Ford Ian, Bezlyak Vladimir, Stott David J, Sattar Naveed, Packard Chris J, Perry Ivan, Buckley Brendan M, Jukema J Wouter, de Craen Anton J M, Westendorp Rudi G J, Shepherd James
Robertson Centre for Biostatistics, University of Glasgow, Glasgow, Scotland.
PLoS Med. 2009 Jan 20;6(1):e16. doi: 10.1371/journal.pmed.1000016.
Reduced glomerular filtration rate (GFR) is associated with increased cardiovascular risk in young and middle aged individuals. Associations with cardiovascular disease and mortality in older people are less clearly established. We aimed to determine the predictive value of the GFR for mortality and morbidity using data from the 5,804 participants randomized in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER).
Glomerular filtration rate was estimated (eGFR) using the Modification of Diet in Renal Disease equation and was categorized in the ranges ([20-40], [40-50], [50-60]) >or= 60 ml/min/1.73 m(2). Baseline risk factors were analysed by category of eGFR, with and without adjustment for other risk factors. The associations between baseline eGFR and morbidity and mortality outcomes, accrued after an average of 3.2 y, were investigated using Cox proportional hazard models adjusting for traditional risk factors. We tested for evidence of an interaction between the benefit of statin treatment and baseline eGFR status. Age, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, C-reactive protein (CRP), body mass index, fasting glucose, female sex, histories of hypertension and vascular disease were associated with eGFR (p = 0.001 or less) after adjustment for other risk factors. Low eGFR was independently associated with risk of all cause mortality, vascular mortality, and other noncancer mortality and with fatal and nonfatal coronary and heart failure events (hazard ratios adjusted for CRP and other risk factors (95% confidence intervals [CIs]) for eGFR < 40 ml/min/1.73m(2) relative to eGFR >or= 60 ml/min/1.73m(2) respectively 2.04 (1.48-2.80), 2.37 (1.53-3.67), 3.52 (1.78-6.96), 1.64 (1.18-2.27), 3.31 (2.03-5.41). There were no nominally statistically significant interactions (p < 0.05) between randomized treatment allocation and eGFR for clinical outcomes, with the exception of the outcome of coronary heart disease death or nonfatal myocardial infarction (p = 0.021), with the interaction suggesting increased benefit of statin treatment in subjects with impaired GFRs.
We have established that, in an elderly population over the age of 70 y, impaired GFR is associated with female sex, with presence of vascular disease, and with levels of other risk factors that would be associated with increased risk of vascular disease. Further, impaired GFR is independently associated with significant levels of increased risk of all cause mortality and fatal vascular events and with composite fatal and nonfatal coronary and heart failure outcomes. Our analyses of the benefits of statin treatment in relation to baseline GFR suggest that there is no reason to exclude elderly patients with impaired renal function from treatment with a statin.
肾小球滤过率（GFR）降低与中青年个体心血管风险增加相关。而其与老年人心血管疾病及死亡率之间的关联尚不明确。我们旨在利用“老年人普伐他汀前瞻性研究（PROSPER）”中5804名随机参与者的数据，确定GFR对死亡率和发病率的预测价值。
采用肾脏病饮食改良公式估算肾小球滤过率（eGFR），并将其分为[20 - 40]、[40 - 50]、[50 - 60]以及≥60 ml/min/1.73m²几个范围。按eGFR类别分析基线风险因素，同时对其他风险因素进行调整和未调整的情况。使用Cox比例风险模型对传统风险因素进行调整，研究平均3.2年后基线eGFR与发病率和死亡率结局之间的关联。我们检验了他汀类药物治疗益处与基线eGFR状态之间相互作用的证据。在对其他风险因素进行调整后，年龄、低密度脂蛋白（LDL）和高密度脂蛋白（HDL）胆固醇、C反应蛋白（CRP）、体重指数、空腹血糖、女性性别、高血压病史和血管疾病史与eGFR相关（p≤0.001）。低eGFR与全因死亡率、血管性死亡率及其他非癌症死亡率风险独立相关，也与致命性和非致命性冠心病及心力衰竭事件相关（相对于eGFR≥60 ml/min/1.73m²，eGFR＜40 ml/min/1.73m²经CRP和其他风险因素调整后的风险比（95%置信区间[CI]）分别为2.04（1.48 - 2.80）、2.37（1.53 - 3.67）、3.52（1.78 - 6.96）、1.64（1.18 - 2.27）、3.31（2.03 - 5.41）。除冠心病死亡或非致命性心肌梗死结局（p = 0.021）外，随机治疗分配与eGFR之间在临床结局方面无名义上具有统计学意义的相互作用（p＜0.05），该相互作用表明他汀类药物治疗对GFR受损受试者的益处增加。
我们已证实，在70岁以上的老年人群中，GFR受损与女性性别、血管疾病的存在以及其他与血管疾病风险增加相关的风险因素水平有关。此外，GFR受损与全因死亡率和致命性血管事件的显著风险增加以及致命性和非致命性冠心病及心力衰竭综合结局独立相关。我们对他汀类药物治疗益处与基线GFR关系的分析表明，没有理由将肾功能受损的老年患者排除在他汀类药物治疗之外。
