老年病學(xué)英文課件：Dyslipidemia in elderly

1、Dyslipidemia in elderly,Definitions,Dyslipidemia: is a diagnosis of “abnormal lipid levels”, as measured on a blood sample and which reflects one of several disorders in the metabolism of lipoproteins. It may be classifieds as: Hypercholesterolemia Low levels of high density lipoproteins (HDL) Hyper

2、triglyceridemia,Cholesterol,A fat-like substance (lipid) that is present in cell membranes and is a precursor of bile acids and steroid hormones. Cholesterol travels in the blood in distinct particles containing both lipid and proteins known as lipoproteins. There major classes of lipoproteins are f

3、ound in the serum of a fasting individual: low density lipoproteins (LDL), high density lipoproteins (HDL), and very low density lipoproteins (VLDL,Lipoprotein,lipid particles surrounded by proteins transport cholesterol within the body. Each lipoprotein is a combination of triglyceride, cholesterol

4、 and protein unique to its type,Low Density Lipoprotein (LDL,is commonly referred to as “bad” cholesterol. It typically makes up 60-70% of the total serum cholesterol and contains a single apolipoprotein, namely apolipoprotein B (apo B). LDL is the major atherogenic lipoprotein and has long been ide

5、ntified by the National Cholesterol Education Program (NCEP) as the primary target of cholesterol lowering therapy; the alternate primary target is apoB. Based on evidence, many experts have concluded that apoB is a better test by providing a better indication of vascular disease than LDL-C, a bette

6、r index of how LDL therapy is working and less laboratory errors than the LDL-C. Not all experts are convinced that apoB should be routinely measure and therefore, they are considered secondary and optional targets,High Density Lipoprotein (HDL,is commonly referred to as “good” cholesterol. It makes

7、 up approximately 20-30% of the total serum cholesterol with highest level of protein. HDL cholesterol levels are inversely correlated with risk for Cardiovascular Disease (CVD). Some evidence indicated that HDL protects against the development of atherosclerosis, although a low HDL level often refl

8、ects the presence of other atherogenic factors,Very Low Density Lipoprotein (VLDL,is triglyceride-rich lipoprotein and makes up 10-15% of the total serum cholesterol. VLDL is produced by the liver and is a precursor of LDL. VLDL remnants appear to promote atherosclerosis similar to LDL,Intermediate

9、Density Lipoproteins (IDL,come from the breakdown of VLDL and are used to form low density lipoproteins,Triglycerides (TG,Another form of lipid in the body. Non-lipid risk factors of obesity, hypertension, diabetes, and cigarette smoking are also interrelated with triglycerides as are several emergi

10、ng risk factors (insulin resistance glucose intolerance and prothrombotic state). Thus, many persons with elevated triglycerides are at increased risk for CVD. In addition, elevated triglycerides are associated with other disorders, most notably pancreatitis,Risk Factors for Dyslipidemia,Men 40 year

11、s old Women 50 years old or postmenopausal Family history of hypercholesterolemia or chylomicronemia Exertional chest discomfort Dyspnea Erectile dysfunction Cigarette smoking (current or within past year) Abdominal obesity (men 94 cm or women 80 cm) Family history of premature coronary artery disea

12、se (CAD) Manifestations of hyperlipidemia (xanthelasma, xanthoma, corneal arcus) Diabetes mellitus (DM) Hypertension (HTN) Chronic kidney disease GFR 60 ml/min/1.73m2 Inflammatory conditions (systemic lupus erythematosus, rheumatoid arthritis, psoriasis) Evidence of atherosclerosis Sedentary lifesty

13、le Stress,Screening,Patients of any age may be screened at the direction of the physician, particularly when lifestyle changes are indicated, but the following represent the usual recommendations: All men 40 years of age, every 1 3 years All women 50 years of age or postmenopausal, every 1 3 years C

14、hildren with a family history of severe hypercholesterolemia or chylomicronemia,All individuals with the following conditions, regardless of age,Diabetes Hypertension Current cigarette smoking Obesity (BMI 27 kg/m2) Family history of premature CAD ( 60 years in first-degree relatives) Inflammatory d

15、iseases (systemic lupus erythematosis, rheumatoid arthritis, psoriasis) Chronic renal diseases (eGFR 60 mL/min/1.73m2) Evidence of atherosclerosis HIV infection treated with highly active antiretroviral therapy Clinical manifestations of hyperlipidemias (xanthomas, xanthelasmas, premature arcus corn

16、ealis) Erectile dysfunction,Signs and Symptoms,elevated cholesterol does not lead to specific signs unless it has been longstanding. Xanthoma (thickening of tendons due to accumulation of cholesterol, lipid deposits under skin that appear as yellow patches or nodules on the surface of the skin) Xant

17、helasma palpabrum (yellowish patches around the eyelids) Arcus senilis (white discoloration of the peripheral cornea) Evidence of atherosclerosis (abdominal bruits, carotid bruits, diminished peripheral pulses, ankle-brachial index 0.0,Symptoms,There are no specific symptoms of elevated cholesterol,

18、 but because it leads to accelerated atherosclerosis, a number of cardiovascular diseases can be the result of hypercholesterolemia. Angina pectoris, leading to Coronary Artery Bypass Grafting (CABG) Myocardial Infarction (MI) Transient Ischemic Attacks (TIAs) Cerebrovascular accidents/strokes Perip

19、heral Artery Disease (PAD,Complications,When triglycerides are elevated 10.0 mmol/L individuals are at risk for developing pancreatitis Hypertriglyceridemia: greater than 11.30 mmol/L may cause acute pancreatitis. A less severe and often unrecognized condition is the chylomicronemia syndrome which i

20、s usually caused by TG levels greater than 1000 mg/dL,Symptoms of Pancreatitis,Pain in upper middle or left part of abdomen (may radiate to back) Sudden pain or gradually building pain that becomes severe Pain often worsens after eating Nausea (occasional vomiting) Swollen or tender abdomen,Classifi

21、cation/Type Staging,Although not used commonly in primary care for the usual investigation and treatment of dyslipidemia, the Fredrickson Classification performed using lipoprotein plasmaphoresis has been the traditional and remains the most rigorous method for classifying dyslipidemias,Classificati

22、on,increases in cholesterol only (pure or isolated hypercholesterolemia), increases in TGs only (pure or isolated hypertriglyceridemia), increases in both cholesterol and TGs (mixed or combined hyperlipidemias). This system does not take into account specific lipoprotein abnormalities (eg, low HDL o

23、r high LDL) that may contribute to disease despite normal cholesterol and TG levels,Secondary causes,Secondary causes contribute to many cases of dyslipidemia in adults. The most important secondary cause in developed countries is a sedentary lifestyle with excessive dietary intake of saturated fat,

24、 cholesterol, and trans fats. Trans fats are polyunsaturated or monounsaturated fatty acids to which hydrogen atoms have been added; they are commonly used in many processed foods and are as atherogenic as saturated fat,Other common secondary causes include diabetes mellitus, alcohol overuse, chroni

25、c kidney disease, hypothyroidism, primary biliary cirrhosis and other cholestatic liver diseases, and drugs, such as thiazides, -blockers, retinoids, highly active antiretroviral agents, cyclosporine, estrogen and progestins, and glucocorticoids. Secondary causes of low levels of HDL cholesterol inc

26、lude cigarette smoking, anabolic steroids, HIV infection, and nephrotic syndrome,Diagnosis,Dyslipidemia is diagnosed by measuring serum lipids. Routine measurements (lipid profile) include total cholesterol (TC), TGs, HDL cholesterol, and LDL cholesterol. Lipid profile measurement: TC, TGs, and HDL

27、cholesterol are measured directly. TC and TG values reflect cholesterol and TGs in all circulating lipoproteins, including chylomicrons, VLDL, intermediate-density lipoprotein (IDL), LDL, and HDL. TC values can vary by 10% and TGs by up to 25% day-to-day even in the absence of a disorder. TC and HDL

28、 cholesterol can be measured in the nonfasting state, but most patients should have all lipids measured while fasting (usually for 12 h) for maximum accuracy and consistency,Other tests,Patients with premature atherosclerotic cardiovascular disease, cardiovascular disease with normal or near-normal

29、lipid levels, or high LDL levels refractory to drug therapy should probably have Lp(a) levels measured. Lp(a) levels may also be directly measured in patients with borderline high LDL cholesterol levels to determine whether drug therapy is warranted. C-reactive protein may be considered in the same

30、populations. Measurements of LDL particle number or apoprotein B-100 (apo B) may be useful in patients with elevated TGs and the metabolic syndrome. Apo B provides similar information to LDL particle number because there is one apo B molecule for each LDL particle. Apo B measurement includes all ath

31、erogenic particles, including remnants and Lp(a,Tests for secondary causes,including measurements of fasting glucose, liver enzymes, creatinine, thyroid-stimulating hormone (TSH), and urinary proteinshould be done in most patients with newly diagnosed dyslipidemia and when a component of the lipid p

32、rofile has inexplicably changed for the worse,Treatment,Risk assessment by explicit criteria Lifestyle changes (eg, exercise, dietary modification) For high LDL cholesterol, statins, sometimes bile acid sequestrants, ezetimibe, and other measures For high TG, niacin, fibrates, omega-3 fatty acids, a

33、nd sometimes other measures,General principles,Treatment is indicated for all patients with cardiovascular disease (secondary prevention) and for some without (primary prevention). The National Institutes of Healths National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATPIII) gui

34、delines are the most common reference for deciding which adults should be treated (Table 4: National Cholesterol Education Program Adult Treatment Panel III Approach to Dyslipidemias and see Table 5: NCEP Adult Treatment Panel III Guidelines for Treatment of Hyperlipidemia). The guidelines focus pri

35、marily on reducing elevated LDL cholesterol levels and secondarily on treating high TGs, low HDL, and metabolic syndrome (see Metabolic Syndrome). New guidelines have just been published by the American Heart Association (late November 2013; see ACC/AHA Guideline on the Treatment of Blood Cholestero

36、l) and will be available on this page shortly,Goal of Management,The goal of management is to reduce the risk of Cardiovascular Disease and in the case of severely elevated triglycerides, to prevent pancreatitis,Lifestyle changes,can involve diet and exercise. Dietary changes include decreasing inta

37、ke of saturated fats and cholesterol; increasing the proportion of dietary fiber, and complex carbohydrates; and maintaining ideal body weight. Referral to a dietitian is often useful, especially for older people. The length of time for which lifestyle changes should be attempted before beginning li

38、pid-lowering drugs is controversial. In patients at average or low cardiovascular risk, 3 to 6 mo is reasonable,Smoking Cessation,The most important health behaviour intervention for the prevention of CVD Results in a 36% reduction in the relative risk of mortality from CAD Advise patients who smoke

39、 to quit and encourage young people not to smoke. Provide patients who are unable to quit on their own with information on smoking cessation programs, nicotine replacement therapy and drug therapy where indicated,Diet,Decrease sodium Decrease simple sugars and refined carbohydrates Increase fruits a

40、nd vegetables Increase whole grain cereals Increase proportion of mono and polyunsaturated oils, including omega-3 fatty acids. Substitute saturated and trans fats for unsaturated fats,Maintain Healthy Body Weight,Advise clients with dyslipidemia whose BMI 25 kg/m2 to reduce their weight. Optimal wa

41、ist circumference for men 94 cm (37 in). Optimal waist circumference for women 80 cm (32 in,Physical Activity,At least 150 minutes (30 minutes/day) of moderate activity,Consume Alcohol in Moderation,Patients who choose to drink should limit their alcohol consumption to 2 or fewer standard drinks per

42、 day. Advise patients with elevated triglyceride levels to decrease or eliminate alcohol consumption,Psychological Factors,Stress management is important because stress can been identified as a CVD risk factor. Depressed patients post MI experience a worse prognosis,Drugs are the next step when life

43、style changes are not effective. However, for patients with extremely elevated LDL cholesterol ( 190 mg/dL 4.9 mmol/L) and those at high cardiovascular risk, drug therapy should accompany diet and exercise from the start,Classes of lipid-lowering medications,Statins Fibric acid derivatives Cholester

44、ol absorption inhibitors Niacin Bile acid sequestrants (resins,Monitoring,Statins,Well tolerated by most individuals. Complaints of muscle pain (myalgia) represent most common side effect and does not necessarily preclude the use of statins unless myositis or rhabdomyolitis are present (these are ra

45、re). Contraindicated in women who are or may become pregnant. Use lower dose ranges in persons of South and East Asian origin. Statin monotherapy will achieve target LDL-C levels in most patients. For patients with moderate hypertriglyceridemia, the addition of salmon oil (1-2 g three times daily) t

46、o statin therapy may be useful to lower triglyceride (TG) levels; helping to achieve TC-HDL-C ratio. If client is on anticoagulants or large doses of aspirin, reduce salmon oil to 1-2 g/day and watch for bleeding. Client should discuss with physician,Bile acid sequestrants,block intestinal bile acid

47、 reabsorption, forcing up-regulation of hepatic LDL receptors to recruit circulating cholesterol for bile synthesis. They are proved to reduce cardiovascular mortality. Bile acid sequestrants are usually used with statins or with nicotinic acid (see Low HDL) to augment LDL cholesterol reduction and

48、are the drugs of choice for women who are or are planning to become pregnant. Bile acid sequestrants are safe, but their use is limited by adverse effects of bloating, nausea, cramping, and constipation. They may also increase TGs, so their use is contraindicated in patients with hypertriglyceridemi

49、a,Fibrates,Lower TGs and VLDL, increase HDL, may increase LDL-C (in patients with high TGs,Dietary supplements,that lower LDL cholesterol levels include fiber supplements and commercially available margarines and other products containing plant sterols (sitosterol and campesterol) or stanols. The la

50、tter reduce LDL cholesterol by up to 10% without affecting HDL or TGs by competitively displacing cholesterol from intestinal micelles,Niacin,In patients with DM or glucose intolerance, initiate therapy at 500 100 mg/day and adjust glycemic control (may cause hyperglycemia). Careful monitoring if gi

51、ven with a statin. Extended release niacin (Niaspan) has similar efficacy and better tolerability than immediate release niacin (generic). Long-acting niacin should not be used due to increased hepatotoxicity and decreased efficacy,Cholesterol absorption inhibitors,such as ezetimibe, inhibit intesti

52、nal absorption of cholesterol and phytosterol. usually lowers LDL cholesterol by 15 to 20% and causes small increases in HDL and a mild decrease in TGs. can be used as monotherapy in patients intolerant to statins or added to statins for patients on maximum doses with persistent LDL cholesterol elev

53、ation. Adverse effects are infrequent,Age-related changes in lipoprotein metabolism,Longitudinal studies have shown that total cholesterol levels increase in males after the onset of puberty until age 50. This is followed by a plateau until age 70, with the serum cholesterol concentration then falli

54、ng slightly. Although it has been suspected that the latter change may be an artifact resulting from CHD deaths in hypercholesterolemic men 3, the most important factor influencing cholesterol may be weight change 4. The reduction in total and LDL cholesterol and the increase in HDL-cholesterol in o

55、lder men, primarily occur in those who lost weight, while age is not a factor,Key Points,Elevated lipid levels are a risk factor for atherosclerosis and thus can lead to symptomatic coronary artery disease and peripheral arterial disease. Causes of dyslipidemia include a sedentary lifestyle with exc

56、essive dietary intake of saturated fat, cholesterol, and trans fats and/or genetic (familial) abnormalities of lipid metabolism. Diagnose using serum lipid profile (measured total cholesterol, TG, and HDL cholesterol and calculated LDL cholesterol and VLDL). Screening tests should be done at age 9 t

57、o 11 years (age 2 if there is a strong family history of severe hyperlipidemia or premature CAD; adults are screened every 5 yr beginning at age 20,Age related change in lipid profile,In women, the serum cholesterol concentration is slightly higher than in men prior to age 20 to 25. Between the ages

58、 of 25 to 55, the serum cholesterol rises although at a slower incremental rate than in men. Cholesterol levels in women are equal to those of men between the ages of 55 to 60 and exceed those in men in older age groups,Age related change in lipid profile,The age-related changes in the serum cholest

59、erol concentration primarily result from an increase in LDL-cholesterol (figure 2)3. In comparison, HDL-cholesterol levels do not vary much with age, being about 10 mg/dL (0.26 mmol/L) higher in women than men,Age related change in lipid profile,The mechanisms responsible for the progressive age-related elevation in LDL-cholesterol have not been fully explained; however, the data support a primary role for a decrease in the fractional catabolic rate of LDL-cholesterol. This reduction in LDL catabolism is thought to result from diminished activity of hepatic LDL receptors,Change in li