A screening method to spot biomarkers that may warn of serious events in a chronic disease – illustrated by cardiological CLARICOR trial data

Abstract Objectives To develop a crude screening method for detecting biomarkers which frequently exhibit a rise (or fall) in level prior to a serious event (e.g. a stroke) in patients with a chronic disease, signalling that the biomarker may have an alarm-raising or prognostic potential. The subsequent assessment of the marker’s clinical utility requires costly, difficult longitudinal studies. Therefore, initial screening of candidate-biomarkers is desirable. Methods The method exploits a cohort of patients with biomarkers measured at entry and with recording of first serious event during follow-up. Copying those individual records onto a common timeline where a specific event occurs on the same day (Day 0) for all patients, the baseline biomarker level, when plotted against the patient’s entry time on the revised timeline, will have a positive (negative) regression slope if biomarker levels generally rise (decline) the closer one gets to the event. As an example, we study 1,958 placebo-treated patients with stable coronary artery disease followed for nine years in the CLARICOR trial (NCT00121550), examining 11 newer biomarkers. Results Rising average serum levels of cardiac troponin T and of N-terminal pro-B-type natriuretic peptide were seen prior to a fatal cardiovascular outcome. C-reactive protein rose prior to non-cardiovascular death. Glomerular filtration rate, seven lipoproteins, and nine newer cardiological biomarkers did not show convincing changes. Conclusions For early detection of biomarkers with an alarm-raising potential in chronic diseases, we proposed the described easy procedure. Using only baseline biomarker values and clinical course of participants with coronary heart disease, we identified the same cardiovascular biomarkers as those previously found containing prognostic information using longitudinal or survival analysis.

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Risk Factors of Cardiac Troponin T Elevation in Patients with Stable Coronary Artery Disease After Elective Coronary Drug-Eluting Stent Implantation

Clinical Cardiology ◽

10.1002/clc.20973 ◽

2011 ◽

Vol 34 (12) ◽

pp. 768-773 ◽

Cited By ~ 3

Author(s):

Zhang-Wei Chen ◽

Ju-Ying Qian ◽

Jian-Ying Ma ◽

Lei Ge ◽

Jun-Bo Ge

Keyword(s):

Risk Factors ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Cardiac Troponin ◽

Troponin T ◽

Stable Coronary Artery Disease ◽

Drug Eluting Stent ◽

Cardiac Troponin T ◽

Drug Eluting ◽

Artery Disease

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Serum Levels of FGF21, β-Klotho, and BDNF in Stable Coronary Artery Disease Patients With Depressive Symptoms: A Cross-Sectional Single-Center Study

Frontiers in Psychiatry ◽

10.3389/fpsyt.2020.587492 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yeshun Wu ◽

Zijun Chen ◽

Jiahao Duan ◽

Kai Huang ◽

Bin Zhu ◽

...

Keyword(s):

Coronary Artery Disease ◽

Depressive Symptoms ◽

Coronary Artery ◽

Stable Coronary Artery Disease ◽

Depression Scale ◽

Serum Levels ◽

Fibroblast Growth Factor 21 ◽

Healthy Population ◽

Cross Sectional ◽

Artery Disease

Background: The incidence of depressive symptoms (DS) in patients with stable coronary artery disease (SCAD) is significantly higher than those in healthy population, and that DS are independent risk factors for cardiovascular events. Previous studies have reported that fibroblast growth factor 21 (FGF21), β-klotho, mature brain-derived neurotrophic factor (mBDNF), and BDNF precursor (proBDNF) play important roles in the pathogenesis and treatment of coronary heart disease and depression. With this in mind, the present study aimed to clarify the relationship between FGF21, β-klotho, mBDNF, and proBDNF and SCAD with comorbid depression, in addition to also exploring the underlying mechanisms of these disease processes.Methods: A total of 116 patients with SCAD and 45 healthy controls were recruited. Patients with SCAD were further divided into two subgroups based on the Zung Self-Rating Depression Scale (SDS), which were characterized as those with no DS (NDS) and those with DS. Baseline data were collected, and serum levels of FGF21, β-klotho, mBDNF, and proBDNF were determined.Results: In SCAD patients, Gensini scores—denoting the degree of coronary arteriostenosis—were significantly greater in the DS group than in the NDS group. There was also a positive correlation between the Gensini scores and the SDS scores. Patients in the SCAD group demonstrated a lower serum FGF21. Serum β-klotho, mBDNF, and mBDNF/proBDNF were also significantly lower in the DS group than in the NDS group. Furthermore, β-klotho and mBDNF were negatively correlated with the SDS scores. Additionally, SCAD patients were divided into lower- and higher-level groups using hierarchical cluster analysis, with the results highlighting that patients in the lower mBDNF group had a higher incidence of DS.Conclusions: The depression score was positively correlated with the severity of coronary artery stenosis, and serum FGF21, β-klotho, mBDNF, and proBDNF were closely related to the development of DS in patients with SCAD. These observations suggest FGF21, β-klotho, mBDNF, and proBDNF as potential diagnostic and/or therapeutic targets for SCAD with co-morbid depression.

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Abstract 18682: Inflammatory Biomarkers for Prognostication of Outcomes in Stable Coronary Artery Disease - Experiences From the STABILITY Trial

Circulation ◽

10.1161/circ.130.suppl_2.18682 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Claes Held ◽

Harvey D White ◽

Ralph A Stewart ◽

Andrzej Budaj ◽

Christopher P Cannon ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Medical Treatment ◽

Cox Regression ◽

Stable Coronary Artery Disease ◽

Cardiac Biomarkers ◽

Prognostic Information ◽

Hs Crp ◽

Artery Disease ◽

The Impact

Introduction: Prognostication of outcome in patients with stable coronary artery disease (CAD) is currently based on clinical characteristics and biomarkers indicating dysglycemia, dyslipidemia, renal dysfunction and possibly cardiac biomarkers. Hypothesis: We assessed the incremental prognostic value of biomarkers of inflammation in the Stabilization of Atherosclerotic Plaque By Initiation of Darapladib Therapy (STABILITY) trial. Methods: In STABILITY, 15,828 patients with chronic CAD on optimal medical treatment were randomized to treatment with darapladib or placebo. Serum levels of hs-C-reactive protein (CRP) and Interleukin (IL)-6 were measured at randomization in 14,373 and 4733 patients, respectively. Centrally adjudicated outcome events were accumulated during a median of 3.7 years follow-up. The associations between levels of the biomarkers and outcomes were evaluated by multivariable Cox regression. Results: The impact of biomarker levels at baseline in relation to the composite endpoint, MACE (major adverse cardiovascular event), of cardiovascular (CV) death, myocardial infarction (MI) and stroke, and its individual components are presented in the Table. Both hs-CRP and IL-6 provided strong prognostic information in addition to clinical predictors for outcomes of MACE, CV death and MI, but not for stroke. Conclusions: In conclusion, the cardiac biomarkers hs-CRP and IL-6, provided important complementary prognostic information on the risk of CV mortality and MI, but not for stroke in patients with stable CAD on optimal medical treatment.

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High-Sensitivity Cardiac Troponin T is Associated with SYNTAX Score and Diabetes Mellitus in Patients with Stable Coronary Artery Disease

Journal of Clinical & Experimental Cardiology ◽

10.4172/2155-9880.1000263 ◽

2013 ◽

Vol 04 (09) ◽

Author(s):

Onur Kaypakl Nermin Yıldız Koyunsever

Keyword(s):

Diabetes Mellitus ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Cardiac Troponin ◽

Troponin T ◽

Stable Coronary Artery Disease ◽

High Sensitivity ◽

Syntax Score ◽

Cardiac Troponin T ◽

Artery Disease

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Simple risk models to predict cardiovascular death in patients with stable coronary artery disease

European Heart Journal - Quality of Care and Clinical Outcomes ◽

10.1093/ehjqcco/qcz070 ◽

2020 ◽

Cited By ~ 1

Author(s):

Ian Ford ◽

Michele Robertson ◽

Nicola Greenlaw ◽

Christophe Bauters ◽

Gilles Lemesle ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Risk Model ◽

Stable Coronary Artery Disease ◽

Cardiovascular Death ◽

Left Ventricular ◽

Cox Proportional Hazards Model ◽

Clinical Variables ◽

Model Based ◽

Artery Disease

Abstract Aims Risk estimation is important to motivate patients to adhere to treatment and to identify those in whom additional treatments may be warranted and expensive treatments might be most cost effective. Our aim was to develop a simple risk model based on readily available risk factors for patients with stable coronary artery disease (CAD). Methods and results Models were developed in the CLARIFY registry of patients with stable CAD, first incorporating only simple clinical variables and then with the inclusion of assessments of left ventricular function, estimated glomerular filtration rate, and haemoglobin levels. The outcome of cardiovascular death over ∼5 years was analysed using a Cox proportional hazards model. Calibration of the models was assessed in an external study, the CORONOR registry of patients with stable coronary disease. We provide formulae for calculation of the risk score and simple integer points-based versions of the scores with associated look-up risk tables. Only the models based on simple clinical variables provided both good c-statistics (0.74 in CLARIFY and 0.80 or over in CORONOR), with no lack of calibration in the external dataset. Conclusion Our preferred model based on 10 readily available variables [age, diabetes, smoking, heart failure (HF) symptom status and histories of atrial fibrillation or flutter, myocardial infarction, peripheral arterial disease, stroke, percutaneous coronary intervention, and hospitalization for HF] had good discriminatory power and fitted well in an external dataset. Study registration The CLARIFY registry is registered in the ISRCTN registry of clinical trials (ISRCTN43070564).

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Clopidogrel Use as Single Antiplatelet Therapy in Outpatients with Stable Coronary Artery Disease: Prevalence, Correlates and Association with Prognosis (from the CORONOR Study)

Cardiology ◽

10.1159/000442706 ◽

2016 ◽

Vol 134 (1) ◽

pp. 11-18 ◽

Cited By ~ 4

Author(s):

Gilles Lemesle ◽

Guillaume Schurtz ◽

Thibaud Meurice ◽

Olivier Tricot ◽

Nestor Lemaire ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Antiplatelet Therapy ◽

Stable Coronary Artery Disease ◽

Significant Proportion ◽

Cardiovascular Death ◽

Drug Eluting Stent ◽

Bleeding Events ◽

Therapy Regimen ◽

Artery Disease

Background: Clopidogrel use as single antiplatelet therapy (SAPT) has never been evaluated in stable coronary artery disease (CAD) outpatients either as compared to placebo or aspirin. Methods: We therefore studied 2,823 outpatients included in a prospective registry. The patients were divided into 2 groups according to their antiplatelet therapy regimen: patients treated with clopidogrel were compared with those treated with aspirin alone. Results: The mean time since CAD diagnosis was 7.9 years. Altogether, 776 (27.5%) patients received clopidogrel as SAPT. Factors independently associated with clopidogrel use were prior aortic or peripheral intervention, drug-eluting stent implantation, stroke, carotid endarterectomy and time since CAD diagnosis. Clopidogrel tended to be used in higher-risk patients: composite of cardiovascular death, myocardial infarction or stroke at 5.8 versus 4.2% (p = 0.056). However, after propensity score matching, similar event rates were observed between the groups: 5.9% when treated with clopidogrel versus 4.4% with aspirin (p = 0.207). The rate of bleeding was also similar between the groups. Conclusions: Our study shows that a significant proportion of stable CAD patients are treated with clopidogrel as SAPT in modern practice. Several correlates of such an attitude were identified. Our results suggest that this strategy is not beneficial as compared to aspirin alone in terms of ischaemic or bleeding events.

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