Blood Lipids and Coronary Heart Disease

The major risk factors for coronary heart disease are well known and include smoking, high blood pressure, and blood cholesterol levels. In addition, obesity, diabetes, and family history are recognized as important factors. While each of these factors is important, the predominant factor may be blood cholesterol levels. Serum total cholesterol and lipoproteins are well-established risk factors for coronary artery disease. Numerous studies have confirmed the relationship between serum total cholesterol and coronary heart disease.1013 A rule of thumb from epidemiologic studies suggest that for every 1% increase in total cholesterol, the risk of CHD increases by 2%.14,15 The National Cholesterol Education Program defines three categories of serum total cholesterol. These are desirable (<200 mg/dL), borderline high (200-239 mg/dL) and high (>240 mg/dL). These classifications have been used as a basis for prescribing preventive treatments including dietary changes and pharmaceutical drugs.14 NCEP guidelines have changed with the development of methods for the measurement of subclasses of serum lipoproteins and recognition that the distribution of cholesterol among lipoproteins improved the prediction of coronary artery disease risk.16 The informative lipoproteins included low-density lipoprotein, high-density lipoprotein, and very low-density lipoproteins. Most of the attention has focused on low-density lipoproteins, which are very atherogenic.

In early studies, low-density lipoprotein cholesterol concentrations have been associated with coronary artery disease17 and this finding was confirmed in numerous subsequent studies. For clinical purposes, LDL levels have been defined as optimal (<100 mg/dL), near optimal (100-129 mg/dL), borderline high (130-159 mg/dL), high (160-189 mg/dL) and very high (>190 mg/dL). Another lipoprotein, HDL is associated inversely with the risk of coronary heart disease. HDL is involved in reverse cholesterol transport, which reduces tissue cholesterol levels and may provide a protective effect. Low HDL cholesterol levels are recognized as a common and powerful risk factor for coronary artery disease.18 The AHA guidelines suggest that levels of HDL lower than 40 mg/dL result in an elevated risk for coronary artery disease. Two additional forms of LDL may be atherogenic particles and should be given consideration for their association with elevated risk. These are LP(a) and small dense low-density lipoproteins. The association of LP(a) with coronary disease is independent of serum LDL cholesterol levels.19 Structural studies have found that this apolipoprotein has a structure similar to plasminogen.20 These structural studies have provided a basis for a possible mechanism of LP(a) action as it could block the binding of plasminogen and prevent the lysis of clots. Risk factor studies have been mixed, sometimes showing LP(a) and isoforms to be a risk factor, but only in the presence of other risk factors and other times showing it to be an independent risk factor for clinical coronary heart disease.21 Thus, definition of its role remains unclear. Small dense LDL is associated with the risk for coronary artery disease. However, this association is complicated by a simultaneous association with components of the metabolic syndrome. It is unclear whether small dense LDL is a primary risk factor or it is only associated with other athero-genic factors.22,23 Very low density lipoproteins are a primary source of circulating triglycerides which has been identified as an independent risk factor for coronary artery disease. The association has been frequent, but inconsistent and may reflect an association with the metabolic syndrome.24 This association was recognized recently and requires further study to define the relationship. More recently, the measurement of nonhigh density lipoprotein cholesterol has been shown to be a simpler or and perhaps equally effective predictor of coronary artery disease as LDL.13 Nonhigh density lipoprotein cholesterol contains all the known and potential atherogenic lipoproteins and is easier to measure than each subclass. Further studies are needed to define the predictive value of nonhigh density lipoprotein cholesterol.

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