使用基因组分析评估心血管疾病风险并确定个体化预防策略——有针对性的基于证据的综述。

Use of genomic profiling to assess risk for cardiovascular disease and identify individualized prevention strategies--a targeted evidence-based review.

机构信息

Women & Infants Hospital/Alpert Medical School of Brown University, Providence, Rhode Island, USA.

出版信息

Genet Med. 2010 Dec;12(12):772-84. doi: 10.1097/GIM.0b013e3181f8728d.

DOI:10.1097/GIM.0b013e3181f8728d

PMID:21045709

Abstract

PURPOSE

To address the key question of whether using available "cardiogenomic profiles" leads to improved health outcomes (e.g., reduction in rates of myocardial infarction and stroke) and whether these profiles help in making medical or personal decisions.

METHODS

A targeted evidence-based review based on published Evaluation of Genomic Applications in Practice and Prevention methodologies.

RESULTS

No study addressed the overarching question directly. Evidence for the analytic validity of genomic profiles was inadequate for most genes (scale: convincing, adequate, and inadequate), but based on gray data, the analytic sensitivity and specificity might be adequate. For the 29 candidate genes (58 separate associations reviewed), the credibility of evidence for clinical validity was weak (34 associations) to moderate (23 associations), based on limited evidence, potential biases, and/or variability between included studies. The association of 9p21 variants with heart disease had strong credibility with odds ratios of 0.80 (95% confidence interval: 0.77-0.82) and 1.25 (95% confidence interval: 1.21-1.30), respectively, for individuals with no, or two, at-risk alleles versus those with one at-risk allele. Using a multiplicative model, we combined information from 24 markers predicting heart disease and from 13 markers for stroke. The areas under the curves (64.7% and 55.2%, respectively), and overall screening performance (detection rates of 24% and 14% at a 10% false-positive rate, respectively) do not warrant use as stand-alone tests.

CONCLUSION

Even if genomic markers were independent of traditional risk factors, reports indicate that cardiovascular disease risk reclassification would be small. Improvement in health could occur with earlier initiation or higher adherence to medical or behavioral interventions, but no prospective studies documented such improvements (clinical utility).

摘要

目的

解决关键问题，即使用现有的“心脏基因组谱”是否能改善健康结果（例如，降低心肌梗死和中风的发生率），以及这些谱是否有助于做出医疗或个人决策。

方法

基于已发表的《基因组应用在实践和预防中的评估》方法进行有针对性的基于证据的综述。

结果

没有研究直接解决总体问题。大多数基因的基因组谱分析有效性证据不足（范围：有说服力、充分和不足），但基于灰色数据，分析的敏感性和特异性可能足够。对于 29 个候选基因（58 个单独的关联进行了审查），基于有限的证据、潜在的偏倚和/或纳入研究之间的差异，临床有效性证据的可信度较弱（34 个关联）到中等（23 个关联）。9p21 变体与心脏病的关联具有较强的可信度，其风险比分别为 0.80（95%置信区间：0.77-0.82）和 1.25（95%置信区间：1.21-1.30），对于没有或有两个风险等位基因的个体与有一个风险等位基因的个体相比。我们使用乘法模型，结合了 24 个预测心脏病的标志物和 13 个预测中风的标志物的信息。曲线下面积（分别为 64.7%和 55.2%）和总体筛查性能（在 10%假阳性率下的检出率分别为 24%和 14%）都不支持作为独立测试使用。