Småbrekke Birgit, Rinde Ludvig Balteskard, Hindberg Kristian, Hald Erin Mathiesen, Vik Anders, Wilsgaard Tom, Løchen Maja-Lisa, Njølstad Inger, Mathiesen Ellisiv B, Hansen John-Bjarne, Brækkan Sigrid
K.G. Jebsen-Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.
PLoS One. 2016 Sep 16;11(9):e0163242. doi: 10.1371/journal.pone.0163242. eCollection 2016.
Single measurements of modifiable risk factors may underestimate associations with outcomes in cohorts. We aimed to compare risk estimates of myocardial infarction (MI) and venous thromboembolism (VTE) by atherosclerotic risk factors during long follow-up using time-fixed analyses without and with correction for regression dilution and time-varying analyses.
The study included 5970 subjects enrolled in the fourth survey of the Tromsø Study (1994/95). Blood pressure, lipid levels, body mass index (BMI), diabetes and smoking status were measured at baseline, and subjects still alive at the fifth (2001/02, n = 5179) and sixth (2007/08, n = 4391) survey were re-measured. Incident events of MI (n = 714) and VTE (n = 214) were recorded until December 2010. Time-fixed and time-varying Cox regression models were used to estimate hazard ratios (HR) for MI and VTE adjusted for age and sex.
Variations in BMI, blood pressure and lipid levels were small, and did not alter the risk estimates when time-varying analyses were compared to time-fixed analyses. For MI, variables that changed considerably over time yielded the greatest changes in risk estimates (HR for smoking changed from 1.80 (95% CI 1.55-2.10) to 2.08 (95% CI 1.78-2.42)). For VTE, only BMI was associated with increased risk in both time-fixed and time-varying analysis, but the risk estimates weakened in the time-varying analysis. Correction of time-fixed HRs with Rosner´s method tended to overestimate risk estimates compared to time-varying analysis.
For MI and VTE, risk estimates based on baseline and repeated measures corresponded well, whereas correction for regression dilution tended to overestimate risks.
对可改变的风险因素进行单次测量可能会低估队列研究中其与结局的关联。我们旨在通过时间固定分析（不校正和校正回归稀释）以及时间变化分析，比较在长期随访期间动脉粥样硬化风险因素对心肌梗死（MI）和静脉血栓栓塞（VTE）的风险估计。
该研究纳入了参加特罗姆瑟研究第四次调查（1994/95年）的5970名受试者。在基线时测量血压、血脂水平、体重指数（BMI）、糖尿病和吸烟状况，在第五次（2001/02年，n = 5179）和第六次（2007/08年，n = 4391）调查时仍存活的受试者进行重新测量。记录至2010年12月的MI（n = 714）和VTE（n = 214）的发病事件。使用时间固定和时间变化的Cox回归模型来估计经年龄和性别校正后的MI和VTE的风险比（HR）。
BMI、血压和血脂水平的变化较小，与时间固定分析相比，时间变化分析时风险估计未改变。对于MI，随时间变化较大的变量导致风险估计变化最大（吸烟的HR从1.80（95%CI：1.55 - 2.10）变为2.08（95%CI：1.78 - 2.42））。对于VTE，在时间固定和时间变化分析中，只有BMI与风险增加相关，但在时间变化分析中风险估计减弱。与时间变化分析相比，用罗斯纳方法校正时间固定的HR往往会高估风险估计。
对于MI和VTE，基于基线和重复测量的风险估计相当一致，而回归稀释校正往往会高估风险。
