IgM antibodies against malondialdehyde and phosphorylcholine are together strong protection markers for atherosclerosis in systemic lupus erythematosus: Regulation and underlying mechanisms.

OBJECTIVES: Phosphorylcholine (PC) and malondialdehyde (MDA) are generated during lipid peroxidation and form adducts with proteins as albumin as studied herein. Atherosclerosis and cardiovascular disease (CVD) are increased in systemic lupus erythematosus (SLE). We here investigate the role and regulation of IgM antibodies against PC (anti-PC) and MDA (anti-MDA). METHODS: IgM anti-PC and anti-MDA in SLE patients (n=114) were compared with age- and sex-matched population-based controls (n=108). Common carotid intima-media thickness (IMT) and plaque occurrence were determined by B-mode ultrasound. Plaques were graded according to echogenicity (potentially vulnerability). Production of IgM anti-PC and anti-MDA by B cells was determined by ELISA and ELISPOT. The effect of anti-PC and anti-MDA on macrophage uptake of apoptotic cells and oxidative stress was studied by flow cytometry. RESULTS: Above 66rd percentile together, IgM anti-PC and anti-MDA were striking protection markers for plaque prevalence and echolucency in SLE (OR: 0.08, CI: 0.01-0.46 and OR: 0.10, CI: 0.01-0.82), respectively, and risk markers for plaque prevalence when below 33rd percentile: OR: 3.79, CI: (1.10-13.00). In vitro, IgM anti-PC and anti-MDA were much higher when B cells were co-cultured with CD3 T cells. Anti-HLA-, anti-CD40 antibody or CD40 silencing abolished these effects. Uptake of apoptotic cells was increased by IgM anti-PC and anti-MDA. MDA induced increased oxidative stress, which was inhibited by IgM anti-MDA. CONCLUSIONS: Unexpectedly, both IgM anti-MDA and IgM anti-PC are T-cell dependent and especially together, are strong protection markers for atherosclerosis in SLE. Underlying mechanisms include increased phagocytosis of apoptotic cells and decrease of oxidative stress.

Discrepancies in recommended criteria for grading of carotid stenosis with ultrasound.

The accuracy of duplex ultrasound for grading of internal carotid artery stenosis has been widely tested and shown to be high. However, different methods for measurement of the degree of carotid stenosis with the golden standard conventional angiography have been used in the different studies. This, together with other factors, has led to some confusion regarding the relation between the ultrasonographically measured flow velocity and the angiographically measured degree of stenosis. The ultrasound criteria that are used in Sweden (and in Germany) differ in an important way from the criteria recommended in North America and the United Kingdom for the same degree of angiographic stenoses. Possible reasons for the discrepancies are discussed in this article. The authors recommend absolute agreement locally whether ECST or NASCET criteria shall be used in the communication between radiologists, clinical physiologists, vascular surgeons, neurologists and other physicians involved in patient management decisions. Angle-dependent ultrasound criteria should be used and flow velocity measurements with ultrasound should be combined with assessment of plaque burden on 2D picture.

Bone mineral density and carotid atherosclerosis in systemic lupus erythematosus: a controlled cross-sectional study.

INTRODUCTION: As osteoporosis is reported to be associated with atherosclerosis in the general population we examined the relationship between bone mass and carotid measurements in patients with systemic lupus erythematosus (SLE) and controls, and possible links between them in SLE. METHODS: In a cross-sectional study, 111 SLE-patient were compared with 111 age- and sex-matched controls, mean age 48.7(12.9) years, 89% were women, of which 51% postmenopausal. Carotid intima media thickness (cIMT), carotid plaque occurrence and echogenicity were determined by B-mode ultrasound and bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA). RESULTS: BMD and cIMT were inversely associated both in patients and controls. Patients, but not controls, with carotid plaque had higher cIMT at low BMD than at normal BMD, p = 0.010. Logistic regression indicated more than doubled odds ratio (OR) of carotid plaque in patients, particularly in post-menopausal women, than in controls in relation to all BMD measurements. For low BMD at hip, significant increased OR for echolucent plaque was shown for patients compared with controls. In patients, significant impact of age, body mass index, smoking, systolic blood pressure, blood lipids, diabetes mellitus, impaired renal function, low levels of complement C3 and C4, history of nephritis, SLE-damage index and ever use of antimalarial was found for association between BMD and higher cIMT and carotid plaque. In multivariate regression, low C4 was independent contributor to association between total BMD and upper cIMT tertile, accounted for OR (95% confidence interval) of 3.2 (1.03-10.01), and also for association with bilateral carotid plaque, OR of 4.8 (1.03-22.66). The contribution of low C4 for the association between BMD and carotid atherosclerosis was enhanced within the second and third tertiles of total BMD. CONCLUSION: This study is the first to demonstrate inverse association between BMD and carotid measurements in both SLE-patients and controls. Our results suggest that SLE-patients may suffer higher burden of (sub)clinical atherosclerotic disease, especially presence of both echolucent and echogenic plaque, than controls with the same bone mineral status. Low complement C4 seems to play an important role in earlier development of carotid atherosclerosis already within (sub)normal ranges of total BMD in patients.

Conventional treatment after myocardial infarction in routine clinical practice results in regression of left common carotid intima-media thickness.

This study aimed to evaluate the effect of standard medical treatment on the progression of atherosclerosis after a myocardial infarction, in an ordinary clinical setting, by measuring the right and left common carotid intima-media thickness (IMT). The first investigation took place 3-12 months after the index event; the second took place 3·3-8·2 years after the first. In both investigations, the right and left carotid arteries of 102 patients were examined with an ultrasound duplex scanner. Common carotid IMT and calculated cross-sectional intima-media area (cIMa) were measured on both sides. More than 90% of the patients were treated with aspirin, beta-blockers and statins. In the first investigation, IMT and cIMa were significantly greater on the left side compared to the right (IMT: 0·83 ± 0·22 and 0·74 ± 0·18 mm, P<0·001; cIMa: 18·2 ± 5·2 and 16·3 ± 5·1 mm(2) , P<0·001). In the second investigation, IMT on the left side was significantly reduced compared to the first investigation (0·79 ± 0·22 and 0·83 ± 0·22 mm, P<0·05) with a corresponding tendency towards a decrease in cIMa on the same side. In our study, conventional medical treatment after a myocardial infarction in ordinary clinical routines resulted in regression of the common carotid IMT on the left side. The significant side difference in IMT emphasizes the importance of where and how the carotid IMT is measured in studies using this surrogate end point.

Low levels of antibodies against oxidized but not nonoxidized cardiolipin and phosphatidylserine are associated with atherosclerotic plaques in systemic lupus erythematosus.

OBJECTIVE: We have reported that the prevalence of atherosclerotic plaques and their echolucency was increased in systemic lupus erythematosus (SLE). We here study antibodies against oxidized cardiolipin (anti-OxCL) and phosphatidylserine (anti-OxPS) in SLE and in relation to atherosclerosis measures. METHODS: Patients with SLE (n = 114) were compared with age- and sex-matched population-based controls (n = 122). Common carotid intima-media thickness and plaque occurrence were determined by B-mode ultrasonography. Plaques were graded according to echogenicity as 1-4, with 1 being echolucent. Antibodies were determined by ELISA. RESULTS: In the SLE group, the prevalence of low IgM anti-OxPS and low total IgM levels (below 33rd percentile) was increased compared to controls (p = 0.045 and p = 0.0079, respectively). Among SLE patients with atherosclerotic plaques, the prevalence of low IgM anti-OxPS (p = 0.0019) and anti-OxCL (p = 0.031) was increased. Only IgM anti-OxPS remained significant (p = 0.019) after adjusting for other significant factors. Echolucent plaques (total, or left side) were more prevalent among SLE patients with low IgM anti-OxCL and anti-OxPS when controlled for other significant factors (p < 0.05). Low total IgM was independently associated with echolucent plaque on left side (p < 0.05), but not other atherosclerosis measures. IgM anticardiolipin antibodies (aCL) and antiphosphatidylserine antibodies (anti-PS) were higher among SLE patients with cardiopulmonary disease, including arterial, valvular, and venous disease (p < 0.05). There were no associations between antibodies and other disease manifestations or activity. Both anti-OxCL and anti-OxPS, in contrast to aCL, and anti-PS, were cofactor-ß2-glycoprotein I (ß2-GPI)-independent. CONCLUSION: The prevalence of low levels of IgM anti-OxCL and anti-OxPS (both cofactor-ß2-GPI-independent) is associated with the presence of plaques and echolucent plaques in SLE.

Echogenicity of the carotid intima-media complex and cardiovascular risk factors.

INTRODUCTION: Increased carotid intima-media thickness (IMT) has been associated with increased risk of myocardial infarction (MI) and stroke. A measure of echogenicity, the grey scale median (GSM), has been shown to be inversely correlated with cardiovascular risk factors and to be predictive of mortality in a community-based cohort. We assessed the factors associated with carotid IM-GSM in younger, non-diabetic patients with a recent MI. METHODS AND RESULTS: A total of 122 patients (women, 25%) aged 31-80 years (61) were recruited 2-3 days after an acute MI. Ultrasound examinations of the carotid arteries were performed 1-12 months after the MI. IMT was 0·78 (SD 0·17) mm on the right side and 0·81 (0·20) mm on the left side (P = 0·05). GSM was 88·60 (range 46-132, SD 18·32) on the right side and 82·10 (40-126, 17·89) on the left side (P = 0·002). Triglycerides (TG) correlated with GSM on both sides (right, r = -0·27, P = 0·003; left, r = -0·18, P = 0·05). On the right side, GSM was 92·15 and 82·26 (P = 0·05) in patients with TG < and ≥1·7, and on the left side, it was 84·04 and 74·55 (P = 0·02) in patients with TG < and ≥2·3. On multivariate analysis, TG were significantly associated with GSM, both on the right side (P = 0·01) and on the left side (P = 0·009). CONCLUSION: We found a negative association between TG and carotid IM-GSM on both sides in patients with a recent MI. Our results also suggest that atherosclerosis progression may be faster on the left side in patients with coronary heart disease.

Carotid atherosclerosis, disease measures, oxidized low-density lipoproteins, and atheroprotective natural antibodies for cardiovascular disease in early rheumatoid arthritis -- an inception cohort study.

OBJECTIVE: Although an enhanced risk of cardiovascular disease (CVD) in persons with rheumatoid arthritis (RA) is well established, the mechanisms behind it remain unclear. We studied whether carotid atherosclerosis, RA disease measures, or potential cardiovascular biomarkers influenced the incidence of CVD in an RA inception cohort. METHODS: RA disease measures and CVD biomarkers were assessed at 0, 3, 12, 24, and 60 months after disease onset, and carotid ultrasonography after 5 years. The study outcome was incident CVD events - acute myocardial infarction, angina pectoris, congestive heart failure, or ischemic cerebrovascular event. Survival analysis and Cox and longitudinal regressions were used for statistical analyses. RESULTS: A total of 105 patients, without CVD events prior to RA onset, experienced 17 CVD events, an incidence rate of 1.35 events per 100 person-years (95% CI 0.71-2.0). The rate of CVD events did not differ with regard to measures of carotid intima-media thickness, but it was higher for patients with bilateral carotid plaques than for those without (p = 0.012). Improvement in Disease Activity Score for 28 joints, visual analog scale for pain, and Stanford Health Assessment Questionnaire score over the first year, as well as usage of methotrexate (MTX), was associated, independent of age, with reduction of risk of CVD event [hazard ratios 0.68 (95% CI 0.5-0.97), 0.97 (95% CI 0.95-0.99), 0.35 (95% CI 0.15-0.82), and 0.34 (95% CI 0.12-0.91), respectively]. In longitudinal analyses, increasing oxidized low-density lipoprotein (oxLDL) and probability for low antiphosphorylcholine antibodies (anti-PC) were observed in those who experienced a subsequent CVD event. CONCLUSION: Bilateral carotid plaques were associated with poor CVD-free survival. Early reductions of inflammation, pain, and disability as well as MTX usage were associated with better CVD outcome. Elevated oxLDL and low IgM anti-PC levels may link chronic inflammation in RA to enhanced risk of CVD events.

C-reactive protein in relation to early atherosclerosis and periodontitis.

Periodontitis may affect atherosclerosis via the chronic inflammation. We investigated high-sensitivity C-reactive protein (hsCRP) in relation to early vascular atherosclerotic changes in non-symptomatic subjects with and without long-term periodontitis. Carotid ultrasonography with calculation of common carotid artery intima-media area (cIMA) was performed, and hsCRP and atherosclerosis risk factors were analysed in randomly chosen 93 patients with periodontitis and 41 controls. The relationship between hsCRP, cIMA and atherosclerosis risk factors was evaluated with multiple logistic regression analysis. Women displayed lower hsCRP (p < 0.05) and higher serum HDL (p < 0.001) than men. In all patients with periodontitis, cIMA values were higher than in controls. Periodontitis appeared to be a major predictor for increased cIMA (odds ratio, 3.82; 95% confidence interval, 1.19-12.26). Neither of these factors was significantly associated with hsCRP which thus appeared not sensitive enough to be a marker for periodontitis or atherosclerosis. Hence, irrespective of low hsCRP levels, periodontitis appeared to increase the risk for atherosclerosis.

Use of annual ABPM, and repeated carotid scan and echocardiography to monitor cardiovascular health over nine yr in pediatric and young adult renal transplant recipients.

In adult hypertensive patients, increased cIMT and LVH are independent risk factors for cardiovascular events. We have previously observed that in pediatric RTRs with tight control of BP, cIMT did not progress over time. This investigation is an extension of the aforementioned study aimed at re-examining cIMT and also reporting serial echocardiography results. Twenty-two RTRs aged 9.4 ± 3.3 yr at their baseline carotid scan underwent two additional vascular ultrasounds during a follow-up of 9.1 ± 0.9 yr. Carotid scan and echocardiography examinations were carried out simultaneously with ABPM. Antihypertensive therapy was determined according to the recipient's ABPM results, which were performed at yearly intervals. Baseline cIMT was significantly greater in RTRs than in healthy controls. There was no statistical evidence of systematic changes in cIMT over time. At the last examination, 14 of 17 RTRs with treated hypertension had controlled hypertension (prevalence 82%; 95% CI, 56.5-96.2), and the overall prevalence of LVH was 4.5% (95% CI, -0.01 to 23.5). The lack of progression of cIMT over time and the low prevalence of LVH might reflect the effect of long-standing BP control.

Longitudinal levels of apolipoproteins and antibodies against phosphorylcholine are independently associated with carotid artery atherosclerosis 5 years after rheumatoid arthritis onset--a prospective cohort study.

OBJECTIVE: RA is associated with premature atherosclerosis. Here, we determined the associations of apolipoproteins and immunoglobulin M (IgM) antibodies against phosphorylcholine (anti-PC) with carotid artery atherosclerosis in a prospective cohort of patients with early RA. METHODS: In all 114 patients, age 50.6 (11.2) years, 68.4% women, with recent RA (<12 months after symptoms onset) were included and assessed at 0, 3, 12, 24 and 60 months after RA diagnosis. At the same time points, apolipoproteins were determined by immunoturbidimetry, and IgM anti-PC by ELISA. Carotid intima-media thickness (cIMT) (common carotid) and occurrence of plaques (common, internal and external carotids) were the principal study outcomes, which were examined with high-resolution B-mode ultrasonography after 5 years of RA disease. Mixed linear modelling and generalized estimating equations (GEEs) were used for longitudinal statistical analyses. RESULTS: Multivariate regression analyses showed that age, male gender, smoking (ever) and history of cardiovascular disease (CVD), hypertension or diabetes mellitus, but no other baseline variables, had independent associations with cIMT (P < 0.05). Plaque detection was positively associated with age and smoking (ever). After adjustment, a longitudinal approach demonstrated an independent negative prediction of cIMT by apoA1 (P = 0.047), but a positive by apoB/apoA1 ratio (P = 0.030). Higher levels of pro-atherogenic apolipoproteins over time, apoB and apoB/apoA1 ratio, and low anti-PC tertile were independently associated with enhanced detection of bilateral carotid plaque (P = 0.002, 0.026 and 0.000, respectively). Both baseline and longitudinal levels of inflammatory/disease-related factors failed to show significant associations with the study outcomes. CONCLUSION: Apolipoproteins and anti-PC may have independent roles in subclinical atherosclerosis in patients with RA.

Increased prevalence of vulnerable atherosclerotic plaques and low levels of natural IgM antibodies against phosphorylcholine in patients with systemic lupus erythematosus.

INTRODUCTION: The risk of cardiovascular disease (CVD) and atherosclerosis is reported to be increased in systemic lupus erythematosus (SLE). We recently reported a negative association between natural IgM-antibodies against phosphorylcholine (anti-PC) in the general population, high anti-PC levels leading to decreased atherosclerosis development and low levels to increased risk of CVD. Potential mechanisms include anti-inflammatory properties and inhibition of uptake of oxidized low density lipoprotein (LDL) in macrophages. The objective herein was to study atherosclerosis in SLE in detail and in relation to traditional and non-traditional risk factors. METHODS: A total of 114 patients with SLE were compared with 122 age- and sex-matched population-based controls. Common carotid intima-media thickness (IMT), calculated intima-media area (cIMa) and plaque occurrence were determined by B-mode ultrasound as a surrogate measure of atherosclerosis. Plaques were graded according to echogenicity and grouped as 1 to 4, with 1 being echoluscent, and considered most vulnerable. Anti-PC was studied by ELISA. RESULTS: Hypertension, triglycerides and insulin resistance (determined by homeostasis model assessment of insulin resistance) and C-reactive protein (CRP) were increased in SLE (P < 0.01) while smoking, LDL, high density lipoprotein (HDL) did not differ between groups. Low levels of anti-PC IgM (lowest tertile) were more common in SLE patients than in controls (P = 0.0022). IMT and cIMa did not differ significantly between groups. However, plaques were more often found in SLE patients (P = 0.029). Age, LDL and IgM anti-PC (lowest tertile) were independently associated with plaque occurrence in SLE. Further, in the left carotid arteries echoluscent plaques (grade 1) were more prevalent in SLE as compared to controls (P < 0.016). CONCLUSIONS: Plaque occurrence in the carotid arteries is increased in SLE and is independently associated with age, LDL and low anti-PC levels. Vulnerable plaques were more common in SLE. Anti-PC could be a novel risk marker also with a therapeutic potential in SLE.

Intima-media thickness of common carotid and brachial arteries and prothrombin fragment 1 + 2 are associated with left ventricular diastolic dysfunction in patients with myocardial infarction.

AIMS: To investigate the association between intima-media thickness of brachial and common carotid arteries and factors of the coagulation- and fibrinolysis-system with left ventricular diastolic dysfunction in patients with a previous myocardial infarction. PATIENTS AND METHODS: One hundred and twenty three patients, men (76%) and women (24%) aged between 32 and 81 years with a history of previous acute myocardial infarction were included. B-mode ultrasound of common carotid and brachial arteries and echocardiography with tissue Doppler imaging (TDI) were evaluated. Factors of the coagulation- and fibrinolysis-system were also measured. RESULTS: In patients with previous myocardial infarction, late diastolic filling time was significantly and positively associated with log Prothrombin fragment 1 + 2 (P < 0.001) and with calculated intima-media area (cIMa) of the both common carotid and brachial arteries (P < 0.05). Mitral early-to-late flow velocity ratio (E/A) was significantly and negatively associated with log Prothrombin fragment 1 + 2 (P < 0.001), total cholesterol and cIMa of the both common carotid and brachial arteries (P < 0.05). Moreover both late diastolic filling time and mitral E/A correlated significantly with age and systolic blood pressure. In stepwise multiple regression analysis, log Prothrombin fragment 1 + 2 remained the only variable with independent significant correlation to late diastolic filling time and mitral E/A. CONCLUSIONS: In a population sample of patients with myocardial infarction, late diastolic filling time and mitral E/A were associated with cIMa of common carotid and brachial arteries, systolic blood pressure, and prothrombin fragment 1 + 2, suggesting a relationship between diastolic dysfunction, thrombin generation and atherosclerosis.

Prothrombin fragment 1 + 2 is associated with intima media thickness of the carotid artery in patients with myocardial infarction.

BACKGROUND AND AIM: Previous studies have shown that a decreased fibrinolytic activity or a hyperactivated coagulation system increase the risk of myocardial infarction. The aim of this study was to investigate the relationship between the presence of atherosclerotic lesions and coagulation and fibrinolysis factors and high sensitivity CRP (hs-CRP) in patients with myocardial infarction. METHODS: In a cross-sectional study, 123 patients, aged 31-80 years, with a history of previous myocardial infarction were examined with B-mode ultrasound of the common carotid artery. Blood samples were collected for measurements of fibrinogen, plasminogen activator inhibitor-1 activity (PAI-1), von Willebrand factor (vWF), prothrombin fragment 1 + 2 and hs-CRP. RESULTS: Prothrombin fragment 1 + 2 and hs-CRP were significantly (p<0. 05) and positively associated with common carotid artery intima media thickness (IMT). PAI-1 was significantly (p<0.05) and negatively associated with IMT. IMT was also significantly associated with systolic blood pressure and age. When IMT was used as an dependent variable and systolic blood pressure, age, PAI-1 and prothrombin fragment 1 + 2 were used as independent variables in the multiple stepwise regression analysis a significant and independent relationship was observed between IMT and systolic blood pressure and age (p<0.05). CONCLUSION: The levels of prothrombin fragment 1 + 2 and hs-CRP are associated with intima media thickness in the common carotid artery in patients with previous history of myocardial infarction.

Prospective analysis of carotid arterial wall structure in pediatric renal transplants with ambulatory normotension and in treated hypertensive recipients.

Increased carotid IMT was found to be associated with cardiovascular risk factors. As pediatric renal transplants are at high risk for cardiovascular disease, we examined whether there is a relationship between BP and IMT in normotensive and in treated hypertensive recipients after transplantation. Thirty-one recipients aged 10 +/- 3.5 yr (16 M, 15 F) underwent repeated carotid ultrasound examinations 5.4 +/- 3.2 yr after transplantation with a 4.1 +/- 1 yr interval and were followed with annual ambulatory BP monitoring. Baseline IMT was significantly higher in transplants compared with controls. When recipients were again investigated, follow-up IMT measurements were similar compared with measurements obtained at baseline. The analysis of variance showed that baseline IMT both in recipients with strict normotension, i.e., ambulatory normotension without antihypertensive therapy at baseline and throughout the study period (n = 9), and in recipients with treated hypertension or newly diagnosed hypertension (n = 22) was significantly higher than in healthy controls (n = 21). Baseline IMT did not differ between these subgroups of recipients. Similarly, pairwise comparisons showed that baseline and follow-up IMT within each subgroup of recipients were not significantly different. Overall and regardless of time-point, no significant associations were found between systolic and diastolic 24-h BP, daytime BP, night-time BP, ambulatory BP standard deviation scores, BP loads and IMT. Our results suggest that increased IMT in pediatric renal transplants does not seem to be related to BP but more likely to other factor(s) not investigated in this study.

The optimal cuff width for measuring toe blood pressure.

To determine the optimal cuff width for measuring toe blood pressure in patients with lower limb ischemia, this experimental prospective study examined 20 patients with symptoms of peripheral arterial disease referred for vascular examination or vascular surgery. Toe blood pressure was measured hydrostatically by the pole test using cuffs of different widths. Pole test reflects the true physiological blood pressure value and was the reference method. Blood pressures obtained using the cuffs were related to this value and to patients' toe circumference. With the 2.5-cm cuff, the patients had a mean pole test toe blood pressure of 28 mm Hg (range, 6-55 mm Hg). Compared with pole test results, the toe blood pressure was 15.6 mm Hg (95% confidence interval [CI], 8-23 mm Hg) higher when measured using the 2.0-cm cuff (P < .001) and 4.5 mm Hg (95% CI, 0-9 mm Hg) higher when measured using the 2.5-cm cuff (P = .07). Using the 1.5-cm and 3.0-cm cuffs, the differences were 27.0 mm Hg (95% CI, 13-43 mm Hg) and -2.0 mm Hg (95% CI, -11 to 8 mm Hg), respectively. The cuff width greatly affects the obtained toe blood pressure value, and larger cuffs correspond better to the hydrostatic pressure. For clinical use and as a reporting standard, we propose that toe blood pressure measurements should be made using a 2.5-cm-wide cuff.

Effects of low-dose prednisolone on endothelial function, atherosclerosis, and traditional risk factors for atherosclerosis in patients with rheumatoid arthritis--a randomized study.

OBJECTIVE: To determine the influence of low-dose prednisolone on atherosclerosis, endothelial function, and risk factors for atherosclerosis in patients with early rheumatoid arthritis (RA). METHODS: At start of the first disease modifying antirheumatic drug, 67 patients with early, active RA were randomized to either 7.5 mg prednisolone daily (n = 34) or no prednisolone (n = 33). In the prednisolone group, 21 were treated for 2 years and 13 continuously. After a mean of 5 years intima-media thickness (IMT) and calculated intima-media area (cIMa) of the carotid arteries were determined by B-mode ultrasound. Endothelial function was determined by flow-mediated dilatation (FMD) of the brachial artery. RESULTS: IMT [median (interquartile range) 0.675 mm (0.58-0.82) vs 0.673 mm (0.0.62-0.80)], cIMa [13.7 mm2 (11.45-20.37) vs 14.1 mm2 (12.34-17.38)], prevalence of atherosclerotic plaques (82.3% vs 81.9%), and endothelial function [FMD% (mean +/- SD) 3.88% +/- 2.8 vs 3.74% +/- 2.9] did not differ between patients treated with and those not treated with prednisolone. There were no differences in lumen diameter of carotid arteries, or levels of lipoproteins, glucose, and blood pressure. Patients treated for at least 4 years (and currently treated) with prednisolone had a trend to higher systolic blood pressure (157 +/- 29 mm Hg) compared with untreated patients (141 +/- 28 mm Hg; p = 0.06) and had higher cholesterol levels (5.6 mmol/L +/- 1.39 vs 4.9 +/- 28; p = 0.03). In the whole cohort, age and HDL were independently associated with IMT; age, HDL, and blood pressure with cIMa; and age and serum creatinine with presence of atherosclerotic plaques. CONCLUSION: Low-dose prednisolone did not influence endothelial function and atherosclerosis in patients with RA. However, total cholesterol was higher in patients treated with prednisolone.

Duplex ultrasonography is an efficient diagnostic tool for the detection of moderate to severe internal carotid artery stenosis.

BACKGROUND: The aim of this prospective national multicentre study with 10 participating university and county hospitals was to establish the diagnostic accuracy of carotid duplex sonography in the identification of >or=70% internal carotid artery (ICA) stenosis defined according to European Carotid Surgery Trial (ECST) criteria. METHODS: In 134 patients, aged 69 +/- 9 years, ICA stenoses were identified by routine carotid duplex ultrasonography, confirmed angiographically within 2 months, and graded according to ESCT criteria. The accuracy of carotid duplex to detect ICA stenosis >or=70% was assessed using receiver operating characteristic (ROC) analysis with carotid angiography as a reference. RESULTS: Measurement of peak systolic velocity in ICA (PSV(ICA)) identified ICA stenosis >or=70% with high diagnostic accuracy that was Doppler angle dependent resulting in different optimal PSV(ICA) cut points within the angle range 0 degrees -49 degrees (1 x 7 m s(-1)) and 50 degrees -62 degrees (2 x 3 m s(-1)). The diagnostic discrimination was significantly better when narrow Doppler angles (0 degrees -49 degrees ) were used (P<0 x 01) providing the sensitivity of 98 +/- 2% and specificity of 94 +/- 4%. DISCUSSION: Ultrasound duplex technique identifies moderate to severe (>or=70%) ICA stenoses (ECST criteria) with high degree of accuracy that can be further improved by the use of Doppler angle specific optimal PSV(ICA) cut points.

Increased leukotriene concentrations in gingival crevicular fluid from subjects with periodontal disease and atherosclerosis.

Recent studies indicate that periodontal disease is associated with the development of early atherosclerotic lesions in the carotid artery. Since inflammation is a key feature in both atherosclerosis and periodontal disease, a common mediator of the two diseases could be anticipated. Leukotrienes are lipid-derived inflammatory mediators recently implicated in the pathogenesis of atherosclerosis and previously shown to be produced in periodontitis. The aim of the present study was to detect leukotrienes in gingival crevicular fluid (GCF) from subjects with atherosclerosis. Carotid ultrasonography and oral clinical examination were performed in 19 periodontitis patients and 16 healthy subjects. Atherosclerotic plaques were detected on ultrasound examination in 13 subjects with periodontis, and in 5 of the healthy subjects. Elevated concentrations of leukotriene B(4) and cysteinyl-leukotrienes were detected in GCF from subjects with a high dental plaque index (PLI>0.3), supporting an increased leukotriene formation in periodontitis. In addition, subjects with atherosclerotic plaques had significantly elevated concentrations of cysteinyl-leukotrienes in their GCF as compared with subjects without a visible plaque. Finally, the increased cysteinyl-leukotriene concentrations in GCF from atherosclerotic subjects were observed also when sub groups of periodontis patients and healthy subjects were compared separately. In summary, increased GCF concentrations of cysteinyl-leukotrienes were correlated to measures of both periodontitis and atherosclerosis. These results suggest that increased leukotriene formation may represent a possible link between periodontitis and atherosclerosis and a risk factor marker for both diseases.