【正文】 6 Specific Dyslipidemias: Very High LDL Cholesterol (?190 mg/dL) Causes and Diagnosis ? Geic disorders – Monogenic familial hypercholesterolemia – Familial defective apolipoprotein B100 – Polygenic hypercholesterolemia ? Family testing to detect affected relatives 77 Specific Dyslipidemias: Very High LDL Cholesterol (?190 mg/dL) (continued) Management ? LDLlowering drugs – Statins (higher doses) – Statins + bile acid sequestrants – Statins + bile acid sequestrants + nicotinic acid 78 Specific Dyslipidemias: Elevated Triglycerides Classification of Serum Triglycerides ? Normal 150 mg/dL ? Borderline high 150–199 mg/dL ? High 200–499 mg/dL ? Very high ?500 mg/dL 79 Specific Dyslipidemias: Elevated Triglycerides (?150 mg/dL) Causes of Elevated Triglycerides ? Obesity and overweight ? Physical inactivity ? Cigarette smoking ? Excess alcohol intake 80 Specific Dyslipidemias: Elevated Triglycerides Causes of Elevated Triglycerides (continued) ? High carbohydrate diets (60% of energy intake) ? Several diseases (type 2 diabetes, chronic renal failure, nephrotic syndrome) ? Certain drugs (corticosteroids, estrogens, retinoids, higher doses of betablockers) ? Various geic dyslipidemias 81 Specific Dyslipidemias: Elevated Triglycerides (continued) NonHDL Cholesterol: Secondary Target ? NonHDL cholesterol = VLDL + LDL cholesterol = (Total Cholesterol – HDL cholesterol) ? VLDL cholesterol: denotes atherogenic remnant lipoproteins ? NonHDL cholesterol: secondary target of therapy when serum triglycerides are ?200 mg/dL (esp. 200–499 mg/dL) ? NonHDL cholesterol goal: LDLcholesterol goal + 30 mg/dL 82 Comparison of LDL Cholesterol and NonHDL Cholesterol Goals for Three Risk Categories LDLC Goal (mg/dL) Risk Category NonHDLC Goal (mg/dL) 100 CHD and CHD Risk Equivalent (10year risk for CHD 20% 130 130 Multiple (2+) Risk Factors and 10year risk 20% 160 160 0–1 Risk Factor 190 83 Specific Dyslipidemias: Elevated Triglycerides NonHDL Cholesterol: Secondary Target ? Primary target of therapy: LDL cholesterol ? Achieve LDL goal before treating nonHDL cholesterol ? Therapeutic approaches to elevated nonHDL cholesterol – Intensify therapeutic lifestyle changes – Intensify LDLlowering drug therapy – Nicotinic acid or fibrate therapy to lower VLDL 84 Specific Dyslipidemias: Elevated Triglycerides Management of Very High Triglycerides (?500 mg/dL) ? Goal of therapy: prevent acute pancreatitis ? Very low fat diets (?15% of caloric intake) ? Triglyceridelowering drug usually required (fibrate or nicotinic acid) ? Reduce triglycerides before LDL lowering 85 Specific Dyslipidemias: Low HDL Cholesterol Causes of Low HDL Cholesterol (40 mg/dL) ? Elevated triglycerides ? Overweight and obesity ? Physical inactivity ? Type 2 diabetes ? Cigarette smoking ? Very high carbohydrate intakes (60% energy) ? Certain drugs (betablockers, anabolic steroids, progestational agents) 86 Specific Dyslipidemias: Low HDL Cholesterol Management of Low HDL Cholesterol ? LDL cholesterol is primary target of therapy ? Weight reduction and increased physical activity (if the metabolic syndrome is present) ? NonHDL cholesterol is secondary target of therapy (if triglycerides ?200 mg/dL) ? Consider nicotinic acid or fibrates (for patients with CHD or CHD risk equivalents) 87 ? Lipoprotein pattern: atherogenic dyslipidemia (high TG, low HDL, small LDL particles) ? LDLcholesterol goal: 100 mg/dL ? Baseline LDLcholesterol ?130 mg/dL – Most patients require LDLlowering drugs ? Baseline LDLcholesterol 100–129 mg/dL – Consider therapeutic options ? Baseline triglycerides: ?200 mg/dL – NonHDL cholesterol: secondary target of therapy Specific Dyslipidemias: Diabetic Dyslipidemia ATP III Guidelines Population Groups 89 Special Considerations for Different Population Groups Younger Adults ? Men 20–35 years。 women 20–45 years ? Coronary atherosclerosis accelerated by CHD risk factors ? Routine cholesterol screening remended starting at age 20 ? Hypercholesterolemic patients may need LDLlowering drugs 90 Special Considerations for Different Population Groups (continued) Older Adults ? Men ?65 years and women ?75 years ? High LDL and low HDL still predict CHD ? Benefits of LDLlowering therapy extend to older adults ? Clinical judgment required for appropriate use of LDLlowering drugs 91 Special Considerations for Different Population Groups (continued) Women (Ages 45–75 years) ? CHD in women delayed by 10–15 years (pared to men) ? Most CHD in women occurs after age 65 ? For secondary prevention in postmenopausal women – Benefits of hormone replacement therapy doubtful – Benefits of statin therapy documented in clinical trials 92 Special Considerations for Different Population Groups (continued) MiddleAged Men (35–65 years) ? CHD risk in men women ? High prevalence of CHD risk factors ? Men prone to abdominal obesity and metabolic syndrome ? CHD incidence high in middleaged men ? Strong clinical trial evidence for benefit of LDLlowering therapy 93 Special Considerations for Different Population Groups (continued) Racial and Ethnic Groups ? Absolute risk for CHD may vary in different racial and ethnic groups ? Relative risk from risk factors is similar for all population groups ? ATP III guidelines apply to: – African Americans – Hispanics – Native Americans – Asian and Pacific Islanders – South Asians ATP III Guidelines Adherence 95 Interventions to Improve Adherence Focus on the patient ? Simplify medication regimens ? Provide explicit patient instruction and use good co