The Heart of Lupus Save

Few people are aware of the EULAR recommendations1 for cardiovascular (CV) risk management in systemic lupus erythematosus (SLE) published in 2022.  The recommendations had 4 overarching principles: increase awareness of elevated cardiovascular risk, need for regular cardiovascular screening, assess and manage modifiable risk factors, and patient education. What was unclear: 1. How prevalent is CV disease now for patients with SLE in the setting of better access to medical care and treatment options,  and 2. What are the best screening tools for CV disease  since most prediction tools currently available are inadequate. They were designed for the general population and did not take into account the risk SLE contributes to CV disease. Traditional CV prediction tools (e.g, SCORE, QRISK3, Framingham Risk Score) have been found to underestimate CV risk in SLE.  The EULAR recommendations suggest the FRS results, if used, should be multiplied by a factor of 2 to enhance sensitivity while maintaining specificity.  However, none of these scores have been adequately validated for use in SLE patients. 

During ACR 2023 Convergence, several abstracts were presented evaluating the prevalence of CV disease and exploring new tools to predict CV disease.  The ones that caught my eye included:

Abstract #1442: Incident Vascular Events in Danish SLE Cohort (20 year registry).  3178 SLE patients were matched to 60,000 controls. The prevalence of myocardial infarction (MI) in SLE was 2.9% vs control 1.4%, cerebrovascular disease 7% vs 2.7%, and peripheral vascular disease 5.5% vs 1.4%. Incidence ate ratio (IRR) ranged 1.7-7.6. Female SLE patients had a 5-fold increase in CVD and PVD and a 3-fold increase in MI. Male SLE patients had 8 fold increased risk for PVD and a 6-fold increased risk for cerebrovascular disease and MI. 

Abstract #1469:  Prevalence of CVD in SLE from the Manhattan Lupus Surveillance Program: 1285 pts with SLE were included, and 14% of patients had CVD. Risk increased with age. Non-Hispanic blacks and Hispanic patients had 3 times higher CVD prevalence compared to national estimates and compared to NYC residents. 

Abstract #0580: Single center study evaluating different CV risk assessment scores in 108 SLE patients without known CVD. Patients were 40-60 years old and matched to healthy controls. Subclinical atherosclerosis was defined by carotid plaque or abnormal carotid intima media thickness on ultrasound. Subclinical atherosclerosis was found in 51% of SLE patients, and 48% controls. QRISK3 and modified Framingham Risk Score (mFRS) had better agreement (k=0.65) with subclinical atherosclerosis than WHO, FRS scores in SLE patients. For healthy controls, QRISK3, WHO, FRS and SCORE tools had substantial agreement.  SLE patients with triple + APAs were more likely to have subclinical atherosclerosis.  (Author’s note: it had been previously suggested by EULAR carotid artery ultrasound may be considered to screen for cardiovascular risk) 

Abstract #1468: Predicting CVD in SLE is more accurate using Machine Learning compared to traditional models.  This was a retrospective Canadian study 1791 patients with SLE followed for up to 25 years (median 8.2 years). 11.8% developed CVD. Patients with CVD were likely older, male, smokers, on steroids, have renal disease, HTN, higher BMI, elevated inflammatory markers and anti-phospholipid antibodies.  Variables with greatest predictive values based on machine learning were: BMI, age, disease activity, and serum creatinine levels. (Author’s note: EULAR recommendations noted target BP should be < 130/80 in SLE patients and low dose aspirin (75-100 mg/day) is recommended in those with high risk profile antiphospholipid antibodies and considered in those with low risk APA profile)

Abstract #1447 and #1448: Should echocardiograms (ECHO) be used for screening CV risk? Two studies evaluated the role of ECHO. Abstract #1447 is a nested case-control study of 48 SLE patients with and without lupus nephritis (LN) using ECHO to evaluate left ventricular (LV) mass. Prior studies have shown higher LV mass may increase risk for CV events as CHF, arrhythmias and CV mortality.  Patients were matched by age, gender, and comorbidities (eg, diabetes, HTN, obesity, dyslipidemia, tobacco use). LV masses were higher in patients with LN (66.9 g/m2) compared to those without LN (54.8 g/m2, p=0.035) regardless of traditional risk factors.  Abstract#1448 is another study evaluating 75 SLE patients without prior CV events.  Using ECHO, a correlation was found between SLEDAI and +dsDNA antibodies with LV mass,  the ratio between early mitral inflow velocity and mitral annular early diastolic velocity (E/e) and PASP. ECHO results suggest a potential role of disease activity and +dsDNA antibodies in development of adverse cardiac remodeling and function. 

Despite knowing CV risk contributes to lupus morbidity and mortality, we need more studies to evaluate cardiovascular risk, prevention and treatment.

References

1. EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases, including systemic lupus erythematosus and antiphospholipid syndrome http://dx.doi.org/10.1136/annrheumdis-2021-221733