Submitted to: American Journal of Cardiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/13/2007
Publication Date: 4/1/2008
Citation: Miller, M., Ginsberg, H.N., Schaefer, E.J. 2008. Relative atherogenicity and predictive value of non-high-density lipoprotein cholesterol for coronary heart disease. American Journal of Cardiology. 101(7):1003-1008. Interpretive Summary: Blood cholesterol levels are carried on particles known as lipoproteins. The major cholesterol carrying particles in the bloodstream are known as low density lipoproteins or LDL. High levels of LDL cholesterol (> 160 mg/dl) have been associated with an increased risk of heart disease, a leading cause of death and disability in our society. Another cholesterol carrying particle in the bloodstream is known as high density lipoprotein cholesterol. Low levels of high density lipoprotein (HDL) cholesterol (< 40 mg/dl in men and < 50 mg/dl in women) have also been associated with an increased risk of coronary heart disease. LDL is known to deposit cholesterol in tissues, while HDL is known to remove it for return to the liver and excretion from the body. It turns out that LDL cholesterol is usually not measured directly, but calculated by subtracting the sume of HDL cholesterol plus triglycerides/5 from total cholesterol. Prospective epidemiologic studies, including the Framingham Heart Study, indicate that non HDL cholesterol calculated by subtracting HDL cholesterol from total cholesterol is a better predictor of heart disease than is calculated LDL cholesterol. Moreover the third Adult Treatment Panel of the National Cholesterol Education Program established targets of therapy for non-HDL cholesterol in 2001 and again in 2004 as being < 100 mg/dl in heart disease patients and those at high risk of developing the disease. In this paper we review all the evidence and strongly endorse the concept of using non HDL cholesterol as a target of therapy, especially in high risk populations. It has clearly been shown that lowering elevated blood cholesterol (> 240 mg/dl) and elevated low density lipoprotein (LDL) cholesterol ( > 160 mg/dl) with diet and statin medications can reduce the risk of heart disease. Moreover goals for LDL cholesterol and non HDL cholesterol have been established by the National Cholesterol Education program. These latter goals are to get the non-HDL cholesterol to < 100 mg/dl in patients with established heart disease or those at high risk of developing heart disease. We have reviewed the literature and endorse these goals.
Technical Abstract: Although low-density lipoprotein cholesterol (LDL-C) is a well-established atherogenic factor for coronary heart disease, it does not completely represent the risk associated with atherogenic lipoproteins in the presence of high triglyceride (TG) levels. Constituent lipoproteins constituting non–high-density lipoprotein cholesterol (non–HDL-C) include atherogenic TG-rich lipoproteins, cholesteryl ester– enriched remnants of TG-rich lipoproteins, and lipoprotein(a). Recent observational and intervention studies suggest that the predictive value of non-HDL-C for cardiovascular risk and mortality is better than lowdensity lipoprotein cholesterol and that non-HDL-C correlates highly with plasma apolipoprotein B levels. Currently, the National Cholesterol Education Program Adult Treatment Panel III guidelines identify non-HDL-C as a secondary target of therapy in patients with TG elevation (>200 mg/dl) after the attainment of LDL-C target goals. In patients with coronary heart disease or coronary heart disease risk equivalents, an optional non- HDL-C goal is <100 mg/dl. To achieve the non-HDL-C goal, statin therapy may be intensified or combined with ezetimibe, niacin, a fibrate, or omega-3 fatty acids. In conclusion, non-HDL-C remains an important target of therapy for patients with elevated TGs, although its widespread adoption has yet to gain a foothold among health care professionals treating patients with dyslipidemia.