Processed B-Type Natriuretic Peptide Is a Biomarker of Postinterventional Restenosis in Ischemic Heart Disease

Abstract

Background: Restenosis, a condition in which the lesion vessel renarrows after a coronary intervention procedure, remains a limitation in management. A surrogate biomarker for risk stratification of restenosis would be welcome. B-type natriuretic peptide (BNP) is secreted in response to pathologic stress from the heart. Its use as a biomarker of heart failure is well known; however, its diagnostic potential in ischemic heart disease is less explored. Recently, it has been reported that processed forms of BNP exist in the circulation. We hypothesized that circulating processed forms of BNP might be a biomarker of ischemic heart disease.

                    

Methods: We characterized processed forms of BNP by a newly developed mass spectrometry–based detection method combined with immunocapture using commercial anti-BNP antibodies.

                    

Results: Measurements of processed forms of BNP by this assay were found to be strongly associated with presence of restenosis. Reduced concentrations of the amino-terminal processed peptide BNP(5–32) relative to BNP(3–32) [as the index parameter BNP(5–32)/BNP(3–32) ratio] were seen in patients with restenosis [median (interquartile range) 1.19 (1.11–1.34), n = 22] vs without restenosis [1.43 (1.22–1.61), n = 83; P < 0.001] in a cross-sectional study of 105 patients undergoing follow-up coronary angiography. A sensitivity of 100% to rule out the presence of restenosis was attained at a ratio of 1.52.

                    

Conclusions: Processed forms of BNP may serve as viable potential biomarkers to rule out restenosis.

© 2013 The American Association for Clinical Chemistry

Low Serum Levels of Pepsinogen and Gastrin 17 Are Predictive of Extensive Gastric Atrophy with High-Risk of Early Gastric Cancer

Atrophic gastritis (AG) is a well-recognized high-risk condition for developing gastric cancer (GC). Gastrin 17 (G17), a hormone secreted from antral G cells, regulates gastric acid secretion, and its serum level is a possible indicator of antral atrophy.

Serum pepsinogen is well established as the indicator of AG involving the corpus. Here we investigated whether serum PG and G17 levels would be useful for determining the topographic pattern of AG and estimating the risk of GC. Enrolled were 122 Japanese patients with early GC (114 well- to moderate-differentiated cancers and 8 poorly-differentiated cancers). In addition, 178 subjects without GC were recruited as control from those undergoing endoscopic examination (non-GC group).

All subjects were histologically assigned to the following four groups: non-AG, antrum-predominant AG, corpus-predominant AG, and multifocal AG, affecting the antrum and corpus. Serum concentrations of pepsinogen and G17 were determined using ELISA. Multifocal AG was more frequent in the GC group than in the adjusted non-GC group, and had the highest risk of GC (OR 25.1). Serum G17 was significantly decreased with the exacerbation of antral atrophy in the coexistence of corpus atrophy.

Serum biomarker profiles showed that the low levels of pepsinogen and G17 could discriminate between multifocal AG and other types of AG, but not with pepsinogen level alone. Serologically defined multifocal AG had the highest cancer risk among other serologically defined AG groups (OR 26.9).

In conclusion, the low serum levels of pepsinogen and G17 are predictive of extensive gastric atrophy with high-risk of early GC.

Researchers Discover New Biomarker That May Improve Cancer Care Strategies

In a preliminary study, researchers identified a novel biomarker that predicts cancer metastasis. If validated in more-rigorous studies, the biomarker could help clinicians improve treatment strategies for patients with certain types of cancer.

Researchers found in a small preliminary study that varying levels of a novel biomarker, an N-terminal truncated protein variant of carboxypeptidase E (CPE-ΔN), may be predictive of metastasis in certain cancers.
Researchers with the National Institutes of Health and the University of Hong Kong in China discovered that an N-terminal truncated protein variant of carboxypeptidase E (CPE-ΔN) induces tumor growth and metastasis. Patients with high levels of this protein were more likely to have their cancer spread, regardless of staging and grading; those with low levels, regardless of staging and grading, were more likely to not have their cancers spread (Lee TK et al. J Clin Invest. doi: 10.1172/JCI40433

Theme: Alzheimer's disease: the biomarker revolution - Review

Epidemiological and molecular studies suggest that Alzheimer’s disease (AD) has multiple etiologies including genetic mutations, genetic variations affecting susceptibility and environmental factors. These aspects can promote the formation and accumulation of insoluble amyloid-β and hyperphosphorylated tau. Since the disease is multifactorial and clinical diagnosis is highly exclusive, the need for a sensitive, specific and reliable biomarker is crucial.

The concept of a biomarker implies sensitivity and specificity relative to the condition being considered. For clinical practice, AD diagnosis has been based on adherence to clinical criteria such as the NINCDS/ADRDA and DSM-IV. A more recent set of diagnostic criteria proposed incorporates imaging findings into the diagnosis of AD.

In this article, we consider the most studied candidates or group of candidates for AD biomarkers, including pathological processes and proteins (amyloid-β, tau, oxidative stress, mitochondrial/metabolic changes and cell-cycle processes), or autoantibodies thereto, as well as genetic factors.

Biomarkers in Alzheimer’s disease: past, present and future
Katarzyna Gustaw-Rothenberg‌1,2, Alan Lerner‌1, David J Bonda‌3, Hyoung-gon Lee‌3, Xiongwei Zhu‌3, George Perry‌3,4 & Mark A Smith‌3††Author for correspondence

Biomarkers in Medicine
February 2010, Vol. 4, No. 1, Pages 15-26

Cerebrospinal fluid biomarkers of Alzheimer’s disease

Alzheimer’s disease will reach epidemic proportions within the next 20–30 years if left unchecked. Currently, there are no treatments that prevent or slow Alzheimer’s disease but many are being developed. Parallel efforts to develop biomarkers to aid in disease diagnosis and prognosis, and assess disease risk are currently underway. Clinicopathological and biomarker studies have demonstrated that Alzheimer’s disease pathology can be detected preclinically.

Using biomarkers to identify affected individuals prior to the onset of clinical symptoms and associated synaptic/neuronal loss should enable novel clinical trial design and early mechanism-based therapeutic intervention. This article summarizes the most promising cerebrospinal fluid biomarkers, highlights novel applications and current challenges, and provides a prediction on how the field may evolve in 5–10 years

Extracellular Cardiac Matrix Biomarkers in Patients With Acute Myocardial Infarction Complicated by Left Ventricular Dysfunction and Heart Failure

Circulation. 2009;119:2471-2479
Insights From the Eplerenone Post–Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) Study

Background— Aldosterone stimulates cardiac collagen synthesis. Circulating biomarkers of collagen turnover provide a useful tool for the assessment of cardiac remodeling in patients with congestive heart failure and left ventricular systolic dysfunction after acute myocardial infarction.

Methods and Results— In a substudy of the Eplerenone Post–Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS), which evaluated the effects of the selective aldosterone receptor antagonist eplerenone versus placebo, serum levels of collagen biomarkers were measured in 476 patients with congestive heart failure after acute myocardial infarction complicated with left ventricular systolic dysfunction. The combination of the type I collagen telopeptide and brain natriuretic peptide levels above median at baseline was associated with all-cause mortality and the composite end point of cardiovascular death or heart failure hospitalization, with hazard ratios of 2.49 (P=0.039) and 3.03 (P=0.002), respectively. During follow-up, levels of aminoterminal propeptide of type I and type III procollagen were found to be consistently lower in the eplerenone group and significantly lower beginning at 6 months.

Conclusions— Changes in biomarkers of collagen synthesis and degradation suggest that extracellular matrix remodeling is an active process in patients with congestive heart failure and left ventricular systolic dysfunction after acute myocardial infarction. High type I collagen telopeptide and high brain natriuretic peptide serum levels are associated with the highest event rate. Eplerenone suppresses post–acute myocardial infarction collagen turnover changes.

Wafae Iraqi, PharmD; Patrick Rossignol, MD, PhD; Michael Angioi, MD; Renaud Fay, PharmD; Josette Nuée, PhD; Jean Marie Ketelslegers, MD, PhD; John Vincent, MD; Bertram Pitt, MD; Faiez Zannad, MD, PhD

RENIN AND HEART FAILURE

THE RENIN SYSTEM AND ATRIAL NATRIURETIC HORMONE IN CONGESTIVE HEART FAILURE

Abstract. The renin angiotensin system is activated in the majority of patients with chronic congestive heart failure of moderate to severe symptomology. Renin release may result from one of several different stimuli: renal tubular sodium delivery and sensing by the macula densa, sympathetic nervous system activity, and baroreceptor to changes in renal blood flow. Difficulties arise with an analysis of renin angiotensin system activity due to the necessity for diuretic therapy in the majority of these patients. Despite the presence of diuretic therapy, however, there is a wide range of renin angiotensin system activity. In evaluating this activity the administration of a converting enzyme inhibitor will block the contribution of angiotensin mediated vasoconstriction, thereby confirming the importance of the renin angiotensin system activity as a mediator of the long-term consequences of heart failure In situations of low plasma renin activity, vasoconstriction is mediated by an alternate mechanism. The mechanisms of this non-renin mediated vasoconstriction are less apparent, but may include calcium mediated vasoconstriction, and the effects of increased cytosolic content.

This low renin group of patients appear to be very sensitive to reversal of vasoconstriction by calcium channel antagonists, especially when converting enzyme inhibitors are ineffective. In an analysis of the factors that may result in renin release, tubular delivery of sodium to the macula densa may emerge as the most important regulator of renin release.

In milder forms of heart failure, or in the absence of diuretic therapy, the renin angiotensin system does not show the degree of activation that occurs in the more severe form of heart failure when diuretics are given. From a theroretical standpoint, endogenous atrial natriuretic factor may emerge as an important regular of sodium and water excretion, acting either independently, or as a regulator of the renin angiotensin system, It will therefore be necessary to evaluate the impact of atrial natriuretic factor in patients with congestive heart failure particularly in relation to the renin angiotensin system.

John H. Laragh M.D., Robert J. Cody M.D., Andrew B. Covit M.D. and Steven A. Atlas M.D.Cardiovascular Center, The New York Hospital-Cornell University Medical Center, New York, N.Y.