Predicting therapeutic response in patients with heart failure: the story of C-reactive protein

Abstract

Heart failure continues to be a major public health burden in the USA. With markedly high rates of morbidity and mortality upon diagnosis, effective treatment and prognosis are critical in the management of chronic heart failure. Growing evidence now supports the hypothesis that inflammation plays a key role in the progression and worsening of heart failure. Of the various inflammatory mediators identified, C-reactive protein, an acute phase inflammatory marker, has been associated with poor prognosis in patients with heart failure. Several interventional studies have been investigated to explore C-reactive protein modulation and potential treatment options and health outcomes; however, further studies are warranted before C-reactive protein-targeted therapy may be recommended in the management of heart failure.

Inflammation in Human Heart Failure: Major Mediators and Therapeutic Targets

“…The proinflammatory cytokine interleukin 6 (IL-6) is an important player in the acute phase response of inflammation, being a stimulus for C-reactive protein production by the liver, but also appears to contribute to the transition from acute to chronic inflammation by favoring the change from neutrophil to monocyte recruitment (Gabay, 2006;Huynh et al, 2015;Hanna and Frangogiannis, 2020). IL-6 is produced by several cell types like macrophages, T-lymphocytes, endothelial cells, cardiomyocytes and fibroblasts (Mihara et al, 2012;Hanna and Frangogiannis, 2020).…”

“…Its synthesis occurs mainly in the liver, being induced by raised IL-6 concentrations under conditions of infection, trauma and other inflammatory states (Huynh et al, 2015;Sheriff et al, 2021). In humans, CRP values markedly increase in the first 72 h after tissue damage, being a sensitive yet non-specific biomarker of inflammation (Huynh et al, 2015;Thiele et al, 2015). CRP is primarily present as a pentamer of five similar polypeptide subunits but can also dissociate into monomers.…”

“…CRP can also be produced outside the liver, namely in vascular smooth muscle cells from human coronary arteries, respiratory epithelium, renal cortical tubular cells, neuronal cells, adipocytes and leukocytes (Huynh et al, 2015;Thiele et al, 2015). Noteworthy, CRP appears to be preferentially expressed in diseased vessels, with its mRNA expression being 7-10-fold higher within atherosclerotic plaque compared to the values found in the liver and normal blood vessels (Yasojima et al, 2001;Calabro et al, 2003;Jabs et al, 2003).…”

Global Longitudinal Strain and Strain Rate in Type Two Diabetes Patients with Chronic Heart Failure: Relevance to Osteoprotegerin

“…10 Currently emerging infl ammatory (high-sensitive C-reactive protein [hs-CRP], osteoprotegerin) and biomechanical stress (N-terminal brain natriuretic peptide [NT-proBNP]) biomarkers are independently associated with all-cause mortality in patients with acute, acutely decompensated and chronic heart failure. [11][12][13][14] However, adding this biomarker into a risk model constructed on clinical data does not improve its prediction value, especially in diabetic population, while they relate to global contractility dysfunction. 15 The aim of this study was to evaluate whether biomarkers predict declining of left ventricular global contractility function in diabetic patients with ischemia-induced CHF.…”

Adverse Cardiac Remodelling after Acute Myocardial Infarction: Old and New Biomarkers

“…Unfortunately, hs-CRP did not add incremental value to NPs, sST2, and galectin-3 in patients with HFpEF rather than HFpEF [133,134]. The ASCEND-HF trial has reported that the levels of hs-CRP at admission in acute HF patients were not associated with acute dyspnea improvement, in-hospital death, advancing HF, short-term (30 days) and long-term (180 days) mortality, and HF readmission [135,136]. On the contrary, at 30 days, elevated levels of hs-CRP among survivors were associated with higher 180-day mortality and readmission [135].…”