Importance of HDL cholesterol levels and the total/HDL cholesterol ratio as a risk factor for coronary heart disease in molecularly defined heterozygous familial hypercholesterolaemia

Aims. To assess the relationship of the lipid profile to coronary heart dis ease in a group of heterozygous familial hypercholesterolaemic subjects wit h similar age, sex, body mass index, prevalence of angiotensin converting e nzyme DD genotype and type of low density lipoprotein receptor mutation. Methods and Results. A total of 66 molecularly defined heterozygous familia l hypercholesterolaemic subjects, 33 of whom had coronary heart disease, we re studied. Clinical features, cardiovascular risk factors and lipid parame ters were compared in both groups. Familial hypercholesterolaemic patients with coronary heart disease showed significantly lower values of mean plasm a HDL cholesterol and a higher total/HDL cholesterol ratio as compared with familial hypercholesterolaemic subjects free of coronary heart disease. To tal and LDL cholesterol concentrations were higher in patients with coronar y heart disease, without reaching statistical significance. No differences in plasma lipoprotein(a) levels on absolute and log-transformed values were observed between the two groups. In the whole familial hypercholesterolaem ia group, plasma HDL cholesterol levels were related to plasma triglyceride values and to LDL receptor gene 'null mutations'. Conclusions. In familial hypercholesterolaemic subjects of similar age, gen der, body mass index, systolic and diastolic blood pressure, and genetic fa ctors that could influence coronary heart disease risk, plasma HDL choleste rol values and total/HDL cholesterol ratios are two important coronary risk factors. Hence, treatment of familial hyper cholesterolaemia should focus not only on lowering total and LDL cholesterol levels, but also on increasi ng HDL cholesterol values for coronary heart disease prevention. More prosp ective and intervention trials should be conducted to establish the relatio nship of HDL cholesterol levels and coronary heart disease in familial hype rcholesterolaemia. (C) 2001 The European Society of Cardiology.