Developing and assessing cardiovascular biomarkers

Baylor College of Medicine and Methodist DeBakey Heart and Vascular Center, 6565 Fannin Street, Houston, TX 77030, USA.
Translational research : the journal of laboratory and clinical medicine 04/2012; 159(4):265-76. DOI: 10.1016/j.trsl.2012.01.003
Source: PubMed

ABSTRACT Atherosclerosis is a slow process that over time can lead to fatal events. Early identification and prediction of future risk can allow for preventive strategies to be instituted. There is an increasing interest in utilizing novel biomarkers in cardiovascular disease screening and management. These novel biomarkers may help in cardiovascular disease risk assessment and treatment monitoring, and some may be treatment targets. To be useful for risk prediction, novel biomarkers need to show a significant association with cardiovascular disease events and bring additional value in risk stratification when added to known risk prediction models. Biomarkers used for treatment monitoring need to show that they can serve as good surrogates of cardiovascular disease status. In this article, we present 3 biomarkers that are currently approved by the U.S. Food and Drug Administration for use in cardiovascular disease management and risk assessment: C-reactive protein, lipoprotein-associated phospholipase A2, and myeloperoxidase. Other new biomarkers have also been shown recently to help in cardiovascular disease risk prediction and management. In this article, we will review 2 of these new biomarkers: cardiac troponin T measured by a highly sensitive assay and brain natriuretic peptide.

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    ABSTRACT: Commercial ELISA kits for substance P (SubP), which are helpful for the clinical diagnosis of acute myocardial infarction, are limited in efficacy because of low sensitivity. A highly sensitive immunoassay was developed using silica spheres encapsulating a quantum dot-layer (SQS) and labeling antibodies, on a Parylene A-modified plate. The high sensitivity was possible by taking advantage of the enhanced photoluminescence of the SQS and dense immobilization of SubP on a Parylene A-modified plate. Glutaraldehyde was used for cross-linking of SQS to the anti-SubP antibody and SubP to the Parylene A coating. The SQS-linked immunosorbent assay (SQSLISA) was optimized and validated. The dynamic range for the assay was 1-10000 pg/mL with a linear correlation factor of 0.9992 when the competitive SQSLISA was employed. The intra- and inter-day accuracies were 93-100% and 87-122%, respectively. The reproducibility was lower than 11%. The developed method was applied to clinical samples collected from healthy controls (n=30) and acute myocardial infarction (n=16) and it displayed a high correlation with the commercial ELISA kit, with a limit of detection that was 30-fold lower. Clinical sample analysis confirmed that SubP is a promising diagnostic marker for acute myocardial infarction. The SQSLISA is expected to be a practical and useful assay tool.
    Analytical Chemistry 09/2014; 86(20). DOI:10.1021/ac502412x · 5.83 Impact Factor
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    ABSTRACT: Background Epidemiologic data for cardiac abnormality predating decreased kidney function are sparse. We investigated the associations of high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro–brain natriuretic peptide (NT-proBNP) with end-stage renal disease (ESRD) risk in a community-based cohort. Study Design A prospective cohort study. Setting & Participants 10,749 white and black participants at the fourth visit (1996-1998) of the Atherosclerosis Risk in Communities (ARIC) Study with follow-up through 2010. Predictor hs-cTnT (3, 6, 9, and 14 ng/L) and NT-proBNP (41.6, 81.0, 142.5, and 272.5 pg/mL) levels were divided into 5 categories at the same percentiles (32th, 57th, 77th, and 91th; corresponding to ordinary thresholds of hs-cTnT), with the lowest category as a reference. Outcomes Incident ESRD defined as initiation of dialysis therapy, transplantation, or death due to kidney disease. Measurements Relative risk and risk prediction of ESRD according to hs-cTnT and NT-proBNP levels based on Cox proportional hazards models. Results During a median follow-up of 13.1 years, 235 participants developed ESRD (1.8 cases/1,000 person-years). hs-cTnT and NT-proBNP levels were associated with ESRD risk independently of each other and of potential confounders, including kidney function and albuminuria (adjusted HRs for highest category, 4.43 [95% CI, 2.43-8.09] and 2.28 [95% CI, 1.44-3.60], respectively). For hs-cTnT level, the association was significant even at the third category (HR for 6-8 ng/L of hs-cTnT, 2.74 [95% CI, 1.54-4.88]). Their associations were largely consistent even among persons without decreased kidney function or history of cardiovascular disease. hs-cTnT and NT-proBNP levels both significantly improved ESRD prediction (C statistic differences of 0.0084 [95% CI, 0.0005-0.0164] and 0.0045 [95% CI, 0.0004-0.0087], respectively, from 0.884 with conventional risk factors). Limitations Relatively small number of ESRD cases and single measurement of hs-cTnT and NT-proBNP. Conclusions hs-cTnT and NT-proBNP levels independently predicted ESRD risk in the general population, with more evident results for hs-cTnT. These results suggest the involvement of cardiac abnormality, particularly cardiac injury, in the progression of reduced kidney function and/or may reflect the useful property of hs-cTnT as an end-organ damage marker.
    American Journal of Kidney Diseases 10/2014; 65(4). DOI:10.1053/j.ajkd.2014.08.021 · 5.76 Impact Factor
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    ABSTRACT: Heart failure (HF) poses a heavy burden on patients, their families and society. The syndrome of HF comes in two types: with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). The latter is on the increase and predominantly present in women, especially the older ones. There is an urgent need for mortality-reducing drugs in HFpEF, a disease affecting around 5 % of those aged 65 years and over. HFpEF develops in patients with risk factors and comorbidities such as obesity, hypertension, diabetes, COPD, but also preeclampsia. These conditions are likely to drive microvascular disease with involvement of the coronary microvasculature, which may eventually evolve into HFpEF. Currently, the diagnosis of HFPEF relies mainly on echocardiography. There are no biomarkers that can help diagnose female microvascular disease or facilitate the diagnosis of (early stages of) HFpEF. Recently a Dutch consortium was initiated, Queen of Hearts, with support from the Netherlands Heart Foundation, with the aim to discover and validate biomarkers for diastolic dysfunction and HFpEF in women. These biomarkers come from innovative blood-derived sources such as extracellular vesicles and circulating cells. Within the Queen of Hearts consortium, we will pursue female biomarkers that have the potential for further evolution in assays with point of care capabilities. As a spin-off, the consortium will gain knowledge on gender-specific pathology of HFpEF, possibly opening up novel treatment options.
    Netherlands heart journal: monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 01/2015; 23(2). DOI:10.1007/s12471-014-0613-1 · 2.26 Impact Factor