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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 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.