- establish an extensive data-base of large European pedigrees with premature CHD and familial dyslipidemia (FD)
- study in detail the genetic and biochemical background of the FDs
- develop reliable diagnostic criteria with genetic and/or metabolic markers
Familial dyslipidemias (FDs) are major determinants of coronary heart disease (CHD). Approximately 50% of patients with angiographically documented CHD before the age of 60 years have FD. In contrast to familial hypercholesterolemia (FH), a relatively rare disease, the genetic and metabolic bases of these common disorders are mostly unknown, and therefore the diagnosis is often not applicable to clinical practice. We aim to collect a total of 300 large families with early CHD and dyslipidemia. The pedigrees are recruited from 5 centers located in the northern and southern parts of Europe. In the first phase of the study probands are selected from middle-aged patients undergoing elective coronary angiography with at least one-vessel disease, dyslipidemia and 5 eligible first-degree relatives. In the second phase the appropriate FD families are selected and included in the final phase, where complete pedigrees are examined with defined extensive clinical, metabolic and genetic studies. The proposed project has 8 top European centers devoted to analytical tasks. The metabolic and genetic studies will be coordinated and closely linked so that normal findings made in one field will support the other. We aim to dissect the molecular pathogenesis of these complex disorders by analysing complete metabolic pathways utilising both genetic and biochemical markers. When reliable markers for the common FDs are available, the identification of FD families with an increased risk for premature death will be an integral part of CHD primary prevention. Further, the diagnosis can be made early in the course of the disease, before extensive atheromatous lesions have developed. In Europe, where CHD is particularly prevalent, the socio-economic impact of an early diagnosis of the FDs is considerable.