Hyperlipidemia

Seminar

1. By, BASIL WILSON 13Q0408 SEMINAR ON HYPERLIPIDEMIA

2. Hyperlipidaemia is an umbrella term that refers to any of several acquired or genetic disorders that result in a high level of lipids (fats, cholesterol and triglycerides) circulating in the blood. These lipids can enter the walls of arteries and increase your risk of developing  atherosclerosis (hardening of the arteries), which can lead to stroke, heart attack  ,etc. A 4-ml sample of hyperlipidemic blood in a vacutainer with EDTA. Left to settle for four hours without centrifugation, the lipids separated into the top fraction.

3. KEY CONCEPTS Hypercholesterolemia, elevated low-density lipoprotein ( LDL) levels , and low high-density lipoprotein (HDL) levels are unequivocally linked to increased risk for coronary heart disease and cerebrovascular morbidity and mortality. Multiple genetic abnormalities and environmental factors are involved in clinical lipid abnormalities, and routinely used clinical laboratory measurements do not define the underlying abnormalities . Initial therapy for any lipoprotein disorder is therapeutic lifestyle changes with restricted intake of total and saturated fat and cholesterol and a modest increase in polyunsaturated fat intake along with a program of regular exercise and weight reduction if needed. If pharmacologic therapy is insufficient after therapeutic lifestyle changes , lipid-lowering agents should be chosen based on the specific lipoprotein disorder presentation and the severity of the lipid abnormality .

4. Patients who do not respond to statin monotherapy can be treated with combination therapy for hypercholesterolemia but should be monitored closely because of an increased risk for adverse effects and drug interactions. Low high-density lipoprotein-cholesterol (HDL-C) levels are addressed with lifestyle modifications, such as smoking cessation and increased exercise. Niacin, gemfibrozil , and fenofibrate can significantly increase HDL-C. Decreasing elevated total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels reduce coronary heart disease mortality and total mortality; increasing HDL reduces coronary heart disease events as well . Considering compliance, adverse effects, and effectiveness, for patients with hypercholesterolemia statins are the drugs of choice because they are the most potent form of monotherapy and are cost effective in patients with known coronary artery disease or multiple risk factors and in high-risk primary prevention patients.

5. ANATOMY &PHYSIOLOGY Hyperlipidaemia simply is a disorder in which there are abnormally elevated levels of fat particles in the blood known as lipids. This lipids can adhere to the walls of the arteries and restrict blood flow which in turn leads to significant risk of heart attack and stroke.

6. There are 3 major lipids in the body CHOLESTEROL TRIGLYCERIDES PHOSPHOLIPIDS

7. These lipids are in soluble in blood plasma, so they have to be transported through out the body in a protein capsule known as Lipoprotein. Depending on the variation in lipid and Apo lipoprotein composition as well as density, lipoproteins can be divided into 4 major types, Chylomicrons VLDL LDL HDL

8. Dietary lipids Deliver energy rich triglycerides to cells throughout the body Synthesis of steroid hormones and cell membrane 50%

9. Now the problem arises when we have abnormally high levels of LDL cholesterol which can accumulate on the innermost layer of the artery wall and lead to formation of atherosclerotic lesions. This is why LDL is often referred to as bad cholesterol. HDL on the other hand prevents formation of atherosclerotic lesions by removing cholesterol as well as suppressing LDL oxidation and vascular inflammation. This is why HDL cholesterol is often referred to as good cholesterol. So abnormally low level of HDL can also leads to atherosclerosis. Cross section of Normal & Clogged artery

10. Classification of Total, LDL, and HDL Cholesterol, and Triglycerides Total cholesterol <200 Desirable 200–239 Borderline high ≥240 High LDL cholesterol <100 Optimal 100–129 Near or above optimal 130–159 Borderline high 160–189 High ≥190 Very high HDL cholesterol <40 Low ≥60 mg/ dL High Triglycerides <150 Normal 150–199 Borderline high 200–499 High ≥500 Very high All values are given in milligrams per deciliters .

11. EPIDEMIOLOGY Cardiovascular disease (CVD) is the leading cause of death among adults in the United States, and people with hyperlipidaemia are at roughly twice the risk of developing CVD as compared to those with normal total cholesterol levels. 1 Patients with familial hypercholesterolemia (FH) have an even greater risk of developing CVD at an earlier age. More than 3 million people have this genetic disorder in the United States and Europe. It is extremely common for those who live in developed countries and follow a Western high-fat diet.

12. ETIOLOGY Hyperlipidemia can be caused by primary causes (genetic predisposition) or secondary causes (diet, underlying disease, or medications). Primary hyperlipidemia is associated with high morbidity and mortality. A defect often occurs in lipid metabolism or transport in primary hyperlipidemia, resulting in reduced LDL receptor activity and accumulation of LDL cholesterol in the plasma, leading to atherogenesis . All patients should be evaluated for secondary causes of hyperlipidemia. Diseases such as diabetes mellitus, hypothyroidism, Cushing's syndrome, obstructive liver disease, nephrotic syndrome, and alcoholism are all common causes of high cholesterol.

13. Conditions Causing Hypertriglyceridemia Conditions Causing Hypercholesterolemia Acromegaly Anorexia nervosa Alcoholism Cholestasis Burns Cushing's syndrome Chronic renal failure Growth hormone deficiency Diabetes mellitus Hypothyroidism Glycogen storage disease Myelomatosis ( immunoglobulinsA and G) Hyperandrogenism in women Nephrotic syndrome Lipodystrophy Obstructive liver disease Pancreatitis Systemic lupus and polyclonal gammopathy Obesity Secondary Causes of Hyperlipidaemia

14. Hypercholesterolemia Low high-density lipoprotein Malnutrition Malabsorption Myeloproliferative diseases Chronic infectious diseases: acquired immune deficiency syndrome, tuberculosis Monoclonal gammopathy Chronic liver disease Malnutrition Obesity Drugs: non-ISA β- blockers, anabolic steroids, probucol , isotretinoin , progestins

15. Medication Total Cholesterol LDL HDL TG VLDL Anabolic steroids ↑ ↑ ↓ — — Anticonvulsants — — ↑ — — Atypical antipsychotics — — ↓ ↑ — β-blockers (non-ISA) — — ↓ ↑ ↑ Corticosteroids ↑ ↑ ↑ ↑ ↑ Cyclosporine ↑ ↑ — — — Estrogen therapy ↓ ↓ ↑ ↑ ↑ Isotretinoin ↑ — ↓ ↑ — Phenothiazines ↑ — ↓ — — Progestins ↑ ↑ ↓ — — Protease inhibitors ↑ ↑ — ↑ — Retinoids ↑ ↑ ↓ ↑ ↑ Thiazide diuretics ↑ ↑ — ↑ ↑ Medications that can induce Hyperlipidaemia

16. CLINICAL PRESENTATION General ■ Most patients are asymptomatic for many years before disease is clinically evident ■ Patients with the metabolic syndrome may have three or more of the following: abdominal obesity, atherogenic dyslipidemia , increased blood pressure, insulin resistance with or without glucose intolerance, prothrombotic state, or proinflammatory state. Symptoms ■ None to severe chest pain, palpitations, sweating, anxiety, shortness of breath, loss of consciousness or difficulty with speech or movement, abdominal pain, sudden death

17. Signs ■ None to severe abdominal pain, pancreatitis, eruptive xanthomas , peripheral polyneuropathy, high blood pressure, body mass index >30 kg/m2 or waist size >40 inches in men ( 35 inches in women ) Laboratory Tests ■ Elevations in total cholesterol, LDL, triglycerides, apolipoprotein B, C-reactive protein ■ Low HDL Other Diagnostic Tests ■ Lipoprotein(a), homocysteine , serum amyloid A, small dense LDL (pattern B), HDL subclassification, apolipoprotein E isoforms, apolipoprotein A-1, fibrinogen, folate , Chlamydia pneumoniae titer , lipoprotein-associated phospholipase A2, omega-3 ■ Various screening tests for manifestations of vascular disease (ankle–brachial index, exercise testing, magnetic resonance imaging ) and diabetes (fasting glucose, oral glucose tolerance test )

18. Physical signs of Hyperlipidaemia

19. Corneal arcus Lipemia retinalis

20. TREATMENT

21. GENERAL APPROACH TO TREATMENT Establishing targeted changes and outcomes with consistent reinforcement of goals and measures at follow-up visits to attain goals are important to reduce barriers for optimizing Therapeutic Lifestyle Changes(TLC) and pharmacologic therapy . TLC should be implemented in all patients prior to considering drug therapy. The components of TLC include reduced intake of saturated fats and cholesterol, dietary options to reduce LDL , such as consumption of plant stanols and sterols and soluble fibre, weight reduction, and increased physical activity. In general, physical activity of moderate intensity 30 minutes per day for most days of the week should be encouraged. Patients with known CAD or who are at high risk should be evaluated before they undertake vigorous exercise. Weight and BMI should be determined at each visit, and lifestyle patterns to induce a weight loss of 10% should be discussed with persons who are overweight. All patients should be counselled to stop smoking.

22. NON-PHARMACOLOGIC TREATMENT Eat a heart-healthy diet Making changes to your diet can lower your “bad” cholesterol levels and increase your “good” cholesterol levels. Here are a few changes you can make: Choose healthy fats.  Avoid saturated fats that are found primarily in red meat, bacon, sausage, and full-fat dairy products. Choose lean proteins like chicken, turkey, and fish when possible. Switch to low-fat or fat-free dairy. And use monounsaturated fats like olive and canola oil for cooking. Cut out the trans fats.  Trans fats are found in fried food and processed foods, like cookies, crackers, and other snacks. Check the ingredients on product labels. Skip any product that lists “partially hydrogenated oil.” Eat more omega-3s.  Omega-3 fatty acids have many heart benefits. You can find them in some types of fish, including salmon, mackerel, and herring. They can also be found in some nuts and seeds, like walnuts and flax seeds . DIET

23. Weight Being overweight is a risk factor for hyperlipidemia and heart disease. Losing weight can help reduce LDL, total cholesterol, and triglyceride levels. It can also boost HDL, which helps to remove the bad cholesterol out of the blood. To lose weight, adopt a low-calorie diet and increase your physical activity Increase your fiber intake.  All fiber is heart-healthy, but soluble fiber , which is found in oats, brain, fruits, beans, and vegetables, can lower your LDL cholesterol levels. Eat more fruits and veggies.  They’re high in fiber and vitamins and low in saturated fat.

24. Physical activity A lack of physical activity is a risk factor for heart disease. Regular exercise and activity helps lower LDL, raise HDL, and encourage weight loss. At least 30 minutes of physical activity is recommended, at least 5 days a week. Brisk walking is an excellent and easy choice . Quit smoking Smoking triggers many problems that contribute to heart disease. It promotes plaque buildup on the walls of the arteries, increases LDL levels, and it encourages blood clot formation and inflammation. Quitting smoking will result in higher HDL. This may be one reason why cardiovascular disease risk falls after quitting.

25. Macronutrient Recommendations for the Therapeutic Lifestyle Changes Diet Component a Recommended Intake Total fat 25 %–35% of total calories Saturated fat Less than 7% of total calories Polyunsaturated fat Up to 10% of total calories Monounsaturated fat Up to 20% of total calories Carbohydrates b 50 %–60% of total calories Cholesterol < 200 mg/day Dietary fibre 20–30 g/day Plant sterols 2 g /day Protein Approximately 15% of total calories Total calories To achieve and maintain desirable body weight a Calories from alcohol not included. b Carbohydrates should derive from foods rich in complex carbohydrates, such as whole grains, fruits, and vegetables.

26. PHARMACOLOGIC THERAPY

27. HMG CoA Reductase Inhibitors

28. Fibrates

29. Niacin

30. Bile Acid Sequestrants

31. REFERENCE Dipiro Herfindal Textbook Of Therapeutics Goodman & Gilman CIMS Micromedex Medscape