analysis demonstrated that EDNRA and ZHX2 were associated with left carotid IMT in the white and overall participants, respectively, while PINX1 was associated with right carotid IMT in both blacks and whites. ConclusionWe identified two novel markers that were associated with IMT in both blacks and whites. One gene-smoking interaction was identified in blacks only. Three genes showed gene-based associations with IMT levels. However, genetic markers with small effects may have been missed due to the limited number of black participants.

Childhood 25-OH Vitamin D Levels and Carotid Intima-Media Thickness in Adulthood: The Cardiovascular Risk in Young Finns Study

Low vitamin D levels in adulthood have been associated with cardiovascular disease. To investigate if low vitamin D levels in childhood are related with increased carotid artery intima-media thickness (IMT) in adulthood. The analyses included 2148 subjects from the Cardiovascular Risk in Young Finns Study, aged 3-18 years at baseline (in 1980). Subjects were re-examined at age 30-45 years (in 2007). Childhood levels of 25-hydroxy-vitamin D were measured from stored serum in 2010. The carotid artery IMT from 2007 was used. When adjusted for age, sex, and childhood risk factors, continuous data of childhood 25-OH vitamin was inversely associated with adulthood carotid IMT levels among females (β ± SE -0.006 ± 0.003, P = 0.03), but not among males (0.001 ± 0.004, P = 0.88). Children with 25-OH vitamin D levels in the lowest quartile (<40 nmol/L) had significantly increased odds of having high-risk IMT (highest decile of common carotid or carotid bulb IMT or carotid plaque) as adults, in analyses adjusted for age, sex and either childhood risk factors (odds ratio 1.70 [95 % CI 1.15-2.31], P = 0.0007) or adult risk factors, including adult vitamin D levels (odds ratio 1.80 [1.30-2.48], P = 0.0004). In sex-specific analyses, these associations were significant both in females and males (P always <0.05). In sensitivity analyses, those with childhood vitamin D levels in the lowest quintile (<37 nmol/L), gave similar results to those using a quartile cut-point. Low 25-OH vitamin D levels in childhood were associated with increased carotid IMT in adulthood.

Association between Fibrinogen and Carotid Atherosclerosis According to Smoking Status in a Korean Male Population.

PurposeAlthough inconsistent, reports have shown fibrinogen levels to be associated with atherosclerosis. Accordingly, since cigarette smoking is associated with increased levels of fibrinogen and atherosclerosis, it may also affect the association between fibrinogen and atherosclerosis. We investigated the associations between fibrinogen and carotid intima-media thickness (IMT) according to smoking status in a Korean male population.Materials and MethodsPlasma fibrinogen levels were measured in 277 men aged 40-87 years without a history of myocardial infarction or stroke. High-resolution B-mode ultrasonography was used to examine the common carotid arteries. IMT level was analyzed both as a continuous (IMT-max, maximum value; IMT-tpm, 3-point mean value) and categorical variable (higher IMT; presence of plaque). Serial linear and logistic regression models were employed to examine the association between fibrinogen and IMT according to smoking status.ResultsFibrinogen levels were positively associated with IMT-max (standardized β=0.25, p=0.021) and IMT-tpm (standardized β=0.21, p=0.038), even after adjusting for age, body mass index, systolic blood pressure, fasting glucose, and total cholesterol to high-density lipoprotein cholesterol ratio in current smokers (n=75). No significant association between fibrinogen and IMT, however, was noted in former smokers (n=80) or nonsmokers (n=122). Adjusted odds ratios (95% confidence interval) for having plaque per one standard deviation higher fibrinogen level were 2.06 (1.09-3.89) for current smokers, 0.68 (0.43-1.10) for former smokers, and 1.06 (0.60-1.87) for nonsmokers.ConclusionOur findings suggest that cigarette smoking may modify the association between fibrinogen and carotid atherosclerosis. Further studies are required to confirm this finding in different populations.

Carotid Endothelial VCAM-1 Is an Early Marker of Carotid Atherosclerosis and Predicts Coronary Artery Disease in Swine.

ObjectiveThe aim was to determine if endothelial VCAM-1 (eVCAM-1) expression in the common carotid artery (CCA) would correlate with predictive markers of atherosclerotic disease, would precede reduction of markers of endothelial cell function and would predict coronary artery disease (CAD).Methods and resultsCarotid arterial segments (bifurcation, proximal and distal CCA) were harvested from 14 and 24 month-old male castrated familial hypercholesterolemic (FH) swine, a model of spontaneous atherosclerosis. Quantification of local expression of eVCAM-1, intimal macrophage accumulation, oxidative stress, intima-media (I/M) ratio, intima-media thickness (IMT), endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (p-eNOS) in selected regions of the carotids revealed a relationship between local inflammation and atheroscle-rotic plaque progression. Importantly, inflammation was not uniform throughout the CCA. Endo-thelial VCAM-1 expression was the greatest at the bifurcation and increased with age. Finally, eV-CAM-1 best estimated the severity of CAD compared to blood levels of glucose, hypercholestero-lemia, carotid IMT, and p-eNOS.ConclusionOur data suggested that eVCAM-1 was closely associated with atherosclerotic plaque progression and preceded impairment of EDD. Thus, this study supported the use of carotid VCAM-1 targeting agents to estimate the severity of CAD.