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A. Contributors to Elevated Cholesterol (Chol)navigator

  1. Diet
    1. Fatty foods increase serum chol
    2. Trans fatty acids particularly dangerous [23,43]
  2. Diabetes Mellitus (DM)
    1. DM with high chol (usually high triglycerides)
    2. As part of insulin resistance syndrome
  3. Smoking
  4. Other Underlying Causes of and Contributors to Elevated Chol
    1. Chronic Renal Failure [21]
    2. Nephrotic Syndrome
    3. Hypothyroidism [2]
  5. Medications
    1. Certain atypical antipsychotics: Olanazepine (Zyprexa®), others
    2. HIV protease inhibitors
    3. Glucocorticoids
    4. Thiazide diuretics
    5. Certain ß-adrenergic blockers
    6. Cyclosporine and related molecules
  6. Familial Hypercholesterolemia

B. Effects of Elevated Cholnavigator

  1. Increased risk for all types of vascular disease
    1. Coronary Artery Disease (CAD)
    2. Cerebrovascular Disease
    3. Peripheral Arterial Disease (PAD)
  2. Chol Level and Mortality [4]
    1. Linear relationship between chol level and mortality across cultures
    2. Total chol and total/HDL chol strongly associated with CAD mortality [4]
    3. Total/HDL chol is the best overall predictor of CAD mortality [4]
    4. Much weaker association of chol with stroke
    5. Chol effects on CAD mortality independent of age and blood pressure
    6. Chol effects on CAD mortality are more pronounced in age 40-49 than in 70-89 years
    7. In another study, low HDL chol (but not total) predicts CAD mortality in both sexes [27]
    8. Individuals with exceptional longetvity (mean 98 years) have significantly larger HDL and LDL particle sizes, and increased homozyogosity for I405V variant in CETP [3]
    9. Increasing HDL improves cardiovascular (CV) outcomes [27,36]
  3. In a direct comparison study, ratio of apolipoprotein B100 (ApoB) to apolipoprotein A (Apo A) was a better predictor of myocardial infarction (MI) than any Chol ratio [57]

C. Biochemistry of Chol Transport [6,7] navigator

  1. Chol is absorbed from the gut and made in the liver
  2. Synthesis is based on acetate conversion to chol
  3. Chol is transported on particles composed of lipids and proteins
  4. These particles are identified by their relative densities:
    1. High denisty lipoprotein (HDL)
    2. Low density lipoprotein (LDL)
    3. Very low density lipoprotein (VLDL)
    4. Intermediate density lipoprotein (IDL)
    5. LDL, IDL, VLDL include apolipoprotein B (ApoB)
    6. Serum ApoB levels correlate with total LDL+IDL+VLDL
    7. Elevated ApoB and high ApoB/ApoA1 ratios may be best markers for coronary risk [5,26]
  5. HDL [27]
    1. HDL carries chol to liver for storage
    2. Increasing HDL will lead to decreased serum chol
    3. HDL retards accumulation of lipid peroxides on LDL (probably by hydrolysis)
    4. HDL <40mg/dL in men and <50mg/dL in women associated with increase cardiac risk [27]
    5. Apolipoprotein A1 (Apo A1) is the major protein component of HDL
    6. High levels of Apo A1 are associated with elevated HDL levels and reduced CAD risk
    7. Increased Apo A1 are associated with reduced risk for fatal MI [26]
    8. An Apo A1 variant "Milano" associated with low HDL (10-30mg/dL) but low rates of CAD
    9. Apo A1 Milano infusions induce regression of coronary atherosclerosis [39]
  6. LDL [7]
    1. LDL carries chol from liver to periphery
    2. Spherical particle composed of phospholipid monolayer, free chol, chol ester, one ApoB100
    3. LDL increases lead to increases in serum chol
    4. LDL binds to the LDL receptor through the ApoB100 protein component
    5. Mutation in the LDL receptor can cause familial severe hypercholesterolemia
    6. Apolipoprotein B100 (Apo B) levels correlate well with total LDL chol (+ VLDL chol)
    7. Increased Apo B is a risk factor MI [26]
    8. ApoB/Apo A1 ratio does not add to CV risk prediction if total chol:HDL is present [29]
    9. In a separate direct comparison study, ratio of ApoB to Apo A was a better predictor of MI than any Chol ratio [57]
    10. Small dense particles are easily oxidized and bind less well to LDL receptors
    11. Subsets of LDL: LDL A, LDL B, oxidized LDL
  7. LDL A and B
    1. Larger particles, more boyant, called LDL A
    2. LDL B are small, dense LDL particles and are particularly atherogenic
    3. Most LDL B particles are formed from LDL A particles
  8. Oxidized LDL [11]
    1. Oxidized LDL (mainly LDL B type) are toxic to endothelium
    2. Oxidized LDL is likely carried in plasma by Lp(a), and possibly C reactive protein (CRP)
    3. These oxidized LDL are normally taken up by macrophages
    4. Macrophages express scavenger receptors, which take up oxidized LDL
    5. Macrophage uptake of oxidized LDL is not regulated
    6. This is in contrast to uptake of normal LDL by macrophage LDL receptor (regulated)
    7. Foam cells are macrophages engourged with oxidized LDL
    8. Elevated levels of oxidized LDL associated with increased risk of metabolic syndrome [47]
  9. LP(a) Liporotein [9,10,11]
    1. Lp(a) - apolipoprotein B100 (Apo B) with apolipoprotein(a) covalently bound
    2. Oxidized phospholipids are strongly associated with Lp(a) in human plasma
    3. Lp(a) has side chain of repeating kringles with homology to plasminogen
    4. Thus, Lp(a) competes for plasminogen receptors on endothelium, a prothrombotic event
    5. Oxidized LDL is likely a major link between atherosclerosis and inflammation
    6. Lp(a) levels show independent correlation with CAD in men and possibly women [9]
    7. Lp(a) >300mg/L are 2X risk factor for venous thromboembolism [19]
  10. Triglycerides [6]
    1. Carried mainly in chylomicrons, VLDL and IDL
    2. Elevated nonfasting triglycerides associated with ~2X increased CAD risk [31,52]
    3. Elevated fasting triglycerides over time associated with 3-8X increased CAD risk in men [25]
  11. VLDL
    1. VLDL carries triglycerides from liver to LDL
    2. Composed of phospholipid monolayer, 90% triglycerides, 10% chol, one ApoB100
    3. VLDL particles are much larger than LDL and ~9X fewer in number than LDL
    4. VLDL is converted to LDL as triglycerides are removed
  12. IDL
    1. IDL are composed of phospholipid monolayer, 50% triglyceride, 50% chol, one ApoB100
    2. Transport of mostly triglyceride with some chol
  13. Cholesteryl Ester Transfer Protein (CETP) [5,50]
    1. Plays key role in metabolism of HDL
    2. Mediates net transfer of chol ester from HDL to other lipoproteins (mainly LDL)
    3. Also leads to update of chol by hepatocytes (for incorporation into bile)
    4. Two polymorphisms in CETP, called B1 and B2, exist in caucasian population
    5. Frequencies of genotypes are: B1B1 35%, B1B2 49%, and B2B2 16%
    6. B2B2 genotype associated with very slow progression of atherosclerosis
    7. B1B1 genotype associated with low HDL levels and rapid progression of atherosclerosis
    8. B1B1 genotype also associated with higher CETP levels than other genotypes
    9. Pravastatin reduces CETP levels and reduces atheroma progression in B1B1, but not B2B2
    10. Torcetrapid is a selective CETP inhibitor that increases HDL levels 46% alone [50]
    11. Torcetrapid had no effect on atheroma progression and increased cardiac events
      [Figure] 1 "Transport of Cholesterol"

D. Plasma Lipoproteins and Atherosclerosis [5] navigator

  1. Atherogenic
    1. Low Density Lipoproteins (LDL) - usually includes IDL, LDL and Lp(a)
    2. Small LDL (LDL B) are highly atherogenic (increased oxidation, decreased clearance)
    3. Role of Apo(a) and Lp(a) is not clear but Lp(a) has shown independent association with coronary risk in men but inconsistently in women [10,13]
    4. However, apo(a) levels correlate with increased risk of Alzheimer's Dementia in ApoE4 (versus ApoE2 or E3) persons [14]
    5. ApoE4 is a 1.4X risk for coronary disease, increases Chol [48]
    6. Very Low Density lipoproteins (VLDL) remnants
    7. Intermediate density lipoproteins (IDL)
    8. Hypertriglyceridemia and low HDL much more common in patients with atherosclerosis than are elevations in total and LDL chol [38]
    9. Chylomicron remnants
    10. Trans-fatty acids are strongly associated with cardiovascular events [23,43]
  2. Anti-Atherogenic Lipids
    1. High Density Lipoproteins (HDL) [27]
    2. Only certain subclasses of HDL are actually anti-atherogenic (HDL2 and 3)
    3. Elevated HDL levels in elderly associated with reduced risk of ischemic stroke [15]
    4. ApoA1 component of HDL reduces risk of vascular disease
  3. Nonatherogenic Lipoproteins
    1. Chylomicrons (intact)
    2. VLDL (intact) - unclear role for VLDL carrying triglycerides
  4. Atherosclerosis
    1. Means "hardening" of the vessels
    2. Mainly affects arteries, particularly the proximal vessels (aorta, carotid, coronaries)
    3. Atherosclerotic lesions are subendothelial deposits of various materials and cells
    4. Lesions classified as stable (older, lipid poor) and unstable (younger, lipid rich)
    5. Unstable lesions rupture easily and form large thrombi
    6. Such lesions cause acute ischemic syndromes and sudden death
    7. Atherogenic lipids are toxic to endothelium and stimulate platelet aggregation
    8. Oxidized LDL are particularly toxic to endothelium and reduce nitric oxide production
    9. Elevated serum chol and low HDL increase risk of plaque rupture
    10. Smoking increases size of thrombus, and probably threshold for formation
    11. Stable lesions show endothelial erosion and macrophage inflammation, microthrombi
    12. Stable lesions usually grow slowly, causing chronic ischemic syndromes
  5. High Fat Meals and Endothelium
    1. Saturated fats are associated with endothelial dysfunction
    2. Both acute and chronic effects have been observed
    3. Single high fat meal blocks arterial vasodilation for 2-4 hours
    4. Triglyceride level increases correlated best with inhibition of vasodilation
    5. Anti-oxidants Vitamins E (800 IU) and C (1gm) given prior to high fat meal can improve vasodilation acutely
    6. No clear evidence that vitamin supplements provides any chronic benefit [16,17]
  6. Reduction of LDL levels leads to improved endothelial function

E. Adult Treatment Panel Classification [1]navigator

  1. Total Chol
    1. Desirable: <200mg/dL (<5.2mMol)
    2. Borderline High: 200-239mg/dL (5.2-6.2 mMol)
    3. High: >239mg/dL (>6.2 mMol)
  2. LDL Chol [24]
    1. Optimal: <100mg/dL (<2.6mMol)
    2. Near or above optimal: 100-129mg/dL
    3. Boderline High: 130-159mg/dL
    4. High: 160-189mg/dL
    5. Very High: >189mg/dL
  3. HDL Chol [27]
    1. Low: <40mg/dL in men, <50mg/dL in women
    2. High: >59mg/dL
  4. Metabolic Syndrome [42]
    1. Defined as having at least 3 of the following 5 criteria:
    2. Abdominal Obesity: waist circumference >102cm men, >88cm women
    3. Hypertriglyceridemia: triglycerides >149 mg/dL (>1.68 mmol/L) [38]
    4. Low HDL: <40mg/dL (1.04 mmol/L) men, <50mg/dL (1.29 mmol/L) women
    5. High blood pressure: >130/85 mm Hg
    6. High fasting glucose: >109 mg/dL (>6.1 mmol/L)
    7. Insulin resistance is not required for syndrome
    8. Overall prevalence of metabolic syndrome is 22% and is age dependent in USA
    9. Chronic intervention is critical to prevent progression to frank diabetes
    10. Often called insulin resistance syndrome

F. Screening Guidelines [1] navigator

  1. All persons >20-25 years should have Total and HDL Chol levels checked
    1. Follow normal tests for total chol (<200mg/dL) every 5 years
    2. Screening can be done in non-fasting state and includes Total and HDL chol
    3. Repeat abnormal tests 1-8 weeks later with complete fasting lipid profile
    4. This includes total Chol, LDL and HDL, and triglycerides
    5. Total Chol values apply only to patients without history of vascular disease
    6. Adding direct LDL, lipoprotein(a), or IDL measurements does not improve prognostic accuracy in young persons without vascular disease [18]
    7. Adding apolipoproteins A1 and B100 to total and HDL chol levels adds no CV prognostic value in women [33]
    8. CRP levels do add CV prognostic value to standard lipids in women [33]
  2. Patients are divided into mild, moderate and high risk categories [1,8]
    1. Mild risk - nonpharmacologic therapy (high Chol and only one other risk factor)
    2. Moderate risk - high total cholesterol; at least 2 other risk factors
    3. High - high Chol with other risk factors and known arterial disease
    4. These are National Chol Education Program (NCEP) categories
  3. Coronary Artery Disease (CAD) Risk Factors
    1. Age: M>44yr, F>55yr or premature menopause without Hormone Replacement Therapy
    2. Family History of premature CAD
    3. Smoking
    4. Hypertension
    5. Diabetes and Insulin Resistance Syndromes
    6. HDL Chol <35mg/dL (0.9mMol)
    7. LDL Chol >130-160mg/dL, particulary with small diameter LDL
    8. Central Obesity (increased waist to hip ratio; correlates with Chol levels)
    9. Negative Risk Factor: HDL Chol >60mg/dL (1.6mMol)
    10. Hyperhomocysteinemia
  4. Non-Classical CAD Risk Factors
    1. Elevated C Reactive Protein (CRP) [20]
    2. Homocysteinuria / Hyperhomocysteinemia
    3. Nephrotic Syndrome
    4. Role of triglycerides is still difficult to separate from LDL
    5. Triglycerides may be a risk factor in women (possible relationship to Estrogen levels)
    6. Elevated Lp(a) is probably a risk factor which is additive to LDL level
    7. Xanthomas and xanthalasmas correlate with lipid levels and ApoE phenotype
    8. Familial Syndromes with elevated lipids, premature atherosclerosis
  5. Chol to HDL Ratios
    1. Likely a better measure of risk for CAD than LDL or total chol
    2. Dietary therapy rarely improves ratio; may actually worsen ratio
    3. Ratio TChol:HDL >7 associated with risk ~30% of CAD event within 8 years
    4. Desirable ratio TChol:HDL <4
    5. Ratio TChol:HDL <3 has RR of CAD of 1/3 of general population
    6. TChol:HDL probably better than LDL:HDL ratio (probably due to inclusion of triglycerides)
    7. Low HDL levels are an independent risk for CAD

G. Hyperlipidemia Phenotypes [32] navigator

  1. Type 1: chylomicronemia, elevated triglycerides
  2. Type 2a: LDL elevation (high cholesterol)
  3. Type 2b: LDL and VLDL (high chol and triglycerides, usually low HDL)
  4. Type 3: chylomicronemia (high triglycerides and chol)
  5. Type 4: VLDL and triglyceride elevations
  6. Type 5: chylomicronemia and VLDL (high triglycerides and chol)
  7. These phenotypes are designated by World Health Organization
  8. Variety of genetic mutations have been discovered

H. Efficacy of Treatment of Elevated Chol navigator

  1. Primary Prevention of CV Events
    1. CV events are reduced ~2-3% for every 1% drop in chol
    2. Overall mortality is decreased by chol reduction with pravastatin
    3. Pravastatin reduces mortality in CAD regardless of initial chol level
    4. Pravastatin for 5 years reduces coronary events for 10 years in men without MI [37]
    5. Primary prevention therapy recommended in all patients with high LDL
    6. Primary prevention of CAD in all type 2 DM patients with atorvastatin [28]
    7. No change in overall mortality using cholestyramine for lowering chol
    8. Statin therapy is safer and more effective than cholestyramine
  2. Secondary Prevention of CV Events [24]
    1. Reducing chol shows definite CV event reduction
    2. Statin ± additional drugs recommended for all patients with previous cardiac event
    3. Goal chol levels for secondary prevention are T-Chol ~100mg/dL but data supporting this are target are weak [24,30]
    4. Cardiac event risk reduction ~1.5-2% for every 1% decrease in Chol
    5. Simvastatin reduced mortality (and event rates) ~30% in post-MI patients
    6. Probably stabilizes plaques and may reduce atherosclerosis in some patients
    7. Pravastatin reduced subsequent events post-MI in patients with normal Chol
    8. Statins are more effective than other drugs and are nearly always first line [6]
    9. Statins reduce primary and secondary stroke rates [6]
  3. Mechanisms
    1. Decreasing chol by ~20% on average leads to 1-5% reduction in angiographic stenosis per year
    2. Coronary Artery Disease (CAD) trial showed reduction in angiographic stenosis
    3. Increased HDL and lowered LDL led to regression in CAD lesions over 2 years
    4. Statins improve endothelial dilatory response independent of chol effect
    5. Quantitative angiography showed lovastatin reduced atherosclerotic lesion size
  4. Meta-Analysis of Statin Therapy
    1. Statin therapies reduce major cardiac events by 31%
    2. Reduce overall mortality 21%
  5. Mortality (overall) decreases with decreasing chol and moreso with total/HDL levels [4]

I. Nonpharmacologic Therapy navigator

  1. Stop Smoking - this is most critical issue
  2. Diet Overview
    1. Standard low Chol diets reduce lipid levels 8-10%
    2. High plant sterol diets can reduce both Chol and CRP levels 28% [53]
    3. Diet is most effective in patients with higher than average fat intake
    4. Lipid lowering margerines (plant sterols) now available reduce chol ~10% [41]
    5. Plant derived Chol include include sitostanol and sitosterol [41]
    6. Reducing trans fatty acids and saturated fats leads to ~10% Chol reduction [23,40]
    7. Reducing trans fatty acids to <1% of calories may reduce CV events 6-19% [23]
    8. Dietary intervention in children was safe with modest lowering of LDL Chol
    9. Changing to diets which include moderate intake of monounsaturated and poly- unsaturated fats (such as Mediterranean diet) can also reduce heart disease risk
    10. Virgin olive oil contains monounsaturated fats (mainly oleic acid) and polyphenols (anti- oxidants), which increase HDL levels [12]
  3. Chol Lowering Diets [5]
    1. Step I (10% of calories saturated fat): Chol <300mg/d, total fat <30% of calories
    2. Step II (7% of calories saturated fat): Chol <250mg/d, total fat <30% of calories
    3. Note that diet may not change TChol:HDL ratio, or may increase the ratio
    4. Step II diet may be no more effective than Step I and can have side effects
    5. Step II diet provided no Chol lowering benefits without exercise
    6. Step I diet is strongly recommended in all persons with increased Chol
    7. Step II diet may be initiated immediately
    8. Most patients on diets lose weight and increase vitamin intake
    9. Step II diet leds to reduction in LDL 8-15%
    10. Diets more restricted than Step II do not reduce LDL and often lower HDL
    11. Low fat and Mediterranean diets improve endothelial function in hypercholesterolemic men [44]
    12. Diets high in plant sterols and fibers are probably most effective and may be as effective as low dose statins [53]
    13. Substantially reduce trans fatty acids [23]
  4. Exercise
    1. Extremely effective method of reducing many cardiac and other risk factors
    2. Reduce TChol, IDL, triglycerides and increases HDL chol [54]
    3. Reduces both cardiac and noncardiac mortality by 20-25% over several years
    4. Exercise + step II diet, but not diet alone, reduced LDL and raised HDL cholesterols
    5. Exercise and weight loss are absolutely essential for optimal reductions in cholesterol
    6. Exercise of minimal benefit on chol in diabetes type 2, but reduced triglycerides [45]
  5. Weight Reduction
    1. Likely very important for long lasting efficacy of drugs
    2. Diet, excercise and dietary fiber should help reduce weight
    3. Stimulants should generally be avoided in persons with coronary artery disease
  6. Dietary Fiber - soluble fiber reduces chol more than insoluble fiber
  7. Moderate Alchol intake increases HDL fraction and reduces MI and stroke risk [46]
  8. Using sitostanol (a plant sterol) based margerine reduces total Chol, LDL levels

J. Pharmacologic Therapy Overview [5,6,49] navigator

  1. HMG CoA Reductase Inhibitors [34]
    1. Most commonly prescribed medications for high Chol
    2. Lead to total and LDL Chol reduction with very mild HDL increases
    3. Most agents (except atorvastatin) do not substantially reduce VLDL
    4. Little or no effect on Lp(a) levels
    5. Mortality reduction overall 12% per mmol/L reduction in LDL chol
    6. Substantial reductions in cardiac and other vascular event rates over time
    7. First line, best tolerated agents in most patients
  2. Niacin / Nicotinic Acid [27,51]
    1. Extremely effective but high side effect profile limits long term use
    2. Leads to total and LDL Chol reduction with increases in HDL
    3. Most effective for raising HDL of any of the compounds
    4. Increases in HDL 20-35%, increasing hepatitic uptake of apo-A1
    5. Low doses raise HDL; higher doses are required to lower LDL significantly
    6. Overall, highly effective, but HMG reductase inhibitors better tolerated
  3. Fibric Acid Derivatives
    1. Gemfibrozil (Lopid®)
    2. Clofibrate (Atromid-S®)
    3. Benzafibrate
    4. Increases HDL chol 10-25%
  4. Bile Acid Sequestrants
    1. Non-absorbed compounds with bind chol in the gut
    2. Low doses are well tolerated but efficacy is only moderate
    3. Higher doses are very poorly tolerated and have little added efficacy
    4. Lead to total and LDL-C reduction, little change in HDL
    5. Cholestyramine (Questran®, Prevalite®) and Colestipol (Colestid®)
  5. Probucol reduces PTCA restenosis
  6. Treatment of Hypertension and Hypercholesterolemia
    1. Certain anti-hypertensive medications should be avoided with hypercholesterolemia
    2. ß-blockers, thiazides and related agents increase total chol
    3. ß-blockers with intrinsic sympathomimetic acitivity decrease total chol
    4. ACE inhibitors and alpha-adrenergic blockers reduce total chol
  7. Familial hypercholesterolemia patients should be referred to a specialist

K. HMG CoA Reductase Inhibitors [6,34,35] navigator

  1. Indications
    1. Types IIa and IIb primary hypercholesterolemia and high LDL
    2. First line agents for Chol reduction
    3. Primary and secondary prevention of CAD in persons with hypercholesterolemia
    4. Approximately 10 patients treated for every one acute cardiac event prevented
    5. Reduces CAD in patients with normal chol and other risk factors
    6. Reduce risk of stroke (primary and secondary)
  2. Effects on Lipids
    1. Typically 25-40% LDL chol and 25% total chol reductions
    2. Superstatins can provide >50% LDL chol and >25% triglyceride reduction [55]
    3. Increase HDL 6-12%
    4. Reduction 10-20% in triglycerides
  3. Biochemical Activities
    1. Clear activities beyond reducing serum chol levels
    2. Endothelial stabilization and normalization
    3. Anti-inflammatory effects
    4. Depletion and physicochemical stability of lipid core
    5. Strengthening of fibrous cap on atheromata
    6. Inhibition of platelet thrombus formation and deposition
    7. Reduction of thrombogenic response
    8. Increase bone mineral density (? block osteoclast function); reduce fractures [56]
  4. Contraindications
    1. Liver Disease and/or concurrent hepatotoxic agents
    2. Concurrent Niacin Therapy (high incidence of rhabdomyolysis)
    3. Caution with patients concurrently on immunosuppressive agents
    4. Only severe renal failure requires dose reduction
  5. Side Effects
    1. Elevated transaminases - AST and ALT (liver function tests, LFTs)
    2. Myopathy - rare with severe myalgias, >10X increase in serum CPK (Rhabdomyolysis)
    3. Long term effects of chol inhibition not known
    4. Monitoring: LFTs and CK each month initially, then every 2-6 months

L. Combination Therapy [6]navigator

  1. Single agents reduce chol to target levels in <50% of patients with CAD
  2. If single agents do not reduce chol to target levels, consider combinations
    1. Two or three agents may be used together
    2. Combinations of a statin and niacin or gemfibrozil are very effective
    3. Pravastatin + Niacin (500mg tid) reduced TChol 28%, LDL 43%, triglycerides 25%
    4. This combination also increased HDL by 14%
    5. Using higher dose Niacin (1000mg tid) increased adverse events with minimal benefit
    6. Gemfibrozil was less effective than cholestyramine, but niacin was best second line
  3. Most HMG-CoA R-Inh have much increased risk of severe myositis / rhabdomyolysis

M. Recommended Therapy [6] navigator

  1. Low threshold to treat depends on risk factors, previous events, and sex
  2. HMG CoA Reductase Inhibitors are first line therapy for high LDL
    1. Statins more effective and better tolerated than bile acids for primary high chol
    2. Pravastatin, simvastatin, lovastatin all approximately equal for chol reduction
    3. Atorvastatin and rosuvastatin provide the greatest reduction in LDL (and triglyceride) levels of any statin [6,55]
  3. Increased HDL with Niacin or Gemfibrozil
    1. Minimal increase in HDL with HMG CoA Agents
    2. Niacin, cholestyramine and colestipol are well proven in outcomes' trials
    3. Relatively low doses of niacin are required to raise HDL
    4. Atorvastatin increases HDL by >10% in most patients
  4. Age at Treatment Initiation
    1. Younger patients are now routinely treated based on NCEP Indications
    2. Familial (genetic) hypercholesterolemia are treated aggressively at any age
    3. Long term effects of drug therapy are being monitored; major side effects unlikely
    4. Benefit of therapy in age >75-80 years is unclear
  5. NCEP Goals of Therapy [1]
    1. In patients with CAD, post-MI, other high risk, LDL should be <100mg/dL
    2. In patients with at least 2 risk factors, LDL should be <130mg/dL
    3. In patients with <2 risk factors, LDL should be <160mg/dL
    4. HDL >35mg/dL should be and additional goal in patients at risk or post-MI
    5. Combinations of agents may be needed to achieve goals
    6. Reduction of LDL to <100mg/dL slowed progression of saphenous vein graft athero- slcerosis in patients after CABG
  6. Trans fatty acids <1% of dietary intake [23]

Resources navigator

calcLDL Cholesterol

References navigator

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