Comparison of PREDICTS atherosclerosis biomarker changes after initiation of new treatments in patients with SLE

Objective Patients with SLE have an increased risk ofatherosclerosis (ATH) that is not adequately explainedby traditional risk factors. We previously described thePredictors of Risk for Elevated Flares, Damage Progression,and Increased Cardiovascular disease in PaTients withSLE (PREDICTS) atherosclerosis-risk panel, which includesproinflammatory HDL (piHDL), leptin, soluble tumournecrosis factor-like weak inducer of apoptosis (sTWEAK)and homocysteine, as well as age and diabetes. A highPREDICTS score confers 28-fold increased odds forfuture atherosclerosis in SLE. The aim of this study is todetermine whether PREDICTS biomarkers are modifiable bycommon lupus therapies.Methods This prospective observational study includedSLE subjects started on new lupus treatments. Leptin,sTWEAK, homocysteine and antioxidant function of HDLwere measured at baseline (prior to drug initiation), 6weeks and 12 weeks.Results 16 subjects started mycophenolate (MMF), 18azathioprine (AZA) and 25 hydroxychloroquine (HCQ).In MMF-treated subjects, HDL function progressivelyimproved from 2.23 ± 1.32 at baseline to 1.37±0.81at 6 weeks (p=0.02) and 0.93±0.54 at 12 weeks(p=0.009). sTWEAK levels also improved in MMF-treatedsubjects from 477.5±447.1 to 290.3±204.6 pg/mLafter 12 weeks (p=0.04), but leptin and homocysteinelevels were not significantly changed. In HCQ-treatedsubjects, only HDL function improved from 1.80±1.29 atbaseline to 1.03±0.74 after 12 weeks (p=0.05). Therewere no changes in the AZA group. MMF treatmentwas still associated with significant improvements inHDL function after accounting for potential confounderssuch as total prednisone dose and changes in diseaseactivity. Overall, the mean number of high-risk PREDICTSbiomarkers at week 12 significantly decreased in theentire group of patients started on a new lupus therapy(2.1±0.9 to 1.8±0.9, p=0.02) and in the MMF-treatedgroup (2.4±0.8 vs 1.8±0.9, p=0.003), but not in theAZA or HCQ groups. In multivariate analysis, the odds ofhaving a high PREDICTS atherosclerosis risk score at 12weeks were lower with MMF treatment (OR 0.002, 95%CI 0.000 to 0.55, p=0.03).Conclusions 12 weeks of MMF therapy improves theoverall PREDICTS atherosclerosis biomarker profile.Further studies will determine whether biomarkerchanges reflect decreases in future cardiovascularevents

High plasma leptin levels confer increased risk of atherosclerosis in women with systemic lupus erythematosus, and are associated with inflammatory oxidised lipids.

BackgroundPatients with systemic lupus erythematosus (SLE) are at increased risk of atherosclerosis, even after accounting for traditional risk factors. High levels of leptin and low levels of adiponectin are associated with both atherosclerosis and immunomodulatory functions in the general population.ObjectiveTo examine the association between these adipokines and subclinical atherosclerosis in SLE, and also with other known inflammatory biomarkers of atherosclerosis.MethodsCarotid ultrasonography was performed in 250 women with SLE and 122 controls. Plasma leptin and adiponectin levels were measured. Lipoprotein a (Lp(a)), oxidised phospholipids on apoB100 (OxPL/apoB100), paraoxonase, apoA-1 and inflammatory high-density lipoprotein (HDL) function were also assessed.ResultsLeptin levels were significantly higher in patients with SLE than in controls (23.7±28.0 vs 13.3±12.9 ng/ml, p<0.001). Leptin was also higher in the 43 patients with SLE with plaque than without plaque (36.4±32.3 vs 20.9±26.4 ng/ml, p=0.002). After multivariate analysis, the only significant factors associated with plaque in SLE were leptin levels in the highest quartile (≥29.5 ng/ml) (OR=2.8, p=0.03), proinflammatory HDL (piHDL) (OR=12.8, p<0.001), age (OR=1.1, p<0.001), tobacco use (OR=7.7, p=0.03) and hypertension (OR=3.0, p=0.01). Adiponectin levels were not significantly associated with plaque in our cohort. A significant correlation between leptin and piHDL function (p<0.001), Lp(a) (p=0.01) and OxPL/apoB100 (p=0.02) was also present.ConclusionsHigh leptin levels greatly increase the risk of subclinical atherosclerosis in SLE, and are also associated with an increase in inflammatory biomarkers of atherosclerosis such as piHDL, Lp(a) and OxPL/apoB100. High leptin levels may help to identify patients with SLE at risk of atherosclerosis

Assessing the validity of QRISK3 in predicting cardiovascular events in systemic lupus erythematosus

Objectives Traditional cardiovascular risk calculators such as the Framingham Risk Score (FRS) have been shown to underestimate risk in patients with SLE. The QRISK3 calculator is unique in including SLE and corticosteroid use as risk factors. This study aims to assess the validity of QRISK3 compared with other cardiovascular risk models in a cohort of patients with SLE in the USA.Methods We studied a prospective cohort of 366 adult patients with SLE without history of any cardiovascular event and followed them for 10 years. We compared the diagnostic performance of QRISK3 with FRS, modified FRS, Atherosclerotic Cardiovascular Disease (ASCVD), and Predictors of Risk for Elevated Flares, Damage Progression and Increased Cardiovascular Disease in Patients with SLE (PREDICTS).Results Sixty-four of the 366 patients (17.4%) experienced at least one cardiovascular event during the 10-year follow-up period. Of these patients 45% had a QRISK3 score >10%, whereas 20.5% of patients who did not have an event had a QRISK3 score >10% (p<0.001). The corresponding numbers for FRS, modified FRS, ASCVD and PREDICTS were 11.0% vs 7.2% (p=ns), 40.6% vs 28.0% (p=0.05), 12.2% vs 5.9% (p=ns), and 77% vs 32.1% (p<0.001), respectively. The areas under the receiver operating characteristic curve using QRISK3 >10% and high-risk PREDICTS were both larger than those using ASCVD >10%, FRS >10% and modified FRS >10%.Conclusions Both QRISK3 and PREDICTS demonstrated better performance in predicting risk of cardiovascular disease in this cohort of patients with SLE compared with FRS, modified FRS and ASCVD

Comparison of PREDICTS atherosclerosis biomarker changes after initiation of new treatments in patients with SLE

Objective Patients with SLE have an increased risk ofatherosclerosis (ATH) that is not adequately explainedby traditional risk factors. We previously described thePredictors of Risk for Elevated Flares, Damage Progression,and Increased Cardiovascular disease in PaTients withSLE (PREDICTS) atherosclerosis-risk panel, which includesproinflammatory HDL (piHDL), leptin, soluble tumournecrosis factor-like weak inducer of apoptosis (sTWEAK)and homocysteine, as well as age and diabetes. A highPREDICTS score confers 28-fold increased odds forfuture atherosclerosis in SLE. The aim of this study is todetermine whether PREDICTS biomarkers are modifiable bycommon lupus therapies.Methods This prospective observational study includedSLE subjects started on new lupus treatments. Leptin,sTWEAK, homocysteine and antioxidant function of HDLwere measured at baseline (prior to drug initiation), 6weeks and 12 weeks.Results 16 subjects started mycophenolate (MMF), 18azathioprine (AZA) and 25 hydroxychloroquine (HCQ).In MMF-treated subjects, HDL function progressivelyimproved from 2.23 ± 1.32 at baseline to 1.37±0.81at 6 weeks (p=0.02) and 0.93±0.54 at 12 weeks(p=0.009). sTWEAK levels also improved in MMF-treatedsubjects from 477.5±447.1 to 290.3±204.6 pg/mLafter 12 weeks (p=0.04), but leptin and homocysteinelevels were not significantly changed. In HCQ-treatedsubjects, only HDL function improved from 1.80±1.29 atbaseline to 1.03±0.74 after 12 weeks (p=0.05). Therewere no changes in the AZA group. MMF treatmentwas still associated with significant improvements inHDL function after accounting for potential confounderssuch as total prednisone dose and changes in diseaseactivity. Overall, the mean number of high-risk PREDICTSbiomarkers at week 12 significantly decreased in theentire group of patients started on a new lupus therapy(2.1±0.9 to 1.8±0.9, p=0.02) and in the MMF-treatedgroup (2.4±0.8 vs 1.8±0.9, p=0.003), but not in theAZA or HCQ groups. In multivariate analysis, the odds ofhaving a high PREDICTS atherosclerosis risk score at 12weeks were lower with MMF treatment (OR 0.002, 95%CI 0.000 to 0.55, p=0.03).Conclusions 12 weeks of MMF therapy improves theoverall PREDICTS atherosclerosis biomarker profile.Further studies will determine whether biomarkerchanges reflect decreases in future cardiovascularevents

A Panel of Biomarkers Associates With Increased Risk for Cardiovascular Events in Women With Systemic Lupus Erythematosus.

ObjectiveThe increase in cardiovascular events (CVEs) in systemic lupus erythematosus (SLE) is not fully explained by traditional risk factors. We previously identified four biomarkers (proinflammatory high-density lipoprotein, leptin, soluble TNF-like weak inducer of apoptosis (sTWEAK), and homocysteine) that we combined with age and diabetes to create the predictors of risk for elevated flares, damage progression, and increased cardiovascular diseasein patients with SLE (PREDICTS) risk profile. PREDICTS more accurately identified patients with SLE at risk for progression of subclinical atherosclerosis than any individual variable. We examined whether PREDICTS can also identify patients with SLE at risk for future CVEs.MethodsA total of 342 patients with SLE and 155 matched control subjects participated in this longitudinal prospective study. A high PREDICTS score was defined as three or more predictors or diabetes + one or more predictor. The biomarkers were measured at baseline using published methods. All major adverse CVEs (MACEs) were confirmed by medical record review.ResultsDuring 116 months of follow-up, 5% of patients with SLE died, 12% had a cerebrovascular event, and 5% had a cardiac event. Overall, 20% of patients with lupus experienced any new MACE compared with 5% of control subjects (P < 0.0001). More patients with SLE with a new MACE had high PREDICTS score at baseline (77%) versus patients with no new events (34%) (P < 0.0001). High baseline PREDICTS score also associated with cerebrovascular (P < 0.0001) and cardiac events (P < 0.0001) in SLE. Using Cox regression, a baseline high PREDICTS score associated with a 3.7-fold increased hazard ratio (HR) for a new MACE (P < 0.0001) in SLE. Hypertension (HR = 2.1; P = 0.006) was also a risk.ConclusionA high PREDICTS score and hypertension confer increased risk for new MACEs in patients with SLE

High plasma leptin levels confer increased risk of atherosclerosis in women with systemic lupus erythematosus, and are associated with inflammatory oxidised lipids.

BackgroundPatients with systemic lupus erythematosus (SLE) are at increased risk of atherosclerosis, even after accounting for traditional risk factors. High levels of leptin and low levels of adiponectin are associated with both atherosclerosis and immunomodulatory functions in the general population.ObjectiveTo examine the association between these adipokines and subclinical atherosclerosis in SLE, and also with other known inflammatory biomarkers of atherosclerosis.MethodsCarotid ultrasonography was performed in 250 women with SLE and 122 controls. Plasma leptin and adiponectin levels were measured. Lipoprotein a (Lp(a)), oxidised phospholipids on apoB100 (OxPL/apoB100), paraoxonase, apoA-1 and inflammatory high-density lipoprotein (HDL) function were also assessed.ResultsLeptin levels were significantly higher in patients with SLE than in controls (23.7±28.0 vs 13.3±12.9 ng/ml, p<0.001). Leptin was also higher in the 43 patients with SLE with plaque than without plaque (36.4±32.3 vs 20.9±26.4 ng/ml, p=0.002). After multivariate analysis, the only significant factors associated with plaque in SLE were leptin levels in the highest quartile (≥29.5 ng/ml) (OR=2.8, p=0.03), proinflammatory HDL (piHDL) (OR=12.8, p<0.001), age (OR=1.1, p<0.001), tobacco use (OR=7.7, p=0.03) and hypertension (OR=3.0, p=0.01). Adiponectin levels were not significantly associated with plaque in our cohort. A significant correlation between leptin and piHDL function (p<0.001), Lp(a) (p=0.01) and OxPL/apoB100 (p=0.02) was also present.ConclusionsHigh leptin levels greatly increase the risk of subclinical atherosclerosis in SLE, and are also associated with an increase in inflammatory biomarkers of atherosclerosis such as piHDL, Lp(a) and OxPL/apoB100. High leptin levels may help to identify patients with SLE at risk of atherosclerosis