A myocardial infarction genetic risk score is associated with markers of carotid atherosclerosis

Abstract

Abstract. Hamrefors V, Hedblad B, Engström G, Almgren P, Sjögren M, Melander O (Lund University, Malmö, Sweden). A myocardial infarction genetic risk score is associated with markers of carotid atherosclerosis. J Intern Med 2012;271: 271-281.Objective. To assess whether or not a genetic risk score that was previously shown to be associated with myocardial infarction (MI) and coronary artery disease (CAD) 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 MI and CAD. The genetic score (Score-MI) was then related to carotid bulb intimamedia thickness (IMT), common carotid artery (CCA) 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 CCA (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 MI 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 or not assessing the genetic score could be valuable for early treatment decisions in these subjects.

Variants on Chromosome 9p21 Confer Risks of Noncardioembolic Cerebral Infarction and Carotid Plaque in the Chinese Han Population

“…These findings are in accordance with those of our study, indicating the promising role in CI of both loci. Furthermore, rs4977574 and rs2383206 polymorphisms were associated with a thicker IMT or carotid atherogenesis among the middle-aged Caucasians 36,37) . Because asymptomatic or subclinical plaque development is becoming a more accurate predictor of AS than IMT 38) , variants on chromosome 9p21 probably confer risks of acute CI in the Chinese Han population.…”

Common genetic risk factors for coronary artery disease: new opportunities for prevention?

“…Of the two community‐based genetic score studies referred in the previous section, the subjects in the second (Finnish) study were younger on average and this study also showed the strongest predictive utility of the GRS (Tikkanen et al ., ). Moreover, in a population‐based study of 4000 middle aged subjects, 97·5% of whom were free of overt CVD, we found that a CAD GRS was strongly associated with occurrence of small carotid plaques (Hamrefors et al ., ), further supporting the hypothesis that genetic variants affect the atherosclerotic process in an early stage. Thus, common genetics may be a potential tool for identifying subjects at future high risk of CAD and atherosclerosis already before atherosclerotic markers could be detected by imaging.…”

“…As an example of implementation, a nine loci lipid GRS was shown to strongly predict incident CVD also after adjusting for baseline lipid levels (Kathiresan et al, 2008). The same concept has been imple-mented also in studies of blood pressure and CAD (Ripatti et al, 2010;Hamrefors et al, 2012;Hughes et al, 2012;Ganna et al, 2013;Tikkanen et al, 2013;Mega et al, 2015a) with various results. It should be clarified that the concept of GRS, simple as it may seem, has a number of limitations.…”

“…Since the discovery in 2007, the SNPs on chromosome 9 have taken much of the focus in clinically oriented genetic research of CAD. Whereas most studies converge on the finding that, whatever the exact molecular mechanisms, the pathophysiological background of these SNPs is likely to be accelerated atherosclerosis (Reilly et al, 2011;Hamrefors et al, 2012;Chan et al, 2013;Dichgans et al, 2014), the clinical utility of these and other common CAD SNPs has been questioned. This stems from the fact that most predictive studies have shown modest, if any, improvement in discrimination or risk reclassification over traditional risk factors when assessing common genetic polymorphisms (Paynter et al, 2010;Ripatti et al, 2010;Patel et al, 2012;Thanassoulis et al, 2012;Vaarhorst et al, 2012;Gransbo et al, 2013;Pechlivanis et al, 2013).…”

Common Sequence Variants Associated With Coronary Artery Disease Correlate With the Extent of Coronary Atherosclerosis

“…2 Multilocus genetic risk scores (GRS) combining multiple SNPs with modest effects on cardiovascular risk have been shown to predict incident cardiovascular events in several prospective cohorts of European ancestry. 3–10 GRSs based on common CAD risk variants have been associated with atherosclerotic phenotypes such as peripheral artery disease 11 and carotid intima-media thickness 12 , and coronary artery calcium 5 , an indirect measure of atherosclerotic burden.…”