LDL Peak Particle Diameter Research Articles

Soy isoflavones improve plasma lipids in normocholesterolemic, premenopausal women

Soy consumption is known to reduce plasma total cholesterol and LDL cholesterol in hypercholesterolemic subjects, but the responsible soy components and the effects in normocholesterolemic subjects remain unclear. The effects of soy isoflavone consumption on plasma total cholesterol, HDL-cholesterol, LDL-cholesterol, triacylglycerol, apolipoprotein A-I, apolipoprotein B, and lipoprotein(a) concentrations and on LDL peak particle diameter were examined in normocholesterolemic, premenopausal women. Thirteen healthy, normocholesterolemic, free-living, premenopausal female volunteers took part in this randomized, crossover-controlled trial. Each subject acted as her own control. Three soy isoflavone intakes (control: 10.0 +/- 1.1; low: 64.7 +/- 9.4; and high: 128.7 +/- 15.7 mg/d), provided as soy protein isolate, were consumed for 3 menstrual cycles each. Total cholesterol, HDL cholesterol, LDL cholesterol, and triacylglycerol were measured over the menstrual cycle. Apolipoprotein A-I, apolipoprotein B, lipoprotein(a), and LDL peak particle diameter were evaluated in the midluteal phase. Total cholesterol, HDL-cholesterol, and LDL-cholesterol concentrations changed significantly across menstrual cycle phases (P < 0.005). During specific phases of the cycle, the high-isoflavone diet lowered LDL cholesterol by 7.6-10.0% (P < 0.05), the ratio of total cholesterol to HDL cholesterol by 10.2% (P < 0.005), and the ratio of LDL to HDL cholesterol by 13.8% (P < 0.002). Isoflavones significantly improved the lipid profile across the menstrual cycle in normocholesterolemic, premenopausal women. Although of small magnitude, these effects could contribute to a lower risk of developing coronary heart disease in healthy people who consume soy over many years.

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

OBJECTIVESTo 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.BACKGROUNDGarlic 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.METHODSA 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.RESULTSFor 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.CONCLUSIONSThis 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.

Visceral adipose tissue and low-density lipoprotein particle size in middle-aged versus young men.

Age is associated with increased deposition of visceral adipose tissue. We examined whether this age-related change in regional adipose tissue distribution had an impact on low-density lipoprotein (LDL) particle size. For this purpose, the plasma lipoprotein-lipid profile, including LDL peak particle diameter as determined by gradient gel electrophoresis, was assessed in 38 young men (aged 26.4 +/- 4.2 years, mean +/- SD) and compared with 40 middle-aged men (55.9 +/- 6.2 years). Middle-aged men had higher values for total body fat and visceral adipose tissue area as measured by computed tomography than young men (P < .001). Although significant differences were noted between the two age groups for plasma cholesterol, triglyceride (TG), apolipoprotein B (apo B), LDL cholesterol, and LDL apo B, as well as the cholesterol to high-density lipoprotein (HDL) cholesterol ratio (P < .001), no difference was found for LDL peak particle size between young and middle-aged men. While visceral adipose tissue was a significant correlate of plasma lipoprotein levels, the fasting TG concentration was the best predictor of LDL particle size, and the regression of TG levels on LDL peak particle diameter was not different between the two age groups. These results suggest that middle-aged men are characterized by an increased concentration of LDL particles (reflected by increased LDL apo B levels) but not by a reduced LDL peak particle size compared with young men. It is therefore proposed that in the absence of an important age-related change in TG levels, age per se is associated with an increased concentration of atherogenic LDL particles rather than a reduction of LDL particle diameter.

Effects of troglitazone on atherogenic lipoprotein phenotype in coronary patients with insulin resistance

Insulin resistance is associated with atherogenic lipoprotein phenotype, including small dense LDL particle, hypertriglycemia and low HDL cholesterol levels. Troglitazone, a novel insulin sensitizing agent, may improve the associated lipid profile in patients with insulin resistance. We examined the effects of troglitazone (400 mg daily for 12 weeks) in 12 non-diabetic coronary patients (60±10 years), all of whom had hyperinsulinemic response to an oral glucose load. Troglitazone markedly reduced the insulin response. After the treatment, plasma triglycerides decreased by 32% ( P<0.05), HDL cholesterol increased by 11% ( P<0.05) and LDL peak particle diameter increased from 24.7±0.3 to 25.5±0.5 nm ( P<0.01). These lipidic improvements were associated with a significant rise in postheparin lipoprotein lipase levels (175±52 to 217±69 ng/ml, P<0.01). In patients with insulin resistance syndrome, troglitazone improved the atherogenic lipoprotein phenotype as well as hyperinsulinemia. Our data suggest that troglitazone therapy could reduce the atherosclerotic risk due to insulin resistance even in non-diabetic patients.

Inheritance of LDL peak particle diameter: Results from a segregation analysis in Israeli families

Genetic and environmental determinants of LDL peak particle diameter (LDL-PPD) were investigated in a sample of 80 kindreds residing in kibbutz settlements in Israel. The sample included 182 males and 191 females ages 15–93 years. LDL-PPD levels were first adjusted for variability in sex and age. Commingling analysis demonstrated that a mixture of two normal distributions fit the adjusted LDL-PPD levels better than did a single normal distribution. Complex segregation analysis was first applied to these sex and age adjusted data but was not conclusive. However, when the regression model for sex and age allowed coefficients to be ousiotype (class) specific, the mixed environmental model was rejected while a major Mendelian model was not. These results suggest that the particular genotypes determined by the major gene, which are associated with different phenotypic variances, are likely to be more realistic, and that this analytic approach can contribute to improving our understanding of the genetics of LDL particle size. Genet. Epidemiol. 16:382–396, 1999. © 1999 Wiley-Liss, Inc.

Inheritance of LDL peak particle diameter: results from a segregation analysis in Israeli families.

Genetic and environmental determinants of LDL peak particle diameter (LDL-PPD) were investigated in a sample of 80 kindreds residing in kibbutz settlements in Israel. The sample included 182 males and 191 females ages 15-93 years. LDL-PPD levels were first adjusted for variability in sex and age. Commingling analysis demonstrated that a mixture of two normal distributions fit the adjusted LDL-PPD levels better than did a single normal distribution. Complex segregation analysis was first applied to these sex and age adjusted data but was not conclusive. However, when the regression model for sex and age allowed coefficients to be ousiotype (class) specific, the mixed environmental model was rejected while a major Mendelian model was not. These results suggest that the particular genotypes determined by the major gene, which are associated with different phenotypic variances, are likely to be more realistic, and that this analytic approach can contribute to improving our understanding of the genetics of LDL particle size.

Low density lipoprotein particle diameter in young, nonobese, normolipidemic Japanese men

Background: prospective studies have demonstrated that a predominance of small, dense LDL particles (pattern B) precedes the clinical onset of coronary heart disease. Prevalence and characteristics of subjects with this LDL size abnormality were studied in young, nonobese, Japanese normolipidemic men. Methods and results: LDL peak particle diameter (PPD) was measured by continuous disc polyacrylamide gel electrophoresis in 223 nonobese normolipidemic men aged 18–20 years (mean±S.D. body mass index: 21.9±3.7 kg/m 2, total cholesterol: 180±29 mg/dl, triglyceride: 62±34 mg/dl, HDL cholesterol: 58±12 mg/dl). Men with small LDL (PPD <25.8 nm) were found in only 5.4% ( n=12) whereas 197 men (88.3%) had a preponderance of large LDL (PPD 26.3 nm). As compared with men in a top tertile (PPD 27.5 nm) those in a low tertile (PPD <26.9 nm) had higher serum levels of LDL cholesterol (120±31 vs 104±24 mg/dl), triglyceride (72±39 vs 49±16 mg/dl) and apolipoprotein (apo) B (84±21 vs 68±14 mg/dl), and lower HDL cholesterol (54±10 vs 60±12 mg/dl). They also had greater body mass index (23.2±4.6 vs 20.9 3.1 kg/m 2) and percent body fat (21.5±7.7 vs 17.5±4.9%). LDL-PPD was positively correlated with HDL cholesterol ( R=0.20, P=0.002) and was negatively correlated with apoB ( R=0.34, P<0.001), triglyceride ( R=0.32, P<0.001), percent body fat ( R=0.26, P<0.001), body mass index ( R=0.24, P<0.001), fat mass ( R=0.23, P=0.001), total cholesterol ( R=0.20, P=0.002). In multiple regression analysis, apoB, triglyceride, HDL cholesterol, apoAI and percent body fat explained 18% of LDLPPD variability. Conclusion: even in young, nonobese, normolipidemic men, LDL size appears to be associated with triglyceride-rich lipoprotein metabolism and body fat.

Small low-density lipoproteins and vascular cell adhesion molecule-1 are increased in association with hyperlipidemia in preeclampsia.

The pregnancy disorder preeclampsia is characterized by endothelial cell dysfunction that may be promoted by abnormal increases in circulating lipids, particularly triglycerides and free fatty acids. Serum triglyceride concentration is a major regulatory determinant of low-density lipoprotein (LDL) size and density distribution. Smaller, denser LDL particles have several intrinsic properties capable of inducing endothelial dysfunction. The present nested, case-control study of gestationally matched preeclamptic and normal pregnant women tested the hypothesis that hypertriglyceridemia in preeclampsia is accompanied by decreases in LDL peak particle diameter (predominant LDL size). Plasma LDL peak particle diameter was determined by nondenaturing 2% to 16% polyacrylamide gel electrophoresis. Correlations of LDL diameter with the concentration of serum triglycerides, free fatty acids, total cholesterol, LDL-cholesterol, and apolipoprotein B (apo B) were determined. In the same individuals, we measured serum concentrations of a marker of vascular dysfunction previously reported to be increased in preeclampsia, soluble vascular cell adhesion molecule-1 (VCAM-1), and examined the association of VCAM-1 with LDL diameter and serum lipids. LDL peak particle diameter was decreased in preeclampsia relative to normal pregnancy (P < .01). The LDL-cholesterol:apo B ratio, which frequently decreases with decreasing LDL diameter, was also decreased (P < .04). Triglyceride concentrations were increased in preeclampsia (P < .0002), and there was a significant inverse relationship between LDL peak particle diameter and triglycerides (r = -.55, P < .02). Serum soluble VCAM-1 concentrations were markedly increased in preeclampsia (P < .0003). Apo B (P < .004), free fatty acids (P < .01), total cholesterol (P < .01), and LDL-cholesterol (P < .02) were also increased. VCAM-1 correlated with apo B (r = .50, P < .03) and LDL-cholesterol (r = .50, P < .03), but showed no relationship with the LDL diameter, LDL-cholesterol:apo B ratio, or other lipids. We conclude that the predominance of smaller, denser LDL, a potential contributor to endothelial cell dysfunction, is a feature of preeclampsia. However, the serum VCAM-1 level, one indicator of endothelial involvement, may be influenced more by quantitative lipoprotein changes (serum apo B or LDL-cholesterol) than by LDL particle size.

Change in dietary saturated fat intake is correlated with change in mass of large low-density-lipoprotein particles in men

We tested whether nutrient intakes estimated from 4-d diet records were associated with plasma lipoprotein subclasses in 103 men who were randomly assigned to a low-fat (24% fat) and a high-fat (46% fat) diet for 6 wk each in a crossover design. Postheparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities were also determined in a subset of 43 men. Changes in intake (ie, high fat minus low fat) of total saturated fatty acids, as well as myristic (14:0) and palmitic (16:0) acids, were positively correlated (P < 0.01) with increases in mass of large LDL particles [measured by analytic ultra-centrifugation as mass of lipoproteins of flotation rate (Sf) 7-12] and with LDL peak particle diameter and flotation rate, but not with changes in LDL-cholesterol concentration. Changes in total saturated fatty acids as well as myristic and palmitic acids were also inversely associated with changes in HL activity (P < 0.05). With the high-fat diet only, variation in dietary total saturated fatty acid intake was inversely correlated (P < 0.01) with concentrations of small, dense LDL of Sf 0-5. This correlation was significant specifically for myristic acid (P < 0.001). Stearic acid (18:0), monounsaturates, and polyunsaturates showed no significant associations with lipoprotein concentrations. These data indicate that a high saturated fat intake (especially 14:0 and 16:0) is associated with increased concentrations of larger, cholesterol-enriched LDL and this occurs in association with decreased HL activity.

Low-Density Lipoprotein Particle Size Distribution in Subjects with Coronary Artery Disease

Background:Low-density lipoprotein (LDL cholesterol has been shown to be a major risk factor for coronary artery disease (CAD in animal studies, clinical trials, and observational epidemiologic studies. It has a hydrated density of 1.019 to 1.063 kg/L, a diameter of 20 to 30 nm, and displays β -mobility on paper or agarose gel electrophoresis. With technique such as density gradient ultracentrifugation and gel electropho- resis, it is possible to separate lipoproteins accurately on the basis of their density, charge, and particle size. Further, it has been shown that a smaller LDL is associated with an increased risk of coronary artery disease, even when total cholesterol level is only slightly raised. The aim of this study was to analyze LDL particle size distribution in patients with angiographically confirmed coronary artery disease and in control subjects, using nondenaturating gradient polyacrylamide gel electrophoresis, and to investigate the relationship between LDL particle size and the other traditional coronary risk factors. Methods:Baseline characteristics such as age, sex, body mass index, history of hypertension or NIDDM, smoking habits, and plasma lipoprotein profiles were obtained in 33 and 27 subjects with and without CAD angiographically confirmed, respectively. We determined LDL peak particle diameter (LDL-PPD using nondenaturating gradient polyacrylmide gel electrophoresis in CAD and control group. 4% to 12% polyacrylamide gradient gels were used for this assay, and the diameters of LDL subclass peaks were calculated by comparison with a standard calibration curve. This procedure permits the assignment according to distribution of particle diameters as exhibiting pattern A, B, or INT. Results:Traditional coronary risk factors(age, sex, body mass index, history of hypertension or NIDDM, smoking habits, plasma triglyceride, HDL-cholesterol, and total to HDL-cholesterol ratio were found to be significantly different between two groups, except the plasma total cholesterol and LDL- cholesterol. The mean value of LDL-PPD in patients with CAD wassignificantly lower than that in control subjects(26.110.4 nm versus 27.011.9 nm, p=0.006. LDL-PPD showed relatively strong associations with plasma triglyceride (r=-0.536, p<0.01), HDL-cholesterol (r=0.497, p<0.01, and total to HDL-cholesterol ratio (r=-0.516, p<0.01, but showed no relation to total cholesterol (r=-0.168 or LDL-cholesterol (r=-

Insulin resistance is not a major determinant of low-density lipoprotein particle size

The relationship between low-density lipoprotein (LDL) peak particle diameter and insulin sensitivity, very—low-density lipoprotein (VLDL) + intermediate-density lipoprotein (LDL) triglyceride, cholesterol, and apoprotein B, postprandial lipemia, and LDL + high-density lipoprotein (HDL) triglyceride was assessed. The subjects were 101 healthy males aged 15 to 45 years. Sixty-one subjects (60.4%) were offspring of a parent with coronary artery disease before age 60, and 40 subjects (39.6%) had no parental history of coronary artery disease. LDL peak particle diameter was measured following polyacrylamide gradient gel electrophoresis. An insulin sensitivity index (S i) was determined from a frequently sampled intravenous glucose tolerance test using a minimal modeling method. A fat tolerance test was performed with a test meal containing 70 g/m 2 fat, with triglyceride concentrations measured hourly for 12 hours. LDL peak particle diameter was significantly correlated with body mass index (BMI) ( r = −.282, P < .01), waist to hip ratio ( r = −.291, P < .01), fasting triglyceride (logarithmically [log] transformed) ( r = −.556, P < .001), area under the postprandial triglyceride (log transformed) ( r = −.562, P < .001), VLDL + IDLL triglyceride (log transformed) ( r = −.321, P < .001), LDL + HDLL triglyceride (log transformed) ( r = .583, P < .001), and HDL cholesterol ( r = .347, P < .001), but there was no significant correlation with S i. Using stepwise regression analysis, LDL + HDL triglyceride showed the strongest relationship to LDL peak particle diameter, accounting for 34% of the variation in size. S I was not an independent predictor of LDL particle size. In conclusion, insulin sensitivity appears to have little influence on LDL particle size. The importance of LDL + HDL triglyceride should be ocnsidered a preliminary finding warranting varification in this and other populations.

Low-density lipoprotein particle size is not a discriminating marker for atherogenic risk in male offspring of parents with early coronary artery disease

The aim of this study was to assess the importance of low-density lipoprotein (LDL) particle size as a marker of atherogenic risk in male offspring of a parent with early coronary artery disease (CAD) before the age of 60 years. CAD-positive (CAD +) offspring were recruited into two groups based on age, 15 to 30 years (In = 20) and 31 to 45 years in = 41), and matched to CAD-negative (CAD −) offspring by age and body mass index (BMI) (n = 20 and 21 per group). LDL peak particle diameter was assessed by polyacrylamide gradient gel electrophoresis. There was no significant difference in LDL peak particle diameter between CAD + and CAD − offspring (26.2 ± 0.1 v 26.2 ± 0.1 nm, mean ± SE). There was also no difference between CAD + offspring and CAD offspring when comparisons were made within their own age group (26.5 ± 0.1 nm in younger CAD + offspring v 26.2 ± 0.1 nm in younger CAD − offspring, and 26.0 ± 0.1 nm in older CAD + offspring v 26.1 ± 0.2 nm in older CAD − offspring. Peak particle diameter was significantly greater in younger CAD + offspring than in older CAD + offspring (26.5 ± 0.1 v 26.0 ± 0.1 nm, P < .05). We conclude that small LDL particle size is not a discriminating marker for early atherogenic risk, and that measurement of LDL particle size has limited value in the assessment of coronary risk, at least in the age ranges we studied.

Effect of fluvastatin on low-density lipoprotein peak particle diameter

In this investigation, there was no appreciable effect on LDL particle diameter and there was no greater or lesser effect in patients classified at baseline as LDL pattern A, B, or I. This investigation indicates that fluvastatin, a 3-Hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitor, can significantly reduce LDL cholesterol, but has no effect on LDL particle diameter and no differential effect on patients characterized by differences in LDL subclass pattern. This contributes additional information on the lack of a differential effect of this statin medication in patients classified at baseline as LDL pattern A, B, or I.

Low‐density lipoprotein subfraction profiles in dialysis patients

Summary: Uraemic dyslipidaemia is a major risk factor for cardiovascular disease in end‐stage renal failure patients. In patients without renal failure, high levels and qualitative abnormalities of low‐density lipoprotein (LDL) are known to be atherogenic. Recently, LDL subfraction analysis has associated premature coronary artery disease with a high prevalence of small, dense LDL particles characterizing the LDL subclass phenotype B. We therefore examined the lipid profiles, LDL subfraction distribution and phenotypes in our population of haemodialysis (HD; n= 30) and peritoneal dialysis patients (PD; n= 17), and compared them to 40 asymptomatic, non‐uraemic volunteers. Dialysis patients had significantly higher triglyceride and VLDL cholesterol concentrations and lower HDL cholesterol and smaller LDL peak particle diameters. PD patients had significantly higher total cholesterol, glycated haemoglobin and fasting blood glucose levels with smaller LDL peak particle diameters (24.4 [0.1] vs 24.8 [0.1 nm] than HD. Both groups showed significant negative correlations between plasma triglyceride and LDL peak particle diameter, and positive correlations between HDL cholesterol and LDL peak particle diameter. All the PD patients expressed the B phenotype (LDL peak diameter ± 25.5 nm) compared to 73% of HD patients. This study demonstrates that HD and especially PD patients have atherogenic lipid profiles which are associated with a predominance of small dense LDL particles and the highly atherogenic LDL subclass phenotype B.

Small, dense low-density lipoprotein particles as a predictor of the risk of ischemic heart disease in men. Prospective results from the Québec Cardiovascular Study.

Case-control studies have reported that patients with ischemic heart disease (IHD) have a higher proportion of small, dense LDL particles than do healthy control subjects. The extent to which the risk attributed to small LDL particles may be independent of concomitant variations in plasma lipoprotein-lipid concentrations remains to be clearly determined, however, particularly through prospective studies. Baseline characteristics were obtained in 2103 men initially free of IHD, among whom 114 developed IHD during a 5-year follow-up period. These 114 case patients were matched with healthy control subjects for age, body mass index, smoking habits, and alcohol intake. LDL peak particle diameter (PPD) was measured a posteriori in 103 case-control pairs by nondenaturing gradient gel electrophoresis of whole plasma. Conditional logistic regression analysis of the case-control status revealed that men in the first tertile of the control LDL-PPD distribution (LDL-PPD < or = 25.64 nm) had a 3.6-fold increase in the risk of IHD (95% CI, 1.5 to 8.8) compared with those in the third tertile (LDL-PPD > 26.05 nm). Statistical adjustment for concomitant variations in LDL cholesterol, triglycerides, HDL cholesterol, and apolipoprotein B concentrations had virtually no impact on the relationship between small LDL particles and the risk of IHD. These results represent the first prospective evidence suggesting that the presence of small, dense LDL particles may be associated with an increased risk of subsequently developing IHD in men. Results also suggest that the risk attributed to small LDL particles may be partly independent of the concomitant variation in plasma lipoprotein-lipid concentrations.

Increase in plasma high-density lipoprotein 2b subclass protein concentration after pravastatin treatment in patients with hypercholesterolemia

To determine the effects of pravastatin on plasma lipid levels, on low-density lipoprotein (LDL), and high-density lipoprotein (HDL) particle size and HDL subclass protein concentration, we studied 31 patients with hypercholesterolemia (9 men and 22 women, aged 36 to 79 years [mean age, 61.5 ± 10.3 years]). Patients were treated with pravastatin 10 mg daily for 12 weeks. After treatment, plasma levels of LDL cholesterol were significantly reduced (from 197 ± 60 to 149 ± 56 mg/dL), plasma levels of total cholesterol were significantly reduced (from 281 ± 58 to 237 ± 51 mg/dL), and levels of HDL 2b subclass protein were significantly increased (from 1.24 ± 0.24 to 1.35 ± 0.23 mg/protein/mL). Significant differences were not noted in the level of HDL cholesterol, LDL peak particle diameter, and the activity of lecithin-cholesterol acyltransferase and cholesteryl-ester transfer protein before and after treatment. The effect of pravastatin on lipoprotein concentration and particle size will need to be confirmed in studies with larger numbers of patients with various lipoprotein abnormalities.

Predominance of Large LDL and Reduced HDL 2 Cholesterol in Normolipidemic Men With Coronary Artery Disease

Previous studies have indicated that a predominance of small, dense LDL particles is associated with coronary artery disease (CAD) risk. In the present study we examined the LDL peak particle diameter (determined by lipid-stained 2% to 16% gradient gel electrophoresis) in 92 normolipidemic men with CAD (total cholesterol < 200 mg/dL and triglyceride < 250 mg/dL) and 92 matched healthy controls. Plasma triglyceride, LDL cholesterol, and apo B levels were similar in subjects with CAD and in control subjects, whereas subjects with CAD had decreased HDL2 cholesterol levels (mean +/- SEM, 10 +/- 0.7 compared with 15 +/- 0.7 mg/dL in control subjects; P < .0002). Mean LDL particle diameter (+/- SEM) was increased in the subjects with CAD compared with control subjects (26.8 +/- 0.08 and 26.4 +/- 0.08 nm, respectively; P < .001). The association between large LDL size and CAD was significant (P < .0001) after adjustments were made for age, body mass index, HDL cholesterol levels, and VLDL cholesterol levels. An LDL particle size distribution characterized by a predominance of the largest of three classes of LDL particles (> 26.8 nm) was more prevalent among subjects with CAD (43%) than among control subjects (25%) (P < .002). Among subjects with this LDL size profile, subjects with CAD had significantly higher (P < .05) VLDL triglyceride, VLDL cholesterol, and VLDL apo B levels and significantly lower (P < .0001) HDL2 cholesterol levels than controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Persistence of Low HDL-C Levels After Weight Reduction in Older Men With Small LDL Particles

LDL subclass pattern B is characterized by a predominance of small LDL particles (LDL peak particle size < or = 255 A) and is associated with increased plasma triglyceride (TG) and reduced HDL cholesterol (HDL-C) concentrations. This study compared the effect of weight loss on lipoprotein and glucose metabolism in 15 healthy, obese (body mass index [BMI], 30.9 +/- 2.4 kg/m2), older (60 +/- 9 years) men with LDL pattern B and in 25 men of comparable age and BMI with LDL pattern A (LDL peak particle size > or = 260 A). At baseline, men with LDL pattern B had higher TG and lower apolipoprotein (apo) A-I, HDL-C, and HDL2-C levels (P < .001) than men with LDL pattern A, while the total cholesterol and LDL cholesterol levels and fasting and 2-hour postprandial glucose and insulin levels did not differ between groups. With weight loss (10.1 +/- 3.6 kg) there were significant decreases in 2-hour postprandial glucose and insulin levels in men with LDL patterns B and A (P < .05). However, the change in plasma TG, HDL-C, HDL2-C, and apoA-I levels with weight loss differed between groups. In men with LDL pattern A, plasma TG levels decreased by 15% (P < .001) compared with a 34% (P < .001) decrease in LDL pattern B (two-factor ANOVA, P < .01). Plasma HDL-C concentrations increased by 0.16 mmol/L (P < .001) in the men with LDL pattern A but by only 0.07 mmol/L in the men with LDL pattern B (two-factor ANOVA, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Hypertriglyceridemia during late pregnancy is associated with the formation of small dense low-density lipoproteins and the presence of large buoyant high-density lipoproteins

Late pregnancy is a unique metabolic state where there are transient increases in the concentrations of plasma triglyceride (TG), cholesterol, and apolipoprotein (apo) B. Despite the hypertriglyceridemic environment, we recently reported that there is an unusual shift in high-density lipoprotein (HDL) subclass distribution from smaller HDL subclasses to the largest, most buoyant HDL 2b subclass. In the present investigation, we determined whether the subclasses of low-density lipoprotein (LDL) also change during this transient hyperlipidemic state and whether such changes were associated with plasma TG and apolipoprotein concentrations. Thirty-six Hispanic subjects at 35 to 36 weeks' gestation and at 6 weeks' postpartum were studied. At 35 to 36 weeks of gestation, plasma concentrations of TG, cholesterol, and apo B were increased (218 ± 62, 234 ± 48, and 130 ± 35 mg/dL, respectively) over levels at 6 weeks' pospartum (112 ± 69, 197 ± 36, and 97 ± 25 mg/dL respectively). However, lipoprotein(a) [Lp(a)] concentrations were not changed during pregnancy compared with postpartum. LDL subclass patterns (A, B, or I) were determined by nondenaturing polyacrylamide gradient gel electrophoresis in our group of 36 pregnant women. During late pregnancy, 97% of subjects were categorized as LDL subclass patterns B or I, indicating that small, dense LDL particles predominated. This predominance of small, dense LDL was associated with plasma TG concentration, where there was a significant inverse relationship ( r = −.45, P < .01) between the LDL peak particle diameter and plasma TG concentration. In an apparent anomaly, there were significant increases in the concentrations of HDL cholesterol (HDL-C) and HDL 2 mass, even though small, dense LDL particles predominated. We speculate that this unusual late-pregnancy lipid/lipoprotein profile is probably the result of insulin resistance combined with the action of the hormone estrogen.

Genetics of LDL subclass phenotypes in women twins. Concordance, heritability, and commingling analysis.

Low density lipoprotein (LDL) subclass phenotype B, characterized by a predominance of small LDL as determined by gradient gel electrophoresis, has been associated with increased risk of coronary heart disease and an atherogenic lipoprotein profile. Previous studies employing complex segregation analysis have demonstrated a major, single gene effect on the inheritance of this phenotype in families. Recently, linkage between this phenotype and variation at the LDL receptor locus on chromosome 19 has been reported. However, variation in LDL subclass phenotypes has also been associated with age, gender, diabetes status, beta-blocker medication, and diet. The present study further evaluates the relative importance of genetic and nongenetic influences on LDL subclass phenotypes and on LDL peak particle diameter (as a reflection of the size of the major LDL subclass) in monozygotic and dizygotic women twin pairs. The analysis is based on 203 monozygotic and 145 dizygotic pairs of adult female twins who participated in the second examination of the Kaiser Permanente Women Twins Study. The average age was 51 years at this exam and 90% were white. Concordance analysis revealed that monozygotic cotwins shared LDL subclass phenotypes more frequently than dizygotic cotwins, and this was confirmed using logistic regression analysis after controlling for potential confounding factors. Heritability analyses suggested that approximately one third to one half of the variation in LDL peak particle diameter, a continuous variable reflecting LDL size, could be attributed to genetic influences. Commingling analysis of the frequency distribution of LDL peak particle diameter identified three distinct subgroups of subjects, one of which corresponded to those subjects with LDL subclass phenotype B.(ABSTRACT TRUNCATED AT 250 WORDS)