Iribarren C, Reed D M, Chen R, Yano K, Dwyer J H
Department of Preventive Medicine, University of Southern California School of Medicine, Los Angeles 90033, USA.
Circulation. 1995 Nov 1;92(9):2396-403. doi: 10.1161/01.cir.92.9.2396.
Many studies have reported an association between a low or lowered blood total cholesterol (TC) level and subsequent nonatherosclerotic disease incidence or death. The question of whether low TC is a true risk factor or alternatively a consequence of occult disease at the time of TC measurement remains unsettled. To shed new light onto this problem, we analyzed TC change over a 6- year period (from exam 1 in 1965 through 1968 to exam 3 in 1971 through 1974) in relation to subsequent 16-year mortality in a cohort of Japanese American men.
The study was based on 5941 men 45 to 68 years of age without prior history of coronary heart disease, stroke, cancer, or gastrointestinal-liver disease at exam 1 who also participated in exam 3 of the Honolulu Heart Program. The association of TC change with mortality end points was investigated with two different approaches (continuous and categorical TC change) with standard survival analysis techniques. Falling TC level was accompanied by a subsequent increased risk of death caused by some cancers (hemopoietic, esophageal, and prostate), noncardiovascular noncancer causes (particularly liver disease), and all causes. The risk-factor-adjusted rate of all-cause mortality was 30% higher (relative risk, 1.30; 95% CI, 1.06 to 1.59) among persons with a decline from middle (180 to 239 mg/dL) to low (< 180 mg/dL) TC than in persons remaining at a stable middle level. By contrast, there was no significant increase in all-cause mortality risk among cohort men with stable low TC levels. Nonillness mortality (deaths caused by trauma and suicide) was not related to either TC change or the average of TC levels in exams 1 and 3.
These results add strength to the reverse-causality proposition that catabolic diseases cause TC to decrease.
许多研究报告了血液总胆固醇（TC）水平降低与随后非动脉粥样硬化性疾病发病率或死亡率之间的关联。低TC究竟是一个真正的危险因素，还是在测量TC时隐匿疾病的结果，这一问题仍未解决。为了阐明这一问题，我们分析了一组日裔美国男性在6年期间（从1965年至1968年的检查1到1971年至1974年的检查3）的TC变化与随后16年死亡率的关系。
该研究基于5941名年龄在45至68岁之间、在检查1时无冠心病、中风、癌症或胃肠道-肝脏疾病既往史且也参加了檀香山心脏项目检查3的男性。采用标准生存分析技术，通过两种不同方法（连续和分类TC变化）研究TC变化与死亡终点的关联。TC水平下降伴随着随后某些癌症（血液系统、食管和前列腺癌）、非心血管非癌症病因（特别是肝脏疾病）以及所有病因导致的死亡风险增加。与保持稳定中等水平的人相比，TC从中等水平（180至239mg/dL）降至低水平（<180mg/dL）的人的全因死亡率经风险因素调整后高出30%（相对风险，1.30；95%CI，1.06至1.59）。相比之下，TC水平稳定较低的队列男性全因死亡风险没有显著增加。非疾病死亡率（由创伤和自杀导致的死亡）与TC变化或检查1和3中的TC水平平均值均无关。
这些结果为分解代谢疾病导致TC降低的反向因果关系命题提供了有力支持。
