Atherosclerosis in patients with biopsy-proven giant cell arteritis

OBJECTIVE: To examine the presence of atherosclerosis in a series of giant cell arteritis (GCA) patients attended to in a community hospital and to determine whether clinical features or steroid therapy might be associated with the development of atherosclerotic disease. METHODS: Forty consecutive patients diagnosed with biopsy-proven GCA, periodically followed at the rheumatology outpatient clinic of Hospital Xeral-Calde, Lugo (Spain), who had ended steroid therapy and had at least 3 years of followup were assessed for the presence of atherosclerosis by determination of the carotid intima-media thickness (IMT) and carotid plaques using high-resolution B-mode ultrasound. Forty matched controls were also studied. RESULTS: GCA patients exhibited less carotid artery IMT than did matched controls (mean +/- SD 1.01 +/- 0.16 mm versus 1.13 +/- 0.20 mm; P = 0.005; difference in means 0.12, 95% confidence interval 0.04-0.20). Patients who required steroid therapy for >2 years had greater mean +/- SD carotid IMT (1.04 +/- 0.17 mm versus 0.95 +/- 0.15 mm) but the difference was not statistically significant (P = 0.10). A positive correlation between age at the time of the study and the carotid artery IMT in GCA patients was observed (r = 0.673, P < 0.001). However, adjusting for age, sex, and classic atherosclerosis risk factors, no significant correlation between carotid IMT and the routine laboratory markers of inflammation assessed at the time of disease diagnosis, disease duration, or cumulative prednisone dose was found. CONCLUSION: The present study demonstrates that atherosclerotic macrovascular disease is not increased in patients with GCA.     

Lymphopenia is a risk factor in the progression of carotid intima‐media thickness in juvenile‐onset systemic lupus erythematosus

Objective

To characterize the atherosclerotic risk factors in the progression of subclinical atherosclerosis in patients with juvenile‐onset systemic lupus erythematosus (SLE).

Methods

This was a longitudinal study of 76 patients with juvenile‐onset SLE. Carotid arteries were evaluated using ultrasonography at baseline and at followup visits at 6‐month intervals over the 6‐year study period. Clinical and laboratory parameters, disease activity, treatment, and traditional risk factors for atherosclerosis were evaluated. Data were analyzed using generalized estimating equations.

Results

The mean ± SD age of the patients at baseline was 15.01 ± 3.48 years and the mean ± SD disease duration was 2.65 ± 2.5 years. The mean ± SD duration of followup was 3.74 ± 1.24 years. The mean ± SD intima‐media thickness (IMT) of the common carotid arteries differed significantly between the patient and control (n = 38) groups (0.63 ± 0.08 mm versus 0.54 ± 0.06 mm; P < 0.001). The presence of lymphopenia at diagnosis and at baseline and higher levels of serum creatinine and C‐reactive protein at baseline were positively associated with progression of carotid IMT (P = 0.006, P = 0.043, P = 0.037, and P = 0.049, respectively). In multivariate analysis, only lymphopenia at baseline and at diagnosis were consistently associated with progression of IMT (P = 0.012 and P = 0.045, respectively).

Conclusion

In patients with juvenile‐onset SLE, some nontraditional risk factors for the progression of subclinical atherosclerosis were identified. Lymphopenia was the only independent risk factor for the progression of IMT. The pathogenic mechanisms warrant further investigation.

     

锡伯族和汉族冠心病患者颈动脉粥样硬化及冠状动脉病变对比分析

目的 对比分析锡伯族、汉族冠心病患者颈动脉粥样硬化及冠状动脉病变情况.方法 对经冠状动脉造影明确的48例锡伯族、57例汉族冠心病患者和50例正常对照者均行颈动脉超声检查,比较各组间颈动脉内膜中膜厚度、斑块的发生率及冠状动脉病变的Gensini积分.结果 锡伯族、汉族冠心病患者内膜中膜厚度及颈动脉斑块的发生率均高于正常对照者(1.1±0.3 mm和1.0±0.1 mm比0.6±0.2 mm、88.3%和77.2%比38.0%,P<0.05),但锡伯族与汉族间比较没有统计学差异(P>0.05);锡伯族患者冠状动脉病变支数少于汉族(1.82±0.24比2.54±0.31, P<0.05),冠状动脉病变的Gensini积分也明显低于汉族(8.23±1.35比15.84±2.68,P<0.05),且冠状动脉病变支数越多,锡伯族、汉族冠心病患者颈动脉粥样硬化程度越重.结论 锡伯族和汉族冠心病患者颈动脉粥样硬化情况均重于正常对照者,但锡伯族和汉族间比较没有统计学意义;锡伯族和汉族冠心病患者冠状动脉病变存在差异,且锡伯族冠心病患者冠状动脉病变严重程度低于汉族;通过颈动脉内膜中膜厚度的程度可预测冠状动脉病变的存在及严重程度.     

老年女性冠心病患者颈动脉粥样硬化和血管内皮依赖性舒张功能的探讨

目的　观察老年女性冠心病患者颈动脉内中膜厚度 (IMT)、粥样斑块发生率及肱动脉内皮依赖性舒张功能的情况。方法　用高分辨超声技术对 89例老年女性行肱动脉血流介导的舒张功能 (FMD)、IMT及颈动脉粥样斑块的检测。结果　老年女性冠心病组FMD较对照组明显减弱 ,分别为 (3.5± 3.1) %及 (7.6± 3.5 ) % ,P <0 .0 0 1,老年女性冠心病组及对照组IMT分别为 (0 .88± 0 .2 0 )mm及 (0 .6 5± 0 .2 3)mm ,颈动脉粥样斑块发生率分别为 6 2 .2 %及11.4 % ,两组比较差异具有显著性意义 ,P <0 .0 0 1。结论　老年女性冠心病患者存在着严重的血管内皮依赖性舒张功能障碍以及颈动脉粥样硬化 ,颈动脉B超及肱动脉血流介导的舒张功能对老年女性冠心病患者有一定的预测价值。     

陈旧性心肌梗死患者颈动脉粥样硬化与危险因素的关系

为探讨陈旧性心肌梗死患者颈动脉粥样硬化情况，对38例陈旧性心肌梗死患者的颈动脉内中膜厚度及斑块进行超声检测，与32例健康者作对照。结果发现，陈旧性心肌梗死患者的颈动脉内中膜厚度、斑块指数及斑块发生率明显高于对照组。多因素回归分析显示，年龄、总胆固醇、收缩压与颈动脉内中膜厚度密切相关。     

Increased thickness of the arterial intima‐media detected by ultrasonography in patients with rheumatoid arthritis

Objective

To determine whether arterial wall thickening is advanced in rheumatoid arthritis (RA) patients compared with healthy controls by measuring the intima‐media thickness (IMT) of the common carotid and femoral arteries, and to evaluate the factors associated with arterial IMT in patients with RA.

Methods

We studied 138 RA patients and 94 healthy controls (matched for age, sex, and other major risk factors for atherosclerosis). IMT was measured on digitized still images of the common carotid and femoral arteries obtained by high‐resolution ultrasonography (10‐MHz in‐line Sectascanner). Laboratory variables relevant to RA activity were measured by routine methods. The degree of RA progression was assessed by scoring (Larsen method) metacarpophalangeal (MCP) joints on hand radiographs. Activities of daily living were determined by a modified Health Assessment Questionnaire (M‐HAQ) score, and physical activity levels were assessed by ultrasound measurement of the calcaneus (expressed as the osteo‐sono assessment index [OSI] Z score).

Results

Common carotid and femoral artery IMTs were significantly higher (P < 0.05) in RA patients (mean ± SD 0.641 ± 0.127 and 0.632 ± 0.125 mm, respectively) compared with controls (0.576 ± 0.115 and 0.593 ± 0.141 mm, respectively). Multiple regression analysis revealed a significant association between RA and the common carotid artery IMT. Moreover, the common carotid artery IMT in RA patients was positively associated with disease duration, the MCP joint Larsen score, and the M‐HAQ score, and was negatively associated with the calcaneus OSI Z score. No significant association was found between corticosteroid treatment and common carotid artery IMT.

Conclusion

RA patients exhibited greater thickness of the common carotid and femoral arteries than healthy controls. The duration and severity of RA and decreased activities of daily living, but not corticosteroid treatment, were independently associated with the increased arterial wall thickness.

     

高频超声评价颈动脉粥样硬化与冠状动脉病变的关系

目的利用高频超声检测颈动脉内中膜厚度(IMT)、斑块形成情况,并与冠状动脉(冠脉)病变程度的关系进行分析。方法应用ASPEN彩色多普勒超声诊断仪,对428例健康人(对照组)及89例冠心病患者(冠心病组)进行颈动脉IMT、斑块形成的检测。冠心病组患者以冠脉病变支数分为3个亚组。结果冠心病组患者颈动脉IMT为(1.19±0.14)mm,而对照组为(0.92±0.13)mm,(P<0.01);IMT增厚检出率及斑块形成检出率冠心病组为43.21%、74.65%,而对照组为14.49%、34.35%,(P<0.01)。1支冠脉病变组IMT为(1.00±0.014)mm,斑块形成检出率为42.86%;2支冠脉病变组IMT为(1.15±0.018)mm,斑块形成检出率为65.52%;3支及以上冠脉病变组IMT为(1.31±0.018)mm,斑块形成检出率为74.49%,(P<0.01)。结论颈动脉IMT增厚、斑块形成对冠心病具有预测价值;颈动脉IMT增厚、斑块形成与冠脉病变严重程度呈正相关。     

Elevated plasma asymmetric dimethyl‐L‐arginine levels are linked to endothelial progenitor cell depletion and carotid atherosclerosis in rheumatoid arthritis

Objective

Similarities between rheumatoid arthritis (RA) and atherosclerosis include endothelial dysfunction (an antecedent of plaque formation) and depletion of circulating bone marrow–derived endothelial progenitor cells. This study was undertaken to test the hypothesis that endothelial progenitor cell depletion and subclinical atherosclerosis in RA may be related to accumulation of an endogenous inhibitor of nitric oxide (NO) synthesis, asymmetric dimethyl‐L ‐arginine.

Methods

We studied 30 patients with active RA and 20 age‐ and sex‐matched healthy controls. Exclusion criteria were clinically evident atherosclerosis, traditional risk factors, hyperhomocysteinemia, and renal dysfunction. The blood endothelial progenitor cell count was assayed by flow cytometry and expressed as a percentage of lymphocytes. Plasma L ‐arginine, asymmetric dimethyl‐L ‐arginine, and symmetric dimethyl‐L ‐arginine were measured with liquid chromatography–mass spectrometry. Mean carotid intima‐media thickness (IMT) was assessed by B‐mode ultrasound.

Results

In RA patients, we found elevated levels of asymmetric dimethyl‐L ‐arginine (mean ± SD 0.49 ± 0.07 μmoles/liter versus 0.40 ± 0.07 μmoles/liter in controls; P < 0.001), a depressed endothelial progenitor cell count (0.039 ± 0.025% versus 0.063 ± 0.035%; P < 0.05), and increased IMT (0.65 ± 0.13 mm versus 0.55 ± 0.10 mm; P < 0.01), with no differences in levels of L ‐arginine or symmetric dimethyl‐L‐ arginine. The endothelial progenitor cell count was inversely correlated with the level of asymmetric dimethyl‐L ‐arginine. IMT was positively related to the ratio of asymmetric dimethyl‐L ‐arginine to L ‐arginine and negatively related to the endothelial progenitor cell count, in univariate and multivariate analyses.

Conclusion

Plasma asymmetric dimethyl‐L ‐arginine levels are elevated in RA patients free of cardiovascular disease or risk factors. Asymmetric dimethyl‐L ‐arginine accumulation may contribute to endothelial progenitor cell depletion via depressed NO‐dependent endothelial progenitor cell mobilization and/or survival, with consequent impairment of endothelial progenitor cell–mediated endothelial repair, which can promote atherogenesis in RA.

     

Atherosclerosis in systemic sclerosis: A systematic review and meta‐analysis

Objective

Systemic sclerosis (SSc) is characterized by calcification, vasculopathy, and endothelial wall damage, all of which can increase the risk of developing atherosclerosis and cardiovascular disease. The aim of this study was to perform a systematic review and meta‐analysis to determine whether the risk of atherosclerosis is increased in SSc patients compared to healthy individuals.

Methods

A systematic search was performed to identify studies published in PubMed and the Cochrane database up to May 2010, and recently published abstracts were also reviewed. Two reviewers independently screened articles to identify studies comparing the rate of atherosclerosis in SSc patients to that in healthy controls. The studies utilized one of the following methods: angiography, Doppler ultrasound to assess plaque and carotid intima‐media thickness (IMT), computed tomography, magnetic resonance imaging, flow‐mediated vasodilation (assessed as the FMD%), the ankle–brachial index, or autopsy. For carotid IMT and FMD% values, we computed a pooled estimate of the summary mean difference and explored predictors of carotid IMT using random‐effects meta‐regression.

Results

Of the 3,156 articles initially identified, 31 were selected for systematic review. The meta‐analysis included 14 studies assessing carotid IMT and 7 assessing brachial artery FMD%. Compared to healthy controls, SSc patients had a higher prevalence of coronary atherosclerosis, peripheral vascular disease, and cerebrovascular calcification. Meta‐analysis showed that SSc patients had increased carotid IMT (summary mean difference 0.11 mm, 95% confidence interval [95% CI] 0.05 mm, 0.17 mm; P = 0.0006) and lower FMD% (summary mean difference −3.07%, 95% CI −5.44%, −0.69%; P = 0.01) compared to controls. There was marked heterogeneity between the studies, which was mainly attributable to variations in disease duration and differences in the mean/median age between SSc patients and controls.

Conclusion

Patients with SSc have an increased risk of atherosclerosis compared to healthy subjects. Further studies should elucidate the mechanism of this increased risk.

     

Association of subclinical carotid atherosclerosis with immediate memory and other cognitive functions

Aim

To clarify whether carotid atherosclerosis and its risk factors are associated with cognitive decline.

Methods

We evaluated 206 individuals who visited our center for health screening. We carried out physical examinations, blood tests, intima‐media thickness (IMT) measurement by carotid ultrasonography, brain magnetic resonance imaging scanning and cognitive function assessments. A total of 30 individuals, who had significant cerebrovascular lesions detected in magnetic resonance imaging scans, were excluded. To detect early cognitive decline, we defined “cognitive impairment (CI)” when a patient satisfied at least one of three criteria. These were Mini‐Mental State Examination score <24, clock‐drawing test score <4 coexisting with forgetfulness and Wechsler Memory Scale‐revised delayed recall score below the normal range for the duration of education (>16 years of education: ≥9, 10–15 years: ≥5, 0–9 years: ≥3).

Results

Among 176 individuals, 27 were placed in the CI group. IMT was significantly higher in the CI group as compared with the non‐CI group (mean ± SD: 2.0 ± 1.0 vs 1.7 ± 0.7, P = 0018 by Student's t‐test). Other atherosclerotic risk factors, such as blood pressure, low‐density lipoprotein cholesterol, and hemoglobin A1c, were not significantly different between the two groups. In multivariate analysis, maximum IMT was associated with impaired immediate recall score on Wechsler Memory Scale‐revised, independent of the presence of deep white matter hyperintensities on the magnetic resonance imaging scan.

Conclusions

Subclinical carotid atherosclerosis, defined as thickened IMT, could be a marker for early stages of CI, especially for immediate memory recall. The impairment is presumably caused by inducing cerebral microvascular dysfunction in the frontal lobe. Geriatr Gerontol Int 2018; 18: 65–71 .     

Effects of rosuvastatin on vascular biomarkers and carotid atherosclerosis in lupus: a randomized, double-blind, placebo-controlled trial

Objective

To study the effect of rosuvastatin on vascular biomarkers and carotid intima‐media thickness (IMT) in systemic lupus erythematosus (SLE).

Methods

SLE patients with inactive disease and subclinical atherosclerosis were randomized in a double‐blinded manner to receive either rosuvastatin (10 mg/day) or matching placebo (half in each group were also randomly allocated low‐dose aspirin). After 12 months, treatment was unblinded. Patients treated with rosuvastatin and aspirin were continued on the same medications for another 12 months. Plasma levels of homocysteine, high‐sensitivity C‐reactive protein (hsCRP), soluble vascular cell adhesion molecule 1, P‐selectin, and thrombomodulin were measured at baseline, 6 months, and 12 months. Measurement of carotid IMT was repeated at 24 months.

Results

Seventy‐two patients were studied (97% women, mean ± SD age 50.8 ± 9.7 years). Thirty‐six patients were randomly assigned to each of the study arms (18 patients in each arm also received aspirin). Baseline clinical characteristics and medications were similar between the two groups. At 12 months, the mean low‐density lipoprotein cholesterol (mean ± SD 2.62 ± 1.04 mmoles/liter to 1.69 ± 0.72 mmoles/liter; P < 0.001) and median hsCRP levels (1.26 mg/liter, interquartile range [IQR] 2.3 to 0.88 mg/liter, IQR 1.1; P = 0.02) decreased significantly in the rosuvastatin group. There was no significant change in homocysteine, and aspirin use did not influence the levels of the biomarkers studied. A subgroup analysis of patients with a Systemic Lupus Erythematosus Disease Activity Index score ≤2 revealed a significant decrease in hsCRP (1.20 mg/liter, IQR 2.3 to 0.92 mg/liter, IQR 1.1; P = 0.04) and thrombomodulin levels (0.76 ng/ml, IQR 1.2 to 0.67 ng/ml, IQR 1.0; P = 0.001) with rosuvastatin treatment. At 24 months, the IMT of the internal carotid arteries appeared to be decreased in patients treated with rosuvastatin, which was well tolerated.

Conclusion

In stable SLE patients, low‐dose rosuvastatin leads to a significant reduction in hsCRP and thrombomodulin levels, which may possibly help to reduce cardiovascular risk.     

Insulin resistance, inflammation, and vascular disease in nondiabetic predialysis chronic kidney disease patients

Background:

Chronic kidney disease (CKD) is associated with high cardiovascular morbidity and mortality, which is not fully explained by traditional risk factors; hence, the interest in nontraditional risk factors such as inflammation and insulin resistance (IR). Though IR is shown in nondiabetic CKD, its association with vascular disease and inflammation in this population is unknown, and is what this study aims to investigate.

Hypothesis:

IR and inflammation are related to vascular disease in nondiabetic predialysis CKD patients.

Methods:

We studied carotid‐artery intima‐media thickness (IMT) and endothelial function (brachial artery flow mediated dilation [FMD]) in 35 nondiabetic predialysis patients with stage 3–5 CKD and 35 age‐ and gender‐matched controls. Insulin resistance was measured using the homeostasis model assessment for insulin resistance score (HOMA‐IR), inflammation by high‐sensitivity CRP (hsCRP), and their relationship with FMD and IMT.

Results:

Patients with CKD showed reduced FMD (3.34 ± 2.14% vs 5.27 ± 1.78%, P<0.001) and increased IMT (0.78 ± 0.22 mm vs 0.64 ± 0.16 mm, P = 0.003) compared with controls. The CKD patients had a higher HOMA‐IR (2.20 ± 1.08 vs 1.13 ± 0.64, P<0.001) and hsCRP (3.25 ± 5.47 mg/L vs 1.10 ± 1.85 mg/L [median ± interquartile range], P = 0.02). In the study population, HOMA‐IR was directly related to hsCRP. After adjusting for traditional risk factors, high HOMA‐IR and hsCRP were significantly related to decreased FMD (adjusted β = ? 0.44, 95% confidence interval [CI]: ? 1.55 to ? 0.08, P = 0.003 and adjusted β = ? 0.51, 95% CI: ? 0.51 to ? 0.15, P = 0.001) and increased IMT (adjusted β = 0.62, 95% CI: 0.54–1.90, P = 0.001 and adjusted β = 0.43, 95% CI: 0.08–0.57, P = 0.011), respectively.

Conclusions:

Subjects with systemic inflammation were more insulin‐resistant, and in nondiabetic predialysis CKD, IR and systemic inflammation were independently associated with endothelial dysfunction and atherosclerosis. © 2011 Wiley Periodicals, Inc. Dr. Debasish Banerjee and Dr. Alejandro Recio‐Mayoral are joint first authors. This study has been supported by grants awarded by the Spanish Society of Cardiology to Dr. A. Recio‐Mayoral and by the St. George's Charitable Foundation to Dr. D. Banerjee. The authors have no other funding, financial relationships, or conflicts of interest to disclose.

     

原发性高血压患者微量白蛋白尿与无症状性脑血管损害的研究

目的探讨原发性高血压(EH)患者微量白蛋白尿(MAU)与无症状性脑血管损害及颈动脉粥样硬化的关系。方法根据24h尿蛋白滤过率(UAER)测定结果,将162例EH患者分为正常白蛋白尿(NAU)组101例和MAU组61例。应用高频多普勒超声检测颈动脉内膜中层厚度(IMT)及颈动脉粥样硬化斑块;头颅MRI评价腔隙性脑梗死。采用logistic回归分析颈动脉IMT增厚和腔隙性脑梗死相关的危险因素。结果162例EH患者中MAU的阳性率为37.7%;与NAU组比较,MAU组颈动脉IMT明显增厚[(1.00±0.26)mmvs(0.86±0.20)mm,P<0.01],腔隙性脑梗死的发生率明显增高(62.3%vs44.6%,P<0.05);MAU与颈动脉IMT增厚及腔隙性脑梗死的发生独立相关(OR=2.639,95%CI:1.240～5.615,P<0.05及OR=2.369,95%CI:1.156～4.856,P<0.05)。结论MAU是高血压患者发生腔隙性脑梗死和颈动脉IMT增厚的一个预测指标,可作为判断无症状性脑血管损害及颈动脉粥样硬化的早期指标。     

The predictive value of retinal vascular findings for carotid artery atherosclerosis: are further recommendations with regard to carotid atherosclerosis screening needed?

Vascular retinopathy is the consequence of vascular disease, and the retina is the only place where the arteries can be visualized directly. The purpose of this study was to evaluate the predictive value of retinal vascular findings for carotid artery atherosclerosis. From December 2009 to January 2011, the carotid intima-media thickness (IMT) and total plaque area (TPA) were measured in 179 consecutive patients, who received a fundoscopic examination. The patients were divided into groups as follows: normal retinal artery (normal; n = 44), diabetic retinopathy (DR; n = 25), retinal artery occlusion (RAO; n = 17), retinal vein occlusion (RVO; n = 67), and hypertensive retinopathy (HTN-R; n = 26). The subjects were classified according to the presence of an increased (≥1 mm) IMT and plaque. The values of the mean carotid IMT in the patients with vascular retinopathy (DR, 0.87 ± 0.14 mm; RAO, 1.18 ± 0.47 mm; RVO, 0.84 ± 0.14 mm; HTN-R, 0.90 ± 0.20 mm) were significantly increased compared with those in the normal subjects (0.77 ± 0.13 mm). A total 77 of 135 vascular retinopathy patients demonstrated an increased IMT (57 %), and 97 vascular retinopathy patients had carotid artery plaque (72 %). The relative risk of vascular retinopathy in the prediction of an increased IMT and the presence of plaque was 2.79 and 3.95, respectively. Although The TPA was significantly increased in the patients with RAO (1.87 ± 2.67 cm²) and RVO (0.27 ± 0.23 cm²) compared with the normal subjects (0.18 ± 0.23 cm², all Ps < 0.05), there was no significant difference in the ipsilateral carotid IMT and TPA of the affected eye compared with that of the contralateral eye. In conclusion, vascular retinopathy demonstrated a good predictive value in identifying asymptomatic carotid artery atherosclerosis, and this was not confined to the ipsilateral carotid artery of the affected eye. Further recommendations with regard to carotid atherosclerosis screening in patients with vascular retinopathy should be considered.     

Clinical relevance of persistently elevated circulating cytokines (tumor necrosis factor α and interleukin‐6) in the long‐term followup of patients with giant cell arteritis

Objective

To assess the clinical relevance of increased circulating cytokines in patients with giant cell arteritis (GCA) after long‐term followup.

Methods

We performed a cross‐sectional evaluation of 54 patients with biopsy‐proven GCA prospectively followed for a median of 5.4 years (range 4–10.5 years). GCA‐related complications, vascular events, relapses, current prednisone dose, time required to achieve a maintenance prednisone dosage <10 mg/day, cumulated prednisone at that point, and adverse effects during followup were recorded. Serum interleukin‐6 (IL‐6) and tumor necrosis factor α (TNFα) were determined by immunoassay.

Results

All patients were in clinical remission. Both cytokines were significantly higher in patients than in controls (mean ± SD 21 ± 35 versus 5 ± 11 pg/ml; P < 0.001 for IL‐6 and mean ± SD 32 ± 14 versus 16 ± 9 pg/ml; P < 0.001 for TNFα). No differences were found in patients with or without GCA‐related complications or vascular events during followup. Circulating cytokines were significantly higher in patients who had experienced relapses (mean ± SD 25 ± 39 versus 10 ± 11 pg/ml; P = 0.04 for IL‐6 and mean ± SD 34 ± 15 versus 25 ± 11 pg/ml; P = 0.042 for TNFα). IL‐6 was significantly higher in patients still requiring prednisone (mean ± SD 29 ± 45 versus 13 ± 17 pg/ml; P = 0.008), and TNFα correlated with cumulated prednisone dose (r = 0.292, P = 0.04). No significant relationship was found between elevated cytokines and prednisone adverse effects or patients' quality of life.

Conclusion

Circulating TNFα and IL‐6 may persist elevated in GCA patients after long‐term followup and remain higher in patients who have experienced more relapsing disease. However, in this patient cohort, elevated circulating cytokines were not associated with increased frequency of GCA complications, vascular events, or treatment‐related side effects.     

Evaluation of Metabolic Syndrome Frequency and Carotid Artery Intima-media Thickness as Risk Factors for Atherosclerosis in Patients with Nonalcoholic Fatty Liver Disease

Aim The aim of this study was to evaluate metabolic syndrome (MetS) frequency and carotid artery intima-media thickness (IMT) as risk factors for atherosclerosis in patients with nonalcoholic fatty liver disease. Methods A case-control study was conducted on 40 biopsy-proven NAFLD patients and 40 age-matched healthy control subjects. Common carotid artery IMT and MetS criteria [according to the Third Report of the National Cholesterol Education Expert Panel on Detection, evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP-ATPIII), the International Diabetes Federation (IDF), the American Heart Association in conjunction with the National Heart, Lung, and Blood Institute (AHA/NHLBI)] were evaluated for all study subjects. Results MetS according to NCEP-ATPIII, IDF and AHA/NHLBI criteria was present in 55, 67.5 and 62.5% of NAFLD patients, respectively. The mean IMT was significantly higher in NAFLD patients (0.646 ± 0.091 mm) than control subjects (0.544 ± 0.067 mm), (P < 0.001). Among the vascular risk factors evaluated, the diagnosis of NAFLD and increased body mass index were significant independent predictors of increased IMT. Conclusions As cardiovascular risk factors, both MetS and increased IMT occur frequently among NAFLD patients. Screening for both conditions might be beneficial for assessment of future atherosclerotic complications.     

A strong initial systemic inflammatory response is associated with higher corticosteroid requirements and longer duration of therapy in patients with giant‐cell arteritis

Objective

To assess whether the intensity of the initial systemic inflammatory response is able to predict response to therapy in patients with giant cell arteritis (GCA).

Methods

Retrospective review of 75 patients (49 women and 26 men) with biopsy‐proven GCA who had regular followup and were treated according to uniform criteria. Four parameters were used to evaluate the baseline inflammatory response at diagnosis: fever, weight loss, erythrocyte sedimentation rate ≥ 85 mm/hour, and hemoglobin < 110 gm/liter. Patients were considered to have a weak inflammatory response if they had 2 or fewer inflammatory parameters (group 1) and a strong inflammatory response if 3 or 4 parameters were present (group 2). Time required to achieve a maintenance dose of less than 10 mg prednisone/day was recorded and analyzed by the Kaplan–Meier survival analysis method. Tumor necrosis factor α (TNFα) and interleukin 6 (IL‐6) serum levels were also determined in 62 patients and 15 controls.

Results

Forty patients had a weak (group 1) and 35 had a strong (group 2) initial inflammatory response. Patients in group 2 had significantly higher levels of circulating TNFα (31.9 ± 16.8 versus 22.3 ± 9 pg/ml; P = 0.01) and IL‐6 (28.2 ± 17.4 versus 16.6 ± 13 pg/ml; P = 0.004) than patients in group 1. In group 1, 50% of patients required a median of 40 weeks (95% CI 37–43) to reach a maintenance dose of <10 mg, whereas in group 2 a median of 62 weeks (95% CI 42–82) was necessary (P = 0.0062). Patients in group 2 experienced more flares than patients in group 1 (P = 0.01) and received higher cumulative steroid doses (8.974 ± 3.939 gm versus 6.893 ± 3.075 gm; P = 0.01).

Conclusion

GCA patients with a strong initial systemic inflammatory reaction have more elevated circulating levels of IL‐6 and TNFα, have higher and more prolonged corticosteroid requirements, and experience more disease flares during corticosteroid therapy than patients with a weak systemic acute phase response.

     

Unusual CD4+CD28− T lymphocyte subset is implicated in the pathogenesis of early atherosclerosis in patients with rheumatoid arthritis

Background

Rheumatoid arthritis (RA) is associated with accelerated atherosclerosis which is not fully explained by traditional risk factors. Such excess risk appears to be driven by systemic inflammation.

Comparison of carotid and lower limb atherosclerotic lesions in both previously known and newly diagnosed type 2 diabetes mellitus

Aims/Introduction

To compare carotid and lower limb atherosclerotic lesions, and examine if carotid atherosclerotic lesions are in line with lower limb atherosclerotic lesions, and can reflect generalized atherosclerosis in inpatients with type 2 diabetes.

Materials and Methods

This was an observational study carried out in 867 Chinese inpatients with type 2 diabetes, including 573 previously known and 294 newly diagnosed patients. Ultrasonographic assessments of intima-media thickness (IMT), plaques, and stenosis in the carotid and lower limb arteries were evaluated. Atherosclerotic lesions between the carotid and lower limb arteries were compared in both previously known and newly diagnosed diabetes, respectively.

Results

In both the known (77.3% vs 49.4%, P < 0.001) and the newly diagnosed diabetes (55.4% vs 29.9%, P < 0.001), the prevalence of atherosclerotic plaques was significantly higher in the lower limb arteries than in the carotid arteries. Likewise, the prevalence of stenosis was also significantly higher (P < 0.001) in the lower limb arteries (16.9%) than in the carotid arteries (4.2%) in the established diabetes patients. However, there was no significant difference in the mean IMT between common carotid and common femoral arteries in both the previously known (0.90 ± 0.24 mm vs 0.89 ± 0.20 mm, P = 0.675) and the newly diagnosed diabetes patients (0.86 ± 0.22 mm vs 0.85 ± 0.16 mm, P = 0.436).

Conclusions

Carotid plaques might underestimate generalized plaques in inpatients with type 2 diabetes, as shown by its significantly lower prevalence compared with that of the lower extremity arteries. A combined carotid and lower limb ultrasound examination can improve the detection of atherosclerotic lesions in inpatients with type 2 diabetes.     

RESEARCH: Effects of Long‐Term Disease‐Modifying Antirheumatic Drugs on Endothelial Function in Patients with Early Rheumatoid Arthritis

Rheumatoid arthritis (RA) is associated with enhanced atherosclerosis and impaired endothelial function early after the onset of the disease and cardiovascular (CV) disease represents one of the leading causes of morbidity and mortality. It is well known that disease modifying antirheumatic drugs (DMARDs) are able to improve the course of the disease and the quality of life of these patients, but little is known about the effects of DMARDs on CV risk and endothelial dysfunction. Our goal was to examine the effects of long‐term therapy with DMARDs on endothelial function and disease activity in early RA (ERA). Twenty‐five ERA patients (mean age 52 ± 14.6 years, disease duration 6.24 ± 4.10 months) without evidence of CV involvement were evaluated for disease activity score (DAS‐28), 2D‐echo derived coronary flow reserve (CFR), common carotid intima‐media thickness (IMT) and plasma asymmetric dimethylarginine (ADMA) levels at baseline and after 18 months of treatment with DMARDs (10 patients with methotrexate and 10 with adalimumab). DMARDs significantly reduced DAS‐28 (6.0 ± 0.8 vs. 2.0 ± 0.7; P < 0.0001) and improved CFR (2.4 ± 0.2 vs. 2.7 ± 0.5; P < 0.01). Common carotid IMT and plasma ADMA levels did not show significant changes. The present study shows that DMARDs, beyond the well known antiphlogistic effects, are able to improve coronary microcirculation without a direct effect on IMT and ADMA, clinical markers of atherosclerosis. Treatment strategies in ERA patients with high inflammatory activity must be monitored to identify beneficial effects on preclinical markers of vascular function.