DYSLIPIDEMIADYSLIPIDEMIA

Lipoproteins transport water-insoluble triglycerides and cholesterol through the bloodstream, and all lipoproteins have a structure similar to that shown for very low density lipoproteins (VLDLs). Triglyceride and cholesteryl ester are isolated within a bipolar layer of phospholipids and apolipoproteins. Most lipoproteins contain several

apolipoproteins; VLDL contains apolipoproteins B-100, C-I, C-II, C-III, and E. LDL, which transports most of the cholesterol found in blood, contains only apo B-100.

Gambar. VLDL

Calculation of LDL cholesterolCalculation of LDL cholesterol

LDL cholesterol is usually calculated rather than LDL cholesterol is usually calculated rather than measured. The formula used is:measured. The formula used is:

LDL cholesterol = Total cholesterol – (TG/5 + HDL LDL cholesterol = Total cholesterol – (TG/5 + HDL cholesterol)cholesterol)

This formula is accurate This formula is accurate unlessunless triglycerides are triglycerides are << 400 400 mg/dL, LDL cholesterol can also be measured mg/dL, LDL cholesterol can also be measured directly.directly.

Role of HDL in AtherosclerosisRole of HDL in Atherosclerosis

HDL cholesterol, is anti-atherogenic; reverse cholesterol HDL cholesterol, is anti-atherogenic; reverse cholesterol transport, that removes excess cholesterol from cells. transport, that removes excess cholesterol from cells.

Low HDL cholesterol has been shown to increase the risk Low HDL cholesterol has been shown to increase the risk of CHD.of CHD.

For every 5 mg/dL decrement in HDL, there is a 25% For every 5 mg/dL decrement in HDL, there is a 25% increased risk of myocardial infarction (MI). increased risk of myocardial infarction (MI).

High levels of HDL cholesterol shown to be High levels of HDL cholesterol shown to be cardio-cardio-protective. protective.

The new National Cholesterol Education Program The new National Cholesterol Education Program guidelines list an HDL cholesterol < 40 mg/dL as a risk guidelines list an HDL cholesterol < 40 mg/dL as a risk factor for CHDfactor for CHD..

Coronary HeartCoronary Heart Disease Risk Based On LDL-C / HDL-C Disease Risk Based On LDL-C / HDL-C

GenderRiskLDL-C/ HDL-C

Men

Women

One-half avergeAverage

2X Average 3X Average

One-half avergeAverage

2X Average 3X Average

1,003,556,257,99

1,473,225,036,14

Framingham Heart –Study

Physical Manifestations of HyperlipidemiaPhysical Manifestations of Hyperlipidemia

1.1. Xanthelasma: irregularly shaped, slightly raised, yellowish-Xanthelasma: irregularly shaped, slightly raised, yellowish-white lesions on the upper or lower eyelids that are cholesterol white lesions on the upper or lower eyelids that are cholesterol deposits in the skin.deposits in the skin.

2.2. Tendinous xanthomas: deposits of cholesterol in the tendons.Tendinous xanthomas: deposits of cholesterol in the tendons.3.3. Eruptive xanthomas: deposits of cholesterol on the trunk and Eruptive xanthomas: deposits of cholesterol on the trunk and

extensor surfaces of the extremities; they appear as painless extensor surfaces of the extremities; they appear as painless papules with yellow centers and are seen in patients with papules with yellow centers and are seen in patients with severe hypertri-glyceridemia.severe hypertri-glyceridemia.

1 3

Physical Manifestations of Physical Manifestations of HyperlipidemiaHyperlipidemia

Con’dCon’d

4-4- Lipemia retinalis: change in color of the blood vessels in Lipemia retinalis: change in color of the blood vessels in the retina from red to pink or white; the retina from red to pink or white;

This occurs when serum triglyceride levels exceed This occurs when serum triglyceride levels exceed 1000mg/dL1000mg/dL

5-5- Arcus cornealis: whitish ring seen around the cornea Arcus cornealis: whitish ring seen around the cornea caused by lipid deposits in the periphery of the cornea.caused by lipid deposits in the periphery of the cornea.

4 5

Effect of Lifestyle ModificationEffect of Lifestyle ModificationDietDiet

Decreased saturated fat (decrease LDL)Decreased saturated fat (decrease LDL)Replacing saturated and trans unsaturated fats with unhydrogenated monounsaturated or Replacing saturated and trans unsaturated fats with unhydrogenated monounsaturated or

polyunsaturated fatspolyunsaturated fatsRecommended dietRecommended diet

•Dietary cholesterol <200 mg/d; total fat <30%; saturated fat <7%Dietary cholesterol <200 mg/d; total fat <30%; saturated fat <7%•CHO (whole grains, fruits,veggies) 50-60% total caloriesCHO (whole grains, fruits,veggies) 50-60% total calories•Dietary fiber 20-30 g/dDietary fiber 20-30 g/d•Protein 10-25 g/dayProtein 10-25 g/day•Plant stanols/sterols 2 grams/dayPlant stanols/sterols 2 grams/day

Effect of LDL lowering should be evident in 6-12 monthsEffect of LDL lowering should be evident in 6-12 monthsElevated BMI associated with decreased dietary responseElevated BMI associated with decreased dietary responseReferral to dietitian helpfulReferral to dietitian helpful

ExerciseExerciseIn a prospective study of 111 sedentary men and women with dyslipidemia randomized to In a prospective study of 111 sedentary men and women with dyslipidemia randomized to

different levels of exercise, decrease in VLDL TG and increase in LDL size observed. Increase different levels of exercise, decrease in VLDL TG and increase in LDL size observed. Increase in HDL and size and largest effect on LDL seen with high amount high intensity exercisein HDL and size and largest effect on LDL seen with high amount high intensity exercise

Mechanisms of benefit: reduction in CETP, elevation in LCAT, reduced hepatic lipase and Mechanisms of benefit: reduction in CETP, elevation in LCAT, reduced hepatic lipase and elevated LPL activityelevated LPL activity

Possible effect on LDL particle sizePossible effect on LDL particle sizeModerate intensity exercise (3-4 mi/hr) for 30 minutes on most days of the weekModerate intensity exercise (3-4 mi/hr) for 30 minutes on most days of the week

Diet SupplementsDiet Supplements

Fish Oil (source of omega-3 polyunsaturated fatty acids)Fish Oil (source of omega-3 polyunsaturated fatty acids)Salmon, flaxseed, canola oil, soybean oil and nutsSalmon, flaxseed, canola oil, soybean oil and nutsAt high doses > 6 grams/day reduces TG by inhibition of VLDL-TG synthesis and apolipoprotein BAt high doses > 6 grams/day reduces TG by inhibition of VLDL-TG synthesis and apolipoprotein B Possibly decreases small LDL (by inhibiting CETP)Possibly decreases small LDL (by inhibiting CETP)Several studies have shown lower risk of coronary eventsSeveral studies have shown lower risk of coronary events22 servings of fish/week recommendedservings of fish/week recommended????Pharmacologic use restricted to refractory hypertriglyceridemiaPharmacologic use restricted to refractory hypertriglyceridemia Number of undesirable side effects (mainly GI)Number of undesirable side effects (mainly GI)

SoySoy Source of phytoestrogens inhibiting LDL oxidationSource of phytoestrogens inhibiting LDL oxidation25-5025-50 grams/day reduce LDL by 4-8%grams/day reduce LDL by 4-8%Effectiveness in postmenopausal women is questionableEffectiveness in postmenopausal women is questionable

GarlicGarlicMixed results of clinical trialsMixed results of clinical trialsIn combination with fish oil and large doses (900-7.2 grams/d), decreases in LDL observedIn combination with fish oil and large doses (900-7.2 grams/d), decreases in LDL observed

Cholesterol-lowering MargarinesCholesterol-lowering MargarinesBenecol and Take Control containing plant sterols and stanolsBenecol and Take Control containing plant sterols and stanolsInhibit cholesterol absorption but also promote hepatic cholesterol synthesisInhibit cholesterol absorption but also promote hepatic cholesterol synthesis10-20%10-20% reduction in LDL and TC however no outcome studiesreduction in LDL and TC however no outcome studiesAHA recommends use only in hypercholesterolemia pts or those with a cardiac event requiring LDL AHA recommends use only in hypercholesterolemia pts or those with a cardiac event requiring LDL

treatmenttreatmentOther agents include soluble fiber, nuts (esp. walnuts), green teaOther agents include soluble fiber, nuts (esp. walnuts), green teaOverall a combination diet with multiple cholesterol-lowering agents causes much more significant LDL Overall a combination diet with multiple cholesterol-lowering agents causes much more significant LDL

reductionsreductions

Measurement of LipoproteinsMeasurement of LipoproteinsLipoprotein analysis 12-14 hours fastingLipoprotein analysis 12-14 hours fasting TC and HDL-C can be measured fasting or non-fastingTC and HDL-C can be measured fasting or non-fastingLDL-Cholesterol = Total cholesterol –VLDL (1/5 TG)-HDLLDL-Cholesterol = Total cholesterol –VLDL (1/5 TG)-HDL

Validity depends on TG <400 mg/dLValidity depends on TG <400 mg/dLMeasured directly if patients have profound hypertrigMeasured directly if patients have profound hypertrigErrors in TC, HDL, and TG can affect valuesErrors in TC, HDL, and TG can affect values

Non-HDL cholesterol= TC – HDL-CNon-HDL cholesterol= TC – HDL-CAll cholesterol in atherogenic lipoproteins incl LDL, Lipoprotein a, IDL, VLDLAll cholesterol in atherogenic lipoproteins incl LDL, Lipoprotein a, IDL, VLDL

Acute phase response (i.e. MI, surgical trauma or infection)Acute phase response (i.e. MI, surgical trauma or infection)Can reduce levels of TC, HDL, LDL, apo A+B through impairment of hepatic Can reduce levels of TC, HDL, LDL, apo A+B through impairment of hepatic

lipoprotein production and metabolismlipoprotein production and metabolismRaise Lpa and TGRaise Lpa and TGLipoprotein analysis should be done as outpatient one month after eventLipoprotein analysis should be done as outpatient one month after event

Screening RecommendationsScreening RecommendationsAdult Treatment Panel III (NCEP)Adult Treatment Panel III (NCEP)Fasting lipid profileFasting lipid profile at least once q 5 years at least once q 5 years

for all persons 20 y.o. or olderfor all persons 20 y.o. or olderIf non-fasting obtained and TC >200 or If non-fasting obtained and TC >200 or

HDL <40, f/u panel recommendedHDL <40, f/u panel recommendedIf no known CHD and serum LDL <160 (0-If no known CHD and serum LDL <160 (0-

1 risk factors) or LDL <130 (2 or more risk 1 risk factors) or LDL <130 (2 or more risk factors) then re-screen in 5 yearsfactors) then re-screen in 5 years

Borderline high cholesterol and <2 risk Borderline high cholesterol and <2 risk factors, re-screen in 1-2 yearsfactors, re-screen in 1-2 years

Metabolic SyndromeMetabolic Syndrome

ATP III criteria: (3 or more)ATP III criteria: (3 or more)Abdominal obesity (waist circumference >40 inches in men or >35 in women)Abdominal obesity (waist circumference >40 inches in men or >35 in women)

Hypertriglyceridemia (TG>150 mg/dL)Hypertriglyceridemia (TG>150 mg/dL)Low HDL <40 men; <50 womenLow HDL <40 men; <50 womenSBP >130 or DBP >85SBP >130 or DBP >85 Fasting glucose >110 mg/dLFasting glucose >110 mg/dL

Increased risk of DM and cardiovascular disease although there has been some Increased risk of DM and cardiovascular disease although there has been some controversy in the literaturecontroversy in the literature

Kuopio Ischemic Heart Disease Risk Factor Study: 1209 Finnish men (42-60 y.o.) without CVD, Kuopio Ischemic Heart Disease Risk Factor Study: 1209 Finnish men (42-60 y.o.) without CVD, cancer or DM at baseline followed for 11.4 years. Results showed that CVD and all-cause cancer or DM at baseline followed for 11.4 years. Results showed that CVD and all-cause

mortality are increased in men with MS even in absence of CVD or DM at baselinemortality are increased in men with MS even in absence of CVD or DM at baselineDyslipidemia is atherogenic with low HDL, elevated TG, and small dense LDLDyslipidemia is atherogenic with low HDL, elevated TG, and small dense LDLTreatment RecommendationsTreatment Recommendations::

Weight reduction and exerciseWeight reduction and exerciseLDL goal is same as in patient w/o MSLDL goal is same as in patient w/o MSIf LDL goal reached, then focus on TG if >200If LDL goal reached, then focus on TG if >200??Calculate non-HDL and goal is 30 above LDL goalCalculate non-HDL and goal is 30 above LDL goalFibrates and nicotinic acid are good choices for elevated TGFibrates and nicotinic acid are good choices for elevated TG

1ry prevention trials to lowering cholesterol1ry prevention trials to lowering cholesterol

1- AFCAPS/Text-CAPS showed that 1- AFCAPS/Text-CAPS showed that lovastatinlovastatin decreased the risk of decreased the risk of first acute major coronary first acute major coronary event in men and women withevent in men and women with::

Average total cholesterol and,Average total cholesterol and, Average LDL cholesterol levels and,Average LDL cholesterol levels and, Below-average HDL cholesterol levels Below-average HDL cholesterol levels

1ry prevention trials to lowering cholesterol1ry prevention trials to lowering cholesterol Cont’d Cont’d

2- WOSCOPS showed that treatment with 2- WOSCOPS showed that treatment with pravastatinpravastatin : : Reduced The incidence of MI and :Reduced The incidence of MI and : Reduced death from cardiovascular causes in men with:Reduced death from cardiovascular causes in men with: - moderately high total cholesterol and - moderately high total cholesterol and - moderately LDL cholesterol level - moderately LDL cholesterol level

2ndry prevention trials to lowering 2ndry prevention trials to lowering cholesterolcholesterol

1- The Scandinavian Simvastatin Survival Study (48) 1- The Scandinavian Simvastatin Survival Study (48) randomized patients :randomized patients :

With With known CHD and moderately high cholesterol known CHD and moderately high cholesterol to simvastatin versus placebo and found:to simvastatin versus placebo and found:

30% decrease in overall death and,30% decrease in overall death and, 42% decrease in cardiovascular death.42% decrease in cardiovascular death.2. The Cholesterol and Recurrent Events (CARE) study 2. The Cholesterol and Recurrent Events (CARE) study

randomized patients with known CHD and average randomized patients with known CHD and average cholesterol levels to pravastatin versus placebo and cholesterol levels to pravastatin versus placebo and found found

24% decrease in risk of coronary event.24% decrease in risk of coronary event.

2ndry prevention trials to lowering cholesterol2ndry prevention trials to lowering cholesterolCont’dCont’d

3. The Long-Term Intervention with 3. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Pravastatin in Ischaemic Disease (LIPID) study randomized patients with known study randomized patients with known CHD and broad range of cholesterol levels CHD and broad range of cholesterol levels to pravastatin versus placebo and found to pravastatin versus placebo and found

24% decrease in risk of coronary events24% decrease in risk of coronary events..

Goals of lipid-lowering therapyGoals of lipid-lowering therapy

1.1. The National Cholesterol Education Program The National Cholesterol Education Program (NCEP)/Adult Treatment Panel (ATP) III in 2001 came (NCEP)/Adult Treatment Panel (ATP) III in 2001 came out with its third report on out with its third report on the treatment of high blood the treatment of high blood cholesterol in adults (NCEP III).cholesterol in adults (NCEP III).

2.2. This report focuses on LDL cholesterol as the primary This report focuses on LDL cholesterol as the primary goal of therapy and lists different LDL cholesterol goals goal of therapy and lists different LDL cholesterol goals

based on an individual's risk factors.based on an individual's risk factors. 0 or 1 risk factor: LDL cholesterol goal < 160 mg/dL 0 or 1 risk factor: LDL cholesterol goal < 160 mg/dL > 2 risk factors: LDL cholesterol goal < 130 mg/dL > 2 risk factors: LDL cholesterol goal < 130 mg/dL Known CHD or CHD equivalents: LDL cholesterol goal Known CHD or CHD equivalents: LDL cholesterol goal

< 100 mg/dL< 100 mg/dL

Cardiac risk factorsCardiac risk factors

Cigarette smoking. Cigarette smoking. Hypertension defined as a blood Hypertension defined as a blood

pressure (BP) = 140/90 mmHg or taking pressure (BP) = 140/90 mmHg or taking an antihypertensive medication.an antihypertensive medication.

Low HDL cholesterol ( 40 mg/dL)Low HDL cholesterol ( 40 mg/dL) Family history of premature CHD:Family history of premature CHD: - Age < 55 years in male first-degree - Age < 55 years in male first-degree

relative relative - Age < 65 years in female first-degree - Age < 65 years in female first-degree

relation · relation · Age:Age: - 45 years in men - 45 years in men - 55 years in women- 55 years in women

What are CHD risk equivalentsWhat are CHD risk equivalents??

Certain patients have diseases Certain patients have diseases = = a a coronary event. coronary event.

These diseases include:These diseases include: Diabetes · Diabetes · Aortic aneurysm · Aortic aneurysm · Symptomatic carotid artery disease Symptomatic carotid artery disease Peripheral vascular disease Peripheral vascular disease Stroke Stroke Multiple risk factorsMultiple risk factors

Are high triglycerides dangerous?Are high triglycerides dangerous?

Triglyceride > 500 mg/dL risk of developing acute Triglyceride > 500 mg/dL risk of developing acute pancreatitis. pancreatitis.

It is not completely clear if high triglycerides are an It is not completely clear if high triglycerides are an independent risk factor for CHD. independent risk factor for CHD.

High triglycerides associated with low HDL and insulin High triglycerides associated with low HDL and insulin resistance.resistance.

Those with a very high triglycerides (> 500 mg/dL) should Those with a very high triglycerides (> 500 mg/dL) should have triglyceride lowering as the primary goal of therapy. have triglyceride lowering as the primary goal of therapy.

After the triglyceride level has decreased to < 500, the focus After the triglyceride level has decreased to < 500, the focus of treatment can be changed to LDL cholesterol goals.of treatment can be changed to LDL cholesterol goals.

Factors elevate triglyceridesFactors elevate triglycerides

Decreased insulin sensitivity (obesity, type II Decreased insulin sensitivity (obesity, type II diabetes)diabetes)

Physical inactivityPhysical inactivity HypothyroidismHypothyroidism Cigarette smokingCigarette smoking AlcoholAlcohol Diseases: nephrotic syndrome, Cushing's Diseases: nephrotic syndrome, Cushing's

syndrome ·syndrome · Medications: estrogens, corticosteroids, Medications: estrogens, corticosteroids,

retinoids, beta-blockers, cyclosporine, tamoxifen, retinoids, beta-blockers, cyclosporine, tamoxifen, diuretics· diuretics·

Genetic disorders: familial combined Genetic disorders: familial combined hyperlipidemia, familial hyper-triglyceridemiahyperlipidemia, familial hyper-triglyceridemia

What can be done to lower cholesterol?What can be done to lower cholesterol?

Therapeutic lifestyle changes Therapeutic lifestyle changes (TLC) are recommended for all (TLC) are recommended for all patients with high cholesterol.patients with high cholesterol.

Pharmacologic therapy is used Pharmacologic therapy is used when TLC cannot lower when TLC cannot lower cholesterol sufficiently.cholesterol sufficiently.

What are therapeutic lifestyle changesWhat are therapeutic lifestyle changes??

1. Diet :1. Diet :a. Saturated fat: < 7% of total daily caloriesa. Saturated fat: < 7% of total daily caloriesb. Monounsaturated fat: < 20% of total daily b. Monounsaturated fat: < 20% of total daily

calories calories c. Total fat: 25-35% of total daily calories c. Total fat: 25-35% of total daily calories d. Total cholesterol: < 200 mg/day d. Total cholesterol: < 200 mg/day e. Carbohydrates: 50-60% of total daily calories e. Carbohydrates: 50-60% of total daily calories f. Protein: about 15% of total daily calories f. Protein: about 15% of total daily calories g. Soluble fiber intake: 10-25 g/day g. Soluble fiber intake: 10-25 g/day

2. Weight loss 2. Weight loss 3. Increased physical activity3. Increased physical activity

How does physical activity affect lipidsHow does physical activity affect lipids??

Aerobic exercise:Aerobic exercise: increases HDL cholesterol increases HDL cholesterol

levels and levels and decreases triglyceride levels. decreases triglyceride levels. If exercise results in weight loss, If exercise results in weight loss,

LDL also decrease.LDL also decrease.However, the effect of exercise on However, the effect of exercise on

LDL cholesterol is highly variableLDL cholesterol is highly variable

Drugs Therapy for High Levels of LDLDrugs Therapy for High Levels of LDL

The 3-hydroxy-3-methylglutaryl coenzyme A The 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, known as (HMG CoA) reductase inhibitors, known as "statins,""statins," are considered first-line therapy for are considered first-line therapy for treating high LDL cholesterol. treating high LDL cholesterol.

HMG CoA, a substrate for cholesterol, and HMG CoA, a substrate for cholesterol, and competitively inhibit the rate-limiting step in competitively inhibit the rate-limiting step in cholesterol synthesischolesterol synthesis..

Drugs Therapy for High Levels of LDLDrugs Therapy for High Levels of LDLCont’dCont’d

The statins currently on the market include The statins currently on the market include atorvastatin , fluvastatin, lovastatin, atorvastatin , fluvastatin, lovastatin, pravastatin and simvastatin .pravastatin and simvastatin .

Atorvastatin is the most potent, and Atorvastatin is the most potent, and fluvastatin is the least potent.fluvastatin is the least potent.

If patients cannot take statins, other If patients cannot take statins, other options include bile acid sequestrants or options include bile acid sequestrants or nicotinic acids.nicotinic acids.

Potential Side effects of StatinsPotential Side effects of Statins

Elevation AST, ALT, can occur and need to be Elevation AST, ALT, can occur and need to be monitored. monitored.

If levels reach above two times normal, the dose needs If levels reach above two times normal, the dose needs to be decreased or the medicine discontinued.to be decreased or the medicine discontinued.

AST, ALT should be checked after AST, ALT should be checked after 6 weeks of start of 6 weeks of start of statin, then every 6 months statin, then every 6 months

Fewer than 1 % of patients taking statins will have an Fewer than 1 % of patients taking statins will have an elevation in transaminases high enough to necessitate elevation in transaminases high enough to necessitate discontinuing the drug.discontinuing the drug.

Myopathy can occur, with elevations of creatinine Myopathy can occur, with elevations of creatinine phosphokinase (CPK). phosphokinase (CPK).

Potential Side effects of StatinsPotential Side effects of StatinsCont’dCont’d

Patients who complain of muscle pain should Patients who complain of muscle pain should have their CPK level checked, and, if elevated, have their CPK level checked, and, if elevated, the medicine should be discontinued. the medicine should be discontinued.

Myopathy is more common when statins are Myopathy is more common when statins are combined with fibrates or other drugs that inhibit combined with fibrates or other drugs that inhibit or compete for the cytochrome enzyme (e.g., or compete for the cytochrome enzyme (e.g., cyclosporine, macrolide antibioticscyclosporine, macrolide antibiotics).).

Other more common side effects include Other more common side effects include gastrointestinal symptoms and muscle aches.gastrointestinal symptoms and muscle aches.

Effective Drugs in Treating High Effective Drugs in Treating High Triglyceride LevelsTriglyceride Levels

Fibric acid derivatives:Fibric acid derivatives: increase fatty acid oxidation in liver and muscle, increase fatty acid oxidation in liver and muscle,

decreasing VLDL production. decreasing VLDL production. They can also increase the metabolic clearance rate of They can also increase the metabolic clearance rate of

VLDL. VLDL. These drugs can lower triglycerides from 20-50% and These drugs can lower triglycerides from 20-50% and

increase HDL cholesterol < 15%.increase HDL cholesterol < 15%.Nicotinic acid (niacin):Nicotinic acid (niacin): inhibits VLDL production in the liver. inhibits VLDL production in the liver. It lowers triglycerides by 20-50%.It lowers triglycerides by 20-50%.HMG CoA reductase inhibitorsHMG CoA reductase inhibitors (statins) have a lesser (statins) have a lesser

effect, achieving a < 35% reduction in triglycerides.effect, achieving a < 35% reduction in triglycerides.

Potential side effects of fibratesPotential side effects of fibrates

Nausea, Nausea, abdominal pain, abdominal pain, myopathy. myopathy.

There is an increased risk of myopathy when There is an increased risk of myopathy when fibrates are combined with statins fibrates are combined with statins

Potential side effects of nicotinic acidPotential side effects of nicotinic acid

With crystalline niacin, flushing occurs in> 90% With crystalline niacin, flushing occurs in> 90% of patients. of patients.

This can be reduced by taking an aspirin about This can be reduced by taking an aspirin about 30 minutes beforehand or 30 minutes beforehand or

by using NiaSpan, a relatively safe extended-by using NiaSpan, a relatively safe extended-release preparation of nicotinic acid. release preparation of nicotinic acid.

Nicotinic acid also can elevate blood glucose Nicotinic acid also can elevate blood glucose and uric acid and, and uric acid and,

Rarely, produces severe hepatotoxicity. Rarely, produces severe hepatotoxicity.