Chapter 15 - Familial arteriosclerosis Flashcards
Familial hypercholesterolemia
1) metabolic disorder
2) severe hypercholesterolemia
3) accumulation of LDL in plasma and cholesterol in tendons
4) premature CAD age 30-40
Gene mutation in familial hypercholesterolemia
AUTOSOMAL DOMINANT
1) LDL receptor
2) apoB (binds LDL receptor)
3) proprotein convertase subtilisin/kexin type 9 (PCSK9) - degrades LDL receptor
AUTOSOMAL RECESSIVE
1) hypercholesterolemia protein LDLRAP - clears LDL
Rate of heterozygous FH
60-80% of all FH
prevalence 1/200-500
Rate of homozygous FH
1/160000-1 million
When does HoFH and HeFH manifest
HeFH 50% CV event by age 50 in men; 30% at 60 in women
HoFH most event in mid 20’s
LDLR defect classes
Class 1: promotor mutation, no detectable miRNA and no LDLR
Class 2: mutation that regard maturation of LDLR with glycosylation (2A complete; 2B incomplete)
Class 3: mature LDLR cannot bind ligand
Class 4: mature LDLR cannot internalize
Class 5: LDLR degradation before reach surface
Class 6: LDLR cannot reach correct surface due to wrong signalling
Epigenetics
Change in gene expression resulting from factors other than direct change in DNA sequence of genome
Diagnostic criteria for familial hypercholesterolemia
Family history: premature CAD (<55 men; <60 women) in first degree relative
Clinical history: premature CAD/CVD
Lab: LDL > 250 in adults or > 200 in age younger than 20
PHysical: tendonxanthomas, arcus cornealis
Genetic: mutation in LDLR, ApoB, PCSK9
No secondary causes
MODY define
Maturity onset diabetes of the young
Treatment of FH
1) fat modified heart healthy diet starting age 8-10
2) reduce LDL by 50%
3) target LDL < 130 (3.5)
HoFH needs to start tx asap and be at specialized center
Familial hypertension treatment
1) ACEi
2) CCB
3) thiazide
4) spironolactone
5) beta-blocker
Treatment drugs for obesity
1) Sibutramine - serotonin/noradrenaline reuptake inhibitor
2) Orlistat - pancreatic lipase inhibitor
3) Rimonabant - cannabinoid type 1 receptor antagonist
