Relationship of CRP, IL-6, and fibrinogen with right ventricular structure and function: The MESA-Right Ventricle Study

Abstract

Background/objectives Inflammation contributes to the pathogenesis of disease associated with the left ventricle (LV); yet, our understanding of the effect of inflammation on the right ventricle (RV) is quite limited. Methods and results The relationships of C-reactive protein (CRP), interleukin-6 (IL-6) and fibrinogen with RV morphology and function (from cardiac MRI) were examined in participants free of clinical cardiovascular disease (n=4,009) from the Multi-Ethnic Study of Atherosclerosis (MESA)-RV study. Multivariable regressions (linear, quantile [25th and 75th] and generalized additive models [GAM]) were used to examine the independent association of CRP, IL-6 and fibrinogen with RV mass, RV end-diastolic volume (RVEDV), RV end-systolic volume (RVESV), RV stroke volume (RVSV) and RV ejection fraction (RVEF). Unadjusted and adjusted analyses revealed strong inverse associations between both CRP and IL-6 with RV mass, RVEDV, RVESV and RVSV (all p<0.01); there were no associations with RVEF. These relationships remained significant after adjustment for the respective LV parameters and lung function. However, GAM models suggested that extreme values of CRP and IL-6 might have positive associations with RV parameters. Fibrinogen showed significant associations in unadjusted models, but no associations after adjustment or in sensitivity analyses. Conclusion Levels of CRP and IL-6 are independently associated with RV morphology even after adjustment for the respective LV measure in this multi-ethnic population free of cardiovascular disease. Systemic inflammation may contribute to RV structural changes independent of effects on the LV.

Cor Pulmonale Parvus in Chronic Obstructive Pulmonary Disease and Emphysema

“…Other mechanisms that reduce blood return to the thorax in severe COPD, affecting filling of both ventricles and the pulmonary vasculature, include a reduced gradient in pressure between the abdomen and chest and abnormal diaphragm orientation compressing the vena cava (42). Alternatively, intrinsic RV diastolic dysfunction, possibly related to increased inflammation or endothelial dysfunction, could decrease RV filling (43, 44). These novel mechanisms may suggest innovative approaches which target diastolic function (for example, soluble guanylate cyclase activators) to treat the cardiac component of exercise limitation in these patients.…”

Right Ventricular Structure and Function Are Associated With Incident Atrial Fibrillation

“…7 In MESA participants, abnormal RV morphology has been linked to subclinical LV dysfunction, 13 conditions associated with abnormal pulmonary vascular function (obesity, emphysema), 17, 29 as well as biomarkers of inflammation and neurohormonal activation. 19, 20, 30 In turn, each of these features – pulmonary pathology, left heart function, systemic inflammation and neurohormonal activation – has been implicated in the pathogenesis of AF. 31, 32 Nevertheless, there has been no assessment of the relationship between RV morphology and incident AF in patients free of cardiovascular disease at baseline.…”

“…33–36 In MESA, the relationship between RV morphology and markers of inflammation has proven complex, although extreme levels of CRP and IL-6 were positively associated with RV mass. 19 Likewise, greater RV mass has been associated with neurohormonal activation, 20 which has been implicated as a risk factor for AF via its influence on myocardial fibrosis, atrial stretch, and modulation of ionic channel function. 36, 3738, 39 Finally, in a subset of the MESA cohort, higher RVEF was associated with higher levels of estradiol, postulated to reflect myocardial effects of estrogen receptor activation.…”

“…14 Whether early changes in RV morphology (RVEF, RVEDM) serve as a more sensitive barometer of systemic drivers of AF (eg. inflammation, neurohormonal activation) 19, 20 that precede atrial remodeling may warrant future investigation.…”

“…obesity, sleep apnea) 17, 18 or biologically relevant pathways (eg. inflammation, neurohormonal activation) 19, 20 implicated in the pathogenesis of AF.…”