病例对照研究能发柳叶刀？ 能！
2015 年 5 月 26 日出版的 The Lancet Diabetes & Endocrinology 刊登一篇论文：Association of HDL cholesterol efflux capacity with incidentcoronary heart disease events: a prospective case-control study
各位会纳闷：既然是病例对照研究，怎么是前瞻性的？
作者在 EPIC-Norfolk 研究（一个前瞻性队列研究，样本量两万五千多人）中挑出在研究随访期间患上冠心病的 1745 人和没得冠心病的 1749 人，然后测定 HDL cholesterol efflux capacity。分析结果发现：cholesterolefflux capacity 和冠心病与否呈负关联，并且这个关联独立于年龄、性别、是否吸烟、是否有糖尿病／高血压，以及各种胆固醇指标，尤其是 HDL。
长青藤编辑张科宏解读：
1）其实这根本不是一个什么前瞻性的研究：HDL cholesterol efflux capacity 的测定是在 EPIC-Norfolk 队列研究的结束点，而非起点。
2）这帮老外会说「故事」。圈子里的人都知道可认可 EPIC-Norfolk 队列研究。这些作者「拉大旗做虎皮」，傍上大款，搞了一个 「nested case-control study」，把这个研究「包装」成了前瞻性的。
3）不可否认，作者的确有能量：把 EPIC-Norfolk 队列研究中的几千个人拉进去，不是一件小土豆能够做到的事情。
4）作者对于研究的定位在概念上有所突破：原先的研究聚焦在 HLD 本身，而这个研究关注点是 HDL cholesterol efflux capacity。
5）研究设计靠谱：对照的匹配好，因此能够得出一个「满意」的结果。
6）数据分析到位：关联分析中该校正的都校正了，最关键的是把 HLD 也作为协变量做了校正。
7）最后结果的展现「傻子」都能懂：监测指标（HDL cholesterol efflux capacity）每增高一个标准差，冠心病风险下降 20%。我见到的中国医生论文中基本上都是到「独立风险因素」为止。人家不一样，把话说到底，而且放在关键的地方（摘要中）。
论文摘要摘录（来自 the Lancet 官网）：
Summary
Background
Although HDL cholesterol concentrations are strongly andinversely associated with risk of coronary heart disease, interventions thatraise HDL cholesterol do not reduce risk of coronary heart disease. HDLcholesterol efflux capacity—a prototypical measure of HDL function—has beenassociated with coronary heart disease after adjusting for HDL cholesterol, butits effect on incident coronary heart disease risk is uncertain.
Methods
We measured cholesterol efflux capacity and assessed itsrelation with vascular risk factors and incident coronary heart disease eventsin a nested case-control sample from the prospective EPIC-Norfolk study of 25639individuals aged 40–79 years, assessed in 1993–97 and followed up to 2009. Wequantified cholesterol efflux capacity in 1745 patients with incident coronaryheart disease and 1749 control participants free of any cardiovasculardisorders by use of a validated ex-vivo radiotracer assay that involvedincubation of cholesterol-labelled J774 macrophages with apoB-depleted serumfrom study participants.
Findings
Cholesterol efflux capacity was positively correlated withHDL cholesterol concentration (r = 0·40; p<0·0001) and apoA-I concentration(r = 0·22; p<0·0001). It was also inversely correlated with type 2 diabetes(r =–0·18; p<0·0001) and positively correlated with alcohol consumption(r = 0·12; p<0·0001). In analyses comparing the top and bottom tertiles,cholesterol efflux capacity was significantly and inversely associated withincident coronary heart disease events, independent of age, sex, diabetes,hypertension, smoking and alcohol use, waist:hip ratio, BMI, LDL cholesterolconcentration, log-triglycerides, and HDL cholesterol or apoA-I concentrations(odds ratio 0·64, 95% CI 0·51–0·80). After a similar multivariable adjustmentthe risk of incident coronary heart disease was 0·80 (95% CI 0·70–0·90) for aper-SD change in cholesterol efflux capacity.
Interpretation
HDL cholesterol efflux capacity might provide an alternativemechanism for therapeutic modulation of the HDL pathway beyond HDL cholesterolconcentration to help reduce risk of coronary heart disease.