scholarly journals Novel cardiovascular risk prediction models in patients with systemic lupus erythematosus

Lupus ◽  
2011 ◽  
Vol 20 (14) ◽  
pp. 1526-1534 ◽  
Author(s):  
VK Kawai ◽  
JF Solus ◽  
A Oeser ◽  
YH Rho ◽  
P Raggi ◽  
...  

Women with systemic lupus erythematosus (SLE) have increased risk for coronary heart disease (CHD) which is underestimated by the Framingham risk score (FRS). We hypothesized that new risk scores that include inflammation or vascular age in the risk calculation would better identify women with SLE at risk for CHD, particularly in those with subclinical coronary atherosclerosis. We calculated the FRS and Reynolds risk score (RRS) in 121 women with SLE and 65 age-matched female controls; coronary age-modified risk scores (camFRS, camRRS) were calculated using coronary age derived from the coronary artery calcium (CAC) score. Risk scores were compared in SLE and controls, and in SLE patients with and without CAC. Although CAC was present in 21 SLE patients (17%) and four controls (6%) ( p = 0.033); the FRS, camFRS, RRS, and camRRS, did not differ significantly among SLE and controls ( p > 0.05), but were all significantly higher in SLE patients with CAC compared with those without ( p < 0.001 for all). The camFRS (8%, p = 0.016) but not camRRS (5%, p = 0.221) assigned significantly more SLE patients to a category of ≥ 10% risk than conventional FRS (1%) and RRS (2%). The RRS was of limited use but coronary age may improve CHD risk prediction in SLE.

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Panafidina ◽  
T V Popkova ◽  
D S Novikova

Abstract Background Nephritis in systemic lupus erythematosus (SLE) is a factor contributing to early development of atherosclerosis (AS). Objectives The aim of the study is to determine differences in cardiovascular risk factors and AS in SLE pts with and without lupus nephritis (LN). Methods The study included 162 females, age 35 [26–43] years (median [interquartile range 25–75%])) with SLE (ACR,1997). We divided SLE pts on two groups, comparable in age: the 1st group is the pts with LN (n=84, 52%), the 2nd - without LN (n=78, 48%). We considered traditional factors of cardiovascular disease (CVD): (smoking, family history of CVD, blood pressure, cholesterol (total, HDL, LDL) and triglyceride (TG) levels, body mass index, diabetes mellitus) and SLE-related factors (age at onset, duration, clinical features, SLE Disease Activity Index (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics damage index (SLICC/DI), treatment with steroids); intima-media thickness (IMT) and the 10-year risk for coronary events. Carotid intima-media wall thickness of common carotid arteries was measured by high resolution B-mode ultrasound. The 10-year risk for coronary events was estimated by the Framingham risk equation. Results Median SLE duration was 8,0 [2,3–17,0] years, SLEDAI 2K – 8 [3–16], SLICC/DI score – 2 [0–3], duration of prednisone treatment – 72 [26–141] months. SLE pts from the 1st group had higher prevalence of hypertension (61% vs 36%, p<0,01), systolic blood pressure (130 [110–150] vs 120 [110–130]mm Hg, p<0,01), diastolic blood pressure (80 [70–95] vs 70 [70–80] mm Hg, p<0,05), TG concentration (136 [98–184] vs 100 [61–162] mg/dl, p<0,01), Framingham Risk Score (5 [1–30] vs 1 [1–27]%, p<0,05), SLEDAI-2K (12 [5–19] vs 4 [2–10], p<0,ehz745.08501), SLICC/DI score (2 [0–4] vs 0 [0–2], p<0,01), prednisone therapy duration (95 [26–192] vs 44 [14–98] months, p<0,05), prednisone cumulative dose (34,4 [13,6–82,5] vs 15,7 [6,2–35,2] g, p<0,001), mean IMT (0,73 [0,65–0,83] vs 0,67 [0,61–0,75] mm, p<0,01), than the pts from the 2nd group. There is no difference in CVD frequency in these groups (17% vs 8%, p=0,084). Conclusions SLE patients with and without LN had no difference in frequency of clinical manifestations of AS (CVD), but had a greater value of mean IMT, Framingham Risk Score and a higher incidence of both traditional (hypertension, TG concentration) and SLE-related (disease activity, prednisone therapy) risk factors for AS.


2021 ◽  
Author(s):  
Sorwe Mojtahed Poor ◽  
Michaela Köhm ◽  
Frank Behrens ◽  
Harald L. Burkhardt

Abstract Background Cardiovascular risk factors and diseases represent the comorbidities with the highest prevalence in rheumatic diseases. Still, actual cardiovascular risk burden is often underestimated in current risk prediction models Methods To assess and compare traditional and nontraditional cardiovascular risk burden in patients with different rheumatic diseases, we analyzed demographical, clinical, laboratory, and non-invasive imaging data on patients with psoriatic arthritis in comparison with a cohort of ANCA-associated vasculitis and systemic lupus erythematosus in a cross-sectional design. Overall, we analyzed 138 patients. Results Data analysis revealed significant differences in traditional and nontraditional markers for cardiovascular disease risk as well as disparities in diastolic (6.67 % in PsA vs. 36% in AAV; OR 0.12 [0.03; 0.42], p < 0.05) and systolic left ventricular function (1.11% in PsA vs. 13.04% in SLE; OR 0.07 [0.005; 0.54], p < 0.05), whereas odds ratios for cardiovascular events did not differ significantly. Conclusion Our findings suggest that cardiovascular risk prediction algorithms should consider disease-specific disparities, which includes non-traditional cardiovascular risk burden, arguing for a patient-oriented risk assessment and consequently accurate risk stratification.


2018 ◽  
Vol 73 (1) ◽  
pp. 19-25 ◽  
Author(s):  
Susanne Rospleszcz ◽  
Barbara Thorand ◽  
Tonia de las Heras Gala ◽  
Christa Meisinger ◽  
Rolf Holle ◽  
...  

BackgroundThe Framingham Risk Score (FRS) and the Pooled Cohort Equations (PCE) are established tools for the prediction of cardiovascular disease (CVD) risk. In the Western world, decreases in incidence rates of CVD were observed over the last 30 years. Thus, we hypothesise that there are also temporal trends in the risk prediction performance of the FRS and PCE from 1990 to 2000.MethodsWe used data from n=7789 men and women aged 40–74 years from three prospective population-based cohort studies enrolled in Southern Germany in 1989/1990, 1994/1995 and 1999/2000. 10-year CVD risk was calculated by recalibrated equations of the FRS or PCE. Calibration was evaluated by percentage of overestimation and Hosmer-Lemeshow tests. Discrimination performance was assessed by receiver operating characteristic (ROC) curves and corresponding area under the curve (AUC).ResultsAcross the three studies, we found significant temporal trends in risk factor distributions and predicted risks by both risk scores (men: 18.0%, 15.4%, 14.9%; women: 8.7%, 11.2%, 10.8%). Furthermore, also the discrimination performance evolved differently for men (AUC PCE: 76.4, 76.1, 72.8) and women (AUC PCE: 75.9, 79.5, 80.5). Both risk scores overestimated actual CVD risk.ConclusionThere are temporal trends in the performance of the FRS and PCE. Although the overall performance remains adequate, sex-specific trends have to be taken into account for further refinement of risk prediction models.


2021 ◽  
Vol 12 ◽  
Author(s):  
Haiping Xing ◽  
Haiyu Pang ◽  
Tian Du ◽  
Xufei Yang ◽  
Jing Zhang ◽  
...  

Background and aims: Patients with systemic lupus erythematosus (SLE) have a significantly higher incidence of atherosclerosis than the general population. Studies on atherosclerosis prediction models specific for SLE patients are very limited. This study aimed to build a risk prediction model for atherosclerosis in SLE.Methods: RNA sequencing was performed on 67 SLE patients. Subsequently, differential expression analysis was carried out on 19 pairs of age-matched SLE patients with (AT group) or without (Non-AT group) atherosclerosis using peripheral venous blood. We used logistic least absolute shrinkage and selection operator regression to select variables among differentially expressed (DE) genes and clinical features and utilized backward stepwise logistic regression to build an atherosclerosis risk prediction model with all 67 patients. The performance of the prediction model was evaluated by area under the curve (AUC), calibration curve, and decision curve analyses.Results: The 67 patients had a median age of 42.7 (Q1–Q3: 36.6–51.2) years, and 20 (29.9%) had atherosclerosis. A total of 106 DE genes were identified between the age-matched AT and Non-AT groups. Pathway analyses revealed that the AT group had upregulated atherosclerosis signaling, oxidative phosphorylation, and interleukin (IL)-17-related pathways but downregulated T cell and B cell receptor signaling. Keratin 10, age, and hyperlipidemia were selected as variables for the risk prediction model. The AUC and Hosmer–Lemeshow test p-value of the model were 0.922 and 0.666, respectively, suggesting a relatively high discrimination and calibration performance. The prediction model had a higher net benefit in the decision curve analysis than that when predicting with age or hyperlipidemia only.Conclusions: We built an atherosclerotic risk prediction model with one gene and two clinical factors. This model may greatly assist clinicians to identify SLE patients with atherosclerosis, especially asymptomatic atherosclerosis.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yong-Fei Wang ◽  
Yan Zhang ◽  
Zhiming Lin ◽  
Huoru Zhang ◽  
Ting-You Wang ◽  
...  

AbstractSystemic lupus erythematosus (SLE), a worldwide autoimmune disease with high heritability, shows differences in prevalence, severity and age of onset among different ancestral groups. Previous genetic studies have focused more on European populations, which appear to be the least affected. Consequently, the genetic variations that underlie the commonalities, differences and treatment options in SLE among ancestral groups have not been well elucidated. To address this, we undertake a genome-wide association study, increasing the sample size of Chinese populations to the level of existing European studies. Thirty-eight novel SLE-associated loci and incomplete sharing of genetic architecture are identified. In addition to the human leukocyte antigen (HLA) region, nine disease loci show clear ancestral differences and implicate antibody production as a potential mechanism for differences in disease manifestation. Polygenic risk scores perform significantly better when trained on ancestry-matched data sets. These analyses help to reveal the genetic basis for disparities in SLE among ancestral groups.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sarfaraz A. Hasni ◽  
Sarthak Gupta ◽  
Michael Davis ◽  
Elaine Poncio ◽  
Yenealem Temesgen-Oyelakin ◽  
...  

AbstractIncreased risk of premature cardiovascular disease (CVD) is well recognized in systemic lupus erythematosus (SLE). Aberrant type I-Interferon (IFN)-neutrophil interactions contribute to this enhanced CVD risk. In lupus animal models, the Janus kinase (JAK) inhibitor tofacitinib improves clinical features, immune dysregulation and vascular dysfunction. We conducted a randomized, double-blind, placebo-controlled clinical trial of tofacitinib in SLE subjects (ClinicalTrials.gov NCT02535689). In this study, 30 subjects are randomized to tofacitinib (5 mg twice daily) or placebo in 2:1 block. The primary outcome of this study is safety and tolerability of tofacitinib. The secondary outcomes include clinical response and mechanistic studies. The tofacitinib is found to be safe in SLE meeting study’s primary endpoint. We also show that tofacitinib improves cardiometabolic and immunologic parameters associated with the premature atherosclerosis in SLE. Tofacitinib improves high-density lipoprotein cholesterol levels (p = 0.0006, CI 95%: 4.12, 13.32) and particle number (p = 0.0008, CI 95%: 1.58, 5.33); lecithin: cholesterol acyltransferase concentration (p = 0.024, CI 95%: 1.1, −26.5), cholesterol efflux capacity (p = 0.08, CI 95%: −0.01, 0.24), improvements in arterial stiffness and endothelium-dependent vasorelaxation and decrease in type I IFN gene signature, low-density granulocytes and circulating NETs. Some of these improvements are more robust in subjects with STAT4 risk allele.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 857.1-857
Author(s):  
S. Bruera ◽  
R. Zogala ◽  
X. Lei ◽  
X. Pundole ◽  
H. Zhao ◽  
...  

Background:Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that carries an increased risk for both viral illnesses and malignancies, including a greater risk for both human papilloma virus (HPV) infection and cervical cancer. Due to this increased risk, the American Society of Colposcopy and Cervical Pathology guidelines for SLE patients recommend more frequent cervical cancer screening. Few studies have examined patient characteristics associated with decreased cervical cancer screening in patients with autoimmune disease, specifically SLE.Objectives:To estimate cervical cancer screening rates in women with recently diagnosed SLE, and to identify characteristics associated with decreased screening.Methods:We identified women with an initial diagnosis of SLE in the United States MarketScan Commercial Claims and Encounter (CCAE, age 18-64) administrative claims database. We included patients with at least three claims with a lupus diagnosis (first and last at least >90 days apart), no lupus claims within the year before initial claim, and who had been on antimalarial drugs for at least 90 days. We excluded all patients with a previous claim for hysterectomy.Cervical cancer screening was ascertained using diagnosis and procedure codes within 1 year before and 2 years after the first SLE claim. Our covariates included the year of first SLE claim (2001-2014), age at first SLE claim, comorbidity score, insurance type, geographical region, and prescriptions for multiple types of corticosteroids. Control patients included age-matched females without autoimmune disease. Univariate comparison and multivariate logistic regression models were built to evaluate determinants of screening.Results:We included 4,316 SLE patients (median age 45) and 86,544 control patients. The screening rate in SLE patients was 73.4% vs 58.5% in the controls (P < 0.001). The screening rate was 71% in 2001, increased to 75% in 2004, then decreased to 70% in 2014 (trend P =0.005). In the multivariate model the following factors were associated with decreased cervical cancer screening: year of first SLE claim 2012-2014 versus 2001-2005 (odds ratio (OR) 0.67, 95% confidence interval (CI) 0.53 – 0.84, P < 0.001); older age 61-64 versus 21-30 (OR 0.27, 95% CI 0.19 – 0.39, P < 0.001); comorbidity score of ≥2 versus <2 (OR 0.71, 95% CI 0.6 – 0.83, P < 0.001); and use of corticosteroids for ≥ 90 days versus <90 days (OR 0.73, 95% CI 0.59 – 0.9, P = 0.003). Insurance type and geographical region were not associated with cervical cancer screening.Conclusion:About three quarters of women with SLE underwent cervical cancer screening within 3 years of their first lupus claim, at higher rates than controls. However, there was a concerning downward trend in screening rates in recent years. In addition, higher risk populations for cervical cancer (older age, increased comorbidities, and longer duration of corticosteroids) had lower screening rates. These findings highlight the need to enhance education for healthcare providers to improve utilization of screening in women with SLE at high risk of cervical cancer.Disclosure of Interests:Sebastian Bruera: None declared, Richard Zogala: None declared, Xiudong Lei: None declared, Xerxes Pundole: None declared, Hui Zhao: None declared, Sharon Giordano: None declared, Jessica Hwang Grant/research support from: MERCK grant funding unrelated to SLE., Maria Suarez-Almazor: None declared


Genes ◽  
2018 ◽  
Vol 9 (10) ◽  
pp. 496 ◽  
Author(s):  
Bethany Wolf ◽  
Paula Ramos ◽  
J. Hyer ◽  
Viswanathan Ramakrishnan ◽  
Gary Gilkeson ◽  
...  

Development and progression of many human diseases, such as systemic lupus erythematosus (SLE), are hypothesized to result from interactions between genetic and environmental factors. Current approaches to identify and evaluate interactions are limited, most often focusing on main effects and two-way interactions. While higher order interactions associated with disease are documented, they are difficult to detect since expanding the search space to all possible interactions of p predictors means evaluating 2p − 1 terms. For example, data with 150 candidate predictors requires considering over 1045 main effects and interactions. In this study, we present an analytical approach involving selection of candidate single nucleotide polymorphisms (SNPs) and environmental and/or clinical factors and use of Logic Forest to identify predictors of disease, including higher order interactions, followed by confirmation of the association between those predictors and interactions identified with disease outcome using logistic regression. We applied this approach to a study investigating whether smoking and/or secondhand smoke exposure interacts with candidate SNPs resulting in elevated risk of SLE. The approach identified both genetic and environmental risk factors, with evidence suggesting potential interactions between exposure to secondhand smoke as a child and genetic variation in the ITGAM gene associated with increased risk of SLE.


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