The association between peptidoglycan recognition protein-1 and coronary and peripheral atherosclerosis: Observations from the Dallas Heart Study

Background: Peptidoglycan recognition protein-1 (PGLYRP-1) is part of the innate immune system and binds to peptidoglycan, a component of bacterial cell walls that has been found in human atherosclerotic lesions. Chronic exposure to bacterial antigens may cause or exacerbate the inflammatory response to lipid deposition within arterial walls. We hypothesized that PGLYRP-1 is associated with subclinical atherosclerosis as measured by computed tomography and magnetic resonance imaging. Methods and results: PGLYRP-1 was measured in 3222 subjects in the Dallas Heart Study, a probability-based population sample age 30-65 including 50% African-Americans and 56% women. Coronary artery calcium (CAC) was measured by electron beam computed tomography (n = 2467), abdominal aortic wall thickness (AWT) by magnetic resonance imaging (MRI) (n = 2270), and abdominal aortic plaque burden (APB) by MRI (n = 2256). In univariable analyses, increasing levels of PGLYRP-1 were associated with all major cardiovascular risk factors, with inflammatory markers such as C-reactive protein, and with CAC, AWT, and APB (p < 0.0001 for each). In multivariable models adjusted for traditional risk factors, log PGLYRP-1 remained significantly associated with CAC (OR 1.1, 95% CI 1.01-1.3 per S.D.; p = 0.04) and AWT (p = 0.009) but not APB (p = 0.09). Further adjustment for novel biomarkers associated with PGLYRP-1 and atherosclerosis attenuated the association with CAC (p = 0.18) but not with AWT (p = 0.01) or APB (p = 0.037). Conclusion: In this first reported clinical study of PGLYRP-1 in humans, PGLYRP-1 levels were independently associated with atherosclerosis phenotypes that represent different vascular beds and stages of atherosclerosis.