Low-density Lipoprotein Subclasses Research Articles

Sleep Apnea Is Related to the Atherogenic Phenotype, Lipoprotein Subclass B

Sleep apnea has been implicated as an independent risk factor for atherosclerotic coronary artery disease (CAD). An association between the severity of sleep apnea and total cholesterol levels has previously been reported. However, the association with small dense low density lipoprotein (LDL) cholesterol concentration (subclass B), one of the strongest predictors of atherosclerosis, is unknown. We examined the relationship between sleep apnea and LDL subclass B, considering body size. This is a cross-sectional observational cohort of participants enrolled in a cardiovascular health study. Sleep apnea was assessed with a validated portable monitor. Lipid panels included total cholesterol, triglycerides, high density lipoprotein cholesterol, LDL cholesterol, and LDL subclasses A, B, and A/B. Sleep apnea was analyzed categorically using the apnea hypopnea index (AHI). A total of 519 participants were evaluated. Mean age was 58.7 ± 7.4 years; BMI was 29.6 ± 5.7; 65% were female; 59% were Caucasian, and 37% were African American. Among participants with abnormal waist circumference by ATP III criteria, moderate to severe sleep apnea (AHI ≥ 25) was not independently associated with LDL subclass B. In contrast, among participants with normal waist circumference, moderate to severe sleep apnea was associated with 4.5-fold odds of having LDL subclass B. Sleep apnea is independently associated with an atherogenic phenotype (LDL subclass B) in non-obese individuals. The association between sleep apnea and LDL subclass B in those with normal waist circumference may account, in part, for the increased risk of atherosclerosis and subsequent vascular events.

Plasma Lipoproteins and Preeclampsia in Women with Type 1 Diabetes: A Prospective Study

In nondiabetic pregnancy, cross-sectional studies have shown associations between maternal dyslipidemia and preeclampsia (PE). In type 1 diabetes mellitus (T1DM), the prevalence of PE is increased 4-fold, but prospective associations with plasma lipoproteins are unknown. The aim of this study was to define lipoprotein-related markers and potential mechanisms for PE in T1DM. We conducted a multicenter prospective study in T1DM pregnancy. We studied 118 T1DM women (26 developed PE, 92 remained normotensive). Subjects were studied at three visits before PE onset [12.2 ± 1.9, 21.6 ± 1.5, and 31.5 ± 1.7 wk gestation (means ± SD)] and at term (37.6 ± 2.0 wk). Nondiabetic normotensive pregnant women (n = 21) were included for reference. Conventional lipid profiles, lipoprotein subclasses [defined by size (nuclear magnetic resonance) and by apolipoprotein content], serum apolipoproteins (ApoAI, ApoB, and ApoCIII), and lipolysis (ApoCIII ratio) were measured in T1DM women with and without subsequent PE. In women with vs. without subsequent PE, at the first and/or second study visits: low-density lipoprotein (LDL)-cholesterol, particle concentrations of total LDL and large (but not small) LDL, serum ApoB, and ApoB:ApoAI ratio were all increased (P < 0.05); peripheral lipoprotein lipolysis was decreased (P < 0.01). These early differences remained significant in covariate analysis (glycated hemoglobin, actual prandial status, gravidity, body mass index, and diabetes duration) but were not present at the third study visit. High-density lipoprotein and very low-density lipoprotein subclasses did not differ between groups before PE onset. Early in pregnancy, increased cholesterol-rich lipoproteins and an index suggesting decreased peripheral lipolysis were associated with subsequent PE in T1DM women. Background maternal lipoprotein characteristics, perhaps masked by effects of late pregnancy, may influence PE risk.

Size and Subclasses of Low-Density Lipoproteins in Patients With Obstructive Sleep Apnea

Patients with obstructive sleep apnea (OSA) have proatherogenic dyslipidemia. We analyzed predictors of low-density lipoproteins' (LDLs) size in patients with OSA. In a cross-sectional study including 58 participants with OSA (30 without the metabolic syndrome [MetS] and 28 with MetS), we evaluated the size of LDL by gradient gel electrophoresis. Compared with patients without the MetS, those with MetS showed lower LDL size (P = .007), due to a reduction in large LDL-I particles (P = .002) and an increase in small, dense LDL-IIIA (P = .048) and LDL-IIIB (P = .037). The size of LDL correlated inversely with age (r = -.268, P = .042) and serum triglycerides (r = -.364, P = .005), and positively with serum high-density lipoprotein cholesterol levels (r = .335, P = .010). In multiple regression analysis, the presence of the MetS was the only independent predictor of LDL size (P = 0.015). In patients with OSA, MetS is an independent predictor of LDL size and subclasses, whereas the severity of OSA does not contribute independently to alterations in LDL phenotype.

The relationship of vitamin D with non-traditional risk factors for cardiovascular disease in subjects with metabolic syndrome

IntroductionSeveral studies implicate an inverse relationship between 25-hydroxy vitamin D (25(OH)Vit D) serum levels and metabolic syndrome (MetS). We sought to investigate a possible relationship between 25(OH)Vit D and emerging risk factors associated with MetS, such as small dense low-density lipoprotein cholesterol (sdLDL-C) concentration, lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and high-sensitivity C-reactive protein (hsCRP) levels.Material and methodsWe studied 110 consecutive otherwise healthy individuals. Of these, 52 were diagnosed with MetS and 58 who did not meet the MetS criteria served as controls. Low-density lipoprotein (LDL) subclass analysis was performed by polyacrylamide gel electrophoresis. Lp-PLA2 activity was determined in total plasma by the trichloroacetic acid precipitation procedure. Serum 25(OH)Vit D was determined quantitatively by an enzyme immunoassay method.ResultsMetabolic syndrome subjects had significantly lower 25(OH)Vit D levels (11.8 [0.6-48.3] ng/ml; 29.5 [1.5-120.75] nmol/l) compared with controls (17.2 [4.8-62.4] ng/ml; 43 [12-156] nmol/l, p = 0.027). Univariate regression analysis showed that 25(OH)Vit D concentration was inversely related to triglycerides (r= − 0.416, p = 0.003) and sdLDL-C (r= − 0.305, p = 0.004). There was no association of 25(OH)Vit D with waist circumference, blood pressure, high-density lipoprotein cholesterol (HDL-C), fasting glucose, Lp-PLA2 and hsCRP. In multivariate regression analysis the relationship between 25(OH)Vit D and sdLDL-C became insignificant when triglycerides were included in the model.ConclusionsSubjects with MetS exhibit lower 25(OH)Vit D serum levels compared with non-MetS individuals. Low 25(OH)Vit D is associated with higher sdLDL-C levels possibly through elevated triglycerides. No association between 25(OH)Vit D and Lp-PLA2 or hsCRP was found.

Methionine adenosyltransferase 1A gene deletion disrupts hepatic very low-density lipoprotein assembly in mice

Very low-density lipoprotein (VLDL) secretion provides a mechanism to export triglycerides (TG) from the liver to peripheral tissues, maintaining lipid homeostasis. In nonalcoholic fatty liver disease (NAFLD), VLDL secretion disturbances are unclear. Methionine adenosyltransferase (MAT) is responsible for S-adenosylmethionine (SAMe) synthesis and MAT I and III are the products of the MAT1A gene. Deficient MAT I and III activities and SAMe content in the liver have been associated with NAFLD, but whether MAT1A is required for normal VLDL assembly remains unknown. We investigated the role of MAT1A on VLDL assembly in two metabolic contexts: in 3-month-old MAT1A-knockout mice (3-KO), with no signs of liver injury, and in 8-month-old MAT1A-knockout mice (8-KO), harboring nonalcoholic steatohepatitis. In 3-KO mouse liver, there is a potent effect of MAT1A deletion on lipid handling, decreasing mobilization of TG stores, TG secretion in VLDL and phosphatidylcholine synthesis via phosphatidylethanolamine N-methyltransferase. MAT1A deletion also increased VLDL-apolipoprotein B secretion, leading to small, lipid-poor VLDL particles. Administration of SAMe to 3-KO mice for 7 days recovered crucial altered processes in VLDL assembly and features of the secreted lipoproteins. The unfolded protein response was activated in 8-KO mouse liver, in which TG accumulated and the phosphatidylcholine-to-phosphatidylethanolamine ratio was reduced in the endoplasmic reticulum, whereas secretion of TG and apolipoprotein B in VLDL was increased and the VLDL physical characteristics resembled that in 3-KO mice. MAT1A deletion also altered plasma lipid homeostasis, with an increase in lipid transport in low-density lipoprotein subclasses and decrease in high-density lipoprotein subclasses. MAT1A is required for normal VLDL assembly and plasma lipid homeostasis in mice. Impaired VLDL synthesis, mainly due to SAMe deficiency, contributes to NAFLD development in MAT1A-KO mice.

Increased plasma visfatin concentration is a marker of an atherogenic metabolic profile

Background and aimsVisfatin is associated with atherosclerosis-related diseases. We assessed in non-diabetic individuals the association of plasma visfatin levels with cardiovascular disease (CVD) risk and the atherosclerosis-related metabolic variables. Methods and resultsWhen study population (n = 179, age 49 ± 11 years) was divided according to visfatin tertiles, the 10-year CVD Framingham risk scores were significantly increased in the top visfatin tertile. We observed a positive association between visfatin tertiles with waist circumference and blood pressure, as well as with total cholesterol and triglyceride levels, but not with apolipoprotein C-III, fibrinogen or pre-beta1 high density lipoprotein (HDL). The percentage of large HDL subclasses was significantly lower and the percentage of small HDL subclasses over the HDL-C concentration was significantly higher in the top visfatin tertile compared with the other tertiles. The atherogenic small dense low density lipoprotein subclasses (sdLDL-C) were significantly increased in the top visfatin tertile compared with the lower tertiles. High sensitivity C-reactive protein (hsCRP) concentration was significantly increased in the top visfatin tertile compared with the lower tertiles. Although age and sex distribution did not differ between visfatin tertiles, the simultaneous adjustment for these parameters attenuated the significance of the differences observed in sdLDL-C and hsCRP levels. Similarly, after adjustment for hsCRP or waist circumference, only triglycerides and blood pressure levels, as well as the distribution of HDL subclasses, remained significantly different between visfatin tertiles. ConclusionsOur results support a role for visfatin in the detection of subjects with many metabolic abnormalities, which result in increased CVD risk.

Early postnatal changes of lipoprotein subclass profile in late preterm infants

BackgroundLate preterm infants (LPIs; 34–37 gestational weeks at birth) have higher risk for several morbidities than do term infants (TIs). It has been suggested that a cholesterol and fatty acid supply may improve their outcomes. We investigated the lipoprotein subclass profile in LPIs to evaluate their early postnatal lipid metabolism. MethodsEighty-one infants (25 LPIs, 56 TIs) were included. Cholesterol and triglyceride (TG) concentrations in 12 lipoprotein subclasses were measured at birth and at 1month using HPLC. ResultsIn LPIs, the cord blood exhibited higher cholesterol concentrations in medium and large subclasses of very low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) compared to the values in TIs. During the first month of life, LPIs had greater increases in cholesterol concentrations of medium and large subclasses of VLDL than TIs, whereas postnatal increases in cholesterol concentrations of medium and large subclasses of LDL and HDL were smaller. TG concentrations were not different in each VLDL subclass at birth and at 1month. ConclusionsIn LPIs, cord blood lipoprotein subclass profiles and the early postnatal change exhibited different, especially in cholesterol concentrations.

Simultaneous Determination of High-Density Lipoprotein, Very Low-Density Lipoprotein and Low-Density Lipoprotein Subclass in Human Serum by Microchip CE

Lipoproteins, especially high-density lipoproteins (HDL), very low-density lipoproteins (VLDL) and small, dense low-density lipoprotein (sdLDL), are believed to play an important role in the development of atherosclerosis. In this work, a simple, selective and sensitive method for the simultaneous monitoring of these lipoproteins in human serum using microchip capillary electrophoresis was developed. Gold nanoparticles were used as an additive to the running buffer to obtain the absolute separation of the lipoproteins. Under optimised conditions, the linear ranges of large buoyant low-density lipoproteins, sdLDL, VLDL and HDL were 10–800, 10–800, 40–1,000 and 20–800 μg L−1, and their limits of detection were 5, 5, 15 and 8 μg L−1, respectively. The intraassay and interassay relative standard deviation of lipoprotein peak areas were in the range of 3.8–7.4%. For practical application, variations in the serum lipoprotein of coronary heart disease patients were monitored by microchip-based CE. The results showed that the method was applicable for routine clinical use and allowed the rapid detection of different lipoprotein classes as well as their subclasses, thus greatly improving the analysis of atherosclerotic risk factors.

&amp;#x201C;European Panel On Low Density Lipoprotein (LDL) Subclasses&amp;#x201D;: A Statement on the Pathophysiology, Atherogenicity and Clinical Significance of LDL Subclasses: Executive Summary

&amp;#x201C;European Panel On Low Density Lipoprotein (LDL) Subclasses&amp;#x201D;: A Statement on the Pathophysiology, Atherogenicity and Clinical Significance of LDL Subclasses: Executive Summary

Cholesteryl ester transfer protein, low density lipoprotein particle size and intima media thickness in patients with coronary heart disease

Cholesteryl ester transfer protein (CETP) plays a key role in reverse cholesterol transport and high density lipoprotein (HDL) metabolism. Predominance of small, dense LDL particles is associated with an increased risk of atherosclerosis and coronary heart disease (CHD).The aim of the study was to determine the potential relationship between the CETP concentration and low density lipoprotein (LDL) particle size and their association with intima media thickness (IMT) in patients with CHD. Lipid parameters, CETP concentration and LDL particle size were determined in 100 healthy subjects (control group) and in 100 patients with CHD, aged 43 to 77 years. Plasma CETP concentrations were measured by an enzyme-linked immuno-sorbent assay with two different monoclonal antibodies. LDL subclasses were separated by nondenaturing polyacrilamide 3-31% gradient gel electrophoresis. CETP concentration was higher in patients compared to controls (2.02 ± 0.75 mg/ml vs. 1.74 ± 0.63 mg/ml, p<0.01). Mean LDL particle size (nm) was significantly smaller in patients than in controls (24.5 ± 1.1 vs. 26.1 ± 0.9; p<0.001). There was no relation between LDL particle size and CETP concentration (r=-0.1807, p=0.072). Age, diastolic blood pressure, CETP concentration and LDL particle size were independent factors for determing IMT by multiple linear regression analysis. They accounted for 35.2 % of the observed variability in IMT. CETP is not an independent contributor of LDL particle size. CETP might play a role in determining lipoprotein distributions, but did not seem to be the sole factor in the formation of small LDL particles.

Characteristics of low-density and high-density lipoprotein subclasses in pediatric renal transplant recipients

Renal transplant recipients often suffer from dyslipidemia which is one of the principal risk factors for cardiovascular disease. This study sought to determine characteristics of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) particles and their associations with carotid intima-media thickness (cIMT) in a group of pediatric renal transplant recipients. We also examined the influence of immunosuppressive therapy on measured LDL and HDL particle characteristics. HDL size and subclass distribution were determined using gradient gel electrophoresis, while concentrations of small, dense LDL (sdLDL)-cholesterol (sdLDL-C) and sdLDL-apolipoprotein B (sdLDL-apoB) using heparin-magnesium precipitation method in 21 renal transplant recipients and 32 controls. Renal transplant recipients had less HDL 2b (P < 0.001), but more HDL 3a (P < 0.01) and 3b (P < 0.001) subclasses. They also had increased sdLDL-C (P < 0.01) and sdLDL-apoB (P < 0.05) levels. The proportion of the HDL 3b subclasses was a significant predictor of increased cIMT (P < 0.05). Patients treated with cyclosporine had significantly higher sdLDL-C and sdLDL-apoB concentrations (P < 0.05) when compared with those on tacrolimus therapy. Pediatric renal transplant recipients have impaired distribution of HDL and LDL particles. Changes in the proportion of small-sized HDL particles are significantly associated with cIMT. Advanced lipid testing might be useful in evaluating the effects of immunosuppressive therapy.

Reversal of Small, Dense LDL Subclass Phenotype by Weight Loss Is Associated With Impaired Fat Oxidation

Adiposity is more prevalent among individuals with a predominance of small, dense low-density lipoprotein (LDL) (pattern B) particles than among those with larger LDL (pattern A). We tested for differences in resting energy expenditure (REE) and respiratory quotient (RQ) in overweight men with pattern A (n = 36) or pattern B (n = 60). Men consumed a standardized isoenergetic diet for 3 weeks after which a ~9kg weight loss was induced by caloric deficit for 9 weeks, followed by 4 weeks of weight stabilization. REE and RQ were measured by indirect calorimetry before and after weight loss. Results were analyzed separately in pattern B men who converted to pattern A (B→A; n = 35) and those who did not (B→B; n = 25). At baseline, B→B men had higher trunk fat, triacylglycerol (TG) and insulin concentrations, homeostasis model assessment of insulin resistance (HOMA(IR)), and smaller LDL particles compared to B→A men and baseline pattern A men who remained pattern A (A→A; n = 35). REE normalized to fat-free mass did not change after weight loss. RQ decreased in A→A men, increased in B→A men, and did not change significantly in B→B men after weight loss. Calculated fat oxidation rates paralleled the RQ results. Baseline plasma TG concentrations were positively correlated with RQ and inversely correlated with the magnitude of weight loss achieved for a given prescribed energy reduction in the entire study population. Pattern B men who converted to pattern A with weight loss may have an underlying impairment in fat oxidation that predisposes to both dyslipidemia and an impaired ability to achieve weight loss by energy restriction.

Carotid atherosclerosis and lipoprotein particle subclasses in familial hypercholesterolaemia and familial combined hyperlipidaemia

Background and AimsFamilial hypercholesterolaemia (FH) and familial combined hyperlipidaemia (FCH) are common atherogenic disorders with great variability in cardiovascular disease (CVD). No direct atherosclerosis burden comparisons have been performed between FH and FCH in relation to lipoprotein particle distribution. Methods and ResultsRisk factors and three measures of carotid intima-media thickness (IMT) in both sides were determined in 572 FH, 250 FCH and 200 controls. Lipoproteins were assessed by nuclear magnetic resonance (NMR) spectroscopy. Compared with controls, IMT measures were increased in FH and FCH. FCH had the highest adjusted mean–maximum IMT. FH had twice low-density lipoprotein (LDL) particles than controls, but similar LDL subclass size and distribution. FCH subjects also had increased LDL particles and the highest number of small LDL (1519 ± 731 nmol l−1 vs. 887 ± 784 nmol l−1 in FH and 545 ± 409 nmol l−1 in controls). Age, gender, cholesterol/high-density lipoprotein (HDL) ratio, smoking and systolic blood pressure were independently associated with IMT in FH (r2 = 0.38). The same variables, except cholesterol/HDL ratio, were associated with IMT in FCH (r2 = 0.40). Among NMR lipoproteins, only VLDL and chylomicrons increased IMT prediction in FCH by 0.8%. ConclusionFH and FCH subjects show increased carotid atherosclerosis in relation to classical risk factors. Lipoprotein subclasses do not substantially contribute to IMT variability.

Estimation of the low-density lipoprotein (LDL) subclass phenotype using a direct, automated assay of small dense LDL-cholesterol without sample pretreatment

A new method (sLDL-EX "SEIKEN") is commercially available for the direct quantification of small dense LDL-cholesterol (sd-LDL) on automated chemistry analyzers, without manual sample pretreatment. We evaluated the performance of this direct assay to estimate the small dense LDL subclass phenotype ("non-A"), defined by polyacrylamide gel tube electrophoresis. Fasting serum samples from 189 healthy subjects (age 18-75y, 96 females) were collected. The direct sd-LDL assay (from Randox Laboratories) was applied on a Roche Modular P analyzer. The Quantimetrix Lipoprint(TM) LDL System was used to define LDL subclass phenotypes (A and non-A). ROC curve analysis was performed for sd-LDL and other lipids and apolipoproteins (apo) with respect to phenotype non-A. sd-LDL concentrations (40.4+/-18.6mg/dl) in the total group correlated (P<0.0001) with apoB (r=0.831), apoB/A-I ratio (r=0.757), non-HDL-cholesterol (r=0.821), triglycerides (r=0.439), and LDL-cholesterol (r=0.641). Higher sd-LDL concentrations (P<0.0001) were measured in subjects with LDL phenotype non-A (53.6+/-17.0mg/dl, n=92) than in those with phenotype A (27.9+/-8.9mg/dl, n=97). In logistic regression analysis, sd-LDL and apoA-I were independently associated with LDL subclass phenotype non-A. Highest areas under ROC curves were obtained for sd-LDL (0.943), triglycerides (0.833), triglyceride/HDL-cholesterol (0.838) and apoB/A-I ratio (0.826) to predict phenotype non-A. The sd-LDL cut-off point for optimal sensitivity (87.9%) and specificity (92.8%) was >38.5mg/dl. The direct, homogeneous sd-LDL method is easily applicable on an automated chemistry analyzer and shows acceptable performance to estimate the electrophoretic LDL subclass phenotype.

Effects of Rosiglitazone on Fasting and Postprandial Low- and High-Density Lipoproteins Size and Subclasses in Type 2 Diabetes

Rosiglitazone may increase cardiovascular risk in patients with type 2 diabetes. Yet, its effects on atherogenic dyslipidemia are still not fully elucidated. In a prospective open-label study rosiglitazone (4 mg/day for 12 weeks) was added to a maximum of 2 oral antidiabetic drugs in 18 diabetic patients. We evaluated the effects on plasma lipids before and after an oral fat load. The size and subclasses of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) were also determined (by gradient gel electrophoresis). Rosiglitazone improved glycosylated hemoglobin ([HbA1c] P = .0023), without significant effects on fasting and postprandial plasma lipids. Fasting LDL size increased (+1.4%, P = .034), with less small, dense LDL-IIIA (-25.1%, P = .018). Postprandially, larger HDL-2b reduced (-8.7%, P = .006) and smaller HDL-3b increased (+12.2%, P = .05), without any effects on HDL size. Rosiglitazone led to antiatherogenic changes in LDL size and subclasses, with proatherogenic changes in HDL subclasses, despite no effects on plasma lipids. Their clinical relevance remains to be established.

FABP4 plasma levels are increased in familial combined hyperlipidemia

FABP4 plasma levels are increased in familial combined hyperlipidemia

Effects of Controlled-Release Alpha Lipoic Acid in Lean, Nondiabetic Patients with Polycystic Ovary Syndrome

The purpose of this study was to determine whether a preparation of controlled-release alpha lipoic acid (CRLA) influences features of the polycystic ovary syndrome (PCOS). We administered CRLA 600 mg twice daily for 16 weeks to six lean, nondiabetic patients with PCOS. Insulin sensitivity was measured by the euglycemic, hyperinsulinemic clamp. Plasma lipids were measured by vertical ultracentrifugation. Oxidative stress markers were measured in serum. At the end of 16 weeks of CRLA treatment, there was a 13.5% improvement in insulin sensitivity as determined by the euglycemic, hyperinsulinemic clamp (p < .03). There was also a lowering of triglyceride levels (p < .04) and a shift in the distribution of low-density lipoprotein (LDL) particles toward the larger, more buoyant LDL subclass fraction. Two of the subjects who were not on oral contraception had an increased number of menstrual cycles. Controlled-release alpha lipoic acid treatment, however, was neither associated with an increase in plasma antioxidant capacity nor with a reduction in plasma lipid oxidation products. These data suggest that the CRLA has positive effects on the PCOS phenotype. The effects of CRLA, however, may have been exerted through a mechanism not involving changes in oxidative stress.

Ethnic differences in serum lipoproteins and their determinants in South African women

The objective of the study was to characterize ethnic differences in lipid levels and low-density lipoprotein (LDL) particle size and subclasses in black and white South African women and to explore the associations with insulin sensitivity ( S I), body composition, and lifestyle factors. Fasting serum lipids and LDL size and subclasses, body composition (dual-energy x-ray absorptiometry), and S I (frequently sampled intravenous glucose tolerance test) were measured in normal-weight (body mass index <25 kg/m 2) black (n = 15) and white (n = 15), and obese (body mass index >30 kg/m 2) black (n = 13) and white (n = 13) women. Normal-weight and obese black women had lower triglycerides (0.59 ± 0.09 and 0.77 ± 0.10 vs 0.89 ± 0.09 and 0.93 ± 0.10 mmol/L, P < .05) and high-density lipoprotein cholesterol (1.2 ± 0.1 and 1.1 ± 0.1 vs 1.7 ± 0.1 and 1.6 ± 0.3 mmol/L, P < .01) than white women. The LDL particle size was not different, but obese black women had more LDL subclass IV (17.3% ± 1.0% vs 12.5% ± 1.0%, P < .01). In white women, triglycerides and LDL particle size correlated with S I ( P < .01), whereas cholesterol levels correlated with body fat ( P < .05). Low socioeconomic status, low dietary protein intake, and injectable contraceptive use were the major determinants of unfavorable lipid profiles in black women. Black women had lower triglyceride and high-density lipoprotein cholesterol levels and more small dense LDL particles than white women. The major determinants of serum lipids in black women were socioeconomic status and lifestyle factors, whereas in white women, S I and body composition most closely correlated with serum lipids.

Reversal of Small, Dense LDL Subclass Phenotype by Normalization of Adiposity

Excess adiposity and high-carbohydrate diets have been associated with an atherogenic lipoprotein phenotype (ALP) characterized by increased concentrations of small, dense low-density lipoprotein (LDL) particles (pattern B). We tested whether weight loss and normalization of adiposity could reverse ALP in overweight men with pattern B. After consuming a moderate-carbohydrate, high-fat diet for 3 weeks, pattern B and nonpattern B (pattern A) men were randomized to a weight loss (n = 60 and n = 36, respectively) or control weight-stable arm (n = 20 and n = 17, respectively). Men in the weight loss arm consumed approximately 1,000 fewer calories per day over 9 weeks to induce an average approximately 9 kg weight loss. In the control group, weight stability was maintained for 4 weeks after randomization. Weight loss led to the conversion of pattern B to pattern A in 58% of baseline pattern B men. Among men who achieved BMIs of <25 kg/m(2) (62% of pattern B men vs. 83% of pattern A men), 81% of pattern B men converted to pattern A. Weight loss was associated with a significantly greater decrease in small, dense LDL subclass 3b in pattern B relative to pattern A men. The lipoprotein profiles of pattern A men who converted from pattern B were comparable to those of men with pattern A at baseline. Conversion of LDL subclass pattern B to pattern A and reversal of ALP can be achieved in a high proportion of overweight men by normalization of adiposity.

Effect of l-carnitine on the size of low-density lipoprotein particles in type 2 diabetes mellitus patients treated with simvastatin

Therapeutic modulation of low-density lipoprotein (LDL) size could be of benefit in reducing the risk of cardiovascular events in diabetic patients. This study evaluated the efficacy of l-carnitine on the size of LDL particles in type 2 diabetes mellitus patients treated with simvastatin. Eighty diabetic patients were randomly assigned to 1 of 2 treatment groups for 3 months. The 2 groups received either simvastatin monotherapy 20 mg (n = 40) or l-carnitine 2 g/d and simvastatin 20 mg (n = 40). The following variables were assessed at baseline; after washout; and at 1, 2, and 3 months of treatment: body mass index, fasting plasma glucose, glycosylated hemoglobin, total cholesterol, LDL cholesterol, LDL subclasses, LDL size, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A-1, and apolipoprotein B-100. After 12 weeks, comparing the 2 groups, we observed a decrease in fasting plasma glucose (1.45 vs 0.61 mmol/L, P < .001) and an increase in glycosylated hemoglobin (0.2% vs 0.4%, P < .05). Moreover, there was a decrease in total cholesterol (2.07 vs 1.45 mmol/L, P < .001), LDL (1.65 vs 1.29 mmol/L, P < .001), triglycerides (1.36 vs 0.41 mmol/L, P < .001), apo B-100 (49 vs 9 g/L, P < .001), and small-sized LDL proportion (10.8% vs 4.9%, P < .001), whereas LDL particle size increased (6 vs 3 Å, P < .001) and HDL increased (0.2 vs 0.11 mmol/L, P < .001). We observed that patients treated with carnitine and simvastatin showed a reduction in small-sized LDL proportion and an increase in LDL particle size.