# Lecture 17 NUTRITION AND DISEASE: CARDIOVASCULAR DISEASE
Cardiovascular Disease (CVD): Background Definition: A group of diseases affecting the heart and blood vessels. Leading single cause of death around the world today. Each year, CVD accounts for ~1M deaths and costs the U.S. ~$260 billion Consequences of CVD are usually coronary heart disease (CHD) and strokes, the first and third leading causes of death for adults, respectively CHD, the most common form of CVD, usually involves atherosclerosis and hypertension o Atherosclerosis: accumulation of lipids and other materials in the arteries o Hypertension: high blood pressure, defined as >140/90
Hypertension
Definition: a blood pressure of 140/90 or higher.
CLASSIFICATION OF BLOOD PRESSURE FOR ADULTS AGE 18 YEARS AND OLDER* Category Normal** High normal Hypertension*** STAGE 1 (mild) 140-159 STAGE 2 (Moderate) STAGE 3 (Severe) STAGE 4 (Very Severe) Systolic (mm Hg) <130 130-139 90-99 160-179 180-209 >210 Diastolic (mm Hg) <85 85-89
100-109 110-119 >120
*Not taking antihypertensive drugs and not actually ill. When systolic and diastolic pressure fall into different categories, the higher category should be selected to classify the individual's blood pressure stages. For instance, 160/92 mm Hg should be classified as Stage2, and 18O/l2Omm Hg should be classified as Stage 4. Isolated systolic hypertension (ISH) is defined as SBP >140 mm Hg and DBP <90 mm Hg and staged appropriately (e.g., 170/85 mm Hg is defined as Stage 2 ISH). **Optimal blood pressure with respect to cardiovascular risk is SBP<120 mm Hg and DBP <80 mm Hg. However, unusually low readings should be evaluated for clinical significance. ***Based on the average of two or more readings taken at each of two or more visits following all initial screening. Note: In addition to classifying stages of hypertension based on average blood pressure levels, the clinician should specify presence or absence of target-organ disease and additional risk factors. For example, a patient with diabetes and a blood pressure of 142/94 mm Hg plus left ventricular hypertrophy should be classified as "Stage 1 hypertension with target-organ disease (left ventricular hypertrophy) and with another major risk factor (diabetes)." This specificity is important for risk classification and management.
Role of diet in the prevention or the production of hypertension. The role of diet in hypertension has been extensively studied. Sodium has been implicated strongly in the pathogenesis of hypertension. Findings from studies... o Populations with low salt intake have lower blood pressure levels, Populations that eat little or no salt have normal blood pressure, Severely restricting sodium reduces high blood pressure; adding sodium back to the diet restores high blood pressure. From research even a mild restriction can produce a decrease in blood pressure. People in areas with soft water (contains sodium) have on the average higher blood pressure than people in areas with hard water (contains calcium and magnesium) Not all individuals are salt-sensitive. Those that are tend to be:
o o o o
Chronic renal failure Whose parents have/had hypertension African-American (genetically predisposed to retain sodium) >50 y of age
Other Dietary Factors: Hypertension has been associated with: Low potassium intake. This leads to high Na/K ratio hypertension Low calcium intake. Dietary calcium appears to exert an antihypertensive effect on salt sensitive AfricanAmericans. Low magnesium intake is correlated to hypertension. Obesity: In a cohort study conducted at Meharry Medical College (Dr. John Thomas) obesity was found to be a risk factor for hypertension. Dietary intervention studies demonstrate that blood pressure can be decreased or increased in hypertensives by altering the fatty acid composition of the diet i.e., adding more polyunsaturated acids i.e., linoleic acid. Hypertension: Interventions Treatment algorithm: Lifestyle modification Weight reduction Moderation of alcohol intake Regular Physical activity Reduction of sodium intake Smoking cessation Inadequate response* Continue lifestyle modifications Initial pharmacological selection: * Diuretics or Beta-blockers are preferred because a reduction in morbidity and mortality has been demonstrated * ACE inhibitors, Calcium agonists, Alpha1-receptors blockers, and the Alpha-beta blocker have not been tested nor shown to reduce morbidity and mortality Inadequate response* Increased drug dose OR substitute another drug OR add a 2nd agent from a different class
Inadequate response* Add a Second or third agent and/or diuretic if not already prescribed Response means achieved goal blood pressure, or patient is making considerable progress towards this goal 1. The Dietary Guidelines recommends that we limit our sodium intake to less than 5 gms/day. Recommended intake of Na 1.1-3.3 g/day. Avoid highly salted food and remove salt shaker from the table. 2. Maintain ideal weight. The overweight hypertensive can reduce blood pressure simply by losing weight. 3. Eat plenty of fresh fruits and vegetables because they are rich in potassium. 4. Eat a variety of foods, including good food sources of calcium and magnesium. 5. Use alcohol in moderation. 6. Exercise regularly 7. Relax 8. Eat fewer processed foods
Progression of atherosclerosis Most CVD is caused by atherosclerotic changes in blood vessels impairing normal blood flow to heart, brain, limbs, and other parts of the body. Atherosclerosis usually develops imperceptively from as early as childhood. Symptoms start developing only decades later when atherosclerotic plaques cause significant narrowing of the lumen or when thrombi occlude a vessel. Progression involves (see figure next page) a. Unaffected artery: thin intimal layer, smooth luminal surface b. Early lesion: soft fatty streaks accumulate in intima attracts monocytes and stimulate cellular immune response. Fatty streaks tend to accumulate at branch points c. Advanced lesions: cholesterol, Ca crystals (ie. Calcification) and cellular debris accumulate within the intima which starts bulging into the arterial lumen. Plaques stiffen the arteries and narrow the passages through them. Most people have well-developed plaques by the age of 30. Progression of atherosclerosis in the coronary arteries may restrict blood flow to the cardiac muscle and limit the delivery of oxygen. d. Thrombus formation: Platelets cause clots to form whenever they encounter injuries in blood vessels. Clots normally form and dissolve in the blood all the time, but in atherosclerosis, clots form faster than they dissolve because platelets respond to plaques as they normally do to injuries. A blood clot may adhere to a plaque in an artery and gradually grow large enough to restrict or close off a blood vessel this is thrombosis. A coronary thrombosis blocks blood flow through an artery that feeds the cardiac muscle; a cerebral thrombosis blocks blood flow through an artery that feeds the brain. e. Blood flow : loss of blood to the area robs the tissue of oxygen and nutrients tissue dies. If heart muscle dies=myocardial infarction. If brain tissue dies=transient ischemic attack (mini stroke, TIA) or stroke (cerebrovascular accident, CVA) f. Blood pressure Many factors promote progression of atherosclerotic CV disease. Some of these act by promoting early lesions, others by promoting late events such as calcification and thrombus formation. Diet influences disease progression at all stages. Early and advanced lesions: Consumption of large amounts of saturated fatty acids and cholesterol is unfavorable; adequate intake of antioxidants and other vitamins with food is protective. Thrombus formation: regular consumption of fish may be protective Risk Factors for CVD Modifiable* Smoking Physical inactivity Stress Personality characteristics (Type A) Hypertension Obesity Insulin resistance/diabetes High blood cholesterol. Age cutoffs: 20's: 220 mg/dL 30's: 240 mg/dL 40's: 260 mg/dL Nutrient deficiencies Non-modifiable* Male gender Female gender (post-menopause) Family history Age Hypertension Obesity Insulin resistance/diabetes High blood cholesterol. Age cutoffs: 20's: 220 mg/dL 30's: 240 mg/dL 40's: 260 mg/dL
*it can be argued that some risk factors, such as obesity and diabetes, are modifiable, whereas others may disagree
Mechanisms of risk factors: High blood cholesterol: Atherogenic: - Chylomicron remnants - LDL (mounting evidence suggests atherosclerosis accelerated by oxidation of LDL-cholesterol by free radicals) - VLDL remnants Non-atherogenic: - Chylomicrons - HDL (may actually reduce atherosclerosis risk) - VLDL Transport remnants remain in the blood from minutes to days, depending on the type:
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chylomicrons and chylomicron remnants: half-life - minutes to hours VLDL and their remnants: half-life - few hours to several days LDL: half-life - several weeks ***The atherogenic potential of these lipid forms is related to the length of their half-life ***Progression of atherosclerosis
Hypertension: injures the artery linings and accelerates plaque formation, setting the stage for atherosclerosis development or exacerbating existing atherosclerosis. Plaques blood flow which induces a further in BP, and hypertension and atherosclerosis become mutually aggravating. Insulin resistance/diabetes: in diabetes, blood vessels often become blocked and circulation . Atherosclerosis progresses rapidly. Like CHD, associated with LDL, TG, HDL, hypertension and obesity, particularly abdominal obesity. Obesity and physical inactivity: both significantly modify several other risk factors, contributing to LDLcholesterol, HDL-cholesterol, hypertension and diabetes
Smoking: HDL-cholesterol; also damages heart directly by BP and cardiac workload. Deprives heart of oxygen and damages platelets, making blood clot formation likely. Toxins in cigarette smoke damage blood vessels, setting stage for atherosclerosis. Gender: in general, men have higher blood cholesterol and a greater risk of CVD at an earlier age than women. CVD occurs about 10-12 years later in women than in men. Women younger than 45 tend to have lower LDLcholesterol than men of same age, but a woman's blood cholesterol typically begins to between ages 45-55. Independently of age, a lack of estrogen influences blood cholesterol: at menopause, LDL-cholesterol and HDL-cholesterol . Estrogen replacement therapy after menopause and regular physical activity CHD risk in women by LDL-cholesterol and HDL-cholesterol. Such therapy protects LDL from oxidation, as does vitamin E supplementation. Insulin Resistance Syndrome By middle age, most adults have at least one risk factor, and many have more than one. Only some of the risk factors are modifiable by diet. These are high blood cholesterol, hypertension, insulin resistance, and obesity. Together, these are termed insulin resistance syndrome, also known as metabolic syndrome or syndrome X. Each of these risk factors risk of developing CHD independently, but when they occur simultaneously, they synergistically risk. Insulin Resistance 2001 Brooks/Cole a division of Thomson Learning Inc Thomson Syndrome
DIETARY RECOMMENDATIONS FOR REDUCING CVD RISK Recommendations focus on LDL-cholesterol. Dietary cholesterol The amount of dietary cholesterol is not a major factor that affects blood cholesterol concentration. We eat perhaps 1 g of cholesterol per day , whereas the amount of cholesterol in the body is approx. 140 g, of which about 8 g is in the plasma. In contrast, we eat several 'plasma's-worth' of glucose in a single meal. Cholesterol
is not rapidly absorbed like glucose: it enters the plasma slowly, like triacylglycerol. Further, cholesterol intake leads to cholesterol entry into cells, which effectively suppresses cholesterol synthesis. For people with familial hypercholesterolemia, a low-cholesterol diet will help, but for most people the blood cholesterol concentration is related far more closely to the dietary intake of saturated fatty acids. Dietary fatty acids The initial evidence for the role of saturated fatty acids in raising serum cholesterol concentrations was epidemiological: the wide differences in average plasma cholesterol concentration between different countries were found to relate to the average consumption of saturated fatty acids. More detailed studies since have shown that this is an over-generalization. Particular saturated fatty acids are worse 'culprits' than others: stearic acid (C 18:0) - relatively inert, palmitic acid (C16:O) and myristic acid (CI4:0) - raise the cholesterol concentration mono-unsaturated acids - oleic acid (C18:1) found in olive oil - relatively neutral polyunsaturated fatty acids, e.g. linoleic acid (Cl8:2) and linolenic acid (C18:3) have a cholesterol-lowering effect. A change in the fatty acid content of the diet will produce a fairly predictable change in serum cholesterol concentration.
Trans Fatty Acids
Trans fats are a type of fat found naturally in some foods. They also are formed when polyunsaturated or monounsaturated fats undergo hydrogenation, a process whereby hydrogen molecules are added to the oils to improve their stability and utility in certain foods. In the body, trans fatty acids even the monounsaturated onesalter blood cholesterol the same way some saturated fatty acids do: they raise LDL and lowers HDL cholesterol, although to lower extent.
Structure of Cis- and Trans- Fatty Acids The unsaturated fatty acids present in foods are usually in the cis configuration, meaning that the hydrogens are on the same side of the double bond. Trans fatty acids are produced from the cis double bonds as a side reaction during partial hydrogenation of an oil. The trans fatty acids have a decreased bond angle compared to the cis isomer, resulting in the higher melting point. Epidemiological studies suggest a weak association between dietary trans fatty acids and heart disease risk. The average amount of trans fatty acids consumed by adults in the U.S. is small-only about 2-4% of total calories-compared to saturated fat, which constitutes 12-14% of the typical diet. Most of that comes from partially hydrogenated vegetable oils, and about 25 percent from foods.The unsaturated fatty acids present in foods are usually in the cis configuration, meaning that the hydrogens are on the same side of the double bond. Trans fatty acids are produced from the cis double bonds as a side reaction during partial hydrogenation of an oil. The trans fatty acids have a decreased bond angle compared to the cis isomer, resulting in the higher melting point. Omega-3 Fatty Acids and 6 Fatty Acids The two principal essential fatty acids (EFA) are Omega-6 (n-6) series and the Omega-3 (n-3) series. The number indicates the position of the first double carbon bond when counting from a specified end of the molecule. These fatty acids must be obtained from the diet because we humans are lack the enzymes necessary to create double bonds in the specific positions. The major dietary sources of EFA are polyunsaturated fatty acid-rich vegetable oils. Omega-6 is particularly high in sunflower, safflower, corn and soybean oils. Omega-3 fatty is particularly high in soybean, flaxseed, linseed and canola oils as well as fish oil and cold water fish.
The EFA are dietary precursors of Arachadonic Acid, eicospentenoic acid (EPA) and docosahexaenoic acid (DHA), which in turn are precursors of eicosanoids and leukotrienes. These are important and potent mediators of many biochemical processes. The biological properties of eicosanoids differ depending upon the FA family (omega-3 or omega-6) from which they are produced: omega-3 fatty acid derived eicosanoids tend to decrease platelet aggregation omega-6 fatty acids derived eicosanoids are more likely to increase platelet aggregation Omega-6 fatty acids also play a role in growth, skin integrity, fertility and maintaining RBC structure, and omega3 in providing structure and function to cell membranes. There is some evidence that regular consumption of foods rich in omega-3 fatty acids reduces cardiovascular risk in the long run. Mechanisms include: reducing serum TG and cholesterol level s moderating tachycardia and lowering blood pressure inhibiting platelet aggregation formation and of blood clots reducing inflammation preventing plaque formation in coronary arteries Dietary Fiber o high fiber diets may protect against heart disease and stroke; such diets are low in animal fat and cholesterol and high in solube fibers, vegetable proteins, and phytochemicals all factors associated with a lower risk of heart disease o soluble fiber (oat bran, barley and legumes): blood cholesterol by binding bile acids, thus their excretion . Consequently, liver must use its cholesterol to make new bile acids. In addition, the bacterial by-products of fiber digestion in the colon also inhibit cholesterol synthesis in the liver. The net result is blood cholesterol. o May also displace fat in the diet (indirect role). Even when dietary fat is low, however, high intakes of soluble fiber exert a separate and significant cholesterol-lowering effect Alcohol moderate alcohol consumption may overall mortality in general and the risk of CHD in particular by HDL-cholesterol, preventing blood blot formation, and interfering with cell growth in the blood vessels benefits are most apparent in people >50 years of age, those with more than one risk factor, and those with high LDL-cholesterol. "moderate" alcohol consumption=1-2 drinks/day. In larger amounts (3 drinks/day), alcohol associated w/ mortality. Alcohol from any source red or white wine, beer, or distilled liquor appears to be equally effective and that alcohol itself may be the protective factor. In addition to alcohol, wine contains phytochemicals that may also protect against CVD. These act as antioxidants ( LDL-cholesterol oxidation) and may alter prostaglandin metabolism ( blood clot formation) o "French Paradox": the wine-drinking people of France enjoy a lower incidence of CHD than people in U.S., even though they have many of the same risk factors. Soy
soyfood is contains high-biologically-available protein, is rich in essential fatty acids, high soluble fiber, low SFA and rich in isoflavones found to be protective against CVD o BP o resistance to LDL-oxidation o vascular reactivity o thrombus formation o suppresses smooth muscle cell proliferation o is positively related to HDL-cholesterol and negatively related to TG, LDL-cholesterol BUT, no data are currently available on direct relationship between soyfood and CLINICAL ENDPOINTS of CHD (just intermediate markers or risk factors)
Vitamin E o found in vegetable oils, margarines, some nuts, wheat germ o slows progession of plaque formation o risk of heart attack in people with CHD o LDL oxidation via antioxidant properties B Vitamins Homocysteine may be a significant risk factor for the atherogenesis and is related to dietary factors. Homocysteine is formed during the normal metabolism of methionine; it can be re-methylated to methionine in a methyltetrahydrofolate and cobalamin-dependent reaction. Since homocysteine concentrations in blood and tissues are dependent on enzyme activities requiring folate, vitamin B12 and B6 as cofactors, they reflect the interplay of genetic, constitutional, and environmental (mostly dietary) factors. Many patients with CARDIOVASCULAR DISEASE have elevated homocysteine concentrations Homocysteine may interfere with vascular endothelial cell wall regulatory mechanisms. Exposure of vascular endothelium to elevated homocysteine disrupts arterial wall function; one of the mechanisms may be impairment of intraendothelial generation of nitric oxide, and important vasodilator. Normal byproducts of homocysteine action include oxygen free radicals that are atherogenic Diets rich in folate, vitamins B6 and B12 may lower homocysteine levels. AMERICAN HEART ASSOCIATION: DIETARY RECOMMENDATIONS TO REDUCE CVD RISK Purpose: The general aim of dietary therapy is to reduce elevated cholesterol levels while maintaining a nutritionally adequate eating pattern. Use: Dietary therapy should occur in two steps, the Step-One and Step-Two Diets, that are designed to progressively reduce intakes of saturated fatty acids and cholesterol and to promote weight loss in patients who are overweight by eliminating excess total energy. The Step-One Diet should be prescribed and explained by the physician and his or her staff. This diet involves an intake of total fat less than 30% of energy, saturated fatty acids less than 10% of energy, and cholesterol less than 300 mg/day. The Step-Two Diet, used if the response to the Step-One Diet is insufficient, calls for a further reduction in saturated fatty acid intake to less than 7% of energy and in cholesterol to less than 200 mg/day. The Step-One Diet calls for the reduction of the major and obvious sources of saturated fatty acids and cholesterol in the diet; for many patients this can be achieved without a radical alteration in dietary habits. The Step-Two Diet requires careful attention to the whole diet to reduce intake of saturated fatty acids and cholesterol to a minimal level compatible with an acceptable and nutritious diet. Involvement of a registered dietitian is useful, particularly for intensive dietary therapy, such as the Step-Two Diet. After starting the Step-One Diet, the total serum cholesterol level should be measured and adherence to the diet assessed at 4 to 6 weeks and at 3 months. If the total cholesterol monitoring goal is met, the LDLcholesterol level should be measured to confirm that the LDL goal has been achieved. If this is the case, the patient enters a long-term monitoring program and is seen quarterly for the first year and twice yearly thereafter. At these visits total cholesterol level should be measured, and dietary and behavior modifications reinforced. If the cholesterol goal has not been achieved with the Step-One Diet, the patient should generally be referred to a registered dietitian. With the aid of the dietitian, the patient should progress to the Step-Two Diet, or to another trial on the Step-One Diet (with progression to the Step-Two Diet if the response is still not satisfactory). On the Step-Two Diet, total cholesterol levels should again be measured and adherence to the diet assessed after 4 to 6 weeks and at 3 months of therapy. If the desired goal for total cholesterol (and for LDL-cholesterol) lowering has been attained, long-term monitoring can begin. If not, drug therapy should be considered. A minimum of 6 months of intensive dietary therapy and counseling should usually be carried out before initiating drug therapy; shorter periods can be considered in patients with severe elevations of LDLcholesterol (> 225 mg/dl) or with definite coronary heart disease. Drug therapy should be added to, and not substituted for, dietary therapy.
Adequacy.- Based on the individual's food choices, the diets are adequate in all nutrients according to the National Research Council's Recommended Dietary Allowances. NATIONAL CHOLESTEROL EDUCATION PROGRAM: STEP-ONE AND STEP-TWO DIETS RECOMMENDED INTAKE NUTRIENT Total fat Saturated fatty acid Polyunsaturated fatty acids Monounsaturated fatty acids Carbohydrates Protein Cholesterol Total energy Step-One Diet Step-Two Diet
Less than 30% of total energy Less than 10% of total energy Less than 7% of total energy Up to 10% of total energy 10% to 15% of total energy 50% to 60% of total energy 10% to 20% of total energy Less than 300 mg/day Less than 200 mg/day To achieve and maintain desirable weight
Source: The National Cholesterol Education Program, Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. U.S. Department of Health and Human Services, Public Health Service National Institutes of Health Publication No. 89-2925, 1989.
In summary: Effective ways to lower LDL cholesterol concentration in blood are: Lower fat intake Reduce excess body fat Replace some of the saturated fat with polyunsaturated fat Eat some cold-water fish (contains omega-3 fatty acids) Avoid partially hydrogenated fats (contain trans fatty-acids) Reduce cholesterol intake Increase dietary fiber intake (fresh fruits and vegetables work best)
Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults
STEP 1: Determine lipoprotein levels - obtain complete lipoprotein profile after 9- to 12-hour fast. Classification of LDL, Total, and HDL Cholesterol (mg/dL)
LDL Cholesterol Primary Target of Therapy
<100 100-129 130-159 160-189 190 Optimal Near Optimal/Above Optimal Borderline High High Very high
Total Cholesterol
<200 200-239 240 Desirable Borderline High High
HDL Cholesterol
<40 60 Low High
STEP 2: Identify presence of clinical atherosclerotic disease that confers high risk for coronary heart disease (CHD) events (CHD risk equivalent): Clinical CHD Symptomatic carotid artery disease Peripheral arterial disease Abdominal aortic aneurysm.
Cholesterol Risk Assessment
Risk assessment
Measure total blood cholesterol
Parental High Blood Cholesterol >240 mg/dL
Positive family history*
Do lipoprotein analysis
Acceptable Blood Cholesterol <170 mg/dL
Repeat cholesterol measurement within 5 years Provide education on recommended eating pattern and risk factor reduction
Borderline Blood Cholesterol 170-199 mg/dL
Repeat cholesterol and average with previous measurement
<170 mg/dL
>170 mg/dL
High Blood Cholesterol >200 mg/dL
Do lipoprotein analysis
*Defined as a history of premature (before age 55 years) cardiovascular disease in a parent or grandparent
STEP 3: Determine presence of major risk factors (other than LDL): Major Risk Factors (Exclusive of LDL Cholesterol) That Modify LDL Goals Cigarette smoking Hypertension (BP 140/90 mmHg or on antihypertensive medication) Low HDL cholesterol (<40 mg/dl)* Family history of premature CHD (CHD in male first degree relative <55 years; CHD in female first degree relative <65 years) Age (men 45 years; women 55 years) * HDL cholesterol 60 mg/dL counts as a "negative" risk factor; its presence removes one risk factor from the total count. Note: in ATP III, diabetes is regarded as a CHD risk equivalent. STEP 4: If 2+ risk factors (other than LDL) are present without CHD or CHD risk equivalent, assess 10-year (short-term) CHD risk Three levels of 10-year risk: >20% -- CHD risk equivalent 10-20% <10% STEP 5: Determine risk category: Establish LDL goal of therapy Determine need for therapeutic lifestyle changes (TLC) Determine level for drug consideration
LDL Cholesterol Goals and Cutpoints for Therapeutic Lifestyle Changes (TLC) and Drug Therapy in Different Risk Categories. LDL Level at Which to Initiate LDL Level at Which to Consider Drug Risk Category LDL Goal Therapeutic Therapy Lifestyle Changes (TLC) CHD or CHD Risk Equivalents (10130 mg/dL (100-129 100 mg/dL <100 mg/dL year risk >20%) mg/dL: drug optional)* 10-year risk 10-20%: 2+ Risk Factors (10-year risk 130 mg/dL 130 mg/dL <130 mg/dL 10-year risk <10%: 20%) 160 mg/dL 190 mg/dL (160-189 mg/dL: LDL0-1 Risk Factor** <160 mg/dL 160 mg/dL lowering drug optional)
* Some authorities recommend use of LDL-lowering drugs in this category if an LDL cholesterol <100 mg/dL cannot be achieved by therapeutic lifestyle changes. Others prefer use of drugs that primarily modify triglycerides and HDL, e.g., nicotinic acid or fibrate. Clinical judgment also may call for deferring drug therapy in this subcategory. ** Almost all people with 0-1 risk factor have a 10-year risk <10%, thus 10-year risk assessment in people with 0-1 risk factor is not necessary.
STEP 6: Initiate therapeutic lifestyle changes (TLC) if LDL is above goal. TLC Features TLC Diet: o Saturated fat <7% of calories, cholesterol <200 mg/day o Consider increased viscous (soluble) fiber (10-25 g/day) and plant stanols/sterols (2g/day) as therapeutic options to enhance LDL lowering
Weight management Increased physical activity
STEP 7: Consider adding drug therapy if LDL exceeds levels shown in Step 5 table: Consider drug simultaneously with TLC for CHD and CHD equivalents Consider adding drug to TLC after 3 months for other risk categories. Drugs Affecting Lipoprotein Metabolism Drug Class Agents and Daily Doses Lovastatin (20-80 mg), Pravastatin (20-40 mg), Simvastatin (20-80 mg), Fluvastatin (20-80 mg), Atorvastatin (10-80 mg), Cerivastatin (0.4-0.8 mg) Cholestyramine (416 g) Colestipol (520 g) Colesevelam (2.6-3.8 g) Lipid/Lipoprotein Effects Side Effects Contraindications Absolute: Active or chronic liver disease Relative: Concomitant use of certain drugs* Absolute: - dysbetalipoproteinemia - TG >400 mg/dL Relative: - TG >200 mg/dL Absolute: - Chronic liver disease - Severe gout Relative: - Diabetes - Hyperuricemia - Peptic ulcer disease
HMG CoA reductase inhibitors (statins)
LDL-C HDL-C TG
18-55% 5-15% 7-30%
Myopathy Increased liver enzymes
Bile acid Sequestrants
15-30% LDL-C HDL-C 3-5% TG No change or increase
Gastrointestinal distress Constipation Decreased absorption of other drugs
Immediate release (crystalline) Flushing nicotinic acid (1.5-3 Hyperglycemia 5-25% gm), extended LDL-C Hyperuricemia (or HDL-C Nicotinic acid release nicotinic 15-35% gout) acid (Niaspan ) TG 20-50% Upper GI distress (1-2 g), sustained Hepatotoxicity release nicotinic acid (1-2 g) Gemfibrozil (600 LDL-C 5-20% Absolute: mg BID) (may be increased Dyspepsia - Severe renal Fenofibrate (200 in patients with high Gallstones disease Fibric acids mg) TG) Myopathy - Severe hepatic Clofibrate (1000 HDL-C 10-20% disease mg BID) TG 20-50% * Cyclosporine, macrolide antibiotics, various anti-fungal agents, and cytochrome P-450 inhibitors (fibrates and niacin should be used with appropriate caution). STEP 8: Identify metabolic syndrome and treat, if present, after 3 months of TLC. Clinical Identification of the Metabolic Syndrome - Any 3 of the Following: Risk Factor Abdominal obesity* Men Women Triglycerides HDL cholesterol Men Women blood pressure Fasting glucose Defining Level Waist circumference** >102 cm (>40 in) >88 cm (>35 in) 150 mg/dL <40 mg/dl <50 mg/dl 130/ 85 mmHg 110 mg/dL
* Overweight and obesity are associated with insulin resistance and the metabolic syndrome. However, the presence of abdominal obesity is more highly correlated with the metabolic risk factors than is an elevated body mass index (BMI). Therefore, the simple measure of waist circumference is recommended to identify the body weight component of the metabolic syndrome. ** Some male patients can develop multiple metabolic risk factors when the waist circumference is only marginally increased, e.g., 94-102 cm (37-39 in). Such patients may have a strong genetic contribution to insulin resistance. They should benefit from changes in life habits, similarly to men with categorical increases in waist circumference. Treatment of the metabolic syndrome Treat underlying causes (overweight/obesity and physical inactivity): o Intensify weight management o Increase physical activity Treat lipid and non-lipid risk factors if they persist despite these lifestyle therapies: o Treat hypertension o Use aspirin for CHD patients to reduce prothrombotic state o Treat elevated triglycerides and/or low HDL (as shown in Step 9 below)
STEP 9: Treat elevated triglycerides. ATP III Classification of Serum Triglycerides (mg/dL) < 150 150-199 200-499 500 Normal Borderline high High Very high
Treatment of elevated triglycerides ( 150 mg/dL) Primary aim of therapy is to reach LDL goal. Intensify weight management. Increase physical activity. If triglycerides are 200 mg/dL after LDL goal is reached, set secondary goal for non-HDL cholesterol (total - HDL) 30 mg/dL higher than LDL goal. Comparison of LDL Cholesterol and Non-HDL Cholesterol Goals for Three Risk Categories Risk Category CHD and CHD Risk Equivalent (10-year risk for CHD >20%) Multiple (2+) Risk Factors and 10year risk 20% 0-1 Risk Factor LDL Goal (mg/dL) <100 <130 <160 <130 <160 <190 Non-HDL Goal (mg/dL)
If triglycerides 200-499 mg/dL after LDL goal is reached, consider adding drug if needed to reach nonHDL goal: intensify therapy with LDL-lowering drug, or add nicotinic acid or fibrate to further lower VLDL. If triglycerides 500 mg/dL, first lower triglycerides to prevent pancreatitis: very low-fat diet ( 15% of calories from fat) weight management and physical activity