Plasma Levels of HDL Subpopulations and Remnant Lipoproteins Predict the Extent of Angiographically-Defined Coronary Artery Disease in Postmenopausal Women

Abstract

Objective-The association of coronary heart disease (CHD) with subpopulations of triglyceride (TG)-rich lipoproteins and high-density lipoproteins (HDL) is established in men, but has not been well characterized in women. Methods and Results-Plasma HDL subpopulation concentrations, quantified by 2-dimensional gel electrophoresis, and plasma remnant-like particle cholesterol (RLP-C) concentrations were measured in 256 postmenopausal women with established CHD and in 126 CHD-free postmenopausal women. Coronary artery disease was assessed in women with CHD by quantitative coronary angiography. Plasma RLP-C and pre␤1 HDL concentrations were higher and ␣1 and ␣2 HDL concentrations were lower in CHD than in CHD-free women. After adjustment for conventional CHD-risk factors, plasma levels of RLP-C were positively associated with the degree of coronary artery disease. In similar analyses, plasma pre␤1 HDL particle concentrations were positively associated and ␣2 HDL particle concentrations were inversely associated with the extent of coronary atherosclerosis. Plasma TG, low density lipoprotein cholesterol, and HDL cholesterol levels were not associated with the degree of coronary atherosclerosis. Key Words: women Ⅲ angiography Ⅲ lipoproteins Ⅲ coronary heart disease P opulation-based prospective studies have established an association between plasma triglyceride (TG) levels and risk of coronary heart disease (CHD). 1 This association is stronger in women than in men. 1 Fasting plasma TG concentrations reflect the concentration of both TG-rich very lowdensity lipoproteins (VLDL) and remnants of VLDL and chylomicrons. Remnant lipoproteins are generated by lipolysis of TG-rich lipoproteins and play a greater role in CHD risk than their precursors. The first evidence that remnant lipoproteins are related to the development of CHD came from studies conducted more than 50 years ago in which remnant lipoproteins with Svedberg flotation rate of 12 to 60 were isolated by ultracentrifugation. 2 More recently, case-control studies conducted predominantly in male patients have supported the concept that remnant lipoproteins play an important role in the development of CHD. [3][4][5] Remnant lipoprotein levels have also been shown to be significantly higher in women with CHD as compared with healthy women in the Framingham Offspring Study. 6 The association between low levels of high-density lipoprotein (HDL) cholesterol (C) and increased risk of CHD is well documented. 7,8 The National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) has defined an HDL-C Ͻ40 mg/dL as an independent risk factor for CHD. 9 HDL comprise a number of subpopulations differing in apolipoprotein and lipid composition and representing different stages of the continuous HDL remodeling occurring in plasma. These HDL subpopulations exhibit a different ability to protect from CHD. 10 Separation of HDL particles by 2-dimensional gel electrophoresis allows the identification of eight major subpopulations: pre␤1 to 2, ␣1 to 3, and pre␣1 to 3....

Effects of weight loss, induced by gastric bypass surgery, on HDL remodeling in obese women

“…However, almost one-half of myocardial infarctions and strokes occur in people with normal LDL-C levels ( 17 ), leading to a search for more specifi c markers for risk of CVD. Emerging data indicate that more detailed characterization of plasma apolipoproteins (apo) and lipoprotein subpopulations, including apoA-I, apoA-II, apoE, apoB, remnant lipoprotein cholesterol (RLP-C), and HDL subpopulations, provides additional information regarding CVD risk (18)(19)(20)(21). Specifi c apoA-I-containing HDL particles (large lipid-rich ␣ -1 and ␣ -2, and small lipid-poor pre ␤ -1) were proven to be superior to standard lipid measurements in CVD risk assessment in large epidemiological studies (19)(20)(21).…”

“…characterized by low levels of ␣ -1 and ␣ -2 and high levels of pre ␤ -1 HDL is signifi cantly associated with increased initial and recurrent CVD events (18)(19)(20)(21). Furthermore, in the HDL-Atherosclerosis Treatment Study, simvastatin + niacin combination therapy increased concentrations of large HDL particles ( ␣ -1 and ␣ -2) and decreased the concentration of the small HDL particle (pre ␤ -1), and this shift was significantly associated with a slower progression of coronary stenosis assessed by angiography ( 18 ).…”

High-Density Lipoprotein Subfractions - What the Clinicians Need to Know

“…In diabetics, the pre-β-HDL concentration was higher compared to non-diabetic subjects and positively correlated with carotid intima media thickness [28]. Also, postmenopausal women with established CAD had higher levels of pre-β-HDL and lower levels of large α-particles than control women, confirming that the profile distribution of HDL subpopulations could be more informative than HDL-C concentrations in the assessment of cardiovascular risk [29]. …”

Risk Factors of Coronary Artery Stenosis in Patients With Rheumatoid Arthritis

“…Популяционные исследования показали, что уровень ЛПВП является лучшим предиктором развития ИБС, чем концентрация ХС и ХС ЛПНП [22][23][24]. Низкий уровень ЛПВП признан независимым ФР развития ИБС [25,26].…”