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Eric Sijbrands Erasmus University Medical Center Rotterdam Mortality from familial hypercholesterolemia (FH)

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Presentation on theme: "Eric Sijbrands Erasmus University Medical Center Rotterdam Mortality from familial hypercholesterolemia (FH)"— Presentation transcript:

1 Eric Sijbrands Erasmus University Medical Center Rotterdam Mortality from familial hypercholesterolemia (FH)

2 Eric Sijbrands Eric Sijbrands is consultant in internal medicine and head of the lipid clinic of the Erasmus University Medical Center Rotterdam. After he obtained his qualification as medical doctor in 1990, he was given the opportunity to receive his training in internal medicine and to work in scientific research at the Universities of Leiden and Amsterdam. He made a Ph.D. thesis on gene-gene and gene-environment interaction in patients with genetic hyperlipidemia. His present research is focussed on genetic epidemiology of cardiovascular disease (hyperlipidemia, diabetes mellitus, and pharmacogenetics of hypertension). resume

3 Learning objectives selection on outcome standardization burden of monogenetic disorder genetic heterogeneity gene-environment interaction

4 Performance objectives understand the clinical consequences of monogenetic disorders

5 FH - characteristics autosomal dominant autosomal dominant heterozygosity 1:500 heterozygosity 1:500 mutations in the LDL receptor gene on chromosome 19 mutations in the LDL receptor gene on chromosome 19 total cholesterol > 8 mmol/L total cholesterol > 8 mmol/L tendon xanthomas tendon xanthomas introduction

6 FH - what is already known cardiovascular disease cardiovascular disease at young age excess mortality excess mortality population data are lacking population data are lacking introduction

7 Burden of untreated FH introduction analyses of mortality in: a large pedigree free from selection on CVD 113 small pedigrees referred to a lipid clinic

8 Monogenetic disorder cause disease death introduction

9 Monogenetic disorder introduction additional factors cause disease death

10 Natural history introduction

11 Large pedigree: FH-V408M Sijbrands EJG, et al. BMJ 2001;322: introduction

12 Standardization SMR = observed / expected deaths strata per gender strata per age category strata per calendar period introduction

13 SMR V408Mdeathp.y.SMR(95%CI) 50% ( ) 100% ( ) large pedigree

14 SMR

15 Kaplan-Meier

16 Conclusion 1 gene-environment interaction large pedigree

17 113 small pedigrees number cardiologist39 GP51 insurance 4 other19 total113 outpatient lipid clinic Sijbrands EJG, et al. Atherosclerosis 1998;136:

18 characteristicn=113 male / female55/58 age48 (20 to 69) xanthomas66 cholesterol mmol/L 113 FH patients outpatient lipid clinic

19 SMR agedeathsp.y.SMR(95%CI) ( ) ( ) ( ) ( ) ( ) ( ) ( ) outpatient lipid clinic

20 SMR

21 Other risk factors premature CVDSMR95% CI – (51 families) (62 families) RR + versus – outpatient lipid clinic

22 Type of LDLR mutation characteristic mRNA +mRNA -p (n=24)(n=14) male, % age BMI xanthomas, % LDL-C HDL-C outpatient lipid clinic

23 Type of LDLR mutation outpatient lipid clinic

24 Conclusion 2 other risk factors for CVD type of mutation is not relevant outpatient lipid clinic

25 FH - what these studies add many untreated patients (40%) reach a normal life span burden of FH depends on time variation in mortality suggests an interaction between genetic and environmental CVD risk factors

26 Future... individual risk – molecular diagnosis – additional genes – environmental factors exact indication for tailored intervention


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