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Acute phase reactants as novel predictors of cardiovascular disease.

ABSTRACT: Acute phase reaction is a systemic response which usually follows a physiological condition that takes place in the beginning of an inflammatory process. This physiological change usually lasts 1-2 days. However, the systemic acute phase response usually lasts longer. The aim of this systemic response is to restore homeostasis. These events are accompanied by upregulation of some proteins (positive acute phase reactants) and downregulation of others (negative acute phase reactants) during inflammatory reactions. Cardiovascular diseases are accompanied by the elevation of several positive acute phase reactants such as C-reactive protein (CRP), serum amyloid A (SAA), fibrinogen, white blood cell count, secretory nonpancreatic phospholipase 2-II (sPLA2-II), ferritin, and ceruloplasmin. Cardiovascular disease is also accompanied by the reduction of negative acute phase reactants such as albumin, transferrin, transthyretin, retinol-binding protein, antithrombin, and transcortin. In this paper, we will be discussing the biological activity and diagnostic and prognostic values of acute phase reactants with cardiovascular importance. The potential therapeutic targets of these reactants will be also discussed.

SUBMITTER: Ahmed MS

PROVIDER: S-EPMC3767354 | biostudies-other | 2012

REPOSITORIES: biostudies-other

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Acute phase reactants as novel predictors of cardiovascular disease.

Ahmed M S MS Jadhav A B AB Hassan A A Meng Qing H QH

ISRN inflammation 20120506

Acute phase reaction is a systemic response which usually follows a physiological condition that takes place in the beginning of an inflammatory process. This physiological change usually lasts 1-2 days. However, the systemic acute phase response usually lasts longer. The aim of this systemic response is to restore homeostasis. These events are accompanied by upregulation of some proteins (positive acute phase reactants) and downregulation of others (negative acute phase reactants) during inflam ...[more]

PMID: 24049653

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Project description:Context: Risk factors for adverse cardiovascular events (ACVE) from drug exposures have been well-characterized in adults but not studied in children. The objective of the present study is to describe the incidence, characteristics, and risk factors for in-hospital ACVEs among pediatric emergency department (ED) patients with acute drug exposures.Methods: This is a prospective cohort design evaluating patients in the Toxicology Investigators Consortium (ToxIC) Registry. Pediatric patients (age <18 years) who were evaluated at the bedside by a medical toxicologist for a suspected acute drug exposure were included. The primary outcome was in-hospital ACVE (myocardial injury, shock, ventricular dysrhythmia, or cardiac arrest). The secondary outcome was in-hospital death. Multiple logistic regression analyses were performed to examine novel clinical risk factors and extrapolate adult risk factors (bicarbonate <20?mEq/L; QTc ?500?ms), for the primary/secondary outcomes.Results: Among the 13,097 patients (58.5% female), there were 278 in-hospital ACVEs (2.1%) and 39 in-hospital deaths (0.3%). Age and drug class of exposure (specifically opioids and cardiovascular drugs) were independently associated with ACVE. Compared with adolescents, children under 2 years old (OR: 0.41, 95% CI: 0.21-0.80), ages 2-6 (OR: 0.37, 95% CI: 0.21-0.80), and ages 7-12 (OR: 0.51, 95% CI: 0.27-0.95) were significantly less likely to experience an ACVE. Serum bicarbonate concentration <20?mEq/L (OR: 2.31, 95% CI: 1.48-3.60) and QTc ? 500?ms (OR: 2.83, 95% CI: 1.67-4.79) were independently associated with ACVE.Conclusion: Previously derived clinical predictors of ACVE from an adult drug overdose population were successfully extrapolated to this pediatric population. Novel associations with ACVE and death included adolescent age and opioid drug exposures. In the midst of the opioid crisis, these findings urgently warrant further investigation to combat adolescent opioid overdose morbidity and mortality.

Project description:IntroductionProteomic profiling of end-stage renal disease (ESRD) patients could lead to improved risk prediction and novel insights into cardiovascular disease mechanisms. Plasma levels of 92 cardiovascular disease-associated proteins were assessed by proximity extension assay (Proseek Multiplex CVD-1, Olink Bioscience, Uppsala, Sweden) in a discovery cohort of dialysis patients, the Mapping of Inflammatory Markers in Chronic Kidney disease cohort [MIMICK; n?=?183, 55% women, mean age 63 years, 46 cardiovascular deaths during follow-up (mean 43 months)]. Significant results were replicated in the incident and prevalent hemodialysis arm of the Salford Kidney Study [SKS dialysis study, n?=?186, 73% women, mean age 62 years, 45 cardiovascular deaths during follow-up (mean 12 months)], and in the CKD5-LD-RTxcohort with assessments of coronary artery calcium (CAC)-score by cardiac computed tomography (n?=?89, 37% women, mean age 46 years).ResultsIn age and sex-adjusted Cox regression in MIMICK, 11 plasma proteins were nominally associated with cardiovascular mortality (in order of significance: Kidney injury molecule-1 (KIM-1), Matrix metalloproteinase-7, Tumour necrosis factor receptor 2, Interleukin-6, Matrix metalloproteinase-1, Brain-natriuretic peptide, ST2 protein, Hepatocyte growth factor, TNF-related apoptosis inducing ligand receptor-2, Spondin-1, and Fibroblast growth factor 25). Only plasma KIM-1 was associated with cardiovascular mortality after correction for multiple testing, but also after adjustment for dialysis vintage, cardiovascular risk factors and inflammation (hazard ratio) per standard deviation (SD) increase 1.84, 95% CI 1.26-2.69, p?=?0.002. Addition of KIM-1, or nine of the most informative proteins to an established risk-score (modified AROii CVM-score) improved discrimination of cardiovascular mortality risk from C?=?0.777 to C?=?0.799 and C?=?0.823, respectively. In the SKS dialysis study, KIM-1 predicted cardiovascular mortality in age and sex adjusted models (hazard ratio per SD increase 1.45, 95% CI 1.03-2.05, p?=?0.034) and higher KIM-1 was associated with higher CACscores in the CKD5-LD-RTx-cohort.ConclusionsOur proteomics approach identified plasma KIM-1 as a risk marker for cardiovascular mortality and coronary artery calcification in three independent ESRD-cohorts. The improved risk prediction for cardiovascular mortality by plasma proteomics merit further studies.

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Acute phase reactants as novel predictors of cardiovascular disease.

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Acute phase reactants as novel predictors of cardiovascular disease.

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