| 1. |
- Davidsson, Lisa, et al.
(författare)
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Ultrasound-assessed plaque occurrence in the carotid and femoral arteries are independent predictors of cardiovascular events in middle-aged men during 10 years of follow-up.
- 2009
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Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150.
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To examine if plaques in the carotid and femoral arteries were associated with cardiovascular events during a 10-year follow-up independently of usual risk factors for such diseases. METHODS: Plaque occurrence in both carotid arteries, and in the right femoral artery were assessed at baseline by B-mode ultrasound in a population-based sample of 58-year-old men (n=391) with no cardiovascular disease, and varying degrees of obesity and insulin sensitivity at entry. Anthropometry and blood pressure were recorded. Fasting venous blood samples were used for measurement of cardiovascular risk factors. Cardiovascular events occurring during follow-up were obtained by access to register data. RESULTS: Systolic blood pressure, serum triglycerides and waist-hip ratio as well as baseline occurrence of carotid and femoral plaques were associated with events. Logistic multi-variate analyses showed that carotid plaques (OR 2.09, 95% CI 1.05-4.16, p=0.037), femoral plaques (OR 1.99, 95% CI 1.01-3.91, p=0.047) and concomitant presence of carotid, and femoral plaques (OR 2.53, 95% CI 1.23-5.21, p=0.011) were associated with cardiovascular events independently of other risk factors. Plaques occurred in 0-3 arteries and there was a parallel increase in cardiovascular risk (p=0.004). CONCLUSION: Occurrence of carotid or femoral plaques at baseline had similar predictive value for cardiovascular events. Increased plaque burden, with plaques in both carotid and femoral arteries increased the cardiovascular risk further. Hence, the results from this study indicate that ultrasound examination of both the carotid and femoral arteries was the preferred method to predict cardiovascular risk.
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| 2. |
- Hägg, Daniel, 1974, et al.
(författare)
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Augmented levels of CD44 in macrophages from atherosclerotic subjects: a possible IL-6-CD44 feedback loop?
- 2007
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 190:2, s. 291-7
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Tidskriftsartikel (refereegranskat)abstract
- The cell-adhesion molecule CD44 likely participates in atherosclerosis development. We have shown previously that pro-inflammatory cytokines affect CD44 expression. Therefore, this work examined the role of elevated CD44 levels in human macrophages. Macrophages from human atherosclerotic subjects (n=15) showed elevated levels of CD44 transcript and protein (1.5-fold) compared to matched controls (n=15) (P=0.050 and 0.044, respectively). To test whether genetic factors influence CD44 expression, two single nucleotide polymorphisms in the CD44 gene were analyzed but these were not associated with coronary artery disease. We also examined the potential connection between plasma cytokine levels and CD44 expression. In atherosclerotic subjects, elevated CD44 expression correlates (P=0.012) with enhanced macrophage IL-6 secretion (3.13+/-2.5 pg/mL versus 0.32+/-0.16 pg/mL in controls, P=0.021). Additionally, CD44-deficient mice exhibit less circulating IL-6 than wild-type controls (9.8+/-0.7 pg/mL versus 14.3+/-0.7 pg/mL; P=0.032). Furthermore, IL-6 augments CD44 expression in primary human macrophages after 24 h (P=0.038) and 48 h (P=0.015). Taken together, our data show an IL-6-CD44 feedback loop in macrophages. Such a positive feedback loop may aggravate atherosclerosis development.
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| 3. |
- Hägg, Daniel, 1974, et al.
(författare)
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Expression of chemokine (C-C motif) ligand 18 in human macrophages and atherosclerotic plaques
- 2009
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Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 204:2
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Using gene expression profiling, we aimed to identify genes that are predominantly expressed in human carotid atherosclerotic plaques. Such genes may be important in atherogenesis and pathophysiology of the plaque, and genes that encode for secreted proteins may be potential biomarkers for atherosclerosis and cardiovascular disease. METHODS: DNA microarray generated expression profiles of human carotid atherosclerotic plaques were compared to expression profiles of 80 different human tissues and cell types, to identify plaque-specific genes. RESULTS: We identified the chemokine (C-C motif) ligand 18 (CCL18) as predominantly expressed in human carotid plaque. Immunohistochemistry showed that CCL18 protein was localized to a subset of macrophages in carotid plaques. Monocyte-derived macrophages from subjects with atherosclerosis had threefold higher expression of CCL18 than macrophages from control subjects (p=0.012). Subjects with A/G genotype of the rs2015086 SNP in the promoter region of the CCL18 gene had threefold higher macrophage expression of CCL18 than subjects with A/A genotype (p=0.049), but we found no association of this SNP with an increased risk of coronary heart disease. We also compared serum levels of CCL18 from subjects with symptomatic carotid artery disease with control subjects. There were no differences in serum levels of CCL18 between the two groups, however CCL18 correlated with measurements of adiposity. CONCLUSION: CCL18 is predominantly expressed in human atherosclerotic plaques and may participate in the atherosclerotic plaque formation.
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| 4. |
- Lindqvist, Helen, 1977, et al.
(författare)
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Plasma phospholipid EPA and DHA in relation to atherosclerosis in 61-year-old men
- 2009
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Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 205:2, s. 574-578
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Increased intake of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been shown to decrease the risk for cardiovascular death and to reduce CVD risk factors. It has also been suggested that EPA and DHA reduce atherosclerosis progression, but data are inconclusive. Carotid intima-media thickness (IMT) is a well-established surrogate measure for sub-clinical atherosclerosis. Our aim was to examine if plasma phospholipid EPA and DHA are associated with IMT and plaque occurrence and size in the carotid and femoral arteries. Methods: IMT and plaque occurrence in carotid and femoral arteries was measured by ultrasound in 487 sixty-one-year-old men in this cross-sectional study. Plasma phospholipid levels of EPA and DHA, serum lipids, cell adhesion molecules, and blood pressure were measured, and occurrence of diabetes and socioeconomic factors were assessed. Results: Plasma phospholipid EPA was negatively associated with IMT in carotid and femoral arteries, and with cigarette years and cell adhesion proteins. EPA was positively associated with HDL, total cholesterol, blood pressure, plasma insulin and years of education. The association between EPA and carotid IMT remained after adjustment for blood pressure, but not for other covariates. Plasma phospholipid DHA was negatively associated with cigarette years and several endothelial markers, and positively associated with years of education and systolic blood pressure. In contrast to other studies, EPA content was higher in diabetic patients compared with patients without diabetes. Conclusion: Plasma phospholipid EPA, but not DHA, was inversely associated with carotid and femoral IMT, as well as several endothelial markers supporting the concept of an effect of EPA on the vascular wall. This association was independent of blood pressure, but not for other covariates. There was no association between plasma phospholipid EPA or DHA and plaque occurrence in the carotid and femoral arteries. © 2008 Elsevier Ireland Ltd. All rights reserved.
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| 5. |
- Fagerberg, Björn, 1943, et al.
(författare)
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Cadmium exposure as measured in blood in relation to macrophage density in symptomatic atherosclerotic plaques from human carotid artery
- 2016
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150. ; 249, s. 209-214
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: The general population is exposed to cadmium through diet and smoking. Cadmium is pro-atherogenic and pro-inflammatory in experimental and observational studies. Cadmium levels in blood and carotid plaque endarterectomies correlate. Cadmium concentrations are much higher in plaque-areas that most frequently rupture. Here we investigated if blood cadmium concentrations are associated with macrophage density and the accumulation of CD14 as indicator of macrophage activation by lipopolysaccharide (LPS) in endarterectomies from patients with symptomatic carotid plaques. Methods: Endarterectomies from ninety nine patients were fixed in formalin, embedded in paraffin, serially sectioned and stained for assessment of morphology. As predefined, the two section levels with most prevalent plaque rupture were used for further analyses. Macrophages were assessed as area of staining for CD68 (%). Blood cadmium was measured with ICP-MS. Results: The CD68 median [25,75 percentiles] from the average of both sections were higher in cadmium tertile 3 than in tertile 1 (9.8 [4.9,16.1] % and 3.8 (0.6,12.4) %, p = 0.017). This difference remained in a multiple linear regression analysis with 10log meanCD68 as dependent variable and adjustment for sex, age, smoking, statin treatment, index event, time between event and surgery (beta coefficient 0.44 [95% CI 0.05-0.87]. CD14 was not associated with blood cadmium. Conclusions: The results showed that blood cadmium was associated with proinflammatory macrophage density in the sections of carotid plaques with most frequent rupture, previously shown to contain most cadmium. No association between cadmium and LPS-mediated macrophage-activation was found. Cadmium exposure may promote plaque inflammation. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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| 6. |
- Fagerberg, Björn, 1943, et al.
(författare)
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Circulating cadmium concentration and risk of aortic aneurysms: A nested case-control study within the Malmo Diet and Cancer cohort
- 2017
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150. ; 261, s. 37-43
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Diet and smoking expose the general population to cadmium (Cd), which is a toxic metal that accumulates in the arterial wall. In experimental studies, Cd causes reductions in proliferation of smooth muscle cells and cellular synthesis of procollagen. The aim of this study was to examine whether blood Cd levels, a valid measure of Cd exposure, are associated with increased risk of abdominal aortic aneurysm (AAA). Methods: All middle-aged men and women enrolled in the Malmo Diet and Cancer study (n = 30 447) were followed from the baseline examination in 1991-1996 through 2009. A total of 297 cases with AAA and two randomly selected control subjects for each case, matched for age and sex, were included. Blood Cd was analysed by inductively coupled plasma mass spectrometry. Diagnoses of AAA, thoracic aortic aneurysm and aortic dissection were obtained from registers. Results: Increased blood Cd was associated with increased risk of incident AAA after adjustment for smoking and other established risk factors for AAA. The highest tertile of blood Cd concentrations had a rate ratio of 2.5 (95% confidence interval 1.3, 5.0) for incident AAA. Concentration of blood Cd (log transformed) was not associated with AAA in never-smokers (n = 24). Conclusions: Blood Cd levels corresponding to the upper tertile of the distribution in the age-and sex-matched control group were associated with a 2.5-fold increase in rate ratio for incident AAA. This relationship was not found in the small group of never-smokers. (C) 2017 Published by Elsevier Ireland Ltd.
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| 7. |
- Schmidt, Caroline, 1966, et al.
(författare)
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apoB/apoA-I ratio is related to femoral artery plaques and is predictive for future cardiovascular events in healthy men
- 2006
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150. ; 189:1, s. 178-85
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of the present study was to investigate the association between serum concentrations of apoB, apoA-I and the apoB/apoA-I ratio and future cardiovascular events in a group of healthy 58-year-old men during 6.6 years of follow-up. A further aim was to investigate the concentrations of apoB, apoA-I and the apoB/apoA-I ratio to the association of plaque occurrence in the carotid and femoral arteries. BACKGROUND: Previous studies have shown that the apoB/apoA-I ratio is an important cardiovascular risk factor, whereas the association between apoB/apoA-I ratio and presence of atherosclerotic plaques in the carotid and femoral arteries has been less investigated. METHODS: The carotid and femoral arteries were examined by high-resolution B-mode ultrasound in 391, 58-year-old men identified by screening in the city of Goteborg, Sweden. Assessment of plaque occurrence and measurement of apolipoproteins (apoA-I and apoB) was performed. RESULTS: Subjects with an apoB/apoA-I ratio >/=0.9 had a significantly increased risk to suffer a cardiovascular event during 6.6 years of follow-up (OR 3.07, 95% CI 1.22-7.71), while no difference in risk for cardiovascular events was observed for subjects with LDL cholesterol >3.4 mmol/L compared to subjects <3.4 mmol/L (OR 1.04, 95% CI 0.37-2.46). A greater risk for plaques in the femoral artery was also observed in subjects with an apoB/apoA-I ratio >/=0.9 compared to subjects <0.9 (OR 3.06, 95% CI 1.22-7.70). In a multiple logistic regression model, both elevated apoB/apoA-I ratio and plaque occurrence in the femoral artery were of significant importance for cardiovascular events during follow-up. CONCLUSIONS: The results showed that the apoB/apoA-I ratio was associated with arteriosclerosis in the femoral artery, and predicted future cardiovascular events. These observations, and the fact that apoB and apoA-I can be measured in the non-fasting state with high precision, in combination with the finding that LDL cholesterol did not predict cardiovascular disease, support results from other studies that the apoB/apoA-I ratio may be a superior risk marker for cardiovascular disease.
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| 8. |
- Schmidt, Caroline, 1966, et al.
(författare)
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ApoB/apoA-I ratio is related to femoral artery plaques in 64-year-old women also in cases with low LDL cholesterol
- 2008
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150. ; 196:2, s. 817-822
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The apolipoproteinB (apoB)/apolipoproteinA-I (apoA-I) ratio mirrors the number of pro-atherogenic and anti-atherogenic lipoprotein particles. This ratio may carry more information on risk for atherosclerosis than LDL in cohorts with impaired glucose tolerance. The aim was to examine the association between the apoB/apoA-I ratio and ultrasound-assessed atherosclerosis in the carotid and femoral arteries in women with varying degrees of glucose tolerance. METHODS: Plaque occurrence, and intima-media thickness in the carotid and femoral arteries were examined by B-mode ultrasound in a random sample of 64-year-old women (n=646) living in Gothenburg, Sweden, representing different degrees of glucose intolerance (diabetes (n=234), impaired (n=212) and normal glucose tolerance (n=200)). Traditional risk factors and serum concentrations of apolipoproteins were analysed. RESULTS: For subjects in the lowest LDL tertile, the risk of having a plaque in the femoral artery was three times greater for subjects in the highest apoB/apoA-I tertile compared to subjects in the lowest tertile (OR: 3.0, 95% CI: 1.2-7.5). A clear increase in the occurrence of femoral plaque was observed already at a cut-off value of 0.63 (OR: 1.8, 95% CI: 1.2-2.6). ApoB/apoA-I was also related to femoral plaque occurrence in women with low HbA1c. ApoB/A-I ratio was associated with carotid and femoral IMT but not carotid plaques. CONCLUSION: The apoB/apoA-I ratio improved the identification of cases with femoral artery atherosclerosis in a cohort of women with varying degrees of glucose tolerance. Such cases could also be identified in women with normal LDL and HbA1c levels. The results indicate that an apoB/apoA-I ratio above 0.63 should be used as a marker of increased risk.
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| 9. |
- Schmidt, Caroline, 1966, et al.
(författare)
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Non-stenotic echolucent ultrasound-assessed femoral artery plaques are predictive for future cardiovascular events in middle-aged men
- 2005
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150. ; 181:1, s. 125-30
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of the present study was to examine the relationship between plaque occurrence, plaque size and plaque echogenicity, assessed by B-mode ultrasound, in the femoral artery and the development of clinical cardiovascular disease. BACKGROUND: The relationship between carotid atherosclerosis assessed by B-mode ultrasound and cardiovascular disease has been thoroughly investigated. In comparison, the femoral arteries have received much less attention. METHODS: The femoral artery was examined by high-resolution B-mode ultrasound in 391, 58-year-old men identified by screening in the city of Goteborg, Sweden. Assessment of plaque occurrence, plaque size (no, small, or moderate/large) and plaque characteristics in terms of echogenicity (no, echogenic or echolucent) were performed. RESULTS: Subjects with a plaque present in the femoral artery at study baseline had a three-fold increase in odds ratio (OR 3.04, 95%, CI 1.24-7.42) for having a cardiovascular event during 6.6 years of follow-up compared to subjects without plaque. After adjustment for cardiovascular risk factors (LDL, triglycerides, systolic blood pressure and smoking) there was a borderline significant association between plaque occurrence and cardiovascular disease (OR = 2.64, p = 0.055). Plaque size could be demonstrated to be associated with cardiovascular events (p = 0.012, for trend). The results also showed that in this group of men, the risk of having a cardiovascular event was to a large extent confined to those with an echolucent plaque at baseline. However, no significant difference in risk prediction was seen between echogenic and echolucent plaques, respectively. CONCLUSIONS: This is the first study to show that the presence of non-stenotic plaques in the femoral artery in middle-aged men without prior cardiovascular events has a predictive value for future cardiovascular events. The relationship was attenuated by adjustment for traditional cardiovascular risk factors. Data also indicates that plaque echolucency predicts increased risk.
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| 10. |
- Sigurdardottir, Vilborg, 1968, et al.
(författare)
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Circulating oxidized low-density lipoprotein is associated with echolucent plaques in the femoral artery independently of hsCRP in 61-year-old men
- 2007
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150. ; 190:1, s. 187-93
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of the study was to test the hypothesis that circulating markers of inflammation (high-sensitive C-reactive protein, hsCRP) and oxidative modification of lipids (oxidized low-density lipoprotein, oxLDL) were associated with the occurrence of echolucent rather than echogenic femoral artery plaques in a cross-sectional population based cohort of 513, 61-year-old men. BACKGROUND: The relationships between circulating oxLDL, hsCRP and the occurrence of echolucent plaques in the femoral artery have not previously been investigated. METHODS: The levels of circulating oxLDL and hsCRP were determined in plasma by ELISA. Plaque occurrence, size and echogenicity were measured by B-mode ultrasound in the right femoral artery. Assessment of plaque echogenicity was based on the classification (grades 1-4) proposed by Gray-Weale et al. RESULTS: A higher frequency of echolucent femoral plaques was observed in subjects with the metabolic syndrome and current smokers (p=0.01 and p<0.001, respectively) as well as with increasing levels of oxLDL and hsCRP (p=0.002 and p=0.005, respectively). In a multiple logistic regression analysis oxLDL and current smokers turned out to be independent associated with the presence of echolucent femoral artery plaques. CONCLUSIONS: The results of the present study support our hypothesis that circulating oxLDL is a marker of an unstable echolucent plaque phenotype in the femoral artery in man.
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