Total Cholesterol <200mg/dL HDL > 40mg/dl LDL <130mg/dl Triglycerides(TG) <200mg/dl

Conversion factor from mg/dl to mmol/l: multiply by 0.0259

 In patients without coronary heart disease (CHD), the NCEP recommends screening with a complete lipid profile after a 12 hours fast for all adults > 20 years of age once every 5 years and as indicated

 DETECTION, EVALUATION and TREATMENT of High Blood Cholesterol in Adults RISK ASSESSMENT in an effort to reduce premature death and disability from CHD

1st NCEP outlined a strategy for primary prevention of CHD in persons with high levels of LDL >160mg/dL or those with borderline high LDL (130-159 mg/dL) and multiple (2+) risk factors

2nd NCEP Affirmed the 1st NCEP approach and added a new feature: the intensive management of LDL in persons with CHD New LDL goal of <100mg/dL

 Expand the prior list of cardiovascular events to include virtually all occlusive vascular diseases of the heart as well as the brain and peripheral arteries. Focus on global risk assessment rather than just lipid parameters GRA quantitation of the 10 year risk of developing CHD

 Major New Feature: Primary prevention in persons with multiple risk factors

 DM CHD risk equivalent Thus, all diabetic px should be treated as aggressively as px who have survived a prior occlusive event of the heart, brain or peripheral arteries

Modifications of Lipid and Lipoprotein Classficiation Identifies LDL <100mg/dL as optimal Raises categorical low HDL cholesterol from <35mg/dL to <40mg/dL because the latter is a better measure of depressed LDL Lowers the TG classification cutpoints to give more attention to moderate elevations

mg/dL LDL Cholesterol <100 100-129 130-159 160-189 >190 Optimal Near or above optimal Borderline high High Very High Desirable Borderline High

Total cholesterol <200 200-239 >240 HDL Cholesterol <40 >60

High
Low

High

 The primary target of therapy Research from experimental animals, lab investigations, epidemiology and genetic forms of hypercholesterolemia indicated that elevated LDL cholesterol is a major cause of CHD

 Any person with elevated LDL or other form of hyperlipidemia should undergo clinical or laboratory assessment to rule out secondary dyslipidemia before initiation of lipid-lowering therapy.

 Causes of secondary dyslipidemia: Hypothyroidism Obstructive Liver Disease Chronic Renal Failure Drugs that inc LDL and dec HDL (progestins, anabolic steroids, and corticosteroids Once secondary causes have been excluded, or, if appropriately treated, the goals for LDL lowering therapy in primary prevention are established according to a persons risk category

 First step in risk management Basic principle of prevention 1st step in selection of LDL lowering therapy to assess a persons risk status

 Risk status in person without clinically manifest CHD or other clinical forms of atherosclerotic disease is determined by a 2-step procedure First, the number of risk factors is counted Second, for persons with multiple (2+) risk factors, 10 yr risk assessment is carried out with Framingham Scoring to identify individuals whose short term (10yr) risk warrants consideration of intensive treatment

 Estimation of the 10 yr CHD risk adds a step to risk assessment beyond risk factor counting, but this step is warranted because it allows better targeting of intensive treatment to people who will benefit from it.

 Cigarette smoking Hypertension (BP >140/90 mmHg or on antihypertensive medication) Low HDL cholesterol (<40mg/dL) Family history of premature CHD (CHD in male first degree relative <55 yrs; CHD in female firstdegree relative <65 yrs) Age (men >45yrs; women >55 yrs) ** HDL cholesterol >60mg/dL counts as negative risk factor; removes 1 risk factor from the total count

Risk Category CHD and CHD risk equivalents

Multiple (2+) risk factors 0-1 risk factor

LDL Goal (mg/dL) <100

<130 <150

 Healthcare providers asked to quantitate the 10 yr risk of all primary prevention px with 2 or more risk factors using the Framingham Risk Assessment System
Sex Age Cholesterol status HDL Systolic BP

 More robust for total cholesterol than LDL Total cholesterol and HDL values should be the average of at least 2 measurements obtained from lipoprotein analysis BP- obtained at the time of assessment, regardless of whether the person is on antihypertensive therapy

 If absolute risk is 20% or greater, primary prevention px should be treated as aggressively as a patient who experience a previous event

 Primary prevention patient at high risk due to multiple metabolic risk factors or metabolic syndrome

3 out of 5 factors: Abdominal obesity (waist >101.6cm/40in in men and >88.9cm/35in in women) Low HDL levels (<40mg/dl or 1.03mmol/L in men and <50mg/dL or 1.29mmol/L in women High TG levels (>150mg/dL or 1.69mmol/L) High BP (systolic>130 or diastolic >85mmHg)

 Large and usually more-than-additive benefits in terms of risk reduction Efficacy of drug therapy with statins is enhanced

 Reduced intake of saturated fats and cholesterol Therapeutic options for enhancing LDL lowering such as plant stanols and sterols and increased viscous fiber Weight reduction Increased physical activity

 Saturated fat less than 7% of total calories and cholesterol <200mg/dL as well as plant stanols and sterols and foods with viscous(soluble) fiber to their patient Stanols and Stenols present in certain margarine products and salad dressings Sources of Soluble Fibers legumes, cereal grains, beans and many fruits and vegetables.

 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors STATINS Recommended by NCEP as the 1st line drug of choice for virtually all pxs eligible for lipid modification Goal -> drug therapy + therapeutic lifestyle changes

STATINS lower TC, LDL, and TG and inc HDL LDL reduction of approx 35% Meta-analysis
Primary and secondary prevention pxs assigned at random to statins 22% reduction in cholesterol 30% reduction in LDL

STATINS Beneficial changes were associated with significantly reduced risks of: MI, stroke vascular death total mortality

STATINS Reduce LDL levels by at least 30-35% Usual starting doses of atorvastatin, fluvastatin and simvastatin provide even larger decreases Starting dose of atorvastatin yield the largest reduction All statins have favorable safe profile

STATINS Induced liver dysfunction and myopathy RARE Higher doses will provide an even greater reduction in LDL with proportionately less increases in HD

STATINS Atorvastatin 10mg, 20mg, 4omg, 80mg: 10-80mg tab OD-HS Simvastatin 10mg, 20mg, 40mg: 540mg/day: start with 10mg OD HS Rosuvastatin 5mg, 10mg, 20mg: 5-20mg OD HS Pravastatin 10mg, 20mg: 10-40mg OD HS

Fibrates Gemfibrozil 300-600mg BID Fenofibrate 100-300mg cap OD Nicotinic Acid Nicotinic acid 50mg, 100mg: 50mg OD then inc up to 100mg TID

 Combination Therapy
Statin + Niacin of fibrates yield greater elevations of HDL and decrease in Triglycerides but increased risk of myopathy

 Progression of Drug Therapy

 NCEP - Sufficient to warrant far more widespread usage of statins to treat and prevent CHD

No level of HDL protects against HDL Thus, there needs to be a wider usage of statins in px with LDL despite the presence of normal or HDL level HDL with LDL at sufficient risk to warrant lipid modification

Airforce/Texas Coronary Atherosclerosis Prevention Study Px with normal LDL but HDL -> statin -> cardiovascular benefits

 Adherence to the NCEP guidelines by both patients and providers is a key to approximating the magnitude of the benefits demonstrated in clinical trials of cholesterol lowering.

 Therapeutic lifestyle changes Diet + drug therapy Statin drugs largest and most conclusive body of evidence to support their use to favorably alter lipids Increased use in accordance with the new NCEP guidelines in secondary and primary prevention could avoid tens of thousands of premature deaths

 These guidelines are intended to inform, not replace, the physicians clinical judgment, which must ultimately determine the appropriate treatment for each individual.