Impact of the Genetic Background as a Risk Factor for Atherosclerotic Cardiovascular Disease in the Brazilian Population

Stroke Clinical Trial

— CV-GENES  

Official title:

Impact of the Genetic Background as a Risk Factor for Atherosclerotic Cardiovascular Disease in the Brazilian Population

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05515653
• Other study ID #: HAlemaoOswaldoCruz
• Secondary ID: CAAE: 56482922.2
• Status: Active, not recruiting
• Start date: July 18, 2022
• Est. completion date: July 15, 2024

Study information

• Verified date: May 2024
• Source: Hospital Alemão Oswaldo Cruz
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 3974
• Est. completion date: July 15, 2024
• Est. primary completion date: February 20, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Atherosclerosis
• Cardiovascular Diseases
• Genetic Predisposition to Disease
• Peripheral Arterial Disease
• Peripheral Vascular Diseases
• Stroke

Intervention

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)

Locations

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

Sponsors (3)

Lead Sponsor	Collaborator
Hospital Alemão Oswaldo Cruz	Grupo Fleury, Ministry of Health, Brazil

Country where clinical trial is conducted

Brazil, 

References & Publications (30)

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* Note: There are 30 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	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
Primary	Polymorphisms genes as an independent risk factor for the occurrence of Acute Myocardial infarction (AMI), stroke and peripherical arterial thrombotic-ischemic events	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