1 / 26

Genetics of Cardiovascular Disease

Genetics of Cardiovascular Disease. John N. Hamaty D.O. FACC, FACOI. Cardiovascular Genetics. Environmental causes- trauma, malnutrition, drug abuse-defined by body response- phenotype Genotype- how patient suffers or recovers

conan
Download Presentation

Genetics of Cardiovascular Disease

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Genetics of Cardiovascular Disease John N. Hamaty D.O. FACC, FACOI

  2. Cardiovascular Genetics • Environmental causes- trauma, malnutrition, drug abuse-defined by body response- phenotype • Genotype-how patient suffers or recovers • Therefore, genetics plays a role in both cause and process; etiology and pathogenesis

  3. Cardiovascular Genetics • Genotype-detrimental in two distinct ways- • Mutant genes upset embryology or physiology • Known as genetic diseases • Facilitate the action of an extrinsic cause in producing a disease-coronary artery disease • Inherited susceptibilities

  4. Cardiovascular Disorders Associated with Chromosome Aberrations • Trisomy 21- Downs Syndrome • Most common phenotype • 1/600 births • Maternal age; >35 years and greatest >45(4%) • CHD present in 40-50% • Endocardial cushion defect • Atrial septal defect with cleft mitral valve • Pulmonary Hypertention

  5. Cardiovascular Disorders Associated with Chromosome Aberrations • Turner syndrome- 45,X karyotype • 1/2500 females lacks an X chromosome • Short stature or amenorrhea is evaluated • 20-50% report cardiovascular abnormalities • Aortic coarctation • Bicuspid aortic valve • Dilated aortic root

  6. Congenital Heart Disease • Incidence- 3.1-3.5/1000 • Two mechanisms- multifactorial and mutations of single genes

  7. Multifactorial Processes • Familial Atrial Septal Defect-primum/secundum • Holt-Oram Syndrome-autosomal dominant • Dysplasia of upper limbs and ASD “Digitalization of the thumb” Secundum ASD

  8. Supravalvular Aortic Stenosis • Asymptomatic • Williams Syndrome-sporadic,,haighly variable autosomal dominant • Elfin facies • Pulmonic stenosis • Supravalvular aortic stenosis • Mitral valve prolapse

  9. Mitral Valve Prolapse • Heterogeneous • Most common abnormality of human heart valve • Autosomal dominant-minimal form • Autosomal dominant-variable • Marfan syndrome

  10. Teratogenic Effects • Ethanol- 50% CHD: VSD, ASD • Most common teratogen to which fetal embryo and fetus are exposed-first trimester • Warfarin- 10% CHD: PDA, PS, intracranial hemorrhage • Fetal Rubella- 50% of fetuses become infected with rubella virus when mother is infected during first trimester. PDA and ASD, PS

  11. Hypertrophic Cardiomyopathy • Phenotype is anatomic and histologic • Myocardial hypertrophy without secondary cause; cellular and myofiber disarray, fibrosis and cad. • No pathognomonic findings • Affects first degree relatives and in families the phenotype is inherited and an autosomal dominant, familial hypertrophic cardiomyopathy

  12. Hypertrophic Cardiomyopathy • Wide range of expression due to age • Older age has less expression • Therefore, pedigree screening by phenotype for clinical, counseling purposes isn’t complete without the following: • Echocardiogram-segmental hypertrophy • LVH without any other explanation

  13. Hypertrophic Cardiomyopathy • FHC-disease of the sarcomere • Classic mutations of at least six loci • The first is 14q1 and the cardiac B-myosin heavy chain gene • 50% of all FHC occur here

  14. HYPERLIPIDEMIA and ATHEROSCLEROSIS FOCUS ON CORONARY HEART DISEASE AND TREATMENT John N. Hamaty D.O. FACC, FACOI

  15. Small dense LDL • LDL A-large buoyant particles • LDL B-small dense particles • Oxidization of LDL results in exposure to endothelial cells, smooth muscle cell and macrophages • Oxidized LDL-adherence to arterial wall-activation of macrophages

  16. High Dense Lipoproteins • Secreted by the liver and intestine • Lecithin activity of cholesterol acyltransferase is generated from the phospholipid and cholesterol molecules producing HDL • HDL-2 and HDL-3 • Women have higher levels

  17. Development of Atherosclerotic Plaques Fatty streak Normal Lipid-rich plaque Foam cells Fibrous cap Lipid core Thrombus

More Related