Historically, total cholesterol concentration was used to assess an individual’s risk of CAD (Bowden & Kingery, 2004). Because cholesterol contributes to the buildup of atherosclerotic plaques, an individual’s blood cholesterol concentration could be a way to measure risk for heart disease. Clinical studies are consistent in supporting the projection that for serum cholesterol levels in the 250-300 mg/dl range, each 1% reduction in serum cholesterol level reduces CAD rates by approximately 2% (NIH, 1989a). However, the degree of stenosis and CAD varies between individuals with the same total cholesterol and other lipid levels (Bowden, Kingery, Rust, 2004, Kmietowicz, 1998; Telenko & Sumner, 2002).

Total cholesterol tends to reflect average dietary habits that affect LDL, and can reasonably provide an assessment of CVD risk between participants. Yet, the differences in risk between individuals can be strongly influenced by many additional factors. Therefore the measurement of total cholesterol alone cannot adequately reflect individual risk of CAD (NIH, 2002) and should rarely be used as the sole lipid measure in cholesterol screenings. Other studies have also demonstrated the process of heart disease to consist of many factors that are independent of total cholesterol (Katerndahl & Lawler, 1999). These other risk factors fall into two three broad categories, consisting of blood markers, behavior, and biology. New blood tests that identify increased cardiovascular risk include various subfractions of cholesterol. Many of these new markers relate to the physiological functions of cholesterol and the interaction between these markers and the cholesterol in the periphery.

The generally accepted ranges for total cholesterol levels (NIH, 2002) consist of desirable (<200mg/dL), borderline high (200-239mg/dL), and high (≥240mg/dL). If a patient’s cholesterol level is in the high category, a LDL cholesterol measure should be performed. If the patient is in the borderline high range, another total cholesterol measurement should be taken within eight weeks and the average of the two readings used to guide future decisions (NIH, 2002).

Cholesterol Subfractions
LDL cholesterol accounts for 60-75% of the total serum cholesterol and is the terminal end of in the pathway of lipoprotein metabolism called cholesterol transport. Numerous epidemio-logical, physiological, and animal models have linked high LDL levels to CAD (American Heart Association, 2004; Assman, Cullen & Schulte, 1998; NIH, 1989a; Smith et al., 2004; Stone, 2005). High levels of LDL cholesterol are able to penetrate the porous endothelium of arteries and begin to accumulate if plasma concentrations are abnormal. This natural plaque is eventually converted to unstable plaque increasing the likelihood of rupture and possible thrombosis (NIH, 2002). Accordingly, the greatest absolute diminution of risk can be achieved by the reduction of LDL which may directly lower platelet aggregation, vascular reactivity, and lower cytokine release leading to a further reduction in risk for myocardial infarction (Sullivan, 2002). In fact, when elevated LDL levels are combined with comorbidity factors of smoking and hypertension, this complex explains over 90% of myocardial infarction cases occurring in middle age (Wilhelmsen, 1997). The landmark INTERHEART data suggests that 90% of risk comes from combination of abnormal levels of apolipoproteins found in LDL and smoking. LDL contains ApoB-100 which has been linked to atherogenesis (Yusef, Hawken, Ounpuu, Dans, Avesum, Lanas et al., 2004).

Finally, it should be noted that although LDL lowering therapy is believe to offer the greatest benefit for CAD risk reduction, LDL alone is insufficient to predict CAD incidence and risk stratification. The best risk prediction strategy requires measurement of other cholesterol components and particle size and concentration (Wald, Law, Watt, Wu et al., 1994).