Laboratory markers of cardiovascular risk in pediatric SLE: the APPLE baseline cohort

Abstract

As part of the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) Trial, a prospective multicenter cohort of 221 children and adolescents with systemic lupus erythematosus (SLE) (mean age 15.7 years, 83% female) underwent baseline measurement of markers of cardiovascular risk, including fasting levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), lipoprotein A (Lpa), homocysteine and high-sensitivity C-reactive protein (hs-CRP). A cross-sectional analysis of the baseline laboratory values and clinical characteristics of this cohort was performed. Univariable relationships between the cardiovascular markers of interest and clinical variables were assessed, followed by multivariable linear regression modeling. Mean levels of LDL, HDL, Lpa, TG, hs-CRP and homo-cysteine were in the normal or borderline ranges. In multivariable analysis, increased Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), prednisone dose, and hypertension (HTN) were independently associated with higher LDL levels. Higher hs-CRP and creatinine clearance were independently related to lower HDL levels. Higher body mass index (BMI), prednisone dose, and homocysteine levels were independently associated with higher TG levels. Only Hispanic or non-White status predicted higher Lpa levels. Proteinuria, higher TG and lower creatinine clearance were independently associated with higher homocysteine levels, while use of multivitamin with folate predicted lower homocysteine levels. Higher BMI, lower HDL, and longer SLE disease duration, but not SLEDAI, were independently associated with higher hs-CRP levels. The R2 for these models ranged from 7% to 23%. SLE disease activity as measured by the SLEDAI was associated only with higher LDL levels and not with hs-CRP. Markers of renal injury (HTN, proteinuria, and creatinine clearance) were independently associated with levels of LDL, HDL, and homocysteine, highlighting the importance of renal status in the cardiovascular health of children and adolescents with SLE. Future longitudinal analysis of the APPLE cohort is needed to further examine these relationships.

Dyslipidemia in Pediatric Systemic Lupus Erythematosus: The Relationship with Disease Activity and Plasma Homocysteine and Cysteine Concentrations

“…Hypertriglyceridemia was the most commonly observed dyslipidemia in our patients, and this finding was also reported in an American multicenter study [3]. …”

“…Given the absence of well-defined cutoff points for the pediatric age range [3], these variables were analyzed continuously. Serum folate and vitamin B 12 serum levels were measured by a solid-phase competitive chemiluminescence enzyme immunoassay (Immulite, Siemens).…”

“…This association is the result of the complex interaction between classic risk factors, chronic inflammation, elevated concentrations of homocysteine (Hcy), the production of autoantibodies, and SLE treatments [2,3,4,5]. The elevation of Hcy concentrations can exacerbate oxidative stress, interfere with the vasodilator and antithrombotic function of nitric oxide, and have a direct toxic effect on the endothelium [6].…”

Adrenal-Specific Scavenger Receptor BI Deficiency Induces Glucocorticoid Insufficiency and Lowers Plasma Very-Low-Density and Low-Density Lipoprotein Levels in Mice

“…In liver transplant patients 53 as well as in a large cohort of SLE patients, 54 exogenous corticosteroid therapy was independently associated with higher total/LDL-cholesterol levels, suggesting that glucocorticoids do also influence the levels of apolipoprotein B-containing lipoproteins in the clinical setting. Our expression analysis revealed that the decrease in plasma VLDL/LDL levels was probably secondary to a decrease in the expression of MYLIP.…”

Dyslipidemia in patients with systemic lupus erythematosus: Association with disease activity and B-type natriuretic peptide levels

“…The association between disease activity, which was evaluated by the SLEDAI, and changes in the lipid profile has commonly been reported in cross-sectional studies in the literature (16)(17)(18)(19)(20). The dyslipoproteinemia (elevated TC, LDL-C and TG) that has been reported in the SLE population has been associated with disease activity (21) and future CV events (22).…”