Title
Additional risk factors influence excess mortality in heterozygous familial hypercholesterolaemia
Author
TNO Preventie en Gezondheid
Sijbrands, E.J.G.
Westendorp, R.G.J.
Paola Lombardi, M.
Havekes, L.M.
Frants, R.R.
Kastelein, J.J.P.
Smelt, A.H.M.
Publication year
2000
Abstract
Life expectancy of patients with familial hypercholesterolaemia is decreased. Some untreated patients reach a normal life span and, therefore, additional risk factors and the type of mutation in the low-density lipoprotein (LDL) receptor gene are likely to influence the clinical outcome. We determined all cause mortality in kindreds with the disorder, who were untreated, in order to study (a) additional risk factors for coronary artery disease (CAD) and (b) the types of LDL receptor gene mutations that may contribute to a poor prognosis. The mortality in all 855 first-degree relatives of 113 unrelated patients was compared to the Dutch population after standardisation for age, gender, and calendar period. Analyses restricted to affected relatives could have underestimated the mortality risk due to lack of information about severe cases, who died prematurely. Therefore, all first-degree relatives were analysed and as a result the standardised mortality ratios (SMRs) exhibit only 50% of the excess mortality from familial hypercholesterolaemia. We observed 190 deaths in 32048 person-years leading to an overall SMR of 1.34 (95% confidence interval (CI) 1.16-1.55, P=0.001). High excess mortality occurred in males between age 40 and 54 (SMR 2.34, 95% CI 1.60-3.31, P
Subject
CAD, coronary artery disease
CI, confidence interval
HDL, high-density lipoprotein
LDL, low-density lipoprotein
SMR, standardised mortality ratio
High density lipoprotein cholesterol
Low density lipoprotein cholesterol
Low density lipoprotein receptor
Allele
Cholesterol blood level
Clinical trial
Controlled clinical trial
Controlled study
Coronary artery disease
Family
Gene expression
Gene mutation
Human experiment
Human tissue
Hypercholesterolemia
Hyperlipoproteinemia type 2
Life expectancy
Major clinical study
Mortality
statistical analysis
Adolescent
Adult
Age Distribution
Aged
Aged, 80 and over
Child
Child, Preschool
Confidence Intervals
Coronary Disease
Data Collection
Female
Heterozygote
Humans
Hyperlipoproteinemia Type II
Male
Middle Aged
Poisson Distribution
Proportional Hazards Models
Risk Factors
Sex Distribution
Survival Analysis
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DOI
https://doi.org/10.1016/s0021-9150(99)00336-6
TNO identifier
235505
ISSN
0021-9150
Source
Atherosclerosis, 149 (149), 421-425
Document type
article