Comparison of the risk of fatal coronary heart disease in treated xanthomatous and non-xanthomatous heterozygous familial hypercholesterolaemia: a prospective registry study

• Published in: Atherosclerosis Vol. 170; no. 1; pp. 73 - 78
• Main Authors: Neil, H.A.W., Huxley, R.R., Hawkins, M.M., Durrington, P.N., Betteridge, D.J., Humphries, S.E.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01.09.2003; Elsevier
• Subjects: Adolescent; Adult; Age Factors; Aged; Biological and medical sciences; Biomarkers - blood; Blood Pressure - genetics; Blood Pressure - physiology; Body Mass Index; Cardiology. Vascular system; Child; Child, Preschool; Cholesterol, LDL - blood; Coronary Disease - genetics; Coronary Disease - mortality; Coronary Disease - therapy; Coronary heart disease; Diastole - genetics; Diastole - physiology; Disorders of blood lipids. Hyperlipoproteinemia; Familial hypercholesterolaemia; Female; Follow-Up Studies; Genetic Predisposition to Disease - epidemiology; Genetic Predisposition to Disease - genetics; Heart; Heterozygote; Humans; Hyperlipoproteinemia Type II - genetics; Hyperlipoproteinemia Type II - mortality; Hyperlipoproteinemia Type II - therapy; Infant; Infant, Newborn; Male; Medical sciences; Metabolic diseases; Middle Aged; Mortality; Prevalence; Prospective Studies; Registries; Risk Factors; Statistics as Topic; Survival Analysis; Systole - genetics; Systole - physiology; Time Factors; Treatment Outcome; Triglycerides - blood; Xanthomatosis - genetics; Xanthomatosis - mortality; Xanthomatosis - therapy; Coronary heart disease; Familial hypercholesterolaemia; Mortality; Human; Xanthomatosis; Skin disease; Cardiovascular disease; Metabolic diseases; Lipids; Hyperlipoproteinemia; Enzymopathy; Hypercholesterolemia; Risk factor; Family environment; Hyperlipemia; Dyslipemia; Comparative study
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/S0021-9150(03)00233-8

Background: A clinical diagnosis of familial hypercholesterolaemia (FH) is often made in the absence of tendon xanthomata (TX), which are not usually present before the fourth decade of life. The prognosis of treated non-xanthomatous (TX−) FH is uncertain and the objective of this study was to compare mortality from coronary heart disease (CHD) in patients with treated TX+ (definite) and TX− (possible) heterozygous FH. Methods: A diagnosis of definite or possible FH was based on raised cholesterol levels (>7.5 mmol/l) and a family history of premature CHD or hypercholesterolaemia. Patients were recruited from 21 outpatient lipid clinics in the UK from 1980 to 1998. The cohort of 1569 patients with TX+ FH were followed for 12 754 person years and the cohort of 1302 patients with TX− FH for 10 238 person years. The standardised mortality ratio (SMR) was calculated from the ratio of the number of deaths observed to the number expected in the general population of England and Wales (SMR=100 for reference population). Findings and discussion: CHD accounted for 64 (63%) of the 102 deaths in the TX+ cohort and 38 (57%) of the 67 deaths in the TX− cohort with the SMR for a fatal coronary event being, respectively, 294 (95% confidence interval 228, 380, P<0.00001) and 205 (95% CI 145, 282, P=0.0001). The similarly elevated CHD mortality risk suggests that, in adulthood, both groups of patients should be treated equally aggressively with HMG Co A reductase inhibitors (statins).