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Cardiovascular DiseasesCV-GENESNCT05515653

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

An observational study of Cardiovascular Diseases and Acute MI, run by Hospital Alemão Oswaldo Cruz at 41 sites in Brazil.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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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… Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Cardiovascular Diseases, Acute MI, Stroke
What is being tested?
Exposure to genetics (polygenic)
How many people
3,974 participants
Where
41 sitesBrazil
Study dates
18 Jul 2022to 15 Jul 2024
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

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.

Who may be able to join

  • 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

Who cannot join

  • 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.

Trial locations and contacts

41 sites in 1 country.

41 sites in 1 country

Brazil41 sites

  • Centro de Pesquisa Clínica do Coração

    Aracaju, Ceará

  • Hospital Cirurgia

    Aracaju, Sergipe

  • Hospital Maternidade São Vicente de Paulo

    Barbalha, Ceará

  • Hospital Municipal de Barueri

    Barueri, São Paulo

  • Santa Casa de Misericordia de Belo Horizonte

    Belo Horizonte, Minas Gerais

  • Santa Casa de Misericórdia de Belo Horizonte

    Belo Horizonte, Minas Gerais

  • Associação Dr. Bartholomeu Tacchini

    Bento Gonçalves, Rio Grande do Sul

  • Maestri e Kormann Consultoria Medico Cientifica

    Blumenau, Santa Catarina

  • Hospital e Maternidade Angelina Caron

    Campina Grande do Sul, Paraná

  • Instituto de Pesquisa Clínica de Campinas

    Campinas, São Paulo

  • Scentryfar Pesquisa Clínica

    Campinas, São Paulo

  • Hospital Universitário Maria Aparecida Pedrossian

    Campo Grande, Mato Grosso do Sul

  • Hospital Geral Filantrópico Universitário - Assoc. de Proteção à Maternidade e Infância de Cuiabá

    Cuiabá, Mount

  • Núcleo de Pesquisa Clínica S/S

    Curitiba, Paraná

  • Universidade Federal de Goiás - UFG

    Goiânia, Goiás

  • Hospital e Clínica São Roque

    Ipiaú, Estado de Bahia

  • H&W Cardiologia LTDA

    Joinville, Santa Catarina, 89204-250

  • Centro de Pesquisas Clínicas Dr. Marco Mota HCOR

    Maceió, Alagoas

  • Hospital Carlos Fenando Malzoni

    Matão, São Paulo

  • Instituto Atena de Pesquisa Clínica

    Natal, Rio Grande do Norte

  • Associacao Hospitalar Beneficente Sao Vicente de Paulo

    Passo Fundo, Rio Grande do Sul

  • Santa Casa de Misericórdia de Pelotas

    Pelotas, Rio Grande do Sul

  • Hospital de Clínicas de Porto Alegre

    Porto Alegre, Rio Grande do Sul

  • Hospital Nossa Senhora Da Conceicao Sa

    Porto Alegre, Rio Grande do Sul

  • Instituto de Cardiologia do Rio Grande do Sul

    Porto Alegre, Rio Grande do Sul

  • Real Hospital Português de Beneficência em Pernambuco

    Recife, Pernambuco

  • Acurácia Serviços Médicos

    Rio Branco, Acre

  • Instituto Cárdio Pulmonar da Bahia

    Salvador, Estado de Bahia

  • Hospital Universitário de Santa Maria

    Santa Maria, Rio Grande do Sul

  • Braile Hospital Dia Ltda

    São José do Rio Preto, São Paulo

  • Fundação Faculdade de Medicina de São José do Rio Preto

    São José do Rio Preto, São Paulo

  • Hospital Universitário da Universidade Federal do Maranhão/HU/UFMA

    São Luís, Maranhão

  • Hospital Alemão Oswaldo Cruz

    São Paulo, São Paulo

  • Instituto Dante Pazzanese de Cardiologia

    São Paulo, São Paulo

  • Instituto de Cardiologia HCFMUSP

    São Paulo, São Paulo

  • Instituto de Pesquisa GNDI

    São Paulo, São Paulo

  • Hospital Santa Paula

    São Paulo

  • Hospital Universitário da Universidade Federal do Piauí

    Teresina, Piauí

  • Hospital de Clínicas da Universidade Federal do Triângulo Mineiro

    Uberaba, Minas Gerais

  • Hospital Evangélico de Vila Velha

    Vila Velha, Espírito Santo

  • Hospital Universitário Cassiano Antônio de Moraes

    Vitória, Espírito Santo

Other trials in Brazil

About this study

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).

Read the 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.

Being tested
Exposure to genetics (polygenic)
Keywords
case-control study, Polymorphism genetic, cardiovascular disease, observational study
Medical subject headings
Cardiovascular Diseases, Stroke, Peripheral Arterial Disease, Genetic Predisposition to Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Exposure to genetics (polygenic)Genetic

    Also called polygenic risk score

    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)

Study groups in NCT05515653
Study groupRoleWhat they receive
Case - atherosclerotic cardiovascular diseasePatients with the first atherosclerotic cardiovascular event (Acute Myocardial Infarction, Stroke and Peripheral Artery Thrombotic-Ischemic Events)
Receives: Genetic: Exposure to genetics (polygenic)
Control - without atherosclerotic cardiovascular disease ou healthyPatients 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
Receives: Genetic: Exposure to genetics (polygenic)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: through study completion, an average of 1 year

  2. 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

    Measured: through study completion, an average of 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Aug 2022
  2. Study start18 Jul 2022
  3. Primary completion20 Feb 2023
  4. Study completion15 Jul 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Case-control
Time perspective
Prospective
Enrolment
3,974 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05515653
Sponsor's protocol ID
HAlemaoOswaldoCruz
Other IDs
CAAE: 56482922.2.1001.0070
Acronym
CV-GENES
Status last verified
May 2024
First submitted
1 Aug 2022
Last updated
30 May 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • O'Donnell MJ, Chin SL, Rangarajan S, Xavier D, Liu L, Zhang H, Rao-Melacini P, Zhang X, Pais P, Agapay S, Lopez-Jaramillo P, Damasceno A, Langhorne P, McQueen MJ, Rosengren A, Dehghan M, Hankey GJ, Dans AL, Elsayed A, Avezum A, Mondo C, Diener HC, Ryglewicz D, Czlonkowska A, Pogosova N, Weimar C, Iqbal R, Diaz R, Yusoff K, Yusufali A, Oguz A, Wang X, Penaherrera E, Lanas F, Ogah OS, Ogunniyi A, Iversen HK, Malaga G, Rumboldt Z, Oveisgharan S, Al Hussain F, Magazi D, Nilanont Y, Ferguson J, Pare G, Yusuf S; INTERSTROKE investigators. Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study. Lancet. 2016 Aug 20;388(10046):761-75. doi: 10.1016/S0140-6736(16)30506-2. Epub 2016 Jul 16.

    PubMed 27431356

  • Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, McQueen M, Budaj A, Pais P, Varigos J, Lisheng L; INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004 Sep 11-17;364(9438):937-52. doi: 10.1016/S0140-6736(04)17018-9.

    PubMed 15364185

  • Stram DO. Design, Analysis, and Interpretation of Genome-Wide Association Scans. Springer; 2014.

  • Gauderman WJ MJ. Quanto 1.1: A computer program for power and sample size calculations for genetic-epidemiology studies. 2006.

  • Yusuf S, Joseph P, Rangarajan S, Islam S, Mente A, Hystad P, Brauer M, Kutty VR, Gupta R, Wielgosz A, AlHabib KF, Dans A, Lopez-Jaramillo P, Avezum A, Lanas F, Oguz A, Kruger IM, Diaz R, Yusoff K, Mony P, Chifamba J, Yeates K, Kelishadi R, Yusufali A, Khatib R, Rahman O, Zatonska K, Iqbal R, Wei L, Bo H, Rosengren A, Kaur M, Mohan V, Lear SA, Teo KK, Leong D, O'Donnell M, McKee M, Dagenais G. Modifiable risk factors, cardiovascular disease, and mortality in 155 722 individuals from 21 high-income, middle-income, and low-income countries (PURE): a prospective cohort study. Lancet. 2020 Mar 7;395(10226):795-808. doi: 10.1016/S0140-6736(19)32008-2. Epub 2019 Sep 3.

    PubMed 31492503

  • Roberts R, Chang CC, Hadley T. Genetic Risk Stratification: A Paradigm Shift in Prevention of Coronary Artery Disease. JACC Basic Transl Sci. 2021 Mar 22;6(3):287-304. doi: 10.1016/j.jacbts.2020.09.004. eCollection 2021 Mar.

    PubMed 33778213

  • Lu H, Zhang J, Chen YE, Garcia-Barrio MT. Integration of Transformative Platforms for the Discovery of Causative Genes in Cardiovascular Diseases. Cardiovasc Drugs Ther. 2021 Jun;35(3):637-654. doi: 10.1007/s10557-021-07175-1. Epub 2021 Apr 15.

    PubMed 33856594

  • Vrablik M, Dlouha D, Todorovova V, Stefler D, Hubacek JA. Genetics of Cardiovascular Disease: How Far Are We from Personalized CVD Risk Prediction and Management? Int J Mol Sci. 2021 Apr 17;22(8):4182. doi: 10.3390/ijms22084182.

    PubMed 33920733

  • Lanas F, Seron P, Lanas A. Coronary heart disease and risk factors in latin america. Glob Heart. 2013 Dec;8(4):341-8. doi: 10.1016/j.gheart.2013.11.005.

    PubMed 25690636

  • Piegas LS, Avezum A, Pereira JC, Neto JM, Hoepfner C, Farran JA, Ramos RF, Timerman A, Esteves JP; AFIRMAR Study Investigators. Risk factors for myocardial infarction in Brazil. Am Heart J. 2003 Aug;146(2):331-8. doi: 10.1016/S0002-8703(03)00181-9.

    PubMed 12891204

  • Teo KK, Ounpuu S, Hawken S, Pandey MR, Valentin V, Hunt D, Diaz R, Rashed W, Freeman R, Jiang L, Zhang X, Yusuf S; INTERHEART Study Investigators. Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study: a case-control study. Lancet. 2006 Aug 19;368(9536):647-58. doi: 10.1016/S0140-6736(06)69249-0.

    PubMed 16920470

  • Gerstein HC, Islam S, Anand S, Almahmeed W, Damasceno A, Dans A, Lang CC, Luna MA, McQueen M, Rangarajan S, Rosengren A, Wang X, Yusuf S. Dysglycaemia and the risk of acute myocardial infarction in multiple ethnic groups: an analysis of 15,780 patients from the INTERHEART study. Diabetologia. 2010 Dec;53(12):2509-17. doi: 10.1007/s00125-010-1871-0. Epub 2010 Aug 14.

    PubMed 20711717

  • Schmidt MI, Duncan BB, Azevedo e Silva G, Menezes AM, Monteiro CA, Barreto SM, Chor D, Menezes PR. Chronic non-communicable diseases in Brazil: burden and current challenges. Lancet. 2011 Jun 4;377(9781):1949-61. doi: 10.1016/S0140-6736(11)60135-9. Epub 2011 May 9.

    PubMed 21561658

  • Pinho Nde A, Pierin AM. Hypertension control in brazilian publications. Arq Bras Cardiol. 2013 Sep;101(3):e65-73. doi: 10.5935/abc.20130173.

    PubMed 24061761

  • Walldius G, Jungner I, Holme I, Aastveit AH, Kolar W, Steiner E. High apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study. Lancet. 2001 Dec 15;358(9298):2026-33. doi: 10.1016/S0140-6736(01)07098-2.

    PubMed 11755609

Questions about this trial

What is this clinical trial studying?

An observational study of Cardiovascular Diseases and Acute MI, run by Hospital Alemão Oswaldo Cruz at 41 sites in Brazil.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 30 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 41 sites in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05515653, which also lists 31 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 May 2024.

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