Pitavastatin decreases plasma prebeta1-HDL concentration and might promote its disappearance rate in hypercholesterolemic patients

AIM: Prebeta1-HDL is involved in the initial step of cholesterol efflux from peripheral cells and plays an important role in reverse cholesterol transport. We studied the effect of pitavastatin on the HDL subfraction profile, prebeta1-HDL concentration and its disappearance rate. METHODS: Twenty-nine hypercholesterolemic patients were treated with pitavastatin at 2 mg/day for 4 weeks, and plasma levels of total cholesterol (TC), triglyceride, HDL-cholesterol (C), HDL(2)-C, HDL(3)-C, prebeta1-HDL, LCAT activity, and CETP mass were assayed. The prebeta1-HDL disappearance rate was determined as the difference in prebeta1-HDL concentration before and after incubation at 37 degrees C for 90 min divided by the pre-incubation prebeta1-HDL concentration. RESULTS: Pitavastatin led to significant decreases in TC by 26.9% and LDL-C by 39.8%. HDL-C and HDL(2)-C increased significantly by 6.0% and 9.0%, respectively, but there was no significant change in HDL(3)-C. Prebeta1-HDL concentration significantly decreased (-8.7%; p<0.05); however, its disappearance rate significantly increased (13.0%; p<0.05). There were significant decreases in both LCAT activity and CETP mass. CONCLUSION: Although pitavastatin decreased plasma prebeta1-HDL concentration, it increased the prebeta1-HDL disappearance rate. These data suggest that pitavastatin might promote the early step of reverse cholesterol transport.     

Total cholesterol/HDL cholesterol ratio vs LDL cholesterol/HDL cholesterol ratio as indices of ischemic heart disease risk in men: the Quebec Cardiovascular Study.

BACKGROUND: Total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)/HDL-C ratios are used to predict ischemic heart disease risk. There is, however, no consensus on which of these 2 indices is superior. The objective of the present study was to present evidence that the LDL-C/HDL-C ratio may underestimate ischemic heart disease risk in overweight hyperinsulinemic patients with high triglyceride (TG)-low HDL-C dyslipidemia. METHODS: A total of 2103 middle-aged men in whom measurements of the metabolic profile were performed in the fasting state were recruited from 7 suburbs of the Quebec metropolitan area. RESULTS: The relationship of LDL-C/HDL-C to TC/HDL-C ratios was examined among men in the Quebec Cardiovascular Study classified into tertiles of fasting TG levels. For any given LDL-C/HDL-C ratio, the TC/HDL-C ratio was higher among men in the top TG tertile (>168 mg/dL [>1.9 mmol/L]) than in men in the first and second TG tertiles. Adjustment of the TC/HDL-C ratio for LDL-C/HDL-C by covariance analysis generated significant differences in average TC/HDL-C ratios among TG tertiles (P<.001). Greater differences in features of the insulin resistance syndrome (insulinemia, apolipoprotein B, and LDL size) were noted across tertiles of the TC/HDL-C ratio than tertiles of the LDL-C/HDL-C ratio. CONCLUSION: Variation in the TC/HDL-C ratio may be associated with more substantial alterations in metabolic indices predictive of ischemic heart disease risk and related to the insulin resistance syndrome than variation in the LDL-C/HDL-C ratio.     

脑梗死患者血浆HDL亚类组成及含量研究

目的:分析脑梗死患者血浆高密度脂蛋白(HDL)亚类组成及含量。方法:采用双向电泳-免疫印迹检测法分析50例脑梗死患者和50例正常者HDL亚类的组成及含量。结果:与对照组比较,脑梗死患者血浆中preβ2-HDL和HDL2b含量显著降低(均P<0.01),小颗粒preβ1-HDL含量显著增加(P<0.01);患者血浆三酰甘油(TG)水平与preβ1-HDL、HDL3b、HDL2a和HDL2b含量呈显著负相关(均P<0.05),HDL-C、载脂蛋白AⅠ含量与preβ1-HDL、preβ2-HDL、HDL3c、HDL3b、HDL3a、HDL2a和HDL2b含量呈显著正相关(均P<0.05)。结论:脑梗死患者血浆大颗粒HDL含量明显降低,小颗粒HDL含量明显增加,提示脑梗死患者HDL代谢过程异常。     

Cigarette smoking,high-density lipoprotein cholesterol subfractions,and lecithin: cholesterol acyltransferase in young women

Much of the published data on the relationship of cigarette smoking (CS) with serum lipids and lipoproteins is based on studies of middle-aged individuals. Data on young women are scarce. This study examined the relationship of CS with high-density lipoprotein cholesterol (HDL-C) subfractions and lecithin:cholesterol acyltransferase (LCAT) activity in Japanese collegiate women. Twenty-three current smokers were individually matched for physical activity scores, age, and body mass index (BMI) with 23 nonsmokers. There were no significant differences between smokers and nonsmokers in the mean nutrient intakes. Smokers had significantly lower mean HDL-C, HDL2-C, total cholesterol, and LCAT activity than nonsmokers. In univariate analyses, BMI significantly negatively correlated with HDL-C and HDL2-C. LCAT activity significantly positively correlated with HDL3-C, LDL-C, total cholesterol (TC) and triglycerides (TG). In multiple regression analyses, the number of CS was positively related to TG. BMI was negatively related to TC. LCAT activity was positively related to LDL-C, TC, and TG. These results suggest that the known associations in older adults of CS with HDL-C subfractions and LCAT activity are already apparent in young women.     

Triglycerides and triglycerides to high-density lipoprotein cholesterol ratio are strong predictors of incident hypertension in Middle Eastern women

Dyslipidemia has been reported as a risk factor for incident hypertension in a few prospective studies, however, no study has specifically assessed different lipid measures including the lipid ratios, that is, total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs)/HDL-C as predictors of hypertension among Middle Eastern women with high prevalences of dyslipidemia and hypertension. The study population consisted of 2831 non-hypertensive women, aged ≥ 20 years. We measured lipoproteins, and calculated non-HDL-C and the lipid ratios. The risk-factor-adjusted odds ratios for incident hypertension were calculated for every 1 standard deviation (s.d.) change in TC, log-transformed TG, HDL-C, non-HDL-C, TC/HDL-C and log-transformed TG/HDL-C using multivariate logistic regression analysis. Over a mean follow-up of 6.4 years, 397 women developed hypertension. An increase of 1 s.d. in TG, TC/HDL-C and TG/HDL-C increased the risk of incident hypertension by 16, 19 and 18%, respectively, and 1 s.d. increase in HDL-C decreased the risk of hypertension by 14% in the multivariable model (all P ≤ 0.05). In models excluding women with diabetes and central or general obesity, TG, TG/HDL-C and TC/HDL-C remained as independent predictors of incident hypertension. In conclusion, dyslipidemia, using serum TG and TG/HDL-C, in particular, may be useful in identification of women at risk of hypertension, even in those without diabetes and central or general obesity.     

Use of the plasma triglyceride/high-density lipoprotein cholesterol ratio to identify cardiovascular disease in hypertensive subjects

This analysis evaluated the hypothesis that the plasma triglyceride (TG)/high–density lipoprotein cholesterol (HDL-C) concentration ratio can help identify patients with essential hypertension who are insulin–resistant, with the cardiovascular disease (CVD) risk profile associated with that defect. Data from a community–based study developed between 2003 and 2012 were used to compare CVD risk factors and outcome. Plasma TG/HDL-C cut–points of 2.5 (women) and 3.5 (men) subdivided normotensive (n = 574) and hypertensive (n = 373) subjects into “high” and “low” risk groups. Metabolic syndrome criteria (MetS) were also used to identify “high” and “low” risk groups. The baseline cardio–metabolic profile was significantly more adverse in 2003 in “high” risk subgroups, irrespective of BP classification or definition of risk (TG/HDL-C ratio vs. MetS criteria). Crude incidence of combined CVD events increased across risk groups, ranging from 1.9 in normotensive–low TG/HDL-C subjects to 19.9 in hypertensive–high TG/HDL-C ratio individuals (P for trends <.001). Adjusted hazard ratios for CVD events also increased with both hypertension and TG/HDL-C. Comparable findings were seen when CVD outcome was predicted by MetS criteria. The TG/HDL-C concentration ratio and the MetS criteria identify to a comparable degree hypertensive subjects who are at greatest cardio–metabolic risk and develop significantly more CVD.     

Relation among the plasma triglyceride/high-density lipoprotein cholesterol concentration ratio, insulin resistance, and associated cardio-metabolic risk factors in men and women

Results of recent studies using the ratio of plasma triglyceride (TG) to high-density lipoprotein (HDL) cholesterol concentration to identify insulin-resistant patients at increased cardiometabolic risk have emphasized that the cut point used for this purpose will vary with race. Because TG and HDL cholesterol concentrations vary with gender, this analysis was initiated to define gender-specific plasma TG/HDL cholesterol concentration ratios that best identified high-risk subjects among women (n = 1,102) and men (n = 464) of primarily European ancestry. Insulin resistance was defined as the 25% of the population with the highest values for fasting plasma insulin concentration and homeostasis model assessment of insulin resistance. Using TG/HDL concentration ratios >2.5 in women and >3.5 in men identified subgroups of men and women that were comparable in terms of insulin resistance and associated cardiometabolic risk, with significantly higher values for fasting plasma insulin, homeostasis model assessment of insulin resistance, blood pressure, body mass index, waist circumference, and glucose and TG concentrations and lower HDL cholesterol concentrations than in women and men below these cut points. The sensitivity and specificity of these gender-specific cut points to identify insulin-resistant subjects were about 40% and about 80%, respectively. In conclusion, the plasma TG/HDL cholesterol concentration ratio that identifies patients who are insulin resistant and at significantly greater cardiometabolic risk varies between men and women.     

Relationship between apolipoprotein C-III concentrations and high-density lipoprotein subclass distribution

High-density lipoprotein (HDL) subclasses have different antiatherogenic potentials and functional properties. This work presents our findings and discussions on their metabolic implications on apolipoprotein (apo) C-III together with other apolipoprotein levels and HDL subclass distribution profile. Apolipoprotein A-I contents of plasma HDL subclasses were quantitated by 2-dimensional gel electrophoresis coupled with immunodetection in 511 subjects. Concentrations of triglycerides and of apo B-100, C-II, and C-III were higher, whereas those of HDL cholesterol were lower, for subjects in the highest tertile of apo C-III levels group, which presented a typical hypertriglyceridemic lipid profile. Subjects in the middle and highest tertile of apo C-III levels groups had increased preβ₁-HDL, HDL_3c, HDL_3b (only in the highest tertile of apo C-III group), and HDL_3a, but decreased HDL_2a and HDL_2b contents compared with subjects in the lowest tertile of apo C-III levels group. With the elevation of apo C-III together with apo C-II levels, contents of small-sized preβ₁-HDL increased successively and significantly; but those of large-sized HDL_2b reduced successively and significantly. With a rise in apo C-III and apo A-I levels, those of preβ₁-HDL increased significantly. Moreover, subjects with high apo A-I levels showed a substantial increase in HDL_2b; on the contrary, HDL_2b declined progressively and obviously for subjects in the low apo A-I levels with the elevation of apo C-III levels. Correlation analysis illustrated that apo C-III levels were positively associated with preβ₁-HDL, preβ₂-HDL, and HDL_3a. The particle size of HDL shifted toward smaller sizes with the increase of plasma apo C-III levels, and the shift was more remarkable when the elevation of apo C-III and apo C-II was simultaneous; and besides, higher apo A-I concentrations could modify the effect of apo C-III on HDL subclass distribution profile. Large-sized HDL_2b particles decreased greatly for hypertriglyceridemic subjects who were characterized by elevated apo C-III and C-II accompanied with significantly lower apo A-I, which, in turn, blocked the maturation of HDL.     

High-density lipoprotein subclasses distribution and composition in Mexican adolescents with low HDL cholesterol and/or high triglyceride concentrations, and its association with insulin and C-reactive protein

We tested whether low high-density lipoprotein cholesterol (HDL-C) and/or high triglycerides are associated to abnormal HDL subclasses distribution and composition, and their relationships with fasting insulin and C-reactive protein (CRP). Four groups of adolescents were studied: group 1 (HDL-C< or =35 mg/dl+TG> or =150 mg/dl; n=16); group 2 (isolated HDL-C< or =35 mg/dl; n=31); group 3 (isolated TG> or =150 mg/dl; n=20); and group 4 (CT<200 mg/dl, HDL-C>35 mg/dl, LDL-C<130 mg/dl, and TG<150 mg/dl; n=39). Tanner score-adjusted proportions of large subspecies (HDL(2b), HDL(2a)) were lower, and small (HDL(3b), HDL(3c)) were higher in groups 1, 2 and 3 than in group 4. As a result, HDL particle size in the three dyslipidemic groups was smaller than in group 4 (p<0.001). HDL CE, FC, PL, and apo AI percent contents were lower, whereas HDL TG percent content was higher in groups 1, 2 and 3 compared to group 4. CRP median values were also significantly higher in the three groups with dyslipidemia than in normolipidemic subjects (group 4). Fasting Insulin concentration and HOMA-IR were significantly higher in group 1 than in the other three groups. In stepwise multivariate analysis HDL subclass distribution and composition were independently associated only with HDL-C and waist circumference. As reported in adults, adolescents with low HDL-C and/or high TG have abnormalities in HDL subclasses distribution and lipid composition, which may render their HDL dysfunctional. In addition, these subjects have high CRP and insulin levels suggesting the presence of chronic low-grade inflammation.     

Omega-3 fatty acids selectively raise high-density lipoprotein 2 levels in healthy volunteers

The effects of omega-3 fatty acid supplementation on high-density lipoprotein (HDL) subfraction distribution and composition were evaluated in five healthy volunteers taking 2.8 g/d of eicosapentaenoic acid (EPA) and 1.7 g/d of docosahexaenoic acid (DHA) for 6 weeks. This supplementation resulted in marked changes of the plasma fatty acid composition. Plasma total cholesterol (TC), HDL-cholesterol (HDL-C), and triglyceride (TG) levels did not change. HDL2-C increased by 74%, with a concomitant 19% decrease of HDL3-C; the HDL2 to HDL3 mass ratio increased from 0.30 +/- 0.19 to 0.47 +/- 0.28. The increase of HDL2 was confirmed by nondenaturing polyacrylamide gradient gel electrophoretic separation of HDL subclasses, otherwise showing no change in HDL particle size. After omega-3 supplementation, both HDL2 and HDL3 became cholesteryl ester (CE)- and TG-enriched and free cholesterol (FC)- and phospholipid (PL)-depleted. The reported findings provide a useful adjunct to the antithrombotic potential of omega-3 fatty acids.     

Effect of weight reduction on the distribution of apolipoprotein A-I in high-density lipoprotein subfractions in obese non-insulin-dependent diabetic subjects

High-density lipoprotein (HDL) plays an important role in the process of reverse cholesterol transport, which may become suboptimal with increasing body fatness. HDL cholesterol that is reduced in obese subjects paradoxically decreases during weight reduction. To determine how weight reduction affects HDL subclasses that are involved in reverse cholesterol transport, we studied HDL from obese diabetic subjects before and after energy restriction within background diets high in either carbohydrate or monounsaturated fatty acids (MUFAs). Body weight, blood glucose, total cholesterol, and LDL cholesterol decreased after 8 and 12 weeks of weight reduction. With the very-low-fat diet, HDL cholesterol decreased significantly at 8 weeks, but recovered to initial levels after 12 weeks as body weight began to stabilize. Plasma apolipoprotein A-I (apo A-I) decreased substantially and significantly at 8 and 12 weeks with both diets, and was reflected in the reduction of apo A-I in HDL subclasses alpha1, alpha2, pre-beta1, and pre-beta2 + pre-beta3. The calculation of the percentage distribution of apo A-I among HDL species showed that only the proportion of pre-beta1-HDL decreased, whereas alpha2-HDL increased. This led to a significant increase in the alpha1 + alpha2/pre-beta ratio, ie, the ratio of the large cholesterol "storage" or "sink" HDL to the HDL "shuttle" fraction considered to be the initial acceptor of cell cholesterol. These data suggest that despite the reduction in HDL cholesterol and apo A-I, the redistribution of apo A-I in pre-beta1-HDL and alpha-HDL observed with weight reduction appears to revert to the pattern that we have previously reported in lean as opposed to overweight subjects.     

Comparison of low-density lipoprotein cholesterol/high-density lipoprotein cholesterol and total cholesterol/high-density lipoprotein cholesterol for the prediction of thin-cap fibroatheroma determined by intravascular optical coherence tomography

BackgroundThe correlation among the ratios of low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/ HDL-C), total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) and thin-cap fibroatheroma has not yet been established.MethodsIt was a single center, retrospective observational study. In total, we recruited 421 patients (82.4% men; mean age 65.73 ± 10.44 years) with one culprit vessel which determined by intravascular optical coherence tomography (OCT). The thinnest-capped fibroatheroma (TCFA) group was defined as lipid contents in > 2 quadrants, with the thinnest fibrous cap measuring less than 65 μm. Univariate and multivariate logistic regression were carried out to explore the relationship between lipoprotein ratios, TCFA and other characteristics of plaque. To compare different ratios, the area under curve (AUC) of receiver-operating characteristic (ROC) curve was assessed.ResultsOCT was performed in 421 patients (TCFA group (n = 109), non-TCFA group (n = 312)). LDL-C/HDL-C in the TCFA group was significantly higher than in the non-TCFA group (2.95 ± 1.20 vs. 2.43 ± 0.92, P < 0.05), as was TC/LDL in TCFA and non-TCFA group (4.57 ± 1.58 vs. 4.04 ± 1.13, P < 0.05). Both LDL-C/HDL-C (OR: 1.002 (1.002-1.003), P < 0.05) and TC/HDL-C (OR: 1.001 (1.001-1.004), P < 0.05) were considered independent factors for the prediction of TCFA according to the logistic regression. Based on the AUC comparison, LDL-C/ HDL-C and TC/HDL-C had no significant difference statistically (LDL-C/HDL-C AUC: 0.63; TC/HDL-C AUC: 0.61; P = 0.10) for the prediction of TCFA.ConclusionsLDL-C/HDL-C and TC/HDL-C could be the independent factors for predicting the presence of TCFA, indicating coronary plaque vulnerability in CAD patients. Moreover, TC/HDL-C also showed a comparative performance for the prediction of TCFA as LDL-C/HDL-C.     

Ability of the plasma concentration ratio of triglyceride/high-density lipoprotein cholesterol to identify increased cardio-metabolic risk in an east Asian population

Aim

The plasma concentration ratio of triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) has identified increased cardio-metabolic risk and outcome in European populations. The goal of this study was to see if this ratio would also have clinical utility in identifying cardio-metabolic risk in an East Asian population.

Methods

Measurements of various cardio-metabolic risk factors, including coronary calcium scores, were available on 12,166 apparently healthy Korean adults. Approximately 25% of men and women with the highest TG/HDL-C ratios were classified as being at high cardio-metabolic risk, and their risk factor profiles compared to the remainder of the population, as well as to individuals with the metabolic syndrome (MetS).

Results

High cardio-metabolic risk (upper 25%) was defined as a TG/HDL-C ratio ≥3.5 (men) or ≥2.0 (women), and all cardio-metabolic risk factors measured, including coronary calcium scores, were significantly more adverse when compared to individuals beneath these cut-points. Although cardio-metabolic risk profiles appeared reasonably comparable in subjects identified by either a high TG/HDL-C or a diagnosis of MetS, use of the TG/HDL-C increased the numbers at high risk.

Conclusion

Evidence that determination of the plasma TG/HDL-C concentration ratio provides a simple way to identify individual at increased cardio-metabolic risk has been extended to an East Asian population. The ability of an elevated TG/HDL-C ratio to accomplish this goal is comparable to that achieved using the more complicated MetS criteria.     

The triglyceride/high-density lipoprotein cholesterol ratio, the small dense low-density lipoprotein phenotype, and ischemic heart disease risk

This study investigated the relevance of using the plasma triglyceride to high-density lipoprotein cholesterol ratio (Log TG/HDL-C) for the prediction of the small dense lowdensity lipoprotein (LDL) phenotype and the risk of ischemic heart disease (IHD). Analyses were based on data from the Quebec Cardiovascular Study in a cohort of 2072 men free of IHD at baseline, among whom 262 had a first IHD event (coronary death, non fatal myocardial infarction and unstable angina) during a 13-year follow-up period. LDL particle size phenotype was characterized using 2-16% polyacrylamide gradient gel electrophoresis (PAGGE) of whole plasma. There were significant associations between the Log TG/HDL-C ratio and features of LDL size phenotype such as the proportion of LDL with a diameter <255A (r = 0.43, p < 0.001) and LDL peak particle size (r = -20.55, p < 0.001). However, the Log TG/HDL-C ratio brought no additional value (p a yen 0.1) in predicting the small dense LDL phenotype (area under the receiver operating curve (AUROC = 71.9%) compared to TG alone (AUROC = 71.2%) or to a combination of Log TG and HDL-C (AUROC = 72.4%) after multivariate adjustment for non lipid risk factors. Finally, elevations in the Log TG/HDL-C ratio did not improve the discrimination of incident IHD cases from non IHD cases compared to the use of plasma TG levels alone (p = 0.5) or a combination of the individual TG and HDL-C values (p = 0.5). The Log TG/HDL-C ratio does not improve our ability to identify individuals with the small dense LDL phenotype compared to plasma TG levels alone. The Log TG/HDLC is also not superior to plasma TG levels alone in predicting IHD risk in men of the QuA(c)bec Cardiovascular Study.     

The relationship between high density lipoprotein subclass profile and apolipoprotein concentrations

The HDL fraction in human plasma is heterogeneous in terms of size, shape, composition, and surface charge. The HDL subclasses contents were quantified by 2-dimensional non-denaturing gel electrophoresis, immunoblotting, and image analysis. This research review systematically analyzed the relationship between the contents of HDL subclasses and the concentrations and ratios of the 5 major plasma apolipoproteins (apo). As the concentration of apoA-I increases, the contents of all HDL subclasses increase significantly. The most significant association was observed between large-sized HDL2b contents and apoA-I. ApoA-II played a dual function in the contents of HDL subclasses, and both small-sized HDL3b and HDL3a and large-sized HDL2b tended to increase with apoA-II concentration. An increase in the concentrations of apoC-II, C-III, and B-100 resulted in higher levels of small-sized HDL particles and lower levels of large-sized HDL particles. Plasma apoB- 100, apoC-II, and apoC-III appear to play a coordinated role in assembly of HDL particles and the determination of their contents. Higher concentrations of apoA-I could inhibit the reduction in content of large-sized HDL2b effected by apoB-100, C-II, and C-III. The preβ1-HDL contents increased significantly and those of HDL2b declined progressively with an increased apoB-100/apoA-I or a decreased apoC-III/apoC-II ratio. In summary, each apo has distinct but interrelated roles in HDL particle generation and metabolism. ApoA-I and apoC-II concentrations are independent determinants of HDL subtypes in circulation and apoA-I levels might be a more powerful factor to influence HDL subclasses distribution. Moreover, apoB- 100/apoA-I ratio could reliably and sensitively reflect the HDL subclass profile.     

Hyperhomocysteinemia decreases circulating high-density lipoprotein by inhibiting apolipoprotein A-I Protein synthesis and enhancing HDL cholesterol clearance

We previously reported that hyperhomocysteinemia (HHcy), an independent risk factor of coronary artery disease (CAD), is associated with increased atherosclerosis and decreased plasma high-density lipoprotein cholesterol (HDL-C) in cystathionine beta-synthase-/apolipoprotein E-deficient (CBS(-/-)/apoE(-/-)) mice. We observed that plasma homocysteine (Hcy) concentrations are negatively correlated with HDL-C and apolipoprotein A1 (apoA-I) in patients with CAD. We found the loss of large HDL particles, increased HDL-free cholesterol, and decreased HDL protein in CBS(-/-)/apoE(-/-) mice, and attenuated cholesterol efflux from cholesterol-loaded macrophages to plasma in CBS(-/-)/apoE(-/-) mice. ApoA-I protein was reduced in the plasma and liver, but hepatic apoA-I mRNA was unchanged in CBS(-/-)/apoE(-/-) mice. Moreover, Hcy (0.5 to 2 mmol/L) reduced the levels of apoA-I protein but not mRNA and inhibited apoA-1 protein synthesis in mouse primary hepatocytes. Further, plasma lecithin:cholesterol acyltransferase (LCAT) substrate reactivity was decreased, LCAT specific activity increased, and plasma LCAT protein levels unchanged in apoE(-/-)/CBS(-/-) mice. Finally, the clearance of plasma HDL cholesteryl ester, but not HDL protein, was faster in CBS(-/-)/apoE(-/-) mice, correlated with increased scavenger receptor B1, and unchanged ATP-binding cassette transporter A1 protein expression in the liver. These findings indicate that HHcy inhibits reverse cholesterol transport by reducing circulating HDL via inhibiting apoA-I protein synthesis and enhancing HDL-C clearance.     

Garlic powder, effect on plasma lipids, postprandial lipemia, low-density lipoprotein particle size, high-density lipoprotein subclass distribution and lipoprotein(a)

OBJECTIVES: To test the hypothesis that a garlic supplement alters plasma lipoproteins, postprandial lipemia, low-density lipoprotein (LDL) size and high-density lipoprotein (HDL) subclass distribution differently in 50 moderately hypercholesterolemic subjects classified as LDL subclass pattern A or B. BACKGROUND: Garlic has been variably reported to reduce or not affect plasma cholesterol values. Low-density lipoprotein pattern B is a common inherited disorder of lipoprotein metabolism that has been shown to have a significantly greater response to several lipid lowering treatments including low fat diet when compared with LDL pattern A individuals. METHODS: A double blind, randomized, placebo controlled trial in an outpatient lipid research clinic was performed and included fifty moderately hypercholesterolemic subjects (mean LDL cholesterol = 166 +/- 22 mg/dl) classified as LDL subclass pattern A (predominantly large LDL, n = 22) or B (predominantly small LDL, n = 28). Following a two-month stabilization period, subjects were randomly assigned to a placebo or 300 mg three times a day of a standardized garlic tablet for three months. RESULTS: For all subjects, LDL pattern A and B subjects combined, garlic treatment for three months resulted in no significant change in total cholesterol, LDL cholesterol, HDL cholesterol, HDL subclass distribution, postprandial triglycerides, apolipoprotein B, lipoprotein (a) (Lp[a]), LDL peak particle diameter or LDL subclass distribution. There was no significant difference in response for the same parameters among subjects classified as LDL pattern A or B with the exception of significantly greater (p = 0.01) reduction in mean peak particle diameter in pattern A subjects treated with either garlic or placebo. There was no significant change in LDL subclass distribution. CONCLUSIONS: This investigation confirms that garlic therapy has no effect on major plasma lipoproteins and further, that it has no impact on HDL subclasses, Lp(a), apolipoprotein B, postprandial triglycerides or LDL subclass distribution. Garlic may have a greater effect on LDL particle diameter in LDL pattern A compared with pattern B subjects. This difference was not reflected in other plasma lipid measurements.     

Bezafibrate increases prebeta 1-HDL at the expense of HDL2b in hypertriglyceridemia

Prebeta1-high density lipoprotein (prebeta1-HDL), the initial acceptor of cell-derived cholesterol, can be generated from HDL(2) by hepatic lipase. Because bezafibrate elevates lipase activity, it may increase prebeta1-HDL at the expense of HDL(2). To answer this question, we determined the apolipoprotein A-I (apoA-I) distribution in 20 hypertriglyceridemics (triglycerides>2.26 mmol/L) and 20 sex-matched normolipidemics by native 2-dimensional gel electrophoresis. At baseline, prebeta1-HDL was 70% higher in hypertriglyceridemics than in normolipidemics (123.5+/-49.9 versus 72.5+/-34.1 mg/L apoA-I, P<0.01). Prebeta1-HDL was positively correlated with triglyceride (r=0.624, P<0.0001). A 4-week bezafibrate treatment (400 mg daily) increased prebeta1-HDL by 30% (160.2+/-64.5 mg/L apoA-I, P<0.05) but decreased HDL(2b) by 31% (from 188.8+/-94.9 to 129.3+/-78.7 mg/L apoA-I, P<0.05). Hepatic lipase activity increased by 24% (P<0.005). Prebeta1-HDL was generated either from ultracentrifugally isolated HDL(2) or from plasma during incubation with triglyceride lipase. In conclusion, bezafibrate increases prebeta1-HDL at the expense of HDL(2). We speculate that such an effect might partly contribute to the antiatherogenic action of bezafibrate.     

The ratio of plasma high-density lipoprotein cholesterol to total and low-density lipoprotein cholesterol: age-related changes and race and sex differences in selected North American populations. The Lipid Research Clinics Program Prevalence Study

The distribution of the ratios of plasma high-density lipoprotein cholesterol (HDL-C) to total cholesterol (TC) and of HDL-C to low-density lipoprotein cholesterol (LDL-C) are presented for 6900 white and 495 black examinees greater than 4 years old. Measurements were obtained during the visit 2 survey of the Lipid Research Clinics (LRC) Program Prevalence Study, and correspond to a 15% random sample of 60,502 participants screened during the LRC visit 1 survey. Age-specific means, medians, and selected percentiles are given by sex and by gonadal hormone use in white women. Apparent in these cross-sectional data was a consistent age-related decline in the ratio of HDL-C to TC for white male participants, from a mean of 0.360 in the age group 5 to 9 to a mean of 0.211 in the age group 50 to 54. Thereafter the mean ratio increased slightly. In white women not using gonadal hormones the age-related decline in the ratio was only evident starting at the age group 35 to 39, from which it declines from 0.329 to 0.258 in the age group 55 to 59. White women using gonadal hormones showed very minor age-related changes in the HDL-C/TC ratio, varying around a mean of 0.300. The number of blacks examined was low and thus the racial comparisons must be interpreted with caution. For each gender, age-related trends were similar in black and white study participants. Black men, however, had a higher percentage of TC carried as HDL-C than white men in all age groups examined. Black women had a higher percentage of TC in HDL-C than white women only below age 20; in the adult age range no appreciable differences were seen. Pearson correlation coefficients between the lipid, lipoprotein, and lipoprotein ratios are presented. The ratio HDL-C/TC correlated highly with the ratio HDL-C/LDL-C (greater than 0.92 for all groups) and the former may be a more conveniently determined surrogate for the latter. Although not exhaustive regarding the information it conveys about a lipid pattern, the ratio HDL-C/TC has the advantage of summarizing complex associations into a single numerical approximation.     

Influence of triglyceride concentration on the relationship between lipoprotein cholesterol and apolipoprotein B and A-I levels

A sample of 2,103 men aged 47 to 76 years from the Québec Cardiovascular Study cohort was examined to quantify the influence of plasma triglyceride (TG) levels on the relationship between plasma lipoprotein cholesterol and either apolipoprotein A-I (apo A-I) or apo B concentrations. Regression analyses between high-density lipoprotein cholesterol (HDL-C) and apo A-I through TG tertiles showed highly significant correlations (.62 < or = r < or = .75, P < .0001) in all TG tertiles between these 2 variables. The associations for plasma apo B versus low-density lipoprotein cholesterol (LDL-C) and non-HDL-C levels were also studied on the basis of TG concentrations, and correlation coefficients between either LDL-C or non-HDL-C and apo B were essentially similar among TG tertiles (.78 < or = r < or = .85 and .83 < or = r < or = .86 for LDL-C and non-HDL-C, respectively, P < .0001). Regression analyses also showed that lower HDL-C levels were found for any given apo A-I concentration among men in the 2 upper TG tertiles, whereas lower LDL-C concentrations were observed at any given apo B level among subjects in the upper TG tertile. We further investigated whether there were synergistic alterations in the HDL-C/apo A-I and LDL-C/apo B ratios as a function of increasing plasma TG. A significant association was noted between these 2 ratios (r = .37; P < .0001). Mean HDL-C/apo A-I and LDL-C/apo B ratios were then calculated across quintiles of plasma TG concentrations. Increased TG concentrations were first associated with a reduced HDL-C/apo A-I ratio, followed by a decreased LDL-C/apo B ratio. These results suggest that a relatively modest increase in TG may rapidly alter the relative cholesterol content of HDL particles. Finally, the cholesterol content of the non-HDL fraction appears to be influenced less by TG levels than HDL-C and LDL-C fractions. Thus, the plasma apo B-containing lipoprotein cholesterol level may provide a better index of number of atherogenic particles than the LDL-C concentration, particularly in the presence of hypertriglyceridemia (HTG).