Palmer Michael K, Barter Philip J, Lundman Pia, Nicholls Stephen J, Toth Peter P, Karlson Björn W
Manchester Metropolitan University, School of Healthcare Science, Manchester, United Kingdom.
University of New South Wales, Sydney, Australia.
Clin Biochem. 2019 Feb;64:24-29. doi: 10.1016/j.clinbiochem.2018.10.011. Epub 2018 Oct 24.
Treating elevated low-density lipoprotein cholesterol (LDL-C) to risk-stratified target levels is recommended in several guidelines. Thus, accurate estimation of LDL-C is required. LDL-C is typically calculated using the Friedewald equation: (total cholesterol) - (non-high-density lipoprotein cholesterol [non-HDL-C]) - (triglycerides [TGs]/5). As the equation uses a fixed value equal to 5 as a divisor for TGs, it does not account for inter-individual variability, often resulting in underestimation of risk and potentially undertreatment. It is specifically inapplicable in patients with fasting triglycerides ≥400 mg/dL. A novel method of LDL-C calculation was derived and validated by Martin et al.: (non-HDL-C) - (triglycerides/adjustable factor). This equation uses an adjustable factor, the median TG:very-low-density lipoprotein cholesterol ratio in strata defined by levels of TG and non-HDLC, as divisor for TGs, and the adjustable factor ranging from 3 to 12 has been shown to provide more accurate estimates of LDL-C compared with the Friedewald equation using a direct assay as the gold standard. We used 70,209 baseline and on-treatment lipid values from the VOYAGER meta-analysis database to determine the difference in calculated LDL-C values using the Friedewald and novel equations. In patients with TGs <400 mg/dL, LDL-C values calculated using the novel equation were plotted against those calculated using the Friedewald equation. The novel equation generally resulted in LDL-C values greater than the Friedewald calculation, with differences increasing with decreasing LDL-C levels; 23% of individuals who reached a LDL-C target of 70 mg/dL with the Friedewald equation did not achieve this target when the novel equation was used to calculate LDL-C; these figures were 8% and 2% for <100 mg/dL and < 130 mg/dL targets, respectively. In patients with triglycerides ≥400 mg/dL, in whom the Friedewald equation is not valid, lipid values calculated using the novel equation were compared with those obtained by β-quantification. Values calculated with the novel equation did not appear to be closely related with those calculated by β-quantification in these patients. In conclusion, the novel equation provides a higher estimation of exact LDL-C values than the Friedewald equation, particularly in patients with low LDL-C levels, which may result in undertreatment of some patients whose LDL-C was calculated using the Friedewald method. However, neither may be suitable for patients with TG ≥400 mg/dL.
多项指南推荐将低密度脂蛋白胆固醇（LDL-C）升高治疗至风险分层的目标水平。因此，需要准确估算LDL-C。LDL-C通常使用Friedewald方程计算：（总胆固醇）-（非高密度脂蛋白胆固醇[非HDL-C]）-（甘油三酯[TGs]/5）。由于该方程使用固定值5作为TGs的除数，未考虑个体间差异，常导致风险低估和潜在的治疗不足。它特别不适用于空腹甘油三酯≥400mg/dL的患者。Martin等人推导并验证了一种新的LDL-C计算方法：（非HDL-C）-（甘油三酯/可调因子）。该方程使用一个可调因子，即由TG和非HDL-C水平定义的分层中甘油三酯与极低密度脂蛋白胆固醇的中位数比值，作为TGs的除数，并且已证明与以直接检测为金标准的Friedewald方程相比，范围为3至12的可调因子能提供更准确的LDL-C估算值。我们使用了VOYAGER荟萃分析数据库中的70209个基线和治疗期血脂值，以确定使用Friedewald方程和新方程计算的LDL-C值的差异。在TGs<400mg/dL的患者中，将使用新方程计算的LDL-C值与使用Friedewald方程计算的LDL-C值进行了绘制。新方程计算出的LDL-C值通常大于Friedewald方程计算出的值，差异随着LDL-C水平的降低而增加；使用Friedewald方程达到LDL-C目标值70mg/dL的个体中，当使用新方程计算LDL-C时，有23%未达到该目标；对于<100mg/dL和<130mg/dL的目标值，这些数字分别为8%和2%。在甘油三酯≥400mg/dL的患者中，Friedewald方程无效，将使用新方程计算的血脂值与通过β定量获得的血脂值进行了比较。在这些患者中，用新方程计算的值似乎与通过β定量计算的值没有密切关系。总之，与Friedewald方程相比，新方程对准确的LDL-C值的估算更高，特别是在LDL-C水平较低的患者中，这可能导致一些使用Friedewald方法计算LDL-C的患者治疗不足。然而，两者可能都不适用于TG≥400mg/dL的患者。
