Assessment of atherosclerotic risk factors and endothelial function in children and young adults with pediatric‐onset systemic lupus erythematosus

Objective

To characterize atherosclerotic risk factors and endothelial function in pediatric‐onset systemic lupus erythematosus (SLE).

Methods

Lipoproteins, oxidized state, and autoantibodies to oxidized low‐density lipoprotein (Ox‐LDL) were assessed. Endothelial function was evaluated using brachial artery reactivity.

Results

Thirty‐three SLE patients and 30 controls were studied. SLE subjects had significantly decreased mean high‐density lipoprotein (HDL) cholesterol (41 mg/dl versus 51 mg/dl; P = 0.002) and apolipoprotein A‐I (97 mg/dl versus 199 mg/dl; P = 0.0004). There was no difference between groups in markers of oxidized state (including nitric oxide metabolites, isoprostanes, and Ox‐LDL) or in endothelial function. However, SLE subjects had increased median anti‐Ox‐LDL IgG (2,480 relative light units [RLU] versus 1,567 RLU; P = 0.0007) and IgG immune complexes with LDL (4,222 RLU versus 2,868 RLU; P = 0.002).

Conclusion

Pediatric SLE patients had significantly decreased levels of HDL cholesterol and apolipoprotein A‐I and elevated titers of autoantibodies to Ox‐LDL. Despite these atherosclerotic risk factors, SLE patients had normal measures of oxidized state and endothelial function.

     

Novel cardiovascular risk factors and cardiac event predictors in female inactive systemic lupus erythematosus patients

Systemic lupus erythematosus (SLE) is associated with severe and premature cardiovascular disease, which cannot be explained by traditional risk factors alone. This study aims to investigate novel cardiovascular risk factors and cardiac event predictors in inactive SLE female patients who do not have any major cardiovascular risk factors. Twenty-five inactive (SLE disease activity index score <4) SLE female patients and 22 healthy control women were studied. SLE patients with a history of diabetes mellitus, hypertension, hyperlipidemia, smoking, or coronary artery disease (CAD) were excluded. Venous blood samples were analyzed for lipid subfractions and novel cardiovascular risk factors such as lipoprotein (a), homocysteine, fibrinogen, high-sensitivity C-reactive protein (hs-CRP), and serum amyloid A (SAA) levels. Endothelial dysfunction was assessed by flow-mediated dilatation (FMD) from the brachial artery at baseline and during reactive hyperemia. SLE patients and controls were similar in terms of age (40±10 years vs 38±10 years, p = NS). No significant difference was found between the groups regarding family history of premature CAD, blood pressure, body mass index, lipoprotein (a), homocysteine, fibrinogen, SAA, apoprotein A-1 and B levels. Compared with the controls, SLE patients had higher levels of hs-CRP [median (range): 1.82 (0.02–0.98) vs 0.68 (0.02–0.35), p=0.04]. FMD was lower in SLE patients than controls (7.1±2.1 vs 11.4±1.2%, p<0.001). Increased levels of hs-CRP and decreased FMD were found in inactive SLE patients. Increased hs-CRP levels may reflect ongoing low-grade inflammation that could be a cause of impaired FMD in SLE patients. These findings suggest that SLE patients without traditional major cardiovascular risk factors may have increased risk of cardiovascular disease and future cardiac events.     

Macrophage activation and coronary atherosclerosis in systemic lupus erythematosus and rheumatoid arthritis

Objective

Activation of macrophages may contribute to increased atherosclerosis and coronary artery disease in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Neopterin, a pteridine derivative, is a novel marker of monocyte and macrophage activation that is associated with atherosclerosis and cardiovascular risk in the general population. We examined the hypothesis that macrophage activation is associated with accelerated atherosclerosis in SLE and RA.

Methods

We compared serum neopterin concentrations, adjusted for age, race, sex, and serum creatinine concentration, in patients with SLE (n = 148) or RA (n = 166) and control subjects (n = 177). In patients with SLE or RA, serum neopterin concentrations were then tested for association (adjusted for age, race, sex, serum creatinine, and medication use) with measures of disease activity or damage, inflammatory markers and mediators, and coronary artery calcium measured by electron beam computed tomography.

Results

Neopterin concentrations were significantly higher in patients with SLE (median 8.0, interquartile range [IQR] 6.5–9.8 nmoles/liter) and RA (median 6.7, IQR 5.3–8.9 nmoles/liter) than controls (median 5.7, IQR 4.8–7.1 nmoles/liter), and were higher in SLE patients than in RA patients (all P < 0.001). In SLE, neopterin was significantly correlated with higher erythrocyte sedimentation rate (ESR; P = 0.001), tumor necrosis factor α (P < 0.001), monocyte chemoattractant protein 1 (P = 0.005), and homocysteine concentrations (P = 0.01), but in RA, it was only associated with ESR (P = 0.01). Neopterin was not associated with coronary calcium in either SLE (P = 0.65) or RA (P = 0.21).

Conclusion

Macrophage activation, reflected by increased serum neopterin concentrations, was increased in both SLE and RA. Neopterin was more robustly associated with atherogenic mediators of inflammation and homocysteine in SLE than in RA, but was not associated with coronary atherosclerosis in either disease.     

Prevalence and relation to risk factors of carotid atherosclerosis and left ventricular hypertrophy in systemic lupus erythematosus and antiphospholipid antibody syndrome

The prevalence of preclinical cardiovascular disease was determined in women with systemic lupus erythematosus (SLE) and control subjects matched for traditional risk factors. Compared with control subjects, patients with SLE had a higher prevalence of carotid atherosclerosis (41% vs 9%, p < 0.005) and left ventricular hypertrophy (32% vs 5%, p < 0.005), supporting the possibility that chronic inflammation predisposes to premature cardiovascular disease in SLE.     

A positive correlation between homocysteine and brachial–ankle pulse wave velocity in patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is associated with premature atherothrombotic complications. Hyperhomocysteinemia is considered a cardiovascular risk factor. Increased vascular stiffness may increase cardiovascular mortality. Pulse wave velocity (PWV) is a noninvasive method of analyzing vascular stiffness in the assessment of atherosclerosis. The objective of this study was to identify the relationship between plasma homocysteine levels and brachial–ankle pulse wave velocity (baPWV) measurement in SLE. Plasma homocysteine, baPWV, ankle–brachial index, blood pressure, C3, C4, anticardiolipin antibody (aCL), and anti-double-stranded DNA antibodies were determined in a total of 58 female patients with SLE. The control group comprised 32 age-matched healthy females. In addition, all patients were further classified into subgroups according to the presence of aCL (SLE/aCL+, n=27 vs SLE/aCL−, n=31) to determine the effect of aCL on the tested variables. The mean values for plasma homocysteine and baPWV were 13.19 μmol/l and 1,482 cm/s, respectively. Plasma homocysteine levels were significantly elevated in SLE patients when compared with the healthy controls. SLE patients with aCL had a significantly higher plasma homocysteine level than those without aCL. A significant positive correlation between plasma homocysteine and baPWV was found in patients with SLE (r=0.335, P=0.028, n=58). Plasma homocysteine also significantly correlated with right baPWV in all SLE patients (r=0.371, P=0.014, n=58) and in the SLE/aCL+ group (r=0.523, P=0.031, n=27). These findings indicate a possible link between plasma homocysteine and baPWV in SLE. In conclusion, SLE patients had an increased level of plasma homocysteine, and this phenomenon appeared to be related to vascular stiffness.     

Rate and determinants of progression of atherosclerosis in systemic lupus erythematosus

OBJECTIVE: To determine the rate of atherosclerosis progression as well as the relationship of traditional risk factors, systemic lupus erythematosus (SLE)-related factors, and treatment to atherosis progression in SLE patients. METHODS: Outpatients in the Hospital for Special Surgery SLE Registry underwent serial carotid ultrasound and clinical assessment in a longitudinal study. RESULTS: Among 158 patients, 77 (49%) had persistent absence of atherosclerosis (carotid plaque), 36 (23%) had unchanged atherosclerosis, and 45 (28%) had progressive atherosclerosis, defined as a higher plaque score (new plaque in 25 patients and more extensive plaque in 20 patients) after a mean +/- SD interval of 34 +/- 9 months. Multivariate determinants of atherosclerosis progression were age at diagnosis (odds ratio [OR] 2.75, 95% confidence interval [95% CI] 1.67-4.54 per 10 years, P < 0.001), duration of SLE (OR 3.16, 95% CI 1.64-6.07 per 10 years, P < 0.001), and baseline homocysteine concentration (OR 1.24, 95% CI 1.06-1.44 per mumoles/liter, P = 0.006). SLE patients with stable plaque and progressive plaque differed only in baseline homocysteine concentration. Atherosclerosis progression was increased across tertiles of homocysteine concentration (16.2%, 36.4%, and 56.1%; P = 0.001), and homocysteine tertile was independently related to progression of atherosclerosis (OR 3.14, 95% CI 1.65-5.95 per tertile, P < 0.001). Less aggressive immunosuppressive therapy and lower average prednisone dose were associated with progression of atherosclerosis in univariate, but not multivariate, analyses. Inflammatory markers and lipids were not related to atherosclerosis progression. CONCLUSION: Atherosclerosis develops or progresses in a substantial minority of SLE patients during short-term followup (10% per year on average). Older age at diagnosis, longer duration of SLE, and higher homocysteine concentration are independently related to progression of atherosclerosis. These findings show that aggressive control of SLE and lowering of homocysteine concentrations are potential means to retard the development and progression of atherosclerosis in SLE.     

Higher circulating levels of OxLDL % of LDL are associated with subclinical atherosclerosis in female patients with systemic lupus erythematosus

Because systemic lupus erythematosus (SLE) is associated with a high risk of atherosclerosis, a process that involves low-density lipoprotein (LDL) oxidation, we examined the hypothesis that raised fraction of LDL that is converted to oxidized (Ox) LDL expressed in OxLDL % of LDL (OxLDL %) is associated with the subclinical atherosclerosis in SLE. A cohort of 60 SLE patients with no previous history of cardiovascular disease had carotid artery ultrasound to identify plaques and to measure intima-media thickness (IMT). Forty females with rheumatoid arthritis (RA) were also enrolled in the study to serve as a control group. Plasma OxLDL concentrations were measured, and the OxLDL % of LDL were calculated. Traditional and SLE-related risk factors for atherosclerosis were evaluated. OxLDL % were significantly higher in SLE patients compared to patients with RA (p = 0.0311). OxLDL % were significantly higher in SLE patients with plaques than in those without plaques (p < 0.001). SLE patients in the highest IMT quartile have higher OxLDL % than patients in the lower three quartiles (p < 0.001). The odd ratio (OR) for the OxLDL % in patients with plaques was 6.143 (p < 0.001) when compared to patient without plaques, while OR for the OxLDL % was 8.34 (p < 0.001) in the patients with highest IMT quartile as compared to patients in the lower three quartiles after adjustment for confounding factors in logistic regression analysis. Our data provide evidence of an association between the circulating levels of OxLDL % of LDL with the risk for developing atherosclerosis in patients with SLE.     

Subclinical atherosclerosis in systemic lupus erythematosus (SLE): the relative contribution of classic risk factors and the lupus phenotype

OBJECTIVES: We aimed to examine the strength of association between traditional cardiovascular risk factors and carotid plaque development in systemic lupus erythematosus (SLE) patients and controls. We also aimed to determine which lupus-related factors are associated with carotid plaque and whether SLE sensitizes patients to the effects of traditional factors. METHODS: We studied 200 women with SLE and 100 controls. Demographic and risk factor data were collected and SLE features, including autoantibody profiles and therapy were noted. All subjects had B- mode ultrasound of their carotid arteries examined for the presence and distribution of plaque. RESULTS: SLE patients <55 years old had more plaque (21% vs 3% P < 0.01) and more SLE patients had plaque in the internal carotid artery (11% vs 4%; P < 0.05). Traditional risk factor models performed less well in SLE compared with controls [area under Receiver Operator Characteristic curves (AUC ROC) = 0.76 vs 0.90; P < 0.01]. A multivariable model using SLE factors only, performed significantly better (AUC ROC = 0.87; P < 0.01). The final model in SLE included age and cigarette pack-years smoking as well as azathioprine exposure ever, antiphospholipid antibodies (APLA) and previous arterial events (AUC ROC = 0.88). CONCLUSIONS: SLE patients have a higher prevalence and different distribution of carotid plaque than controls. SLE factors perform significantly better than traditional risk factors in their association with atherosclerosis in SLE and these factors add to the influence of traditional risk factors rather than sensitizing lupus patients to traditional factors. The SLE phenotype helps identify patients at increased risk of atherosclerosis.     

Dysfunctional proinflammatory high‐density lipoproteins confer increased risk of atherosclerosis in women with systemic lupus erythematosus

Objective

Women with systemic lupus erythematosus (SLE) have an increased risk of atherosclerosis. Identification of at‐risk patients and the etiology underlying atherosclerosis in SLE remain elusive. The antioxidant capacity of normal high‐density lipoproteins (HDLs) is lost during inflammation, and these dysfunctional HDLs might predispose individuals to atherosclerosis. The aim of this study was to determine whether dysfunctional proinflammatory HDL (piHDL) is associated with subclinical atherosclerosis in SLE.

Methods

Carotid artery ultrasound was performed in 276 women with SLE to identify carotid plaques and measure intima‐media thickness (IMT). The antioxidant function of HDL was measured as the change in oxidation of low‐density lipoprotein after the addition of HDL cholesterol. Two antiinflammatory HDL components, paraoxonase 1 and apolipoprotein A‐I, were also measured.

Results

Among the SLE patients, 48.2% were determined to have piHDL on carotid ultrasound, while 86.7% of patients with plaque had piHDL compared with 40.7% of those without plaque (P < 0.001). Patients with piHDL also had a higher IMT (P < 0.001). After multivariate analysis, the only factors found to be significantly associated with plaque were the presence of piHDL (odds ratio [OR] 16.1, P < 0.001), older age (OR 1.2, P < 0.001), hypertension (OR 3.0, P = 0.04), dyslipidemia (OR 3.4, P = 0.04), and mixed racial background (OR 8.3, P = 0.04). Factors associated with IMT measurements in the highest quartile were the presence of piHDL (OR 2.5, P = 0.02), older age (OR 1.1, P < 0.001), a higher body mass index (OR 1.07, P = 0.04), a cumulative lifetime prednisone dose ≥20 gm (OR 2.9, P = 0.04), and African American race (OR 8.3, P = 0.001).

Conclusion

Dysfunctional piHDL greatly increases the risk of developing subclinical atherosclerosis in SLE. The presence of piHDL was associated with an increased prevalence of carotid plaque and with a higher IMT. Therefore, determination of piHDL may help identify patients at risk for atherosclerosis.

     

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.     

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.

     

Platelet‐activating factor–acetylhydrolase and other novel risk and protective factors for cardiovascular disease in systemic lupus erythematosus

Objective

There is an important inflammatory component to atherosclerosis and cardiovascular disease (CVD). It is therefore interesting that the risk of CVD is high in inflammatory diseases such as systemic lupus erythematosus (SLE). In this study, we investigated nontraditional risk factors for the development of CVD in patients with SLE.

Methods

Twenty‐six women (mean age 52 years) with SLE and a history of CVD were compared with 26 age‐matched women with SLE and no clinical manifestations of CVD (SLE controls) and 26 age‐matched healthy women (population controls). Serum levels of several novel nontraditional risk and protective factors were determined: heat‐shock protein (HSP)–related factors (Hsp60, Hsp70, anti–human Hsp60, anti–human Hsp70, and anti–mycobacterial Hsp65), platelet‐activating factor–acetylhydrolase (PAF‐AH) activity, secretory phospholipase A₂ GIIA (sPLA₂), and anti–endothelial cell antibody (AECA). The intima‐media thickness and the presence of plaques in the common carotid arteries were determined by B‐mode ultrasound as a surrogate measure of atherosclerosis.

Results

Levels of PAF‐AH, but not HSP‐related factors, AECA, or sPLA₂, were significantly increased in SLE cases. Only PAF‐AH discriminated between SLE cases and SLE controls (P = 0.005). PAF‐AH was significantly associated with low‐density lipoprotein (LDL) cholesterol and total cholesterol in the SLE cases (r = 0.50, P = 0.0093 and r = 0.54, P = 0.0045), but not in either control group.

Conclusion

The increased levels of PAF‐AH in SLE cases and the association between PAF‐AH and LDL cholesterol adds support to the notion that PAF‐AH may promote atherothrombosis in SLE. The role of HSPs in CVD is complex, since anti‐Hsp65 appears to be associated with the presence of CVD, whereas Hsp70 might protect against it. In this cross‐sectional study, levels of HSP‐related factors, AECA, and sPLA₂ were not associated with CVD in SLE.

     

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.

     

Anticardiolipin antibody titre and plasma homocysteine level independently predict intima media thickness of carotid arteries in subjects with idiopathic antiphospholipid antibodies

This study evaluated whether IgG anticardiolipin antibody (aCL) titre and traditional risk factors for atherosclerosis bore any relationship to the intima media thickness (IMT) of carotid arteries of patients with idiopathic antiphospholipid antibodies (aPL). IMT was assessed by high-resolution sonography at the common carotid, carotid bifurcation and internal carotid in 42 (13 male, 29 female, mean age 31+/-10 years) aPL subjects, 29 with primary thrombotic antiphospholipid syndrome and 13 with persistence of aPL in the absence of any underlying disorder. In the same subjects the following were measured: plasma fibrinogen (FNG), von Willebrand factor (vWF), plasminogen activator inhibitor (PAI), homocysteine (HC), total cholesterol (CHO), triglycerides (TG), high density and low density lipoprotein (HDL and LDL), platelet numbers and aCL of IgG and IgM isotype. IMT of the internal carotid was greater in males than females (0.48+/-0.03 vs 0.39+/-0.01 mm, P=0.02). IMT of the carotid bifurcation was greater in thrombotic than nonthrombotic subjects (0.50+/-0.02 vs 0.42+/-0.02 mm, P=0.04). By simple regression, IMT of the common carotids correlated with age (P< 0.0001) IgG aCL titre (P=0.001), FNG (P=0.006), LDL (0.01), CHO (0.02) and PAI (P=0.02). IMT of the carotid bifurcation correlated with age (P=0.002), IgG aCL titre (P=0.0002), FNG (P=0.0001), HC (P=0.009), CHO (P=0.02), vWF (P=0.01) and number of thrombotic events (P=0.03). IMT of the internal carotids correlated with age (P=0.002), IgG aCL titre (P=0.0001), FNG (P=0.0008), PAI (P=0.002) and HC (P=0.01). By stepwise multiple regression analysis, IgG aCL titre independently predicted IMT at all carotid segments examined (P always <0.005). In addition, plasma FNG and HC also resulted independent predictors of IMT at the carotid bifurcation (P=0.001 and P<0.0001, respectively) and internal carotid (P=0.03 and P<0.0001, respectively). These data strongly support an atherogenic role for IgG aCL in patients with aPL. Measurement of plasma HC and FNG may help define aPL subjects at higher vascular risk who may require lowering of HC and FNG by vitamin and/or pharmacologic intervention.     

Association between endothelial biomarkers and arterial elasticity in young adults: the CARDIA Study

Reduced arterial elasticity and endothelial dysfunction both may indicate early cardiovascular (CV) disease in young adults. Pulse waveform analysis estimates large (LAE) and small (SAE) artery elasticity noninvasively. We assessed the associations between LAE and SAE and markers of endothelial dysfunction and CV risk factors. The Coronary Artery Risk Development in Young Adults (CARDIA) assessed arterial elasticity and other characteristics cross-sectionally in 389 men and 381 women age 27 to 42 years in 1995 (CARDIA year 10) and circulating levels of P-selectin and soluble intercellular adhesion molecule 1 (sICAM1) in 2000. We adjusted for variables included in the estimation of arterial elasticity (year 10 height, body mass index, age, heart rate, and blood pressure) and other year 10 characteristics. Mean adjusted SAE was 8.5 vs. 7.6 mL/mm Hg × 100 in those with urine albumin/creatinine ratio ≤4 vs. microalbuminuria (ratio >25; P_trend = .008). Mean LAE was 25.6 vs. 24.2 mL/mm Hg × 10 in the lowest vs. highest quintile of P-selectin (P_trend = .004). sICAM1 was unrelated to either LAE or SAE. Plasma triglycerides were inversely related to LAE (P_trend = .029). Cigarette smokers had lower SAE than nonsmokers (P_trend = .009). In addition to smoking and triglycerides, biomarkers for endothelial dysfunction were associated with impaired LAE and SAE in young adults.     

Hyperhomocysteinaemia and Risk of Thrombosis in Systemic Lupus Erythematosus Patients

Hyperhomocysteinaemia is strongly associated with increased relative risk of occlusive vascular disease, mainly of the carotid and coronary arteries. The aim of our study was to assess whether raised plasma homocysteine is a risk factor for thrombotic events in patients with systemic lupus erythematosus (SLE), a condition known to be associated with premature atherothrombotic complications. The study included 34 consecutive consenting SLE patients who were seen in the Rheumatology Unit of Al-Amiri hospital, one of the main teaching hospitals in Kuwait. Twenty consenting healthy subjects were included in the control group. Twenty-four patients were grouped as SLE without thrombosis and 10 had different types of thromboses. Vitamin B₁₂, folate, anticardiolipin antibodies (IgG and IgM), activated partial thromboplastin time (APTT) and total homocysteine level were measured for both patients and controls. A raised homocysteine concentration was defined as plasma homocysteine level above 9.4 mmol/l. Hyperhomocysteinaemia was found in 21 (61.8%) SLE patients. Low levels of folate and vitamin B₁₂ were significantly associated with high concentrations of plasma homocysteine (r = −0.35 and −0.39, respectively, P<0.01). SLE patients with elevated homocysteine concentration have a threefold increase in odds ratio of thrombotic events after adjusting for other risk factors (male sex, shortened APTT, treatment with prednisone, low folate and vitamin B₁₂ levels). We concluded that homocysteine is an independent risk factor for thrombosis in patients with SLE and is potentially modifiable. Received: 27 December 2001 / Accepted: 14 April 2002 Correspondence and offprint requests to: Dr I. H. Al-Salem, PO Box 16434, Al-Qadeseyah 35855, Kuwait. Tel: 965 2532025; Fax: 965 2666205; E-mail: driqbalham@hotmail.com     

Association between Arterial Elasticity Indices and Coronary Artery Calcium in a Healthy Multi-Ethnic Cohort

Objectives: Reduced arterial elasticity is a risk factor for coronary artery disease. Our main objective was to evaluate the association between large arterial elasticity (LAE) and small arterial elasticity (SAE) with subclinical atherosclerosis as reflected by the coronary artery calcium score (CACS). Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) includes a multi-ethnic, population-based cohort (n = 6,814), aged 45-84 years, free from clinical cardiovascular disease. We undertook a post hoc analysis of the NHLBI limited access data set of MESA subjects (n = 6,278) to evaluate the association between LAE and SAE with CACS [divided in to 4 categories: none (reference), 1-99, 100-299, and ≥300] using multivariable adjusted logistic regression analysis. Results: After adjustments for age, sex, systolic blood pressure, anti-hypertensive medications use, race, smoking, diabetes, high-density lipoprotein and total cholesterol, and high-sensitivity C-reactive protein, both LAE [adjusted odds ratio (aOR) 0.65; 95% CI 0.49-0.87 for CACS ≥300] and SAE (aOR 0.68, 95% CI 0.56-0.83 for CACS ≥300) were significantly (p < 0.001 for both) associated with a higher CACS. Conclusion: Both LAE and SAE, independent of traditional risk factors and inflammation, are associated with subclinical coronary atherosclerosis.     

Pentraxin 3 is associated with disease activity but not atherosclerosis in patients with systemic lupus erythematosus

Abstract

Objectives Pentraxin 3 (PTX3) plays an important role in inflammation, immunity, and atherosclerosis. Plasma PTX3 level has drawn attention as a marker that responds to local inflammation. Systemic lupus erythematosus (SLE), a chronic inflammatory disorder which can affect multiple organs, develops atherosclerosis prematurely. We examined the hypotheses that the concentration of plasma PTX3 increases in patients with SLE and that PTX3 is associated with the disease activity and premature atherosclerosis.

Methods Plasma PTX3 concentrations were measured in 65 patients with SLE and 53 control subjects. The patients were also evaluated with respect to their clinical characteristics, disease activity indices, and corticosteroid therapy. We performed carotid ultrasonography to measure subclinical atherosclerosis in patients with SLE.

Results Plasma PTX3 concentration of the SLE patients was significantly higher than that of the healthy controls (median 3.9 vs. 2.0 ng/mL, p < 0.001). In patients with SLE, PTX3 concentrations were correlated with SLEDAI (p = 0.011), BILAG index (p < 0.001), C-reactive protein (p < 0.001), anemia (p = 0.020), hypoalbuminemia (p = 0.022), and daily dose of prednisolone (p = 0.008) after adjustment for age and sex. PTX3 was not associated with disease duration, anti-ds DNA antibody, CH50, or carotid atherosclerosis.

Conclusions Patients with SLE have increased concentrations of PTX3 compared with control subjects. PTX3 was significantly associated with disease activity but not with carotid atherosclerosis.     

Low physical activity is associated with proinflammatory high‐density lipoprotein and increased subclinical atherosclerosis in women with systemic lupus erythematosus

Objective

To investigate the association between physical activity, functional activity of high‐density lipoprotein (HDL), and subclinical cardiovascular disease in patients with systemic lupus erythematosus (SLE).

Methods

A total of 242 SLE patients (all women) participated in this cross‐sectional study from February 2004 to February 2008. Carotid plaque and intima‐media thickness (IMT), antioxidant function of HDL, and traditional cardiac risk factors were measured. Physical activity was assessed from self‐reports by calculating the metabolic equivalents (METS) per week and by the physical function domain of the Medical Outcomes Study Short Form 36 (SF‐36). Data were analyzed using bivariate and multivariate regression analyses.

Results

Number of METS per week spent performing strenuous exercise was negatively correlated with IMT (r = ?0.4, P = 0.002) and number of plaques (r = ?0.30, P = 0.0001). Physical function as assessed by the SF‐36 was also negatively correlated with IMT (r = ?0.14, P = 0.03) and number of plaques (r = ?0.14, P = 0.04). In multivariate analyses, number of strenuous exercise METS was significantly associated with IMT (t = ?2.2, P = 0.028) and number of plaques (t = ?2.5, P = 0.014) when controlling for markers of SLE disease activity and damage, but not after controlling for traditional cardiac risk factors. Low physical activity, defined as <225 total METS per week, was associated with the presence of proinflammatory HDL (P = 0.03).

Conclusion

Low physical activity is associated with increased subclinical atherosclerosis and proinflammatory HDL in patients with SLE. Increased strenuous exercise may reduce the risk of atherosclerosis in SLE.     

Cardiovascular risk factors and LDL subfraction profile in Type 2 diabetes mellitus subjects with good glycaemic control

Objectives: To compare cardiovascular risk factors and LDL particle size in well-controlled Type 2 diabetes mellitus and normal subjects. Methods: Ninety-three Type 2 diabetic males and 186 age-matched, male controls were studied. Glycaemic control was stable for at least 3 months prior to recruitment. None were on insulin or lipid lowering therapy. Anthropometric indices, blood pressure, lipids, glucose, insulin, apolipoprotein A1 and B, LDL subfraction by density ultracentrifugation were obtained after an overnight fast of 10 h. Results: Diabetic subjects (mean HbA(1c) 6.6%+/-0.10) did not differ from controls in total cholesterol levels (5.04+/-0.08 vs. 5.16+/-0.05 mmol/l, respectively) but had lower serum HDL cholesterol (0.98+/-0.03 vs. 1.12+/-0.02 mmol/l, P<0.001), higher serum triglyceride (2.38+/-0.16 vs. 1.80+/-0.08 mmol/l, P<0.001), lower LDL(1) and LDL(2) and higher LDL(3) concentration. An LDL(3) concentration exceeding 100 mg/dl was found in 59.1% of diabetics and 39.1% of non-diabetics (P<0.001). Diabetic subjects also had higher body mass index, waist to hip ratio and insulin resistance (HOMA). Difference in LDL subfraction between groups disappeared after adjustments were made for either triglyceride or HDL cholesterol. Conclusion: Well controlled Type 2 diabetes mellitus subjects exhibit an increased cardiovascular burden through low HDL cholesterol and predominance of small, dense LDL particles.