The Analysis Of Cardiovascular Risk Factors In Patients With Long-term But Well-controlled Systemic Lupus Erythematosus

Background and objectiveSystemic lupus erythematosus(SLE)is a multi-system autoimmune disease with diverse clinical manifestations.The etiology of SLE is unknown.Most patients initially present with skin lesions,hair loss,fatigue,and joint pain.However,as the disease progresses,the kidneys,cardiovascular,respiratory,and central nervous systems are also affected.Cardiovascular disease(CVD)is one of the main causes of the high mortality of SLE patients,which is bimodal and has been high in recent decades.Although the etiology of CVD is not fully understood,traditional cardiovascular risks combined with immune dysfunction and adverse reactions to glucocorticoid(GC)therapy play important roles in cardiac involvement.However,there is still a lack of data on risk factors for CVD in long-term but well-controlled patients who receive very low doses or even no prednisone.Framingham score and QRISK3 are two can be widely applied to evaluate the risk of cardiovascular disease rating system,Framingham score links the traditional cardiovascular disease risk and morbidity rates,while QRISK3 algorithm on the basis of into the traditional cardiovascular disease risk factors,included eight other indicators,including the use of corticosteroids,whether patients with systemic lupus erythematosus and male erectile dysfunction.Recent studies have shown that the application of QRISK3 predictive algorithm in SLE is more capable of detecting high-risk patients than the Framingham score.Therefore,QRISK3 is considered to be an excellent algorithm for assessing the risk of central vascular disease in SLE patients.However,whether this conclusion is applicable in patients with SLE who are well controlled for a long time remains to be verified.The objective of this study was to compare the effectiveness of the Framingham score and the QRISK3 predictive algorithm in assessing the risk of cardiovascular disease in patients with SLE with a long and stable disease course,and to explore the correlation between clinical characteristics and cardiovascular risk factors in patients with SLE with a long and stable disease course.Subjects and methodsPatients enrolled in our prospective study met the 1997 American College of Rheumatology diagnostic criteria for SLE.All patients were over 25 years of age(according to QRISK3)and had been diagnosed with SLE for more than 5 years.Enrolment was assessed by an experienced rheumatologist with a SLEDAI-2K score of 4 or less.Exclusion criteria included:1)patients who were taking medications that affected blood glucose and lipid levels;2)Patients with incomplete information at onset;3)patients with heart disease and other autoimmune diseases;4)Pregnant patients.Since the Framingham score is targeted at patients over 30 years old,patients over 30 years old are selected when comparing the effectiveness of two different algorithms.In order to eliminate confounding factors of gender and age,relative risk(RR)calculated by QRISK3 was used to compare cardiovascular risk factors.Patients were divided into three groups according to their relative risk,low relative risk group(0-2.5;Group 1),moderate relative risk group(2.5-10;Group 2)and high relative risk group(>10,group 3)were subgroup analyzed.Demographic data and history of disease duration,resting heart rate(RHR),cardiac symptoms including angina and chest discomfort,femoral head necrosis(ONFH),Raynold’s phenomenon(RP),pulmonary arterial hypertension(PAH),and lupus nephritis(LN)were collected.The current and onset GC dose and SLEDAI-2K score,average daily aerobic exercise time and QRISK3 requirements including migraine,severe mental illness,and chronic kidney disease were also recorded.The QRISK3 score and relative risk are given via https://qrisk.org/three/.Laboratory assessments included routine blood,urine,liver and kidney function,fasting blood glucose and lipids,serum complement(C3 and C4),C-reactive protein(CRP),and erythrocyte sedimentation rate(ESR).Result1.176 patients participated in the study.Fifteen patients(8.5%)were excluded because information about their disease at the time of onset was not available.Among the remaining 161 patients,148(91.9%)were female,13(8.1%)were male,and 140(87.0%)were over 30 years old.The median duration of disease was 10 years(7.013.0),and the median age was 37 years(32-38).Median resting heart rate was 78 beats/min(72.5 to 87.0).Patients had a median SLEDAI-2K score of 4(2-7)at initial SLE,and all patients were treated with glucocorticoids at a median dose of 60(42.580.0)mg daily(prednisone equivalent).In terms of clinical features,12 patients(7.5%)had a history of precardiac pain,29 patients(18.0%)had a history of precardiac discomfort,28 patients(17.4%)had femoral head necrosis,64 patients(39.8%)had a history of Raynaud’s phenomenon,12 patients(7.5%)had a history of pulmonary hypertension,and 60 patients(37.3%)had a history of lupus nephritis.2.There were 12 patients(8.6%)who were defined as high risk by Framingham and 22(16.7%)who were defined as high risk by QRISK3.Patients identified by Framingham as high CVD risk were all identified by QRISK3 algorithm,and 10 patients(15.2%)were not identified by Framingham as high risk but were identified by QRISK3 as high risk.3.The overall RR ranges from 1 to 66(2.3 to 16.2).In order to explore the potential influencing factors,we performed a linear regression analysis.Multiple linear regression analysis was performed using a step-by-step approach,and results were adjusted for age at enrolment and onset,current glucocorticoid dose,current SLEDAI-2K score,average daily aerobic exercise time,initial SLEDAI-2K score,initial GCS dose,disease duration,inflammatory biomarkers,and lipid profile.We found an R2 of 66.9%(adjusted R2 of 65.8%)for predicting the relative risk of cardiovascular disease using the multiple linear regression model.Initial SLEDAI-2K score and resting heart rate were positively associated with relative risk of cardiovascular disease,while initial glucocorticoid dose and age at onset were negatively associated with relative risk factors of cardiovascular disease.SLEDAI-2K score at onset of disease(β=0,54,P<0.001)was the strongest predictor.This was followed by the dosage of hydroxychloroquine(β=-0.31,P<0.001),age at onset(β=0.23,P<0.001),resting heart rate(β=0.13,P=0.003),and initial dose of glucocorticoids(β=-0.12,P=0.006).4.The daily dose of currently used glucocorticoids was significantly higher in the 3 groups than in Group 1(2.5mg vs.0.8 mg,P<0.001)and Group 2(2.5mg vs.1.3 mg,P<0.001).Patients in Group 3 had a significantly lower mean time of aerobic exercise per day than patients in Group 1(0 vs.15 minutes/day,P<0.001)and Group 2(0 vs.0 minutes/day,P<0.001).The mean daily dose of mycophenolate in group 1 was higher than that in group 3(0.3 g vs.0.04g,P=0.009).Although there was a statistically significant difference in the course of disease between the three groups,pairwise comparisons did not show a significant difference.Similarly,the SLEDAI2K score at the time of enrollment did not show statistically significant difference between groups or in multiple regression analysis(P>0.05).Continuous correction for the chi-square test showed a significantly higher incidence of SLE-lupus nephritis and metabolic syndrome in Group 3 than Group 1(P=0.004;P=0.039)and group 2(P=0.002;P=0.042).ConclusionIn patients with systemic lupus erythematosus(SLE)with long duration and good control,QRISK3 algorithm can identify more patients with high cardiovascular disease risk than Framingham score system.High relative risk factors for cardiovascular disease associated with SLE in patients with long-term but wellcontrolled systemic lupus erythematosus include metabolic syndrome,resting heart rate,history of SLE-LN,and initial SLEDAI-2K.However,the initial dose of GC,the dose of hydroxychloroquine and mycopfenolate and the age of onset were protective factors.The relative risk of CVD was significantly higher in younger patients with SLE than in older patients.Measures should be taken both at the beginning of disease and during treatment to reduce the risk of CVD in patients with SLE.