Department of Clinical Sciences, Lund University, Malmö, Sweden.
J Intern Med. 2012 Mar;271(3):271-81. doi: 10.1111/j.1365-2796.2011.02472.x. Epub 2011 Nov 21.
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.
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 intima-media thickness (IMT), common carotid artery (CCA) IMT and to the occurrence of carotid plaques in the study population.
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.
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.
评估先前与心肌梗死（MI）和冠状动脉疾病（CAD）相关的遗传风险评分是否也与颈动脉粥样硬化的标志物相关。
总共对来自一般瑞典人群的 4022 名中年受试者进行基因分型，并根据先前与 MI 和 CAD 相关的 13 个单核苷酸多态性（SNP）为每个个体分配遗传风险评分。然后将遗传评分（Score-MI）与颈动脉球部内膜中层厚度（IMT）、颈总动脉（CCA）IMT 以及研究人群中颈动脉斑块的发生相关联。
在未调整的分析中，Score-MI 与球部（P<0.001）和 CCA 的 IMT（P<0.001）相关，在调整心血管危险因素后，与球部 IMT 相关（P=0.003）。Score-MI 对 IMT 的影响大小与 LDL 胆固醇相似。在调整心血管危险因素后，Score-MI 也与颈动脉斑块的发生相关（Score-MI 每五分位的比值比=1.11；95%置信区间 1.04-1.18；P=0.001）。除了与已知影响 LDL 水平的 SNP 相关外，Score-MI 还与收缩压升高和 C-反应蛋白水平降低呈名义相关。
该遗传风险评分与颈动脉球部 IMT 和颈动脉斑块独立相关，为与动脉粥样硬化早期标志物的相关性提供了证据。这可能意味着评分所赋予的遗传 MI 风险与早期动脉粥样硬化有关，并且风险评分可能在早期识别出具有发展为动脉粥样硬化中间表型风险的候选者。进一步的研究应该检验评估遗传评分是否对这些患者的早期治疗决策有价值。
