Prediction of Primary Cardiovascular Events Using the Multimarker Approach

Sponsor

Karaganda Medical University (Other)

Overall Status

Completed

CT.gov ID

NCT05704569

Collaborator

(none)

1,500

Enrollment

102

Actual Duration (Months)

Study Details

Study Description

Brief Summary

The study of biochemical risk factors for cardiovascular diseases is important not only for analysis, but also for preventive measures, given that changes in the level of biomarkers can be detected before the first clinical manifestations of CVD. Accordingly, patients at high CV risk may have additional motivation to lead a healthy lifestyle. In addition, information on biochemical risk markers can be used to optimize the clinical management of patients.

Condition or Disease	Intervention/Treatment	Phase
Cardiovascular Diseases Stroke Myocardial Infarction Death Coronary Artery Disease	Diagnostic Test: measurement of multiple biomarkers

Detailed Description

Recruitment of 1500 people randomly without previous cardiovascular events. Examination, questioning of patients, laboratory tests. Patient follow-up for 6 years. Registration of the facts of the occurrence of cardiovascular events.

Cohort study with a retrospective and prospective component

Stage I (Conducted in 2014 as part of the scientific and technical project "Environmental risks and public health")

Questionnaire and general clinical examination (anthropometry, measurement of blood pressure, BMI, WC)
determination of cholesterol, glucose and total cardiovascular risk according to the SCORE scale
Determination of the quality of life, the level of depression and anxiety, the level of physical activity.

For an in-depth biochemical blood test for onco- and cardiomarkers, the MILLIPLEX MAP Human panel was used. This panel allows you to simultaneously study 23 onco- and 11 cardiac markers, which are the most common among oncological and cardiac diseases. Tumor markers included: alpha-fetoprotein (Afp), carbohydrate antigen 125 (CA125), carbohydrate antigen 15-3 (CA15-3), cancer embryonic antigen (CEA), cytokeratin fragment 19 (CYFRA21-1), fibroblast growth factor 2 (FGF2), human epididymis protein 4 (HE4), hepatocyte growth factor (HGF-α), interleukin 6 (IL6), interleukin 8 (IL8), leptin (LEPTIN), anti-Mullerian hormone (MIF), osteopontin (OPN ), prolactin (PROLACTIN), common prostate specific antigen (PSAtotal), cystatin C (SCF), apoptosis inducer (SFAS), transforming growth factor (TGF-α), tumor necrosis factor (TNF), TRAIL, vascular endothelial growth factor ( VEGF), Beta chorionic gonadotropin (bHCG), apoptosis inducer L (SFAS) L.

In respondents with cardiovascular risk (1% or more on the SCORE scale), the level of cardiomarkers was determined. Cardiomarkers included: creatine kinase MB (CK MB), chemokine C-X-C motif, ligand 16 (CXCL16), fatty acid binding protein, cardiac form (FABP3), N-terminal fragment of the brain natriuretic peptide (NT-ProBNP), oncostatin M (OSM), placental growth factor isoform (PIGF 4), C-X-C motif chemokine, ligand 6 (CXCL6), endocan 1 (ENDOCAN1), fatty acid binding protein 4 (FABP-4), TNF superfamily protein ( LIGHT), troponin I (TROPONINI).

Determination of the content of biochemical markers in the blood (carried out at the Collective Use Laboratory of the NJSC "Medical University of Karaganda").

STAGE II Prospective observation for 6 years, For a cardiovascular event we take the development of: Acute forms of ischemic disease (ACS with and without ST-segment elevation / myocardial infarction), chronic forms of IHD-angina pectoris, Acute cerebrovascular accident, transient ischemic attack, Lethal outcome from CVD, death from all causes.

Statistical data processing will be carried out using the SPSS program (version 22.0). Quantitative variables with a normal distribution will be presented as mean values and their standard deviations (M ± SD), with a difference from the normal distribution - median and interquartile range (Me (IQR). Dichotomous signs are presented as shares (absolute number of patients (%) Descriptive statistics will use the Mann-Whitney U-test for independent samples to compare quantitative data, categorical data will be analyzed using Pearson's χ2, Spearman's (Rho) correlation analysis will be used to determine the relationship between parameters, Using binary logistic regression (one-way and multivariate) if independent predictors of the NSS and the odds ratio (OR) are established at a 95% confidence interval (CI) for each factor.Based on the results of multivariate regression analysis on the values of exp(B) of significant variables and constants, a predictive model will be built, predictive value ( specificity, h Sensitivity, % of false positive and false negative results. Cox regression, Kaplan-Meier survival analysis will also be used, there will be a comparison of C-statistics of models. The critical level of significance (p) when testing statistical hypotheses will be taken as 0.05.

Study Design

Study Type:

Observational

Actual Enrollment :

1500 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Prediction of Primary Cardiovascular Events Using a Multimarker Approach (Prospective Clinical Study)

Actual Study Start Date :

Jun 1, 2014

Actual Primary Completion Date :

Mar 1, 2020

Actual Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
the outcome group The composite endpoint included the presence of any of the following events: cardiovascular death, MI, stroke, hospitalization and/or application due to CHD, and transient ischemic attack	Diagnostic Test: measurement of multiple biomarkers All patients were tested for glucose and cholesterol levels. The capillary blood glucose level was measured by an electrochemical method using an Accu-Chek Active by AkkuChek blood glucose meter. The DM was considered to be verified when there were criteria which the World Health Organization (WHO) set in 2001: glucose concentration in whole blood is >6.1 mmol/l, and glucose concentration is >11.1 mmol/l in random measurement. Plasma for the study was obtained via the standard phlebotomy technique from ethylenediaminetetraacetic acid (EDTA) anticoagulants. Plasma was aliquoted into cryovials and got frozen quickly. The samples were stored in a low-temperature refrigerator (-70°C) until the study commencement (up to 3 months). All biomarkers were measured by magnetic bead-based multiplex immunofluorescence assay through the Xmap technology using the Milliplex map Human CVD Magnetic Bead Panel 1 (Millipore)
no-outcome group individuals who did not experience any events during the observation period	Diagnostic Test: measurement of multiple biomarkers All patients were tested for glucose and cholesterol levels. The capillary blood glucose level was measured by an electrochemical method using an Accu-Chek Active by AkkuChek blood glucose meter. The DM was considered to be verified when there were criteria which the World Health Organization (WHO) set in 2001: glucose concentration in whole blood is >6.1 mmol/l, and glucose concentration is >11.1 mmol/l in random measurement. Plasma for the study was obtained via the standard phlebotomy technique from ethylenediaminetetraacetic acid (EDTA) anticoagulants. Plasma was aliquoted into cryovials and got frozen quickly. The samples were stored in a low-temperature refrigerator (-70°C) until the study commencement (up to 3 months). All biomarkers were measured by magnetic bead-based multiplex immunofluorescence assay through the Xmap technology using the Milliplex map Human CVD Magnetic Bead Panel 1 (Millipore)

Arm

Intervention/Treatment

the outcome group

The composite endpoint included the presence of any of the following events: cardiovascular death, MI, stroke, hospitalization and/or application due to CHD, and transient ischemic attack

Diagnostic Test: measurement of multiple biomarkers

All patients were tested for glucose and cholesterol levels. The capillary blood glucose level was measured by an electrochemical method using an Accu-Chek Active by AkkuChek blood glucose meter. The DM was considered to be verified when there were criteria which the World Health Organization (WHO) set in 2001: glucose concentration in whole blood is >6.1 mmol/l, and glucose concentration is >11.1 mmol/l in random measurement. Plasma for the study was obtained via the standard phlebotomy technique from ethylenediaminetetraacetic acid (EDTA) anticoagulants. Plasma was aliquoted into cryovials and got frozen quickly. The samples were stored in a low-temperature refrigerator (-70°C) until the study commencement (up to 3 months). All biomarkers were measured by magnetic bead-based multiplex immunofluorescence assay through the Xmap technology using the Milliplex map Human CVD Magnetic Bead Panel 1 (Millipore)

no-outcome group

individuals who did not experience any events during the observation period

Diagnostic Test: measurement of multiple biomarkers

Outcome Measures

Primary Outcome Measures

stroke or transient ischemic attack [66 months]
stroke was defined as a sudden onset of nonconvulsive and focal neurological deficit due to ischemia or hemorrhage that lasts >24 hours, and it is transient ischemic attack if neurological recovery occurred within 24 hours. &e diagnosis of stroke and the transient ischemic attack was based on the disease history, neurological examination, and all available clinical data, including computed tomography (CT)/magnetic resonance imaging (MRI) results.
Coronary heart disease [66 months]
Coronary heart disease included myocardial infarction, sudden cardiac death, and newly diagnosed angina. The criteria for MI were at least two of the following: (1) typical symptoms, including prolonged severe anterior chest pain; (2) elevated cardiac enzymes-higher than twice the upper limit of the standard values; sudden cardiac death within 1 hour of the acute condition onset; (3) progressive diagnostic electrocardiographic changes. The cases of newly diagnosed angina were determined based on typical angina-type pain, reversed by the use of nitrates, confirmed by a doctor's examination, and via the electrocardiography (ECG) exercise test.
cardiovascular death [66 months]
death reported as a complication of cardiovascular disease

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

iInclusion Criteria:

• respondents living in the territory of the Republic of Kazakhstan from 25 to 65 years without previous cardiovascular events.

Exclusion criteria: pregnant women; persons with mental and severe neurological diseases; survivors of an acute event associated with atherosclerosis; persons with diagnosed chronic forms of coronary artery disease; persons with verified CHF; persons with myocarditis and cardiomyopathies of various origins, congenital and acquired heart defects, atherosclerosis of peripheral arteries.