Outcome of case finding among relatives of patients with known heterozygous familial hypercholesterolaemia.

Abstract

Objectives To assess the feasibility of detecting new cases of heterozygous familial hypercholesterolaemia by using a nurse led genetic register.

Design Case finding among relatives of patients with familial hypercholesterolaemia.

Setting Two lipid clinics in central and south Manchester.

Subjects 259 (137 men and 122 women) probands and 285 first degree relatives.

Results Of the 200 first degree relatives tested, 121 (60%) had inherited familial hypercholesterolaemia. The newly diagnosed patients were younger than the probands and were generally detected before they had clinically overt atherosclerosis. Concentrations of serum cholesterol were, respectively, 8.4 (1.7 SD) mmol/l and 8.1 (1.9 SD) mmol/l in affected men and women and 5.6 (1.0 SD) mmol/l and 5.6 (1.1 SD) mmol/l in unaffected men and women. Screening for risk factors as recommended in recent guidelines for coronary heart disease prevention would have failed to identify most of the affected relatives in whom hypertension, diabetes mellitus, cigarette smoking, and obesity were uncommon.

Conclusions By performing cholesterol tests on 200 relatives, 121 new patients with familial hypercholesterolaemia were discovered. Because 1 in 500 people in the United Kingdom are affected by this condition, to detect a similar number by population screening over 60 000 tests would be required, and only a few of these patients would have been detected had cholesterol testing been restricted to those with other risk factors for coronary heart disease. A case exists for organising a genetic register approach, linking lipid clinics nationally.

Introduction

Familial hypercholesterolaemia in its heterozygous form occurs in around 1 in 500 people in Europe and North America, making it the most common potentially lethal genetic disorder. The characteristic clinical syndrome in adulthood comprises an increased serum cholesterol concentration, tendon xanthomas, and premature coronary heart disease, the median age of onset for coronary heart disease being around 50 years in men and 59 in women.[1 2] Statin treatment and the opportunity for prompt access to cardiological services for patients with familial hypercholesterolaemia seem to have improved survival.[3] In trials using coronary angiography, cholesterol lowering treatment is at least as effective in patients with familial hypercholesterolaemia as it is in other types of patients with coronary disease.[1] Most of the potential 100 000 patients with familial hypercholesterolaemia in the United Kingdom are probably undiagnosed, because only a small proportion attend lipid clinics.[4] The same is also likely to be true in other countries.[5] Often the clinical syndrome of familial hypercholesterolaemia is due to a mutation of the low density lipoprotein receptor. However, genetic testing is not currently a feasible means of establishing the diagnosis, except perhaps under special circumstances.[6-9]

It is generally agreed that screening the population for high cholesterol concentrations should be undertaken only as part of a multifactorial approach for the detection of people with a high coronary risk so that cholesterol lowering and antihypertensive treatments can he used in the most cost effective way.[10] Familial hypercholesterolaemia, however, seems to be a condition in which a single risk factor (high cholesterol from birth) often leads to an absolute coronary risk in the range for statin treatment well before middle age.[1 3] We aimed to assess the possibility of using a genetic register method to diagnose new cases of familial hypercholesterolaemia, which has the potential to be adopted nationally.

Participants and methods

Probands aged 18 years or over attending two adjacent lipid clinics (Manchester Royal Infirmary and University Hospital of South Manchester) for the first time between 1987 and 1998 were identified if serum cholesterol concentrations exceeded 7.5 mmol/l (or low …