Clinical and genetic risk factors in acute coronary syndromes

Research output: ThesisDoctoral ThesisCollection of Articles

Abstract

Coronary artery disease (CAD), acute coronary syndromes (ACS), and other conditions related to atherosclerosis are leading causes of death in developed countries. The incidence of CAD cannot be explained only by clinical risk factors, such as hypertension, dyslipidemia, diabetes and smoking; the genetics also matters. Major findings concerning the genetics of CAD have emerged during the last decade with many CAD-related risk variants found. This study evaluated the characteristics of the Corogene cohort of Finnish consecutive patients who underwent coronary angiography between 2006 and 2008. Furthermore, it evaluated the importance of clinical risk factors and genetic risk scores (GRS) formed of known CAD risk variants in predicting the ACS prognosis and sought for genetic differences between patients with non-ST-elevation myocardial infarction (NSTEMI) and ST-elevation myocardial infarction (STEMI). The most common reason for coronary angiography in the Corogene Study during the study period was ACS. About half of all patients were finally revascularized either by percutaneous coronary intervention or coronary artery by-pass grafting. One-fourth of the patients had no signs of obstructive CAD in coronary angiography. GRS formed of 47 confirmed risk variants was found to be associated with recurrent ACS independent of clinical factors. Smoking and STEMI had an inverse association with the GRS. When compared to other studies evaluating GRS in recurrent ACS prediction, the GRS with 47 confirmed CAD variants included the greatest number of risk variants. As it did not improve the accuracy of prediction by clinical factors, the GRS has thus not yet proven useful in clinical practice. Smoking, having an inverse association with the GRS, may outweigh the genetic predisposition to CAD. Both clinical and genetic differences between STEMI and NSTEMI patients were studied and genome-wide association analysis revealed variants, including rs656843, at a locus near 1p13.3, to be associated nominally with NSTEMI. This finding could be replicated in another case-control sample of MI patients, but not in a prospective sample of FINRISK participants. The inverse correlation of the GRSs with STEMI, the finding of a genetic variant linked nominally to NSTEMI, and the fact that patients with NSTEMI and STEMI present with different clinical risk-factor profiles suggest that these two ACS subtypes may have somewhat different etiologies. The genetic variant conferring the risk for NSTEMI (rs656843) was also associated with peripheral artery disease (PAD) in ACS patients, but not in a general population sample of FINRISK individuals. The heterogeneity in PAD phenotypes and genetics may explain why the association could not be shown in a general population sample but only in a selected cohort of ACS patients.
Original languageEnglish
Place of PublicationHelsinki
Publisher
Print ISBNs978-951-51-2820-1
Electronic ISBNs978-951-51-2821-8
Publication statusPublished - 2017
MoE publication typeG5 Doctoral dissertation (article)

Fields of Science

  • 3121 Internal medicine

Cite this

@phdthesis{2bbb06db750846678e58d480307e50ff,
title = "Clinical and genetic risk factors in acute coronary syndromes",
abstract = "Coronary artery disease (CAD), acute coronary syndromes (ACS), and other conditions related to atherosclerosis are leading causes of death in developed countries. The incidence of CAD cannot be explained only by clinical risk factors, such as hypertension, dyslipidemia, diabetes and smoking; the genetics also matters. Major findings concerning the genetics of CAD have emerged during the last decade with many CAD-related risk variants found. This study evaluated the characteristics of the Corogene cohort of Finnish consecutive patients who underwent coronary angiography between 2006 and 2008. Furthermore, it evaluated the importance of clinical risk factors and genetic risk scores (GRS) formed of known CAD risk variants in predicting the ACS prognosis and sought for genetic differences between patients with non-ST-elevation myocardial infarction (NSTEMI) and ST-elevation myocardial infarction (STEMI). The most common reason for coronary angiography in the Corogene Study during the study period was ACS. About half of all patients were finally revascularized either by percutaneous coronary intervention or coronary artery by-pass grafting. One-fourth of the patients had no signs of obstructive CAD in coronary angiography. GRS formed of 47 confirmed risk variants was found to be associated with recurrent ACS independent of clinical factors. Smoking and STEMI had an inverse association with the GRS. When compared to other studies evaluating GRS in recurrent ACS prediction, the GRS with 47 confirmed CAD variants included the greatest number of risk variants. As it did not improve the accuracy of prediction by clinical factors, the GRS has thus not yet proven useful in clinical practice. Smoking, having an inverse association with the GRS, may outweigh the genetic predisposition to CAD. Both clinical and genetic differences between STEMI and NSTEMI patients were studied and genome-wide association analysis revealed variants, including rs656843, at a locus near 1p13.3, to be associated nominally with NSTEMI. This finding could be replicated in another case-control sample of MI patients, but not in a prospective sample of FINRISK participants. The inverse correlation of the GRSs with STEMI, the finding of a genetic variant linked nominally to NSTEMI, and the fact that patients with NSTEMI and STEMI present with different clinical risk-factor profiles suggest that these two ACS subtypes may have somewhat different etiologies. The genetic variant conferring the risk for NSTEMI (rs656843) was also associated with peripheral artery disease (PAD) in ACS patients, but not in a general population sample of FINRISK individuals. The heterogeneity in PAD phenotypes and genetics may explain why the association could not be shown in a general population sample but only in a selected cohort of ACS patients.",
keywords = "Acute Coronary Syndrome, +genetics, Cardiovascular Diseases, +epidemiology, Coronary Angiography, Coronary Artery Disease, Electrocardiography, Genetic Association Studies, Genetic Loci, Genetic Predisposition to Disease, Genetic Variation, Genotype, Genome-Wide Association Study, Health Behavior, Membrane Proteins, Myocardial Infarction, Proportional Hazards Models, Recurrence, Risk Factors, Smoking, 3121 Internal medicine",
author = "Satu Vaara",
note = "M1 - 106 s. + liitteet Volume: Proceeding volume:",
year = "2017",
language = "English",
isbn = "978-951-51-2820-1",
publisher = "[S. Vaara]",
address = "Finland",

}

Clinical and genetic risk factors in acute coronary syndromes. / Vaara, Satu.

Helsinki : [S. Vaara], 2017. 106 p.

Research output: ThesisDoctoral ThesisCollection of Articles

TY - THES

T1 - Clinical and genetic risk factors in acute coronary syndromes

AU - Vaara, Satu

N1 - M1 - 106 s. + liitteet Volume: Proceeding volume:

PY - 2017

Y1 - 2017

N2 - Coronary artery disease (CAD), acute coronary syndromes (ACS), and other conditions related to atherosclerosis are leading causes of death in developed countries. The incidence of CAD cannot be explained only by clinical risk factors, such as hypertension, dyslipidemia, diabetes and smoking; the genetics also matters. Major findings concerning the genetics of CAD have emerged during the last decade with many CAD-related risk variants found. This study evaluated the characteristics of the Corogene cohort of Finnish consecutive patients who underwent coronary angiography between 2006 and 2008. Furthermore, it evaluated the importance of clinical risk factors and genetic risk scores (GRS) formed of known CAD risk variants in predicting the ACS prognosis and sought for genetic differences between patients with non-ST-elevation myocardial infarction (NSTEMI) and ST-elevation myocardial infarction (STEMI). The most common reason for coronary angiography in the Corogene Study during the study period was ACS. About half of all patients were finally revascularized either by percutaneous coronary intervention or coronary artery by-pass grafting. One-fourth of the patients had no signs of obstructive CAD in coronary angiography. GRS formed of 47 confirmed risk variants was found to be associated with recurrent ACS independent of clinical factors. Smoking and STEMI had an inverse association with the GRS. When compared to other studies evaluating GRS in recurrent ACS prediction, the GRS with 47 confirmed CAD variants included the greatest number of risk variants. As it did not improve the accuracy of prediction by clinical factors, the GRS has thus not yet proven useful in clinical practice. Smoking, having an inverse association with the GRS, may outweigh the genetic predisposition to CAD. Both clinical and genetic differences between STEMI and NSTEMI patients were studied and genome-wide association analysis revealed variants, including rs656843, at a locus near 1p13.3, to be associated nominally with NSTEMI. This finding could be replicated in another case-control sample of MI patients, but not in a prospective sample of FINRISK participants. The inverse correlation of the GRSs with STEMI, the finding of a genetic variant linked nominally to NSTEMI, and the fact that patients with NSTEMI and STEMI present with different clinical risk-factor profiles suggest that these two ACS subtypes may have somewhat different etiologies. The genetic variant conferring the risk for NSTEMI (rs656843) was also associated with peripheral artery disease (PAD) in ACS patients, but not in a general population sample of FINRISK individuals. The heterogeneity in PAD phenotypes and genetics may explain why the association could not be shown in a general population sample but only in a selected cohort of ACS patients.

AB - Coronary artery disease (CAD), acute coronary syndromes (ACS), and other conditions related to atherosclerosis are leading causes of death in developed countries. The incidence of CAD cannot be explained only by clinical risk factors, such as hypertension, dyslipidemia, diabetes and smoking; the genetics also matters. Major findings concerning the genetics of CAD have emerged during the last decade with many CAD-related risk variants found. This study evaluated the characteristics of the Corogene cohort of Finnish consecutive patients who underwent coronary angiography between 2006 and 2008. Furthermore, it evaluated the importance of clinical risk factors and genetic risk scores (GRS) formed of known CAD risk variants in predicting the ACS prognosis and sought for genetic differences between patients with non-ST-elevation myocardial infarction (NSTEMI) and ST-elevation myocardial infarction (STEMI). The most common reason for coronary angiography in the Corogene Study during the study period was ACS. About half of all patients were finally revascularized either by percutaneous coronary intervention or coronary artery by-pass grafting. One-fourth of the patients had no signs of obstructive CAD in coronary angiography. GRS formed of 47 confirmed risk variants was found to be associated with recurrent ACS independent of clinical factors. Smoking and STEMI had an inverse association with the GRS. When compared to other studies evaluating GRS in recurrent ACS prediction, the GRS with 47 confirmed CAD variants included the greatest number of risk variants. As it did not improve the accuracy of prediction by clinical factors, the GRS has thus not yet proven useful in clinical practice. Smoking, having an inverse association with the GRS, may outweigh the genetic predisposition to CAD. Both clinical and genetic differences between STEMI and NSTEMI patients were studied and genome-wide association analysis revealed variants, including rs656843, at a locus near 1p13.3, to be associated nominally with NSTEMI. This finding could be replicated in another case-control sample of MI patients, but not in a prospective sample of FINRISK participants. The inverse correlation of the GRSs with STEMI, the finding of a genetic variant linked nominally to NSTEMI, and the fact that patients with NSTEMI and STEMI present with different clinical risk-factor profiles suggest that these two ACS subtypes may have somewhat different etiologies. The genetic variant conferring the risk for NSTEMI (rs656843) was also associated with peripheral artery disease (PAD) in ACS patients, but not in a general population sample of FINRISK individuals. The heterogeneity in PAD phenotypes and genetics may explain why the association could not be shown in a general population sample but only in a selected cohort of ACS patients.

KW - Acute Coronary Syndrome

KW - +genetics

KW - Cardiovascular Diseases

KW - +epidemiology

KW - Coronary Angiography

KW - Coronary Artery Disease

KW - Electrocardiography

KW - Genetic Association Studies

KW - Genetic Loci

KW - Genetic Predisposition to Disease

KW - Genetic Variation

KW - Genotype

KW - Genome-Wide Association Study

KW - Health Behavior

KW - Membrane Proteins

KW - Myocardial Infarction

KW - Proportional Hazards Models

KW - Recurrence

KW - Risk Factors

KW - Smoking

KW - 3121 Internal medicine

M3 - Doctoral Thesis

SN - 978-951-51-2820-1

PB - [S. Vaara]

CY - Helsinki

ER -