Impact of the Genetic Background as a Risk Factor for Atherosclerotic Cardiovascular Disease in the Brazilian Population (CV-GENES)

May 29, 2024 updated by: Álvaro Avezum Junior, Hospital Alemão Oswaldo Cruz

The main objective of this project is to evaluate the genomic information previously associated with cardiovascular diseases (CVD) and its importance as an independent risk predictor (expressed in Odds Ratio) when adjusted for traditional risk factors (smoking, diabetes, arterial hypertension, obesity , anxiety and depression, inadequate diet, physical inactivity, alcohol consumption and apolipoprotein B/A1 ratio (ApoB/ApoA1).

An unpaired case-control study of individuals over 18 years of age will be carried out. Cases (N = 1867) will be enrolled right after the occurrence of the first atherosclerotic cardiovascular event (Acute Myocardial Infarction, Stroke and Peripheral Artery Thrombotic-Ischemic Events). The ratio between cases and controls will be 1:1. The controls (N = 1867) will be adult individuals over 18 years of age who sought medical care at the same locations for other clinical reasons (no CVD) or individuals without any overt disease. The genetic evaluation will be performed through the association of Low-covering Whole Genome Sequencing (coverage 0.5-5x) and Whole Exome Sequencing (average coverage 30x).

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

The study will be carried out in about 50 centers, comprising the five Brazilian regions. The study will be conducted from July 2022 to December 2023. Data collection will be performed at each center consecutively, for cases and controls, through electronic Case Report Form (CRF).

Cases (N = 1867) will be selected by the occurrence of the first atherosclerotic cardiovascular event (Acute Myocardial Infarction, Stroke and Peripheral Arterial Thrombotic-Ischemic Events) during the hospitalization phase for the management of the acute atherothrombotic event. The ratio between cases and controls will be 1:1. Controls (N = 1867) will be adult individuals over 18 years of age who sought medical care at the same locations for other clinical reasons (no CVD) or individuals without any overt disease. The definitions of acute atherothrombotic events follow classic clinical and complementary exam criteria and are based on national and international guidelines. The complete project was submitted to the local Institutional Review Board (IRB)/National Research Ethics Commission (CONEP) system and has ethical approval (CAAE: 56482922.2.1001.0070). All cases and controls will be invited to participate and, if they agree, an Informed Consent Form will be obtained.

Investigators will assess exposures to traditional risk factors in combination with genomic data (polygenic risk score) in both cases and controls, and these exposures will be expressed as odds ratios. Multiple logistic regression models will be built to adjust and determine the strengths of association between demographic variables, traditional risk factors and genetic data: gender, age, ethnicity, weight, body mass index, smoking, diabetes, hypertension, obesity, anxiety and depression, inadequate diet, physical inactivity, alcohol consumption and apolipoprotein B/A1 ratio (ApoB/ApoA1). For each association variable with a greater chance of cardiovascular disease (significant OR), an attributable risk will be calculated to estimate the fraction of risk attributable to the genetic component (Polygenic Risk Score) and to other clinical and demographic variables.

The polygenic risk score will be calculated through a hybrid approach by taking into account the following features: effect size of each Single Nucleotide Polymorphism (SNP), number of effect alleles observed, sample ploidy, total number of SNPs included in the Polygenic Risk Score, and the number of nonmissing SNPs in the sample. Each risk allele will be given points in the risk score, and the total score will range between 0 (absence of risk alleles) and the maximum value (yet to be defined), based on the distribution of risk alleles that will be identified in the population included in the study. The scale will be interpreted in a direct (positive) association, i.e., the higher the score, the higher the number of alleles and respective weighted effect sizes. Finally, the polygenic risk score will be adjusted to previously reported traditional risk factors for atherosclerotic cardiovascular disease to determine the attributable risk fraction associated with the genomic profile.

Study Type

Observational

Enrollment (Actual)

3974

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
      • São Paulo, Brazil
        • Hospital Santa Paula
    • AC
      • Rio Branco, AC, Brazil
        • Acurácia Serviços Médicos
    • Alagoas
      • Maceió, Alagoas, Brazil
        • Centro de Pesquisas Clínicas Dr. Marco Mota HCOR
    • Bahia
      • Ipiaú, Bahia, Brazil
        • Hospital e Clínica São Roque
      • Salvador, Bahia, Brazil
        • Instituto Cárdio Pulmonar da Bahia
    • CE
      • Aracaju, CE, Brazil
        • Centro de Pesquisa Clinica do Coracao
    • Ceará
      • Barbalha, Ceará, Brazil
        • Hospital Maternidade Sao Vicente De Paulo
    • ES
      • Vila Velha, ES, Brazil
        • Hospital Evangélico de Vila Velha
      • Vitória, ES, Brazil
        • Hospital Universitario Cassiano Antonio de Moraes
    • GO
      • Goiânia, GO, Brazil
        • Universidade Federal de Goiás - UFG
    • MA
      • São Luís, MA, Brazil
        • Hospital Universitário da Universidade Federal do Maranhão/HU/UFMA
    • MG
      • Belo Horizonte, MG, Brazil
        • Santa Casa de Misericórdia de Belo Horizonte
      • Uberaba, MG, Brazil
        • Hospital de Clínicas da Universidade Federal do Triângulo Mineiro
    • MS
      • Campo Grande, MS, Brazil
        • Hospital Universitário Maria Aparecida Pedrossian
    • Mount
      • Cuiabá, Mount, Brazil
        • Hospital Geral Filantrópico Universitário - Assoc. de Proteção à Maternidade e Infância de Cuiabá
    • PE
      • Recife, PE, Brazil
        • Real Hospital Português de Beneficência em Pernambuco
    • PI
      • Teresina, PI, Brazil
        • Hospital Universitário da Universidade Federal do Piauí
    • PR
      • Campina Grande Do Sul, PR, Brazil
        • Hospital e Maternidade Angelina Caron
      • Curitiba, PR, Brazil
        • Núcleo de Pesquisa Clínica S/S
    • RN
      • Natal, RN, Brazil
        • Instituto Atena de Pesquisa Clinica
    • RS
      • Passo Fundo, RS, Brazil
        • Associação Hospitalar Beneficente São Vicente de Paulo
      • Pelotas, RS, Brazil
        • Santa Casa de Misericordia de Pelotas
      • Porto Alegre, RS, Brazil
        • Hospital de Clínicas de Porto Alegre
      • Porto Alegre, RS, Brazil
        • Instituto de Cardiologia do Rio Grande do Sul
      • Porto Alegre, RS, Brazil
        • Hospital Nossa Senhora Da Conceicao Sa
      • Santa Maria, RS, Brazil
        • Hospital Universitario de Santa Maria
    • Rio Grande Do Sul
      • Bento Gonçalves, Rio Grande Do Sul, Brazil
        • Associacao Dr. Bartholomeu Tacchini
    • SE
      • Aracaju, SE, Brazil
        • Hospital Cirurgia
    • SP
      • Barueri, SP, Brazil
        • Hospital Municipal de Barueri
      • Campinas, SP, Brazil
        • Instituto de Pesquisa clinica de Campinas
      • Campinas, SP, Brazil
        • Scentryfar Pesquisa Clínica
      • São José Do Rio Preto, SP, Brazil
        • Fundação Faculdade de Medicina de São José do Rio Preto
      • São Paulo, SP, Brazil
        • Instituto Dante Pazzanese de Cardiologia
      • São Paulo, SP, Brazil
        • Instituto de Cardiologia HCFMUSP
      • São Paulo, SP, Brazil
        • Instituto de Pesquisa GNDI
    • Santa Catarina
      • Blumenau, Santa Catarina, Brazil
        • Maestri e Kormann Consultoria Medico Cientifica
      • Joinville, Santa Catarina, Brazil, 89204-250
        • H&W Cardiologia LTDA
    • Sao Paulo
      • São Paulo, Sao Paulo, Brazil
        • Hospital Alemao Oswaldo Cruz
    • São Paulo
      • Matão, São Paulo, Brazil
        • Hospital Carlos Fenando Malzoni
      • São José Do Rio Preto, São Paulo, Brazil
        • Braile Hospital Dia Ltda

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Probability Sample

Study Population

In-hospital patients with the first atherosclerotic event will be enrolled (Cases). Patients being attended in the same hospitals without cardiovascular events or without any overt disease will be the controls. The sample size calculation assumed a dominant inheritance pattern, within a non-matched case-control study design 1:1. A sample of 1867 cases and 1867 controls would have a statistical power of 90% to detect a genetic OR of 1.3, assuming an allelic frequency of 10%, considering an unpaired control 1:1 of the genetic factor.

A prevalence of 10% of the disease in the target population was considered, an alpha significance level of 5%, bilateral hypothesis test.

Description

Inclusion Criteria:

  • Cases: adults over 18 years with first atherosclerotic cardiovascular event (Acute Myocardial Infarction, Stroke and Peripheral Artery Thrombotic-Ischemic Events)
  • Controls: adult individuals over 18 years of age who sought medical care at the same locations for other clinical reasons (no CVD) or individuals without any overt disease

Exclusion Criteria:

  • Previous occurrence of Cardiovascular Event (Myocardial Infarction, Stroke or Peripheral Artery Thrombotic Events
  • Patients already recruited in another study linked to the GENOMA Brazil Program.

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: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Case - atherosclerotic cardiovascular disease
Patients with the first atherosclerotic cardiovascular event (Acute Myocardial Infarction, Stroke and Peripheral Artery Thrombotic-Ischemic Events)
Genetic: Exposure to genetics (polygenic)
The polygenic risk score (PRS) aggregates the effects of genetic variants into a single number that predicts the genetic predisposition to a phenotype. PRS are typically composed of hundreds to millions of genetic variants, usually Single Nucleotide Polymorphisms (SNPs). For each individual, the number of risk alleles computed in each variant is summed and weighted by the estimated value of the obtained effects (log odds ratio for traits with binary values or Beta coefficients for traits with continuous value) obtained from large-scale genomic studies ( GWAS)
Other Names:
  • polygenic risk score
Control - without atherosclerotic cardiovascular disease ou healthy
Patients who sought medical care at the same site as cases without atherosclerotic cardiovascular event (Acute Myocardial Infarction, Stroke and Peripheral Artery Thrombotic-Ischemic Events) or healthy individuals
Genetic: Exposure to genetics (polygenic)
The polygenic risk score (PRS) aggregates the effects of genetic variants into a single number that predicts the genetic predisposition to a phenotype. PRS are typically composed of hundreds to millions of genetic variants, usually Single Nucleotide Polymorphisms (SNPs). For each individual, the number of risk alleles computed in each variant is summed and weighted by the estimated value of the obtained effects (log odds ratio for traits with binary values or Beta coefficients for traits with continuous value) obtained from large-scale genomic studies ( GWAS)
Other Names:
  • polygenic risk score

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Population attributable risk fraction measured for the Polygenic Risk Score. Scale will range from 0 to maximum number of risk alleles. The higher the score, the higher the number of risk alleles (worse).
Time Frame: through study completion, an average of 1 year
Population attributable risk fraction of atherosclerotic cardiovascular diseases adjusted for other risk factors related to: diet, physical exercise, smoking, alcoholism, chronic disease history (diabetes, hypertension, dyslipidemia, etc) and biochemical parameters.
through study completion, an average of 1 year
Polymorphisms genes as an independent risk factor for the occurrence of Acute Myocardial infarction (AMI), stroke and peripherical arterial thrombotic-ischemic events
Time Frame: through study completion, an average of 1 year
As it is a case-control study, there will be no follow-up for the occurrence of clinical events. Therefore, we will assess exposures to traditional risk factors to cardiovascular events (MI, Stroke and acute peripheral atherothrombotic event) in combination with genomic data (polygenic risk score) in both cases and controls, and these exposures will be expressed as odds ratios. Multiple logistic regression models will be built to adjust and determine the strengths of association between demographic variables, traditional risk factors and genetic data
through study completion, an average of 1 year

Collaborators and Investigators

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

Sponsor

Hospital Alemão Oswaldo Cruz

Collaborators

Ministry of Health, Brazil
Grupo Fleury

Investigators

  • Study Chair: Álvaro Avezum, MD, PhD, Hospital Alemao Oswaldo Cruz

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)

July 18, 2022

Primary Completion (Actual)

February 20, 2023

Study Completion (Estimated)

July 15, 2024

Study Registration Dates

First Submitted

August 1, 2022

First Submitted That Met QC Criteria

August 23, 2022

First Posted (Actual)

August 25, 2022

Study Record Updates

Last Update Posted (Actual)

May 30, 2024

Last Update Submitted That Met QC Criteria

May 29, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HAlemaoOswaldoCruz
  • CAAE: 56482922.2.1001.0070 (Other Identifier: Brazilian National Ethics Committee)

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.

Clinical Trials on Cardiovascular Diseases

Clinical Trials on Exposure to genetics (polygenic)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Costa Rica

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe