Acquired liver fat is a key determinant of serum lipid alterations in healthy monozygotic twins

Objective: The effects of acquired obesity on lipid profile and lipoprotein composition in rare BMI‐discordant monozygotic (MZ) twin pairs were studied. Design and Methods: Abdominal fat distribution, liver fat (magnetic resonance imaging and spectroscopy), fasting serum lipid profile (ultracentrifugation, gradient gel‐electrophoresis, and colorimetric enzymatic methods), and lifestyle factors (questionnaires and diaries) were assessed in 15 BMI‐discordant (within‐pair difference [Δ] in BMI >3 kg/m²) and nin concordant (ΔBMI <3 kg/m²) MZ twin pairs, identified from two nationwide cohorts of Finnish twins. Results: Despite a strong similarity of MZ twins in lipid parameters (intra‐class correlations 0.42‐0.90, P < 0.05), concentrations of apolipoprotein B (ApoB), intermediate‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein 3a% (HDL3a%), and HDL3c% were higher (P < 0.05) and those of HDL cholesterol, HDL2‐C, and HDL2b% were lower (P < 0.01) in the heavier co‐twins of BMI‐discordant pairs. The composition of lipoprotein particles was similar in the co‐twins. When BMI‐discordant pairs were further divided into liver fat‐discordant and concordant (based on median for Δliver fat, 2.6%), the adverse lipid profile was only seen in those heavy co‐twins who also had high liver fat. Conversely, BMI‐discordant pairs concordant for liver fat did not differ significantly in lipid parameters. In multivariate analyses controlling for Δsubcutaneous, Δintra‐abdominal fat, sex, Δsmoking and Δphysical activity, Δliver fat was the only independent variable explaining the variation in ΔApoB, Δtotal cholesterol, and ΔLDL‐C concentration. Conclusions: Several pro‐atherogenic changes in the amounts of lipids but not in the composition of lipoprotein particles were observed in acquired obesity. In particular, accumulation of liver fat was associated with lipid disturbances, independent of genetic effects.     

Fasting Plasma Insulin Modulates Lipid Levels and Particle Sizes in 2‐ to 3‐Year‐Old Children

Objective: Obesity and hyperinsulinemia are associated with dyslipidemia in adults and older children, but little is known about these relationships in very young children. We examined the relation of fasting insulin to lipid levels and lipid particle size in young healthy children. Research Methods and Procedures: Analyses were performed on data from 491 healthy 2‐ and 3‐year old Hispanic children enrolled in a dietary study conducted in New York City, 1992–1995. Obesity measures included BMI, ponderal index, skinfold thickness, and waist circumference. Low‐density lipoprotein (LDL)‐ and high‐density lipoprotein (HDL)‐cholesterol particle size were measured by nuclear magnetic resonance. Results: Fasting insulin level was positively correlated with triglyceride levels (r = 0.24 for boys and r = 0.23 for girls; p < 0.001 for both) and inversely correlated with HDL‐cholesterol level in boys (r = ?0.20; p < 0.01). Higher fasting insulin level was also correlated with smaller mean HDL particle size in both boys (r = ?0.21; p < 0.001) and girls (r = ?0.14; p < 0.05) and smaller mean LDL particle size in boys (r = ?0.13; p < 0.05). The associations of fasting insulin level with triglyceride and HDL‐cholesterol levels and HDL and LDL particle size remained significant after multivariate regression adjustment for age, sex, and BMI or ponderal index. Discussion: Fasting insulin level is associated with relative dyslipidemia in healthy 2‐ and 3‐year‐old Hispanic children.     

Effects of exercise cessation on lipids and lipoproteins in distance runners and power athletes

The purpose of this study was to determine the effects of short-term exercise cessation on lipid and lipoprotein profile and insulin sensitivity in highly trained runners (n=12; mean age 19.9 years) and power athletes (n=12; mean age 24.4 years). Following 14 days of exercise cessation, running time to exhaustion and maximal oxygen uptake decreased by 9.2% and 4.8% (P < 0.05) in the runners, while in the power athletes one repetition maximum squat and bench press did not change (P>0.05). No changes occurred in body composition. Data from a 2-h oral glucose tolerance test revealed an impairment of the glycemic state in all athletes (P<0.05). In contrast, exercise cessation did not significantly (P>0.05) alter plasma levels of cholesterol, triglycerides, and low density (LDL) and high density lipoprotein (HDL). No changes were observed in HDL₂, HDL_2b, and HDL₃ subfractions, LDL diameter, and qualitative LDL pattern (P>0.05). These data thus suggest that despite a decrease in insulin sensitivity, short-term exercise cessation, independent of exercise mode, was insufficient to alter plasma lipid and lipoprotein profiles in well-trained athletes.     

Volumetric determination of apolipoprotein stoichiometry of circulating HDL subspecies

Although HDL is inversely correlated with coronary heart disease, elevated HDL-cholesterol is not always protective. Additionally, HDL has biological functions that transcend any antiatherogenic role: shotgun proteomics show that HDL particles contain 84 proteins (latest count), many correlating with antioxidant and anti-inflammatory properties of HDL. ApoA-I has been suggested to serve as a platform for the assembly of these protein components on HDL with specific functions - the HDL proteome. However, the stoichiometry of apoA-I in HDL subspecies is poorly understood. Here we use a combination of immunoaffinity chromatography data and volumetric analysis to evaluate the size and stoichiometry of LpA-I and LpA-I,A-II particles. We conclude that there are three major LpA-I subspecies: two major particles, HDL[4] in the HDL₃ size range (d = 85.0 ± 1.2 Å) and HDL[7] in the HDL₂ size range (d = 108.5 ± 3.8 Å) with apoA-I stoichiometries of 3 and 4, respectively, and a small minor particle, HDL[1] (d = 73.8 ± 2.1Å) with an apoA-I stoichiometry of 2. Additionally, we conclude that the molar ratio of apolipoprotein to surface lipid is significantly higher in circulating HDL subspecies than in reconstituted spherical HDL particles, presumably reflecting a lack of phospholipid transfer protein in reconstitution protocols.     

Relations between particle size of HDL and LDL lipoproteins and cholesterol esterification rate

Particle size of low density (LDL) and high density (HDL) lipoproteins and cholesterol esterification rate in HDL plasma (FER(HDL)) are important independent predictors of coronary artery diseases (CAD). In this study we assessed the interrelations between these indicators and routinely examined plasma lipid parameters and plasma glucose concentrations. In 141 men, healthy volunteers, we examined plasma total cholesterol (TC), triglycerides (TG), HDL and LDL cholesterol (HDL-C, LDL-C) and HDL unesterified cholesterol (HDL-UC). Particle size distribution in HDL and LDL was assessed by gradient gel electrophoresis and FER(HDL) was estimated by radioassay. An effect of particle size and FER(HDL) on atherogenic indexes as the Log(TG/HDL-C) and TC/HDL-C was evaluated. Subjects in the study had plasma concentrations (mean +/- S.D.) of TC 5.2+/-0.9 mmol/l, HDL-C 1.2+/-0.3 mmol/l, TG 2.1+/-1.7 mmol/l, glucose 5+/-0.8 mmol/l. Relative concentration of HDL(2b) was 17.6+/-11.5 % and 14.6+/-11.8 % of HDL(3b,c). The mean diameter of LDL particles was 25.8+/-1.5 nm. The increase in FER(HDL) significantly correlated with the decrease in HDL(2b) and LDL particle size (r = -0.537 and -0.583, respectively, P<0.01) and the increase in HDL(3b,c) (0.473, P<0.01). Strong interrelations among TG and HDL-C or HDL-UC and FER(HDL) and particle size were found, but TC or LDL-C did not have such an effect. Atherogenic indexes Log(TG/HDL-C) and TC/HDL-C correlated with FER(HDL) (0.827 and 0.750, respectively, P<0.0001) and with HDL and LDL particle size.     

Particle size interconversion of human low density lipoproteins during incubation of plasma with phosphatidylcholine vesicles

Incubation of plasma (37°C, 6hr) in the presence of increasing amounts of phosphatidylcholine (PC) vesicles, above a threshold concentration, results in an increase in particle diameter of LDL relative to that from nonincubated plasma. With further PC addition, the major peak of LDL in the gradient gel electrophoretic pattern is transformed, first, into a bimodal and, subsequently, into a single peak distribution. PC-induced interconversion of LDL requires factors(s) in the d > 1.20 g/ml fraction and, at PC concentrations below approximately 2 mg/ml, is not inhibited by p-chloromercuriphenylsulfonic acid. Plasma incubation with increasing PC levels also leads to characteristic particle size transformations in HDL₃ species, with the transformation products ultimately converging to form a single peak pattern within the HDL_2a size interval. In certain subjects, incubation of plasma, in the absence of added PC, shifts the particle size distribution of LDL towards smaller species; this can be prevented by addition of PC. We propose that incubation-induced shifts of LDL towards larger or smaller species result from changes in phospholipid (PL) content of LDL.     

Plasma factors affecting the in vitro conversion of high-density lipoproteins labeled with a non-transferable marker

We studied the in vitro conversion of HDL₃ labeled with a radioiodinated diacyl lipid associating peptide (diLAP). DiLAP was previously shown to be nontransferable, which permitted its' use as a reliable marker of HDL particles. DiLAP-labeled HDL₃ was incubated for 23 h at 37°C in human or rat plasma or in reconstituted media containing delipidated plasma and/or lipoproteins and/or partially purified CETP. At the end of the incubations, the samples were adjusted to a density of 1.125 g/ml and ultracentrifuged. The two resulting fractions containing HDL₂ and HDL₃, respectively, were analyzed by gradient gel electrophoresis. Depending upon experimental conditions, diLAP-labeled HDL₃ was converted into HDL_2b- and/or small HDL_3c-like particles. LCAT inhibition and to a lesser extent CETP promoted the formation of small HDL_3c. Reactivation of LCAT led to the disappearance of small HDL_3c. No HDL_3c formed from HDL₂ even in the absence of LCAT activity. When the incubations were performed in the presence of 100 mM thimerosal, which inhibited PLTP but not CETP activity, the conversion of diLAP-labeled HDL₃ into HDL₂ was almost completely blocked. Collective consideration of these data indicates that the formation of small HDL is moderately facilitated by CETP; that small HDL are converted to larger HDL species by LCAT and that the transformation of HDL₃ into HDL₂ is a process which largely depends upon PLTP activity.     

Gender specific effect of LIPC C‐514T polymorphism on obesity and relationship with plasma lipid levels in Chinese children

Hepatic lipase (LIPC) is a key rate‐limiting enzyme in lipoprotein catabolism pathways involved in the development of obesity. The C‐514T polymorphism in the promoter region is associated with decreased LIPC activity. We performed a case‐controlled study (850 obese children and 2119 controls) and evaluated the association between LIPC C‐514T polymorphism, obesity and plasma lipid profile in Chinese children and adolescents. Additionally, we conducted a meta‐analysis of all results from published studies as well as our own data. A significant association between the polymorphism and obesity is observed in boys (P = 0.042), but not in girls. And we observed a significant relationship of the polymorphism with total cholesterol (TC) and high density lipoprotein cholesterol (HDL‐C) independent of obesity in boys. The T allele carriers have higher levels of low density lipoprotein cholesterol (LDL‐C) in obese boys, and triglyceride (TG), TC and LDL‐C in non‐obese girls (all P < 0.05). In the meta‐analysis, under dominant model the T allele increased body mass index (BMI) level in boys, while it decreased BMI in girls, and increased the levels of TC both in the overall and subgroups, TG and HDL‐C in the overall and boys, and LDL‐C in the overall (all P < 0.05). Our results suggest that the T allele might carry an increased risk of obesity in Chinese boys. The meta‐analysis suggests that T allele acts as a risk allele for higher BMI levels in male childhood, while it is a protective allele in female childhood. And the polymorphism is associated with the levels of plasma lipids, which may be modulated by obesity and gender.     

Body Mass Index and the Prevalence of Hypertension and Dyslipidemia

Objective: To describe and evaluate relationships between body mass index (BMI) and blood pressure, cholesterol, high‐density lipoprotein‐cholesterol (HDL‐C), and hypertension and dyslipidemia. Research Methods and Procedures: A national survey of adults in the United States that included measurement of height, weight, blood pressure, and lipids (National Health and Nutrition Examination Survey III 1988–1994). Crude age‐adjusted, age‐specific means and proportions, and multivariate odds ratios that quantify the association between hypertension or dyslipidemia and BMI, controlling for race/ethnicity, education, and smoking habits are presented. Results: More than one‐half of the adult population is overweight (BMI of 25 to 29.9) or obese (BMI of ≥30). The prevalence of high blood pressure and mean levels of systolic and diastolic blood pressure increased as BMI increased at ages younger than 60 years. The prevalence of high blood cholesterol and mean levels of cholesterol were higher at BMI levels over 25 rather than below 25 but did not increase consistently with increasing BMI above 25. Rates of low HDL‐C increased and mean levels of HDL‐C decreased as levels of BMI increased. The associations of BMI with high blood pressure and abnormal lipids were statistically significant after controlling for age, race or ethnicity, education, and smoking; odds ratios were highest at ages 20 to 39 but most trends were apparent at older ages. Within BMI categories, hypertension was more prevalent and HDL‐C levels were higher in black than white or Mexican American men and women. Discussion: These data quantify the strong associations of BMI with hypertension and abnormal lipids. They are consistent with the national emphasis on prevention and control of overweight and obesity and indicate that blood pressure and cholesterol measurement and control are especially important for overweight and obese people.     

Effect of Feeding Xenobiotics on Serum High Density Lipoprotein and Apolipoprotein A-I in Rats

The effects on serum cholesterol level were examined in rats fed on various xenobiotics. The hypercholesterolemia induced by polychlorinated biphenyls (PCB) was characterized in rats, from which lipoproteins were isolated by ultracentrifugation. A dietary addition of 0.03% PCB, 0.3% chloretone, 0.1% aminopyrine, or 0.2% 2,6-di-tert-butyl-p-cresol (BHT) resulted in a significant increase in serum cholesterol, although the chemical structure of each of these xenobiotics was different. The serum cholesterol level was markedly increased by one month of PCB feeding, the effect of PCB on the serum phospholipid level being similar. The serum triglyceride level transiently increased within 7 days of feeding with PCB diet. PCB feeding resulted in the elevation of all lipoproteins, including VLDL, LDL, HDL₁, and HDL₂, a marked increase being observed in HDI₁. Both HDL₁ and HDL₂ isolated from PCB-treated rats contained more apolipoprotein A-I (apo A-I) and less apo E than normal. VLDL isolated from PCB-treated rats had more cholesterol and apo E, but less apo C than that of the control animals. These data demonstrate that PCB feeding resulted in increased VLDL rich in cholesterol and apo E, and increased HDL rich in apo A-I. This experimentally induced hypercholesterolemia resulting in apo A-I-rich HDL would be a useful model for investigating the metabolism of apo-A-I and HDL.     

Cholesteryl ester transfer protein in metabolic syndrome

Objective: Low high‐density lipoprotein cholesterol (HDL‐C), hypertriglyceridemia, and small dense‐low density lipoprotein (LDL) are key components of metabolic syndrome (MS). Cholesteryl ester transfer protein (CETP) mediates the transfer of triglycerides (TGs) from TG‐rich lipoproteins to HDL and LDL particles in exchange for cholesteryl esters, leading to low HDL‐C and small dense‐LDL. The aim of this study was to investigate the role of CETP in subjects with MS. Research Methods and Procedures: In a cross‐sectional cohort of 234 middle‐aged men and 252 women randomly selected from the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR) study, MS was diagnosed according to the National Cholesterol Education Program guidelines. CETP mass was determined by enzyme‐linked immunosorbent assay and LDL size‐by‐gradient polyacrylamide gel electrophoresis. Results: Men and women with MS had lower HDL‐C (45 ± 7 vs. 58 ± 13 and 48 ± 10 vs. 71 ± 14 mg/dL for men and women, respectively; p < 0.001 for all) and higher TG levels (222 ± 71 vs. 98 ± 54 and 167 ± 67 vs. 90 ± 35 mg/dL for men and women, respectively; p < 0.001 for all) than healthy subjects. LDL size was lower in subjects with MS (256 ± 11 Å vs. 267 ± 11 Å and 262 ± 10 Å vs. 273 ± 8 Å for men and women, respectively; p < 0.001 for all). CETP mass was higher in men with MS (1.87 ± 0.78 vs. 1.40 ± 0.65 μg/mL; p < 0.001) but not in women (1.74 ± 0.79 vs. 1.62 ± 0.62 μg/mL). CETP mass correlated inversely with LDL size in both men and women (r = ?0.19, p < 0.01 and r = ?0.13, p < 0.05 in men and women, respectively). Discussion: MS is associated with increased CETP mass in men. Increased CETP mass may be responsible for reduced HDL‐C and reduced LDL particle diameter in MS.     

Separation of the principal HDL subclasses by iodixanol ultracentrifugation

HDL subclasses detection, in cardiovascular risk, has been limited due to the time-consuming nature of current techniques. We have developed a time-saving and reliable separation of the principal HDL subclasses employing iodixanol density gradient ultracentrifugation (IxDGUC) combined with digital photography. HDL subclasses were separated in 2.5 h from prestained plasma on a three-step iodixanol gradient. HDL subclass profiles were generated by digital photography and gel scan software. Plasma samples (n = 46) were used to optimize the gradient for the resolution of HDL heterogeneity and to compare profiles generated by IxDGUC with gradient gel electrophoresis (GGE); further characterization from participants (n = 548) with a range of lipid profiles was also performed. HDL subclass profiles generated by IxDGUC were comparable to those separated by GGE as indicated by a significant association between areas under the curve for both HDL₂ and HDL₃ (HDL₂, r = 0.896, P < 0.01; HDL₃, r = 0.894, P < 0.01). The method was highly reproducible, with intra- and interassay coefficient of variation percentage < 5 for percentage area under the curve HDL₂ and HDL₃, and < 1% for peak Rf and peak density. The method provides time-saving and cost-effective detection and preparation of the principal HDL subclasses.     

The Lipid Accumulation Product and All‐cause Mortality in Patients at High Cardiovascular Risk: A PreCIS Database Study

The BMI is the most frequently used marker to evaluate obesity‐associated risks. An alternative continuous index of lipid over accumulation, the lipid accumulation product (LAP), has been proposed, which is computed from waist circumference (WC, cm) and fasting triglycerides (TGs) (mmol/l): (WC ? 65) × TG (men) and (WC ? 58) × TG (women). We evaluated LAP and BMI as predictors of mortality in a high‐risk cohort. Study population included 5,924 new consecutive patients seen between 1995 and 2006 at a preventive cardiology clinic. Fifty‐eight percent of patients were discordant for their LAP and BMI quartiles. Patients whose LAP quartile was greater than BMI quartile had higher mortality compared with those with LAP quartile was lower than BMI quartile (8.2 vs. 5.4% at 6 years, P = 0.007). After adjustment for age, gender, smoking, diabetes mellitus, blood pressure, low‐density lipoprotein‐cholesterol (LDL‐C) and high‐density lipoprotein‐cholesterol (HDL‐C), (ln)LAP was independently associated with mortality (hazard ratio (HR) = 1.46, P < 0.001). BMI was not associated with increased mortality (HR = 1.06, P = 0.39). Adding LAP to a model including traditional risk factors for atherosclerosis increased its predictive value (C statistic 0.762 vs. 0.750, P = 0.048). Adding BMI to the same model did not change its predictive value (0.749 vs. 0.750, P = 0.29). Subgroup analyses showed that LAP predicted mortality in the nondiabetic patients (adjusted HR for (ln)LAP 1.64, P < 0.001), but did not reach significance in the diabetic patients (HR = 1.21, P = 0.11). In conclusion, LAP and not BMI predicted mortality in nondiabetic patients at high risk for cardiovascular diseases. LAP may become a useful tool in clinical practice to stratify the risk of unfavorable outcome associated with obesity.     

Adiposity significantly modifies genetic risk for dyslipidemia

Recent genome-wide association studies have identified multiple loci robustly associated with plasma lipids, which also contribute to extreme lipid phenotypes. However, these common genetic variants explain <12% of variation in lipid traits. Adiposity is also an important determinant of plasma lipoproteins, particularly plasma TGs and HDL cholesterol (HDLc) concentrations. Thus, interactions between genes and clinical phenotypes may contribute to this unexplained heritability. We have applied a weighted genetic risk score (GRS) for both plasma TGs and HDLc in two large cohorts at the extremes of BMI. Both BMI and GRS were strongly associated with these lipid traits. A significant interaction between obese/lean status and GRS was noted for each of TG (P_Interaction = 2.87 × 10⁻⁴) and HDLc (P_Interaction = 1.05 × 10⁻³). These interactions were largely driven by SNPs tagging APOA5, glucokinase receptor (GCKR), and LPL for TG, and cholesteryl ester transfer protein (CETP), GalNAc-transferase (GALNT2), endothelial lipase (LIPG), and phospholipid transfer protein (PLTP) for HDLc. In contrast, the GRS_{LDL cholesterol} × adiposity interaction was not significant. Sexual dimorphism was evident for the GRS_HDL on HDLc in obese (P_Interaction = 0.016) but not lean subjects. SNP by BMI interactions may provide biological insight into specific genetic associations and missing heritability.     

The Value and Distribution of High-Density Lipoprotein Subclass in Patients with Acute Coronary Syndrome

Background

High-density lipoprotein (HDL) enhances cholesterol efflux from the arterial wall and exhibits potent anti-inflammatory and anti-atherosclerosis (AS) properties. Whether raised HDL levels will clinically benefit patients with acute coronary syndrome (ACS) and the value at which these effects will be apparent, however, is debatable. This study examined the HDL subclass distribution profile in patients with ACS.

Methods

Plasma HDL subclasses were measured in 158 patients with established ACS and quantified by two-dimensional gel electrophoresis and immunoblotting. ACS diagnosis was based on symptoms of cardiac ischemia, electrocardiogram (ECG) abnormalities, speciality cardiac enzyme change along with presence of coronary heart disease (CHD) on coronary angiography.

Results

The small-sized preβ₁-HDL, HDL_3b, and HDL_3a levels were significantly higher, and the large-sized HDL_2a and HDL_2b levels were significantly lower in patients with ACS than in those with stable angina pectoris (SAP) and in normal control subjects. Meanwhile, with an elevation in the low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), body mass index (BMI), and blood pressure (BP), and the reduction in the high density lipoprotein cholesterol (HDL-C) levels, the HDL_2b contents significantly decreased and the preβ₁-HDL contents significantly increased in patients with ACS. The correlation analysis revealed that the apolipoprotein (apo)A-I levels were positively and significantly with all HDL subclasses contents; plasma total cholesterol (TC) and fasting plasma glucose (FPG) levels were inversely associated with HDL_2a, and HDL_2b. Moreover, the FPG levels were positively related to HDL_3c, HDL_3b, and HDL_3a in ACS patients.

Conclusion

The HDL subclass distribution profile remodeling was noted in the patients with ACS. Plasma lipoprotein and FPG levels, BP, and BMI play an important role in the HDL subclass metabolism disorder for patients with ACS. The HDL subclass distribution phenotype might be useful as a novel biomarker to assist in the risk stratification of patients with ACS.     

Comparative-biochemical analysis of lipids of blood serum lipoproteins of human and some animal species

Lipid composition of blood serum and total lipids of low density lipoproteins (LDL) and high density lipoproteins (HDL₂ and HDL₃) were studied in human (donors, patients with ischemic heart disease, bronchial asthma, chronic obstructive bronchitis, as well as with a combined pathology), in mammals predisposed to atherosclerosis (pig, rabbit) and resistant to atherosclerosis (rat, mink, Arctic fox), in birds (hen, pigeon), in teleost fish (white fish, pike-perch, pike, bream, burbot) and cartilaginous fish (sturgeon, housen). It has been established that the most enriched in lipids is the blood serum of animals, particularly of cartilaginous fish. Twice lower is the lipid content in blood serum of donors than of animals. However, in the vascular, bronchopulmonary, and combined human pathologies the lipid level rises statistically significantly. In human and in animals predisposed to atherosclerosis the main mass of lipid is located in LDL, whereas in animals resistant to this disease—in HDL. The ratio of the human lipid content in LDL/HDL increases from 1.4 (in donors) to 2.7 in pathological states—in ischemic heart disease and its combination with chronic obstructive disease. In animals, a decrease of this ratio is noted from 1.0 to 0.2 in cartilaginous fish. By the example of one taxon (fish) there is established a regularity that indicates that evolution of lipoproteins occurred with an increase of the lipid amount in the “younger” LDL and with a decrease of concentration of the “older” HDL.     

Lipoprotein Subpopulation Distributions in Lean,Obese, and Type 2 Diabetic Women: A Comparison of African and White Americans

Objective: Abnormal subpopulation distributions of plasma lipoproteins have been reported in white American (WA) women with obesity and type 2 diabetes that explain part of the elevated rate of cardiovascular disease in these patients. This study examined if these perturbations also occur in obese and diabetic African American (AA) women and compared the lipoprotein profiles with WA counterparts. Research Methods and Procedures: We determined the lipoprotein subpopulation distribution in the plasma of 51 lean women (29 WA, 22 AA, body mass index [BMI] < 30), 50 obese women (27 WA, 23 AA, BMI > 30), and 43 obese women with type 2 diabetes (27 WA, 16 AA), by nuclear magnetic resonance spectroscopy. Results: AA diabetic women, like WA diabetic women, had a larger average very low density lipoprotein (VLDL) size, elevated levels of small low density lipoprotein cholesterol (LDL‐C), and lower levels of small high density lipoprotein cholesterol (HDL‐C), when compared to lean controls (p < 0.05). These differences were accompanied by higher VLDL‐triglycerides (TG) and LDL‐C in WA (p < 0.05), but not in AA. Although the effects of obesity and diabetes on lipoprotein subpopulation were fairly similar for AA and WA, some racial differences, particularly with respect to HDL, were observed. Discussion: The atherogenic perturbations in lipoprotein profiles of obese AA women, particularly those with diabetes, were relatively similar to those found in WA women and may be contributing to the increased rate of cardiovascular disease (CVD) in AA with obesity and diabetes. The parameters of subpopulation distribution may provide better markers for CVD than lipid concentrations alone, particularly in AA women. Furthermore, subtle racial differences in lipoprotein profiles suggest that race‐specific criteria may be needed to screen patients for CVD.     

Lipid profile of a French-Canadian population: 1. Association of plasma lipid and lipoprotein levels with age,relative body weight and education

Plasma lipid and lipoprotein levels were determined in a randomly selected population of 1169 French-Canadian men in the Quebec City area. The mean levels of total plasma cholesterol and triglycerides were 224.0 and 166.5 mg/dL respectively. The mean level of low-density lipoprotein cholesterol was higher and the mean level of high-density lipoprotein (HDL) cholesterol lower than those reported in a recent study in English-Canadian men. The mean HDL₂ and HDL₃ levels were lower than those reported in American men. Stratification of plasma triglyceride levels for all age groups showed that mean HDL₂ levels decreased rapidly with moderate rises in triglyceride levels. Less than 9% of the variation in lipid or lipoprotein levels was related to age or relative body weight. Education had no significant effect on the levels.     

Lipoprotein subfraction oxidation in acute exercise and ageing

Exercise and ageing can independently increase free radical production that may enhance the susceptibility of LDL to oxidation and create a more atherogenic LDL particle. This investigation was designed to examine exercise and ageing on the susceptibility of LDL subfractions to oxidation. Eleven aged (55?± 4 years) and twelve young (21?± 2 years) participants completed a progressive exercise test to exhaustion and within one week performed a 1?h bout of moderate intensity (65% VO_2max) exercise. Blood was assayed for metabolites associated with lipid composition (total cholesterol, free cholesterol, triglycerides) and lipoprotein susceptibility to oxidation. Exercise increased small density (sdLDL) oxidation, independently of age (p?<?0.05). However, sdLDL oxidation further increased 24?h post exercise in the aged group (p?<?0.05). With regards to the changes in lipid components within LDL, free and total cholesterol and triglycerides in large buoyant (lbLDL) were all elevated 24?h post exercise in aged compared with young (p?<?0.05 for all comparisons). There was a decrease in triglycerides in medium density (mdLDL) 24?h post exercise in the aged group (p?<?0.05). The lipid composition of sdLDL, VLDL, HDL₂, HDL₃ and serum lipid hydroperoxides remained unchanged as a function of exercise and ageing (p?>?0.05). Although regular exercise training is known to be protective against cardiovascular disease (CVD) onset, our data demonstrates that acute exercise can increase sdLDL oxidative susceptibility, and this is independent of age and regardless of a change in LDL lipid composition. However, age seems to be a determining factor with regards the susceptibility of sdLDL to oxidation 24?h following exercise.     

Triglyceride‐to‐HDL‐cholesterol Ratio and Metabolic Syndrome as Contributors to Cardiovascular Risk in Overweight Patients

Insulin resistance increases cardiovascular risk of obese patients. Triglyceride to high‐density lipoprotein cholesterol ratio (TG/HDL) ≥3.0 (in mg/dl) is a marker of insulin resistance in overweight persons. We aimed at assessing cardiovascular risk profile in 301 overweight elderly Neapolitan outpatients, according to TG/HDL ratio and metabolic syndrome (MS), diagnosed by National Cholesterol Education Program (NCEP) and International Diabetes Federation (IDF) criteria. TG/HDL ratio was ≥3.0 in 97 patients (group A) and <3.0 in 204 (group B). Overall, 93–97% of group A patients and 38–51% of group B patients had MS, depending on the diagnostic criterion. Group A patients with MS had significantly higher waist‐to‐hip ratio, total and non‐HDL cholesterol than group B patients with MS. In group B, MS and non‐MS patients had similar waist‐to‐hip ratio, blood pressure, total and non‐HDL cholesterol. Ten year coronary risk, calculated by the Framingham equations (n = 243), was 10.3 ± 5% in group B, non‐MS patients; 13.1 ± 6% in group B, MS patients; 19.9 ± 8% in group A (F = 32.8; P < 0.001). At the multiple regression analysis, TG/HDL ratio was associated with coronary risk (r² = 0.227) more closely than gender, blood pressure, waist‐to‐hip ratio, non HDL cholesterol, and MS considered as a whole. A separate regression analysis showed that the logarithmically transformed TG/HDL ratio, an index of the HDL cholesterol esterification rate, is also associated with coronary risk (r² = 0.252). Thus, TG/HDL ratio could help to characterize high‐risk overweight patients deserving a special therapeutic effort. Cardiovascular risk profile of insulin‐sensitive patients, identified by lower values of this parameter, is only moderately affected by MS.