Subclinical atherosclerosis and endothelial dysfunction in young South-Asian patients with systemic lupus erythematosus

Patients with systemic lupus erythematosus (SLE), especially Asian Indians, are at increased risk of developing premature atherosclerosis. To find out the prevalence and predictors of carotid intima-medial thickness (IMT) and brachial artery flow-mediated dilatation (FMD). Endothelial dysfunction was assessed by FMD in brachial artery and IMT was measured in common carotid artery in SLE patients and healthy controls. Sixty SLE patients (mean age 31 ± 9 years) and 38 healthy controls (mean age 34 ± 6 years) were included. The IMT was higher in SLE patients as compared to controls (0.49 ± 0.08 mm vs. 0.39 ± 0.05 mm, p < 0.0001). SLE and damage were independent predictors of abnormal IMT. FMD was impaired in SLE patients compared to controls (9.97% vs. 18.97%, p < 0.00001). None of the classical cardiovascular risk factors were predictors of FMD or abnormal IMT. Indian patients with SLE have higher prevalence of subclinical atherosclerosis and endothelial dysfunction. Presence of damage was associated with abnormal IMT in SLE patients.     

Subclinical carotid atherosclerosis in patients with psoriatic arthritis

OBJECTIVE: To examine the prevalence of subclinical atherosclerosis in patients with psoriatic arthritis (PsA) compared with healthy controls, and to identify clinical and biologic markers for atherosclerotic disease in this patient population. METHODS: Subclinical atherosclerosis was defined as the average of intima-media thickness (IMT) measures in the common carotid artery, bifurcation, and internal carotid artery on both sides above the 95th percentile of healthy controls. IMT was measured using carotid ultrasonography in 82 consecutive PsA patients and 82 healthy controls matched on age, sex, and ethnicity. We also ascertained traditional and novel cardiovascular (CV) risk factors, Framingham risk score (FRS), disease severity, treatment, and inflammatory markers in all PsA patients. RESULTS: No PsA patients had clinically overt CV diseases. After adjusting for traditional CV risk factors, PsA patients had a higher prevalence of subclinical atherosclerosis. PsA patients with subclinical atherosclerosis had significantly increased sugar, total triglyceride levels, total cholesterol/high-density cholesterol, white cell count, and patients' global assessment score compared with those without subclinical atherosclerosis. Using logistic regression analysis, independent explanatory variables associated with subclinical atherosclerosis in PsA included increased sugar and total triglyceride levels. The FRS was similar in PsA patients with or without subclinical atherosclerosis. Twenty-six (35%) of 74 patients had subclinical atherosclerosis despite having a low CV risk. CONCLUSION: PsA is associated with subclinical atherosclerosis after adjusting for traditional CV risk factors. Independent explanatory variables associated with subclinical atherosclerosis in PsA included increased sugar and total triglyceride levels. Carotid IMT can identify PsA patients with subclinical atherosclerosis who may benefit from early intervention.     

Dissociation between microalbuminuria and common carotid thickness in essential hypertensive men

BACKGROUND: The reasons why microalbuminuria (albuminuria > or = 15 microg/min), an expression of a renal microcirculatory abnormality, predicts cardiovascular disease in essential hypertension are unsettled. To test the hypothesis that microalbuminuria represents a marker of subclinical atherosclerosis, we evaluated its association with common carotid artery (CCA) intima media thickness (IMT), a measure of preclinical atherosclerosis and an independent predictor of cardiac and cerebrovascular events, in uncomplicated essential hypertensive individuals. MATERIALS AND METHODS: Albuminuria, ultrasonographic CCA IMT (the mean of six bilateral far wall measurements within 1.5 cm proximally to the flow divider), brachial blood pressure (BP), smoking habits and lipids were evaluated in 136 stage 1-3 untreated essential hypertensive men free of cardiovascular disease. RESULTS: CCA IMT did not differ between normo- (n = 99) and microalbuminuric (n = 37) patients. The correlation between CCA IMT and albuminuria was not significant, and the prevalence of microalbuminuria across IMT quartiles was not different. Microalbuminuric patients showed higher systolic BP and that parameter was the only independent correlate in a multivariate logistic regression model including also age, CCA IMT, diastolic BP, lipids and smoking habits as independent variables and microalbuminuria as the dependent one. CONCLUSION: This cross-sectional study in hypertensive subjects free of cardiovascular disease has shown a dissociation between microalbuminuria and CCA IMT, a surrogate measure of subclinical atherosclerosis, and a parameter linearly related to cardiovascular events. The data do not support the theory of microalbuminuria as a surrogate measure of subclinical atherosclerosis, while confirming the importance of systolic BP levels as an independent correlate of increased albuminuria in essential hypertension. Journal of Human Hypertension (2000) 14, 831-835     

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 micromoles/liter versus 0.40 +/- 0.07 micromoles/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 rheumatoid arthritis: morphologic evidence obtained by carotid ultrasound

OBJECTIVE: Recent studies have suggested increased cardiovascular disease among patients with rheumatoid arthritis (RA). We undertook this study to obtain morphologic evidence of subclinical atherosclerosis in RA patients. METHODS: We used high-resolution B-mode ultrasound to compare carotid artery intima-media wall thickness (IMT) between 53 postmenopausal women with RA and 53 controls matched by age, sex, and menopause status. No subject in either group had a history of atherosclerosis or its complications. We investigated the association between IMT and relevant clinical and therapeutic variables, including the impact of low-dose corticosteroid therapy (< or = 10 mg/day prednisolone). RESULTS: The mean +/- SD IMT of the left and right common carotid arteries in RA patients was significantly greater than that in controls (0.77 +/- 0.09 mm versus 0.68 +/- 0.14 mm; P < 0.001). Early RA (duration < or = 1 year) was associated with lesser IMT than was RA of longer duration (0.72 +/- 0.03 mm versus 0.78 +/- 0.01 mm; P < 0.04). Prednisolone use was not associated with increased IMT (0.78 +/- 0.02 mm in nonusers versus 0.76 +/- 0.01 mm in users; P = 0.38). CONCLUSION: Our data indicate that RA patients have an ultrasonic marker of early atherosclerosis consistent with an increased risk for atherosclerosis.     

高血压患者颈动脉亚临床病变与动态脉压指数及相关危险因素研究

目的探讨动态脉压指数（24h ambulatory pulse pressure index,24hAPPI）对原发性高血压（essentialhypertension,EH）患者颈动脉亚临床病变的影响。方法对255例EH患者进行动态血压监测（ambulatory blood pressure monitoring,ABPM）和颈动脉超声检查。所有患者分为3组：A组（PPI≤0.40）、B组（PPI：0.40～0.49）和C组（PPI≥0.50）。结果颈动脉斑块积分及颈动脉内膜中层厚度（intima media thickness,IMT）随着PPI的增加而增加,24hAPP、24hAPPI以及斑块的严重程度（颈动脉斑块积分）与IMT间呈相关性。多因素Logistic回归分析表明,24hAPP、24hAPPI、吸烟、高血压病程是颈动脉亚临床病变独立的预测指标。结论颈动脉斑块积分及颈动脉IMT随着PPI的增加而增加,24hPPI与动态PPI、斑块的严重程度与IMT间有相关性。24hAPP、24hAPPI、吸烟、高血压病程是颈动脉亚临床病变独立的预测指标。     

Increased prevalence of severe subclinical atherosclerotic findings in long-term treated rheumatoid arthritis patients without clinically evident atherosclerotic disease

We conducted the current study to search for subclinical atherosclerosis in patients with rheumatoid arthritis (RA) without clinically evident atherosclerosis or its complications who had been treated for a long duration, and to assess whether demographic or clinical factors affect the development of atherosclerotic disease. Forty-seven white patients fulfilling the 1987 American College of Rheumatology classification criteria for RA were recruited from Hospital Xeral-Calde, Lugo, Spain. Patients were required to have been treated for at least 5 years, including current treatment with 1 or more disease-modifying antirheumatic drugs. Patients with diabetes mellitus, renal insufficiency, hypertension, cardiovascular or cerebrovascular disease, and smokers were excluded. Forty-seven matched controls were also studied. Carotid intima-media wall thickness (IMT) and carotid plaques were measured in the right common carotid artery. The study was performed using high-resolution B-mode ultrasound.Patients had greater carotid IMT (0.779 +/- 0.164 mm) than did controls (0.699 +/- 0.129 mm); (p = 0.010). Sixteen (34%) patients showed carotid plaques compared with only 7 (15%) controls (p = 0.031). There was a positive correlation between the age at the time of study and the carotid IMT. Patients with carotid plaques had significantly greater carotid IMT (0.859 +/- 0.116 mm) than those without plaques (0.739 +/- 0.171 mm) (p = 0.014). Also, RA patients with carotid plaques had a significantly longer disease duration (mean, 21.0 yr) and more extraarticular manifestations (63%) than those without plaques (mean, 12.7 yr and 26%, respectively). Age at the time of the study and disease duration were the best predictive factors for the development of severe morphologic expression of atherosclerotic disease.The present study confirms an increased frequency of severe subclinical atherosclerotic findings in long-term actively treated RA patients from northwest Spain.     

Early treatment reduces the cardiovascular risk factors in newly diagnosed rheumatoid arthritis patients

OBJECTIVE: To investigate subclinical atherosclerosis and the effect of treatment in patients with early rheumatoid arthritis (RA). PATIENTS AND METHODS: Forty patients with early RA who met the revised American College of Rheumatology (ACR) criteria and disease duration of <1 year were included in the study. Smokers and patients with classical risk factors for atherosclerosis were excluded. The serum levels of total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol were determined in all patients before and after 1 year of therapy. Carotid artery intima-media thickness (IMT) and carotid plaque were measured before and after treatment. RA disease activity was measured using the 28 joint indices score (DAS-28) and clinical improvement was determined by the ACR response criteria. Forty-five age- and sex-matched nonsmoking volunteers were used as controls. All patients were treated with methotrexate and prednisone. RESULTS: RA patients had a baseline mild dyslipidemia characterized by a decrease in serum HDL-C levels and a high TC/HDL-C atherogenic ratio compared with controls. Both lipid parameters were significantly improved after treatment (P<0.01). Common carotid artery IMTs at baseline were higher in RA patients compared with controls (P<0.05). After 1 year of therapy there was a significant decrease in the IMTs (P<0.001). Thirty-five patients (88%) achieved the ACR 20%, while 30 (75%) reached the ACR 50% response criteria. A significant decrease of DAS-28 was observed after treatment (P<0.03). CONCLUSIONS: The atherogenic lipid profile and subclinical atherosclerosis are features of early RA, which improved after therapy. Early intervention and control of the disease activity may reduce the risk of atherosclerosis and cardiovascular events in patients with RA.     

A dietary and exercise intervention slows menopause-associated progression of subclinical atherosclerosis as measured by intima-media thickness of the carotid arteries

OBJECTIVES: The object of this study was to assess the effects of menopause and a diet/exercise intervention on subclinical atherosclerosis progression. BACKGROUND: Subclinical atherosclerosis has been linked to higher coronary heart disease and stroke rates and is greater among postmenopausal women according to cross-sectional analyses. Whether menopause is associated with an accelerated progression of subclinical disease is unknown, as is the extent to which lifestyle intervention can alter the course of progression. METHODS: Intima-media thickness (IMT) measures of the common carotid artery (CCA), internal carotid artery (ICA), and bulb segments of the carotid arteries were measured twice during the course of 4 years in 353 women from the Women's Healthy Lifestyle Project, a dietary and exercise clinical trial designed to prevent adverse risk factor changes through the menopause. A third measure was obtained 2.5 years later for 113 women. RESULTS: The progression of IMT was observed for the average of all segments (AVG), the CCA, and the bulb (0.007 mm/year, 0.008 mm/year, and 0.012 mm/year; p < 0.01 for all), but not for the ICA. Among controls, menopause was associated with accelerated IMT progression (0.003 mm/year for premenopausal women vs. 0.008 mm/year for perimenopausal/postmenopausal women for AVG IMT; p = 0.049). Additionally, among the 160 perimenopausal/postmenopausal women, the intervention slowed IMT progression (0.008 mm/year for the control group vs. 0.004 mm/year for the intervention group for AVG IMT; p = 0.02). Similar results were found for the CCA and bulb segments. CONCLUSIONS: These data demonstrate that the menopause transition is associated with accelerated subclinical atherosclerosis progression and that a diet/exercise intervention slows menopause-related atherosclerosis progression.     

Carotid intima-media thickness and serum leptin in psoriasis

Background

Psoriasis, a chronic inflammatory immune disorder, has been linked to increased cardiovascular mortality and morbidity. Leptin, an obesity-related peptide, has been shown to exert direct effects on the vascular endothelium and on vascular smooth muscle cells. Carotid intima-media thickness (IMT) measurement is a promising tool for detecting atherosclerosis in its pre-occlusive/subclinical phase.

Objective

The objective of the study was to evaluate carotid IMT and serum leptin levels in psoriatic patients as an indicator of subclinical atherosclerosis.

Materials and methods

The study was conducted in 50?psoriatic patients and 10?healthy controls. The clinical severity of skin affection in psoriatic patients was estimated using the psoriatic area and severity index (PASI). Serum leptin levels (ng\ml) and lipid profiles [including serum triglyceride (TG), serum low density lipoproteins (LDL) and serum high density lipoproteins (HDL)] were measured from blood samples. Carotid IMT was measured using carotid duplex ultrasonography.

Results

Psoriatic patients showed significantly higher leptin levels and higher IMT than controls. The mean of the intima-media thickness of the four vessels examined (MIMT) showed a positive correlation with patients’ mean ages, disease duration, body mass index, PASI scores, systolic blood pressure, diastolic blood pressure, leptin levels, LDL levels and triglyceride levels and no correlation with the mean HDL level.

Conclusion

Psoriasis is an independent risk factor for subclinical atherosclerosis. This cardiovascular impairment is influenced mainly by disease severity, serum TG levels and serum leptin levels.     

Common carotid intima-media thickness and von Willebrand factor serum levels in rheumatoid arthritis female patients without cardiovascular risk factors

High atherosclerosis prevalence was found in rheumatoid arthritis (RA), and the von Willebrand factor (vWF) was shown to be a marker for endothelial damage. The aim of this study was to evaluate the association of intima-media thickness of the left common carotid artery with vWF serum levels in rheumatoid arthritis patients without cardiovascular risk factors. We included 55 RA female patients, each with at least 5 years of duration of the disease, and 20 healthy female subjects as members of the control group. The vWF, cholesterol, triglycerides, and the immune variables—rheumatoid factor and reactive C protein—were evaluated. The media thickness and intima-media thickness (IMT) in patients and in the control subjects were assessed by Doppler ultrasound of the left common carotid artery. Although the ages for RA patients and healthy female controls were not different, the IMT of the left common carotid artery (IMT CCA) in rheumatoid arthritis patients was increased in comparison with healthy control measurements, the mean being 0.67 mm (SD 0.18) vs 0.58 mm (SD 0.10) with a p value 0.01. The vWF serum levels showed differences in RA patients from those in control patients, 145.6 (SD 30.08) vs 121.8 (SD 37.17), respectively, with p=0.007. A correlation was also found between vWF with IMT CCA in the RA patients: r=0.390 and p<0.05. We concluded that the measurements of the left common carotid artery intima-media thickness together with the von Willebrand factor serum levels could give valuable information about the artery status and the atherosclerosis process in early stages in patients with rheumatoid arthritis without cardiovascular risk factors.     

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 Behçet's Syndrome

OBJECTIVES: We had the impression and preliminary evidence that atherosclerosis was not much increased in Beh?et's syndrome (BS). Thus, we evaluated the presence of subclinical atherosclerosis in a sizeable group of patients with BS both with major organ involvement and mucocutaneous disease along with diseased and healthy controls. METHODS: We studied 239 (162 M/ 77 F; mean age: 40.7+/-7.0) patients with BS. Seventy-two (32 M/ 40 F) had only mucocutaneous and/or joint disease and 167 (130 M/ 37 F) had major organ involvement. Also 100 (24 M/ 76 F; mean age: 44.7+/-7.1) patients with rheumatoid arthritis (RA), 74 (58 M/ 16 F; mean age: 39.4+/-7.0) patients with ankylosing spondylitis (AS) and 156 (83 M/ 73 F; mean age: 39.2+/-6.6) healthy controls (HC) were studied as the control groups. We used B-mode USG to assess the frequency of plaques and intima-media thickness (IMT) in the carotid and femoral arteries. Traditional atherosclerotic risk factors were also evaluated. Men and women were analyzed separately. RESULTS: The frequency of plaques and the mean IMT in the carotid and femoral arteries were similar between patients with BS, AS and HC and also between the 2 subgroups of BS, among both men and women. Only men with RA were found to have significantly increased frequency of carotid artery plaques after adjustment for atherosclerotic risk factors. CONCLUSION: Increased atherosclerosis is not a prominent feature of BS, even among those patients with major organ involvement.     

Carotid artery intima-media thickness in patients with autoimmune connective tissue diseases: a case–control study

Patients with autoimmune rheumatic disorders have an increased incidence of cardiovascular (CV) events and mortality. Despite this being related to a high prevalence of the traditional CV risk factors, systemic inflammation has been postulated to be an independent CV risk factor, particularly in patients with rheumatoid arthritis (RA). However, data are still controversial. We designed a case–control study, in which patients with autoimmune rheumatic disorders were matched with age-, sex-matched controls. Prevalence of early atherosclerosis was assessed by carotid artery intima-media thickness (IMT) measurement. IMT values were considered normal (IMT ≤ 0.9 mm) or abnormal (IMT > 0.9). Multivariate analysis was performed to identify predictors of pathological IMT. Overall, 152 patients and 140 matched controls were enrolled. Prevalence of >0.9 mm IMT values did not significantly differ between patients with autoimmune rheumatic disorders and controls (61 vs. 69%, p = 0.1). In detail, a similar IMT distribution between the 69 RA patients and controls was observed. Cases with a CV risk factor showed a higher prevalence of pathological IMT as compared to those without any risk factor, both in patients (77.1 vs. 38.6%; p < 0.0001) and controls (84.6 vs. 25%; p < 0.0001). At multivariate analysis, age and presence of CV risk factors were found to be independent predictors of >0.9 mm IMT, while RA as well as any other considered rheumatic disease were not. Our data found a similar prevalence of preclinical arterial wall atherosclerotic damage in patients with autoimmune rheumatic diseases and matched controls. Presence of traditional CV risk factors and patient age remain the main factors involved in preclinical atherosclerosis in patients with autoimmune rheumatic disorders, including RA.     

Rheumatoid arthritis and macrovascular disease

OBJECTIVE: To measure the extent of subclinical atherosclerosis in patients with rheumatoid arthritis (RA) compared with controls, and to evaluate any potential vascular risk factors. METHODS: Forty RA patients were compared with an age- and sex-matched control group. Non-invasive vascular tests, i.e. carotid duplex scanning [measuring common carotid artery intima-media thickness (IMT)], ankle-brachial blood pressure index (ABPI) and QT dispersion on ECG (QTD), were performed. Traditional risk factors such as high blood pressure, blood sugar, lipids and steroid usage were assessed. RESULTS: The average IMT (S.E.) in RA patients was 0.73 (0.03) mm, compared with 0.62 (0.03) mm in the control group (P=0.01, Mann-Whitney). Ten out of 40 RA patients (25%) had an ABPI < 1.0 compared with 1/40 (2.5%) in the control group (P=0.007, Fisher's). QTD was higher in RA patients; mean (S.E.) 55 (2.70) ms compared with 40 (2.50) ms in the control group (P < 0.001, t-test). There were no significant differences in the prevalence of high blood pressure, diabetes or lipid profiles. However, patients on steroids had a higher mean QTD (S.E.): 63.5 (4) compared with 48 (2.7) ms in those patients who had not received long-term steroids (P=0.003, t-test). CONCLUSION: RA patients have an increased risk of subclinical vascular disease as was shown by a higher prevalence of carotid disease, peripheral arterial disease and increased QTD. Among traditional risk factors we found a history of steroid usage to be one of the potential risk factors.     

Role of insulin resistance in increased frequency of atherosclerosis detected by carotid ultrasonography in rheumatoid arthritis

OBJECTIVE: We evaluated the presence of subclinical atherosclerosis and factors influencing atherosclerosis, including insulin resistance (IR), in patients with rheumatoid arthritis (RA). METHODS: Sixty-three patients with RA and 34 controls were studied. Patients' cardiovascular risk factors were recorded; biochemical variables were determined. Intima-media thickness (IMT) of carotid arteries was determined by B-mode ultrasonography, and presence of atheromatous plaques was determined. IR was calculated according to the HOMA-IR homeostasis model. RESULTS: There were no differences in atherosclerotic risk factors between patients with RA and controls. In the RA group, the median carotid IMT was 0.61 mm (range 0.56-0.74), greater than the 0.54 mm (range 0.50-0.64) in controls (p = 0.01). There was a tendency to a higher frequency of carotid plaques in the RA group compared to controls [12 RA patients (19%) vs 2 controls (5.9%); p = 0.10]. Multivariate regression analysis revealed the factors that had an independent effect on increased carotid IMT: age (p < 0.001), male sex (p = 0.01), and total cholesterol level (p = 0.02). In RA patients with plaques, age (64.5 vs 48 yrs; p = 0.005), carotid IMT (0.75 vs 0.60 mm; p = 0.001), frequency of hypertension (58.3% vs 23.5%; p = 0.03), and IR (83.3% vs 29.4%; p = 0.001) were higher. Multivariate logistic regression analysis showed that factors independently associated with the presence of plaques were IR (OR 15.85, 95% CI 2.23-112.89, p = 0.006) and age (OR 1.11, 95% CI 1.02-1.21, p = 0.02). In RA patients, HOMA-IR correlated with age (r = 0.26, p = 0.04), Health Assessment Questionnaire score (r = 0.28, p = 0.04), and concentrations of triglyceride (r = 0.39, p = 0.003) and cholesterol (r = 0.33, p = 0.02). CONCLUSION: IR in the setting of active rheumatoid disease may contribute to mechanisms of accelerated atherogenesis observed in patients with RA.     

Intima-Media Thickness and Flow-Mediated Vasodilation in Asymptomatic Subjects with Newly Detected Severe Hypercholesterolemia

Background: The aim was to establish the predictors of early functional and structural vascular alterations (using intima-media thickness (IMT)) and flow-mediated vasodilation (%FMD) as well as to investigate the interrelationship between IMT and %FMD in asymptomatic, never-treated, severe hypercholesterolemia (HH). Methods: One hundred and twenty patients with asymptomatic, severe, untreated HH and 100 controls were included. ELISA was used for asymmetric dimethylarginine (ADMA) and cellular adhesion molecules, and fluid chromatography for total homocysteine (tHcy). Hewlett Packard SONOS 5500 with a 7.5 MHz transducer and MedicaSoft IMT software were used for evaluation of %FMD and IMT of common carotid artery (CCA). Results: Patients and controls differ with respect to all tested biomarkers (P < 0.05), except for P-selectin and E-selectin (P < 0.05). %FMD was lower in patients (P < 0.001). The IMT of the CCA was higher in patients (P < 0.001). Inverse correlations were found between %FMD and IMT mean and age, ADMA, Apo-B, Apo-B/Apo-A₁, and tHcy. ADMA was established as the most important factor related to %FMD. Age and Apo-B were established as the most important factors related to IMT mean. An inverse correlation was established between %FMD and IMT mean (r_xy= 0.546; P < 0.001)). If cases with IMT mean ≥1 were excluded, the correlation weakened. In patients with IMT mean ≥1 mm, the correlation did not change. Conclusion: In conclusion, asymptomatic, untreated patients with severe hypercholesterolemia are at high risk of having increased IMT of the CCA, especially if there is endothelial dysfunction, verified by %FMD of the brachial artery.     

Inflammatory mediators and premature coronary atherosclerosis in rheumatoid arthritis

Objective

Rheumatoid arthritis (RA) is an inflammatory disease associated with premature atherosclerosis. We hypothesized that mediators of inflammation associated with atherosclerosis in other populations (interleukin‐6 [IL‐6], tumor necrosis factor α [TNFα], serum amyloid A [SAA], vascular endothelial growth factor, neutrophil count, IL‐1α, E‐selectin, intercellular adhesion molecule 1 [ICAM‐1], myeloperoxidase [MPO], matrix metalloproteinase 9, and vascular cell adhesion molecule 1) would be increased and associated with the severity of coronary atherosclerosis in patients with RA.

Methods

Clinical variables, concentrations of inflammatory mediators, and coronary artery calcification were measured in 169 patients with RA and 92 control subjects. Differences in concentrations of inflammatory mediators were compared using median quantile regression. The relationship of inflammatory mediators with the severity of coronary calcification in RA and control subjects was examined using proportional odds logistic regression, allowing for interaction with disease status. Models were adjusted for traditional cardiovascular risk factors.

Results

Median serum concentrations of IL‐6, SAA, ICAM‐1, E‐selectin, TNFα, and MPO and peripheral blood neutrophil count were higher in patients with RA than controls (all P < 0.05), independent of Framingham risk score and diabetes mellitus (DM). IL‐6 (main effect odds ratio [OR] 1.72; 95% confidence interval [95% CI] 1.12, 2.66) and TNFα (main effect OR 1.49; 95% CI 1.16, 1.90) concentrations were significantly associated with higher amounts of coronary calcium, independent of Framingham risk score and DM, and such main effects significantly differed from controls (P = 0.001 and 0.03 for interaction, respectively).

Conclusion

TNFα and IL‐6 are significantly associated with the severity of subclinical atherosclerosis, independent of Framingham risk score, in RA.     

Prevalence and risk factors of atherosclerosis in patients with psoriatic arthritis

OBJECTIVES: To evaluate the extent of subclinical atherosclerosis by measuring the intima-media wall thickness (IMT) of the common carotid artery in patients with psoriatic arthritis (PsA) and to identify vascular risk factors associated with PsA. METHODS: Forty-seven patients with PsA were compared with 100 allegedly healthy subjects. Carotid duplex scanning was used to measure common carotid artery IMT. Traditional risk factors, such as gender, age, body mass index (BMI), hypertension, smoking, and lipids were checked. Assessment of PsA activity included clinical patterns of involvement, degree of severity, duration of morning stiffness, number of tender and swollen joints, degree of pain and fatigue, the Bath Ankylosing Spondylitis Disease Activity Index, the Psoriasis Area and Severity Index, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and fibrinogen. RESULTS: The average IMT (mean +/- standard deviation) for PsA patients was significantly higher compared with controls (0.76 +/- 0.11 versus 0.64 +/- 0.27, respectively, P < 0.00001) for the whole group and after adjustment for age, gender, BMI, hypertension, and hyperlipidemia. The PsA subjects had significantly higher levels of hypertension, hyperlipidemia, ESR, CRP, and fibrinogen, and their average IMT significantly correlated with age, BMI, duration of skin and joint disease, spine involvement, ESR, and fibrinogen. IMT did not correlate with the presence of oligo- or polyarthritis but was increased in patients with clinical spinal involvement. IMT was not associated with the degree of severity or the use of different therapies for PsA, including methotrexate or tumor necrosis factor-alpha-blocking agents. CONCLUSIONS: PsA patients exhibited greater IMT than healthy controls. Increased IMT independently correlated with parameters of disease activity and conventional risk factors of atherosclerosis.     

Inflammation and bone resorption as independent factors of accelerated arterial wall thickening in patients with rheumatoid arthritis

OBJECTIVE: We recently reported that rheumatoid arthritis (RA) patients had increased intima-media thickness (IMT) of the common carotid artery (CCA). The present longitudinal study was performed to determine whether the change in arterial thickness was accelerated in RA patients and to determine which factor was important in the progression of arterial wall changes. METHODS: We studied 62 female RA patients with stable disease activity and 63 healthy female controls. IMT of the CCA was measured twice by high-resolution B-mode ultrasonography. The second examination was performed 18-36 months after the first, and changes were expressed as millimeters of increase per year. Baseline examinations included blood markers of inflammation and urinary calcium excretion (expressed as the calcium-to-creatinine ratio). RESULTS: RA patients showed a significantly greater increase in IMT of the CCA compared with controls. In univariate analyses of the RA patient data, the C-reactive protein (CRP) level correlated with the increase in CCA IMT. Other markers of inflammation (the erythrocyte sedimentation rate and white blood cell and platelet counts) also showed significant positive associations with the annual increase in CCA IMT in multiple regression models when adjusted for age, smoking status, blood pressure, and serum cholesterol level. The urinary calcium-to-creatinine ratio was also significantly associated with an increase in CCA IMT. Moreover, both the CRP level and the urinary calcium-to-creatinine ratio were significantly and independently associated with the increase in IMT of the CCA. CONCLUSION: Patients with RA have a higher rate of increase in thickening of the arterial wall. Inflammation and calcium mobilization are factors closely associated with the accelerated arterial wall changes.