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.

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.

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.

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.

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.

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.

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.

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.

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 local arteriosclerosis on carotid baroreflex sensitivity and on heart rate and arterial pressure variability in humans.

The study examined whether the alterations in heart rate variability (HRV) and baroreflex sensitivity (BRS) observed in patients with coronary artery disease can also be discerned in otherwise healthy subjects with mild-to-moderate arteriosclerosis in the carotid artery bifurcation. Based on the results of carotid duplex ultrasonography, subjects were designated as either having no arteriosclerotic lesions (n = 18), unilateral (n = 19) or bilateral lesions (n = 18) in the bifurcation. Electrocardiograms were recorded and simultaneous and continuous records of arterial pressure were obtained. Resting HRV was determined by calculating the spectral power density in three frequency bands: 0-0.05 Hz [very low frequency (VLF) band], 0.05-0.15 [low frequency (LF) band] and 0.15-2 Hz (high frequency band), whereas the arterial pressure variability (APV) was determined from spectral power density of the VLF and LF bands. Carotid BRS was evaluated by measuring R-R intervals during application of pulse-synchronous graded pressures (40 to -65 mmHg) in a neck-chamber device. Analysis of variance revealed no effect of mild-to-moderate carotid arteriosclerosis on the spectral components of HRV and APV or on BRS. It thus appears that mild-to-moderate asymptomatic carotid arteriosclerosis does not affect carotid BRS, APV or HRV at rest.

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.

Early carotid atherosclerosis in subjects with periodontal diseases.

BACKGROUND AND PURPOSE: There is growing experimental evidence implicating chronic inflammation/infection as an atherosclerotic risk factor. In this study, the involvement of periodontal disease in the development of early atherosclerotic vascular lesions has been evaluated. METHODS: In randomly chosen 82 patients with periodontal disease and 31 periodontally healthy individuals subjected to a clinical oral examination in 1985, atherosclerotic risk factor analysis and carotid ultrasonography was performed during reexamination 16 years later. Common carotid artery intima-media thickness (IMT) and lumen diameter were measured and intima-media area (cIMA) was calculated. The relationship between IMT and cIMA as dependent variables and periodontal disease, age, gender, body mass index, heredity for atherosclerosis, diabetes mellitus, hypertension, plasma cholesterol, smoking, and education as independent variables was evaluated in a multiple logistic regression model. RESULTS: The mean values of IMT and cIMA were significantly higher in patients with periodontal disease than in controls, both at the right (P<0.01 and P<0.001, respectively) and left side (P<0.001 for both variables). When the means of the bilateral measurements of these 2 ultrasonographic variables were tested, multiple logistic regression analysis identified periodontal disease as a principal independent predictor of the common carotid artery cIMA (odds ratio [OR], 5.20; P=0.003) and IMT (OR, 4.64; P=0.004). CONCLUSIONS: The present results indicate that periodontal disease is associated with the development of early atherosclerotic carotid lesions.

Interrelation between the extent of atherosclerosis in the thoracic aorta, carotid intima-media thickness and the extent of coronary artery disease.

Intima-media thickness (IMT) of the common carotid artery and atherosclerosis of the thoracic aorta have been shown to correlate with coronary artery disease (CAD). This study compares the relation between wall changes in the thoracic aorta and the carotid arteries and the angiographic severity and extent of atherosclerotic lesions in the coronary arteries in patients with verified CAD. Atherosclerotic wall changes in the carotid arteries and the thoracic aorta were measured by B-mode ultrasonography and transesophageal echocardiography (TEE), respectively, in 37 subjects aged 65+/-10 years with angiographically verified CAD. The mean value of the common carotid IMT of the right and left sides was 0.87+/-0.21 mm. All subjects had carotid plaques. TEE detected grades II-IV atherosclerotic plaques in the thoracic aorta in 32 of the 37 (86%) patients. A significant correlation was seen between the extent of coronary artery stenosis and aortic plaques score (r=0.46, p=0.008). Mean carotid IMT was also significantly correlated with coronary artery stenosis extent score (r=0.44, p=0.007). Moreover, a significant correlation was seen between the aortic plaque score and the mean carotid IMT (r=0.39, p=0.02). In conclusion, we found a clear and significant relationship between wall changes in the thoracic aorta, common carotid IMT and the angiographic extent of coronary artery stenosis in patients with severe CAD. These findings indicate a potential of B-mode ultrasonography of the carotid arteries and transesophageal echocardiographic aortic examination in the diagnostic and prognostic evaluation of patients with suspected CAD.

Intima-media complex of both the brachial artery and the common carotid artery are associated with left ventricular hypertrophy in patients with previous myocardial infarction.

OBJECTIVES: Prospective trials have established intima-media thickness (IMT) of the carotid artery, flow-mediated dilation (FMD) of the brachial artery and cardiac left ventricular hypertrophy (LVH) as predictors of cardiovascular events. The aim of this study was to examine the relationship between intima-media complex of the brachial artery to FMD, intima-media complex of the common carotid artery and cardiac hypertrophy in patients with coronary heart disease. METHODS AND PROCEDURES: Cross-sectional design. Procedures were undertaken within the Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden. A total of 123 patients with a previous acute myocardial infarction (MI) were investigated. Calculated intima-media area (cIMa) of the brachial and common carotid arteries and FMD of the brachial artery and left ventricular dimensions were examined. RESULTS: The brachial cIMa was significantly associated with age, p-triglycerides, common carotid cIMa, ejection fraction, septum thickness, posterior wall thickness and left ventricular mass index (P < 0.05). Brachial cIMa also tended to be associated with systolic blood pressure (P = 0.056). Common carotid cIMa was significantly associated with age, systolic blood pressure, brachial cIMa, FMD and septum thickness (P < 0.05). FMD was significantly associated with age and carotid cIMa (P < 0.05). CONCLUSION: Both cIMa of the common carotid artery and the cIMa of the brachial artery were independently and significantly associated with ventricular septum thickness of the heart in patients with previous myocardial infarction.

Morphological changes rather than flow-mediated dilatation in the brachial artery are better indicators of the extent and severity of coronary artery disease.

OBJECTIVES: The aim of this study was to examine the relationship between morphological and functional parameters of the brachial and carotid arteries and the angiographic extent and severity of coronary artery stenosis in patients with severe coronary artery disease (CAD). DESIGN: A cross-sectional study. SETTING: University hospital. MAIN OUTCOME MEASURES: Flow-mediated dilatation (FMD), intima-media thickness (IMT) in the brachial artery and atherosclerotic wall changes in the carotid arteries were measured by B-mode high-resolution ultrasound in 58 patients who had undergone coronary angiography. RESULTS: A significant correlation was seen between the extent of coronary artery stenosis defined as the coronary angiographic score and both the mean brachial artery IMT and intima-media area (IMa; P = 0.01 and P = 0.04, respectively). There was no significant correlation between FMD and the extent of coronary artery stenosis. A significant correlation was seen between the mean carotid artery IMT and the mean brachial artery IMT (r = 0.30, P = 0.03). However, there was no significant correlation between FMD and the mean carotid artery IMT or IMa (r = 0.16, P = 0.23 and r = 0.17, P = 0.24, respectively). CONCLUSIONS: Morphological but not functional parameters of the brachial artery are associated with the extent of coronary artery stenosis and atherosclerotic wall changes in the carotid arteries in patients with severe CAD. These findings indicate a potential of B-mode ultrasonography of morphological parameters in the brachial artery in the diagnostic and prognostic evaluation of patients with suspected CAD.

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.

Elevated interleukin-6 predicts progressive carotid artery atherosclerosis in dialysis patients: association with Chlamydia pneumoniae seropositivity.

The cardiovascular mortality rate is unacceptably high in patients with end-stage renal disease (ESRD), which suggests an accelerated atherogenic process. The cause(s) of the accelerated atherogenesis in ESRD patients are not known, though recent studies suggest that persistent infection, such as Chlamydia pneumoniae, and proinflammatory cytokines may contribute. Forty-five ESRD patients (26 men) aged 51 +/- 2 years was studied at a time-point close to start of dialysis treatment and again after about 12 months of dialysis treatment. By using noninvasive B-mode ultrasonography, we evaluated changes in a surrogate marker of atherosclerosis, calculated intima media (cIM) area, in the common carotid artery. C-reactive protein (CRP), S-albumin, and interleukin-6 (IL-6) assessed the presence of an inflammatory reaction. We also measured C pneumoniae antibodies by microimmunofluorescence, nutritional status by subjective global assessment, lipid parameters, smoking habits, and the presence of comorbidity close to the start of dialysis. No significant changes in the prevalence of carotid plaques or the mean cIM area were observed during the first 12 months of dialysis. However, because some patients showed marked increases in the cIM area during only 12 months of dialysis we divided the patients into 2 groups: 23 nonprogressors ((delta)cIM area -2.7 +/- 0.4 mm2) and 22 progressors ((delta)cIM area 3.6 +/- 0.7 mm2). Sex, age, body mass index, comorbidity, blood lipid levels, S-albumin, and CRP levels did not differ significantly between the 2 groups. On the other hand, progressors had a significantly elevated basal median level of IL-6 (5.7 versus 3.1 pg/mL; P < 0.05) and an increased prevalence of positive (> or 1/64) immunoglobulin (Ig) A antichlamydia antibodies (59% versus 17%; P < 0.01) compared with nonprogressors. A significant positive (R = 0.41; P < 0.01) correlation was found between Log IL-6 and changes in the cIM area during 12 months of dialysis. In a stepwise multiple regression model, Log IL-6 did predict, independently (P < 0.01) of traditional risk factors and C pneumoniae antibodies, changes in the cIM area. These data suggest that a persistent chlamydial infection stimulates IL-6 levels, which in turn may be involved in the pathogenesis of accelerated carotid atherosclerosis in dialysis patients.

Micro- and macrocirculatory effects of apheresis in patients with familial hyperlipidemia.

High lipid levels have been shown to coexist with a disturbed vascular endothelial function. Thus, acute lipid lowering could be expected to improve vascular reactivity. Patients with familial hyperlipidemia (FH) have substantial and rapid decreases in lipid levels after low-density lipoprotein apheresis. Thus, an opportunity exists to study acute effects of lipid lowering on vascular reactivity. Flow mediated vasodilation (FMD) is commonly used to assess endothelial function in conduit vessels, whereas vital capillary microscopy during the post-reactive hyperemia (PRH) phase is used to assess response at the microvascular level. It is not known whether endothelial dysfunction is a general phenomenon in all kinds of vessels or if there are differences between micro- and macrovessels. In the present study, we were not able to demonstrate an improved vascular response after acute lipid lowering in FH patients. This was true both in the microcirculation (PRH) and in the conduit vessels (FMD). However, the two methods gave concordant results, demonstrating disturbed vascular reactivity in the patients as compared with healthy subjects. We have found no previous report with parallel assessments at the microcirculatory and macrocirculatory levels.

[Recommendations by the Swedish Quality Board for Carotid Surgery. Ultrasound good preoperative method for evaluating degree of carotid stenosis]. / Rekommendationer från Svenska kvalitetskommittén för karotiskirurgi. Ultraljud bra preoperativ metod för gradering av karotisstenos.

The estimated degree of carotid stenosis is decisive for the selection of patients who would benefit from surgical treatment. Carotid thrombendarterectomy is recommended in patients with symptomatic > or = 80 procent internal carotid artery stenosis (ECST method). Many vascular centers now often rely entirely on duplex ultrasonography to select the patients for carotid surgery. The results of a recently published Swedish multicenter study (Jogestrand et al., Eur J Vasc Endovasc Surg 2002; 23:510-8) demonstrate that certain technical aspects of the ultrasound examination are of importance for the estimation of the degree of stenosis. Based on these results, the Swedish Quality Board for Carotid Surgery recommends the use of Doppler angle range specific cut off points for the peak systolic velocity in the internal carotid artery for identification of high-grade internal carotid artery stenosis: These cut off points are > or = 2.1 m/s for insonation angles of 0-49 degrees and > or = 3.2 m/s for angles 50-60 degrees. The angle of insonation should be kept as small as possible and should always be stated in the investigators report.