Abstract P249: Central Obesity and Systemic Inflammation Predict Subsequent Levels of Procollagen Type III N-Terminal Peptide in Framingham Offspring Study Adults

Abstract

Background: Fibrosis is a process that, in healthy individuals, is characterized by deposition of extracellular matrix (ECM) components. However, in pathological states, such as the low-grade inflammation associated with obesity, excessive tissue ECM production is associated with dysfunction of various organs such as liver, kidney, and adipose tissue. Procollagen Type III N-terminal peptide (P3NP) is produced during collagen synthesis and is linked to adverse outcomes including cardiovascular events. Few studies have examined the relationship between systemic inflammation or body fat distribution and P3NP. Methods: Data from the prospective Framingham Offspring study were used to examine the link between systemic inflammation, body fat distribution and P3NP. Of the 944 individuals with P3NP measured at exam 6, 737 had CRP measured at exam 2 and 859 had waist circumference measured at exam 4, along with potential confounders including sex, age, smoking, and body mass index (BMI). Levels of serum CRP at exam 2 were classified into 3 groups (≤1.0, 1.0 to ≤3.0, >3.0 mg/L) and waist circumference was divided in sex specific quintiles. Due to non-normality, levels of P3NP were log transformed. Multivariable general linear models were used to assess the associations between both CRP and waist circumference and P3NP. Age, sex, smoking status, physical activity and BMI were assessed as potential confounders. Results: Compared with individuals with the lowest levels of CRP at exam 2 (≤1mg/L) those with intermediate or high levels (CRP: 1.0 to ≤3.0, and >3.0) had statistically significantly higher levels of plasma P3NP at exam 6 (3.8 ± 0.2, 4.2 ± 0.3, and 4.3 ± 0.3 mg/L, from lowest to highest category, respectively, p-trend<0.001). Additionally, men in the two highest quintiles of waist circumference at exam 4 had statistically significantly (p<0.05) higher plasma P3NP levels than those in the lowest quintile (4.6 ± 0.4, 4.5 ± 0.4 vs. 3.7 ± 0.4 mg/L for quintiles 5 and 4 vs. 1, respectively). No effect was seen in women. Conclusions: These results suggest a link between both systemic inflammation and waist size (a simple indicator of central adiposity) and circulating markers of fibrosis. These findings may suggest that adverse health outcomes associated with visceral adiposity and systemic inflammation may be linked with development of fibrosis.