Impact of the Genetic Background as a Risk Factor for Atherosclerotic Cardiovascular Disease in the Brazilian Population
- Conditions
- Genetic Predisposition to DiseaseCardiovascular DiseasesAcute MIStrokePeripheral Arterial Disease
- Interventions
- Genetic: Exposure to genetics (polygenic)
- Registration Number
- NCT05515653
- Lead Sponsor
- Hospital Alemão Oswaldo Cruz
- Brief 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).
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 3974
- 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
- 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 & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Case - atherosclerotic cardiovascular disease Exposure to genetics (polygenic) Patients with the first atherosclerotic cardiovascular event (Acute Myocardial Infarction, Stroke and Peripheral Artery Thrombotic-Ischemic Events) Control - without atherosclerotic cardiovascular disease ou healthy Exposure to genetics (polygenic) 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
- Primary Outcome Measures
Name Time Method 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). 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.
Polymorphisms genes as an independent risk factor for the occurrence of Acute Myocardial infarction (AMI), stroke and peripherical arterial thrombotic-ischemic events 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
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (41)
Hospital Universitário Cassiano Antônio de Moraes
🇧🇷Vitória, ES, Brazil
Hospital Universitário da Universidade Federal do Maranhão/HU/UFMA
🇧🇷São Luís, MA, Brazil
Centro de Pesquisas Clínicas Dr. Marco Mota HCOR
🇧🇷Maceió, Alagoas, Brazil
Acurácia Serviços Médicos
🇧🇷Rio Branco, AC, Brazil
Centro de Pesquisa Clínica do Coração
🇧🇷Aracaju, CE, Brazil
Real Hospital Português de Beneficência em Pernambuco
🇧🇷Recife, PE, Brazil
Hospital Universitário Maria Aparecida Pedrossian
🇧🇷Campo Grande, MS, Brazil
Hospital Universitário da Universidade Federal do Piauí
🇧🇷Teresina, PI, Brazil
Santa Casa de Misericórdia de Pelotas
🇧🇷Pelotas, 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 Alemão Oswaldo Cruz
🇧🇷São Paulo, Sao Paulo, Brazil
Instituto Cárdio Pulmonar da Bahia
🇧🇷Salvador, Bahia, Brazil
Hospital Carlos Fenando Malzoni
🇧🇷Matão, São Paulo, Brazil
Instituto Atena de Pesquisa Clínica
🇧🇷Natal, RN, Brazil
Scentryfar Pesquisa Clínica
🇧🇷Campinas, SP, Brazil
Maestri e Kormann Consultoria Medico Cientifica
🇧🇷Blumenau, Santa Catarina, Brazil
H&W Cardiologia LTDA
🇧🇷Joinville, Santa Catarina, Brazil
Hospital e Clínica São Roque
🇧🇷Ipiaú, Bahia, Brazil
Hospital Evangélico de Vila Velha
🇧🇷Vila Velha, ES, Brazil
Universidade Federal de Goiás - UFG
🇧🇷Goiânia, GO, Brazil
Santa Casa de Misericórdia de Belo Horizonte
🇧🇷Belo Horizonte, MG, Brazil
Hospital de Clínicas da Universidade Federal do Triângulo Mineiro
🇧🇷Uberaba, MG, 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
Instituto de Pesquisa Clínica de Campinas
🇧🇷Campinas, SP, Brazil
Fundação Faculdade de Medicina de São José do Rio Preto
🇧🇷São José Do Rio Preto, SP, Brazil
Instituto de Cardiologia HCFMUSP
🇧🇷São Paulo, SP, Brazil
Hospital Maternidade São Vicente de Paulo
🇧🇷Barbalha, Ceará, Brazil
Hospital Universitário de Santa Maria
🇧🇷Santa Maria, RS, Brazil
Santa Casa de Misericordia de Belo Horizonte
🇧🇷Belo Horizonte, MG, Brazil
Hospital e Maternidade Angelina Caron
🇧🇷Campina Grande Do Sul, PR, Brazil
Associacao Hospitalar Beneficente Sao Vicente de Paulo
🇧🇷Passo Fundo, RS, Brazil
Hospital Nossa Senhora Da Conceicao Sa
🇧🇷Porto Alegre, RS, Brazil
Associação Dr. Bartholomeu Tacchini
🇧🇷Bento Gonçalves, Rio Grande Do Sul, Brazil
Hospital Cirurgia
🇧🇷Aracaju, SE, Brazil
Instituto Dante Pazzanese de Cardiologia
🇧🇷São Paulo, SP, Brazil
Hospital Municipal de Barueri
🇧🇷Barueri, SP, Brazil
Instituto de Pesquisa GNDI
🇧🇷São Paulo, SP, Brazil
Hospital Santa Paula
🇧🇷São Paulo, Brazil
Braile Hospital Dia Ltda
🇧🇷São José Do Rio Preto, São Paulo, Brazil