UNRECOGNIZED DYSLIPOPROTEINEMIA IN UNITED-KINGDOM FAMILIES RECRUITED TO A GENETIC REGISTER BECAUSE OF UNEXPLAINED CORONARY HEART-DISEASE

A register was built up of DNA from United Kingdom families with prema ture coronary heart disease and no perceived risk associations in the expectation that obscure causal factors could be defined through futur e genetic analysis. Referrals came from interested, predominantly card iologic units in southern England. For inclusion, probands had documen ted coronary heart disease before age 55 years that was regarded as un explained, 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 heal th and habits and were examined for body mass index, blood pressure, r esting electrocardiogram, and lipoprotein profile. Data are presented on 276 living members from 26 families, representing 75.4% of all memb ers 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 s ame period and for a similar but unselected general British population . Further genetic analysis for a major occult risk factor in these fam ilies is inappropriate. Present concerns with potential adverse associ ations with low chotesterol, or with lipid-lowering treatment, should be addressed In the knowledge that uncontrolled dyslipoproteinemia als o has severe adverse associations. These associations are still not wi dely appreciated in the management of patients and families with prema ture coronary heart disease.