Department of Medicine University of Queensland Brisbane Australia.
National Health and Medical Research Council Clinical Trials CentreUniversity of Sydney Sydney Australia.
J Am Heart Assoc. 2022 Mar;11(5):e020745. doi: 10.1161/JAHA.121.020745. Epub 2022 Feb 18.
Background Elevated plasma cystatin C levels reflect reduced renal function and increased cardiovascular risk. Less is known about whether the increased risk persists long-term or is independent of renal function and other important biomarkers. Methods and Results Cystatin C and other biomarkers were measured at baseline (in 7863 patients) and 1 year later (in 6106 patients) in participants in the LIPID (Long-Term Intervention with Pravastatin in Ischemic Disease) study, who had a previous acute coronary syndrome. Outcomes were ascertained during the study (median follow-up, 6 years) and long-term (median follow-up, 16 years). Glomerular filtration rate (GFR) was estimated using Chronic Kidney Disease Epidemiology Collaboration equations (first GFR-creatinine, then GFR-creatinine-cystatin C). Over 6 years, in fully adjusted multivariable time-to-event models, with respect to the primary end point of coronary heart disease mortality or nonfatal myocardial infarction, for comparison of Quartile 4 versus 1 of baseline cystatin C, the hazard ratio was 1.37 (95% CI, 1.07-1.74; =0.01), and for major cardiovascular events was 1.47 (95% CI, 1.19-1.82; <0.001). Over 16 years, the association of baseline cystatin C with coronary heart disease, cardiovascular, and all-cause mortality persisted (each <0.001) and remained significant after adjustment for estimated GFR-creatinine-cystatin C. Cystatin C also predicted the development of chronic kidney disease for 6 years (odds ratio, 6.61; 95% CI, 4.28-10.20) independently of estimated GFR-creatinine and other risk factors. However, this association was no longer significant after adjustment for estimated GFR-creatinine-cystatin C. Conclusions Cystatin C independently predicted major cardiovascular events, development of chronic kidney disease, and cardiovascular and all-cause mortality. Prediction of long-term mortality was independent of improved estimation of GFR. Registration URL: https://anzctr.org.au; Unique identifier: ACTRN12616000535471.
背景 血浆胱抑素 C 水平升高反映肾功能降低和心血管风险增加。但人们对这种风险是否长期持续存在，或者是否独立于肾功能和其他重要生物标志物，知之甚少。
方法和结果 在 LIPID（缺血性疾病中普伐他汀的长期干预）研究中，先前患有急性冠状动脉综合征的参与者在基线（7863 例患者）和 1 年后（6106 例患者）测量了胱抑素 C 和其他生物标志物。在研究期间（中位随访 6 年）和长期（中位随访 16 年）确定了结局。使用慢性肾脏病流行病学合作（Chronic Kidney Disease Epidemiology Collaboration，CKD-EPI）方程（首先使用肌酐估计肾小球滤过率[glomerular filtration rate，GFR]-肌酐，然后使用肌酐-胱抑素 C 估计 GFR）估计肾小球滤过率。在经过充分调整的多变量时间事件模型中，对于主要终点——冠心病死亡率或非致死性心肌梗死，与基线胱抑素 C 第 4 四分位与第 1 四分位相比，风险比为 1.37（95%CI，1.07-1.74；=0.01），而对于主要心血管事件为 1.47（95%CI，1.19-1.82；<0.001）。在 16 年的随访中，基线胱抑素 C 与冠心病、心血管疾病和全因死亡率的相关性仍然存在（均<0.001），且在调整肌酐-胱抑素 C 估计肾小球滤过率后仍然显著。胱抑素 C 还可预测 6 年内慢性肾脏病的发生（比值比，6.61；95%CI，4.28-10.20），且独立于肌酐估计肾小球滤过率和其他危险因素。然而，在调整肌酐-胱抑素 C 估计肾小球滤过率后，这种相关性不再显著。
结论 胱抑素 C 独立预测主要心血管事件、慢性肾脏病的发生以及心血管疾病和全因死亡率。长期死亡率的预测独立于肾小球滤过率的改善估计。
