Staunton A, Vallance D T, Child A, Camm A J, Winder A F
Department of Cardiological Sciences, St. Georges Hospital Medical School, London, England.
J Lab Clin Med. 1994 Jun;123(6):842-8.
A register was built up of DNA from United Kingdom families with premature coronary heart disease and no perceived risk associations in the expectation that obscure causal factors could be defined through future genetic analysis. Referrals came from interested, predominantly cardiologic units in southern England. For inclusion, probands had documented coronary heart disease before age 55 years that was regarded as unexplained, in families with at least two living affected first-degree and two other members, in most families over two generations. Referred probands and family members completed a questionnaire on general health and habits and were examined for body mass index, blood pressure, resting electrocardiogram, and lipoprotein profile. Data are presented on 276 living members from 26 families, representing 75.4% of all members age 15 years and older. The striking observation was the extent of dyslipoproteinemia that was not identified by the referring units as relevant to the expression of accelerated coronary heart disease. This was expressed as hypercholesterolemia, reduced levels of high-density lipoprotein, or both, in comparison with profiles recorded over the same period and for a similar but unselected general British population. Further genetic analysis for a major occult risk factor in these families is inappropriate. Present concerns with potential adverse associations with low cholesterol, or with lipid-lowering treatment, should be addressed in the knowledge that uncontrolled dyslipoproteinemia also has severe adverse associations. These associations are still not widely appreciated in the management of patients and families with premature coronary heart disease.
建立了一个来自英国患有早发性冠心病且无明显风险关联的家庭的DNA登记册，期望通过未来的基因分析确定潜在的因果因素。转诊来自英格兰南部感兴趣的主要是心脏病学单位。纳入标准为：先证者在55岁之前患有冠心病且被认为原因不明，家庭中至少有两名在世的受影响一级亲属和另外两名成员，大多数家庭跨越两代。被转诊的先证者和家庭成员填写了一份关于一般健康和生活习惯的问卷，并接受了体重指数、血压、静息心电图和脂蛋白谱的检查。数据来自26个家庭的276名在世成员，占所有15岁及以上成员的75.4%。引人注目的观察结果是脂蛋白异常血症的程度，转诊单位未将其确定为与加速性冠心病的表现相关。与同期记录的以及类似但未经选择的英国普通人群的情况相比，这表现为高胆固醇血症、高密度脂蛋白水平降低或两者兼而有之。对这些家庭中的主要潜在危险因素进行进一步的基因分析是不合适的。目前对低胆固醇或降脂治疗潜在不良关联的担忧，应在认识到未控制的脂蛋白异常血症也有严重不良关联的情况下加以解决。在早发性冠心病患者及其家庭的管理中，这些关联仍未得到广泛认识。
