Hyperlipidemias Flashcards
Primary causes of hyperlipidemia
familial dyslipidemia syndrome
types IIa, IIb, and IV account for >80% of all familial dyslipidemias
Hyperlipidemia basics
modifiable risk factor for coronary artery disease!
causes accelerated atherosclerosis
Secondary causes of hyperlipidemia
- endocrine disorders: hypothyroidism, diabetes mellitus, Cushing’s syndrome
- renal disorders: nephrotic syndrome, uremia
- chronic liver disease
- medications: glucocorticoids, estrogen, thiazide diuretics, beta blockers
- pregnancy
Clinical pearl: Risk factors for coronary artery disease in evaluation of patients with hyperlipidemia
(p. 433)
current cigarette smoking (dose-dependent risk), hypertension, diabetes mellitus, low HDL cholesterol (60 mg/dL) is negative risk factor (subtract 1 from total), age (male:>45 years, female: >55 years), male gender (if you count this as risk factor do not count age), family hx of premature CAD (MI/sudden death in male first degree relative <65 yo)
Dietary risk factors for hyperlipidemia
saturated fatty acids and cholesterol –> elevation in LDL + total cholesterol
high-calorie diets do not increase LDL or cholesterol levels (are “neutral”) but do increase triglyceride levels
alcohol –> increase triglyceride levels but does not affect total cholesterol levels
Risk factors for hyperlipidemia
- diet
- age (cholesterol levels increase with age until about 65 yrs;
greatest increase in early adulthood 2 mg/dL per yr) - inactive lifestyle, abdominal obesity
- family hx hyperlipidemia
- gender (men generally > cholesterol levels than women); when women reach menopause cholesterol levels equalize (and may be higher in women)
- medications: thiazides (increase LDL, total cholesterol, triglycerides (VLDL levels); beta blockers (propanolol-increases triglycerides (VLDL) and lower HDL levels); estrogens (triglyceride levels may further increase in patients with hypertriglyceridemia); corticosteroids and HIV protease inhibitors can elevate serum lipids
- genetic mutations that predispose to most severe hyperlipidemias
- secondary causes of dyslipidemia
LDL cholesterol and CAD risk
accounts for 2/3 of total cholesterol
CAD risk primarily due to LDL component bc LDL thought to be the most atherogenic of all lipoproteins
Levels > 160 mg/dL significantly increase CAD risk
–> LDL cholesterol not directly measured but calculated:
LDL = total cholesterol - HDL - TG/5
Threshold levels for hyperlipidemia: total cholesterol
all in mg/dL:
ideal: 240
remember: total cholesterol will be higher than LDL!
Threshold levels for hyperlipidemia (LDL)
all in mg/dL:
ideal: 160
Threshold levels for hyperlipidemia (triglycerides)
for Triglycerides high level is Two Times low level
“T”
all in mg/dL:
ideal: 250
uncertain whether lowering triglyceride levels reduces coronary risk
HDL cholesterol
- protective effect (removes excess cholesterol from arterial walls) at least as strong as atherogenic effect of LDL
- for every 10 mg/dL increase in HDL level, CAD risk decreases by 50%
Low HDL ( 60 mg/dL) = “negative” risk factor (counteracts one risk factor)
Total cholesterol to HDL ratio
average/standard risk: 5.0
desirable: <4.5
LDL levels in diabetic patients
goal for LDL in diabetic patient: 100 mg/dL or lower
all diabetics with LDL > 100 mg/dL should be started on statin
if patient has CAD and diabetes mellitus: goal for LDL is 70 mg/dL or less
Clinical features hyperlipidemia
most patients asymptomatic
if severe, may see:
- Xanthelasma: yellow plaques on eyelids
- Xanthoma: hard, yellowish masses found on tendons (finger extensors, Achilles’ tendon, plantar tendons)
- Pancreatitis can occur with severe hypertriglyceridemia
Diagnosis of Hyperlipidemia
- lipid screening
- measure total cholesterol and HDL levels (nonfasting ok)
- -> if either abnormal, order full fasting lipid profile - full fasting lipid profile: triglyceride levels + calculation of LDL levels
- consider checking laboratory tests to exclude secondary causes of hyperlipidemia:
a. TSH (hypothyroidism)
b. LFTs (chronic liver disease)
c. BUN and Cr, urinary proteins (nephrotic syndrome)
d. glucose levels (diabetes)
Statins and fibrates and liver “function”!
statins and fibrates can induce transient elevation in serum transaminases
LFT must be monitored
all patients on statins should have AST and ALT monitored even if asymptomatic
(about 1% of patients on statins will develop elevations in AST and ALT such that statin will need to be discontinued)
Treatment of hyperlipidemia
long-term goal: reduce coronary heart disease
short-term goal: reduce LDL levels
if patient has no established CHD: target LDL < 100 mg/dL
Statin beneficial effects
significantly reduce rates of MI, stroke, coronary and all-cause mortality
statins are most common drugs used!
can reduce LDL by 20-60%
–> added benefit: statins also have antioxidant effect on endothelial lining of coronary arteries
Coronary heart disease risk equivalents
diabetes mellitus, peripheral vascular disease, coronary artery disease, abdominal aortic aneurysm
Therapy for hyperlipidemia: CHD or CHD risk equivalents
LDL goal: < 100 mg/dL
Initiate lifestyle changes: 100 mg/dL (all patients regardless of LDL)
Consider drug therapy: 130 mg/dL
Therapy for hyperlipidemia (No CHD but > 2 risk factors)
all in mg/dL
LDL goal: <130
initiate lifestyle change: 130 (all pts regardless of LDL)
consider drug therapy: 130
Therapy for hyperlipidemia (No CHD but 2 risk factors)
all in mg/dL
LDL goal: 130
initiate lifestyle changes: 130
consider drug therapy: 160
Therapy for hyperlipidemia (No CHD and 0-1 risk factors)
all in mg/dL
LDL goal: 160
initiate lifestyle changes: 160
consider drug therapy: 190
Therapy for high LDL cholesterol
- dietary therapy (lowering fat intake esp sat fat reduces serum cholesterol more than lowering cholesterol intake)
- -> foods rich in omega 3 fatty acids (fish)
LDL can be reduced by 10% on avg:
<300 mg/day cholesterol
exercise (increases HDL, lowers BP, enhances efficiency of peripheral oxygen extraction) weight loss (reduces myocardial work, risk of diabetes)
HMG CoA reductase inhibitors (statins)
Drug therapy hyperlipidemia
effects: lower LDL levels (most potent for lowering LDL); minimal effect on HDL and TG levels
comments: have been shown to reduce mortality from cardiovascular events and significantly reduce total mortality
* drugs of choice for lowering LDL*
side effects: monitor LFTs (monthly for 1st 3 months, then every 3-6 months). Harmless elevation in muscle enzymes (creatine phosphokinase) may occur
First line treatment hyperlipidemia
Patients given drug therapy should almost always be treated with statin
statins can reduce relative cardiovascular risk by 20-30% regardless of baseline LDL levels
Niacin
drug therapy hyperlipidemia
effects: lowers TG levels, lowers LDL levels, increases HDL levels
comments: do not use in diabetic patients (may worsen glycemic control
- -> most potent agent for increasing HDL levels and lowering TG levels
side effects: flushing effect (cutaneous flushing of face/arms; pruritus may be present);
Check LFTs and Creatine phosphokinase levels as with statin drugs
Bile acid-binding resins (cholestyramine, colestipol)
drug therapy for hyperlipidemia
effects: lowers LDL, increases triglyceride levels
comments: effective when used in combination with statins or niacin to treat severe disease in high-risk patients
side effects: adverse GI side effects, poorly tolerated
–> useful in treating bile salt-induced diarrhea (e.g., resection distal ileum) but worsens bile salt depletion (e.g., ileal resection > 100 cm)
Fibrates (gemfibrozil)
drug therapy for hyperlipidemia
effects: lower VLDL and TG, increase HDL
comments: primarily for lowering TG levels
side effects: GI side effects (mild), mild abnormalities in LFTs, gynecomastia, gallstones, weight gain, myopathies
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Amiodarone affects:
Statin metabolism
