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A Clinical Overview
Thrombus
Lipid core
Vulnerable Plaque Thin fibrous cap Inflammatory cell infiltrates: proteolytic activity Lipid-rich plaque Stable Plaque
Lumen
Lipid Core
Fibrous Cap
Thick fibrous cap Smooth muscle cells: more extracellular matrix Lipid-poor plaque
Plaque Stabilization
Unstable plaque
Fibrous cap Fibrous cap
Stable plaque
Inflammatory cells
Occlusive thrombus
Q-wave MI Sudden death
Factors limiting thrombosis: Minor plaque disruption High flow Low thrombotic tendency
Factors favoring thrombosis: Major plaque disruption Low flow or vasospasm Thrombotic tendency
Cerebrovascular disease
Stroke, TIAs
Nonmodifiable
Age : male 45 years female 55 years Sex Family history of premature CHD
Smoking Hypertension Diabetes mellitus Obesity Dietary factors Thrombogenic factors Sedentary lifestyle
CHD in male first-degree relative <55 years CHD in female first-degree relative <65 years
2
1.73
2.21
1.29
LDL Cholesterol
Remains the cornerstone of dyslipidemia therapy1 Strongly associated with atherosclerosis and CHD events1 10% increase results in a 20% increase in CHD risk1 Most patients with elevated LDL untreated
Only 4.5 million out of 28.4 million treated 2,3
1. Wood D et al. Atherosclerosis. 1998;140:199-270. 2. National Centre for Health Statistics. National Health and Nutrition Examination Survey (III), 1994. 3. Jacobson TA, et al. Arch Intern Med. 2000;160:1361-1369.
HDL Cholesterol
Low HDL cholesterol is a strong independent predictor of CHD1 The lower the HDL cholesterol level the higher the risk for atherosclerosis and CHD2 Low HDL is defined categorically as a level < 40 mg/dL (a change from < 35 mg/dL in ATP II)1 HDL cholesterol tends to be low when triglycerides are high2
1. NCEP, Adult Treatment Panel III. JAMA. 2001;285:2486-2497. 2. Wood D, et al. Atherosclerosis. 1998;140:199-270.
Triglycerides
Recent data suggest that elevated triglycerides are an independent risk factor for CHD Normal triglyceride levels: < 150 mg/dL Borderline-high triglycerides: 150 to 199 mg/dL High triglycerides: 200 to 499 mg/dL Very high triglycerides: ( 500 mg/dL) increase pancreatitis risk
Initial aim of therapy is prevention of acute pancreatitis
Non-HDL Cholesterol
Non-HDL Cholesterol = TC HDL Cholesterol1 Secondary target of therapy when serum TG 200 mg/dL1 New non-HDL-C goal for patients with elevated TG is LDL-C goal + 30 mg/dL1 Non-HDL-C includes all atherogenic lipoprotein particles including LDL-C, Lp(a), IDL-C, and VLDL-C2
1. NCEP, Adult Treatment Panel III. JAMA. 2001;285:2486-2497. 2. Cui Y, et al. Arch Intern Med. 2001;161:1413-1419.
LDL Cholesterol Goals for Therapeutic Lifestyle Changes (TLC) and Drug Therapy According to NCEP ATP III
LDL-C Goal (mg/dL) < 100 LDL-C Level for Initiation of TLC (mg/dL) 100 LDL-C Level for Consideration of Drug Therapy (mg/dL)
Risk Category CHD or CHD Risk Equivalents (10-y risk > 20%)
< 130
130
10-y risk 10%-20%: 130 10-y risk < 10%: 160 190 (160-189: LDL-C-lowering drug optional)
< 160
160