Cardiovascular risk in lupus nephritis: Do renal disease-related and other traditional risk factors play a role?

Abstract

This study was performed to evaluate the prevalence of thickened carotid intima media thickness (CIMT) in a Sri Lankan cohort of lupus nephritis (LN) patients and to identify associations between traditional cardiovascular disease (CVD) and LN-related risk factors with increased CIMT. Consecutive patients with biopsy-proven LN were evaluated for conventional CVD risk factors, renal parameters and extent of organ involvement in this cross-sectional study. Current disease activity and damage were assessed by the British Isles Lupus Activity Group (BILAG) score and the Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) damage index, respectively. CIMT was assessed by B Mode grey scale ultrasonography. Increased CIMT was defined as CIMT more than the 75th percentile based on cutoffs from the "Carotid Atherosclerosis Progression Study." Forty patients (98% female), with a mean age of 38 years (age range of 20-50) and of South Asian descent, were evaluated. The mean duration of disease of 6.15 years (SD = 4.66). The overall prevalence of cardiovascular events was low and included previous acute coronary syndromes in 7.5%, stable angina in 5%, cerebrovascular accidents in 7.5% and transient ischemic attacks in 2.5% of the patients; 72.5% had hypertension (HTN) [mean blood pressure (BP) 140/80 mm Hg]; 32.5% had dyslipidemias (mean serum cholesterol 5.9; SD = 5.6) and 25% had diabetes (mean blood sugar 103.7; SD = 15.6). Forty percent were obese and 20% were overweight (Asian cutoffs). Increased CIMT (57.5%) and atherosclerotic plaques (15.36%) indicated a high CVD risk in this cohort. Diabetes (P = 0.016), HTN (P = 0.002), dyslipidemia (P = 0.002) and obesity (P = 0.048) were associated with thickened CIMT. The only LN-related risk factor associated with thickened CIMT (P <0.05) was the SLICC/ACR damage index. The independent predictors of thickened CIMT determined by logistic regression analysis were HTN and dyslipidemia.

Atherosclerosis Progression in the APPLE Trial Can Be Predicted in Young People With Juvenile‐Onset Systemic Lupus Erythematosus Using a Novel Lipid Metabolomic Signature

“…Although accelerated atherosclerosis has been linked to many autoimmune rheumatic diseases, the association between JSLE disease activity and CIMT progression remains controversial, with some studies finding an association, 6 whereas others did not 38 . In our analysis, the untreated CIMT progression correlated positively with a proatherogenic lipid profile and presence of SLICC JSLE damage, suggesting that JSLE severity contributes to atherosclerosis, similar to previous reports 39 . However, we acknowledge the limitations of our correlation analyses between CIMT progression and baseline biomarkers due to the exploratory nature of these analyses and lack of multiple testing correction despite the use of a more stringent P value cutoff (<0.01), as well as inability to account for the potential impact of the variation of these biomarkers over 36 months, which is also likely to have influenced the CIMT progression in both the placebo and atorvastatin arms.…”

“…38 In our analysis, the untreated CIMT progression correlated positively with a proatherogenic lipid profile and presence of SLICC JSLE damage, suggesting that JSLE severity contributes to atherosclerosis, similar to previous reports. 39 However, we acknowledge the limitations of our correlation analyses between CIMT progression and baseline biomarkers due to the exploratory nature of these analyses and lack of multiple testing correction despite the use of a more stringent P value cutoff (<0.01), as well as inability to account for the potential impact of the variation of these biomarkers over 36 months, which is also likely to have influenced the CIMT progression in both the placebo and atorvastatin arms. This suggests a limited predictive value of individual baseline biomarkers for a disease that is recognized to fluctuate significantly over time.…”

Management of lupus nephritis: a systematic literature review informing the 2019 update of the joint EULAR and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations

“…Similarly, contradictory results were obtained from studies that used surrogate CVD endpoints, such as subclinical atherosclerosis. 114 – 117 In the single prospective trial that explored the possible atheroprotective effect of ACE inhibitors and angiotensin receptor blockers in patients with LN, there was no difference in the cumulative occurrence of CVD between the treatment and the control arm (p = 0.7). 118 The increased risk for infections in patients with LN is supported by a number of studies (HR: 1.4–5.3) 119 – 122 ; regarding treatment-related risk factors, a network meta-analysis of 32 RCTs identified that high-dose GC therapy was associated with the highest risk for serious infections compared to TAC as reference drug (OR 12.8, 95% CI 1.53 to 119.90), followed by low-dose CY (OR 4.8, 95% CI 1.48 to 17.64) and high-dose CY (OR 6.6, 95% 2.25 to 20.50).…”