Rate and determinants of progression of atherosclerosis in systemic lupus erythematosus

Abstract

Objective. To determine the rate of atherosclerosis progression as well as the relationship of traditional risk factors, systemic lupus erythematosus (SLE)-related factors, and treatment to atherosis progression in SLE patients.Methods. Outpatients in the Hospital for Special Surgery SLE Registry underwent serial carotid ultrasound and clinical assessment in a longitudinal study.Results. Among 158 patients, 77 (49%) had persistent absence of atherosclerosis (carotid plaque), 36 (23%) had unchanged atherosclerosis, and 45 (28%) had progressive atherosclerosis, defined as a higher plaque score (new plaque in 25 patients and more extensive plaque in 20 patients) after a mean ؎ SD interval of 34 ؎ 9 months. Multivariate determinants of atherosclerosis progression were age at diagnosis (odds ratio [OR] 2.75, 95% confidence interval [95% CI] 1.67-4.54 per 10 years, P < 0.001), duration of SLE (OR 3.16, 95% CI 1.64-6.07 per 10 years, P < 0.001), and baseline homocysteine concentration (OR 1.24, 95% CI 1.06-1.44 per moles/liter, P ‫؍‬ 0.006). SLE patients with stable plaque and progressive plaque differed only in baseline homocysteine concentration. Atherosclerosis progression was increased across tertiles of homocysteine concentration (16.2%, 36.4%, and 56.1%; P ‫؍‬ 0.001), and homocysteine tertile was independently related to progression of atherosclerosis (OR 3.14, 95% CI 1.65-5.95 per tertile, P < 0.001). Less aggressive immunosuppressive therapy and lower average prednisone dose were associated with progression of atherosclerosis in univariate, but not multivariate, analyses. Inflammatory markers and lipids were not related to atherosclerosis progression.Conclusion. Atherosclerosis develops or progresses in a substantial minority of SLE patients during short-term followup (10% per year on average). Older age at diagnosis, longer duration of SLE, and higher homocysteine concentration are independently related to progression of atherosclerosis. These findings show that aggressive control of SLE and lowering of homocysteine concentrations are potential means to retard the development and progression of atherosclerosis in SLE.

Cardiovascular Manifestations of Rheumatologic Diseases

“…61 Atherosclerosis progresses at twice the rate seen in non-SLE populations; rate of progression is directly related to duration of disease and homocysteine levels. 62 Similar considerations regarding preventive and screening strategies as discussed in the RA section apply to patients with SLE. …”

Subclinical Atherosclerosis in Systemic Autoimmune Disorders

“…Determinants of atherosclerotic progression after multivariate analysis were patient age at diagnosis, disease duration, and baseline homocysteine concentration. Lupus patients with stable plaque and progressive plaque were different only in baseline homocysteine concentration (Roman, Crow et al 2007). A recent study by Perna et al implied a relationship of both asymmetric dimethylarginine and homocysteine to arterial stiffness, but not to the presence or extent of carotid atherosclerosis (Perna, Roman et al 2010).…”

“…An inverse relationship between SLE activity and plaque size was reported by Manzi et al and longer disease duration was independently associated with carotid plaque (Manzi, Selzer et al 1999) and coronary calcium scores (Von Feldt, Scalzi et al 2006). In a cross-sectional and in a longitudinal study, Roman et al found that longer disease duration and higher Systemic Lupus International Collaborative Clinics (SLICC) damage index were independent predictors of carotid plaque formation (Roman, et al 2003;Roman, et al 2007). In another report, SLE specific variables were associated with aortic stiffness and included older age, hypertension, higher C3 levels, lower white blood cell count, higher insulin levels, and renal disease (Selzer, Sutton-Tyrrell et al 2004).…”

Atherosclerosis and Other Cardiovascular Manifestations of Rheumatologic Diseases

“…As in rheumatoid arthritis, patients with systemic lupus erythematosus also have an increased risk of atherosclerosis [29][30][31][32][33][34][35]. The highest risk group is young females with 2-fold increase in atherosclerosis above the general population [29,[35][36][37].…”