Background/Purpose: Patients with rheumatic diseases have an increased risk of cardiovascular disease (CVD). Cardiometabolic disease includes an alteration in metabolic organs and CV system that might contribute to the development of CVD. Complement factors have recently been associated with metabolic events such as metabolic syndrome. 

Objectives: 1) To evaluate the levels of complement C3 in rheumatic diseases with increased prevalence of cardiovascular risk and 2) to analyze the relationship of the complement C3 with the different cardiometabolic risk factors in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA) and systemic lupus erythematosus (SLE).

Methods: Methods:  570 subjects: cross-sectional study including 200 RA, 150 AS, 60 PsA, 60 SLE patients and 100 healthy donors (HD) recruited from the Rheumatology department of Reina Sofia Hospital, Cordoba (Spain). The prevalence of traditional cardiovascular risk factors was analyzed in the different rheumatic diseases. Inflammatory markers (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), complement C3 and insulin resistance (HOMA-IR) was measured. Serum glucose, insulin, triglycerides (TG), total cholesterol, low density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, apolipoprotein A (apo-A), apoliprotein B (apo-B) were measured in overnight fasting conditions.

Kruskall wallis tests were performed for multiple comparisons. Chi-squared test were performed to analyze qualitative data. ROC analysis was carried out to identify biomarkers for cardiometabolic comorbidities.  Spearman’s rho correlation coefficient was used for correlation studies.

Results: All patients had significant increase in the prevalence of obesity, insulin resistance, hyperlipidemia and hypertension. PsA patients showed the worst cardiometabolic profile followed by RA, SLE and AS. Levels of complement C3 were significantly elevated in RA, AS and PsA patients. Although complement C3 levels were not increased in SLE patients, complement C3 levels were associated with HOMA-IR index in all the diseases, due to the strong correlation with insulin levels. ROC analyses showed that C3 levels could be a marker of IR in RA, PsA and SLE patients. Besides, complement C3 levels were strongly correlated with CRP in all the diseases. On the other hand, in RA, AS and PsA patients, levels of complement C3 correlated with ERS and altered lipid profile.  Hard clustering analysis identified two distinctive phenotypes in our cohort of rheumatic disease patients depending on the complement C3 levels. Patients from cluster 1 presented higher levels of complement C3 alongside increased prevalence of cardiometabolic comorbidities (obesity, diabetes, IR, hyperlipidemia, hypertension, apoB/apoA ratio, atherogenic risk) compared to cluster 2.

Conclusion: 1) Complement C3 could be a marker of IR in the rheumatic diseases most associated with cardiometabolic risk.  2) Complement C3 could be considered a cardiometabolic risk factor in RA, PsA and AS.

Funded by ISCIII (PI17/01316, PI18/00837 RIER and RD16/0012/0015) co-funded with FEDER.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/complement-component-3-as-biomarker-of-cardiometabolic-risk-in-rheumatic-diseases-rheumatoid-arthritis-ankylosing-spondylitis-psoriatic-arthritis-and-systemic-lupus-erythematosus/