CVD 2 Flashcards
Apo E2/E2 genotype
1% mutation where apoE-2 does not bind LDL receptors which increases VLDL remnants leading to plaque build up
Normally HDL competes VLDL due to apoE but in apoE-2 HDL cannot keep up clearance of CE
Primary dyslipidemia causes, diagnosis and categories
Single/polygenic abnormalities affecting lipoprotein function –> hyperlipidemia/hypolidipemia
Diagnosis: history or onset, physical signs, lipid/apoprotein/LPL activity biomarkers, serum appearance and genetic sequencing
Hypolipoproteinemias and Hyperlipoproteinemias
Hypolipoproteinemias types and biomarkers
Hypolipoproteinemias:
1) Abetalipoproteinemia: defective apoprotein B synthesis
2) Familial hypobetalipoproteinemia: [LDL] 10-50% of normal + chylomicron formation
3) Familial alpha-lipoprotein deficiency (Tangier disease): absence of HDL (Apo-AI), CE accumulation in tissues and mdoerate hyperTG
Hyperlipoproteinemias types I - IIb, biomarkers and main symptoms
Most common
I: Hyperchylomicronemia –> skin xanthomas, pancreatitis
Pale, fatty serum
IIa: Hypercholesterolemia –> vascular disease and xanthelasma
Dark serum
IIb: Combined hyperproteinemia
↑ LDL + VLDL, mutation of LDL receptor or ↑ ApoB
Other: ↓ HDL + ↑ Chol + TG –> vascular diseases
Pink serum
Hyperlipoproteinemias types III - V, biomarkers and main symptoms
III: Dysbetalipoproteinemia –> tuberoeruptive and palmar xanthomas
Pink serum + some fatty layer
IV: Hypertriglyceridemia
High VLDL affected
Other: ↑ TG/↓HDL
Worsened by alcohol and diabetes
White serum
V: Mixed hyperlipidemia
White serum + fatty layer
Secondary dyslipidemia defining features and causes (lifestyle, diseases and meds)
Non genetic, more prevalent and can exacerbate primary dyslipidemia
Causes: diet (high chol, satfat trans fat and sugar), alcohol, smoking and lack of PA
- Sugar ↓ HDL and ↑ TG
- Saturated fat ↑ chol, LDL and HDL
- Transfat ↑ Chol/LDL and ↓ HDL
- Alcohol ↑ HDL and TG
Disease causes: diabetes, hypothyroidism, renal failure, obesity, cholestasis, cirrhosis, myelomas, and Cushing syndrome
Can also be caused by medications such as thiazides, beta-blockers, corticosteroids, estrogens, progesterone, benzos, retinoic acid and antiretrovirals
How does obesity effect lipoprotein metabolism?
What is the lipolytic effect?
What is the cause of hypercholesterolemia in obesity?
Postprandial: Excess lipids/CHO increase substrate flux to liver
OR
Postabsorptive: high WAT + hormone-sensitive lipase activity due to IR ↑ FFA flux to liver
OR
Alcohol decrease acyl-coA oxidation
↑ Increased FFA flux to liver = ↑ VLDL production –> VLDL remnants return to liver or become LDL
Lipolytic effect: ↑ VLDL which are high in TAG cause ↑ lipolysis by vascular endothelial LPL causing hypertriglyceridemia
Hypercholesterolemia caused by satfat/FA/chol intake which ↓ hepatic LDL-R activity causing ↑ VLDL/LDL-C through ⊣ uptake
Theory for ↓ HDL-C in obesity
Associated phenotypes with low HDL-C
More CE transfer by CETP from HDL to VLDL in exchange for lipids inside the liver –> ↑ HDL lipids causes their increases catabolism by the liver
BMI inverse linear correlation with HDL (more so than LDL)
- Not a good indicator of clinical obesity
Abdominal/visceral fat/WC increases risk of low HDL more so than total body fat
- Stronger association in men and post-meno women
Canadian Cardiovascular Society’s Dyslipidemia Guidelines 2021: Who to screen?
Screen men + women ≥ 40 or post-meno or anyone with a related condition
How to screen: history, physical exam, lipid profile, FPG/A1c, eGFR, lipoprotein(a) 1x, apoB and albumin:creatinine urine ratio
- Secondary testing: Coronary artery calcium (CAC) Measurement ≥ 40 or intermediate risk patients
Framingham Risk Score (FRS)
Double CVD risk for who?
Statin indicated conditions and risk stratification
Tool for assessing 10-year CVD risk based on a 20-year long study
2x risk for 30-59 yo w/o diabetes if FHx of premature CVD in 1° family member (< 55 men, <65 women)
Statin indicated conditions are automatically considered high risk
LDL ≥ 5 mmol/L: Low risk < 10% risk
T2D and CKD: intermediate risk FRS 10-19.9%
Atherosclerotic CVD (ASCVD): high risk FRS ≥ 20%
Apoproteins traded between chylomicrons and HDL
Apoproteins traded between VLDL and HDL
TG from HDL –> chylomicrons are ApoC + ApoE
TG from chylomicrons –> HDL are ApoA + ApoC
TG from HDL –> VLDL are ApoC + ApoE
TG from VLDL –> HDL are ApoC
–> VLDL can be taken by liver, converted to LDL and taken by liver or converted to LDL and taken by extrahepatic tissues
Simplified steps of reverse cholesterol transport
1) Efflux of cholesterol
2) Esterification: Nascent HDL –> HDL
3) Transfer: HDL passes CE w/ CETP to VLDL, LDL and other HDL for hepatic clearance
4) Hepatic clearance
Primary and alternate targets for high and moderate risk groups based on FRS scores
≥ 20% FRS score: treatment for all
1° Goal: ≤ 2 mmol/L or ≥ 50% ↓ LDL-C
Alternate target: apoB ≤ 0.8 g/L or non-HDL-C ≤ 2.6 mmol/L
10-19% FRS score: treat if LDL-C ≥ 3.5 mmol/L or additional risk factor with ≥50 men or ≥ 60 women (low HDL-C, impair FBG, high WC, smoker, HTN)
