Hyperlipidemia Flashcards
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*spefically remember: medication
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What lab results would suggest a genetic underlying cause of hyperlipidemia?
Is genetic testing routinely performed?
Why would diagnosis of genetic underlying cause be beneficial?
very high (>95% of normal) LDL
no, genetic testing is not routinely performed
diagnosis of underlying primary cause may aid in prognostic (risk of ASCVD, response to treatment, risks in family members)
What genetic disorders cause hypertriglyceridemia?
Combined hyperlipidemia?
Hypercholesterolemia?
In each of these disorder, also identify the protein defect & elevated lipoproteins
** specifically know family hypercholesterolemia
Fill out the provided table
- Pneumonic:
- One LP, Two LD, Three with E, Four gets more
- Most important
- Type 1: pancreatitis
- Type 2: tenxon xanthomas
- Type 3: palmar xanthomas
- Type 4: pancreatitis
How common is the homozygous & heterozygous forms of familial hypercholesterolemia?
Diagnostic criteria for each of these forms?
How is it diagnosed?
What is the relevent biochemisty of this mutation?
- Homozygous- rare
- total cholesterol 600-1000 mg/dL
- LDL 550-950 mg/dL
- Coronary heart disease & aortic stenosis
- Fatal MI before age 20 if untreated
- Heterozygous - 1/500
- total cholesterol 300-600 mg/dL
- LDL 250-500 mg/dL
- premature heart disease
- Typically diagnosed clinically based on values & family history
- Biochemistry
- mutation in LDL receptor
- increased total cholesterol & LDL
What are the imporant clinical considerations of Familial Defective Apolipoprotein B1000?
What is the relevant biochemistry of this mutation?
- Clinical Considerations
- autosomal dominant in 1/750 caucasions
- appearance similar to familial hypercholesterolemia but less severe
- Biochemistry
- defective Apo B100 causing poor LDL bindign to LDL receptor
- increased total cholesterol and LDL
What are the important clinical considerations of elevated plasma lipoprotein (a)?
What is the relevant biochemistry to this disorder?
- Clinical Considerations
- causes premature coronary heart disease
- 1:14 myocardial infarctions
- 1:7 aortic valve disease
- causes premature coronary heart disease
- Biochemistry
- increase in LDL binding to apolipoprotein (a)
- increased lipprotein (a) (aspecialized form of LDL)
What are the important clinical considerations of familial combined hyperlipoproteinemia?
What is the relevant biochemistry of this disorder?
- Clinical Considerations
- autosomal dominant polygenic condition affecting 1-2% of the population
- triglycerides >175, Total cholesterol >250, & HDL <35
- Biochemistry
- polygenic causes…
- increase VLDL production
- lipoprotein lipase gene defect
- elecated total cholesterol, LDL, & triglycerides
- decreased HDL
- polygenic causes…
What are the significant clinical considerations of familial dysbetalipoproteinemia?
What is the relevent biochemistry of this disorder?
- Clinical considerations
- only a problem when there is another issue…
- diabetes
- hypothyroidism
- alcohol consumption
- total cholesterol 300-400 mg/dL & Triglycerides 300-400 mg/dL
- only a problem when there is another issue…
- Biochemistry
- decreased ApoE2 affinity for LDL receptor
- increased triglycerides, total cholesterol & LDL
What are the significant clinical considerations of lipoprotein lipase deficiency?
What is the relevent biochemistry of this disorder?
- Clinical considerations
- homozygous: TG> 1,000 mg/dL
- heterozygous: TG 250-750 mg/dL
- worse with secondary factors
- diabetes estrogen therapy
- clinical presentations
- pancreatitis
- hepatosplenomegaly
- eruptive xanthomas
- lipemia retinalis (creamy white vessels)
- Biochemistry
- lipoprotein lipase (LPL) gene deficiency
- severely increased triglycerides
What are the significant clinical considerations of apolipoprotein C-II deficiency?
What is the relevent biochemistry of this disorder?
- clinical considerations
- autosomal recessive
- rare
- biochemistry
- Apo C-II deficiency causing decreaed liporotein lipase activation
- elevated triglycerides
What are the significant clinical considerations of familial hypertriglyceridemia?
What is the relevent biochemistry of this disorder?
- Clinical considerations
- autosomal dominant
- triglycerides 200-500mg/dL
- HDL <35mg/dL
- Biochemistry
- liver overproduces VLDL and increased catabolism of HDL
- elevated triglycerides & decreased HDL
Fill out the provided table by indicating which conditions cause elevated or reduced LDL?
Also, identify which conditions cause elevated or reduced HDL?
Identify the conditions that elevate VLDLs, IDLs, Chylomicrons, and Lp(a)s?
Saturated fats have have what impact on lipid levels?
What is the major conern with trans fats?
- Saturated fats increase
- total cholesterol
- LDL
- may or may not effect coronary heart disease
- Trans fats
- harmful in regards to cardiovascular health
Why can obesity lead to hyperlipidemi?
obesity can lead to insulin resistance , which can cause an incerease in liver synthesis of fatty acids & a decrease of lipolysis
decreased HDL and an increased triglycerides
it has a variable effect on LDL
Describe the following diseases effects on lipid
hypothyroidism
nephrotic syndrome
diabetes
liver failure
cholestasis
- hypothyroidism
- due to decrease in LDL receptor synthesis and function
- nephrotic syndrome
- comlex, but increased production of LDL and VLDL
- diabetes
- increased insulin–> increases HMG CoA reductase
- liver failure
- decreased cholesterol and triglycerides
- cholestasis
- decreased bile secretion –> increase in total cholesterol
Describe the effect of the following substances on lipids
estrogen
thiazides
beta blockers
clozapine & olanzapine
protease inhibitors
- estrogen
- elevated triglycerides and HDL (can be pronounced)
- thiazides
- elevated LDL and triglycerides
- beta blockers
- increased triglycerides and decreased HDL
- clozapine & olanzapine
- weight gain / obesity / diabetes –> elevated triglycerides
- protease inhibitors
- lipodystrophy –> elevated triglycerides
In the process of evaluating for hyperlipidemia, what will you be sure to ask about when taking a history?
Whtat will you be looking for during the physical?
What lab tests will you order?
- History
- family, social, medical (ASCVD, Nephrotic syndrome, diabetes, pancreatitis, etc.)
- Physical
- xanthoma (fatty deposits under eyes or on palms)
- hepatosplenomegaly
- Lab evaluation
- lipi panel
- creatinine
- urine protein
- urine protein
- liver enzymes
- thyroid stimulating hormone
- fasting glucose
the provided image is an example of what condition?
xanthoma
cholesterol rich deposition in the skin
What are the AHA screening guidelines for assessing cardiovascular risk?
What clinical findings warrent treatment?
assess risk factors for those age >21 every 4-6 years
- Risk factors
- smoking, diabetes, hypertension, HDL, total cholesterol
- Treatment is warrented if
- triglycerides >500mg/dL
- LDL-C >190
- secondary cause
- if primary cause, screen family
- unexplained ALT > 3x ULN
What is the goal of treating hyperlipidemia?
What are the 2 approaches to treatment?
- Goal
- reduce the risk of acute pancreatitis
- specifically when high triglycerides
- prevent coronary heart disease and decrease the risk of heart attack
- prolong life
- reduce the risk of acute pancreatitis
- Approaches
- therapeutic lifestyle changes
- decrease saturated fatty acids, trans fatty acids
- decrease added sugar intake
- increase exercise
- increase plant sterols and soluble fiber intake
- reduce body weight
- antihyperlipidemic drug therapy
- therapeutic lifestyle changes
What are the Key Points of the ACC / AHA guidelines?
- Heart healthy lifestyle should be emphasized across all age groups
- If patient has ASCVD (i.e. secondary prevention) treat wiht high dose statin theapy - atorvastatin or rosuvastatin (or maximally tolerated statin therapy)
- In high risk ASCVD patients, consider additional therapy with statin to goal LDL <70 (specific agents recommended)
- If LDL >190 recommend high dose statin therapy (do not need to calculate risk first)
- Diabetic patients age 40-75 with LDL >70, treat with moderate or high dose statin (based on risk factors)
- Before starting statin for primary prevention in those age 40-75, have a risk/benefit discussion
- In patients age 40-75 without DM and with LDL >70 and ADCVD risk score >7.5 start moderate dose statin (if risk/benefit discussion facors)
- In patients age 40-75 without DM but ASCVD risk score 7.5-19.9 consider risk factors and if present favor statin therapy
- In patients age 40-75 without DM and with LDL 70-160 and ASCVD score 7.5-19.9% but statin decision unclear, get coronary artery calcium measure
- Reassess for adherence to statin adn lifestye interventions
