Abstract
Biomarkers of chronic inflammation (such as C-reactive protein) have long been associated with cardiovascular disease and mortality; however, biomarkers involved in antiviral cytokine induction and adaptive immune system activation remain largely unexamined. We hypothesized the cytokine interferon gamma inducible protein 10 (IP-10) would be associated with clinical and subclinical cardiovascular disease and all-cause mortality in African Americans. We assessed these associations in the Jackson Heart Study (JHS) cohort and the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. There was a modest association of IP-10 with higher odds of left ventricular hypertrophy (OR = 1.20 (95% confidence interval (CI) 1.03, 1.41) per standard deviation (SD) higher natural log-transformed IP-10 in JHS). We did not observe associations with ankle brachial index, intima-media thickness, or arterial calcification. Each SD higher increment of ln-transformed IP-10 concentration was associated with incident heart failure (hazard ratio (HR) 1.26; 95% CI 1.11, 1.42, p = 4x10-4) in JHS, and with overall mortality in both JHS (HR 1.12 per SD, 95% CI 1.03, 1.21, p = 7.5x10-3) and REGARDS (HR 1.31 per SD, 95% CI 1.10, 1.55, p = 2.0 x 10−3), adjusting for cardiovascular risk factors and C-reactive protein. However, we found no association between IP-10 and stroke or coronary heart disease. These results suggest a role of IP-10 in heart failure and mortality risk independent of C-reactive protein. Further research is needed to investigate how the body’s response to chronic viral infection may mediate heart failure and overall mortality risk in African Americans.
Highlights
Low-grade chronic inflammation, as characterized by elevated circulating levels of innate immunity biomarkers (e.g., C-reactive protein (CRP), interleukin-6, soluble TNF receptor), has been long recognized as an independent risk factor for numerous aging-related chronic diseases such as atherosclerotic cardiovascular disease (CVD) and heart failure (HF), as well as all-cause mortality
While IFN is not readily measurable in plasma, interferon gamma-inducible protein 10 (IP-10, known as C-X-C motif chemokine 10 or CXCL10) may serve as a surrogate chemokine marker for chronic activation of the IFN-1 pathway, distinct from the acute inflammation cascade which is marked by chemokines such as IL-6 and IL-8.[9]. Differences in rates of chronic viral infections (including hepatitis B (HBV)[10] and HCV[11]) among African American (AA) populations, as well as known racial disparities in other chronic inflammation measures,[12] may make biomarkers of innate immunity like IP10 of particular interest in CVD risk assessment in AAs
We examined the relationship of circulating levels of IP-10, an IFN-dependent chemokine, with CVD outcomes and mortality in two community-based prospective studies of AAs
Summary
Low-grade chronic inflammation, as characterized by elevated circulating levels of innate immunity biomarkers (e.g., C-reactive protein (CRP), interleukin-6, soluble TNF receptor), has been long recognized as an independent risk factor for numerous aging-related chronic diseases such as atherosclerotic cardiovascular disease (CVD) and heart failure (HF), as well as all-cause mortality. The recent CANTOS trial demonstrated that inhibition of the pro-inflammatory cytokine interleukin 1-β, which is closely tied to innate immune system function[1], by canakinumab reduced both the risk of CVD events[2] and lung cancer mortality.[3] While immune dysregulation is a common feature of aging, some immunity-related pathways have not been extensively studied in the context of CVD risk. Chronic viral infections such as HIV[4] and hepatitis C (HCV)[5] are associated with increased coronary artery disease risk independent of traditional risk factors. Differences in rates of chronic viral infections (including hepatitis B (HBV)[10] and HCV[11]) among African American (AA) populations, as well as known racial disparities in other chronic inflammation measures,[12] may make biomarkers of innate immunity like IP10 of particular interest in CVD risk assessment in AAs
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