Background/Purpose:   Certain traditional and disease-related factors have been identified to accelerate atherosclerosis in systemic lupus erythematosus (SLE). Due to the lack of long-term prospective studies, the evolution over time and relative importance of these variables in the development of atherosclerotic cardiovascular events (CVEs) is not known. We aimed to determine the evolution of CVE risk factors over 15 years,

Methods:   250 female lupus patients (mean age at enrollment 44.5±12 years, mean disease duration 13.7±9.7 years) and 250 age-matched healthy women (mean age 44.1±14 years) were recruited between 1998 and 2000. All subjects had similarly low (3.2%) 10-year Framingham Risk Score (FRS) Variables assessed at study entry included family history of premature for coronary artery disease (CAD). CAD, hypertension, diabetes, dyslipidemia (total cholesterol, triglycerides, LDL, VLDL, HDL, lipoprotein a), smoking, physical activity, body mass index (BMI), menstrual status, use of oral contraceptives or hormone replacement therapy, serum creatinine, homocysteine and C-reactive protein. For lupus patients, SLEDAI-2K and the 3-year adjusted mean SLEDAI (AMS) (1998-2000 and 2005-2007) were calculated to quantify global disease activity. Additional parameters included antiphospholipid antibodies; information on antimalarials, prednisone and immunosuppressants were also collected. Subjects were followed for 15 years for the development of CVEs [angina, myocardial infarction (fatal, non-fatal), transient ischemic attack, stroke (fatal, non-fatal)]. Analysis was performed with SAS 9.3 software for 2000-2007 and 2008-2015; p<0.05 was considered significant.

Results:  SLE patients had consistently higher rates of CVEs, the difference becoming greater with longer follow up (p=0.0001). CVEs occurred in 41/210 patients (19.5%) and 8/138 controls (5.8%), mostly in the second part (2008-2015) (24/41, 58.5% vs. 17/41, 41.5% in patients, 4 CVEs in each part in controls). Coronary artery disease was more common in SLE (32/210, 15.2% vs. 5/138, 3.6%, p=0.0041). There was no significant difference for cerebrovascular disease (10/210, 4.8% vs. 3/138, 2.2%, p=0.213). SLE [HR=2.8, 95% CI 1.3-6.3], older age and triglycerides>2.8mmol/L were predictive of CAD in the early phase. In the late phase, hypertension, diabetes, dyslipidemia and high BMI were more prominent in patients who suffered a CVE. Time-adjusted disease activity (AMS) was lower in those late phase patients; however their cumulative prednisone dose between 2000-2007 was significantly higher. Of note, 60% of the new hypertension and all new diabetes cases were attributed to glucocoricoids. Thirty-one deaths occurred in patients (10 due to CVEs) and 6 in controls (none due to CVEs); all CVE-related deaths occurred between 2008 and 2015.

Conclusion:   SLE patients had a 4-fold increased risk for CVEs and all-cause mortality as compared to healthy controls after 15 years. Disease-related factors dominate cardiovascular risk during the early stages while traditional factors, partially related to corticosteroid treatment, play a significant role later in disease course.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/long-term-evolution-of-risk-factors-for-atherosclerotic-cardiovascular-events-in-systemic-lupus-erythematosus-in-a-large-case-control-cohort-study/