Harrison’s Manual of Medicine



Established Risk Factors
Emerging Risk Factors
Atherosclerosis is the leading cause of death in developed societies. Established major risk factors are listed in Table 123-1.

Table 123-1 Major Risk Factors of Atherosclerosis

DYSLIPIDEMIAS    (See Chap. 178)Both elevated LDL and low HDL cholesterol correlate with cardiovascular risk. Fasting lipid profile (total cholesterol, triglycerides, HDL, LDL) should be obtained at least once every 5 years in all adults. Recommended dietary and/or pharmacologic therapy depends on presence or risk of coronary artery disease (CAD) and LDL level (Table 123-2). Treatment approach should be most aggressive in pts with established atherosclerosis (i.e., history of CAD, stroke, peripheral vascular disease). If HDL is low [<1.0 mmol/L (<40 mg/dL)], encourage beneficial life-style measures: discontinue smoking, weight-loss diet if obese, exercise.

Table 123-2 Treatment Decisions Based on LDL Cholesterol

HYPERTENSION    (See Chap. 124) Treatment of elevated bp (>140/ 90 mmHg) reduces risk of stroke and CHF; weight of evidence also suggests decreased risk of coronary events. Risk in elderly pts with isolated systolic hypertension (systolic > 160 mmHg but diastolic <90 mmHg) is also reduced by antihypertensive therapy.
DIABETES MELLITUS/INSULIN RESISTANCE   (See Chap. 173) Fasting serum glucose ³6.9 mmol/L (³125 mg/dL) establishes diagnosis of diabetes; most diabetics develop atherosclerosis. Type 2 diabetes often clusters with other risk factors, including low HDL cholesterol, elevated triglycerides, small dense LDL particles. Tight control of serum glucose reduces microvascular diabetic complications (retinopathy, renal disease) but not macrovascular disease (CAD, stroke). Management of associated risk factors in diabetics (e.g., dyslipidemia) reduces cardiovascular events and should be vigorously pursued. If needed, HMG-CoA reductase inhibitor should be used to lower LDL to <2.6 mmol/L (<100 mg/dL) in diabetics, even if pt has no symptoms of CAD.
MALE GENDER/POSTMENOPAUSAL STATE   Coronary risk is greater in men compared to women of same age, but female risk accelerates after menopause. Estrogen replacement therapy lowers LDL and raises HDL in postmenopausal women and in observational studies has been associated with reduced coronary events. However, recent rigorous clinical trials do not support such a benefit, and hormone replacement therapy should not be prescribed routinely for purpose of cardiovascular risk reduction.
LIFE-STYLE MODIFICATIONS   For cardiac risk reduction, encourage smoking cessation, good exercise habits (>30 min moderate intensity physical activity daily), and sensible diet (low in saturated and trans fat, high in fruits, vegetables, and low-fat dairy products). Encourage elimination of obesity (Chap. 55).
May be useful in assessing pts without the above traditional risk factors who have premature vascular disease or a strong family history of premature vascular disease.
HOMOCYSTEINE   There is a graded correlation between serum homocysteine levels and risk of cardiovascular events and stroke. Folic acid and other B vitamins lower serum levels, but no study has yet evaluated if such reduction improves cardiovascular risk. For pts with hyperhomocystinemia, folic acid supplements are safe, starting at 400 µg/d; avoid doses > 1 mg/d unless serum B12 has been evaluated (higher dose folic acid could mask presence of pernicious anemia).
OTHER POTENTIAL RISK FACTORS   C-reactive protein is a marker of inflammation that prospectively predicts risk of MI; its usefulness and role in prevention is currently being defined. Potential benefits of assessing other emerging risk factors [e.g., lipoprotein(a), fibrinogen, infections by Chlamydia or CMV] remain unproven and controversial.

For a more detailed discussion, see Libby P: Prevention and Treatment of Atherosclerosis, Chapter 242, p. 1382, in HPIM-15.



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