Abstract

Introduction: Inflammation plays an important role in the pathogenesis of coronary heart disease (CHD). Chronic inflammatory diseases (CIDs) may serve as models to provide insights into the relationships between immune dysfunction, inflammation, and CHD. To investigate this further, we analyzed the risk of incident CHD across different CIDs. Methods: We created a cohort of individuals with CIDs and non-CID controls (frequency-matched on demographics and CHD risk factors), free of baseline CHD, receiving regular outpatient care in a large medical system from 2000 to 2019. CIDs included psoriasis, rheumatoid arthritis (RA), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), human immunodeficiency virus (HIV), and inflammatory bowel disease (IBD). CHD was defined as myocardial infarction (MI), angina, or coronary revascularization. We used adjusted hazards models to determine incident CHD risk for each CID relative to controls. We also analyzed incident CHD risk by severity of inflammation (baseline C-reactive protein) or immune dysfunction (baseline CD4 T cell level in HIV). Results: Of 18,129 individuals with CIDs and 18,988 controls, there were 1,011 incident CHD events over a median of 3.5 years. After adjusting for demographics and CHD risk factors, CHD risk was significantly elevated in SLE [hazard ratio (HR) 2.85, 95% confidence interval (CI) 2.19-3.71, p<0.01], SSc (HR 2.14, 95% CI 1.54-2.99, p<0.01), HIV (HR 1.38, 95% CI 1.12-1.69, p<0.01), and RA (HR 1.22, 95% CI 1.00-1.49, p=0.05). Findings were similar with MI as the lone outcome. When CIDs were categorized by inflammation or immune dysfunction, there was a pattern of higher CHD risk with higher levels of inflammation/immune dysfunction across CIDs (Figure). Conclusions: Our results show that SLE, SSc, HIV, and RA were associated with significantly elevated risks of incident CHD and MI. Higher levels of inflammation or immune dysfunction were associated with heightened CHD risk within CIDs.

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