Omega-3 fatty acids (abundant in fish oils) are beneficial, whereas (trans)-unsaturated fats produced by artificial hydrogenation of polyunsaturated oils (used in baked goods and margarine) adversely affect cholesterol profiles.
Exercise and moderate consumption of ethanol raise HDL levels, whereas obesity and smoking lower them.
Statins are a widely used class of drugs that lower circulating cholesterol levels by inhibiting hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in hepatic cholesterol biosynthesis (Chapter 7).
Hypertension (see earlier discussion) is another major risk factor for development of atherosclerosis. On its own, hypertension can increase the risk for IHD by approximately 60% (see
Fig. 10.8 ). Hypertension also is the major cause of left ventricular hypertrophy (LVH), which also can contribute to myocardial ischemia (see
Fig. 10.8
Cigarette smoking is a well-established risk factor in men and probably accounts for the increasing incidence and severity of atherosclerosis in women. Prolonged (years) smoking of one or more packs of cigarettes per day doubles the rate of IHD-related mortality, while smoking cessation reduces the risk.
Diabetes mellitus is associated with raised circulating cholesterol levels and markedly increases the risk for atherosclerosis. Other factors being equal, the incidence of myocardial infarction is twice as high in diabetics as in non-diabetics. In addition, this disorder is associated with an increased risk for stroke and a 100-fold increase in atherosclerosis-induced gangrene of the lower extremities.
Roughly 20% of cardiovascular events occur in the absence of identifiable risk factors. For example, in previously healthy women, more than 75% of cardiovascular events occur in those with LDL cholesterol levels below 130 mg/dL (a cutoff value considered to connote only borderline risk). Other factors that contribute to risk include the following: • Inflammation. Inflammatory cells are present during all stages of atheromatous plaque formation and are intimately linked with plaque progression and rupture (see the following discussion). There is some evidence that a systemic pro-inflammatory state is associated with the development of atherosclerosis and hence measures of systemic inflammation have been used in risk stratification. Of various systemic markers of inflammation, determination of C-reactive protein (CRP) has emerged as one of the simplest and most sensitive. CRP is an acute-phase reactant synthesized primarily by the liver in response to a variety of inflammatory cytokines. In some studies,
CRP levels independently predict the risk for myocardial infarction, stroke, peripheral arterial disease, and sudden cardiac death, even among apparently healthy individuals
Fig. 10.9 ). However, such studies are confounded by lack of precise definition of “healthy individuals” because clinically asymptomatic individuals may harbor http://ebooksmedicine.net
C-Reactive protein (mg/L) 1.0–3.0<1.0 >3.0
Framingham estimate of 10-year risk (%)