Number Of Small LDL Particles Research Articles

NMR Insights into Lipoprotein Particles: analyzing correlations with traditional lipid measurements

Abstract Introduction Lipid metabolism plays a crucial role in various physiological processes. Lipid molecules are transported by lipoproteins, and the intricate involvement of lipoproteins in cardiovascular disease (CVD) is well-established, given their diverse size, density, and lipid composition. The emergence of Nuclear Magnetic Resonance (NMR) spectroscopy, a high-resolution analytical technique, promotes the assessment of lipoprotein particle numbers and sizes. Studies suggest that the measurement of total low-density lipoprotein particle numbers (LDL-P), small LDL-P (SLDL-P), and total high-density lipoprotein particle numbers (HDL-P) provides better evaluation of risk of CVD than enzymatic-based measurements of LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C). Our study examined the correlation between NMR-derived lipoprotein profiles and traditional cholesterol measurements in control and patient populations. Methods Fasting serum samples were collected from healthy male and female donors (n=148), ages 21-64 years. The analysis also included the results from >20,000 patients’ samples submitted to our laboratory for NMR lipid testing. We assessed LDL-P, SLDL-P, HDL-P, large HDL (LHDL-P), and HDL size (HDL-S) by NMR. In addition, total cholesterol (TC) and HDL-C were measured using traditional automated enzymatic assays (Roche Diagnostics); LDL-C was calculated. Statistical analyses, including Spearman correlation, were performed using GraphPad Prism software. Spearman coefficient (r) ≥0.75 indicated a strong correlation, r <0.5 indicated a weak correlation. Results HDL-C only moderately correlated with total HDL-P in samples collected from controls (rcontrols=0.52) and patients (rpatients=0.68), while showing better correlation with LHDL-P (rcontrols=0.90, rpatients=0.89). Traditional LDL-C strongly correlated with total LDL-P (rcontrols=0.76, rpatients=0.81), but showed only weak correlation with SLDL-P (rcontrols=0.42, rpatients=0.28), which is considered more atherogenic and predictive of CVD risk than LDL-C or total LDL-P. Interestingly, among various lipoprotein parameters, SLDL-P correlated the strongest with HDL-S in both study populations (rcontrols=-0.87, rpatients=-0.84). Samples with higher number of SLDL-P also had smaller size of HDL-P, although the number of total HDL-P did not differ between high vs low SLDL-P samples. In contrast, only moderate negative correlation was observed between SLDL-P and traditional HDL-C (rcontrols=-0.74, rpatients=-0.68), suggesting that the size of HDL particles might add value in evaluating CVD risk. Conclusion The NMR technology has advantage over traditional measurements in stratifying an individual’s lipoprotein milieu. It provides insights into the number of small LDL particles and size of HDL particles, which are not included in standard lipid testing and may allow for more individualized patient care. Incorporation of lipoprotein size and particle number in clinical guidelines may help physicians with assessment CVD risk and treatment monitoring.

Association of Advanced Lipoprotein Subpopulation Profiles with Insulin Resistance and Inflammation in Patients with Type 2 Diabetes Mellitus.

Plasma lipoproteins exist as several subpopulations with distinct particle number and size that are not fully reflected in the conventional lipid panel. In this study, we sought to quantify lipoprotein subpopulations in patients with type 2 diabetes mellitus (T2DM) to determine whether specific lipoprotein subpopulations are associated with insulin resistance and inflammation markers. The study included 57 patients with T2DM (age, 61.14 ± 9.99 years; HbA1c, 8.66 ± 1.60%; mean body mass index, 35.15 ± 6.65 kg/m2). Plasma lipoprotein particles number and size were determined by nuclear magnetic resonance spectroscopy. Associations of different lipoprotein subpopulations with lipoprotein insulin resistance (LPIR) score and glycoprotein acetylation (GlycA) were assessed using multi-regression analysis. In stepwise regression analysis, VLDL and HDL large particle number and size showed the strongest associations with LPIR (R2 = 0.960; p = 0.0001), whereas the concentrations of the small VLDL and HDL particles were associated with GlycA (R2 = 0.190; p = 0.008 and p = 0.049, respectively). In adjusted multi-regression analysis, small and large VLDL particles and all sizes of lipoproteins independently predicted LPIR, whereas only the number of small LDL particles predicted GlycA. Conventional markers HbA1c and Hs-CRP did not exhibit any significant association with lipoprotein subpopulations. Our data suggest that monitoring insulin resistance-induced changes in lipoprotein subpopulations in T2DM might help to identify novel biomarkers that can be useful for effective clinical intervention.

Erradication of HCV with direct-acting antivirals increased small LDL particle number in SVR48

Erradication of HCV with direct-acting antivirals increased small LDL particle number in SVR48

Lipid findings from the Diabetes Education to Lower Insulin, Sugars, and Hunger (DELISH) Study

BackgroundA carbohydrate-restricted (CR) diet can improve glycemic control in people with type 2 diabetes mellitus (T2DM). There are concerns, however, that the high dietary fat content of CR diets can increase low-density lipoprotein cholesterol (LDL-C), thus increasing cardiovascular disease (CVD) risk. Quantifying CVD risk associated with changes in LDL-C in the context of CR diets is complicated by the fact that LDL-C reflects heterogeneous lipids. For example, small LDL particle number (sLDL-P) is more closely associated with CVD risk than is total LDL-C, and CR diets tend to decrease the proportion of sLDL-C in LDL-C, which standard lipid measures do not indicate. Advanced lipoprotein assays, such as nuclear magnetic resonance (NMR) testing, can subfractionate lipoproteins by size and density and may better depict the effects of CR diets on CVD risk.MethodsAdults (N = 58) with T2DM (n = 37 women; baseline HbA1c ≥ 6.5%) completed a 6-month group-based CR diet intervention. We obtained a standard lipid panel, advanced lipoprotein assays (NMR testing), and two 24-h diet recalls at baseline and post-intervention (6 months). Participants also completed home-based blood ketone testing (a biological index of dietary adherence) during the final five weeks of the intervention.ResultsFrom baseline to post-intervention, participants had increased mean HDL-C, decreased triglycerides and triglyceride/HDL ratio, decreased mean sLDL-P, and increased LDL size, which reflect reductions in CVD risk (ps < 0.05). Participants did not have statistically significant changes in total cholesterol, non-HDL-C cholesterol, LDL-P, or HDL-P. Twelve participants (23.1%) had a ≥ 5% increase in sLDL-P. Exploratory analyses revealed that participants with sLDL-P increases of ≥ 5% reported larger increases in servings of red meat than participants without sLDL-P increases of ≥ 5% (+ 0.69 vs − 0.29 servings; p = 0.033). Changes in saturated fat intake were not associated with changes in sLDL-P.ConclusionsAmong most participants, we observed changes in several lipid measures consistent with decreased CVD risk. Approximately one in four participants evidenced increases in sLDL-P. Further research should clarify whether individuals with increased sLDL-P after implementing a CR diet can reverse observed increases by limiting red meat consumption.Trial registrationClinicalTrials.gov, NCT03207711, Registered 6/11/2017. Retrospectively registered.

Lipoprotein profile assessed by 2D-1H-NMR and subclinical atherosclerosis in children with familial hypercholesterolaemia

Background and aimsFamilial hypercholesterolaemia (FH) is underdiagnosed in children. In addition to lipid concentrations, lipoprotein particle quantity and quality could influence cardiovascular risk. We aimed to perform a comprehensive plasma lipid study, including lipoprotein particle number and size assessment by two-dimensional nuclear magnetic resonance (2D-1H-NMR), in children with FH compared to non-affected children and to evaluate the clinical value of these factors as subclinical atherosclerosis biomarkers. MethodsOne hundred eighty-three children participating in the broad “Hypercholesterolemia Early Detection Programme” (Decopin Project) were recruited. They were categorized as FH, if they had either a positive genetic test or clinical certainty, or as control children (CCh). Medical history, anthropometry and clinical variables were recorded. Standard biochemical measurements were performed. The lipoprotein profile was studied by 2D-1H-NMR. Carotid intima-media thickness (cIMT) was assessed by sonography in 177 children. ResultsFH children had a significant 36% increase in LDL particles. The small LDL fraction was increased by 33% compared to CCh. The relative relationship between large, medium and small LDL and the mean LDL particle size was similar between FH children and CCh. The total and small LDL particle numbers were directly associated with and contributed to the determination of the mean cIMT according to bivariate and multivariate analyses in FH children. ConclusionsThe higher cholesterol levels of FH children are due to an overall increased number of all LDL particle subclasses, including a notable 33% increase in small LDL. Total and small LDL particle number shows a good correlation with cIMT in FH children.

Randomized double blind clinical trial on the effect of oral α-cyclodextrin on serum lipids.

BackgroundThis single center, double-blinded, cross-over, placebo controlled clinical trial investigated the effect of oral α-cyclodextrin (α-CD), a soluble dietary fiber, on blood lipid and lipoprotein levels in healthy human subjects. α-CD, a cyclical polymer containing 6 glucose subunits, is currently sold as an over the counter food supplement and is also a common additive in many foods. α-CD forms a hydrophobic central cavity that binds lipids and has been shown in animal studies and in previous clinical trials to alter plasma lipid levels.MethodsWe screened for healthy subjects, males and females, between ages 18 to 75. Out of total 103 subjects interviewed, 75 subjects completed the study. Qualified individuals in each gender group were randomized into two groups in terms of which treatment arm they received first (placebo vs. α-CD, receiving 6 grams P.O. a day, for 12–14 weeks with a 7 day wash out between arms). The primary outcome variable, plasma total cholesterol, as well as other tests related to lipids and lipoprotein and glucose metabolism, were measured at baseline and at the end of each arm of the study.Resultsα-CD was well tolerated; no serious adverse events related to α-CD were observed. Approximately 8 % of the subjects on α-CD complained of minor gastrointestinal symptoms versus 3 % on placebo (p = 0.2). Small-LDL particle number decreased 10 % (p < 0.045) for subjects on α-CD versus placebo. Fasting plasma glucose (1.6 %, p < 0.05) and Insulin resistance index (11 %, p < 0.04) were also decreased when on α-CD versus placebo.Conclusionα-CD treatment appears to be safe and well tolerated in healthy individuals and showed a modest reduction in small LDL particles, and an improvement in glucose related parameters.Trial registrationNCT01131299

Olive Oil Polyphenols Decrease LDL Concentrations and LDL Atherogenicity in Men in a Randomized Controlled Trial1–3

Background: Olive oil polyphenols have shown protective effects on cardiovascular risk factors. Their consumption decreased oxidative stress biomarkers and improved some features of the lipid profile. However, their effects on LDL concentrations in plasma and LDL atherogenicity have not yet been elucidated.Objective: Our objective was to assess whether the consumption of olive oil polyphenols could decrease LDL concentrations [measured as apolipoprotein B-100 (apo B-100) concentrations and the total number of LDL particles] and atherogenicity (the number of small LDL particles and LDL oxidizability) in humans.Methods: The study was a randomized, cross-over controlled trial in 25 healthy European men, aged 20–59 y, in the context of the EUROLIVE (Effect of Olive Oil Consumption on Oxidative Damage in European Populations) study. Volunteers ingested 25 mL/d raw low-polyphenol-content olive oil (LPCOO; 366 mg/kg) or high-polyphenol-content olive oil (HPCOO; 2.7 mg/kg) for 3 wk. Interventions were preceded by 2-wk washout periods. Effects of olive oil polyphenols on plasma LDL concentrations and atherogenicity were determined in the sample of 25 men. Effects on lipoprotein lipase (LPL) gene expression were assessed in another sample of 18 men from the EUROLIVE study.Results: Plasma apo B-100 concentrations and the number of total and small LDL particles decreased (mean ± SD: by 5.94% ± 16.6%, 11.9% ± 12.0%, and 15.3% ± 35.1%, respectively) from baseline after the HPCOO intervention. These changes differed significantly from those after the LPCOO intervention, which resulted in significant increases of 6.39% ± 16.6%, 4.73% ± 22.0%, and 13.6% ± 36.4% from baseline (P < 0.03). LDL oxidation lag time increased by 5.0% ± 10.3% from baseline after the HPCOO intervention, which was significantly different only relative to preintervention values (P = 0.038). LPL gene expression tended to increase by 26% from baseline after the HPCOO intervention (P = 0.08) and did not change after the LPCOO intervention.Conclusion: The consumption of olive oil polyphenols decreased plasma LDL concentrations and LDL atherogenicity in healthy young men. This trial was registered at www.controlled-trials.com as ISRCTN09220811.

Abstract 239: LDL Apheresis Is Associated With a Reduction in Markers of Chronic Inflammation in Patients With Familial Hypercholesterolemia

Background: Familial Hypercholesterolemia is an inherited disease characterized by severely elevated levels of LDL cholesterol (LDL-C) and associated with premature coronary artery disease (CAD). LDL apheresis (LA) is indicated for management of CAD patients with LDL-C&gt;200 mg/dl despite medical therapy. LA may reduce LDL-C concentrations by up to 70%; this in turn has been associated with regression of atherosclerosis. NMR measurement of signals corresponding to methyl group protons of glycoproteins (GlycA and GlycB) has recently been validated in prediction of atherosclerosis and chronic systemic inflammation. Studies have demonstrated a reduction in inflammatory cytokines with LA, but no study to date has evaluated the impact of LA on levels of glycoproteins as markers of chronic inflammation. Objective: To determine the effect of LA on plasma levels of glycoproteins using a novel NMR based technique, and to correlate these findings with changes in lipoprotein subclasses. Methods: Comprehensive NMR lipoprotein analysis was performed on serum obtained from seven subjects prior to and following LA sessions performed at two-week intervals (N = 47 paired samples). Three subjects had homozygous FH, three had heterozygous FH with CAD and/or LDL-C &gt; 200 mg/dL, one patient had severe mixed dyslipidemia with CAD and LDL-C &gt; 200 mg/dL. Results: Mean GlycA and GlycB levels were 335±91 μmol/L and 125±31 μmol/L respectively prior to LA. Following LA treatment, there was a significant reduction in GlycA to 277±73 μmol/L (P&lt;0.001) and in GlycB to 102±28 μmol/L (P&lt;0.001). The reduction in GlycA was strongly correlated with a decrease in total small LDL particle number (r = 0.68, p &lt; 0.001) and with a reduction in medium VLDL particle number (r = 0.52, P &lt; 0.001). GlycB level was weakly correlated with small LDL (r = 0.39, P = 0.007) and IDL particle numbers (r = 0.32, P = 0.028). In addition, GlycA and GlycB levels were correlated to each other (r = 0.49, P &lt; 0.001). Conclusion: This is the first report of NMR detection of glycoproteins as inflammatory biomarkers in patients with severe dyslipidemia undergoing LA. LA was associated with a significant reduction in levels of both GlycA and GlycB, which correlated with reductions in LDL and VLDL particle number.

Plasma Triglyceride Levels May Modulate Hepatitis C Viral Replication

Plasma and hepatic lipid abnormalities are frequent in hepatitis C infected individuals. Plasma lipid and medical records profiles were prospectively obtained in 130 consecutive individuals seen by a single hepatologist in a university liver disease clinic. The relationships between viral load, genotype, plasma lipid fractions, HDL, LDL particle number and particle size were examined. Of 130 individuals studied, 74 had hepatitis C while 15 had NAFLD/NASH and 30 had alcohol related liver disease. The LDL particle number and LDL-C levels did not differ between those with and without hepatitis C although the number of small LDL particles was greater in those with hepatitis C infection. The HDL-C and total cholesterol levels were greater in those without hepatitis C than those with hepatitis C (P = 0.009). In contrast, the serum triglyceride level was greater in the hepatitis C viral group (P = 0.013). Importantly, the hepatitis C viral load regardless of the genotype correlated directly with the triglyceride and VLDL levels with r values of 0.73 and 0.84, respectively. There are: (1) important differences in lipid classes, number and the size of lipid particles exist between hepatitis C virus infected and noninfected liver disease groups, (2) the serum total triglyceride and the LDL levels correlate significantly with the hepatitis C viral load and, (3) Serum triglyceride level may play an important role in viral replication. These data further suggest that therapies directed at lowering plasma triglyceride levels may enhance the efficacy of current antiviral treatment regimens.

Genetic Modulation of Lipid Profiles following Lifestyle Modification or Metformin Treatment: The Diabetes Prevention Program

Weight-loss interventions generally improve lipid profiles and reduce cardiovascular disease risk, but effects are variable and may depend on genetic factors. We performed a genetic association analysis of data from 2,993 participants in the Diabetes Prevention Program to test the hypotheses that a genetic risk score (GRS) based on deleterious alleles at 32 lipid-associated single-nucleotide polymorphisms modifies the effects of lifestyle and/or metformin interventions on lipid levels and nuclear magnetic resonance (NMR) lipoprotein subfraction size and number. Twenty-three loci previously associated with fasting LDL-C, HDL-C, or triglycerides replicated (P = 0.04–1×10−17). Except for total HDL particles (r = −0.03, P = 0.26), all components of the lipid profile correlated with the GRS (partial |r| = 0.07–0.17, P = 5×10−5–1×10−19). The GRS was associated with higher baseline-adjusted 1-year LDL cholesterol levels (β = +0.87, SEE±0.22 mg/dl/allele, P = 8×10−5, P interaction = 0.02) in the lifestyle intervention group, but not in the placebo (β = +0.20, SEE±0.22 mg/dl/allele, P = 0.35) or metformin (β = −0.03, SEE±0.22 mg/dl/allele, P = 0.90; P interaction = 0.64) groups. Similarly, a higher GRS predicted a greater number of baseline-adjusted small LDL particles at 1 year in the lifestyle intervention arm (β = +0.30, SEE±0.012 ln nmol/L/allele, P = 0.01, P interaction = 0.01) but not in the placebo (β = −0.002, SEE±0.008 ln nmol/L/allele, P = 0.74) or metformin (β = +0.013, SEE±0.008 nmol/L/allele, P = 0.12; P interaction = 0.24) groups. Our findings suggest that a high genetic burden confers an adverse lipid profile and predicts attenuated response in LDL-C levels and small LDL particle number to dietary and physical activity interventions aimed at weight loss.

Lipoprotein Subfractions and Particle Size in End-Stage Renal Disease

It is interesting to note that the most heavily relied upon measures in nephrology and cardiology are both derived from calculations based on laboratory and clinical values, that is, the estimated GFR and the estimated concentration of low-density lipoprotein cholesterol (LDL-C). The actual particles of LDL in the bloodstream represent the end product of multiple hydrolysis steps that allow the initial nutritional packet, very low-density lipoprotein (VLDL), to deliver fatty acids, as well as cholesterol esters, to tissues for cellular metabolism and maintenance. The half-life of LDL is approximately 3 days, and it is believed that LDL itself has no nutritional value (1). In an ideal situation, LDL would meet its catabolic fate by docking with the LDL receptor and clearance from the circulation. However, in most adults, there is an age-related increase in LDL-C due to impaired clearance and perhaps recirculation of particles via cholesteryl esterase transfer protein. Smaller LDL particles have a longer clearance time and are more densely packed with cholesterol ester than larger particles, giving them more opportunity for tissue deposition (Figure 1) (1). While LDL-C has served reasonably well as an estimate and a proxy for the pathogenic LDL particles, many have believed that measurement of either the number or concentration of particles according to size, or determination of the apolipoprotein B concentration (1:1 with the number of LDL particles) should bring us closer to appreciating ongoing deposition of LDL into the vessel wall, advancing atherosclerosis, and translation into binary events such as myocardial infarction and cardiovascular death (2,3). Figure 1. Depiction of smaller dense LDL particles with ingress into the subintimal space initiating the pathogenesis of atherosclerosis. HSPG, heparin sulfate proteoglycans. In this issue of the journal, Noori and colleagues performed detailed LDL particle analysis on a random sample (n = 235) of hemodialysis patients who were part of a well established cohort followed for all-cause mortality (4). One of the most striking findings in this study is the influence of obesity, as stratified above and below a body mass index of 27 kg/m2, which was associated with an approximately 20 to 40% increase in triglycerides, and statistically significantly higher LDL-C, total LDL particles, and very small to medium LDL particles. The very small LDL particles were only significantly correlated (R = 0.21) with one nonlaboratory measure: fat mass percent. This influence of excess adiposity on lipid subfractions in end-stage renal disease (ESRD) appear to be greater than those observed in the general population (5). These relationships are important to remember, as the detailed tables and figures in this article suggest that there are modest relationships between small LDL particle number and concentration with all-cause mortality, which is a relatively crude and diluted proxy for translated atherosclerotic events. Thus, this article indirectly brings into focus, perhaps, a special pathogenicity of excess adiposity in patients with chronic uremia that is related, in part, to greater numbers of smaller LDL particles. These nuances are fairly well concealed in the standard lipid profile, which features the calculated LDL-C. Many articles suggest that chronic kidney disease (CKD), independent of other risk factors, appears to accelerate the atherosclerotic process, including the gradient dependent deposition of LDL particles, recruitment of monocytes, upregulation of adhesion molecules, ingress of monocytes and conversion to macrophages and foam cells, oxidation of lipid material, mobilization of vascular smooth muscle cells, breakdown of the elastic lamina, and development of an atheroma, which expands both toward the lumen and outward toward the adventitia (6–8). The most prominent component of atherosclerosis influenced by CKD is calcification, which, interestingly, is not associated with LDL particle size or number, nor is it influenced by lipid-lowering therapy (9,10). The present article by Noori and coworkers suggests that, beyond calcification, an atherogenic dyslipidemia is more prominently related to excess adiposity and is in the causal for pathway for earlier, more severe, and consequential atherosclerosis in patients with ESRD (11–13). Future research in ESRD using advanced clinical lipidology measures, including oxidized lipids and quantity, size, content, and circulatory time of particles, is warranted. More detail will be needed on the effects of adiposity, concurrent medications, and state of vascular disease determined by imaging. Finally, the end points of future studies will deserve to be more focused on atherosclerotic vascular events that experts can adjudicate and agree upon, including unstable angina, acute myocardial infarction, and ischemic stroke. The clinical use of commercially available lipoprotein subfractionation or particle tests in patients with ESRD is premature at the present time, due to the complexity of the biologic relationships in uremia, degree of uncontrolled confounding, lack of harmony between testing methodologies on the market, and the absence of a clear therapeutic mandate above and beyond what we currently have in the conventional lipid profile (14).

High-fat meal effect on LDL, HDL, and VLDL particle size and number in the Genetics of Lipid-Lowering drugs and diet network (GOLDN): an interventional study

BackgroundPostprandial lipemia (PPL) is likely a risk factor for cardiovascular disease but these changes have not been well described and characterized in a large cohort. We assessed acute changes in the size and concentration of total and subclasses of LDL, HDL, and VLDL particles in response to a high-fat meal. Participants (n = 1048) from the Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN) Study who ingested a high-fat meal were included in this analysis. Lipids were measured at 0 hr (fasting), 3.5 hr, and 6 hr after a standardized fat meal. Particle size distributions were determined using nuclear magnetic resonance spectroscopy. Analyses were stratified by baseline triglycerides (normal vs. elevated) and gender. The effect of PPL on changes in lipoprotein subclasses was assessed using repeated measures ANOVA.ResultsPostprandially, LDL-C, HDL-C, VLDL-C, and triglycerides increased regardless of baseline triglyceride status, with the largest increases in VLDL-C and TG; however, those with elevated triglycerides demonstrated larger magnitude of response. Total LDL particle number decreased over the 6-hour time interval, mostly from a decrease in the number of small LDL particles. Similarly, total VLDL particle number decreased due to reductions in medium and small VLDL particles. Large VLDL particles and chylomicrons demonstrated the largest increase in concentration. HDL particles demonstrated minimal overall changes in total particle number.ConclusionsWe have characterized the changes in LDL and VLDL particle number, and their subclass patterns following a high-fat meal.

Consumption of either one egg or lutein‐enriched egg per day increases HDL cholesterol, reduces apolipoprotein B while increasing plasma carotenoids and macular pigment density in adult subjects

In this study, subjects were assigned to consume either one egg (n =11), one egg substitute (n = 12) or one egg fortified with 600 μg of lutein (n = 11) per day. We measured plasma lipids, LDL subfractions and circulating carotenoids, macular pigment density (MPOD) by use of a densitometer, and hand carotenoids by use of a biophotonic scanner at baseline and after 12 wk. No changes in plasma LDL cholesterol or triglycerides were observed over time. However, both egg groups presented increases in HDL cholesterol compared to baseline (P &lt; 0.01). All subjects had decreases in apolipoprotein B (P &lt; 0.05) associated with a lower number of small LDL particles (P &lt; 0.01). Independent of source, egg intake increased MPOD (P &lt; 0.01) while hand carotenoids did not change over time for any of the groups. Plasma lutein concentrations increased by 9% (P &lt; 0.01) and by 35% (P &lt; 0.001) in the egg and lutein‐enriched egg groups, respectively. In this study we have demonstrated that MPOD increases whether subjects are consuming regular eggs or lutein enriched eggs. However, circulating lutein concentrations were associated with higher intake of this carotenoid, which may increase antioxidant protection in plasma. These studies demonstrate that consuming one egg per day may protect the eye against macular degeneration while increasing HDL cholesterol and favoring the formation of less atherogenic particles. [Supported by the Egg Board]

Relation of long-term body weight change to change in lipoprotein particle size in Japanese men and women: The INTERMAP Toyama Study

ObjectiveThis study investigated the relationship between changes in lipoprotein particle size and body weight change over a 9-year period in Japanese adult men and women. MethodsAmong 299 INTERMAP Toyama Study participants aged 40–59 in 1997, 260 were followed up in 2006 (129 men and 131 women). Their body weight and lipoprotein particle sizes were measured in 1997 and 2006. Nuclear Magnetic Resonance spectroscopy was used for the measurement of lipoprotein particle size. ResultsThe number of small LDL particles decreased from 774.3 to 617.4nmol/L in men (p=0.005) while the number increased from 353.2 to 414.5nmol/L in women (p=0.028) over this period. No significant changes in mean body weight were noted in either sex. Nine-year body weight change was positively associated with changes in the numbers of small LDL particles (men, r=0.37, p<0.001; women, r=0.21, p=0.018), but inversely associated with changes in LDL particle size (men, r=−0.30, p=0.001; women, r=−0.16, p=0.066) and HDL particle size (men, r=−0.42, p<0.001; women, r=−0.42, p<0.001). These relationships were similar even when adjusted for age, baseline body mass index, baseline values for LDL and HDL particle sizes, and other factors. The number of small LDL particles increased in both men and women in the body weight gain group. In the body weight loss group, the number of small LDL particles decreased in men but did not decrease in women. ConclusionThis 9-year observational study showed that the number and size of lipoprotein particles were strongly influenced by long-term body weight change.

The Association between Leisure Physical Activity and Lipoprotein Subclasses in 40-49 Year Old Men

Participation in physical activity has been shown to be beneficially related to traditional lipid measures. Recent advances in technology have produced new techniques that have the ability to measure specific lipoprotein subclasses; however evidence regarding the association between physical activity and these lipoprotein subclasses is limited. It has been suggested that the amount of cholesterol carried inside lipoprotein subclasses is highly variable among individuals with the same measured cholesterol. Individual lipoprotein subclasses can now be differentiated by this new technique. PURPOSE: To determine the association between leisure physical activity and both traditional lipid measures and lipoprotein subclasses in middle-aged Caucasian and African American men. METHODS: A population-based sample of 216 randomly-selected Caucasian and African American men aged 40–49 (mean age 44.8 ± 2.9, 17.1 % African American) was examined. Physical activity was assessed using a validated past six-month, interviewer administered questionnaire. Traditional lipid measures were obtained from fasting blood samples analyzed at the Department of Epidemiologys Heinz Laboratory. Lipoprotein subclasses were measured with nuclear magnetic resonance (NMR) spectroscopy. Multivariate linear regression models were created to examine the association between physical activity and both traditional lipid measures and lipoprotein subclasses. Each model was adjusted for potential confounding factors. RESULTS: After adjusting for age, BMI, race, and lipid lowering drug usage, physical activity was not significantly related to traditional lipid measures with the exception of triglycerides (p = 0.03). However, physical activity was significantly related to many important lipoprotein subclasses. More specifically, large VLDL (p=0.002), medium LDL (p=0.02), small LDL (p=0.04), and very small LDL particle number (p=0.04), triglycerides (p=0.01) and VLDL triglycerides (p=0.02) decreased as physical activity increased. CONCLUSIONS: Physical activity was not associated with traditional lipid measures with the exception of triglycerides. However using newer techniques, such as NMR, many more important associations were noted that otherwise would not have been evident using traditional measures. As more precise techniques are being used, the relationship between physical activity and blood lipids is becoming more evident, reaffirming the importance of a physically active lifestyle. Supported by: RO1HL068200

Increased Small Low-Density Lipoprotein Particle Number

Levels of LDL cholesterol (LDL-C) are frequently not elevated in individuals with the metabolic syndrome (MetSyn). However, the atherogenic potential of LDL may depend on the number and size of LDL particles in addition to the cholesterol content of LDL. We examined the sex-specific cross-sectional relations of small LDL particle number (determined by nuclear magnetic resonance spectroscopy) to the presence of MetSyn and its components in 2993 Framingham Heart Study participants (mean age, 51 years; 53% women) without cardiovascular disease (CVD) and the relations of small LDL particle number to CVD incidence in people with MetSyn. The MetSyn (> or =3 of 5 traits as defined by the National Cholesterol Education Adult Treatment Panel III) was present in 27% of men and 17% of women. In both sexes, small LDL particle number increased from 0 to 5 MetSyn traits, a pattern partly accounted for by strong correlations between small LDL particle number and serum triglycerides (r=0.61, P<0.0001) and HDL-C (r=-0.55, P<0.0001). Compared with participants without the MetSyn, those with the MetSyn had a higher CVD event rate. However, among participants with the MetSyn, CVD rates were similar for groups with an elevated versus a lower number of small LDL particles (defined by the sex-specific median). Small LDL particle number is elevated in the MetSyn, increases with the number of MetSyn components, and most prominently is correlated with triglycerides and HDL-C. Whereas increased small LDL particle number identified the MetSyn with high sensitivity, a higher small LDL particle number was not associated with greater CVD event rates in people with the MetSyn.