Thayabaran Darmiga, Tsui Anson P T, Ebmeier Stefan, Cegla Jaimini, David Alessia, Jones Ben
Imperial College Healthcare NHS Trust, London, UK (Drs Thayabaran, Cegla, David and Jones).
Imperial College London, London, UK (Mr Tsui).
J Clin Lipidol. 2023 Mar-Apr;17(2):244-254. doi: 10.1016/j.jacl.2023.01.006. Epub 2023 Jan 26.
Familial hypercholesterolaemia (FH) diagnostic tools help prioritise patients for genetic testing and include LDL-C estimates commonly calculated using the Friedewald equation. However, cholesterol contributions from lipoprotein(a) (Lp(a)) can overestimate 'true' LDL-C, leading to potentially inappropriate clinical FH diagnosis.
To assess how adjusting LDL-C for Lp(a)-cholesterol affects FH diagnoses using Simon Broome (SB) and Dutch Lipid Clinic Network (DLCN) criteria.
Adults referred to a tertiary lipid clinic in London, UK were included if they had undergone FH genetic testing based on SB or DLCN criteria. LDL-C was adjusted for Lp(a)-cholesterol using estimated cholesterol contents of 17.3%, 30% and 45%, and the effects of these adjustments on reclassification to 'unlikely' FH and diagnostic accuracy were determined.
Depending on the estimated cholesterol content applied, LDL-C adjustment reclassified 8-23% and 6-17% of patients to 'unlikely' FH using SB and DLCN criteria, respectively. The highest reclassification rates were observed following 45% adjustment in mutation-negative patients with higher Lp(a) levels. This led to an improvement in diagnostic accuracy (46% to 57% with SB, and 32% to 44% with DLCN following 45% adjustment) through increased specificity. However all adjustment factors led to erroneous reclassification of mutation-positive patients to 'unlikely' FH.
LDL-C adjustment for Lp(a)-cholesterol improves the accuracy of clinical FH diagnostic tools. Adopting this approach would reduce unnecessary genetic testing but also incorrectly reclassify mutation-positive patients. Health economic analysis is needed to balance the risks of over- and under-diagnosis before LDL-C adjustments for Lp(a) can be recommended.
家族性高胆固醇血症（FH）诊断工具有助于确定患者进行基因检测的优先级，其中包括通常使用弗瑞德瓦尔德方程计算的低密度脂蛋白胆固醇（LDL-C）估计值。然而，脂蛋白（a）[Lp（a）]对胆固醇的贡献可能会高估“真实”的LDL-C，从而导致潜在的不恰当的临床FH诊断。
评估根据Lp（a）胆固醇调整LDL-C对使用西蒙·布鲁姆（SB）和荷兰脂质诊所网络（DLCN）标准进行的FH诊断有何影响。
纳入转诊至英国伦敦一家三级脂质诊所的成年人，这些人已根据SB或DLCN标准接受了FH基因检测。使用17.3%、30%和45%的估计胆固醇含量对Lp（a）胆固醇进行LDL-C调整，并确定这些调整对重新分类为“不太可能”FH以及诊断准确性的影响。
根据所应用的估计胆固醇含量，使用SB和DLCN标准时，LDL-C调整分别将8%-23%和6%-17%的患者重新分类为“不太可能”FH。在Lp（a）水平较高的突变阴性患者中，调整45%后观察到最高的重新分类率。这通过提高特异性导致诊断准确性得到改善（SB标准下从46%提高到57%，DLCN标准下调整45%后从32%提高到44%）。然而，所有调整因素都会导致将突变阳性患者错误地重新分类为“不太可能”FH。
根据Lp（a）胆固醇调整LDL-C可提高临床FH诊断工具的准确性。采用这种方法将减少不必要的基因检测，但也会错误地将突变阳性患者重新分类。在推荐对Lp（a）进行LDL-C调整之前，需要进行卫生经济分析以平衡过度诊断和诊断不足的风险。
