Traditional Framingham risk factors fail to fully account for accelerated atherosclerosis in systemic lupus erythematosus

OBJECTIVE: The frequency of coronary heart disease (CHD) and stroke are increased in systemic lupus erythematosus (SLE), but the extent of the increase is uncertain. We sought to determine to what extent the increase could not be explained by common risk factors. METHODS: The participants at two SLE registries were assessed retrospectively for the baseline level of the Framingham study risk factors and for the presence of vascular outcomes: nonfatal myocardial infarction (MI), death due to CHD, overall CHD (nonfatal MI, death due to CHD, angina pectoris, and congestive heart failure due to CHD), and stroke. For each patient, the probability of the given outcome was estimated based on the individual's risk profile and the Framingham multiple logistic regression model, corrected for observed followup. Ninety-five percent confidence intervals (95% CIs) were estimated by bootstrap techniques. RESULTS: Of 296 SLE patients, 33 with a vascular event prior to baseline were excluded. Of the 263 remaining patients, 34 had CHD events (17 nonfatal MIs, 12 CHD deaths) and 16 had strokes over a mean followup period of 8.6 years. After controlling for common risk factors at baseline, the increase in relative risk for these outcomes was 10.1 for nonfatal MI (95% CI 5.8-15.6), 17.0 for death due to CHD (95% CI 8.1-29.7), 7.5 for overall CHD (95% CI 5.1-10.4), and 7.9 for stroke (95% CI 4.0-13.6). CONCLUSION: There is a substantial and statistically significant increase in CHD and stroke in SLE that cannot be fully explained by traditional Framingham risk factors alone.     

Novel cardiovascular risk prediction models in patients with systemic lupus erythematosus

Women with systemic lupus erythematosus (SLE) have increased risk for coronary heart disease (CHD) which is underestimated by the Framingham risk score (FRS). We hypothesized that new risk scores that include inflammation or vascular age in the risk calculation would better identify women with SLE at risk for CHD, particularly in those with subclinical coronary atherosclerosis. We calculated the FRS and Reynolds risk score (RRS) in 121 women with SLE and 65 age-matched female controls; coronary age-modified risk scores (camFRS, camRRS) were calculated using coronary age derived from the coronary artery calcium (CAC) score. Risk scores were compared in SLE and controls, and in SLE patients with and without CAC. Although CAC was present in 21 SLE patients (17%) and four controls (6%) (p?=?0.033); the FRS, camFRS, RRS, and camRRS, did not differ significantly among SLE and controls (p?>?0.05), but were all significantly higher in SLE patients with CAC compared with those without (p?相似文献   

Distribution of lifestyle and emerging risk factors by 10-year risk for coronary heart disease.

BACKGROUND: The Framingham risk score has been used for coronary heart disease (CHD) risk assessment. Recently, additional risk factors not included in the Framingham algorithm have received much attention and may help improve risk assessment. We examined the distributions of lifestyle and emerging risk factors by 10-year risk of CHD. METHODS: We calculated 10-year CHD risk (<10%, 10-20%, and >20%) for 8355 participants in the National Health and Nutrition Examination Survey (NHANES) 1999-2002 using the Framingham risk score as modified by the National Cholesterol Education Program Adult Treatment Panel III guidelines. We examined the prevalence of lifestyle risk factors [body mass index (BMI) and waist circumference] and various emerging risk factors [C-reactive protein (CRP), white blood cell count, fibrinogen, homocysteine, glycosylated hemoglobin, and albuminuria] as well as prevalence of high CHD risk by levels of these risk factors. RESULTS: All examined CHD risk factors were significantly associated with increasing 10-year CHD risk among men and women. Odds of being in the highest CHD risk group were greater at higher levels of examined risk factors. Means for most risk factors were slightly higher for women than the means for men. Sizeable proportions of participants with lower 10-year CHD risk had high levels of lifestyle and emerging risk factors: 60.8% were overweight, 33.8% had high CRP concentrations, 24.1% had serum fibrinogen >400 mg/dl and 6% had an albumin/creatinine ratio >/=30. CONCLUSIONS: Lifestyle and emerging risk factors, in addition to those included in the Framingham risk score, may be important in CHD risk assessment.     

Risk of coronary heart disease and stroke in a large British cohort of patients with systemic lupus erythematosus

OBJECTIVES: Patients with systemic lupus erythematosus (SLE) are at increased risk of myocardial infarction and stroke. We sought to determine how much of this risk was dependent on recognized cardiovascular risk factors. METHODS: Initially a software package 'Cardio-Risk-Manager', which utilizes Framingham data, was used to calculate a 10-yr risk of coronary heart disease (CHD) and stroke for 202 patients with SLE (Group 1) in comparison with hypothetical age- and sex-matched comparators. Subsequently 47 patients who had been followed since 1991 (Group 2) were studied to compare their predicted risks in 1991 with the actual number of cardiovascular events that occurred during the subsequent decade. RESULTS: Patients in Group 1 had a higher predicted 10-yr risk of stroke (P<0.0001), but not of CHD, than their comparators. However, following age stratification, traditional risk factors predicted a higher risk of CHD (P<0.0001) and of stroke (P<0.0001) in patients under 40 with SLE compared with age-matched comparators. The predicted 10-yr risks of CHD and stroke for patients aged 40 and above were not significantly different from those of their comparators. Predicted risks, however, were lower than the true 10-yr event rate for CHD and stroke in patients in Group 2. In this group, during the 10 yr of follow-up four patients (8.5%) suffered a CHD event and five patients (10.6%) had a stroke, significantly more than were predicted by the presence of conventional risk factors (P<0.001 for CHD and P<0.001 for stroke, respectively). CONCLUSIONS: Conventional risk factors predicted an increased risk of stroke and CHD in younger patients. They do not, however, fully explain the high risk of cardiovascular disease in patients with SLE. Although it is important to address the management of orthodox risk factors for cardiovascular disease in patients with SLE, other causes must be sought to explain the increased incidence of CHD and stroke, especially in those aged over 40.     

Cardiovascular risk scores and the presence of subclinical coronary artery atherosclerosis in women with systemic lupus erythematosus

The Framingham risk score is widely used to identify patients at increased cardiovascular risk, and women with systemic lupus erythematosus (SLE) have a marked increased prevalence of cardiovascular events. Thus, we examined the hypothesis that cardiovascular risk scores would identify women with SLE who had asymptomatic coronary atherosclerosis. Ninety-three women with SLE and 65 control subjects were studied. The Framingham score and a score for younger populations developed from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study were compared in both groups. Coronary atherosclerosis was ascertained by electron beam computed tomography. There were no significant differences in the median (interquartile range) Framingham [5 (2-10) compared to 7 (0-10), P = 0.88] and PDAY [15 (14-18) compared to 16 (13-18), P = 0.99] scores in patients with SLE and controls, respectively. Coronary atherosclerosis was associated with higher Framingham [12 (3-15) compared to 4 (1-8), P = 0.008] and PDAY [17 (15-19 compared to 15 (12-18), P = 0.03)] scores in patients with SLE; however, 99% of patients were classified as low-risk with a 10-year predicted risk of 1% (<1-3%). Our data indicate that cardiovascular risk scores are not adequate for risk stratification in women with SLE. Measurement of coronary calcification may add information to identify asymptomatic women with lupus who might benefit from aggressive preventive measures.     

Hyperinsulinemia, insulin resistance, and circulating oxidized low density lipoprotein in women with systemic lupus erythematosus

OBJECTIVE: Women with systemic lupus erythematosus (SLE) have increased risk of coronary heart disease (CHD) that is not fully explained by the classic CHD risk factors. Insulin resistance is an established risk factor for CHD in the general population. We compared insulin secretion and sensitivity in patients with SLE and healthy controls, and assessed the prevalence of the metabolic syndrome in women with SLE and its relation to circulating oxidized low density lipoprotein (ox-LDL). METHODS: Fasting insulin, glucose, and lipid profiles were measured in nondiabetic women with SLE (>or= 4 revised 1997 criteria) not undergoing antimalarial therapy (n = 44), and in age matched controls recruited from the hospital staff and the local community (n = 45). Using the Homeostatic Model Assessment equations, insulin sensitivity (HOMA-S) and pancreatic beta cell function (HOMA-B) were calculated from fasting insulin and glucose. The metabolic syndrome, defined according to the Adult Treatment Panel (ATP III) criteria, was determined in a consecutive series of 61 women with SLE. RESULTS: Patients with SLE had significantly higher fasting insulin [median (range) 10 (2.8-38) vs 6.6 (3.1-26) mU/l; p < 0.01], higher pancreatic beta cell function (HOMA-B) [165 (54-1567) vs 111 (28-653); p < 0.01], and lower insulin sensitivity (HOMA-S) [0.46 (0.09-1.9) vs 0.73 (0.16-1.3); p < 0.01]. SLE patients also had significantly higher triglycerides (p < 0.01) and lower high density lipoprotein cholesterol (p < 0.01) than controls. HOMA-S did not correlate with disease activity or steroid therapy, but was associated with components of the insulin resistance syndrome. HOMA-S showed a significant negative correlation with levels of ox-LDL in patients, but not in controls. Eleven (18%) patients had the metabolic syndrome. Again, this was not related to current steroid therapy. SLE patients with the metabolic syndrome had no difference in LDL, but had significantly higher levels of ox-LDL. CONCLUSION: Nondiabetic patients with SLE have evidence of significant decrease in sensitivity to insulin, and overall this population has a high prevalence of the metabolic syndrome (18%). Insulin resistance in the context of SLE was not strongly related to current or recent steroid therapy; it was, however, associated with higher levels of ox-LDL. Insulin resistance may therefore represent an additional CHD risk factor in patients with SLE.     

'Not only...but also': factors that contribute to accelerated atherosclerosis and premature coronary heart disease in systemic lupus erythematosus

Premature coronary heart disease (CHD) has emerged as a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Overall SLE patients have a 5-6-fold increased risk of CHD and this excess risk is especially pronounced in younger women where the excess risk may be >50-fold. Studies from our group and others have also demonstrated that SLE patients have a higher prevalence of subclinical atherosclerosis compared with controls, with approximately 30% having evidence of subclinical involvement. It is important to consider what factors may underlie this excess risk. We have found that certain 'classic' risk factors, i.e. hypertension and diabetes mellitus, are more prevalent in SLE and that persistent hypercholesterolaemia independently predicts patients who will develop CHD. These risk factors alone do not completely explain the excess risk observed, and after adjusting for classic risk factors SLE remains independently associated with both clinical and subclinical outcomes. Certain other metabolic changes also occur more frequently in SLE, namely premature menopause, renal impairment, high triglycerides and higher plasma homocysteine. In addition, insulin resistance is more pronounced in patients with SLE, and approximately 18% have the metabolic syndrome. It is also increasingly accepted that atherosclerosis is a chronic inflammatory condition, and in SLE systemic complement activation as well as immune complex formation can result in changes that promote the development of atheroma. Similarly, autoantibody production, especially antibodies directed against lipoprotein subtypes and those in the antiphospholipid (APLA) family, are gaining increasing attention. The role of the latter are particularly controversial as different subtypes have been shown to both promote and protect against atherogenesis. In a study looking at carotid plaque in SLE, we found that APLA was independently associated with the presence of plaque; this study also found that patients with plaque had higher white cell counts, suggesting ongoing chronic inflammation. We have also noted a negative correlation between activation of transforming growth factor beta-1 and carotid intima-medial thickness. This cytokine, which is known to be a potent anti-inflammatory molecule, has also been shown to be protective against atherogenesis. With regard to therapy, steroids may be a true double-edged sword, with low doses exerting a beneficial anti-inflammatory role whereas higher doses may be detrimental through exacerbation of metabolic risk factors. In contrast, we have found that antimalarials have a beneficial effect on lipids especially when co-prescribed with steroids, and this, along with anti-inflammatory and proposed antiplatelet effects, may confer protection against CHD in lupus. The risk of premature CHD in SLE is therefore mediated by a number of factors that involve not only classic risk factors but also a range of factors associated with SLE itself. Preventative strategies will therefore need to address all potential risk factors of relevance. A more through understanding of the interplay between autoimmunity and atherogenesis should be possible by the study of SLE, and this may not only benefit lupus patients but also may have implications for our understanding of atherosclerosis in general.     

Progression of carotid intima-media thickness and plaque in women with systemic lupus erythematosus

OBJECTIVE: Women with systemic lupus erythematosus (SLE) are at high risk of cardiovascular disease (CVD). The goals of this study were to determine the extent of atherosclerotic progression among women with SLE compared with a group of healthy controls and to determine whether factors attributed to SLE or its treatment were associated with atherosclerotic progression independent of traditional CVD risk factors. METHODS: A longitudinal study of women with SLE from the Pittsburgh Lupus Registry was conducted. Women 18 years of age and older (n = 217) underwent carotid ultrasound at baseline and at followup, an average of 4.19 years later. Clinical, serologic, and SLE-related factors, and disease treatment were evaluated. Outcomes were changes in carotid intima-media thickness (IMT) and plaque. Progression of CVD in a sample of women without lupus was used for comparison. RESULTS: The patients' mean +/- SD age at baseline was 45.1 +/- 10.3 years, and the mean +/- SD IMT progression rate was 0.011 +/- 0.03 mm per year. After controlling for traditional CVD risk factors, higher serum creatinine levels were associated with IMT progression (P = 0.0006). Plaque prevalence was 31% at baseline and 40% at followup; plaque progression occurred in 27% of the patients. Higher serum C3 levels and immunosuppressant use at baseline were related to plaque progression (P = 0.04 and P = 0.02, respectively) independent of traditional CVD risk factors. The plaque progression rate was higher than, and the IMT progression rate was similar to, those in the control group. CONCLUSION: SLE patients have accelerated plaque progression compared with controls. SLE-related risk factors are associated with the progression of IMT and plaque after controlling for traditional CVD risk factors. Carotid B-mode ultrasound may serve as a surrogate end point in SLE intervention trials and clinically to track SLE management.     

Accumulation of coronary artery disease risk factors over three years: data from an international inception cohort

OBJECTIVE: To examine the accumulation of risk factors over 3 years in a multicenter, international inception cohort of patients with systemic lupus erythematosus (SLE). METHODS: The Systemic Lupus International Collaborating Clinics registry for atherosclerosis comprises 27 centers from 11 countries. An inception cohort of 935 patients with SLE was assembled, according to a standardized protocol, from 2000 to 2006 to study risk factors for atherosclerosis. Both classic and other coronary artery disease (CAD) risk factors were collected at entry and through 3 years of followup. Therapy was documented over the 3 years. The Framingham 10-year risk factor profile was calculated for each patient at year 1 and year 3. RESULTS: A total of 278 patients from the inception cohort were followed for 3 years and constituted the population for this study. At enrollment a substantial number of patients already demonstrated several risk factors for CAD, both classic and other. All risk factors increased from enrollment over the 3 years of followup. Treatment of hypertension and hypercholesterolemia also increased over 3 years, but less so for hypercholesterolemia. The Framingham 10-year CAD risk profile was higher in men than in women both at entry and at 3 years, and remained unchanged over the 3 years. Corticosteroid use increased only slightly over 3 years, but use of antimalarials and immunosuppressive agents increased to a greater extent. CONCLUSION: Patients with SLE should be monitored for CAD risk factors from the time of diagnosis and appropriate treatment should be instituted early.     

Preclinical vascular disease in systemic lupus erythematosus and primary antiphospholipid syndrome

OBJECTIVE: To determine the prevalence of preclinical vascular disease and associated risk factors in patients with systemic lupus erythematosus (SLE) or primary antiphospholipid syndrome (APS). METHODS: We consecutively studied 70 SLE patients and 25 primary APS patients without clinical coronary artery disease. The control group included 40 healthy women. Carotid ultrasound was performed and the intima-media wall thickness (IMT) and presence of plaque was investigated in all patients and controls. Traditional vascular risk factors and SLE-disease and treatment related factors were also analysed. RESULTS: SLE patients had a higher prevalence of traditional atherosclerosis risk factors: hypertension (P<0.005) and dyslipidaemia (P<0.05) and higher levels of total cholesterol (P = 0.03), triglycerides (P = 0.004) and apolipoprotein B (P = 0.04). The prevalence of carotid plaque was higher and appeared earlier in SLE patients than in the primary APS patients or controls (P<0.001). The IMT was similar in the three groups. SLE patients with secondary APS had a higher prevalence of carotid plaque than patients with primary APS (37.5% vs 8%, P = 0.03). The presence of plaque in SLE patients was associated with a higher SLICC score (2.40 +/- 1.78 vs 1.02 +/- 1.18, P = 0.002), higher ECLAM score (3.10 +/- 2.32 vs 1.84 +/- 1.59, P = 0.02) and older age (47.3 +/- 8.44 vs 37.38 +/- 11.28, P = 0.003) at the time of carotid ultrasound study. CONCLUSION: Plaque prevalence in patients with primary APS is similar to that of controls and inferior to that of SLE patients with secondary APS. SLE patients have a high prevalence of early carotid atherosclerosis that is associated with cumulative disease damage and disease activity.     

系统性红斑狼疮合并冠心病临床特点

目的总结系统性红斑狼疮（SLE）患者合并冠心病的临床特点。方法对1970—2006年北京协和医院院诊断为SLE合并冠心病11例患者传统危险因素、第一次心脏事件发作时的情况、SLE诊断、治疗及活动情况进行了回顾性分析。结果SLE患者发生冠心病的年龄较小为（53．9±8．1）岁;冠心病传统危险因素较少为（1．3±0．8）个／例;糖皮质激素使用前后各项血脂指标均有显著增高（P〈0．05）;发生心脏事件时的狼疮活动评分（SLEDAI）较高为（12．0±10．3）分;SLE患者冠状动脉（冠脉）病变程度较重,表现为弥漫狭窄、重度钙化。结论SLE患者早发冠心病不能完全用传统危险因素来解释,而且冠脉病变程度往往较重,预后差,需要尽早干预,尽量延缓疾病进程,并使用无创检查加强早期检出率,从而改善预后。     

An analysis of the metabolic syndrome phenotype in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is associated with an increased risk of coronary heart disease (CHD) not fully explained by classic risk factors. Metabolic syndrome (MetS) is associated with an increased risk of CHD in the general population and whilst its prevalence is increased in SLE, its phenotypic expression may differ. We studied 200 women with SLE and 100 controls and compared the prevalence of MetS and its individual components. We examined whether any SLE features were associated with MetS and whether MetS in SLE patients was associated with carotid plaque. Patients with SLE were more likely to meet the MetS criteria (age-adjusted OR 2.1 (1.1-3.8)). However, this was not due to increased central obesity (median waist circumference 84 cm vs. 82 cm, p = 0.65) but rather increased prevalence of hypertension (p <0.01) and low HDL-cholesterol (p = 0.01). In a multivariable analysis, age, disease duration, low complement C3 and corticosteroid use ever, were associated with the presence of MetS in SLE. Overall MetS was not associated with the presence of carotid plaque in either SLE or controls. We have shown that MetS is more prevalent in SLE, but the lupus-MetS phenotype reflects risk factor changes driven by disease activity and steroid exposure, rather than obesity. Reliance on clinical measures of central obesity to consider MetS in SLE is not reliable and continued attention to individual CHD risk factors is recommended.     

Atherosclerotic vascular events in a single large lupus cohort: prevalence and risk factors

OBJECTIVE: To determine prevalence and type of atherosclerotic vascular events (AVE) occurring after entry to the University of Toronto Lupus Clinic; and to compare risk factors in patients with systemic lupus erythematosus (SLE) with AVE to matched SLE controls without AVE. METHODS: Patients with SLE attending the University of Toronto Lupus Clinic who did not have AVE prior to clinic entry were included. Patients have been followed at 2-6 months since 1970 according to a standard protocol. Cases with AVE were matched for sex, era at first clinic visit (1970s, 1980s, 1990s +), inception status, age at first visit, and duration of followup. Chi-square, Fisher's exact, paired T test, and McNemar test were used. Comparison of risk factors for the development of AVE was done using a stepwise conditional logistic regression model for matched pairs. RESULTS: In a total cohort of 1087 SLE patients followed from 1970 until 2004, the prevalence of AVE was 10.9%, and in 561 inception patients it was 9.6%. In multivariate analyses, neuropsychiatric involvement was significantly associated with AVE in both the total and inception cohorts. Smoking was also associated with AVE in the inception cohort, whereas the number of coronary artery disease (CAD) risk factors and vasculitis were significant in the total cohort. CONCLUSION: AVE are major contributors to the clinical presentation of late-stage lupus. A combination of lupus related factors and classic CAD risk factors contributed to the development of AVE.     

系统性红斑狼疮合并冠心病的临床特点及危险因素研究

目的 分析系统性红斑狼疮(SLE)并发冠状动脉性心脏病(冠心病)患者的临床特点,评价传统及非传统动脉粥样硬化危险因素对SLE患者发生冠心病的影响.方法 选取我院SLE并发冠心病的患者32例作为冠心病组,同时选取与其年龄和性别匹配的SLE但无冠心病症状或事件记录的患者64例作为对照组.对冠心病组的临床特点进行回顾性分析,并在传统危险因素、SLE情况等方面对2组进行单因素比较及多因素Logistic回归分析.结果 32例并发冠心病的患者中12例接受了冠状动脉造影或冠状动脉CT检查,11例为动脉粥样硬化病变,其中10例存在>75%的重度冠状动脉狭窄,多支病变多见.与无冠心病的对照组进行单因素比较,冠心病组患者具有更多的传统危险因素个数[(3.9±1.8)和(2.0±1.6)个,P<0.01],其中高血压、高脂血症、绝经及吸烟患者的数量明显多于对照组.SLE相关因素方面:冠心病组患者SLE病程更长[12.0(6.3~19.8)和2:0(0.8～9-0)年,P<0.01],糖皮质激素应用总量更多[28.8(0～49.8)和24.0(0~24.6)g,P<0.05];对照组患者补体C3水平更低[(750±364):和(598±267)mg/L,P<0.05]:SLE相关的脏器受累、其他免疫学指标、狼疮疾病活动性评分在2组间差异均无统计学意义.多因素分析显示,患者所具有的传统危险因素的数量及SLE病程是SLE患者并发冠心病的独立危险因素.结论 动脉粥样硬化是SLE患者出现冠状动脉病变的常见病理改变.传统危险因素在SLE患者动脉粥样硬化的发生中仍然发挥了重要作用,但SLE的病程也是导致动脉粥样硬化发生的独立危险因素.重视财传统危险因素的控制对防治动脉粥样硬化的发生具有重要的临床意义,随着SLE病程的延长,更应该加强对于动脉粥样硬化的监测与防治.

Abstract：

Objective To assess the clinical features and risk factors of coronary heart disease(CHD)in patients with systemic lupus erythematosus (SLE).Methods The clinical data of 32 lupus patients with CHD and 64 age and sex-matched lupus patients without CHD from a total of 1792 in-patients with lupus from January 1994 to December 2008 were collected and retrospectively analyzed.The traditional risk factors of atherosclemsis as well as their association with the characteristics of lupus were evaluated and compared between the two group of patients.Results The average age of CHD group was(51±12)years with an average disease duration of((8±6) years、.The most common coronary events were acute myocardial infaretio(53%)and non-stable,angina[34%).Among the 12 patients who accepted coronary angiography or computed tomography scan of coronary artery,11 patients had significant atheroselerosis lesions and 1 had thrombosis in coronary arteries.Their atheroselerosis lesions were severe,which manifested as diffuse stenosis and severe calcification.Compared to the control group,the CHD group patients had more traditional risk factors[(3.9±1.8)vs(2.0±1.6),P<0.01 j as well as higher prevalence of hypertension,hyperlipidemia,postmenopausal and smoking(P<0.05).Meanwhile,the CHD group patients had longer SLE duration[12.0(6.3~19.8)vs 2.0[O.8～9.0)years,P<0.01)J,higher C3 level[(750±364)vs(598±267)mg/L,P<0.05]and higher totalprednisone dose[28.8(0~49.8)vs 24.0(0~24.6)g,P<0.05]compared to patients without CHD.No significant differences were found in auto-antibodies,SLE disease activity,organ damage,average Drednisone dose and cyclophosI,hamide usage between the two groups of patients.Multi-variate analysls showed more traditional risk factors(OR:1.62)and longer SLE duration(OR=1.09)Were independent predictors of CHD.Condusion Atherosclerosis is a common pathological change of coronary in lupus patients with CHD.Traditional risk flactors of atherosclerosis and lupus duration are identified to be the independent risk factors of CHD in SLE patients.Early interventions for traditional risk factors and appropriate control of lupus arerecommended.     

Risk factors for recurrent thrombosis: prospective study of a cohort of Japanese systemic lupus erythematosus

Not only antiphospholipid antibodies (aPLs) but also other factors should be considered in assessing the risk of thrombosis development in patients with systemic lupus erythematosus (SLE) and antiphospholipid antibodies (aPLs). The kinds of risk factors, including past history of thrombotic event (PHTE), hypertension, hypercholesterolemia, diabetes mellitus (DM), obesity, and smoking, in conjunction with aPLs, that contribute to the development of new thrombotic events in patients with SLE and aPLs were studied prospectively over a 5-year observation period. One-hundred and sixty-six Japanese patients with SLE (55 patients with aPLs and 111 patients without aPLs) were examined and followed up for 5 years. Five major risk factors for ischemic coronary disease and stroke according to the Framingham heart cohort study were evaluated objectively in these patients. A significant difference was seen for 4 factors: past history of thrombotic event (PHTE; odds ratio: 101.93; 95% confidence interval: 12.29-845.22; p < 0.0001), hypertension (odds ratio: 8.87; 95% CI: 2.58-30.53; p < 0.001), DM (odds ratio: 5.42; 95% CI: 1.44-20.46; p < 0.05), and lupus anticoagulant (LAC; odds ratio: 47.41; 95% CI: 5.88-382.03, p < 0.0001) as aPLs, when the incidence of these risk factors was compared between patients with and without new thrombotic events. Furthermore, PHTE (odds ratio: 30.19, 95% CI: 1.33-683.13), hypertension (odds ratio: 15.44; 95% CI: 1.77-134.80), and LAC (odds ratio: 14.11; 95% CI: 0.48-412.42) showed higher odds ratios than DM (odds ratio: 11.53; 95% CI: 0.83-159.94) on multivariate logistic analysis as well as analysis of the combination of risk factors, suggesting that these are important risk factors for the development of new thrombotic events in patients with SLE and aPLs.     

The prevalence of dyslipoproteinemia in Thai patients with systemic lupus erythematosus

Fasting blood samples taken from 93 pairs of outpatient systemic lupus erythematosus (SLE) women and matched controls were assessed for total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL)- and low-density lipoprotein (LDL)-cholesterol. The demographic data, clinical manifestations, Mexican-SLE Disease Activity Index (MEX-SLEDAI), Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index and medication prescribed in the SLE patients were reviewed. A significant elevation of TG levels was observed in the SLE patients compared to controls (mean+/-SD 113.3+/-59.5 versus 77.7+/-45.7 mg/dL, P < 0.001). The HDL-c level was also significantly lower in SLE patients than controls (mean+/-SD 49.7+/-12.7 versus 65.0+/-14.8 mg/dL, P < 0.001). The percentage of samples with low HDL-c (<35 mg/dL) was higher in the SLE group (9.7%) than controls (0%; P = 0.002). The LDL-c and TC levels were comparable in both groups. The use of antimalarial drugs was negatively associated with TC (OR 0.22, 95%CI 0.08-0.61) and LDL-c levels (OR 0.27, 95%CI 0.09-0.80). The increased prevalence of dyslipoproteinemia in SLE patients in this report has confirmed the results of previous studies and emphasized the importance of controlling this modifiable cardiovascular risk factor by the combination of lifestyle modification and medical treatments.     

Atorvastatin therapy improves endothelial-dependent vasodilation in patients with systemic lupus erythematosus: an 8 weeks controlled trial

INTRODUCTION: Patients with systemic lupus erythematosus (SLE) have recognized reduction in endothelium-dependent vasodilation. Evidence demonstrates that statins are able to improve endothelial function independently on their hypolipemic action. OBJECTIVES: To evaluate the efficacy of atorvastatin in improving vasodilation in SLE patients with and without conventional risk factors for coronary heart disease (CHD). PATIENTS AND METHODS: Sixty-four SLE women, mean age 31 +/- 8 yrs, received atorvastatin 20 mg/day during 8 weeks. Thirty-one patients in this intervention group did not have conventional risk factors for CHD, while 33 others had hypertension, dyslipidaemia and/or obesity. Twenty-four SLE control patients, mean age 34 +/- 7.5 yrs, not receiving atorvastatin were followed during the same time period. High-resolution ultrasound was used to measure brachial artery diameter in resting conditions, during reactive hyperaemia and after sub-lingual glyceryl trinitrate (GTN). Measurements were performed at baseline and at the end of the study (8 weeks). RESULTS: Atorvastatin was associated with a significant increase in flow-mediated dilation (FMD) [3.8 (2.8-7.9%) vs 6.9 (4.2-10.7%), P < 0.001] while GTN-mediated dilation (GTND) was unaffected [20.9 (16.6-26.1%) vs 20.1(16.6-25.4%), P = 0.514]. FMD increase was observed in patients with conventional risk factors [4.1 (3.1-8.7%) vs 6.5 (4-10%), P = 0.046] and also for those without conventional risk factors for CHD [3.6 (2.6-7.3%) vs 7.1 (4.5-10.9%), P = 0.001]. Resting brachial artery diameter also increased significantly in patients receiving atorvastatin (2.79 +/- 0.30 mm vs 2.92 +/- 0.40 mm, P < 0.001). No significant difference in artery diameter and FMD was seen in control patients at the end of the study. When compared to the control patients, atorvastatin treatment was associated with significant increase in resting diameter (+0.13 +/- 0.1 mm vs -0.02 +/- 0.07 mm, P < 0.001) and FMD (+1.9 +/- 3.9% vs -0.3 +/- 1.8%, P = 0.009). CONCLUSION: Our results demonstrate that an 8-week 20 mg/day atorvastatin series improved endothelium-dependent vasodilation in SLE patients independently on the presence of conventional risk factors for atherosclerotic disease.     

Proinflammatory high-density lipoprotein as a biomarker for atherosclerosis in patients with systemic lupus erythematosus and rheumatoid arthritis

OBJECTIVE: Women with systemic lupus erythematosus (SLE) have a 7-50-fold increased risk of coronary artery disease (CAD). In the general population, oxidized low-density lipoprotein (ox-LDL) increases the risk for CAD. Normal high-density lipoproteins (HDLs) protect LDL from oxidation; proinflammatory HDLs do not. This study was undertaken to determine whether patients with SLE, who have chronic inflammation that causes oxidative damage, have more proinflammatory HDL and higher levels of ox-LDL, thus predisposing them to atherosclerosis. METHODS: One hundred fifty-four women with SLE, 48 women with rheumatoid arthritis (RA), and 72 healthy controls were studied. The ability of the patients' HDL to prevent oxidation of normal LDL was measured. Values >1.0 (the value assigned for LDL oxidation in the absence of HDL) after the addition of HDL indicated proinflammatory HDL. Plasma ox-LDL levels were measured as the amount of oxidation produced by the patient's LDL after the removal of HDL. RESULTS: SLE patients had more proinflammatory HDL (mean +/- SD score 1.02 +/- 0.57, versus 0.68 +/- 0.28 in controls [P < 0.0001] and 0.81 +/- 0.22 in RA patients [P = 0.001 versus SLE patients]). A higher proportion of SLE patients had proinflammatory HDL: 44.7% of SLE patients versus 4.1% of controls and 20.1% of RA patients had scores >1.0 (P < 0.006 between all groups). Levels of ox-LDL correlated with levels of proinflammatory HDL (r = 0.37, P < 0.001). SLE patients with CAD had significantly higher proinflammatory HDL scores than patients without CAD (P < 0.001). CONCLUSION: HDLs are proinflammatory in a significant proportion of SLE patients and are associated with elevated levels of ox-LDL. Abnormal HDLs impair the ability to prevent LDL oxidation and may predispose to atherosclerosis.     

Association between dental caries and pneumonia in patients with systemic lupus erythematosus

OBJECTIVE: To establish the association between oral pathology and pneumonia in patients with systemic lupus erythematosus (SLE). METHODS: Thirty women with SLE, consecutively admitted for hospitalization because of pneumonia, and 60 noninfected controls with SLE (30 hospitalized and 30 ambulatory), matched by age, sex, and date of hospitalization to the cases, were enrolled. At entry, information about sociodemographic variables, traditional infection risk factors, SLE characteristics, treatment, and comorbidity was gathered by medical chart review. In every patient, one rheumatologist performed a complete physical examination, and assessed disease activity and chronic damage using validated indices; and one periodontist performed a standardized oral health evaluation including the use of 6 international oral health indices. RESULTS: Twenty-eight patients with community-acquired and 2 patients with nosocomial pneumonias were included. Age of the total study population was 38.8 +/- 14.6 years, mean number of SLE criteria 6.3 +/-1.95, and disease duration 6.6 +/- 7.2 years, with no differences among the 3 groups. Cases had greater disease activity and damage, and were taking higher doses of prednisone than ambulatory controls (p 相似文献   

Contribution of traditional risk factors to coronary artery disease in patients with systemic lupus erythematosus.

OBJECTIVE: Several factors have been implicated in the high prevalence of premature coronary artery disease (CAD) in patients with systemic lupus erythematosus (SLE). We hypothesize that variables independent of traditional risk factors contribute significantly to the development of CAD in SLE. We investigated the relative contribution of traditional risk factors in SLE patients with CAD compared to non-SLE patients with premature CAD. METHODS: An age matched retrospective cohort analysis. The prevalence of traditional cardiovascular risk factors (hypertension, hypercholesterolemia, diabetes, smoking, family history) in patients with SLE who developed CAD during the course of their illness was compared to a group of age matched non-SLE subjects with premature CAD. Sexes were analyzed separately using Fisher's exact test and unpaired t tests. RESULTS: Thirty-five patients with SLE (27 women, 8 men) with definite ischemic heart disease were identified along with 397 non-SLE subjects (83 women, 314 men). In women with SLE the mean number of CAD risk factors per cardiac event was 2.0 +/- 0.77 versus 2.90 +/- 1.19 for the comparison group (p = 0.0008). In men with SLE the mean number of CAD risk factors was 1.87 +/- 0.83 versus 2.73 +/- 0.99 in the comparison group (p = 0.016). CONCLUSION: SLE patients with a cardiac event have fewer traditional risk factors than non-SLE patients with premature CAD. Thus premature CAD in SLE cannot be attributed solely to an excess of traditional risk factors.