An observational study in Cardiovascular Diseases, Acute MI and Stroke, sponsored by Hospital Alemão Oswaldo Cruz. Status unknown at 41 sites in Brazil. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-05-30.
Sponsored by Hospital Alemão Oswaldo Cruz · Observational
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).
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.
5,025 studies on the registry are indexed under Cardiovascular Diseases; 930 are open to participants now.
This study's enrollment of 3,974 is above the median of 600 across 1,524 observational studies indexed under Cardiovascular Diseases.
Browse Cardiovascular Diseases studies →Hospital Alemão Oswaldo Cruz is the lead sponsor of 10 studies on the registry; 3 are open to participants now.
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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.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Patients with the first atherosclerotic cardiovascular event (Acute Myocardial Infarction, Stroke and Peripheral Artery Thrombotic-Ischemic Events)
Genetic: 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
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)
Also known as: polygenic risk score
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.
Time frame: 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
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
Time frame: through study completion, an average of 1 year
Plan to share: No
Ran from Jul 2022 to primary completion in Feb 2023, 7 months.
Of 565 non-industry observational studies under Cardiovascular Diseases, half reached primary completion within 72 months of starting (the median), counting those still running; a quarter within 28 and three quarters within 304. This study's 7 months is below that.
Counting every sponsor, half of 636 studies reached it within 65 months; a quarter within 25 and three quarters within 196.
Cardiovascular Diseases covers many different conditions, not one, so the studies compared here vary widely. Read these figures as a rough guide.
How these figures are worked out, and which studies are left out of them.
This study is status unknown, as verified in May 2024. You cannot join it, but the record below documents what was studied.
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Hospital Alemão Oswaldo Cruz