Published Online
on December 12, 2002

A more recent version of this article appeared on January 1, 2003

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Submitted on July 18, 2002
Accepted on August 12, 2002

Risk of Fatal Stroke in Patients With Treated Familial Hypercholesterolemia. A Prospective Registry Study

R. R. Huxley DPhil; M. H. Hawkins DPhil; S. E. Humphries FRCPath; F. Karpe MD; H. A.W. Neil FRCP^*; and for the Simon Broome Familial Hyperlipidaemia Register Group and Scientific Steering Committee

From the Division Public Health and Primary Health Care, Institute of Health Sciences (R.R.H., H.A.W.N.), and Oxford Lipid Metabolism Group, Nuffield Department of Medicine (F.K.), University of Oxford, Oxford, UK; Department of Public Health and Epidemiology, University of Birmingham, Birmingham, UK (M.H.H.); and Cardiovascular Genetics, British Heart Foundation Laboratories, Royal Free and University College Medical School (S.E.H.).

^* To whom correspondence should be addressed. E-mail: andrew.neil{at}wolfson.ox.ac.uk.

Background and Purpose—Although it is recognized that in heterozygous familial hypercholesterolemia, large extracranial carotid vessels are affected by atherosclerosis, the risk of fatal stroke after treatment with cholesterol-lowering therapy remains uncertain. The goal of this study was to determine the risk of fatal stroke in patients with treated familial hypercholesterolemia.

Methods—A cohort of 1405 men and 1466 women with definite or possible heterozygous familial hypercholesterolemia was recruited from 21 outpatient lipid clinics in the United Kingdom. Patients were followed up prospectively from 1980 to 1998 for 22 992 person-years for a median duration of 7.9 years (interquartile range, 4.9 to 12.0 years). The mortality rate was calculated, and the standardized mortality ratio for men and women 20 to 79 years of age was derived from the ratio of the observed deaths to the number expected in the general population of England and Wales (standardized mortality ratio=100 for the standard population).

Results—A total of 169 deaths occurred; 9 (5.3%) were a result of stroke. The mortality rate from stroke was 0.39 per 1000 person-years (95% confidence interval, 0.18 to 0.74), and the standardized mortality ratio for fatal stroke was nonsignificantly lower than in the general population (79; 95% CI, 36 to 150).

Conclusions—The results suggest that patients with treated familial hypercholesterolemia are not at increased risk of fatal stroke. However, the possibility cannot be excluded that untreated individuals are at increased risk, which would be consistent with the evidence that familial hypercholesterolemia is a panvascular disease.

Key words: hypercholesterolemia, familial • mortality • stroke

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