Heart:多种策略确定家族性高胆固醇血症

　　英国学者的一项研究表明，伴有腱黄色瘤（TX）的确定性家族性高胆固醇血症（FH）患者应行基因分型。在可疑性FH患者中，冠心病病史或粥样斑块影像学证据是确认可能伴有单基因FH患者的最佳方法。论文于2012年12月4日在线发表于《心脏》（Heart）杂志。

　　此项研究共纳入204例年龄为（55±14）岁的患者，其中36%伴有TX，21%伴有冠心病[低密度脂蛋白胆固醇（LDL-C）为（6.20±2.24） mmol/l]，并且55%伴有遗传性FH。评估不同分期系统（SB和Dutch标准）、TX存在、LDL-C水平应用、冠心病病史和粥样斑块影像学证据对遗传性FH鉴别的影响。转归指标为C统计值变化和净重分类指数（NRI）。

　　结果显示，SB标准得出的C统计值为0.64；其由TX阳性和阴性患者中C统计值分别为0.65和0.5所组成。TX阳性和阴性患者中分别有75%和44%存在遗传性FH。Dutch标准得出的C统计值为0.72。将影像学标准添加至既往冠心病可使C统计值由0.64升高至0.65，并且在所有患者中NRI为19%。在TX阴性患者中，影像学标准可使C统计值由0.50升高至0.65，并且NRI和加权比较指数分别为0.38和0.28，提示每1000例可多检出14例FH。

Effectiveness of alternative strategies to define index case phenotypes to aid genetic diagnosis of familial hypercholesterolaemia
Objective
To determine the utility of secondary stratification measures to improve the ascertainment of index cases of familial hypercholesterolaemia (FH).
Design
A retrospective study of genotyped index patients with Simon Broome (SB) FH.
Setting University teaching hospital.
Patients
204 patients aged 55±14years; 36% had tendon xanthoma (TX), 21% had coronary heart disease (CHD), low-density lipoprotein cholesterol (LDL-C) was 6.20±2.24mmol/l and 55% had genetic FH.
Interventions
The effects of different staging systems (SB vs Dutch criteria), presence of TX, use of LDL-C level, personal history of CHD and imaging evidence of atheroma by carotid intima-media thickness or coronary artery calcium score to identify genetic FH was explored.
Outcome measures
Changes in C-statistic and net reclassification index (NRI).
Results
SB criteria gave a C-statistic of 0.64 comprising C=0.65 in TX(+) and C=0.5 in TX(-) patients. Genetic FH was present in 75% of TX(+) compared with 44% in TX(-) patients. The Dutch criteria gave C=0.72. Addition of imaging criteria to prior CHD raised C=0.64 to C=0.65 in all patients with a NRI of 19% (p=0.06). In TX(-) patients imaging raised C=0.50 to C=0.65 with a NRI of 0.38 (p=0.001) and a weighted comparison index of 0.28, implying the detection of 14 more FH cases per thousand.
Conclusions
Patients with tendon xanthoma (definite FH) should be genotyped. In patients with possible FH, the presence of a personal history of CHD or imaging evidence of increased atheroma offers the best method of identifying index patients likely to have monogenic FH.