Prediction of Primary Cardiovascular Events Using the Multimarker Approach

March 12, 2023 updated by: Karaganda Medical University

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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")

  1. Questionnaire and general clinical examination (anthropometry, measurement of blood pressure, BMI, WC)
  2. determination of cholesterol, glucose and total cardiovascular risk according to the SCORE scale
  3. 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 Type

Observational

Enrollment (Actual)

1500

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

25 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

persons living in the Republic of Kazakhstan, aged 25 to 65 years without previous cardiovascular events

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
number of respondents with stroke or transient ischemic attack
Time Frame: 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.
66 months
Number of respondents with Coronary heart disease
Time Frame: 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.
66 months
Number Of respondents wirh cardiovascular death
Time Frame: 66 months
death reported as a complication of cardiovascular disease
66 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Karaganda Medical University

Investigators

  • Principal Investigator: Lyudmila Turgunova, MD, PhD, ScD, Karaganda Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2014

Primary Completion (Actual)

March 1, 2020

Study Completion (Actual)

December 1, 2022

Study Registration Dates

First Submitted

January 19, 2023

First Submitted That Met QC Criteria

January 19, 2023

First Posted (Actual)

January 30, 2023

Study Record Updates

Last Update Posted (Actual)

March 15, 2023

Last Update Submitted That Met QC Criteria

March 12, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CV risk markers

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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