Lipoprotein Particle Subfractions Research Articles

Effect of Hormone Therapy on Lipoprotein Subfractions in Early and Late Postmenopausal Women.

The Early vs Late Intervention Trial with Estradiol (ELITE) showed that hormone therapy (HT) reduced atherosclerosis progression among early but not late postmenopausal women (PMW). Determined by time-since-menopause (1) HT effects on lipids and lipoprotein particle subfractions (LPs), (2) associations of estradiol (E2) level with lipids and LPs, (3) associations of lipids and LPs with atherosclerosis progression. Randomized controlled trial stratified by time-since-menopause. Academic institution. Healthy postmenopausal women. Oral E2 with/without sequential vaginal progesterone. Standard lipids and 21 LPs quantitated by ion mobility every 6 months. Among 562 PMW (240 early, 322 late), HT significantly increased total triglycerides (TG), high-density lipoprotein (HDL) cholesterol, small low-density lipoproteins (LDL), large HDL, and TG/C ratio in LDL and HDL and decreased LDL-cholesterol, total very low density lipoproteins (VLDL), small VLDL, intermediate-density lipoproteins, large LDL, and LDL peak diameter. HT showed no lipid or LP differences between time-since-menopause. Associations of E2 level with lipids and LPs explained the HT effects. Despite the nonsignificant P interaction by time-since-menopause, we observed that very small LDL and total HDL LPs were associated with atherosclerosis progression in late PMW. HT effects on standard lipids and LPs are consistent with the literature. HT has similar effect on lipids and LPs in early and late PMW. Novel findings include discordant effects of HT on TG and VLDL particles, which can be explained by increased catabolism of atherogenic remnants of TG-rich lipoproteins. Our findings extend the well-known HT effects on standard lipids and LPs that may contribute to the beneficial effects on atherosclerosis progression in PMW.

Changes in soluble LDL receptor and lipoprotein fractions in response to diet in the DIETFITS weight loss study

Circulating levels of the soluble ligand-binding ectodomain of the LDL receptor (sLDLR) that is proteolytically cleaved from the cell surface have been shown to correlate with plasma triglycerides, but the lipid and lipoprotein effects of longitudinal changes in sLDLR have not been examined. We sought to assess associations between changes in sLDLR and detailed lipoprotein measurements between baseline and 6 months in participants in the DIETFITS (Diet Intervention Examining The Factors Interacting with Treatment Success) weight loss trial who were randomly assigned to the low-fat (n = 225) or low-carbohydrate (n = 236) diet arms. sLDLR was assayed using a proteomic procedure, lipids and apoprotein (apo) B and apoAI were measured by standard assays, and lipoprotein particle subfractions were quantified by ion mobility methodology. Changes in sLDLR were significantly positively associated with changes in plasma cholesterol, triglycerides, apoB, large-sized and medium-sized VLDL, and small and very small LDL, and inversely with changes in large LDL and HDL. The lipoprotein subfraction associations with sLDLR were independent of age, sex, diet, and BMI, but all except for large LDL were reduced to insignificance when adjusted for triglyceride change. Principal component analysis identified three independent clusters of changes in lipoprotein subfractions that accounted for 78% of their total variance. Change in sLDLR was most strongly correlated with change in the principal component that was loaded positively with large VLDL and small and very small LDL and negatively with large LDL and HDL. In conclusion, sLDLR is a component of a cluster of lipids and lipoproteins that are characteristic of atherogenic dyslipidemia.

Effect of PCSK9 inhibitor on lipoprotein particles in patients with acute coronary syndromes

BackgroundTo assess the effects of proprotein convertase subtilisin/kexin type 9 inhibitor (evolocumab) on lipoprotein particles subfractions with Nuclear Magnetic Resonance spectroscopy in patients with acute coronary syndromes.MethodsA total of 99 consecutive patients with ACS were enrolled and assigned to either the experimental group (n = 54) or the control group (n = 45). The combination therapy of PCSK9 inhibitor (Repatha®, 140 mg, q2w) and moderate statin (Rosuvastatin, 10 mg, qn) was administered in the experimental group, with statin monotherapy (Rosuvastatin, 10 mg, qn) in the control group. The therapeutic effects on lipoprotein particle subfractions were assessed with NMR spectroscopy after 8 weeks treatment, and the achievement of LDL-C therapeutic target in both groups were analyzed.ResultsIn the experimental group, after 8 weeks of evolocumab combination treatment, the concentrations of blood lipids (TC, LDL-C and its subfractions [LDL-1 to 6], VLDL-C and its subfractions [VLDL-1 to 5], IDL-C, and HDL-C), lipoprotein particles, and their subfractions [VLDL-P, IDL-P, LDL-P, and its subfractions [LDL-P1 to 6], apoB, and LP(a)] demonstrated therapeutic benefits with statistical significance (P < 0.05). The decrease in total LDL-P concentrations was mainly due to a decreased concentration of small-sized LDL particles (LDL-P 5 + 6), which was significantly more prominent than the decrease in medium-sized LDL-P (LDL-P3 + 4) and large-sized LDL-P (LDL-P1 + 2) (P < 0.001). According to lipid control target recommended by the latest China Cholesterol Education Program Expert Consensus in 2019, after 8 weeks treatment, 96.3% patients in the experimental group and 13.3% in the control group had achieved the LDL-C therapeutic target (P < 0.01).ConclusionsEvolocumab combination treatment for 8 weeks significantly improves the plasma lipid profiles in ACS patients, and significantly decrease the concentration of lipoprotein particles which might contribute to the pathonesis of atherosclerosis.

Impact of a 2-year trial of nutritional ketosis on indices of cardiovascular disease risk in patients with type 2 diabetes

BackgroundWe have previously reported that in patients with type 2 diabetes (T2D) consumption of a very low carbohydrate diet capable of inducing nutritional ketosis over 2 years (continuous care intervention, CCI) resulted in improved body weight, glycemic control, and multiple risk factors for cardiovascular disease (CVD) with the exception of an increase in low density lipoprotein cholesterol (LDL-C). In the present study, we report the impact of this intervention on markers of risk for atherosclerotic cardiovascular disease (CVD), with a focus on lipoprotein subfraction particle concentrations as well as carotid-artery intima-media thickness (CIMT).MethodsAnalyses were performed in patients with T2D who completed 2 years of this study (CCI; n = 194; usual care (UC): n = 68). Lipoprotein subfraction particle concentrations were measured by ion mobility at baseline, 1, and 2 years and CIMT was measured at baseline and 2 years. Principal component analysis (PCA) was used to assess changes in independent clusters of lipoprotein particles.ResultsAt 2 years, CCI resulted in a 23% decrease of small LDL IIIb and a 29% increase of large LDL I with no change in total LDL particle concentration or ApoB. The change in proportion of smaller and larger LDL was reflected by reversal of the small LDL subclass phenotype B in a high proportion of CCI participants (48.1%) and a shift in the principal component (PC) representing the atherogenic lipoprotein phenotype characteristic of T2D from a major to a secondary component of the total variance. The increase in LDL-C in the CCI group was mainly attributed to larger cholesterol-enriched LDL particles. CIMT showed no change in either the CCI or UC group.ConclusionConsumption of a very low carbohydrate diet with nutritional ketosis for 2 years in patients with type 2 diabetes lowered levels of small LDL particles that are commonly increased in diabetic dyslipidemia and are a marker for heightened CVD risk. A corresponding increase in concentrations of larger LDL particles was responsible for higher levels of plasma LDL-C. The lack of increase in total LDL particles, ApoB, and in progression of CIMT, provide supporting evidence that this dietary intervention did not adversely affect risk of CVD.

Unfavorable Triglyceride-rich Particle Profile in Subclinical Thyroid Disease: A Cross-sectional Analysis of ELSA-Brasil.

Subclinical thyroid disorders have been associated with atherosclerosis and increased cardiovascular risk. As triglyceride-rich lipoprotein particles (TRLPs) have recently emerged as a casual factor for atherogenesis, the aim of this study was to evaluate the relationship between subclinical hypo- and hyperthyroidism and TRLP subfractions. We selected 5066 participants from the ELSA-Brasil cohort with available data of thyroid function and lipid profile measured by nuclear magnetic resonance (NMR) spectroscopy. Individuals were divided into 3 groups by baseline thyroid function (subclinical hypothyroidism, euthyroidism, and subclinical hyperthyroidism). Triglyceride-rich lipoprotein particle subfractions were analyzed through NMR spectroscopy. To examine the association between TRLP subfractions and thyroid function, we conducted univariate and multivariate linear regression models adjusted for demographic characteristics, body mass index, diabetes, smoking status, and alcohol use. Of 3304 individuals, 54% were women, with a mean age of 50.6 ± 8.7 years, 51% white, and 53% with at least a college education. Of these individuals, 92% were euthyroid, whereas 6.8% had subclinical hypothyroidism and 1.2% had subclinical hyperthyroidism. The univariate linear regression showed that very small TRLPs (P = 0.026) and very large TRLPs (P = 0.008) were statistically increased in subclinical hypothyroidism when compared with euthyroidism. In subclinical hyperthyroidism, there was a reduction in total TRLPs (P = 0.003), seemingly driven by reduced very small TRLPs (P = 0.067). The findings were confirmed when adjusted for demographic characteristics, as well as comorbidities. This study suggests that subclinical hypothyroidism is associated with very small and very large TRLPs, which are related to an unfavorable atherogenic profile. Subclinical hyperthyroidism is associated to lower very small TRLPs.

Untying the correlation between apolipoproteins and rheumatoid arthritis.

The concentration of lipoproteins and apolipoprotein are extremely low in the synovial fluid of any healthy person as compared to the concentrations in plasma. However, in the synovial fluid of any diseased patient the amount of cholesterol and lipids is sharply increased. The current review defines the role of various apolipoproteins and lipoproteins and their constituent subfractions in the synovial fluid embarking its principal role in rheumatoid arthritis. It also explains the need to define synovial fluid lipids, lipoprotein particle subfractions and their constituent apolipoproteins in synovial fluid. Various research and review articles highlighting the role of apolipoproteins and lipoproteins were procured from medical websites mainly Pubmed, Medline, Science Direct, etc., and studied for the writing of the review paper. Mainly apolipoproteins A-1, B and E are prominently increased in chronic inflammatory joint disorders. Several theories have been proposed to understand the source of increase of lipids and apolipoproteins in synovial fluid of the diseased patients compared to healthy individuals, yet the precise mechanism is still not lucid. Lipoproteins are believed to play both functional role and pathological role in the synovial fluid. The activated T-lymphocytes in patients of RA lead to activation of inflammatory cytokines such as tumor necrosis factor and interleukins which embark to be the principal mechanism for induction of the disease. It can be thus concluded that the apolipoproteins prevent the activation of monocytes by blocking their contact of activation and thus play critical role in management of RA by inhibiting the production of proinflammatory cytokines.

Differences in response to egg-derived dietary cholesterol result in distinct lipoprotein profiles while plasma concentrations of carotenoids and choline are not affected in a young healthy population

Abstract Background It has been demonstrated that some individuals (approximately 1/3 of the population) can be classified as hyper-responders to dietary cholesterol. Objective The objective of this study was to evaluate whether the response to dietary cholesterol (provided by eggs) would mediate lipoprotein metabolism and the bioavailability of lutein, zeaxanthin, and choline, nutritional components present in eggs. Methods We recruited 36 healthy subjects who underwent a two-week washout period in which they consumed zero eggs. Participants were then consecutively fed 1, 2, and 3 eggs/day for 4 weeks each. In this analysis, we compared intake of 0 eggs/day to 3 eggs/day (540 additional mg of dietary cholesterol/day). Plasma lipids, lipoprotein particle subfractions, and plasma lutein, zeaxanthin, and choline were measured. We classified the normal plasma response to dietary cholesterol as an increase of 2.2 mg/dL for each 100 mg of dietary cholesterol/day. Therefore, those individuals with >12 mg/dL increase in plasma cholesterol after the intervention (n = 12) were considered hyper-responders while the remaining 24 subjects presented changes in plasma cholesterol ranging from −16 to 9 mg/dL and were considered normal responders. Results Compared to 0 eggs, hyper-responders had significant increases in plasma total, LDL and HDL cholesterol (p Conclusions These results suggest that egg intake increases the bioavailability of carotenoids and choline present in eggs independently of individual responses to dietary cholesterol. Further, the observed increases in large HDL in all individuals could be associated with HDL being a major transporter of lutein and zeaxanthin in plasma.

Effects of red meat, white meat, and nonmeat protein sources on atherogenic lipoprotein measures in the context of low compared with high saturated fat intake: a randomized controlled trial

Dietary recommendations to limit red meat are based on observational studies linking intake to cardiovascular disease (CVD) risk together with the potential of its saturated fatty acid (SFA) content to raise low-density lipoprotein (LDL) cholesterol. However, the relation of white meat to CVD risk, and the effects of dietary protein source on lipoprotein particle subfractions, have not been extensively evaluated. We tested whether levels of atherogenic lipids and lipoproteins differed significantly following consumption of diets with high red meat content compared with diets with similar amounts of protein derived from white meat or nonmeat sources, and whether these effects were modified by concomitant intake of high compared with low SFAs. Generally healthy men and women, 21-65 y, body mass index 20-35 kg/m2, were randomly assigned to 1 of 2 parallel arms (high or low SFA) and within each, allocated to red meat, white meat, and nonmeat protein diets consumed for 4 wk each in random order. The primary outcomes were LDL cholesterol, apolipoprotein B (apoB), small+medium LDL particles, and total/high-density lipoprotein cholesterol. Analysis included participants who completed all 3 dietary protein assignments (61 for high SFA; 52 for low SFA). LDL cholesterol and apoB were higher with red and white meat than with nonmeat, independent of SFA content (P<0.0001 for all, except apoB: red meat compared with nonmeat [P=0.0004]). This was due primarily to increases in large LDL particles, whereas small+medium LDL and total/high-density lipoprotein cholesterol were unaffected by protein source (P=0.10 and P=0.51, respectively). Primary outcomes did not differ significantly between red and white meat. Independent of protein source, high compared with low SFA increased LDL cholesterol (P=0.0003), apoB (P=0.0002), and large LDL (P=0.0002). The findings are in keeping with recommendations promoting diets with a high proportion of plant-based food but, based on lipid and lipoprotein effects, do not provide evidence for choosing white over red meat for reducing CVD risk. This trial was registered at Clinicaltrials.gov as NCT01427855.

Gene-Based Elevated Triglycerides and Type 2 Diabetes Mellitus Risk in the Women's Genome Health Study.

Objective- Higher triglyceride (TG) is a risk factor for incident type 2 diabetes mellitus (T2DM), but paradoxically, genetic susceptibility for higher TG has been associated with lower T2DM risk. There is also evidence that the genetic association may be modified by baseline TG. Whether such associations can be replicated and the interaction is selective for certain TG-rich lipoprotein particles remains to be explored. Approach and Results- Cox regression involving TG, TG-rich lipoprotein particles, and genetic determinants of TG was performed among 15 813 participants with baseline fasting status in the WGHS (Women's Genome Health Study), including 1453 T2DM incident cases during a mean 18.6 (SD=5.3) years of follow-up. A weighted, 40-single-nucleotide polymorphism TG genetic risk score was inversely associated with incident T2DM (hazard ratio [95% CI], 0.66 [0.58-0.75]/10-TG risk alleles; P<0.0001) with adjustment for baseline body mass index, HDL (high-density lipoprotein) cholesterol, and TG. TG-associated risk was higher among individuals in the low compared with the high 40-single-nucleotide polymorphism TG genetic risk score tertile (hazard ratio [95% CI], 1.98 [1.83-2.14] versus 1.68 [1.58-1.80] per mmol/L; Pinteraction=0.0007). In TG-adjusted analysis, large and medium but not small TG-rich lipoprotein particles were associated with higher T2DM incidence for successively lower 40-single-nucleotide polymorphism TG genetic risk score tertiles, Pinteraction=0.013, 0.012, and 0.620 across tertiles, respectively. Conclusions- Our results confirm the previous observations of the paradoxical associations of TG with T2DM while focusing attention on the larger TG-rich lipoprotein particle subfractions, suggesting their importance in clinical profiling of T2DM risk.

The small dense LDL particle/large buoyant LDL particle ratio is associated with glucose metabolic status in pregnancy

BackgroundThe lipoprotein subfraction particle profile can be used to improve clinical assessments of cardiovascular disease risk and contribute to early detection of atherogenic dyslipidemia. Lipid alterations in gestational diabetes have been extensively studied, but the results have been inconsistent. Here, we investigated serum lipoprotein subfraction particle levels and their association with glucose metabolic status in pregnancy.MethodsTwenty-eight pregnant women with gestational diabetes and 56 pregnant women with normal glucose tolerance matched for body mass index were enrolled in this study. We assessed fasting serum lipid concentrations and lipoprotein subfraction particle levels in participants between 24 and 28 weeks of gestation.ResultsThe level of low-density lipoprotein (LDL) cholesterol was significantly lower in women with gestational diabetes than in those with normal glucose tolerance, but the triglyceride and high-density lipoprotein (HDL) cholesterol levels of the two groups were similar. Lipoprotein particle analysis showed that very-low-density lipoprotein (VLDL) particle number and the small dense LDL particle/large buoyant LDL particle (sdLDL-P/lbLDL-P) ratio were significantly higher in women with gestational diabetes than in those with normal glucose tolerance (P = 0.013 and P = 0.015, respectively). In multivariate analysis, fasting glucose was independently and positively associated with sdLDL-P/lbLDL-P ratio even after adjustment for maternal age, gestational weight gain, BMI and LDL cholesterol (standardized Beta = 0.214, P = 0.029).ConclusionsThe sdLDL-P/lbLDL-P ratio is higher in GDM compared with non-diabetic pregnant women, and positively and independently associated with fasting glucose in pregnant women.

Comparison of four methods of analysis of lipoprotein particle subfractions for their association with angiographic progression of coronary artery disease

BackgroundCompare gradient gel electrophoresis (GGE), vertical auto profile ultracentrifugation (VAP-II), nuclear magnetic resonance spectroscopy (NMR), and ion mobility for their ability to relate low- (LDL), intermediate- (IDL), very-low-density (VLDL) and high-density lipoprotein (HDL) subfraction concentrations to atherosclerotic progression. Methods and resultsRegression analyses of 136 patients who received baseline and follow-up coronary angiographies and subfraction measurements by all four methods in the HDL Atherosclerosis Treatment Study. Prior analyses have shown that the intervention primarily affected disease progression in proximal arteries with <30% stenoses at baseline.Three-year increases in percent stenoses were consistently associated with higher on-study plasma concentrations of small, dense LDL as measured by GGE (LDLIIIb, P = 10−6; LDLIVa, P = 0.006; LDLIVb, P = 0.02), VAP-II (LDL4, P = 0.002), NMR (small LDL, P = 0.001), and ion mobility (LDL IIb, P = 0.04; LDLIIIa, P = 0.002; LDLIIIb, P = 0.0007; LDLIVa, P = 0.05). Adjustment for triglycerides, HDL-cholesterol, and LDL-cholesterol failed to eliminate the statistical significance for on-study GGE estimated LDLIIIb (P = 10−5) and LDLIVa (P = 0.04); NMR-estimated small LDL (P = 0.03); or ion mobility estimated large VLDL (P = 0.02), LDLIIIa (P = 0.04) or LDLIIIb (P = 0.02). All methods show that the effects were significantly greater for the on-study than the baseline small, dense LDL concentrations, thus establishing that the values concurrent to the progression of disease were responsible. The rate of disease progression was also related to individual VLDL, IDL, and HDL subclasses to differing extents among the various analytic methods. ConclusionFour methodologies confirm the association of small, dense LDL with greater coronary atherosclerosis progression, and GGE, NMR, and ion mobility confirm that the associations were independent of standard lipid measurements.Clinical Trial Registration: clinicaltrials.gov/ct2/show/NCT00000553.

Abstract 397: Changes in Lipoprotein Subfraction Concentrations After Treatment with the Cholesteryl Ester Transfer Protein Inhibitor Anacetrapib Alone or in Combination with Atorvastatin

Background Anacetrapib (ANA), a cholesteryl ester transfer protein inhibitor, has been shown to increase plasma HDL cholesterol and reduce LDL cholesterol, both as monotherapy and in combination with atorvastatin (ATORVA). The effects of these regimens on lipoprotein subfractions have not been reported. Methods ApoB-containing lipoprotein particle subfractions were measured by ion mobility in a post-hoc analysis of baseline and 8 week on-treatment samples from 464 dyslipidemic participants who had been randomized to placebo, ATORVA 20 mg/d, or to ANA at several doses administered with and without ATORVA ( clinicaltrials.gov NCT00325455 ). Results ANA (combined 150 mg/d and 300 mg/d groups) significantly reduced total LDL particle concentration by 51%, and levels of large, medium, and small LDL particles (LDL 1, 2, and 3a) by 43-72% but significantly increased levels of the less abundant cholesterol-depleted very small LDL 4a and 4b species by ~64%. In contrast, ATORVA, despite producing a similar reduction of total LDL particle concentration (50%), reduced the levels of all LDL particle subfractions, although the magnitude was smaller for LDL 4a, with a much smaller non-significant reduction for LDL 4b. Compared with ANA monotherapy, results for combination treatment were generally consistent with additive effects. Notably, for individuals with baseline triglyceride (TG) above the median (&gt;154 mg/dL), increases of very small LDL after ANA were markedly attenuated, whereas after ATORVA there was greater reduction of LDL 4a in the higher TG group. Conclusions Similar reductions of LDL levels after ANA or ATORVA were not associated with comparable effects on all LDL particle subfractions, and neither drug was effective in lowering levels of the smallest LDL particles. Assessment of the clinical impact of the effects of ANA on LDL subfractions, and the differential changes in very small LDL in individuals with normal versus elevated TG, await cardiovascular outcome data from REVEAL.

Multidimensional profiling of plasma lipoproteins by size exclusion chromatography followed by reverse-phase protein arrays

The composition of lipoproteins and the association of proteins with various particles are of much interest in the context of cardiovascular disease. Here, we describe a technique for the multidimensional analysis of lipoproteins and their associated apolipoproteins. Plasma is separated by size exclusion chromatography (SEC), and fractions are analyzed by reverse-phase arrays. SEC fractions are spotted on nitrocellulose slides and incubated with different antibodies against individual apolipoproteins or antibodies against various apolipoproteins. In this way, tens of analytes can be measured simultaneously in 100 μl of plasma from a single SEC separation. This methodology is particularly suited to simultaneous analysis of multiple proteins that may change their distribution to lipoproteins or alter their conformation, depending on factors that influence circulating lipoprotein size or composition. We observed changes in the distribution of exchangeable apolipoproteins following addition of recombinant apolipoproteins or interaction with exogenous compounds. While the cholesteryl ester transfer protein (CETP)-dependent formation of pre-β-HDL was inhibited by the CETP inhibitors torcetrapib and anacetrapib, it was not reduced by the CETP modulator dalcetrapib. This finding was elucidated using this technique.

Cardiorespiratory fitness and metabolic risk factors in obesity

An increase in cardiorespiratory fitness (CRF) through exercise training appears to partly ameliorate the health hazards of obesity and a number of mechanisms might explain the potential benefits. We review recent evidence about the relationships between CRF, exercise training and metabolic risk factors in obesity. Epidemiological data have shown that the anti-inflammatory effects of exercise could be an important mechanism in explaining cardio-protective effects of physical activity. Emerging evidence suggests that exercise training reduces markers of inflammation and improves glucose control in obesity, independent of weight loss. Novel mechanisms appear to involve exercise-induced changes in CD14+CD16+ cell populations, expression of toll-like receptors, and key changes in the metabolic regulation of visceral white adipose tissue. Other promising recent research has focused on exercise-induced signalling pathways governing glucose metabolism, such as insulin receptor substrate and Akt substrate. Using novel imaging techniques, studies have demonstrated exercise-induced improvements in lipoprotein subfraction particle size, and reduction in visceral adipose tissue and liver fat, independent of weight loss. These effects appear to be mostly restricted to interventions consisting of relatively high doses of exercise or exercise combined with calorie restriction, although further work is required to elucidate the dose-response relationships. Physical activity and the pursuit of physical fitness are important in the treatment of obesity because exercise training can improve a number of metabolic risk factors independent of weight loss. Thus exercise can provide important health benefits irrespective of weight loss in obese and overweight individuals.

Endurance exercise training raises high-density lipoprotein cholesterol and lowers small low-density lipoprotein and very low-density lipoprotein independent of body fat phenotypes in older men and women

Endurance exercise training improves plasma lipoprotein and lipid profiles and reduces cardiovascular disease risk. However, the effect of endurance exercise training, independent of diet and body fat phenotypes, on plasma lipoprotein subfraction particle concentration, size, and composition as measured by nuclear magnetic resonance (NMR) spectroscopy is not known. We hypothesized that 24 weeks of endurance exercise training would independently improve plasma lipoprotein and lipid profiles as assessed by both conventional and novel NMR measurement techniques. One hundred sedentary, healthy 50- to 75-year-olds following a standardized diet were studied before and after 24 weeks of aerobic exercise training. Lipoprotein and lipid analyses, using both conventional and NMR measures, were performed at baseline and after 24 weeks of exercise training. Relative and absolute maximum oxygen consumption increased 15% with exercise training. Most lipoprotein and lipid measures improved with 24 weeks of endurance exercise training, and these changes were consistently independent of baseline body fat and body fat changes with training. For example, with exercise training, total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C) decreased significantly (2.1 ± 1.8 mg/dL, P = .001; −17 ± 3.5 mg/dL, P < .0001; and −0.7 ± 1.7 mg/dL, P < .0001, respectively), and high-density lipoprotein cholesterol subfractions (HDL 3-C and HDL 2-C) increased significantly (1.9 ± 0.5 mg/dL, P = .01, and 1.2 ± 0.3 mg/dL, P = .02, respectively). Particle concentrations decreased significantly for large and small very low-density lipoprotein particles (−0.7 ± 0.4 nmol/L, P < .0001, and −1.1 ± 1.7 nmol/L, P < .0001, respectively), total, medium, and very small LDL particles (−100 ± 26 nmol/L, P = .01; −26 ± 7.0 nmol/L, P = .004; and −103 ± 27 nmol/L, P = .02, respectively), and small HDL particles (−0.03 ± 0.4 μmol/L, P = .007). Mean very low-density lipoprotein particle size also decreased significantly (−1.7 ± 0.9 nm, P < .0001) and mean HDL particle size increased significantly with exercise training (0.1 ± 0.0 nm, P = .04). These results show that 24 weeks of endurance exercise training induced favorable changes in plasma lipoprotein and lipid profiles independent of diet and baseline or change in body fat.