TY - JOUR
T1 - A myocardial infarction genetic risk score is associated with markers of carotid atherosclerosis.
AU - Hamrefors, Viktor
AU - Hedblad, Bo
AU - Engström, Gunnar
AU - Almgren, Peter
AU - Sjögren, Marketa
AU - Melander, Olle
PY - 2012
Y1 - 2012
N2 - Objective: To assess whether a genetic risk score that was previously shown to be associated with myocardial infarction and coronary artery disease is also associated with markers of carotid atherosclerosis. Design: A total of 4022 middle-aged subjects from the general Swedish population were genotyped and individually assigned a genetic risk score based on 13 single-nucleotide polymorphisms (SNPs), previously associated with myocardial infarction and coronary artery disease. The genetic score (Score-MI) was then related to carotid bulb intima-media thickness (IMT), common carotid artery IMT and to the occurrence of carotid plaques in the study population. Results: Score-MI was associated with IMT of the bulb (P<0.001) and the common carotid artery (P<0.001) in unadjusted analyses, and with IMT of the bulb after adjustment for cardiovascular risk factors (P=0.003). The effect size of Score-MI on IMT of the bulb was similar to that of LDL cholesterol. After adjustment for cardiovascular risk factors, Score-MI was also associated with the occurrence of carotid plaques (odds ratio per quintile of Score-MI=1.11; 95% confidence interval 1.04-1.18; P=0.001). In addition to SNPs with known effects on LDL levels, Score-MI showed nominal associations with increasing systolic blood pressure and decreasing C-reactive protein levels. Conclusions: This genetic risk score was independently associated with carotid bulb IMT and carotid plaques, providing evidence of an association with early markers of atherosclerosis. This might imply that the genetic myocardial infarction risk conferred by the score is related to early atherosclerosis and that the risk score may identify at an early stage candidates at risk of developing intermediate phenotypes of atherosclerosis. Further studies should test whether assessing the genetic score could be valuable for early treatment decisions in these subjects.
AB - Objective: To assess whether a genetic risk score that was previously shown to be associated with myocardial infarction and coronary artery disease is also associated with markers of carotid atherosclerosis. Design: A total of 4022 middle-aged subjects from the general Swedish population were genotyped and individually assigned a genetic risk score based on 13 single-nucleotide polymorphisms (SNPs), previously associated with myocardial infarction and coronary artery disease. The genetic score (Score-MI) was then related to carotid bulb intima-media thickness (IMT), common carotid artery IMT and to the occurrence of carotid plaques in the study population. Results: Score-MI was associated with IMT of the bulb (P<0.001) and the common carotid artery (P<0.001) in unadjusted analyses, and with IMT of the bulb after adjustment for cardiovascular risk factors (P=0.003). The effect size of Score-MI on IMT of the bulb was similar to that of LDL cholesterol. After adjustment for cardiovascular risk factors, Score-MI was also associated with the occurrence of carotid plaques (odds ratio per quintile of Score-MI=1.11; 95% confidence interval 1.04-1.18; P=0.001). In addition to SNPs with known effects on LDL levels, Score-MI showed nominal associations with increasing systolic blood pressure and decreasing C-reactive protein levels. Conclusions: This genetic risk score was independently associated with carotid bulb IMT and carotid plaques, providing evidence of an association with early markers of atherosclerosis. This might imply that the genetic myocardial infarction risk conferred by the score is related to early atherosclerosis and that the risk score may identify at an early stage candidates at risk of developing intermediate phenotypes of atherosclerosis. Further studies should test whether assessing the genetic score could be valuable for early treatment decisions in these subjects.
U2 - 10.1111/j.1365-2796.2011.02472.x
DO - 10.1111/j.1365-2796.2011.02472.x
M3 - Article
C2 - 22017383
SN - 1365-2796
VL - 271
SP - 271
EP - 281
JO - Journal of Internal Medicine
JF - Journal of Internal Medicine
ER -