LAUSR

Background: Recent meta-analysis reported that rheumatoid arthritis (RA) is associated with high frequency of hypertension and stroke (1). IGF1 is an important angioprotector and its deficiency predisposes to development of ischemic stroke (2). Objectives: Since levels of active IGF1 are affected by systemic inflammation, we analyze if low IGF1 is associated with increased cardiovascular disease (CVD) in women with RA. Methods: The CVD risk was estimated (eCVR) in 184 female RA patients (median age 53 years, range 21-71) using the Framingham algorithm. A 5-year prospective follow-up for new CVD events, type II diabetes and medication for hypertension and hyperlipidemia was completed in all the patients. The event-free survival curves were built and the Mantel-Cox analysis was performed with respect to serum IGF1, where IGF1 levels below or equal to the median 139 ng/ml were considered low. Results: Low IGF1 was clinically significant. These patients were recognized by high prevalence of hypertension (26% vs. 7.9%, p=0.001), overweight (19% vs 6.8%, p=0.016) and hypercholesterolemia (71% vs 48%, p=0.0025), which resulted in a higher eCVR in these RA patients (7.2% and 3.3%, p<0.001). When adjusted by age, low IGF1 group had higher serum IL6 (pg/ml: 2.1[0.2-3.0] vs 0.7[0.1-4.2], p=0.038) and ESR (mm/h: 12[7-15.5] vs 5.5[4-9], p=0.02), and higher prevalence of MTX monotherapy (56% vs. 39%, p=0.024). At prospective follow-up, 12 CVD events were registered. The median age at CVD event was 67 years and disease duration 14 years. Among the new CVD events were 4 ischemic strokes, 3 chronic atrial fibrillations and 2 incidental aorta aneurysms, which all could be viewed as directly related to hypertension. Low IGF1 showed high probability for new CVD events (OR 4.96, [95%CI:1.17-34.2], p=0.029). Additionally, low IGF1 group had a significant increase in medication for hypertension (+19.5% vs +4.8%, p=0.00011), but not type II diabetes and statins. In a prediction model, a combination of low IGF1 and RA duration>10 years indicated 80.5% specificity for development of new CV events. Conclusion: We identified low normal levels of IGF1 to be associated with higher prevalence of CVD events in RA patients. Importantly, low IGF1 appeared to be an independent predictor of hypertension in middle-aged female patients. References: [1] Wiseman SJ, Ralston SH, Wardlaw JM. Cerebrovascular Disease in Rheumatic Diseases: A Systematic Review and Meta-Analysis. Stroke. 2016;47(4):943-50. [2] Laughlin GA, Barrett-Connor E, Criqui MH, Kritz-Silverstein D. The prospective association of serum insulin-like growth factor I (IGF-I) and IGF-binding protein-1 levels with all cause and cardiovascular disease mortality in older adults: the Rancho Bernardo Study. J Clin Endocrinol Metab. 2004;89(1):114-20. Disclosure of Interests: None declared