Influence of mild to moderately elevated triglycerides on low density lipoprotein subfraction concentration and composition in healthy men with low high density lipoprotein cholesterol levels

Epidemiologic studies have shown that a dyslipoproteinemia with low concentrations of high density lipoprotein (HDL) cholesterol and elevated serum triglycerides (TG) is associated with a particularly high incidence of coronary artery disease. This lipid profile is associated with increased concentrations of small, dense low density lipoprotein (LDL) particles. To evaluate the role of mild to moderately elevated TG on the LDL subfraction profile in patients with low HDL cholesterol, concentration and composition of six LDL subfractions was determined by density gradient ultracentrifugation in 41 healthy men (31+/-9 years, body mass index (BMI) 25.1+/-3.9 kg/m2) with equally low HDL cholesterol levels < 0.91 mmol/l but different TG levels: TG < 1.13 mmol/l, n = 16; TG = 1.13-2.26 mmol/l, n = 13: TG = 2.26-3.39 mmol/l, n = 12. Those men with moderately elevated TG levels between 2.26 and 3.39 mmol/l had significantly higher concentrations of very low density lipoprotein (VLDL), intermediate low density lipoprotein (IDL), and small, dense LDL apoB and cholesterol than men with TG < 1.13 mmol/l. With increasing serum TG, the TG content per particle also increased in VLDL, IDL as well as total LDL particles while the cholesterol and phospholipid (PL) content decreased in VLDL and IDL, but not in LDL particles. LDL subfraction analysis revealed that only large, more buoyant LDL particles (d < 1.044 g/ml) but not the smaller, more dense LDL, were enriched in TG. Small, dense LDL particles were depleted of free cholesterol (FC) and PL. This study has shown that in men with low HDL cholesterol levels mild to moderately elevated serum TG strongly suggest the presence of other metabolic cardiovascular risk factors and in particular of a more atherogenic LDL subfraction profile of increased concentration of small, dense LDL particles that are depleted in surface lipids.     

The small, dense LDL phenotype as a correlate of postprandial lipemia in men

The atherogenic dyslipidemia of the insulin resistance syndrome is characterized by hypertriglyceridemia (hyperTG), elevated apolipoprotein (apo) B levels, reduced high-density lipoprotein (HDL) cholesterol concentrations and by an increased proportion of small, dense low-density lipoprotein (LDL) particles. Although the hyperTG-low HDL cholesterol dyslipidemia has been associated with an impaired clearance of dietary fat, the contribution of the small, dense LDL phenotype as an independent predictor of postprandial triglyceride (TG) clearance remains uncertain. We have therefore compared the postprandial TG response among three subgroups of men characterized by small, intermediate or large LDL particles in a total sample of 69 men (mean age +/- SD; 45.1 +/- 10.5 years). To identify men with small versus large LDL particles, the first (LDL peak particle diameter < 251.9 A) and the third (> 257.6 A) tertiles of the distribution of LDL particle diameters were used as cutoff points. Men with small, dense LDL particles had the expected fasting dyslipidemic profile (high TG-low HDL cholesterol levels) compared to men with large, buoyant LDL particles. The oral lipid tolerance test revealed that men with small, dense LDL particles had significantly higher total-, large-, and medium-TG-rich lipoprotein (TRL) responses to a fatty meal than men with large LDL particles (P < 0.03). In addition, within a subgroup of normolipidemic men (TG < 2.3 mmol/l and HDL cholesterol > 0.9 mmol/l), those with small, dense LDL particles had higher levels of total-, medium- and small-TRL responses compared to men with large, buoyant LDL particles (P < 0.05). Moreover, normotriglyceridemic men with small, dense LDL had higher levels of small-TRLs measured 8 h after the ingestion of the fat meal (P < 0.05) compared to normolipidemic men with large, buoyant LDL particles. Results of the present study suggest that the dense LDL phenotype may be an additional fasting marker of an exaggerated postprandial TG response and of an impaired clearance of TRLs.     

Is Lipoprotein(a) an Independent Risk Factor for Ischemic Heart Disease in Men? The Quebec Cardiovascular Study

Objectives. This study was undertaken to determine whether lipoprotein(a) [Lp(a)] is an independent risk factor for ischemic heart disease (IHD) and to establish the relation of Lp(a) to the other lipid fractions.Background. Several, but not all, studies have shown that elevated Lp(a) concentrations may be associated with IHD; very few have been prospective.Methods. A 5-year prospective follow-up study was conducted in 2,156 French Canadian men 47 to 76 years old, without clinical evidence of IHD. Lipid measurements obtained at baseline included total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, apoprotein B and Lp(a). During the follow-up period, there were 116 first IHD events (myocardial infarction, angina, death). Adjusted proportional hazards models were used to estimate the relative risk for the different variables. The cohort was also classified according to Lp(a) levels and other lipid risk factor tertiles to evaluate the relation of elevated Lp(a) levels to these risk factors. A cutoff value of 30 mg/dl was used for Lp(a). Risk ratios were calculated using the group with low Lp(a) levels and the first tertile of lipid measures as a reference.Results. Lp(a) was not an independent risk factor for IHD but seemed to increase the deleterious effects of mildly elevated LDL cholesterol and elevated total cholesterol and apoprotein B levels and seemed to counteract the beneficial effects associated with elevated HDL cholesterol levels.Conclusions. In this cohort, Lp(a) was not an independent risk factor for IHD but appeared to increase the risk associated with other lipid risk factors.     

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

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

Triglycerides, high-density lipoprotein cholesterol, and risk of ischemic heart disease: a view from the Copenhagen Male Study

The role of lipids and lipoproteins as important risk factors of ischemic heart disease (IHD) is well established. With the demonstration in large-scale randomized clinical trials that aggressive lowering of low-density lipoprotein (LDL) cholesterol levels with statins reduced the risk of IHD, the central role of LDL cholesterol in the pathogenesis of IHD was proven. However, many IHD cases occur in people with normal LDL cholesterol levels, and it is well known that the ability to predict who will develop IHD based on LDL cholesterol levels alone is limited. Plasma triglycerides and high-density lipoprotein (HDL) cholesterol are two other lipid variables that over the years have attracted attention in cardiovascular epidemiology. Recently, much more attention has been paid to the relationship between triglycerides, HDL cholesterol, and risk of IHD because the combined lipid profile of a high fasting triglyceride level and a low HDL cholesterol level is the characteristic dyslipidemia in the metabolic syndrome X. The objective of the present review article is to use data from the Copenhagen Male Study to demonstrate that, in men, fasting hypertriglyceridemia is a strong risk factor of IHD independent of other major risk factors of IHD, and that the combined lipid profile of a high fasting triglyceride level and a low HDL cholesterol level, the characteristic dyslipidemia in the metabolic syndrome X, is a very strong and important risk factor of IHD, at least as strong and important as a high LDL cholesterol level.     

Low-density lipoprotein size and subclasses are markers of clinically apparent and non-apparent atherosclerosis in type 2 diabetes

The atherogenic lipoprotein phenotype is characterized by an increase in plasma triglycerides, a decrease in high-density lipoprotein (HDL), and the prevalence of small, dense low-density lipoprotein (LDL) particles. The present study investigated the clinical significance of LDL size and subclasses as markers of atherosclerosis in diabetes type 2. Thirty-eight patients with type 2 diabetes, total cholesterol of less than 6.5 mmol/L, and hemoglobin A1c (HbA1c) of less than 9% were studied. Median age was 61 years, mean (+/-SD) body mass index 29 +/- 4.3 kg/m2 , and mean HbA1c 7.1 +/- 0.9 %. Laboratory parameters included plasma lipids and lipoproteins, lipoprotein (a), apolipoprotein (apo) A-I, apo B-100, apo C-III, and high-sensitivity C-reactive protein. Low-density lipoprotein size and subclasses were measured by gradient gel electrophoresis and carotideal intima media thickness (IMT) by duplex ultrasound. By factor analysis, 10 out of 21 risk parameters were selected: age, body mass index, systolic blood pressure, smoking (in pack-years), HbA1c, high-sensitivity C-reactive protein, lipoprotein (a), LDL cholesterol, HDL cholesterol, and LDL particle size. Multivariate analysis of variance of these 10 risk parameters identified LDL particle size as the best risk predictor for the presence of coronary heart disease (P = .002). Smaller LDL particle size was associated with an increase in IMT (P = .03; cut-off >1 mm). Within the different lipid parameters (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, apo B, apo A-I, apo C-III, LDL particle size), LDL particle size was most strongly associated with the presence of coronary heart disease (P = .002) and IMT (P = .03). It is concluded that LDL size is the strongest marker for clinically apparent as well as non-apparent atherosclerosis in diabetes type 2.     

Atherogenic lipoprotein phenotype and low-density lipoprotein size and subclasses in patients with growth hormone deficiency before and after short-term replacement therapy

OBJECTIVE: Patients with growth hormone deficiency (GHD) have increased cardiovascular risk and may show elevated triglyceride and reduced high density lipoprotein (HDL) cholesterol concentrations, two lipid abnormalities usually accompanied by increased small dense LDL in the 'atherogenic lipoprotein phenotype' (ALP). In the present study, we directly investigated (1) whether hypopituitary patients with GHD have increased small dense LDL; (2) whether growth hormone replacement therapy (GHRT) beneficially impact on such particles; (3) the prevalence of ALP in GHD and GHRT patients. DESIGN AND METHODS: In 14 hypopituitary patients with GHD (44 +/- 13 years, body mass index (BMI) 27 +/- 3) before and after 4 months of GHRT, and in 11 healthy age- and BMI-matched controls we measured plasma lipids and LDL size and subclasses by gradient gel electrophoresis. RESULTS: Compared with controls, GHD showed increased triglycerides (P = 0.0024), similar total and LDL cholesterol levels and a tendency towards reduced HDL cholesterol concentrations (P = 0.0894). GHRT reduced total and LDL cholesterol levels (P = 0.0303 and 0.0120 respectively), but no effect was found on triglycerides and HDL cholesterol levels. LDL size was unchanged in GHD versus controls (269 +/- 9 vs 274 +/- 6 A, P = ns), but LDL subclass analysis revealed a shift towards more dense particles (P = 0.0046). GHRT had no significant impact on LDL size and subclasses. The prevalence of ALP was 14% in GHD and 7% in GHRT. CONCLUSIONS: In GHD patients, individual features of ALP (including increased small dense LDL) may be common, but complete ALP is relatively uncommon. Short-term replacement therapy seems to be ineffective on such lipid alterations, but the effect of a longer GHRT remains to be assessed.     

Low-density lipoprotein size,high-density lipoprotein concentration,and endothelial dysfunction in non-insulin-dependent diabetes

We examined endothelial function (nitric-oxide mediated) in 29 men with diet-treated non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) and 18 male age-matched controls. Forearm blood flow was measured by venous occlusive plethysmography during intra-arterial administration of acetylcholine (ACh, 7.5 and 15 μg min⁻¹) and sodium nitroprusside (SNP, 3 and 10 μg min⁻¹). LDL particle size was estimated by non-denaturing gel electrophoresis. Serum lipids, blood pressure, and glycated haemoglobin were also measured. LDL particle size was smaller (p = 0.048) in the diabetic patients than controls. In the diabetic patients, LDL particle size was a significant positive predictor (p = 0.01) of the area under the dose–response curve for ACh, after adjusting for age, HbA_1c, systolic BP, and cholesterol (R² 0.20). In stepwise regression including serum lipid and lipoprotein concentrations and LDL particle size, decreased HDL cholesterol was the best predictor of an impaired vasodilatory response to ACh. Vasodilatory responses to sodium nitroprusside were not significantly correlated with LDL particle size or serum lipid and lipoprotein concentrations. We conclude that in men with NIDDM, small, dense LDL particle size is associated with abnormal endogenous release of nitric oxide. The contribution of small, dense LDL particles to the development of endothelial dysfunction and early diabetic vasculopathy may not, however, be as great as decreased HDL cholesterol. © 1997 John Wiley & Sons, Ltd.     

Serum adiponectin level is correlated with the size of HDL and LDL particles determined by high performance liquid chromatography

ObjectiveAdiponectin (APN) improves insulin resistance and prevents atherosclerosis, and HDL removes cholesterol from atherosclerotic lesions. We have demonstrated that serum HDL-cholesterol (HDL-C) and APN concentrations are positively correlated and that APN accelerates reverse cholesterol transport (RCT) by increasing HDL synthesis in the liver and cholesterol efflux from macrophages. We previously reported that APN reduced apolipoprotein (apo) B secretion from the liver. It is well-known that insulin resistance influences the lipoprotein profile. In this study, we investigated the clinical significance of APN levels and insulin resistance in lipoprotein metabolism.Material/methodWe investigated the correlation between serum APN concentration, HOMA-R, the lipid concentrations and lipoprotein particle size by high-performance liquid chromatography (HPLC) in 245 Japanese men during an annual health checkup.ResultsSerum APN level was positively correlated with the cholesterol content in large LDL and HDL particles, but inversely correlated with the cholesterol content in large VLDL and small LDL particles. HOMA-R was negatively correlated with the cholesterol content in large LDL and HDL particles and positively correlated with the cholesterol content in large VLDL and small LDL particles. By multivariate analysis, APN was correlated with the particle size of LDL-C and HDL-C independently of age, BMI and HOMA-R.ConclusionsAPN may be associated with the formation of both HDL and LDL particles, reflecting the enhancement of RCT and the improvement in TG-rich lipoprotein metabolism and insulin resistance.     

Lipids in type 2 diabetes

Type 2 diabetes increases the risk of cardiovascular disease two- to fourfold compared to the risk in nondiabetic subjects. Although type 2 diabetes is associated with a clustering of risk factors, the cause for an excess risk of cardiovascular disease remains unknown. Lipid and lipoprotein abnormalities in type 2 diabetes include particularly elevated levels of total and very low-density lipoprotein triglycerides and reduced levels of high-density lipoprotein (HDL) cholesterol. Total and low-density lipoprotein (LDL) cholesterol levels are usually normal if glycemic control is adequate but LDL particles are small and dense. According to prospective population-based studies, total cholesterol is a similar risk factor for coronary heart disease (CHD) in patients with type 2 diabetes as it is in nondiabetic subjects. High total triglycerides and low HDL cholesterol may be even stronger risk factors for CHD in patients with type 2 diabetes than in nondiabetic subjects. Recent drug treatment trials have indicated that the lowering of total and LDL cholesterol by statins, and the lowering of total triglycerides and the raising of HDL cholesterol by fibrates, are at least as beneficial in diabetic patients as in nondiabetic subjects in the prevention of cardiovascular disease.     

The effects of niacin on lipoprotein subclass distribution

Dyslipidemia is a heterogeneous metabolic condition; high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very-low-density lipoprotein represent families of lipoprotein particles that differ in size and composition and vary in atherogenicity. Lipoprotein subclasses containing apolipoprotein B promote atherosclerosis, of which the most atherogenic appear to be the small, dense LDL and large very-low-density lipoprotein subclasses, while the large HDL2 subclass, which transports esterified cholesterol from the periphery to the liver, is considered the more cardioprotective. Niacin has long been known to improve concentrations of all major lipids and lipoproteins, but it also has consistently favorable effects on subclass distribution. A MEDLINE search was conducted for clinical studies reporting the effects of niacin on lipoprotein subclasses. The niacin-associated elevations in HDL cholesterol likely stem from differential drug effects on subclasses, producing favorable changes in levels of HDL2 and apolipoprotein A-I. Niacin has more moderate LDL cholesterol-lowering efficacy, but this change is associated with an increase in LDL particle size and a shift from small LDL to the less atherogenic, large LDL subclasses. In addition, it also tends to decrease concentrations of the larger very-low-density lipoprotein subclasses. Niacin confers diverse benefits with respect to both the quantity and quality of lipid and lipoprotein particles.     

Reversal of atherogenic lipoprotein profile in HIV-1 infected patients with lipodystrophy after replacing protease inhibitors by nevirapine

BACKGROUND: The widespread use of protease inhibitors (PI) has been associated with abnormalities in the lipid profile of HIV-1-infected patients. Treatment simplification approaches in which PI are replaced by nevirapine (NVP) have been shown to improve PI-related toxicity. OBJECTIVE: To assess the impact on plasma lipids of replacing the PI by NVP in HIV-1 infected patients with lipodystrophy. METHODS: We studied 34 patients with lipodystrophy who had been the first to be enrolled in a prospective, randomized trial of continuing current treatment, or replacing PI with NVP. Sixteen patients replaced their PI with NVP and 18 continued their current PI-containing treatment. Total, low density lipoprotein (LDL), very low density lipoprotein (VLDL), intermediate density lipoprotein and high density lipoprotein (HDL) cholesterol and triglyceride levels, the size and particle number of LDL were determined at baseline and after 24 weeks, by nucleic magnetic resonance spectroscopy. FINDINGS: After 24 weeks of replacing the PI with NVP, we observed a reduction of total cholesterol (P = 0.028), LDL-cholesterol (P = 0.001), the number of circulating LDL particles (P = 0.003) and the VLDL-1 triglyceride level (P = 0.032). A concomitant significant increase was observed in both HDL-cholesterol level (P = 0.002) and HDL particle size (P < 0.001). No significant changes were observed in the group that continued taking the PI. CONCLUSIONS: The replacement of PI by NVP improved the lipid profile both by reducing the number and lipid content of atherogenic LDL particles, and increasing the protective HDL fraction. Although total triglyceride levels remained unchanged, a reduction in the VLDL-1 fraction contributes to the reduction of LDL particles. These changes are expected to reduce the risk of cardiovascular disease in HIV-1-infected patients on highly active antiretroviral therapy.     

Postprandial hyperlipidemia, small and dense LDL, HDL sub-fractions]

The association of postprandial hyperlipidemia, small and dense LDL particles and low HDL cholesterol levels is a major cardiovascular risk factor, highly prevalent in insulin resistant and diabetic patients. Several recent epidemiological studies have demonstrated that an abnormal increase in the postprandial triglyceride levels is an independent cardiovascular risk factor, independent from fasting triglyceride levels. A decreased clearance of postprandial triglycerides is related to an abnormal intravascular lipoprotein metabolism, most of the time secondary to an insulin resistant state and genetic factors. This abnormal lipoprotein metabolism also induces a redistribution of LDL particles towards small and dense particles and a decrease in the HDL cholesterol levels. Small, dense LDL are associated with a 3 fold increase in the risk of ischemic heart disease, but does not remain a significant risk factor after adjustment for triglyceride levels. Decreased HDL cholesterol and apolipoprotein A-I levels are strong cardiovascular risk factors, which does not seem to be better assessed with the assay of various HDL sub-fractions (HDL(2) et HDL(3), LpA-I et LpA-I: A-II.).     

Influence of dietary carbohydrate and fat on LDL and HDL particle distributions

Variations in the size and density distributions of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles have been related to risk for cardiovascular disease. In particular, increased levels of small, dense LDL particles, together with reduced levels of large HDL and increases in small HDL, are integral features of the atherogenic dyslipidemia found in patients with insulin resistance, obesity, and metabolic syndrome. Increased dietary carbohydrates, particularly simple sugars and starches with high glycemic index, can increase levels of small, dense LDL and HDL, primarily by mechanisms that involve increasing plasma triglyceride concentrations. Low-carbohydrate diets may have the opposite effects. Diets with differing fatty acid composition can also influence LDL and HDL particle distributions.     

Thyroid function and lipid subparticle sizes in patients with short-term hypothyroidism and a population-based cohort

CONTEXT: Relations between thyroid function and lipids remain incompletely understood. OBJECTIVE: Our objective was to determine whether lipoprotein subparticle concentrations are associated with thyroid status. DESIGN AND SETTING: We conducted a prospective clinical study and cross-sectional cohort analysis at a university endocrine clinic and the Framingham Heart Study. SUBJECTS: Subjects included 28 thyroidectomized patients with short-term overt hypothyroidism and 2944 Framingham Offspring cohort participants. MAIN OUTCOME MEASURES: Fasting subclass concentrations of very-low-density lipoprotein (VLDL), intermediate-density lipoprotein, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) particles were measured by nuclear magnetic resonance spectroscopy. TSH values were also measured. RESULTS: Total cholesterol and LDL-C were increased during short-term overt hypothyroidism. Large LDL subparticle concentrations increased during hypothyroidism (917+/-294 vs. 491+/-183 nmol/liter; P<0.001), but more atherogenic small LDL was unchanged. Triglycerides marginally increased during hypothyroidism, small VLDL particles significantly increased (P<0.001), whereas more atherogenic large VLDL was unchanged. Total HDL-C increased during hypothyroidism (76+/-13 mg/dl vs. 58+/-15 mg/dl; P<0.001). There was no change in large HDL-C particle concentrations, whereas small (P<0.001) and medium (P=0.002) HDL-C particle concentrations decreased. Among Framingham women, adjusted total cholesterol and LDL-C were positively related to TSH categories (P相似文献   

Low-density lipoprotein cholesterol bulk is the pivotal determinant of atherosclerosis in familial hypercholesterolemia

This study's aim was to determine whether biochemical risk factors such as lipoprotein(a), fibrinogen, homocysteine, and insulin, as well as low-density lipoprotein (LDL) particle size, were predictive of carotid intimamedia thickness (IMT), an early marker of atherosclerosis, in subjects with familial hypercholesterolemia (FH). We also determined whether plasma 8-isoprostane, as a marker of in vivo lipid oxidation, correlated with carotid IMT. Twenty-two homozygous and 20 heterozygous subjects with FH were compared with 20 normocholesterolemic controls. On univariate analysis, plasma total and LDL cholesterol, the cholesterol-years score (CYS), lipoprotein(a), and fibrinogen, but not homocysteine or insulin, were positively related, and high-density lipoprotein (HDL) cholesterol was negatively related to carotid IMT. However, on multivariate analysis, only LDL cholesterol and the CYS predicted carotid IMT (multiple r = 0.82; r2 = 0.68; p <0.0001). The subjects with FH had large rather than small dense LDL particles, and plasma 8-isoprostane levels were not increased. LDL cholesterol and the CYS, or "cholesterol bulk" are the pivotal determinants of atherosclerosis and are the strongest predictors of carotid IMT in FH.     

Low-density lipoprotein particle size, insulin resistance, and proinsulin in a population sample of 58-year-old men

The relationship between insulin sensitivity and low-density lipoprotein (LDL) peak particle size was examined in 104 clinically healthy 58-year-old men recruited from the general population. Insulin sensitivity was measured by the euglycemic hyperinsulinemic clamp method with adjustment for lean body mass. LDL peak particle size was determined by gradient gel electrophoresis, and insulin, proinsulin, and 32,33 split proinsulin were determined by 2-site immunoradiometric assays. The results showed that 16 subjects (15%) had pattern B, with a predominance of small LDL particles. These cases and a small LDL peak particle size were characterized by the features of the insulin resistance syndrome, ie, general and central obesity, elevated diastolic blood pressure, low serum concentrations of high-density lipoprotein (HDL) and apolipoprotein A1 (apoA1), increases in serum triglycerides and circulating insulin peptides, and low insulin-mediated glucose uptake. The correlation between insulin sensitivity and LDL peak particle size was significant (r = .33, P = .001) and independent of obesity. In a traditional multiple regression analysis, LDL peak particle size was independently associated not with insulin-mediated glucose uptake but with circulating triglycerides and HDL cholesterol, which together explained 67% of the variability in LDL particle size (P = .000). Of all insulin peptides, only proinsulin showed an independent relation to LDL peak particle size, but it disappeared after adjustment for other variables. We conclude that a small LDL particle size was associated with insulin resistance among these clinically healthy men, but this was not independent of serum triglycerides and HDL cholesterol. Serum proinsulin was more directly related to LDL particle size than insulin.     

Nuclear magnetic resonance-determined lipoprotein abnormalities in nonhuman primates with the metabolic syndrome and type 2 diabetes mellitus

The lipid profile in patients with the metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) is commonly characterized by increased levels of triglycerides and decreased levels of high-density lipoprotein (HDL) cholesterol. However, within each lipoprotein class, the changes are more complex. The present study defined the characteristics of dyslipidemia among nonhuman primates, using nuclear magnetic resonance (NMR) spectroscopy as well as the classic beta-quantification method, and examined the pattern of multiple lipoprotein fractions in relation to the main factors identified with the MetS. Seventy-three rhesus monkeys were classified into 3 groups: healthy monkeys, monkeys with MetS, and monkeys with T2DM. Characteristics of dyslipidemia in the MetS and T2DM groups included increased levels of triglyceride-rich very low-density lipoprotein, intermediate-density lipoprotein, and small, dense, low-density lipoprotein (LDL) particles. Reduced concentrations of large LDL and large HDL particles together with reduction of LDL and HDL particle sizes were also observed. Correlation analysis revealed that poor glycemic and lipid profiles, glucose intolerance, and insulin resistance were associated with an atherogenic NMR profile. Compared with the conventional lipid panel, the NMR lipoprotein profile presented in greater detail distinctive differences between the dyslipidemia of the MetS and that of diabetes and demonstrated significant and divergent shifts in both particle size and number within lipoprotein classes between those 2 groups. Detailed lipoprotein profiling may provide additional indicators for more timely intervention. Rhesus monkeys are likely to provide an excellent model for novel drug testing designed to address the specific differences in lipoprotein fraction profile across these 3 groups that reflect the progression of pathophysiology from normal to overt diabetes.     

Comparison of levels of large and small high-density lipoprotein cholesterol in Asian Indian men compared with Caucasian men in the Framingham Offspring Study

Asian Indians have a higher incidence of coronary artery disease (CAD) than do other ethnic groups, despite similar standard risk factors and lipid profiles. The large subclass of high-density lipoprotein (HDL) cholesterol is predominantly associated with protection against coronary artery disease. We compared various lipoprotein concentrations and sizes in 211 healthy Asian Indian men with those in 1,684 Caucasian men from the Framingham Offspring Study as measured by nuclear magnetic resonance spectroscopy. Concentrations of HDL cholesterol were similar in the 2 groups, but concentrations of large HDL cholesterol were lower and concentrations of small HDL cholesterol were significantly higher in Asian Indian than in Caucasian men. HDL particle size was smaller in Asian Indians. Levels of low-density lipoprotein cholesterol, low-density lipoprotein particle size, and prevalence of pattern B were similar in the 2 groups.     

Triglyceride as a risk factor for ischaemic heart disease in British men: effect of adjusting for measurement error

OBJECTIVE: To assess the influence of differential precision in the measurement of the correlated variables total cholesterol and high density lipoprotein (HDL) cholesterol on the estimates of the risk of ischaemic heart disease (IHD) associated with plasma triglyceride levels. DESIGN, SETTING AND PARTICIPANTS: The Caerphilly Heart Disease Study (CHDS), a prospective cohort study of 2512 middle-aged men living in the town of Caerphilly, south Wales, UK. The results from two sub-studies were used to estimate the degree of measurement imprecision (laboratory error and within-person variation) in triglycerides, total cholesterol and HDL cholesterol. MAIN OUTCOME MEASURES: Multivariable risk estimates for major IHD calculated from logistic regression analysis, adjusted and not adjusted for measurement imprecision. Major IHD events were defined as death from IHD, clinical non-fatal myocardial infarction or electrocardiographic myocardial infarction. RESULTS: There were 261 men with major IHD events during follow-up. In age-adjusted analyses, taking measurement imprecision into account strengthened associations with IHD for all lipid factors. The odds ratio (OR) for one S.D. increase in triglycerides, ignoring measurement imprecision, was 1.36 (95% confidence interval [95% CI] 1.20-1.55) but 1.57 (95% CI 1.30-1.89) when taking imprecision into account. The standardised odds ratio for triglycerides adjusted for measurement imprecision and the two other lipid factors was 1.35 (95% CI 1.09-1.69). In this model, the triglyceride level showed a stronger association than total cholesterol (OR 1.28; 95% CI 1.05-1.56) and HDL cholesterol (OR for one S.D. decrease 1.20; 95% CI 0.97-1.49). When adding fasting blood glucose and diastolic blood pressure, however, the effect of triglycerides was reduced and ceased to be statistically significant (OR 1.19; 95% CI 0.95-1.49). This was further attenuated upon inclusion of body mass index, smoking status and history of pre-existing IHD. Total cholesterol remained a statistically significant (P < 0.05) risk factor in all models. CONCLUSIONS: In contrast to other cohort studies, triglyceride concentration in the CHDS shows an association with the risk of IHD which is independent of total and HDL cholesterol. This effect was pronounced after adjustment for measurement imprecision. It was reduced, however, when adjusted for other factors. While hypertriglyceridaemia may exert an influence independent of other lipid factors, insulin resistance is probably the underlying metabolic disturbance.