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Low serum IGF1 is associated with hypertension and predicts early cardiovascular events in women with rheumatoid arthritis

Journal article
Authors Malin Erlandsson
Lovisa Lyngfelt
N David Åberg
Caroline Wasén
Rachelle A. Espino
Sofia Töyrä Silfverswärd
Mitra Nadali
Katarina Jood
Karin Andersson
Rille Pullerits
Maria Bokarewa
Published in BMC Med
Volume 17
ISSN 1741-7015
Publication year 2019
Published at Institute of Neuroscience and Physiology
Institute of Medicine, Department of Rheumatology and Inflammation Research
Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
Language en
Links dx.doi.org/10.1186/s12916-019-1374-...
Keywords IGF1, Ischemic stroke, Hypertension, Rheumatoid arthritis, Inflammation, growth-factor-i, blood-pressure, ischemic-stroke, risk-factors, incident, disease, heart, atherosclerosis, deficiency, mortality, General & Internal Medicine
Subject categories Rheumatology and Autoimmunity

Abstract

ObjectivesSince low insulin-like growth factor (IGF) 1 is often linked to inflammation, we analyze whether serum levels of IGF1 are associated with cardiovascular disease (CVD) in rheumatoid arthritis (RA) in a longitudinal observational study.MethodsA CVD risk was estimated (eCVR) in 184 female RA patients (mean age 52years) and in 132 female patients after ischemic stroke (mean age 56years) with no rheumatic disease, using the Framingham algorithm. The median level of IGF1 divided the cohorts in IGF1(high) and IGF1(low) groups. A 5-year prospective follow-up for new CVD events was completed in all RA patients. The Mantel-Cox analysis and event-free survival curves were prepared. Unsupervised clustering of proteins within the IGF1 signaling pathway was employed to identify their association with eCVR.ResultsLow IGF1 resulted in a higher eCVR in RA patients (7.2% and 3.3%, p=0.0063) and in stroke (9.3% and 7.1%, p=0.033). RA had higher rate for new CVD events at prospective follow-up (OR 4.96, p=0.028). Hypertension was the major risk factor associated with low IGF1 in RA and stroke. In hypertension, IGF1 was no longer responsible for intracellular activation and lost its correlation to IRS1/2 adaptor proteins. The clustering analysis confirmed that combination of low IGF1 and IRS1/2 with high IL6, insulin, and glucose predisposed to high eCVR and emphasized the functional role of serum IGF1.ConclusionsLow serum IGF1 precedes and predicts development of early CVD events in female RA patients. Hypertension and aberrant IGF1 receptor signaling are highlighted as the important contributors to IGF1-related CVD events.

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