10. Lipids in Heart Disease Flashcards
Why are lipids important to the body?
How are lipids synthesised (briefly)?
How do statins work?
What is cholesterol used to synthesise?
Consitituent of cell membranes, help absorb fat soluble vitamins, maintain membrane fluidity, thermal insulator and cellular metabolic regulator, hormone synthesis, organ padding.
Excess carb -> acetyl CoA -> malonyl CoA via acetyl CoA carboxylase -> FAs via fatty acid synthase.
Reduce serum cholesterol by inhibiting HMG CoA reductase (involved in making chol). Chol production by liver decreases and there’s increased clearance of LDL-cholesterol from the blood, reducing LDL-cholesterol levels. Also indirectly reduce triglycerides and slightly increase HDL-cholesterol levels.
Liver -> bile salts. Adrenals, gonads -> steroids. Lanosterol -> vit D.
List some modifiable and non-modifiable cardiovascular risk factors.
Briefly describe the pathophysiology of plaque formation.
What can VLDL be converted to?
Modifiable: smoking, high chol, hypertension, high BG, obesity.
Non-modifiable: age, gender, family history, ethnicity.
Endothelial injury. Activated endothelium. Inflammation and monocyte infiltration -> maturation to macrophages. Oxidised LDLs engulfed by macrophages -> foam cells -> die -> lipid-rich core of plaque. Contractile SM converted to proliferating SM -> secretes collagen and starts breaking down internal elastic lamina. Cytokines secretred by endothelium and macrophages stimulates migration of SM cells. Collagen forms fibrous cap. Fragility increased by calcification. Plaque may rupture -> collagen exposed to blood -> thrombus formation. (pic)
VLDL -> IDL -> LDL (large, buoyant) -> LDL (small, dense)
Describe the path of fats from the intestinal mucosa. What do LDLs and HDLs do?
What is hyperlipidaemia? What are the 2 categories?
What does a fasting lipid profile include?
Chylomicrons (CM) transport them to liver. In liver, CM release triglycerides and some cholesterol and become LDL. LDL carries fat and cholesterol to the body’s cells. HDL carry fat and cholesterol back to liver for excretion.
Abnormally elevated levels of any or all lipids or lipoproteins in the blood.
Primary: familial, caused by specific genetic abnormalities.
Secondary: resulting from another underlying disorder. More common.
Serum total cholesterol, serum LDL cholestrol, serum HDL cholesterol, cholesterol-HDL ratio, serum (fasting) triglyceride.
List some causes of 2o hyperlipidaemia.
Describe 3 1o hereditary causes of hyperlipidemia:
a) Familial hypercholesterolemia (FH)
b) Familial combined hyperlipidemia
c) Dysbetalipoproteinemia
Diet, alcohol, hypothyroidism, nephrotic syndrome, anorexia nervosa, obstructive liver disease, obesity, diabetes mellitus, pregnancy, acute hepatitis, SLE, drug induced (thiazides, β-blockers, antiretrovirals, anti-depressants).
a) Autosomal dominant genetic disorder, occurs in heterozygous form. Occurs in 1/500. Mutation in LDL receptor (normally receptor on liver, clears LDL from blood)= elevated LDL at birth and through life. High risk for atherosclerosis, premature CHD, tendon xanthomas (75%), tuberous xanthomas, xanthelasmas of eyes. Important to ID those with FH/poss FH. Early tx = normal life expectancy. Consider FH in all adults with total cholesterol >7.5mmol/L
b) Autosomal dominant, increased secretions of VLDLs
c) 1/10,000, results in apo E2 (binding-defective form of apoE, which usually plays important role in catabolism of chylomicron and VLDLD). Increased risk of atherosclerosis, peripheral vascular disease. Tuberous xathomas, striae palmaris.
What is the Simon Broome criteria?
CDV risk examination tools should not be used on pts with suspected FH. What should all patients with definite/possible FH be offered?
Used to make diagnosis of definite/possible FH (familial hypercholesterolaemia).
Diagnose definite FH in adult with: total cholesterol >7.5 and LDL-C >4.9 AND tendon xanthomata/ evidence of these in 1st or 2nd degree relative. OR an identified genetic mutaion for FH.
Diagnose possible FH in adult with: total cholesterol >7.5 and LDL-C >4.9 and at least one of:
1) Family hx premature CHD e.g. MI aged <60 in 1st deg relative or <50 in 2nd deg relative.
2) Family hx raised total cholesterol in 1st or 2nd deg relative (>7.5 in adult OR >5.7 in child).
Referral to specialist lipid clinic to confirm dx, initiate cascade testing, and treat.
What effect can tissue lipid accumulation have on:
a) arterial walls
b) subcutaneous tissue
c) tendons
d) cornea
a) IDL/LDL associated cholesterol accumulation, fibrous tissue formation, atheromatous plaques
b) Eruptive xanthomata: small itchy nodules, VLDL/chylomicron associated, reversible (pic). Tuberous xanthomata: yellow plaques over elbows/knees, IDL induced. Xanthelasma: periorbital skin deposits, LDL associated.
c) Tendon xanthomata - extensor tendons, Achiles tendons (in FH)
d) Corenal arcus (pic), <40 yo
Name a statin a patient with high cholesterol may typically be started on.
If the drug above is not tolerated, what else could be given?
What is mixed hyperlipidaemia?
What can you conclude from the investigation results? How would the pt be managed?
Atorvastatin - competitive inhibitor of HMG-CoA reductase.
Ezetimibe - decreases cholesterol absorption in small intestine.
Both chylomicrons and VLDL are high.
Total chol high. High triglycerides. Hypothyroidism. Diabetes. Urate high. CK high (could be due to ethnicity + hypothyroidism).
MX: Insulin, levothyroxine mainly.
DX: 2o hyperlipidaemia 2o to hypothyroidism, diabetes and metabolic syndrome.
What can you conclude from the investigation results? How would the pt be managed?
Only thing that is high is total chol and LDL-C. Pt started on atorvastatin. Ezetimibe added after suboptimal response.
DX: 1o hyperlipidaemia - familial hypercholesterolaemic.
