Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Arterioscler Thromb Vasc Biol. 2013 Sep;33(9):2233-9. doi: 10.1161/ATVBAHA.113.301236. Epub 2013 Jun 13.
Circulating levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides are recognized risk factors for cardiovascular disease. We tested the hypothesis that the cumulative effects of common genetic variants for lipids are collectively associated with subclinical atherosclerosis and incident coronary heart disease.
Participants were drawn from the Erasmus Rucphen Family Study (n=2269) and the Rotterdam Study (n=8130). Linear regression and Cox proportional hazards models were applied to assess the influence of 4 risk scores derived from common genetic variants for lipids (total cholesterol, LDL-C, high-density lipoprotein cholesterol, and triglycerides) on carotid plaque, intima-media thickness, incident myocardial infarction, and coronary heart disease. Adjusted for age and sex, all 4 risk scores were associated with carotid plaque. This relationship was the strongest for the LDL-C score, which increased plaque score by 0.102 per SD increase in genetic risk score (P=3.2 × 10(-8)). The LDL-C score was also nominally associated with intima-media thickness, which increased 0.006 mm per SD increase in score (P=0.05). Both the total cholesterol and LDL-C scores were associated with incident myocardial infarction and coronary heart disease with hazard ratios between 1.10 and 1.13 per SD increase in score. Inclusion of additional risk factors as covariates minimally affected these results.
Common genetic variants with small effects on lipid levels are, in combination, significantly associated with subclinical and clinical cardiovascular outcomes. As knowledge of genetic variation increases, preclinical genetic screening tools might enhance the prediction and prevention of clinical events.
总胆固醇、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇和甘油三酯的循环水平被认为是心血管疾病的危险因素。我们检验了这样一个假设，即脂质常见遗传变异的累积效应与亚临床动脉粥样硬化和冠心病事件的发生有关。
参与者来自伊拉斯谟鹿特丹研究（n=2269）和鹿特丹研究（n=8130）。线性回归和 Cox 比例风险模型被用来评估由脂质（总胆固醇、LDL-C、高密度脂蛋白胆固醇和甘油三酯）的常见遗传变异衍生的 4 个风险评分对颈动脉斑块、内膜中层厚度、心肌梗死和冠心病的影响。在调整年龄和性别后，所有 4 个风险评分都与颈动脉斑块有关。其中 LDL-C 评分的相关性最强，遗传风险评分每增加一个标准差，斑块评分增加 0.102（P=3.2×10(-8)）。LDL-C 评分与内膜中层厚度也有显著的相关性，评分每增加一个标准差，内膜中层厚度增加 0.006mm（P=0.05）。总胆固醇和 LDL-C 评分都与心肌梗死和冠心病事件相关，评分每增加一个标准差，风险比在 1.10 到 1.13 之间。将其他风险因素作为协变量纳入后，这些结果基本不变。
对血脂水平有微小影响的常见遗传变异，综合起来与亚临床和临床心血管结局显著相关。随着遗传变异知识的增加，临床前遗传筛查工具可能会增强对临床事件的预测和预防。
