Atherosclerosis

Publications in this journal

• Article: Lipoprotein lipase gene polymorphism rs1059611 functionally influences serum lipid concentrations.

  Xingbo Mo, Xuehui Liu, Laiyuan Wang, Hongfan Li, Xiangfeng Lu, Jianfeng Huang, Jichun Chen, Jie Cao, Jianxin Li, Shufeng Chen, Yida Tang, Xiaozhong Peng, Dongfeng Gu
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  ABSTRACT: OBJECTIVE: Dozens of single nucleotide polymorphisms (SNPs) in the lipoprotein lipase (LPL) gene have been reported to be associated with lipid concentrations. The aim of this study was to validate the association between rs1059611 in the LPL gene and serum lipid concentrations in the Chinese Han population and explore the biological relevance. METHODS: A total of 5664 participants were recruited and genotyped for the SNP. Gene expression levels of LPL in blood cells were evaluated by real-time PCR and western blotting analysis. The functional potential of the SNP was examined by luciferase reporter assay and electrophoretic mobility-shift assay (EMSA). RESULTS: We observed significant associations between rs1059611 and increased HDL-C (P = 5.65 × 10(-5)) and decreased TG concentrations (P = 2.68 × 10(-7)). We also found that participants with the C allele had higher mRNA expression level (P = 0.0334) and protein expression level (P = 0.0641) of LPL. The luciferase activity of the rs1059611 T construct was 0.69-fold of the rs1059611 C construct (P = 0.0009). The EMSA showed that the binding of the transcription factor(s) differed for the alleles of the SNP. CONCLUSION: The results of our study demonstrated that rs1059611 was associated with HDL-C and TG concentrations in Chinese Han population and might have a functional effect on the transcription of LPL by differential binding of transcription factors.
  Atherosclerosis 05/2013;
• Article: Stroke in sickle cell anemia patients: A need for multidisciplinary approaches.

  Farid Menaa
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  ABSTRACT: Sickle cell anemia (SCA) is an autosomal recessive disorder, with Mendelian inheritance pattern, caused by a missense mutation in the β-polypeptide chain of the hemoglobin B. SCA preferentially affects populations in countries where malaria was/is present (e.g. Africa, USA, Brazil). Thereby, in USA, the incidence of SCA is relatively high, around 1/500, and the prevalence is about 1/1000. In Brazil, SCA represents a major public health problem with an incidence ranging from 1/2000 to 1/600 depending on the regions. Homozygotic patients present more severe medical conditions and reduced life expectancy than heterozygous individuals who generally are asymptomatic. Eventually, this life-threatening disease displays a complex etiology owing to heterogeneous phenotypes and clinical outcomes, subsequently affecting the management of the patients. One of the most critical complications associated with SCA is stroke, a leading neurologic cause of death and disability. About 24% of SCA patients have a stroke by the age of 45 and 11% by the age of 20. From the general population, twin and familial aggregation studies as well as genome-wide association studies (GWAS), mostly in pediatric populations with ischemic stroke, showed that the risk of stroke has a substantial genetic component. Nevertheless, to fully characterize genomic contributors of stroke and permit reliable personalized medicine, multidisciplinary studies incorporating knowledge from clinical medicine, epidemiology, genetics, and molecular biology, are required. In this manuscript, stroke in SCA patients is extensively reviewed with emphasis to the US and Brazilian populations. Recent advances in genomics analysis of stroke in SCA patients are highlighted.
  Atherosclerosis 05/2013;
• Article: FOXP3 demethylation as a means of identifying quantitative defects in regulatory T cells in acute coronary syndrome.

  Cai-Xia Lü, Ren-De Xu, Ming Cao, Guan Wang, Feng-Qin Yan, Sha-Sha Shang, Xiao-Fen Wu, Lei Ruan, Xiao-Qing Quan, Cun-Tai Zhang
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  ABSTRACT: OBJECTIVE: The contribution of regulatory T cells (Tregs) to the pathogenesis of acute coronary syndrome (ACS) remains poorly understood. One core obstacle is the lack of Treg-specific markers. A highly conserved CpG enriched element in forkhead box P3 intron 1 (FOXP3 i l) is unmethylated only in Tregs, and measuring the unmethylation of FOXP3 i l can be used to identify the role of Tregs in clinical diseases. This study investigated whether analyzing the demethylation status of FOXP3 i 1 is a more reliable means than using Treg-specific surface markers in ACS. METHODS AND RESULTS: We evaluated circulating Tregs percentages on different levels including cell frequencies (CD4(+)CD25(hi)FOXP3(+)Tregs and CD4(+)CD25(hi)CD45(+)naïve Tregs) or FOXP3 mRNA, FOXP3 i 1 demethylation status and related cytokine secretion in 89 patients with ACS and 35 controls. FOXP3 i 1 demethylation assay showed that the amount of Tregs in ACS patients was significantly reduced than that in controls (p = 0.0005). However, flow cytometry analysis did not identify any reduction of CD4(+)CD25(hi)FOXP3(+)Tregs in ACS patients. Notably, younger patients had higher percentage of CD4(+)CD25(hi)FOXP3(+)Tregs but decreased percentage of CD4(+)CD25(hi)CD45(+)naïve Tregs than either controls or older patients. Furthermore, a DNA hypomethylation agent increased the amount of CD4(+)CD25(hi)FOXP3(+)Tregs and Tregs related cytokine IL-10 and suppressed the production of pro-inflammatory cytokine interferon-γ by inducing FOXP3 i 1 demethylation in vitro. CONCLUSIONS: A quantitative defect of Tregs, suggestive of decreased peripheral tolerance, could be a potential hallmark of ACS disease. Targeting FOXP3 i l demethylation might elevate the inhibitory activity of Tregs in ACS.
  Atherosclerosis 05/2013;
• Article: Body mass index is inversely associated with mortality in patients with peripheral vascular disease.

  Jonathan Golledge, Oliver Cronin, Vikram Iyer, Barbara Bradshaw, Joseph V Moxon, Maggie A Cunningham
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  ABSTRACT: BACKGROUND: Current guidelines contain no advice on how to manage obesity and underweight in patients with peripheral vascular disease (PVD). OBJECTIVES: The aim of this study was to assess the association of underweight, overweight and obesity with mortality in patients with PVD. PATIENTS AND METHODS: We recruited 1472 patients with a broad range of presentations of PVD. Underweight, overweight and obesity were defined by body mass index (BMI) and associated with mortality using Kaplan Meier and Cox proportional hazard analyses. RESULTS: Survival at 3 years was 37.5, 78.1, 86.8 and 87.0% for patients that were underweight, normal weight, overweight and obese at recruitment, respectively, p<0.001. Patients that were underweight had approximately twice the risk of dying (RR 2.15, 95% CI 1.31-3.55, p=0.003), while patients that were overweight (RR 0.67, 95% CI 0.49-0.91, p=0.011) or obese (RR 0.59, 95% CI 0.41-0.85, p=0.005) had approximately half the risk of dying, after adjustment for other risk factors and using normal weight subjects as the reference group. 823 patients had waist circumference measured at recruitment. Patients with waist circumference in the top quartile had half the risk of dying (RR 0.50, 95% CI 0.26-0.98, p=0.045). In 267 patients we assessed the relationship between BMI and abdominal fat volumes using computed tomography. BMI was highly correlated with both intra-abdominal and subcutaneous fat volumes. CONCLUSIONS: Obesity whether assessed by BMI or central fat deposition is associated with reduced risk of dying in patients with established PVD. Underweight is highly predictive of early mortality in patients with PVD.
  Atherosclerosis 05/2013;
• Article: Obesity paradox in peripheral vascular disease.

  Johji Kato
  Atherosclerosis 05/2013;
• Article: Relation of eggs with incident cardiovascular disease and diabetes: Friends or foes?

  Luc Djoussé
  Atherosclerosis 05/2013;
• Article: Pro-atherogenic lipid changes and decreased hepatic LDL receptor expression by tocilizumab in rheumatoid arthritis.

  Aart C Strang, Radjesh J Bisoendial, Ruud S Kootte, Dominik M Schulte, Geesje M Dallinga-Thie, Johannes H M Levels, Marc Kok, Koen Vos, Sander W Tas, Uwe J F Tietge, Nike Müller, Matthias Laudes, Danielle M Gerlag, Erik S G Stroes, Paul P Tak
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  ABSTRACT: OBJECTIVES: Blocking the interleukin-6 pathway by tocilizumab (TCZ) has been associated with changes in the lipoprotein profile, which could adversely impact cardiovascular (CV) risk in patients with rheumatoid arthritis (RA). In the present study, we addressed the effect of TCZ on lipoproteins in both fasting and non-fasting state in RA patients and tested the effect of TCZ on LDL receptor (LDLr) expression in vitro. METHODS: Twenty patients with active RA and an inadequate response to TNF blockers received monthly TCZ intravenously. On week 0, 1 and 6 blood was drawn before and after an oral fat load, the lipid profiles and HDL antioxidative capacity were measured. Effects of TCZ on LDLr expression in transfected HepG2 cells were subjected. RESULTS: After 6 weeks of TCZ, total cholesterol increased by 22% (4.8 ± 0.9 to 5.9 ± 1.3 mmol/L; p < 0.001), LDLc by 22% (3.0 ± 0.6 to 3.6 ± 0.8 mmol/L; p < 0.001) and HDLc by 17% (1.4 ± 0.4 to 1.7 ± 0.7 mmol/L; p < 0.016). Fasting triglycerides (TG) increased by 48% (1.0 ± 0.4 to 1.4 ± 0.8 mmol/L; p = 0.011), whereas postprandial incremental area under the curve TG increased by 62% (p = 0.002). Lipid changes were unrelated to the change in disease activity or inflammatory markers. No difference in HDL antioxidative capacity was found. In vitro, LDLr expression in cultured liver cells was significantly decreased following TCZ incubation (P < 0.001). CONCLUSIONS: TCZ adversely impacts on both LDLc as well as fasting and postprandial TG in patients with RA. The changes in hepatic LDLr expression following TCZ imply that adverse lipid changes may be a direct hepatic effect of TCZ. The net effect of TCZ on CV-morbidity has to be confirmed in future clinical trials.
  Atherosclerosis 05/2013;
• Article: rHDL administration increases reverse cholesterol transport in mice, but is not additive on top of ezetimibe or cholestyramine treatment.

  Cyrille Maugeais, Wijtske Annema, Denise Blum, Jean-Luc Mary, Uwe J F Tietge
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  ABSTRACT: OBJECTIVE: Promoting reverse cholesterol transport (RCT) is a major atheroprotective property of HDL. The present study explored the effect of stimulating the first step of RCT (cholesterol efflux from macrophages) alone or in combination with stimulating the last step of RCT (fecal sterol excretion). METHODS AND RESULTS: Reconstituted HDL (rHDL) was injected into wild-type mice either with or without administration of the cholesterol absorption inhibitor ezetimibe or the bile acid sequestrant cholestyramine. Single dose administration of rHDL (100 mg apoA-I/kg) resulted in an early (4 h) increase in plasma free cholesterol levels (p < 0.001), without affecting hepatic cholesterol levels or fecal mass sterol excretion. rHDL injection also increased [(3)H]cholesterol appearance in plasma at an early time-point (4 h) after intraperitoneal administration of [(3)H]cholesterol-labeled mouse macrophage foam cells and fecal radioactivity excretion indicating completed RCT was increased by 26% (p < 0.05). Ezetimibe treatment inhibited intestinal cholesterol absorption by 74% (p < 0.01), but also the bile acid sequestrant cholestyramine decreased cholesterol absorption significantly (24%, p < 0.01). Consequently, ezetimibe increased RCT 2.1-fold (p < 0.001) primarily within fecal neutral sterols, while cholestyramine increased RCT by 3.6-fold (p < 0.001), primarily within bile acids (p < 0.001), but also within neutral sterols (p < 0.001). However, no additive effects of both intestinal sterol uptake inhibitors were observed on top of rHDL administration. CONCLUSION: These data demonstrate that increasing the first step of RCT by rHDL administration results in transient cholesterol mobilization from macrophages to plasma. This effect is not further enhanced by stimulating the last step of RCT, fecal sterol excretion.
  Atherosclerosis 05/2013;
• Article: Hypoxia enhances lipid uptake in macrophages: Role of the scavenger receptors Lox1, SRA, and CD36.

  Margot Crucet, Sophia J A Wüst, Patrick Spielmann, Thomas F Lüscher, Roland H Wenger, Christian M Matter
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  ABSTRACT: OBJECTIVES: The core of advanced atherosclerotic plaques turns hypoxic as the arterial wall thickens and oxygen diffusion capacity becomes impaired. Macrophage-derived foam cells play a pivotal role in atherosclerotic plaque formation by expressing scavenger receptors that regulate lipid uptake. However, the role of hypoxia in scavenger receptor regulation remains incompletely understood. METHODS AND RESULTS: Using RT-qPCR, flow cytometry and immunoblotting, we found that mRNA and protein expression levels of the scavenger receptor A (SRA) and the cluster of differentiation 36 (CD36) were upregulated by oxidized low-density lipoprotein (oxLDL), but decreased following exposure of macrophages to hypoxia. In contrast, lectin-like oxLDL receptor (Lox-1) mRNA and protein levels were upregulated under hypoxic conditions. Flow cytometry confirmed the increased lipid content in macrophages after exposure to 0.2% oxygen and the hypoxia-mimetic dimethyloxalylglycine (DMOG). Antibody-mediated blocking of Lox-1 receptor decreased the hypoxic induction of oxLDL uptake and lipid content. RNAi-mediated knock-down of hypoxia-inducible factor (HIF)-1α in macrophages attenuated the hypoxic induction of Lox-1. CONCLUSIONS: Hypoxia increases lipid uptake into macrophages and differentially regulates the expression of oxLDL receptors. Lox-1 plays a major role in hypoxia-induced foam cell formation which is, at least in part, mediated by HIF-1α.
  Atherosclerosis 05/2013;
• Article: Calcium-phosphorus product concentration is a risk factor of coronary artery disease in metabolic syndrome.

  Woo Shin Kim, Dong-Hyun Lee, Ho-Joong Youn
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  ABSTRACT: BACKGROUND: High serum phosphorus and the calcium-phosphorus product concentration has been associated with increased mortality and cardiovascular events in patients with chronic kidney disease. OBJECTIVE: This study was designed to determine the relationship between calcium-phosphorus product concentration and the presence of coronary artery calcification in subjects with metabolic syndrome (MetS). METHODS: We reviewed the medical records of 2056 general subjects with a mean age of 55.1 ± 9.9 years and a glomerular filtration rate of 88.9 ± 16.2 mL/min/1.73 m(2). The enrolled subjects consisted of 384 (18.7%) subjects with MetS and 1672 (81.3%) subjects without MetS. The severity of coronary artery calcification was assessed by the coronary artery calcification score (CACS) using multi-detector computed tomography (MDCT). RESULTS: The CACS correlated with calcium-phosphorus product concentration in subjects with MetS (r = 0.184, P < 0.01). The odds ratio of calcium-phosphorus product concentration having CACS >50 was 1.053 in subjects with MetS (P < 0.05). After adjustment for age, sex, diabetes, and dyslipidemia, calcium-phosphorus product concentrations had a positive correlation with CACS in subjects with MetS. In single regression analysis, calcium-phosphorus product concentration as independent variable was the significant predictor of CACS in subjects with MetS. Using a multivariate analysis, calcium-phosphorus product concentration remained a significant factor associated with CACS in subjects with MetS. CONCLUSIONS: Calcium-phosphorus product concentration was weakly associated with CACS and an independent factor predicting for CACS by MDCT in subjects with MetS. These results suggest that calcium-phosphorus product concentration might be considered as a risk factor of coronary artery disease in subjects with MetS.
  Atherosclerosis 05/2013;
• Article: HDL function and cardiovascular risk: Debate continues…

  Jane Stock
  Atherosclerosis 05/2013;
• Article: Cystatin C is independently associated with total and cardiovascular mortality in individuals undergoing coronary angiography. The Ludwigshafen Risk and Cardiovascular Health (LURIC) study.

  Rainer P Woitas, Marcus E Kleber, Andreas Meinitzer, Tanja B Grammer, Günther Silbernagel, Stefan Pilz, Andreas Tomaschitz, Gisela Weihrauch, Harald Dobnig, Winfried März, Hubert Scharnagl
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  ABSTRACT: AIMS: Cystatin C is a well established marker of kidney function. There is evidence that cystatin C concentrations are also associated with mortality. The present analysis prospectively evaluated the associations of cystatin C with all-cause and cardiovascular (CV) mortality in a well-characterized cohort of persons undergoing angiography, but without overt renal insufficiency. METHODS: Cystatin C was available in 2998 persons (mean age: 62.7 ± 10.5 years; 30.3% women). Of those 2346 suffered from coronary artery disease (CAD) and 652 (controls) did not. Creatinine (mean ± SD: 83.1 ± 47.8 vs. 74.1 ± 24.7 μmol/L, p = 0.036) but not Cystatin C (mean ± SD: 1.02 ± 0.44 vs. 0.92 ± 0.26 mg/L, p = 0.065) was significantly higher in patients with CAD. After a median follow-up of 9.9 years, in total 898 (30%) deaths occurred, 554 (18.5%) due to CV disease and 326 (10.9%) due to non-CV causes. Multivariable-adjusted Cox analysis (adjusting for eGFR and established cardiovascular risk factors, lipid lowering therapy, angiographic coronary artery disease, and C-reactive protein) revealed that patients in the highest cystatin C quartile were at an increased risk for all-cause (hazard ratio (HR) 1.93, 95% CI 1.50-2.48) and CV mortality (HR 2.05 95% CI 1.48-2.84) compared to those in the lowest quartile. The addition of cystatin C to a model consisting of established cardiovascular risk factors increased the area under the receiver-operating characteristic curve for CV and all-cause mortality, but the difference was statistically not significant. However, reclassification analysis revealed significant improvement by addition of cystatin C for CV and all-cause mortality (p < 0.001), respectively. CONCLUSION: The concentration of cystatin C is strongly associated with long-term all-cause and cardiovascular mortality in patients referred to coronary angiography, irrespective of creatinine-based renal function.
  Atherosclerosis 05/2013;
• Article: Obstructive sleep apnea and cardiovascular risk: Meta-analysis of prospective cohort studies.

  Jia-Yi Dong, Yong-Hong Zhang, Li-Qiang Qin
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  ABSTRACT: BACKGROUND: Previous studies suggest obstructive sleep apnea (OSA) may increase cardiovascular risk, but the results are inconclusive due to various limitations. We aimed to systematically evaluate the effect of OSA on the incidence of cardiovascular events by a meta-analysis of prospective cohort studies. METHODS: We searched multiple electronic databases for studies that examined the prospective relationship between OSA and incidence of coronary heart disease (CHD), stroke, or total cardiovascular diseases (CVD) among adults. Either fixed- or random-effects models were used to calculate the pooled risk estimates. Sensitivity analysis was conducted to examine the robustness of pooled outcomes. RESULTS: Of 17 studies included, 9 reported results on total CVD, 7 reported on fatal or non-fatal CHD, and 10 reported on fatal or non-fatal stroke. The pooled relative risks (95% confidence interval) for individuals with moderate-severe OSA compared with the reference group were 2.48 (1.98-3.10) for total CVD, 1.37 (0.95-1.98) for CHD, and 2.02 (1.40-2.90) for stroke. These results did not materially change in the sensitivity analyses according to various inclusion criteria. CONCLUSIONS: In conclusion, findings from this meta-analysis supported that moderate-severe OSA significantly increased cardiovascular risk, in particular stroke risk.
  Atherosclerosis 05/2013;
• Article: Elevated levels of asymmetric dimethylarginine are associated with lower CD4+ count and higher viral load in HIV-infected individuals.

  Rushi V Parikh, Rebecca Scherzer, Carl Grunfeld, Elaine M Nitta, Anna Leone, Jeffrey N Martin, Steven G Deeks, Peter Ganz, Priscilla Y Hsue
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  ABSTRACT: OBJECTIVES: To compare asymmetric dimethylarginine (ADMA) among HIV-infected and uninfected individuals and to evaluate predictors of ADMA in HIV infection. BACKGROUND: HIV-infected individuals have high rates of atherosclerosis. Endothelial dysfunction is central to atherogenesis and is one possible mechanism underlying this increased cardiovascular risk. ADMA is an endogenous inhibitor of endothelial nitric oxide synthase. Among uninfected individuals, higher ADMA levels predict cardiovascular events and mortality. The association between HIV infection, HIV-related factors, and ADMA has not been well described. METHODS: We compared ADMA in 248 HIV-infected individuals and 50 uninfected controls. We performed multivariable analysis using traditional cardiovascular and HIV-specific factors as covariates to identify factors associated with ADMA. RESULTS: HIV-infected men were older, less often Caucasian, more hypertensive, and had lower HDL than uninfected men. The median duration of HIV infection was 13 years, median CD4+ count was 592 cells/μL, 76% had an undetectable viral load, and 76% were on antiretroviral therapy. ADMA levels were modestly higher in HIV-infected individuals than controls [median (IQR): 0.46 μM (0.41-0.52) vs. 0.44 μM (0.38-0.46), p = 0.019], but the association lost statistical significance after controlling for cardiovascular risk factors (+0.028 μM, p = 0.054). Lower CD4+ count and both detectable and higher viral load were independently associated with increased ADMA. CONCLUSIONS: ADMA levels were modestly elevated in the setting of HIV infection. Notably, a greater HIV-associated inflammatory burden, as evidenced by lower CD4+ counts and higher viral loads, was associated with increased ADMA levels. Our findings suggest that HIV infection impairs endothelial function and predisposes to atherosclerosis through chronic inflammation and subsequent accumulation of ADMA.
  Atherosclerosis 04/2013;
• Article: Liver involvement in sphingosine 1-phosphate dynamism revealed by adenoviral hepatic overexpression of apolipoprotein M.

  Makoto Kurano, Kazuhisa Tsukamoto, Ryunosuke Ohkawa, Masumi Hara, Junko Iino, Yuko Kageyama, Hitoshi Ikeda, Yutaka Yatomi
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  ABSTRACT: OBJECTIVES: Sphingosine 1-phosphate (S1P) is a vasoprotective lipid mediator that is mainly carried on HDL in the circulation and several anti-atherosclerotic properties of HDL is considered to be ascribed to S1P. Since S1P riding on HDL was recently shown to bind to apolipoprotein M (apoM), which is derived from liver, we analyzed the possible involvement of liver in S1P metabolism. METHODS AND RESULTS: Using adenoviruses, we overexpressed apoM in HepG2 cells and mice livers and found that both the medium/plasma and cell/liver S1P contents increased. Among lipoprotein subclasses, S1P contents increased mainly in HDL fractions. On the other hand, hepatectomy resulted in the reduction of plasma S1P levels in mice. The incubation of S1P in the conditional medium of apoM-overexpressing HepG2 cells interfered with S1P degradation. Furthermore, adenoviral hepatic overexpression of apoM resulted in increase in the S1P level of plasma but not of blood cells, while combination of hepatic apoM overexpression and intraperitoneal administration of C17-sphingosine resulted in the increase in the C17-S1P level both in livers and in plasma, but again not in blood cells. CONCLUSIONS: Livers are involved in S1P dynamism, and it was suggested that apoM, produced from livers, increases circulating plasma S1P by augmenting the S1P output from livers and modifies extracellular S1P metabolism.
  Atherosclerosis 04/2013;
• Article: Total and high molecular weight adiponectin levels and risk of cardiovascular disease in individuals with high blood glucose levels.

  Isao Saito, Kazumasa Yamagishi, Choy-Lye Chei, Renzhe Cui, Tetsuya Ohira, Akihiko Kitamura, Masahiko Kiyama, Hironori Imano, Takeo Okada, Tadahiro Kato, Shinichi Hitsumoto, Yoshinori Ishikawa, Takeshi Tanigawa, Hiroyasu Iso
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  ABSTRACT: OBJECTIVE: The association of adiponectin levels with cardiovascular disease (CVD) may vary by age and health condition. It is unknown whether adiponectin predicts CVD events among individuals with high blood glucose levels. METHODS: We conducted a nested case-control study among 15,566 men and women aged 40-85 years from four communities, who were free of CVD at baseline. During 192,181 person-years of follow-up, 117 individuals subsequently developed coronary heart disease or ischemic stroke and had high plasma glucose concentrations (fasting/nonfasting ≥ 5.6/7.2 mmol/L or treated) at baseline. Controls were randomly selected at a 2:1 ratio and matched for sex, age, blood glucose, year of survey, fasting conditions, and community (n = 234). Baseline total and high molecular weight (HMW) adiponectin and their ratio were examined for total subjects and the association with CVD was compared between ages of 40-69 and 70-85 years. RESULTS: After adjustment for matched variables and traditional risk factors, total and HMW adiponectin and their ratio were not associated with overall risk of CVD. However, significant interactions of the associations between the age groups were found. The highest quartile for HMW adiponectin and HMW/total adiponectin ratio decreased risk of CVD compared with the lowest quartile among middle-aged individuals (multivariable-adjusted odds ratio = 0.33 [95%CI, 0.13-0.83] and 0.47 [0.22-0.98], respectively), while this association was not seen among the elderly. CONCLUSIONS: High HMW adiponectin levels may decrease the risk of CVD in middle-aged adults with high blood glucose.
  Atherosclerosis 04/2013;
• Article: Measures of cardiovascular risk and subclinical atherosclerosis in a cohort of women with a remote history of preeclampsia.

  Sarah D McDonald, Joel Ray, Koon Teo, Hyejung Jung, Omid Salehian, Salim Yusuf, Eva Lonn
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  ABSTRACT: OBJECTIVE: We assessed for subclinical atherosclerosis using carotid intima-media thickness (CIMT) among women with and without a remote history of preeclampsia. Secondarily, we contrasted cardiovascular risk factors and electrocardiography between both groups. Women with a history of preeclampsia are at higher risk of future cardiovascular disease (CVD). The degree to which this is mediated by atherosclerosis is less understood, especially after several decades. METHODS: We performed a nested cohort study comprising 109 women with a remote history of preeclampsia 1:2 matched to 218 women with an uncomplicated pregnancy. After a median of 20 years since the index pregnancy, we measured blood pressure, height, weight, waist and hip circumference, and performed an oral 75 g glucose tolerance test (OGTT), fasting lipids, electrocardiography, albumin:creatinine ratio (ACR) and CIMT among all participants. RESULTS: While women with and without preeclampsia had similar family histories of CVD, those with preeclampsia had a higher rate of chronic hypertension (32% versus 10%, p < 0.0001), greater waist (p = 0.008) and hip circumferences (p = 0.001). No differences were seen on in OGTT, lipid or ACR measures. Average maximum CIMT was similar among those with versus without preeclampsia (0.831 mm versus 0.817, p = 0.38), and preeclampsia was not a significant predictor of CIMT in a multiple linear regression model (p = 0.63), despite more electrocardiograms compatible with coronary disease. CONCLUSION: Two decades after delivery, women with a remote history of preeclampsia had more CVD risk factors than women with unaffected pregnancies, but this was not reflected in a difference in CIMT.
  Atherosclerosis 04/2013;
• Article: Low-dose of oral factor Xa inhibitors in patients with a recent acute coronary syndrome: A systematic review and meta-analysis of randomized trials.

  Karolina Obonska, Eliano Pio Navarese, Alexandra Lansky, Giuseppe Tarantini, Roberta Rossini, Marek Kozinski, Giuseppe Musumeci, Giuseppe Di Pasquale, Bartosz Górny, Anna Szczesniak, Mariusz Kowalewski, Paul Alfred Gurbel, Jacek Kubica
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  ABSTRACT: BACKGROUND: Recently, randomized controlled trials (RCTs) have shown that therapy with new oral activated factor X (Xa) inhibitors in acute coronary syndrome (ACS) yielded a reduction of ischemic events. However, this therapy was associated with a dose-related increase in major bleeding complications. We aimed to perform a systematic review and meta-analysis to appraise the clinical efficacy and safety of the lowest doses of oral factor Xa inhibitors compared with placebo in patients after a recent ACS. METHODS: The primary endpoint was cardiovascular mortality. The rate of new myocardial infarction (MI) was the secondary efficacy endpoint, whereas major bleeding complications were recorded as a safety endpoint. Five RCTs were included in the meta-analysis enrolling a total of 25,643 patients. RESULTS: There was no significant difference in mortality between patients treated with new antithrombotics compared with those receiving the standard therapy: odds ratio (OR), [95% confidence interval (CI)] = 0.97 [0.72-1.31], p = 0.86. Recurrent MI rates were decreased in the anti-Xa group: OR [95%CI] = 0.86 [0.76-0.98], p = 0.02, number needed to treat (NNT) = 189. The administration of new oral anticoagulants was associated with a strongly increased risk of major bleedings compared with the standard treatment: OR [95%CI] = 3.24 [2.29-4.59], p < 0.001, number needed to harm (NNH) = 104; similarly, intracranial bleeding rates were significantly higher in the anti-Xa arm. CONCLUSIONS: The addition of the new oral anticoagulants on top of standard therapy in the setting of ACS results in an excessive risk of major bleedings without any clear evidence of outweighing clinical benefits.
  Atherosclerosis 04/2013;
• Article: Association between carotid intima-media thickness and retinal arteriolar and venular diameter in patients with hypertension: A cross-sectional study.

  Felipe Soares Torres, Sandra C Fuchs, Marcelo K Maestri, Flavio D Fuchs, Manuel M Oliveira, Leila B Moreira, Miguel Gus
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  ABSTRACT: OBJECTIVE: Abnormalities in retinal vessels are frequent, but its association with findings in other vascular sites has been scarcely investigated. This study aimed to examine the association between ultrasound-measured carotid intima-media thickness (IMT) and retinal arteriolar and venular diameters, in hypertensive patients. METHODS: In this cross-section study, 173 hypertensive patients had both retinography taken and digitized to determine vessel diameters by an edge-detecting computerized method and carotid ultrasound for semi-automated carotid IMT measurement. The association between the mean common carotid IMT and retinal arterioles and venules diameters was assessed by using multiple linear regression models. RESULTS: The mean (±SD) arteriolar and venular diameters were 102. 8 (±11.6) μm and 128.9 (±15.5) μm, respectively, and common carotid IMT was 0.87 (±0.19) mm. A significant and independent association was demonstrated for carotid IMT and retinal arteriolar caliber (adjusted β -0.245, p = 0.001) and for carotid IMT and retinal venular caliber (adjusted β 0.191, p = 0.009) after controlling for age, gender, systolic blood pressure, total cholesterol and HDL (high-density lipoprotein) cholesterol, prior cardiovascular disease, carotid plaque and the retinal fellow vessel. CONCLUSION: In patients with hypertension, carotid intima-media thickness, a marker of macrovascular damage, is significantly and independently associated with microvascular damage, determined by retinal arteriolar and venular calibers.
  Atherosclerosis 04/2013;
• Article: Cigarette-smoke-induced atherogenic lipid profiles in plasma and vascular tissue of apolipoprotein E-deficient mice are attenuated by smoking cessation.

  Michael Lietz, An Berges, Stefan Lebrun, Kris Meurrens, Yvonne Steffen, Katrin Stolle, Jutta Schueller, Stephanie Boue, Grégory Vuillaume, Patrick Vanscheeuwijck, Michaela Moehring, Walter Schlage, Hector De Leon, Julia Hoeng, Manuel Peitsch
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  ABSTRACT: Tobacco smoke exerts perturbations on lipid metabolism and arterial cell function that accelerate atherosclerosis. Lipidomics has emerged as a key technology in helping to elucidate the lipid-related mechanisms of atherosclerosis. In this study, we investigated the effects of smoking cessation on plaque development and aortic arch content of various lipid molecular classes and species. Apolipoprotein E-deficient mice were exposed to fresh air (sham) or to mainstream cigarette smoke (CS) for 6 months, or to CS for 3 months followed by sham for 3 months (cessation group). Lipids from plasma and aortic arches, plasma lipoprotein profiles and plaque morphometry measurements were analyzed. We already showed that CS exposure accelerated plaque size and total cholesterol content of the aortic arch at 3 and 6 months. Marked increases were seen in the relative enrichment of cholesteryl esters, phospholipids, sphingomyelins, and glycosphingolipids. Smoking cessation slowed plaque progression and resulted in lower levels of many lipid species in plasma and aortic arch. While CS exposure promoted rapid lipid accumulation in mouse aorta, smoking cessation translated into a slow removal of lipids from the vessel wall. Despite the smoking cessation-dependent metabolic changes leading to increased animal body weight, accumulation of proatherogenic lipids in the vessel was halted after exposure cessation, indicating that the clinical benefits of smoking cessation translate directly to the vessel wall and its lipid makeup.
  Atherosclerosis 04/2013;