Hyper lipidemia
- 2. • DEFINITION • Disorders of lipoprotein metabolism together with high fat diets, obesity and physical inactivity have all contributed to the current epidemic of therosclerotic disease seen in developed countries. • Hyperlipidemia is a term for abnormally high levels of fats (lipids) in the blood. • The two major types of lipids found in the blood are triglycerides and cholesterol.
- 3. • Triglycerides are made when our body stores the extra calories it doesn’t need for energy. • it also come directly from our diet in foods such as red meat and whole-fat dairy. • A diet high in refined sugar, fructose, and alcohol raises triglycerides. • Cholesterol is produced naturally in our liver because every cell in our body uses it. • Similar to triglycerides, cholesterol is also found in fatty foods like eggs, red meat, and cheese. • High cholesterol can be inherited, it’s more often the result of unhealthy lifestyle choices. • Cholesterol is a fatty substance that travels through our bloodstream on proteins called lipoproteins. • When too much cholesterol in our blood, it can build up on the walls of our blood vessels and form plaque. • Over time, plaque deposits grow larger and begin to clog up our arteries, which can lead to heart disease, heart attack, and stroke.
- 4. The causes of Hyperlipidemia can be due to: • Genetic factors: This is known as primary Hyperlipidemia. • Poor diet and other factors: This is known as secondary Hyperlipidemia. • When the body cannot use or remove excess fat, it builds up in the blood. Over time, this damages the arteries and internal organs and contributes to the development of heart disease. • Other causes include: excessive alcohol consumption,Obesity , DM • medications such as hormones or steroids, • kidney disease an underactive thyroid gland, or hypothyroidism pregnancy • Familial hyperlipidemia stems from a genetic disorder. A mutated gene is passed down from a parent and causes a missing or malfunctioning LDL receptor.
- 5. Risk groups • Age: in individuals under 40 years of age the charts overestimate risk; over the age of 70 years risk is • underestimated by the charts and most have a 10-year risk >20%. • • Gender: there are separate charts for men and women. • • Ethnicity: the risk prediction charts have only been validated in white caucasians and underestimate risk in • individuals from the Indian subcontinent (India, Pakistan, Bangladesh and Sri Lanka) by a factor of 1.5. • • Smoking history: individuals who have stopped smoking within 5 years of assessment should be considered as • current smokers. • • Family history: risk increases by a factor of 1.5 when CHD has occurred in a first- degree relative male <55 years or female <65 years, when a number of family members have developed CHD risk increases by a factor of 2. • • Body mass index (BMI) and waist circumference: the charts do not adjust for either BMI or waist circumference;these factors need to be taken into account in the clinical decision-making process. • • Non-fasting blood glucose: if non-fasting glucose >6.1 mmol/L, the individual should be assessed for impaired glucose regulation or diabetes. Individuals with type 2 diabetes aged over 40
- 6. Types of hyperlipidemia • Primary hyperlipidemia: There are many types of familial dyslipidemia; • common forms include: • Familial hyeprcholestrolemia (FH): – Autosomal dominant • LDL receptor defects, familial hypercholesterolaemias in which LDL-C is raised, • the primary mixed (combined) hyperlipidaemias in which both LDL-C and triglycerides are raised – In heterozygotes, cholesterol levels are in the range of 6 - 12 mmol/L, while in homozygotes, levels can be as high as 20 mmol/L – Clinical features: tendon xanthoma, corneal arcus and xanthelasma . • Polygenic hypercholesterolemia: – Most common form of familial hyperlipidemia – Plasma cholesterol is not as high as FH and is influenced by environmental factors such as diet •
- 7. • Familial combined hyperlipidemia: has an incidence of 1 in 200 and is associated with excessive synthesis of VLDL-C. In addition to increases in triglyceride and LDL-C levels, patients also typically have raised levels of apoB and elevated levels of • small, dense LDL particles. – Results in elevated cholesterol and TG – Associated with diabetes, obesity, cutaneous manifestations of hyperlipidemia and premature ischemic heart disease (IHD) • Familial chylomicronemia: In the heterozygous state, familial apoC-II – Failure to metabolise the chylomicrons due to deficiency of lipoprotein lipase or apoC-II – Presents with pancreatitis, hepatosplenomegaly and eruptive xanthomata • Familial hypertriglyceridemia: – Autosomal dominant – Associated with eruptive xanthomas, diabetes and pancreatitis •
- 8. • Familial type III hyperlipoproteinaemia : • has an incidence of 1 in 5000. • It is characterised by the accumulation of chylomicron and VLDL remnants that fail to get cleared at a normal rate by hepatic receptors due to the presence of less active polymorphic forms of apoE. • Triglycerides and TC are both elevated and accompanied by corneal arcus, xanthelasma, • Familial lipoprotein lipase deficiency • is characterised by marked hypertriglyceridaemia and chylomicronaemia, and usually presents in childhood. It has an incidence of 1 per million and is due to a deficiency of the extrahepatic enzyme lipoprotein lipase,
- 9. • Secondary hyperlipidemia: Alcoholism Diabetes • Type 2 diabetes, typically have • increased triglycerides and decreased HDL-C. Levels of TC • may be similar to those found in non-diabetic individuals but • the patient with type 2 diabetes often has increased levels of • highly atherogenic small dense LDL particles.: • Cushing syndrome • Renal failure • Cholestasis • Nephrotic syndrome • Hypothyroidism • Drugs: β blockers, thiazides, steroids and antiretrovirals
- 10. • obesity : Chronic, excessive intake of calories leads to increased concentrations of triglycerides and reduced HDL-C. •
- 11. • The clinically important lipids in the blood (unesterified and esterified cholesterol and triglycerides. • There are six main classes of lipoproteins: • 1 chylomicrons, • 2. chylomicron remnants, • 3. very low-density lipoproteins (VLDL-C), • 4.intermediate-density lipoproteins (IDL-C) • 5., lowdensity lipoproteins (LDL-C) and • 6. high-density lipoproteins (HDL-C).
- 13. Metabolic path way of lipids • The protein components of lipoproteins are known as apoproteins (apo), of which apoproteins A-I, E, C and B are the most important. • Apo protein B exists in two forms: B-48, which is present in chylomicrons and associated with the transport of ingested lipids, and B-100, • which is found in endogenously secreted VLDL-C and associated with the transport of lipids from the liver.
- 14. • When dietary cholesterol and triglycerides are absorbed from the intestine they are transported in the intestinal lymphatics as chylomicrons. • These are the largest of the lipoprotein particles of which triglycerides normally constitute approximately 80% of the lipid core. • The chylomicrons pass through blood capillaries in adipose tissue and skeletal muscle where the enzyme lipoprotein lipase is located, bound to the endothelium. Lipoprotein lipase is activated by apoprotein C-II on the surface of the chylomicron. • The lipase catalyses the breakdown of the triglyceride in the chylomicron to free fatty acid and glycerol, which then enter adipose tissue and muscle.
- 15. • The cholesterol-rich chylomicron remnant is taken up by receptors on hepatocyte membranes, and in this way dietary cholesterol is delivered to the liver and cleared from the circulation. • VLDL-C is formed in the liver and transports triglycerides, which again make up approximately 80% of its lipid core, to the periphery. • The triglyceride content of VLDL-C is removed by lipoprotein lipase in a similar manner to that described for chylomicrons above, and forms IDL-C particles. The core of IDL-C particles is roughly 50% triglyceride and 50% cholesterol esters, acquired from HDL-C under the
- 16. • influence of the enzyme lecithin-cholesterol acyltransferase (LCAT). Approximately 50% of the body's IDL particles are cleared from serum by the liver. • The other 50% of IDL-C are further hydrolysed and modified to lose triglyceride and apoprotein E1 and become LDL-C particles. LDL-C is the major cholesterol-carrying particle in serum.
- 17. • LDL-C provides cholesterol, an essential component of cell membranes, bile acid and a precursor of steroid hormones to those cells that require it. • LDL-C is also the main lipoprotei n involved in atherogenesis, although it only appears to take on • this role after it has been modified by oxidation. For reasons that are not totally clear, the arterial endothelium becomes • permeable to the lipoprotein. • Monocytes migrate through the permeable endothelium and engulf the lipoprotein, resulting in the formation of lipid-laden macrophages that have a key role in the subsequent development of atherosclerosis. • Theaim of treatment in dyslipidaemia is normally to reduce concentrations of LDL-C (and consequently atherogenesis) and thus reduce TC at the same time. • .
- 18. • While VLDL-C and LDL-C are considered the ‘bad’ lipoproteins, HDL-C is often considered to be the ‘good’ anti atherogenic lipoprotein. • In general, about 65% of TC is carried in LDL-C and about 25% in HDL. High-density lipoprotein HDL-C is formed from the un esterified cholesterol and phospholipid removed from peripheral tissues and the surface of triglyceride-rich proteins. • The major structural protein is apoA-I. HDL-C mediates the return of lipoprotein and cholesterol from peripheral tissues to the liver for excretion in a process known as reverse cholesterol transport. • Reverse cholesterol transport pathway The reverse cholesterol transport pathway
- 19. • Assess the following before starting treatment: – Blood pressure – Body mass index (BMI) – Total cholesterol, non HDL cholesterol, HDL cholesterol and triglycerides – HbA1c – Renal function and eGFR – Transaminase levels – Thyroid stimulating hormone • Primary prevention (treatment of those with no evidence of disease): – Treat with statins if lipids remain high despite nondrug therapy and 10 year CVD risk is ≥ 10% • Secondary prevention (treatment of those who have proven CVD): – Start treatment immediately, irrespective of initial cholesterol levels – Patients with diabetes are considered as secondary prevention •
- 20. • Hyperlipidemia is screened using a blood test called a lipid profile. • It is important to have nothing to eat or drink for 9 to 12 hours before the test. • Screening may start at the age of 20 years for men at high risk, and later for lower-risk men and women. If the result is normal, it should be repeated at least every 5 years. • A normal lipid profile consists of the following levels: • Total cholesterol: less than 200 • LDL: less than 100 • HDL: greater than 40 for men, greater than 50 for women (higher is even better) • Triglycerides: less than 140 • If the person has high cholesterol levels, monitoring and treatment are likely to be necessary.
- 21. Management • Exclude secondary causes of dyslipidemia • Lifestyle modifications : – Diet • Reduce total fat intake to 30% or less of total energy and intake of dietary cholesterol to less than 300 mg/day • Eat at least 5 portions of fruits and vegetables per day and ≥ 2 portions of fish per week • Reduce alcohol consumption to 2 drinks per day for men and 1 drink per day for women – Smoking cessation – Encourage physical activity
- 22. • There are five main classes of lipid-lowering agents available: • • Statins • • Fibrates • • Bile acid binding agents • • Cholesterol absorption inhibitors • • Nicotinic acid and derivatives. • Agents such as soluble fibre and fish oils • Statins • are the drugs of choice for the treatment of hypercholesterolemia .They inhibit HMG CoA reductase required for cholesterol synthesis in the liver . • Statins are currently the lipid-lowering agents of choice in both primary and secondary prevention of CVD. • Possible side effects: myalgia, myositis, abdominal pain and abnormal liver function tests – Statins are contraindicated in pregnancy, breastfeeding and active liver disease – atorvastatin (Lipitor) -20mg – simvastatin (Zocor) - 10MG low cost – fluvastatin (Lescol XL) – lovastatin (Altoprev) – pravastatin (Pravachol) – rosuvastatin (Crestor) 40mg potent drug
- 23. fibrates • They are thought to act by binding to peroxisome proliferator-activated receptor α (PPAR-α) on hepatocytes. This then leads to changes in the expression • of genes involved in lipoprotein metabolism. Consequently, • fibrates reduce triglyceride and, to a lesser extent, LDL-C levels • while increasing HDL-C. Fibrates take 2–5 days to have a • measurable effect on VLDL-C, with their optimum effect present after 4 weeks. In addition to their effects on serum lipids and lipoproteins, the fibrates may also have a beneficial . • SE: Gastro-intestinal-symptoms such as nausea, diarrhoea and abdominal pain
- 24. bile-acid-binding resins, • Bile acid sequestrants: they act by binding bile acids, preventing their reabsorption, which promotes hepatic conversion of cholesterol into bile acids – cholestyramine (Prevalite)-4gm-bd – colesevelam (WelChol)-625mg – colestipol (Colestid)-5gms-od
- 25. • Colesevalam -625mg -4-6 times • is up to six times as potent as the other bile acid.binding agents, probably because of a greater binding to glycocholic acid.
- 26. cholesterol absorption inhibitors • Cholesterol absorption inhibitors • Ezetimibe-10mg • It is the intestinal brush border membrane and thereby blocks cholesterol re-absorption from the gastro-intestinal tract. • It can reduce LDL-C by 15–20% when added to diet. • Ezetimibe also brings about a small increase in HDL-C and a reduction in triglycerides. • statin alone. • Ezetimibe • injectable medications, such as alirocumab (Praluent) or evolocumab (Repatha) • fibrates, like fenofibrate (Fenoglide, Tricor, Triglide) or gemfibrozil (Lopid) • niacin (Niacor) • omega-3 fatty acid supplements • other cholesterol-lowing supplements
- 27. • Nicotinicacid;100mg • in pharmacological doses .lowers serum LDL- C, TC, VLDL-C, apolipoprotein B, triglycerides and Lp(a) and increases levels of HDL-C (particularly the beneficial HDL3 subfraction). It clearly has a range ofbeneficial effects on the lipid profile and is licensed for use in combination with a statin,
- 28. • Fish oils • Fish oil preparations rich in omega-3 fatty acids have been shown to markedly reduce serum triglyceride levels by decreasing VLDL-C synthesis, although little change has been observed in LDL-C or HDL-C levels. • Soluble fibre • Preparations containing soluble fibre, such as ispaghula husk, have been shown to reduce lipid levels. • The fibre is thought to bind bile acids in the gut and increase the conversion of cholesterol to bile acids in the liver.
- 29. • Cholesterol ester transfer protein (CETP) • Inhibitors: • Low levels of CETP are associated with increased levels of HDL-C and reduced cardiovascular risk. CETP transfers cholesterol from HDL-C to LDL-C and VLDL-C, thereby
- 30. • Lifestyle changes are the key to managing hyperlipidemia • Eat a heart-healthy diet • Making changes to diet can lower your “bad” cholesterol levels and increase your “good” cholesterol levels. • Choose healthy fats. Avoid saturated fats that are found primarily in red meat, 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. • Increase your fiber intake. All fiber is heart-healthy, but soluble fiber, which is found in oats, brain, fruits, beans, and vegetables, can lower LDL cholesterol levels.
- 31. • Eat more fruits and veggies. They’re high in fiber and vitamins and low in saturated fat. • Lose weight • overweight or obese, losing weight can help lower total cholesterol levels.