Valdes A M, Wolfe M L, Tate H C, Gefter W, Rut A, Rader D J
Department of Human Genetics, Smithkline Beecham Pharmaceuticals, Philadelphia, PA, USA.
J Investig Med. 2001 Jul;49(4):353-61. doi: 10.2310/6650.2001.33901.
Genetic factors strongly influence the risk of coronary heart disease (CHD), but their contribution to variation in coronary atherosclerosis beyond that measured by traditional CHD risk factors is uncertain.
We recruited healthy subjects with family histories of premature CHD. We assessed traditional risk factors and performed electron beam tomography (EBT) to quantitate coronary artery calcification (CAC), a marker of coronary atherosclerosis. Persons with significant risk factors that included diabetes, total cholesterol >300 mg/dL, active cigarette smoking, and poorly controlled hypertension were excluded from the study. In this paper, we report on the relationship between traditional risk factors and CAC in this cohort.
The incidence of coronary calcification was significantly higher in this cohort than in the population-based Rochester Heart Study. In our cohort, most traditional risk factors were significantly associated with CAC on univariate analysis. On the other hand, in stepwise logistical regression, age and triglycerides were the only predictors of variation in CAC in men and accounted for only 30% of the variation; in women, age, body mass index (BMI), and triglycerides were the only traditional risk factors significantly associated with CAC variation and accounted for 22.2% of CAC variance.
In a cohort of subjects specifically selected for the characteristic of a family history of premature CHD, traditional risk factors accounted for less than one-third of the variation in CAC, and the most important predictors of CAC after age were plasma triglycerides. This supports the opinion that other inherited risk factors have important effects on the variation in coronary atherosclerosis and that the strategy of using EBT to phenotype clinically asymptomatic subjects with regard to coronary atherosclerosis may be a useful tool for identification of genes that are associated with CHD.
遗传因素对冠心病(CHD)风险有强烈影响,但其对冠状动脉粥样硬化变异的贡献超出传统CHD风险因素所测范围尚不确定。
我们招募了有早发CHD家族史的健康受试者。我们评估了传统风险因素,并进行电子束断层扫描(EBT)以定量冠状动脉钙化(CAC),这是冠状动脉粥样硬化的一个标志物。有显著风险因素(包括糖尿病、总胆固醇>300mg/dL、当前吸烟和控制不佳的高血压)的人被排除在研究之外。在本文中,我们报告了该队列中传统风险因素与CAC之间的关系。
该队列中冠状动脉钙化的发生率显著高于基于人群的罗切斯特心脏研究。在我们的队列中,大多数传统风险因素在单变量分析中与CAC显著相关。另一方面,在逐步逻辑回归中,年龄和甘油三酯是男性CAC变异的唯一预测因素,仅占变异的30%;在女性中,年龄、体重指数(BMI)和甘油三酯是与CAC变异显著相关的仅有的传统风险因素,占CAC方差的22.2%。
在一个因早发CHD家族史特征而特意挑选的受试者队列中,传统风险因素占CAC变异的不到三分之一,年龄之后CAC最重要的预测因素是血浆甘油三酯。这支持了以下观点,即其他遗传风险因素对冠状动脉粥样硬化变异有重要影响,并且使用EBT对临床上无症状的受试者进行冠状动脉粥样硬化表型分析的策略可能是识别与CHD相关基因的有用工具。