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

Abstract

Objectives Since 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. Methods A CVD risk was estimated (eCVR) in 184 female RA patients (mean age 52 years) and in 132 female patients after ischemic stroke (mean age 56 years) 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. Results Low 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. Conclusions Low 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.

Inferring Relationship of Blood Metabolic Changes and Average Daily Gain With Feed Conversion Efficiency in Murrah Heifers: Machine Learning Approach

“…Pro-insulin and IGF1 modulate carbohydrate metabolism, which stimulates glucose transport and inhibits insulin sensitivity. Low IGF I estimated in efficient conversant is found to be associated with metabolic deviations related to lower cholesterol at day 60 ( p < 0.05) and day 90 ( p < 0.001) and lower triglycerides on day 60 ( p < 0.001) during the feed trial in the present study ( Table 2 ) instead of hyperlipidemia and hyperinsulinemia reported in other studies ( 49 ). A higher level of IGF1 in the subgroup of less efficient energy-utilizing animals indicates a higher stimulus to body for making metabolic changes for growth; however, secretion of higher IGF1 in circulation might also suggest inhibitory feedback influence on the GH/pituitary axis, thus affecting feed utilization efficiency.…”

Cumulative inflammatory burden and obesity as determinants of insulin resistance in patients with established rheumatoid arthritis: cross-sectional study

“…The same finding was observed in other studies in which these parameters were associated with increased cardiovascular risk in RA. 56 57 …”

The Neuroprotective Effects of Insulin-Like Growth Factor 1 via the Hippo/YAP Signaling Pathway is Mediated by the PI3K/AKT Pathway Following Cerebral Ischemia-Reperfusion Injury

“…Recent studies have shown that circulating IGF-1 levels can predict cardiovascular events and ischemic stroke risk [69,70]. Higher IGF-1 levels have been associated with early carotid artery atherosclerosis [71].…”