High-Density Lipoprotein Subpopulation Profile and Coronary Heart Disease Prevalence in Male Participants of the Framingham Offspring Study

Abstract

Objective-High-density lipoprotein (HDL) is a heterogeneous lipoprotein class and there is no consensus on the value of HDL subspecies in coronary heart disease (CHD) risk assessment. We tested the hypothesis whether specific HDL subpopulations are significantly associated with CHD-prevalence. Methods and Results-ApoA-I concentrations (mg/dL) in HDL subpopulations were quantitatively determined by native 2d gel electrophoresis, immunoblotting, and image analysis in male participants in the Framingham Offspring Study (FOS). CHD cases (nϭ169) had higher pre␤-1 and ␣-3 particle and lower ␣-1, pre␣-3, and pre␣-1 particle levels than either all (nϭ1277) or HDL cholesterol-matched (nϭ358) controls. ␣-1 and pre␣-3 levels had an inverse association, whereas ␣-3 and pre␣-1 particle levels had a positive association with CHD prevalence after adjusting the data for established CHD risk factors. Standardized logit coefficients indicated that ␣-1 HDL was most significantly associated with CHD prevalence. Moreover, each mg/dL increase in ␣-1 particle level decreased odds of CHD by 26% (PϽ0.0001), whereas each mg/dL increase in HDL cholesterol decreased odds of CHD by 2% in a model including all established CHD risk factors. Conclusions-Specific HDL subpopulations were positively correlated, whereas others were inversely correlated with CHD prevalence in male subject in the FOS, indicating that the various HDL particles might have different roles in the cause of CHD. [1][2][3][4] Traditionally, HDL has been separated into major subclasses by polyanion precipitation, ultracentrifugation (HDL2 and HDL3), or by the apolipoprotein content, distinguishing particles containing only apoA-I (LpA-I), the major apolipoprotein of HDL, from particles containing both apoA-I and apoA-II (LpA-I:A-II). None of these techniques has provided any convincing evidence that 1 kind of HDL subfraction has any greater cardioprotective function than another. [5][6][7][8][9][10] The lack of agreement among these studies is probably related to the fact that all of these HDL subfractions are themselves heterogeneous, containing a variety of different HDL subspecies with possibly different physiological functions.Our laboratory uses native 2-dimensional gel electrophoresis, immunoblotting, and image analysis to separate HDL subpopulations quantitatively from plasma with highresolution based on electrophoretic charge and particle size. 11 We determine apoA-I content, not cholesterol, in these particles. This method has been useful in studies of HDL metabolism and cholesterol transport from cells because it separates intermediates in these processes. 12 A small casecontrol study indicated that coronary heart disease (CHD) patients not only had HDL deficiency but also had a major rearrangement in the apoA-I-containing HDL subpopulations with significantly lower levels of the large ␣-1 and pre␣-1 (Ϸ11 nm), and higher levels of the small ␣-3 (Ϸ8.4 nm) and pre␤-1 (Ϸ5.6 nm) HDL particles than controls. 13 Among these particles, ␣-3 contains both apoA-I and apoA-...

Prevalence of Emerging Cardiovascular Risk Factors in Younger Individuals with a Family History of Premature Coronary Heart Disease and Low Framingham Risk Score

“…Low levels of HDL 2 are associated with an increased risk of CV disease, and in the Framingham Offspring Study, the measurement of larger HDL 2 particles better differentiated those individuals who developed CHD from controls than did levels of either HDL or LDL cholesterol. 17 As with traditional CV risk factors, the more emerging risk factors present in an individual patient the higher the CV risk. Wang et al 18 measured multiple emerging biomarkers in 3,209 participants from the Framingham Heart Study, and found persons with high multi-marker scores had a risk of death 4-fold higher than persons with low multi-marker scores.…”

Association of HDL-C and apolipoprotein A-I with the risk of type 2 diabetes in subjects with impaired fasting glucose

“…It has been reported that the biological activities of HDLs differ according to HDL subpopulations (21). For example, the Framingham Offspring Study showed that large a1 HDL particles are inversely associated with CHD prevalence after adjusting for established CHD risk factors (22). Similarly, small discoid HDL particles are often elevated in patients with CHD, whereas large a2 HDL particles are decreased in patients with CHD (23).…”

A case-control study on the relationship between HDL2b and non-alcoholic fatty liver disease in Chinese type 2 diabetic patients

“…HDL2b plays a significant role of protection against atherosclerosis and coronary artery disease (21). In humans, HDL subclasses may be influenced by several factors including ethnicity (22), TG concentrations (23), antidiabetic or lipid regulating drugs (24,25), blood glucose (26,27) and CHD (5,7). In this matched case-control study using a representative sample population with strict inclusion criteria to exclude the impact of factors such as FBG and HbA1c, we found significantly decreased HDL2b (p-0.01) and a decreased HDL2b to total HDL ratio (p-0.01) in T2DM patients with NAFLD as compared with the control group.…”

“…HDL-C is an important factor associated with an increased risk of future ischaemic heart disease (3). There is a significant inverse correlation between the large and low-density subfractions of HDL (HDL2a, HDL2b and HDL3a) and CHD, and a significant positive correlation between the small but high-density subfraction of HDL (HDL3b and HDL3c) and CHD (4,5). Moreover, it has been shown that HDL2b is a more significant factor correlated with CHD compared with total HDL (6,7).…”