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

Abstract

Objective The 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. Methods A 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. Results During 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. Conclusion A high PREDICTS score and hypertension confer increased risk for new MACEs in patients with SLE.

Extent of vascular plaque predicts future cardiovascular events in patients with systemic lupus erythematosus

“…Like Frerix et al [7], we confirm the importance of scanning all four bifurcations, since there is a significant gain through being able to identify patients with plaque in more than two sites. We found no associations between traditional risk factors and subsequent CVD events whereas some other groups did find associations with age, lipid levels and hypertension [5,20,27,28]. We also found no association with medications, though other authors have reported that corticosteroids may promote development of CVD in patients with SLE whereas antimalarials may be protective as described in the systematic review by Tselios et al [23].…”

“…High PREDICTS score at baseline was strongly associated with developing any of these outcomes (AUC 0.71, HR 3.7, p< 0.0001) or with cardiac events (HR 7.3, P ¼ 0.02) or with cerebrovascular events (HR 4.0, P ¼ 0.001) [20]. The cohort studied by this group underwent carotid ultrasound scanning and both IMT and plaque at baseline were associated with increased risk of CVD events [20]. The actual prevalence of plaque is lower in this group than in most other groups-16.3% vs 30-40% [26].…”

Systematic review and meta-analysis of cardiovascular associated biomarkers in adults with asymptomatic autoimmune diseases

“…A total of 4 studies were assessed ( 26 , 35 , 74 , 81 ). Figure 7A presents a forest plot of four studies evaluating the association between homocysteine and incident CVD among adults with autoimmune conditions.…”

Subclinical atherosclerosis is associated with future cardiovascular events in lupus patients at apparent low cardiovascular risk

“…Therefore, they suggested that carotid scanning might be done in patients with renal impairment and at least one traditional cardiovascular risk factor. In another longitudinal prospective study including 342 SLE patients, 14 the presence of a carotid plaque was one of the few markers associated with a clinical cardiovascular event during follow-up. Taken together, these results support the idea that subclinical atherosclerosis assessment by cardiovascular ultrasound should be part of the global evaluation of SLE patients.…”