Location: Location not imported yet.Title: High-density lipoprotein particles, coronary heart disease, and niacin) Author
|Asztalos, Bela f.|
Submitted to: Clinical Lipidology
Publication Type: Review article
Publication Acceptance Date: 8/7/2010
Publication Date: 9/1/2010
Citation: Asztalos, B. 2010. High-density lipoprotein particles, coronary heart disease, and niacin. Clinical Lipidology. 4(5):405-410. Interpretive Summary:
Technical Abstract: In clinical trials, the use of statins in patients with high risk for cardiovascular disease (CVD) has resulted in a 25% to 40% decrease in major clinical events. However, despite a marked reduction (up to 60%) in LDL-C, approximately 50% (or more) of patients continue to have CVD events. This high residual risk in statin-treated patients initiated the search for new ways to reduce CVD risk. High-density lipoprotein (HDL) is the next logical target. The authors of epidemiological and cross-sectional studies identified low HDL-C level as an independent risk factor for CVD. On the basis of the Framingham Heart Study data, HDL-C less than 35 mg/dL was established as an independent risk factor and HDL-C greater than 60 mg/dl was defined as protective and considered to reduce the global risk estimate. Presently the cut point for defining HDL-C as low is less than 40 mg/dL for men and less than 50 mg/dL for women. Whether an HDL-C level greater than 60 mg/dL can be regarded as protective in all patients has recently been debated. Some investigators have provided evidence for the existence of dysfunctional HDL in patients with vascular disease; however, the term “dysfunctional HDL” has not been well and consistently defined. Dysfunctional HDL is generally thought of as not protective against CVD even if HDL-C is present in high levels. It is assumed that dysfunctional HDL has altered composition and altered functions. Studies in mice have demonstrated that decreased scavenger receptor B1 (SR-B1) reduces clearance of HDL-C and results in greater plasma concentrations. HDL particles become larger with more cholesterol content, but the cholesterol transport into the liver and into the bile is decreased; cholesterol transport from peripheral tissues is impeded and the resulting fails to protect from developing arteriosclerosis. Low HDL-C levels can be inherited dyslipidemia expressed as increased concentrations of the triglyceride-rich lipoproteins, very low density lipoproteins (VLDL), and chylomicrons. This form of dyslipidemia is responsible for 15% or more of premature CHD cases. The specific disorders of familial combined hyperlipidemia (FCHL) have been reported to be responsible for 14% of premature CHD cases, and to be responsible for approximately 4% of premature CHD cases. Factors associated with sedentary lifestyle, obesity, smoking, and poor control of diabetes mellitus contribute to both increased triglycerides and low HDL-C.