Assessment of Coronary Risk Based on Cumulative Exposure to Lipids in Systemic Lupus Erythematosus

2013 ◽  
Vol 40 (12) ◽  
pp. 2006-2014 ◽  
Author(s):  
Mandana Nikpour ◽  
Dafna D. Gladman ◽  
Dominique Ibanez ◽  
Paula J. Harvey ◽  
Murray B. Urowitz

Objective.To quantify the independent role of each of low-density lipoprotein cholesterol (LDL-C), total cholesterol:high-density lipoprotein cholesterol ratio (TC:HDL-C), triglyceride (TG) level, and HDL-C as a marker of coronary risk in systemic lupus erythematosus (SLE).Methods.Patients with lipid measurements taken before a coronary event (or last clinic visit) were included. Mean and time-adjusted mean (TAM) levels were calculated for each lipid variable in each patient. Time-dependent proportional hazards regression models were used to quantify the risk of coronary event [myocardial infarction (MI) or angina], after adjustment for age.Results.Among 384 patients, over a mean (SD) followup of 3.81 (2.58) years, there were 21 “first” coronary events (6 MI, 15 angina). Mean and TAM LDL-C (HR 1.83, 95% CI 1.19–2.81, p = 0.006), TC:HDL ratio (HR 1.43, 95% CI 1.02–2.00, p = 0.04), and TG (HR 2.11, 95% CI 1.32–3.39, p = 0.0019) were predictive of coronary event at subsequent visits. In contingency table analysis, TAM LDL-C cutpoint of 2.0 mmol/l had a sensitivity and negative predictive value for coronary event of 85.7% (95% CI 63.7–97.0) and 93.9% (95% CI 83.1–98.7), respectively. However, at this cutpoint the specificity was only 12.7% (95% CI 9.4–16.5).Conclusion.This study links LDL-C, TC:HDL-C ratio, and TG to coronary risk in patients with SLE and quantifies the magnitude of this risk. SLE-specific risk assessment levels for lipids may be selected to optimize positive or negative predictive values.

2009 ◽  
Vol 36 (8) ◽  
pp. 1639-1645 ◽  
Author(s):  
MARIA URQUIZU-PADILLA ◽  
EVA BALADA ◽  
PILAR CHACON ◽  
EDUARDO HERMOSILLA PÉREZ ◽  
MIQUEL VILARDELL-TARRÉS ◽  
...  

Objective.To determine the lipid profile of patients with systemic lupus erythematosus (SLE) according to the disease activity, and to calculate the percentage of patients that diverged from optimal values.Methods.Serum was collected from 52 patients with SLE at flare and at remission. SLE disease activity was measured by using the SLE Disease Activity Index (SLEDAI). Clinical and biological measures were evaluated in both situations. Total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC), and triglyceride (TG) levels were analyzed after overnight fasting. We also calculated the atherogenic ratios of TC/HDLC and LDLC/HDLC.Results.SLE patients had significantly higher median TC/HDLC and LDLC/HDLC ratios at flare than during remission: 4.5 ± 1.5 versus 3.9 ± 1.0 (p = 0.007) and 2.7 ± 1.1 versus 2.4 ± 0.8 (p = 0.015), respectively. The differences persisted after adjustments based on kidney disease and treatment but not after adjusting by creatinine clearance < 60 ml/min/1.73 m2in remission. The variation between flare and remission of the percentage of SLE patients with high-risk levels of lipid profile to desirable values, and vice versa, was statistically significant for the LDLC/HDLC ratio (9 vs 1; p = 0.021).Conclusion.Our results reflect a higher risk of atherosclerosis phenomena in SLE patients during flare than during clinical remission. This might explain the propensity to develop coronary heart disease in patients with SLE.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1785.1-1785
Author(s):  
S. Ganhão ◽  
A. Mendes ◽  
F. Aguiar ◽  
M. Rodrigues ◽  
I. Brito

Background:Systemic lupus erythematosus (SLE) is an autoimmune systemic disease associated with premature atherosclerosis. Risk factors include dyslipoproteinemia, inflammation, oxidized low-density lipoprotein (LDL), hyperhomocysteinemia and antiphospholipid antibodies. Hyperlipidemic condition is being reported to promote the production of proinflammatory cytokines such as IL-1β, IL-6, and IL-27 and lowering blood lipid levels improves the disease. Oxidative stress is elevated, mainly due to mitochondrial dysfunction, further disrupting lipid metabolism. Some drugs also have an impact on lipid profile, such as chronic steroid use, which worsens LDL, HDL, and TG levels.Objectives:To assess the relationship between lipid profile and disease activity in juvenile SLE (jSLE) patients.Methods:Retrospective study of jSLE patients, fulfilling both 2012 and 2019 EULAR/ACR classification criteria for SLE. Juvenile-onset was defined as age at diagnosis <18 years. Demographics and clinical characteristics were collected. To evaluate the activity of jSLE, the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) was used. Statistical analysis was performed with SPSS®. Spearman’s rank non-parametric test or Pearson’s parametric test were used to assess the bivariate correlation for inflammatory and metabolic variables. P value <0.05 was considered significant for all the statistical tests.Results:35 patients were included, with current median (min-max) age of 22 (16-35) years, mean (SD) age of diagnosis of 15.8 (2.4) years; 91.4%female. Median ESR was 19 (2-75) mm/h, CRP 1.65 (0.1-9.6) mg/L, albumin 41.6 (16.7-46.3) g/L, proteinuria 0.2 (0-3) g/dL, leukocyturia 0 (0-1362.7)/uL, erythrocyturia 0 (0-501.9)/uL and anti-double stranded DNA 89.3 (10-800) U/mL. Mean C3 was 102.1 (21.6), C4 17.1 (7.4) mg/dL and creatinine 0.63 (0.1) mg/dL. Median SLEDAI was 2 (0-12). All were ANA positive, 40 % positive for antinucleossome antibodies, 25.7% anti-ribossomal P protein antibody, 11.4% anti-Sm, 8.6% autoantibodies againstβ2-glycoproteinI, 8.6% anti-cardiolipin, 14.3% lupus anticoagulant, 37.1% anti-SSA and 8.6% anti-SSB. Articular manifestations were present in 48.6%, mucocutaneous in 77.1%, haematological in 45.7%, lupus nephritis in 42.9%, serositis in 8.6% and pulmonary interstitial disease in 2.9%. Mean (SD) total cholesterol values (TC) was 165.5 (44.7) mg/dL and LDL 94.5 (29.9) mg/dL. Median high-density lipoprotein was 52 (28-92) and triglycerides (TG) 81.5 (41-253) mg/dL. Median daily prednisolone dose was 5 (0-40) mg. 88.6% were treated with hydroxychloroquine, 31.4% with mychophenolate mophetil and 14.3% with azathioprine. TC was negatively correlated with serum albumin (p=0.043, rho=-378) and positively with SLEDAI (p=0.032; rho= 0.392), proteinuria (p=0.009; rho= 0.469) and leukocyturia (p=0.031; rho= 0.394). A positive correlation was found between LDL and proteinuria (p=0.043; rho= 0.385) and between TG and CRP (p=0.001; rho= 0.575). TG were also positively correlated with prednisolone daily dose (p=0.035; rho= 0.394). Mean LDL was higher in anti-Sm positive patients (p=0.022). No differences were found regarding anti-phospholipids antibodies. Nephritic lupus patients had worse lipid metabolism, but this did not reach statistical significance.Conclusion:In out cohort, increased expression of TC, LDL and TGs is associated with disease activity in SLE. As expected, higher doses of prednisolone also correlated with lipid metabolism.References:[1]Machado D et al. Lipid profile among girls with systemic lupus erythematosus. Rheumatol Int. 2017 Jan;37(1):43-48Disclosure of Interests:None declared


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Hua-Chen Chan ◽  
Liang-Yin Ke ◽  
Hsiu-Chuan Chan ◽  
Hung Su ◽  
An-Sheng Lee ◽  
...  

Background: Patients with systemic lupus erythematosus (SLE) are twice more likely to develop cardiovascular disease than the general population, even though their plasma LDL cholesterol (LDL-C) levels are usually not elevated. To delineate the mechanisms, we examined the chemical properties of their LDL. Methods and Results: LDL isolated from SLE patients (LDL-C, 105±33 mg/dL; n=24) exhibited greater mobility in agarose gel electrophoresis than LDL of healthy control subjects (LDL-C, 121±25 mg/dL; n=24), secondary to an increased distribution of L5 (2.30±1.3% vs. 0.7±0.3%; P <0.0001), the most electronegative subfraction of LDL identified by anion-exchange chromatography, in total LDL. CX3CL1 is a membrane-bound chemokine expressed in injured endothelial cells (ECs). CD16 + monocytes are CX3CR1-expressing cells that recognize CX3CL1. Compared with control, SLE patients had a twofold ( P <0.001) increase in CX3CL1 and a threefold ( P <0.0001) increase in CD16 + monocytes in the plasma. Moreover, there was a positive correlation between the CX3CL1 and L5 levels (R=0.45; P <0.018). MALDI/TOF mass spectrometry of the lipid extracted from SLE-LDL revealed a shift from phosphatidylcholines (PCs) to lyso-PCs (LPCs), including m/ z 496.33, 524.36, 537.01, 550.94, when compared with the lipid of control LDL (Figure). The shift was especially prominent in L5. Exposing human aortic ECs to L5 but not normal LDL resulted in a fivefold ( P <0.0001) increase in CX3CL1 expression with concomitant apoptosis. These effects of L5 were significantly attenuated by blocking the platelet-activating receptor, confirming the role of phospholipids in L5’s bioactivity. Conclusions: The increased distribution of LPC-rich electronegative LDL, which induces CX3CL1-CX3CR1 interactions between vascular cells, may contribute to the increased cardiovascular disease prevalence in SLE in the absence of LDL-C elevation.


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