High serum level of lutein may be protective against early atherosclerosis: the Beijing atherosclerosis study

Objective

We investigated whether early atherosclerosis before calcified plaque appeared as assessed by carotid intima-media thickness (IMT) was associated with levels of the major carotenoids, and assessed the associations among these serum carotenoids, carotid IMT, and arterial stiffness.

Methods

The case-control study comprised 125 subjects with early atherosclerosis and 107 controls aged 45–68 years. We simultaneously measured common carotid IMT and arterial stiffness by carotid ultrasonography, and serum carotenoids were determined by high-pressure liquid chromatograph (HPLC).

Results

In cases of early atherosclerosis, serum level of lutein was significantly lower than that in controls. Serum lutein was inversely associated with carotid IMT. Zeaxanthin and β-carotene were both negatively correlated with right common carotid artery stiffness β, elastic modulus (E_p), and pulse wave velocity (PWV). After adjusting for age and gender, the associations remain significantly (P < 0.05). However, there is no significant difference for zeaxanthin and β-carotene between the cases and controls.

Conclusion

These findings suggest that lutein may play a protective role in the prevention of early atherosclerosis, and the associations between serum carotenoids and arterial stiffness remained to be investigated.     

Clinically evident polyvascular disease and regression of coronary atherosclerosis after intensive statin therapy in patients with acute coronary syndrome: serial intravascular ultrasound from the Japanese assessment of pitavastatin and atorvastatin in acute coronary syndrome (JAPAN-ACS) trial

Aim

To clarify whether the effects of statin treatment on plaque regression vary according to the presence or absence of polyvascular disease (PVD) in patients with acute coronary syndrome (ACS).

Methods

307 patients with ACS who underwent percutaneous coronary intervention for the culprit lesion at 33 centers were treated with atorvastatin or pitavastatin. Noncoronary atherosclerosis was defined as coexistent, clinically recognized arterial disease other than coronary artery disease (CAD) (cerebral, aortic, or lower extremity). Intravascular ultrasound (IVUS) was performed to assess non-culprit coronary atherosclerosis at baseline and at 8–12 months follow-up. Serial IVUS examinations were obtained in 252 patients. Atheroma volume and percent change in atheroma volume of the target plaque was assessed.

Results

Patients of the CAD + PVD (n = 19) were older (68 vs. 62 years, p = 0.02), had lower low-density lipoprotein cholesterol (LDL-C) levels at baseline (116 vs. 134 mg/dL, p = 0.03) than those of the CAD-only group (n = 233), whereas LDL-C levels at follow-up were similar (81 vs. 83 mg/dL). Although the baseline plaque volume was similar in the two groups (59 vs. 57 mm³), patients of the CAD + PVD group showed milder regression of atherosclerosis than those of the CAD-only group (−8.9% vs. −18.2%, p = 0.005). This difference remained significant even after adjustment for coronary risk factors including age and serum LDL-C (p = 0.047).

Conclusions

Statin treatment results in milder regression of coronary atherosclerosis in CAD patients with polyvascular disease compared to those with CAD only.     

Association of plasma soluble E-selectin and adiponectin with carotid plaque in patients with systemic lupus erythematosus

Background

Systemic lupus erythematosus (SLE) is associated with premature atherosclerosis but the mechanisms underlying this association are not understood. The role of endothelial dysfunction is hypothesized.

Methods

In predominantly non-Caucasian patients with SLE (N = 119) and controls (N = 71), carotid ultrasonography was performed and circulating endothelial cells (CECs), soluble endothelial protein C receptor and gene polymorphism at A6936G, soluble E-selectin (sE-selectin), and adiponectin were assessed.

Results

Carotid plaque was more prevalent among patients than controls (43% vs 17%, p = 0.0002). Mean CCA IMT was greater in patients compared to controls (0.59 ± 0.19 mm vs 0.54 ± 0.11 mm, p = 0.03). Among SLE patients, plaque was not associated with smoking, body-mass index, LDL, triglycerides, homocysteine, C-reactive protein, anti-ds DNA antibody, C3, C4, SLE activity, or medications. Age and levels of soluble E-selectin and adiponectin were significantly higher in the SLE patients with plaque compared to those without plaque in univariate and multivariate analyses. sE-selectin and adiponectin were found to serve as independent predictors of carotid plaque and that elevations were persistent over more than one visit. Unexpectedly, these biomarkers were present despite clinical quiescence.

Conclusion

Premature atherosclerosis is a consistent feature of SLE and extends across ethnicities. Higher levels of adiponectin may represent a physiological attempt to limit further endothelial damage already reflected by the elevation in sE-selectin and the observed increase in plaque represents overwhelming of this reparative process by atherogenic stimuli.     

The metabolic syndrome, atherosclerosis and cognitive functioning in a non-demented population: the Hoorn Study

Background

The metabolic syndrome (MetS) is associated with cognitive deficits and atherosclerotic vascular disease. We examined whether the relation between the MetS and cognitive dysfunction is mediated by measures of atherosclerosis or the presence of clinically manifest cardiovascular disease.

Methods

In 380 individuals (153 with MetS; 60–87 years) from the population based Hoorn Study, measures of atherosclerosis including carotid intima-media thickness (c-IMT), flow mediated dilation (FMD), ankle-brachial index and the presence of clinically manifest cardiovascular disease were assessed at baseline and 7 later years at follow-up. Cognitive functioning (information processing speed, memory, and attention and executive functioning) was assessed at follow-up. The relation between the MetS, atherosclerosis and cognitive functioning was assessed with linear regression analysis.

Results

Individuals with MetS showed worse performance on information processing speed (adjusted mean difference z-score ± SE: −0.22 ± 0.6; p = 0.01) and attention and executive functioning (−0.32 ± 0.07; p < 0.001), but not on the domain memory. The affected cognitive domains were also associated with measures of atherosclerosis (standardised B (95%CI) c-IMT: −0.14 (−0.24; −0.05); p < 0.01; FMD: 0.13 (0.02; 0.24), p < 0.05) and a history of clinically manifest cardiovascular disease: (−0.29 (−0.47; −0.11); p < 0.01). However, the relation between the MetS and cognitive functioning did not change after adjustment for c-IMT, FMD or a history of clinically manifest cardiovascular disease (p > 0.05).

Conclusion

In this population based cohort, the relation between the MetS and cognitive dysfunction was not mediated by atherosclerosis or a history of cardiovascular disease. These findings should stimulate future studies to elucidate alternative mechanisms underlying cognitive deficits in individuals with MetS.     

Low plasma levels of the soluble receptor for advanced glycation end products in HIV-infected patients with subclinical carotid atherosclerosis receiving combined antiretroviral therapy

Objective

Combined antiretroviral therapy (cART) has significantly improved the survival rate and quality of life for HIV-infected subjects, but it contributes to the development of metabolic complications including coronary artery disease (CAD). Recent studies have reported that high plasma levels of the soluble receptor for advanced glycation end products (sRAGE) were associated with a lower incidence of CAD in non-HIV infected patients. However, there has been no report of an association of sRAGE and subclinical carotid atherosclerosis in HIV-infected patients receiving cART.

Methods

We examined the association of circulating sRAGE in HIV-infected patients with carotid intima–media thickness (IMT) and other metabolic variables. We prospectively enrolled 76 HIV-infected patients receiving cART for ≥6 months.

Results

sRAGE had a significantly negative correlation with body mass index (r = −0.324, p = 0.005), waist-to-hip ratio (r = −0.335, p = 0.003), systolic blood pressure (BP) (r = −0.359, p = 0.002), diastolic BP (r = −0.343, p = 0.004), total cholesterol (r = −0.240, p = 0.037), low-density lipoprotein-cholesterol (r = −0.284, p = 0.024), log(homeostasis model assessment of insulin resistance [HOMA-IR]) (r = −0.380, p = 0.002) and carotid IMT including max-IMT and mean-IMT (r = −0.358, p = 0.001 and r = −0.329, p = 0.004, respectively). By the use of multiple stepwise regression analyses, systolic BP (p = 0.001) and log[HOMA-IR] (p = 0.001) remained significant independently.

Conclusions

These results suggest that sRAGE may have a protective effect against subclinical atherosclerosis by preventing inflammatory responses mediated by the activation of cell surface RAGE in HIV-infected patients receiving cART.     

Vulnerable plaque features on coronary CT angiography as markers of inducible regional myocardial hypoperfusion from severe coronary artery stenoses

Objective

We explored whether the presence of 3 known features of plaque vulnerability on coronary CT angiography (CCTA) – low attenuation plaque content (LAP), positive remodeling (PR), and spotty calcification (SC) – identifies plaques associated with greater inducible myocardial hypoperfusion measured by myocardial perfusion imaging (MPI).

Methods

We analyzed 49 patients free of cardiac disease who underwent CCTA and MPI within a 6-month period and were found on CCTA to have focal 70–99% stenosis from predominantly non-calcified plaque in the proximal or mid segment of 1 major coronary artery. Presence of LAP (≤30 Hounsfield Units), PR (outer wall diameter exceeds proximal reference by ≥5%), and SC (≤3 mm long and occupies ≤90° of cross-sectional artery circumference) was determined. On MPI, reversible hypoperfusion in the myocardial territory corresponding to the diseased artery was quantified both as percentage of total myocardium (RevTPD_ART) by an automatic algorithm and as summed difference score (SDS_ART) by two experienced readers. RevTPD_ART ≥ 3% and SDS_ART ≥ 3 defined significant inducible hypoperfusion in the territory of the diseased artery.

Results

Plaques in patients with RevTPD_ART ≥ 3% more frequently exhibited LAP (70% vs. 14%, p < 0.001) and PR (70% vs. 24%, p = 0.001) but not SC (55% vs. 34%, p = 0.154). RevTPD_ART increased from 1.3 ± 1.2% in arteries with LAP−/PR− plaques to 3.2 ± 4.3% with LAP+/PR− or LAP−/PR+ plaques to 8.3 ± 2.4% with LAP+/PR+ plaques (p < 0.001); SDS_ART showed a similar increase: 0.3 ± 0.7 to 2.3 ± 2.8 to 6.0 ± 3.8 (p < 0.001). Using the same LAP/PR categorization, there was a marked increase in the frequency of significant hypoperfusion as determined by both RevTPD_ART ≥ 3% (1/19 to 10/21 to 9/9, p < 0.001) and SDS_ART ≥ 3 (1/19 to 8/21 to 8/9, p < 0.001). LAP and PR, but not SC, were strong predictors of RevTPD_ART and SDS_ART in regression models adjusting for potential confounders.

Conclusions

Presence of low attenuation plaque and positive remodeling in severely stenotic plaques on CCTA is strongly predictive of myocardial hypoperfusion and may be useful in assessing the hemodynamic significance of such lesions.     

Associations of matrix metalloproteinase-9 and monocyte chemoattractant protein-1 concentrations with carotid atherosclerosis,based on measurements of plaque and intima–media thickness

Purpose

To examine associations of matrix metalloproteinase-9 (MMP-9) and monocyte chemoattractant protein-1 (MCP-1) concentrations with the severity of carotid atherosclerosis, based on measurements of carotid plaque and intima–media thickness (IMT).

Methods

This cross-sectional study included 116 stroke-free participants (45.7% males, 54.3% females; mean age, 64.73 ± 14.53 years). Serum MMP-9 and MCP-1 concentrations were measured, and plaque morphology, including total plaque score (PS), plaque stability, and IMT, was assessed ultrasonographically. Participants were grouped according to total PS (0, 1–2, ≥3), plaque stability (no plaque, stable, unstable) and IMT tertiles (<0.8 mm, 0.8–1 mm, >1 mm). Multinomial logistic regression models were used to assess the associations of MMP-9 and MCP-1 concentrations with plaque and IMT values after adjusting for vascular risk factors.

Results

MMP-9 quartiles (vs. quartile 1) were significantly associated with a greater prevalence of plaque instability [Q2: odds ratio (OR) = 5.13, 95% confidence interval (CI) = 1.01–24.9, p = 0.042; Q3: OR = 15.5, 95% CI = 3.1–78.1, p = 0.001; Q4: OR = 13.2, 95% CI = 2.7–64.97, p = 0.001] and high total PS (Q3: OR = 10.02, 95% CI = 1.5–65.33, p = 0.016; Q4: OR = 21.5, 95% CI = 3.5–132.1, p = 0.001). MCP-1 concentration was significantly associated with IMT (OR = 22.94, 95% CI = 2.14–245.66, p = 0.01).

Conclusions

Elevated serum MMP-9 concentration was independently associated with high total carotid artery PS, plaque instability, and large IMT value. MCP-1 concentration was independently associated with IMT, but not with plaque morphology.     

Proprotein convertases in human atherosclerotic plaques: the overexpression of FURIN and its substrate cytokines BAFF and APRIL

Background

Proprotein convertase subtilisin/kexin (PCSK) enzymes cleave proproteins into mature end products. Previously, MBTPS1 and PCSK9 have been shown to regulate cholesterol metabolism and LDL receptor recycling, whereas FURIN and PCSK5 have been suggested to inactivate lipases and regulate inflammation in atherosclerosis. Here, we systematically analyzed the expression of PCSKs and their targets in advanced atherosclerotic plaques.

Methods and results

Microarray and quantitative real-time PCR experiments showed that FURIN (42.86 median fold, p = 2.1e−8), but no other PCSK, is universally overexpressed in the plaques of different vascular regions. The mRNA expression screen of PCSK target proteins in plaques identified many known factors, but it also identified the significant upregulation of the previously overlooked furin-processed B cell activating cytokines APRIL (TNFSF13, 2.52 median fold, p = 3.0e−5) and BAFF (TNFSF13B, 2.97 median fold, p = 7.6e−6). The dysregulation of FURIN did not associate with its htSNPs or the previously reported regulatory SNP (−229, rs4932178) in the promoter. Immunohistochemistry experiments showed the upregulation of FURIN in the plaque lymphocytes and macrophages where it was co-expressed with BAFF/TNFSF13B and APRIL/TNFSF13.

Conclusions

Our data unequivocally show that FURIN is the primary PCSK that is dysregulated in the immune cells of advanced human atherosclerotic plaques, which implies a role for this enzyme in plaque pathology. Therefore, drugs that inhibit FURIN in arteries may modulate the course of this disease.     

Relation of cholesterol and lipoprotein parameters with carotid artery plaque characteristics: the Atherosclerosis Risk in Communities (ARIC) carotid MRI study

Objective

There is a paucity of data regarding relations of apolipoproteins (apolipoprotein B [ApoB] and apolipoprotein A-1 [Apo A-1]), lipoprotein particle measures (low-density lipoprotein particle concentration [LDLp] and high-density lipoprotein particle concentration [HDLp]), and lipoprotein cholesterol measures (low-density lipoprotein cholesterol [LDL-C], non-high-density lipoprotein cholesterol [non-HDL-C], and high-density lipoprotein cholesterol [HDL-C]) with atherosclerotic plaque burden, plaque eccentricity, and lipid-rich core presence as a marker of high-risk plaques.

Methods

Carotid artery magnetic resonance imaging was performed in 1670 Atherosclerosis Risk in Communities study participants. Vessel wall and lipid cores were measured; normalized wall index (NWI), standard deviation (SD) of wall thickness (measure of plaque eccentricity) were calculated; and lipid cores were detected in vessels with ≥1.5 mm thickness. Fasting concentrations of cholesterol, ApoB and Apo A-1, and LDLp and HDLp were measured.

Results

Measures of plaque burden (carotid wall volume, wall thickness, and NWI) were positively associated with atherogenic cholesterol and lipoproteins (p < 0.05 for total cholesterol, LDL-C, non-HDL-C, ApoB, and LDLp), but not with HDL-C, Apo A-1, or HDLp. SD of wall thickness was associated with total cholesterol (p 0.01) and non-HDL-C (p 0.02). Although measures of atherogenic or anti-atherogenic cholesterol or lipoprotein were not individually associated with detection of a lipid-rich core, their ratios (total cholesterol/HDL-C, non-HDL-C/HDL-C, and LDLp/HDLp) were associated with lipid-rich core presence (p ≤ 0.05).

Conclusion

Extent of carotid atherosclerosis is associated with atherogenic cholesterol and lipoproteins. Atherogenic/anti-atherogenic cholesterol or particle ratios were associated with presence of a detectable lipid-rich core.     

Serial F-18-FDG PET/CT distinguishes inflamed from stable plaque phenotypes in shear-stress induced murine atherosclerosis

Background

Detection of inflamed atherosclerotic plaques is of crucial importance. The carotid artery cuff-model in ApoE^−/− mice results in shear-stress induced atherosclerosis with inflamed plaques upstream (US) and ‘stable’ plaques downstream (DS) of the cuff. We evaluated the potential of F-18-FDG PET/CT to differentiate these plaque phenotypes.

Methods

A predefined cuff was implanted round the left (n = 23) or right (n = 12) common carotid artery (CCA) of 35 ApoE^−/− mice on a cholesterol-rich diet. Small animal F-18-FDG PET/CT was performed after 4, 6 and 8 weeks. F-18-FDG uptake was quantified US and DS of the cuff and on the contralateral CCA. Subsequently, regional F-18-FDG uptake was normalized by the contralateral CCA uptake to obtain plaque-to-background (P/B)-ratios. Thereafter, CCA were explanted and investigated by immunohistology.

Results

P/B-ratio in the US-plaques increased from 1.22 ± 0.23 at 4 weeks over 1.23 ± 0.32 at 6 weeks to 1.37 ± 0.56 (p = ns) at 8 weeks after cuff implantation (left and right side of cuff implantation considered together). Uptake in the DS-plaques remained stable (1.14 ± 0.23, 1.10 ± 0.26 and 1.11 ± 0.25; p = ns). Uptake in the US-plaques was significantly higher than in the DS-plaques (all p < 0.05). P/B-ratios correlated with plaque size, degree of stenosis and macrophage density in the plaques. Moreover, there was a correlation between plaque size and macrophage density in the plaque.

Conclusions

F-18-FDG-PET/CT distinguishes atherosclerotic plaques with an inflamed from those with a ‘stable’ phenotype in a mouse model of shear-stress induced atherosclerosis in vivo.     

Meta-analysis on the effect of the Ala54Thr polymorphism of the fatty acid-binding protein 2 gene on body mass index

Background and aim

The results from studies published on the association of fatty acid-binding protein 2 (FABP2) Ala54Thr polymorphism with body mass index (BMI) are conflicting. In this meta-analysis, we investigated the association of the FABP2 Ala54Thr polymorphism with BMI.

Methods and results

We searched for articles published prior to June 2009 using PubMed, HugeNavigator and China National Knowledge Internet. The languages were limited to English and Chinese. Data on BMI were collected. A pooled weighted mean difference (WMD), together with 95% confidence interval (CI), was used for this meta-analysis.A total of 27 studies with 10 974 subjects were included in this meta-analysis. The pooled effect for dominant, recessive and co-dominant model comparisons did not suggest the significant association between the FABP2 Ala54Thr polymorphism and BMI in overall populations: WMD_{fixed effects} = −0.00, 95% CI: (−0.16 to 0.15), p = 0.99, WMD_{random effects} = −0.00, 95% CI: (−0.16 to 0.15), p = 0.99, p_Q = 0.77, I² = 0%, WMD_{fixed effects} = −0.12, 95% CI: (−0.39 to 0.14), p = 0.35, WMD_{random effects} = −0.12, 95% CI: (−0.39 to 0.14), p = 0.35, p_Q = 0.47, I² = 0% and WMD_{fixed effects} = 0.07, 95% CI: (−0.11 to 0.25), p = 0.45, WMD_{random effects} = 0.07, 95% CI: (−0.11 to 0.25), p = 0.45, p_Q = 0.90, I² = 0%, respectively. The results from the comparisons of ThrThr versus AlaAla and AlaThr versus AlaAla showed no evidence that the FABP2 Ala54Thr polymorphism is significantly associated with BMI in overall populations (p > 0.05). All the results from the subgroup analyses for these genetic models comparisons were not significant (p > 0.05).

Conclusions

Our meta-analysis does not support the association between the FABP2 Ala54Thr polymorphism and BMI.     

Plasma metalloproteinase levels and left ventricular remodeling in hypertrophic cardiomyopathy in patients with an identical mutation

Background and purpose

Although it has been reported that matrix metalloproteinases (MMPs) are associated with left ventricular (LV) remodeling in patients with hypertrophic cardiomyopathy (HCM), the impact of plasma MMP levels in patients with HCM is somewhat vague.

Methods and subjects

Plasma levels of MMP-2, MMP-9, and clinical/echocardiographic findings were evaluated in 16 HCM patients with preserved LV ejection fraction (defined as LV ejection fraction more than 50%) caused by an identical frameshift mutation (S593fs: a one-base deletion of a thymidine at nucleotide 11,645) in the cardiac myosin-binding protein C gene.

Results

MMP-2 levels were inversely related to LV ejection fraction (r² = −37, p = 0.01). MMP-9 levels were inversely related to LV end-diastolic dimension (r² = −0.24, p = 0.06) and positively related to the maximum LV wall thickness (r² = 0.25, p = 0.04). During follow-up period of 4.1 ± 1.2 years, LV ejection fraction decreased from 68.5 ± 7.4% to 64.9 ± 9% (p = 0.03). Among clinical, echocardiographic findings at baseline and levels of biomarkers, high MMP-9 levels were only related to the decrease of LV ejection fraction from baseline to follow-up (r² = 0.39, p = 0.009).

Conclusions

MMP-2 levels are related to reduced LV systolic function in HCM patients with preserved LV ejection fraction caused by an identical cardiac myosin-binding protein C gene abnormality. On the other hand, MMP-9 levels are associated with small LV size and the degree of LV hypertrophy and related to the deterioration in LV systolic function during follow-up. These results suggest that MMPs are important in the process of LV remodeling in HCM.     

Omentin-1 is associated with carotid atherosclerosis in patients with metabolic syndrome

Aim

The goal of this study was to investigate the association between omentin-1 and carotid atherosclerosis in patients with metabolic syndrome (MetS).

Method

We enrolled randomly 60 MetS patients, evaluated their carotid atherosclerosis employing ultrasonography and then divided them into two subgroups, MetS with atherosclerosis (MetS + AS) and MetS without atherosclerosis (MetS−AS) according to the level of carotid intima-media thickness (CIMT) and presence of plaque. Stiffness, strain and distensibility were calculated. Waist circumference and blood pressure (BP) were measured. Fasting blood sample was collected to determine biochemical indicators and insulin resistance index (HOMA-IR). Omentin-1 plasma level was assessed by ELISA. Association of omentin-1 with CIMT and metabolic markers were studied.

Results

Levels of omentin-1 were lower in MetS than in controls and reduced further in MetS + AS compared with MetS−AS. In correlation analysis, omentin-1 was negative associated with CIMT, stiffness, waist circumference, body mass index (BMI), systolic blood pressure (SBP), fast blood glucose (FBG), and HOMA-IR.

Conclusions

Omentin-1 is closely related to MetS and might play an important role in atherosclerosis in MetS patients.     

Carotid intima-media thickness in plaque-free site, carotid plaques and coronary heart disease risk prediction in older adults. The Three-City Study

Objectives

We sought to address the respective association between carotid intima-media thickness (IMT) in plaque-free sites and plaques with coronary heart disease (CHD) and their usefulness for CHD risk prediction in the Three-City Study.

Methods

At baseline, 5895 CHD-free adults aged 65–85 years underwent a bilateral ultrasound examination of carotid arteries. Mean IMT was measured in the far wall of the right and left common carotid arteries (CCA) at plaque-free site while the presence of focal plaques was assessed in the near and the far walls of the CCAs, the bifurcations and the origin of the internal carotid arteries.

Results

After a median follow-up of 5.4 years, 223 subjects had a first ever CHD event. In multivariate analysis, carotid plaques were independent predictors of CHD (Hazard ratio (HR)_{plaques at 1 site} = 1.5; 95% confidence interval (CI) = 1.0–2.2; HR_{plaques at ≥2 sites} = 2.2; 95% CI = 1.6–3.1; p_{for trend} < 0.001), contrary to mean CCA-IMT (HR_{fifth vs. first quintile} = 0.8; 95% CI = 0.5–1.2; p_{for trend} < 0.48). Adding carotid plaques to conventional risk factors significantly improved CHD risk prediction as measured by the area under the ROC curve (from 0.728 to 0.745; p = 0.04), the Harrell's c (from 0.748 to 0.762; p < 0.001), and the integrated discrimination improvement (IDI = 0.007; p = 0.002)/net reclassification improvement (NRI = 13.7%; p < 0.001) indices.

Conclusion

Carotid plaques, but not CCA-IMT measured at a plaque-free site, were independent predictors of CHD and improved CHD risk prediction in older adults.     

Race-specific associations of myeloperoxidase with atherosclerosis in a population-based sample: the Dallas Heart Study

Objective

Myeloperoxidase (MPO) is a leukocyte-derived enzyme that appears to be directly involved in atherosclerosis development. We evaluated the association of circulating MPO with coronary and aortic atherosclerosis in a large, multiethnic population.

Methods and results

Plasma levels of MPO were measured in 3294 subjects participating in the Dallas Heart Study, a probability-based population sample. Coronary artery calcification (CAC) was measured by EBCT, and abdominal aorta plaque prevalence (AP) and burden (APB), as well as abdominal aorta wall thickness (AWT) were determined by MRI. Associations between MPO and atherosclerosis phenotypes were assessed in multivariable analyses adjusting for traditional atherosclerosis risk factors. MPO levels in the 4th compared with 1st quartile independently associated with prevalent AP (OR 1.41, 95% CI 1.08–1.84), APB (beta coefficient 0.23, p = 0.02), and AWT (beta coefficient 0.04, p = 0.03), but not with prevalent CAC (OR 0.84, 95% CI 0.61–1.17). MPO remained associated with aortic atherosclerosis phenotypes but not coronary calcification after adjustment for other inflammatory biomarkers. A significant interaction was observed between race/ethnicity, MPO and AP (p_interaction = 0.038), such that MPO levels in the 4th vs 1st quartile associated with prevalent AP in African Americans, (OR 1.81, 95% CI 1.23–2.65) but not in White or Hispanic participants (OR 0.99, 95% CI 0.68–1.44).

Conclusion

Higher levels of MPO associated with aortic but not coronary atherosclerosis, with significant associations limited to African American participants. These findings suggest that MPO might be a novel risk factor contributing to racial disparities in peripheral vascular disease.     

Dysfunctional proinflammatory high‐density lipoproteins confer increased risk of atherosclerosis in women with systemic lupus erythematosus

Objective

Women with systemic lupus erythematosus (SLE) have an increased risk of atherosclerosis. Identification of at‐risk patients and the etiology underlying atherosclerosis in SLE remain elusive. The antioxidant capacity of normal high‐density lipoproteins (HDLs) is lost during inflammation, and these dysfunctional HDLs might predispose individuals to atherosclerosis. The aim of this study was to determine whether dysfunctional proinflammatory HDL (piHDL) is associated with subclinical atherosclerosis in SLE.

Methods

Carotid artery ultrasound was performed in 276 women with SLE to identify carotid plaques and measure intima‐media thickness (IMT). The antioxidant function of HDL was measured as the change in oxidation of low‐density lipoprotein after the addition of HDL cholesterol. Two antiinflammatory HDL components, paraoxonase 1 and apolipoprotein A‐I, were also measured.

Results

Among the SLE patients, 48.2% were determined to have piHDL on carotid ultrasound, while 86.7% of patients with plaque had piHDL compared with 40.7% of those without plaque (P < 0.001). Patients with piHDL also had a higher IMT (P < 0.001). After multivariate analysis, the only factors found to be significantly associated with plaque were the presence of piHDL (odds ratio [OR] 16.1, P < 0.001), older age (OR 1.2, P < 0.001), hypertension (OR 3.0, P = 0.04), dyslipidemia (OR 3.4, P = 0.04), and mixed racial background (OR 8.3, P = 0.04). Factors associated with IMT measurements in the highest quartile were the presence of piHDL (OR 2.5, P = 0.02), older age (OR 1.1, P < 0.001), a higher body mass index (OR 1.07, P = 0.04), a cumulative lifetime prednisone dose ≥20 gm (OR 2.9, P = 0.04), and African American race (OR 8.3, P = 0.001).

Conclusion

Dysfunctional piHDL greatly increases the risk of developing subclinical atherosclerosis in SLE. The presence of piHDL was associated with an increased prevalence of carotid plaque and with a higher IMT. Therefore, determination of piHDL may help identify patients at risk for atherosclerosis.

     

Longitudinal association between toenail selenium levels and measures of subclinical atherosclerosis: The CARDIA trace element study

Objectives

To examine the longitudinal association between toenail selenium levels and subclinical atherosclerosis over an 18-year period.

Methods

Toenail selenium concentrations were examined among 3112 Americans age 20–32 years in 1987 and measured by instrumental neutron-activation analysis. Subclinical atherosclerosis, including common, bulb and internal carotid intima–media thickness (CIMT), was measured in 2005 and coronary artery calcium (CAC) score in 2000 and 2005. General linear regression was developed examining the relation between toenail selenium levels and CIMTs, and logistic regression for repeated outcomes was employed estimating the risk of having CAC > 0.

Results

After adjustment for potential confounders, no associations were observed between toenail selenium levels and CIMTs as well as CAC score. Comparing participants in the highest with the lowest quintile of selenium, the CIMT was 0.005 mm (SE = 0.008 mm, P_trend = 0.39), 0.018 mm (SE = 0.019 mm, P_trend = 0.49), and 0.017 mm (SE = 0.014 mm, P_trend = 0.21) thicker measured in common, bulb and internal carotid, respectively. The adjusted odds ratio of having CAC > 0 was 0.95 (95% CI: 0.67–1.35; P_trend = 0.999).

Conclusions

No associations were observed between toenail selenium and measures of subclinical atherosclerosis among American young adults. This study does not support an atherosclerotic mechanism of selenium for risk reduction of cardiovascular disease.     

Dietary polyunsaturated fatty acids may increase plasma LDL-cholesterol and plasma cholesterol concentrations in carriers of an ABCG1 gene single nucleotide polymorphism: study in two Spanish populations

Background

ABCG1 mediates cellular cholesterol transport, but there is very little known about the influence of ABCG1 polymorphisms on human plasma lipoprotein cholesterol concentrations or on the interactions of these polymorphisms with diet.

Objective

Our objective was to investigate whether interactions between PUFA intake and ABCG1 polymorphisms modulate associations with plasma total cholesterol (TC), LDL- and HDL-cholesterol in two Spanish populations.

Methods

We grounded our investigation on two general population-based studies: the Hortega study (population A) and the Pizarra study (population B). Participants included 1178 individuals (50.0% women, age range 21–85 years) and 763 individuals (66% women, age range 23–73 years) from populations A and B, respectively, without lipid lowering drugs. Subjects were genotyped for ABCG1 variants. Biochemical measurements were taken by standard procedures. Dietary intakes were estimated with a validated questionnaire.

Results

In population A, the A allele homozygotes of SNP rs4148102 had higher TC and LDLc concentrations in subjects on a high PUFA diet than did the carriers of the G allele (242.1 ± 38.9 vs. 198.0 ± 36.0 mg/dL, p = 0.003, and 149.8 ± 37.9 vs. 111.4 ± 32.1 mg/dL, p = 0.005, respectively), and significant gene–diet interactions were observed (p = 0.020 and p = 0.013, respectively). In population B, similar differences in TC and LDLc concentrations were also found in association with this SNP under a high PUFA diet (253.2 ± 24.9 vs. 197.7 ± 39.9 mg/dL, p = 0.009, and 171.8 ± 20.5 vs. 120.4 ± 34.2 mg/dL, p = 0.004, respectively), but the gene–diet interactions observed were not significant (p = 0.379 and p = 0.422, respectively). In the pooled populations, differences in the TC and LDLc concentrations increased (246.8 ± 32.9 vs. 198.0 ± 37.5, p = 6 × 10⁻⁵, and 159.0 ± 32.6 vs. 114.3 ± 33.1, p = 3 × 10⁻⁵, respectively), and significant gene–diet interactions were maintained (p = 0.006 and p = 0.003, respectively).

Conclusion

In two Spanish populations, the ABCG1 polymorphism rs4148102 was associated with variations in plasma lipoprotein cholesterol concentrations in subjects with high PUFA intakes. Carriers of the AA genotype consuming high PUFA diet showed higher plasma LDLc concentrations.