Medium HDL Particles Research Articles

High-density lipoprotein metrics during midlife and future subclinical atherosclerosis in women: the SWAN HDL study.

The clinical utility of high-density lipoprotein cholesterol (HDL-C) in risk classification is limited, especially in midlife women. Novel metrics of HDL may better reflect this risk. We clustered a comprehensive profile of HDL metrics into favorable and unfavorable clusters and assessed how these two clusters are related to future subclinical atherosclerosis (carotid intima media thickness [cIMT], interadventitial diameter [IAD], and carotid plaque presence) in midlife women. Four hundred sixty-one women (baseline age: 50.4 [2.7] years; 272 White, 137 Black, 52 Chinese) from the Study of Women's Health Across the Nation HDL ancillary study who had baseline measures of HDL cholesterol efflux capacity (HDL-CEC), lipid contents (HDL-phospholipids [HDL-PL] and HDL triglycerides [HDL-Tg]), and HDL particle (HDL-P) distribution and size, followed by carotid ultrasound (average 12.9 [SD: 2.6] years later), were included. Using latent cluster analysis, women were clustered into a favorable (high HDL-CEC, HDL-PL, large and medium HDL-P, less HDL-Tg and small HDL-P, larger size) or an unfavorable HDL cluster (low HDL-CEC, HDL-PL, large and medium HDL-P, more HDL-Tg, and small HDL-P, smaller size) and then linked to future subclinical atherosclerosis using linear or logistic regression. The favorable HDL cluster was associated with lower cIMT, IAD, and odds of carotid plaque presence. These associations were attenuated by body mass index, except in Chinese women where the association with cIMT persisted (0.72 [0.63, 0.83]). The association between favorable HDL clusters and a better postmenopausal subclinical atherosclerosis profile is largely explained by body mass index; however, racial/ethnic differences may exist.

Total carotene plasma concentrations are inversely associated with atherosclerotic plaque burden: A post-hoc analysis of the DIABIMCAP cohort

Atherosclerosis is the major risk factor for cardiovascular disease (CVD), the first cause of death worldwide. Chronic low-grade inflammation and a sustained oxidative milieu are causatively related to atherosclerosis onset and progression, and therefore, dietary patterns rich in bioactive compounds with anti-inflammatory and antioxidant activities might likely contribute to revert or slowing the progression of atherosclerosis. The aim of this study is to analyse the association between fruit and vegetables intake, quantitatively measured through carotene plasma concentrations, and atherosclerotic burden, as a surrogate biomarker of CVD, in free-living subjects from the DIABIMCAP cohort study. The 204 participants of the DIABIMCAP Study cohort (Carotid Atherosclerosis in Newly Diagnosed Type 2 Diabetic Individuals, ClinicalTrials.gov Identifier: NCT01898572), were included in this cross-sectional study. Total, α-, and β-carotenes were quantified by HPLC-MS/MS. Lipoprotein analysis in serum was performed by 2D- 1H NMR- DOSY, and atherosclerosis and intima media thickness (IMT) were measured through standardized bilateral carotid artery ultrasound imaging. Subjects with atherosclerosis (n=134) had lower levels of large HDL particles than subjects without atherosclerosis. Positive associations were found between α-carotene and both large and medium HDL particles, and inverse associations were found between β- and total carotene, and VLDL and its medium/small particles. Subjects with atherosclerosis presented significantly lower plasma concentrations of total carotene compared with subjects without atherosclerosis. Plasma concentrations of carotene decreased as the number of atherosclerotic plaques increased, although after multivariate adjustment, the inverse association between β- and total carotene with plaque burden remained significant only in women. A diet rich in fruit and vegetables results in higher plasmatic carotene concentrations, which are associated with a lesser atherosclerotic plaque burden.

Lower levels of small HDL particles associated with increased infectious disease morbidity and mortality: a population-based cohort study of 30 195 individuals.

Low levels of HDL cholesterol have been associated with increased risk of infectious disease morbidity and mortality. Nuclear magnetic resonance (NMR) spectroscopy permits the measurement of HDL particle count and allows further subclassification according to particle size. We tested the hypothesis that low number of different HDL subfractions is associated with increased infectious disease morbidity and mortality. HDL particle counts were measured using NMR spectroscopy in 30 195 individuals aged 22-99 years from the Copenhagen General Population Study. Using multiple-event Cox regression and cause-specific hazard models, we assessed risk of hospitalizations due to infection and infectious disease-related death, from 2003 through 2018. During follow-up, 9303 individuals had one or more infectious disease events, and 1558 experienced infectious disease-related death. In multifactorial adjusted analyses, low number of small and medium HDL particles was associated with increased risk of any infection and infectious disease-related death, whereas low number of large and extra-large HDL particles was not. A very high number of small and medium HDL particles was also associated with increased risk of any infection, but not with infectious disease-related death. For small and medium HDL particles and compared to individuals in the 91-95th percentile, hazard ratios (HRs) in individuals in the lowest percentile were 2.31 (95% confidence interval: 1.75, 3.05) for any infection and 3.23 (2.08, 5.02) for infectious disease-related death. For the highest percentile, corresponding HRs were 1.36 (1.07, 1.74) and 1.06 (0.57, 1.98), respectively. Individuals in the lowest percentile had increased risk of pneumonia (HR: 1.86; 95% confidence interval: 1.30, 2.65), sepsis (2.17; 1.37, 3.35), urinary tract infection (1.76; 1.17, 2.63), skin infection (1.87; 1.24, 2.81), gastroenteritis (1.78; 1.01, 3.16), and other infections (2.57; 1.28, 5.16). Low number of the small HDL particles was associated with increased infectious disease morbidity and mortality.

Causal effects of genetically predicted type 2 diabetes mellitus on blood lipid profiles and concentration of particle-size-determined lipoprotein subclasses: A two-sample Mendelian randomization study.

BackgroundObservational studies have shown inconsistent results of the associations between type 2 diabetes mellitus (T2DM) and blood lipid profiles, while there is also a lack of evidence from randomized controlled trials (RCTs) for the causal effects of T2DM on blood lipid profiles and lipoprotein subclasses.ObjectivesOur study aimed at investigating the causal effects of T2DM on blood lipid profiles and concentration of particle-size-determined lipoprotein subclasses by using the two-sample Mendelian randomization (MR) method.MethodsWe obtained genetic variants for T2DM and blood lipid profiles including high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglycerides (TG), and total cholesterol (TC) from international genome-wide association studies (GWASs). Two-sample MR method was applied to explore the potential causal effects of genetically predicted T2DM on blood lipid profiles based on different databases, respectively, and results from each MR analysis were further meta-analyzed to obtain the summary results. The causal effects of genetically predicted T2DM on the concentration of different subclasses of lipoproteins that are determined by particle size were also involved in MR analysis.ResultsGenetically predicted 1-unit higher log odds of T2DM had a significant causal effect on a higher level of TG (estimated β coefficient: 0.03, 95% confidence interval [CI]: 0.00 to 0.06) and lower level of HDL-C (estimated β coefficient: −0.09, 95% CI: −0.11 to −0.06). The causality of T2DM on the level of TC or LDL-C was not found (estimated β coefficient: −0.01, 95% CI: −0.02 to 0.01 for TC and estimated β coefficient: 0.01, 95% CI: −0.01 to 0.02 for LDL-C). For different sizes of lipoprotein particles, 1-unit higher log odds of T2DM was causally associated with higher level of small LDL particles, and lower level of medium HDL particles, large HDL particles, and very large HDL particles.ConclusionEvidence from our present study showed causal effects of T2DM on the level of TG, HDL-C, and concentration of different particle sizes of lipoprotein subclasses comprehensively, which might be particularly helpful in illustrating dyslipidemia experienced by patients with T2DM, and further indicate new treatment targets for these patients to prevent subsequent excessive cardiovascular events from a genetic point of view.

Healthy lifestyle, metabolomics and incident type 2 diabetes in a population-based cohort from Spain

BackgroundThe contribution of metabolomic factors to the association of healthy lifestyle with type 2 diabetes risk is unknown. We assessed the association of a composite measure of lifestyle with plasma metabolite profiles and incident type 2 diabetes, and whether relevant metabolites can explain the prospective association between healthy lifestyle and incident type 2 diabetes.MethodsA Healthy Lifestyle Score (HLS) (5-point scale including diet, physical activity, smoking status, alcohol consumption and BMI) was estimated in 1016 Hortega Study participants, who had targeted plasma metabolomic determinations at baseline examination in 2001–2003, and were followed-up to 2015 to ascertain incident type 2 diabetes.ResultsThe HLS was cross-sectionally associated with 32 (out of 49) plasma metabolites (2.5% false discovery rate). In the subset of 830 participants without prevalent type 2 diabetes, the rate ratio (RR) and rate difference (RD) of incident type 2 diabetes (n cases = 51) per one-point increase in HLS was, respectively, 0.69 (95% CI, 0.51, 0.93), and − 8.23 (95% CI, − 16.34, − 0.13)/10,000 person-years. In single-metabolite models, most of the HLS-related metabolites were prospectively associated with incident type 2 diabetes. In probit Bayesian Kernel Machine Regression, these prospective associations were mostly driven by medium HDL particle concentration and phenylpropionate, followed by small LDL particle concentration, which jointly accounted for ~ 50% of the HLS-related decrease in incident type 2 diabetes.ConclusionsThe HLS showed a strong inverse association with incident type 2 diabetes, which was largely explained by plasma metabolites measured years before the clinical diagnosis.

Abstract P105: Associations Of Subclasses, Content And Function Metrics Of High-density Lipoprotein With Carotid Intima-media Thickness In Women Transitioning Through Menopause Swan Hdl And Swan Heart Studies

Objective: Higher levels of high-density lipoprotein cholesterol (HDL-C) may not always be cardio-protective in midlife women. Novel metrics of HDL including nuclear magnetic resonance (NMR) spectroscopy subclasses (large, medium and small HDL particles (HDL-P), and size), HDL content of phospholipids (HDL-PL) and triglycerides (HDL-Tg), and HDL function as measured by cholesterol efflux capacity (HDL-CEC) show strong associations with cardiovascular disease (CVD) risk beyond HDL-C. Women experience increases in carotid Intima-media thickness (cIMT), a subclinical measure of atherosclerosis, over the menopause transition. Associations of novel metrics of HDL with cIMT have not been well characterized in midlife women. Our objective was to assess the associations of HDL subclasses, HDL-PL, HDL-Tg, and HDL-CEC with cIMT and to determine whether these associations vary by age at menopause. Design: We assessed 303 women (at baseline: age 51.0 ± 2.8 years; 67.8% White and 32.2% Black; 56.6% Pre-/Early perimenopausal) who had HDL metrics and cIMT measured once (N=37 [12%]) or twice (N=266 [88%]) over the menopause transition. Age at menopause was observed prospectively among 73% of women (defined as no menses for 12 consecutive months) and imputed among the rest. Linear mixed effect models were used to individually assess the association of each HDL metric with cIMT, and to test whether the association varied by age at menopause (<50, 50-53, >53 years old). Final models were adjusted for race, education, and time varying: age, systolic blood pressure, body mass index, menopausal status, triglycerides, low density lipoprotein cholesterol and HDL-C. Results: In unadjusted analyses, higher concentrations of large HDL-P, medium HDL-P, HDL-PL, and HDL-CEC, and larger HDL size, and lower concentrations of small HDL-P were associated with lower cIMT; all p <0.05. In final models, only associations of medium HDL-P (p=0.008) and HDL-PL (p=0.005) with cIMT remained statistically significant. Age at menopause modified associations of HDL-Tg with cIMT in both unadjusted and final models (p=0.05 for both); in the final model, per 1 SD unit increase in HDL-Tg, women with age at menopause >53 had thicker cIMT(β(SE): 6.72(6.27) μm) than those with age at menopause <50 (β(SE): -17.88(8.48) μm), p for comparison=0.01. Conclusions: In midlife women, higher concentrations of medium HDL-P and greater content of HDL phospholipids were associated with thinner cIMT beyond traditional CVD risk factors including HDL-C. Associations of HDL triglycerides content with thicker cIMT was more pronounced in women who reached menopause at older ages. Findings support utilizing other metrics of HDL rather than HDL-C to better characterize CVD risk in midlife women.

Compositional Features of HDL Particles Interact with Albuminuria to Modulate Cardiovascular Disease Risk.

Lipoproteins containing apolipoprotein B modify associations of elevated urinary albumin excretion (UAE) with cardiovascular disease (CVD). Additionally, it is known that elevated UAE alters high-density lipoprotein functionality. Accordingly, we examined whether HDL features might also modify UAE-associated CVD. Multivariable Cox proportional-hazards modeling was performed on participants of the PREVEND (Prevention of Renal and Vascular Endstage Disease) study at the baseline screening with standard lipid/lipoprotein analyses and, three-to-four years later (second screen), with nuclear magnetic resonance lipoprotein analyses focusing on HDL parameters including HDL particle (HDL-P) and apolipoprotein A-I concentrations. These were used with UAE and derived measures of HDL apoA-I content (apoA-I/HDL-C and apoA-I/HDL-P) in risk models adjusted for gender, age, apoB, diabetes, past CVD history, CRP and GFR. Interaction analysis was also performed. Baseline screening revealed significant associations inverse for HDL-C and apoA-I and direct for apoA-I/HDL-C. The second screening demonstrated associations inverse for HDL-P, large HDL-P, medium HDL-P, HDL size, and apoA-I/HDL-P. Significant interactions with UAE included apoA-I/HDL-C at the baseline screening, and apoA-I/HDL-P and medium HDL-P but not apoA-I/HDL-C at the second screening. We conclude that features of HDL particles including apoA-I/HDL-P, indicative of HDL apoA-I content, and medium HDL-P modify associations of elevated UAE with CVD risk.

Abstract P101: Menopause and its Related Endogenous Sex Hormone Alterations are Associated with Changes in Function and Subclasses of High-density Lipoprotein in Women at Midlife

Objective: Growing evidence challenges the cardioprotective effects of high-density lipoprotein-cholesterol (HDL-C) in postmenopausal women. HDL particle size and concentration are heterogeneous and HDL-C only measures the cholesterol content of all HDL particles. Therefore, HDL-C does not necessarily reflect HDL subclasses or functionality, which may be more important in predicting CVD risk. Our main objective was to characterize HDL subclasses and functional alterations over menopause and to evaluate their associations with changes in estradiol (E2) and follicle stimulating hormone (FSH), cardinal hormonal markers of menopause. Methods: Participants were drawn from the Study of Women’s Health Across the Nation (SWAN) at the Pittsburgh site. The women had stored blood specimens at two time points; one before and one after they reached menopause. HDL particle concentration and size using calibrated ion mobility analyses and HDL cholesterol efflux capacity (HDL-CEC) with radiolabeled J774 macrophages were measured at the two time points. None of the study participants were on lipid lowering medications or hormone therapy. Results: The study included 50 women (66% White and 34% Black), who were 47 (45, 49) years old (median (Q1, Q3)) and were either pre- (38%) or early peri-menopause (62%) at the first time point. At the second time point, all participants were postmenopausal with a median (Q1, Q3) time since their final menstrual period of 2.14 (1.55, 3.41) years. After menopause, women had significantly higher concentrations of total and large HDL particles, and smaller sizes of medium and small HDL particles (all P<0.05), independent of race and change in age. HDL-CEC was significantly higher after menopause. Independent of age and race, larger declines in E2 were correlated with a more atherogenic changes (smaller increases in large HDL particles and larger increases in small HDL particles concentrations, P<0.05). Additionally, greater rises in FSH were correlated with bigger reductions in sizes of large and medium HDL particles (P<0.05). Conclusions: Within a median of 2.14 years of menopause, an improvement in HDL-CEC and significant alterations in HDL particle subclasses were observed. Whether patterns of these alterations change further in late postmenopause and how they relate to atherosclerotic risk are not known. The reported changes in HDL metrics over menopause warrant further evaluation of their potential risk on CVD after menopause.

Lipoprotein particles and size, total and high molecular weight adiponectin, and leptin in relation to incident coronary heart disease among severely obese postmenopausal women: The Women's Health Initiative Observational Study

BackgroundWe hypothesized that higher concentrations of LDL particles (LDL-P) and leptin, and lower concentrations of HDL particles (HDL-P), and total and high molecular weight (HMW) adiponectin, would predict incident coronary heart disease (CHD) among severely obese postmenopausal women. MethodsIn a case–cohort study nested in the Women's Health Initiative Observational Study, we sampled 677 of the 1852 white or black women with body mass index (BMI) ≥40kg/m2 and no prevalent cardiovascular disease (CVD), including all 124 cases of incident CHD over mean 5.0year follow-up. Biomarkers were assayed on stored blood samples. ResultsIn multivariable-adjusted weighted Cox models, higher baseline levels of total and small LDL-P, and lower levels of total and medium HDL-P, and smaller mean HDL-P size were significantly associated with incident CHD. In contrast, large HDL-P levels were inversely associated with CHD only for women without diabetes, and higher total and HMW adiponectin levels and lower leptin levels were associated with CHD only for women with diabetes. Higher total LDL-P and lower HDL-P were associated with CHD risk independently of confounders including CV risk factors and other lipoprotein measures, with adjusted HR (95% CIs) of 1.55 (1.28, 1.88) and 0.70 (0.57, 0.85), respectively, and similar results for medium HDL-P. ConclusionsHigher CHD risk among severely obese postmenopausal women is strongly associated with modifiable concentrations of LDL-P and HDL-P, independent of diabetes, smoking, hypertension, physical activity, BMI and waist circumference. General significanceSeverely obese postmenopausal women should be considered high risk candidates for lipid lowering therapy.

Abstract P291: Adipocytokines, Lipoproteins & Obesity Among Black & White Postmenopausal Women from the Women’s Health Initiative

Background: Despite the prevalence of severe obesity, particularly among women and African-American women, there is little data on CV risk factor differences across the BMI spectrum including extreme obesity. Methods: Participants were 1200 black and white postmenopausal women sampled from the Women’s Health Initiative Observational Study according to BMI categories and waist circumference tertiles: 300 black and 300 white women with BMI 40-65 kg/m 2 and 75 black and 75 white women in BMI categories 8.5-<25, 25-<30, 30-<35 and 35-<40 kg/m 2 . Using stored baseline serum, total and high molecular-weight (HMW) adiponectin, leptin, ghrelin and insulin were measured by immunoassay; plasma lipoproteins and subclasses were measured by NMR spectroscopy. Race-ethnicity differences were tested in linear regression models adjusted for age, diabetes, BMI, waist, hip, hormone therapy and lipid-lowering medication. Results: Compared with white women, black women had lower levels of total and HMW adiponectin and ghrelin, and higher levels of insulin and leptin. Despite similar levels of total LDL particles (LDL-P), black women had lower levels of small LDL-P and higher levels of large LDL-P and larger mean LDL size. Levels of large HDL particles (HDL-P) and small HDL-P were also similar for black and white women, but black women had lower levels of total and medium HDL-P and larger mean HDL particle size. Black women also had lower levels of total, large, medium and small VLDL particles (VLDL-P) which increased little across BMI category, such that mean levels of total or large VLDL-P among black women with BMI≥ 40 kg/m 2 were lower than white women of normal BMI (<25 kg/m 2 ) (Figure). Among white, but not black women, total LDL-P was higher and total HDL-P was lower with higher BMI category (Figure). Conclusions: Among postmenopausal women of similar BMI and waist circumference, black women have lower levels of ghrelin and total and HMW adiponectin, but better lipoprotein levels that are less related to obesity compared with white women.

Abstract P066: Associations Between Coronary Artery Calcium and HDL Particle Characteristics in MESA Participants with Very-High Levels of HDL Cholesterol (>80mg/dL)

Despite the inverse association between HDL-C and CHD risk across HDL-C values of 20-80mg/dL CHD risk persists in people with very-high levels of HDL-C (> 80mg/dL). These risks may be explained by traditional risk factors and by structural and functional polymorphisms in HDL particles in people with HDL-C >80mg/dL. In Multi-Ethnic Study of Atherosclerosis (MESA) participants with HDL-C >80mg/dL we assessed differences in traditional risk factors and NMR-spectroscopy-derived (NMR) HDL particle characteristics between individuals with and without CAC. We included MESA participants with HDL-C values > 80mg/dL (not on niacin, fibrates, or statins), traditional risk factor and CAC data at baseline exam. We examined the associations between HDL-C, NMR data (HDL particle number, particle size, and the concentrations of large, medium and small-HDL particles and in post hoc analysis ratios of particle size concentrations) and baseline CAC > 0 in separate logistic regression models. We included 269 participants in the analysis, 105 had prevalent CAC. Individuals with CAC>0 were older, had higher fasting blood glucose, higher carotid IMT; there were more men, more people taking blood pressure lowering medications, and more with diabetes as well. There were no significant differences in mean values of traditional lipid fractions between groups, however individuals with CAC>0 had a lower concentration of medium-sized HDL particles and a higher ratio of large to medium HDL particle concentration. There were no significant associations between NMR HDL characteristics and CAC> 0 after multivariable adjustment. In post hoc analysis there was a significant adjusted association between the ratio of large to medium sized HDL particle concentration and the presence of CAC>0 (OR [95% CI]: 1.86 [1.15, 3.00]). In conclusion, participants with CAC and very-high HDL-C had a higher burden of traditional risk factors. However, the ratio of particle size concentrations may help differentiate those with HDL>80mg/dL who are at risk for CAC as well.

Weight change and lipoprotein particle concentration and particle size: A cohort study with 6.5-year follow-up

ObjectiveObesity and overweight are related to unfavourable lipoprotein subclass profiles. Here we studied the relation between weight change and lipoprotein particle concentrations and sizes in a general population cohort in a longitudinal setting. MethodsThe cohort included 683 adults with a 6.5-year follow-up. Lipoprotein particle subclasses and mean particle sizes of VLDL, LDL, and HDL were measured by nuclear magnetic resonance spectroscopy. ResultsDuring the follow-up period, a weight loss of at least 5% was associated with decreased particle concentrations of all apoB-containing subclasses and increased concentrations of large HDL particles. Coherently, weight gain (≥5%) was associated with increases in all apoB-containing subclasses and decreases in total and medium HDL particle concentrations. The relatively largest increase occurred for large HDL particle concentration (24.1%, 95% CI 15.8–32.5) in weight loss and for large VLDL particle concentration (33.0%, 19.6–46.4) in weight gain. Weight change correlated positively with changes in apoB-containing lipoprotein particle concentrations and also with the change in average VLDL particle size. Negative correlations were found between weight change and the change in average LDL (r = −0.10) and HDL (r = −0.32) particle size, but not between weight change and total HDL particle concentration. ConclusionModerate weight loss is related to favourable and weight gain to unfavourable changes in lipoprotein subclass profiles. These population level findings underline the importance of weight control as a modifier of cardiovascular risk factors.

HDL Measures, Particle Heterogeneity, Proposed Nomenclature, and Relation to Atherosclerotic Cardiovascular Events

A growing body of evidence from epidemiological data, animal studies, and clinical trials supports HDL as the next target to reduce residual cardiovascular risk in statin-treated, high-risk patients. For more than 3 decades, HDL cholesterol has been employed as the principal clinical measure of HDL and cardiovascular risk associated with low HDL-cholesterol concentrations. The physicochemical and functional heterogeneity of HDL present important challenges to investigators in the cardiovascular field who are seeking to identify more effective laboratory and clinical methods to develop a measurement method to quantify HDL that has predictive value in assessing cardiovascular risk. In this report, we critically evaluate the diverse physical and chemical methods that have been employed to characterize plasma HDL. To facilitate future characterization of HDL subfractions, we propose the development of a new nomenclature based on physical properties for the subfractions of HDL that includes very large HDL particles (VL-HDL), large HDL particles (L-HDL), medium HDL particles (M-HDL), small HDL particles (S-HDL), and very-small HDL particles (VS-HDL). This nomenclature also includes an entry for the pre-β-1 HDL subclass that participates in macrophage cholesterol efflux. We anticipate that adoption of a uniform nomenclature system for HDL subfractions that integrates terminology from several methods will enhance our ability not only to compare findings with different approaches for HDL fractionation, but also to assess the clinical effects of different agents that modulate HDL particle structure, metabolism, and function, and in turn, cardiovascular risk prediction within these HDL subfractions.

Algal Docosahexaenoic Acid Affects Plasma Lipoprotein Particle Size Distribution in Overweight and Obese Adults1–3

Fish oils containing both EPA and DHA have been shown to have beneficial cardiovascular effects, but less is known about the independent effects of DHA. This study was designed to examine the effects of DHA on plasma lipid and lipoprotein concentrations and other biomarkers of cardiovascular risk in the absence of weight loss. In this randomized, controlled, double-blind trial, 36 overweight or obese adults were treated with 2 g/d of algal DHA or placebo for 4.5 mo. Markers of cardiovascular risk were assessed before and after treatment. In the DHA-supplemented group, the decrease in mean VLDL particle size (P ≤ 0.001) and increases in mean LDL (P ≤ 0.001) and HDL (P ≤ 0.001) particle sizes were significantly greater than changes in the placebo group. DHA supplementation also increased the concentrations of large LDL (P ≤ 0.001) and large HDL particles (P = 0.001) and decreased the concentrations of small LDL (P = 0.009) and medium HDL particles (P = 0.001). As calculated using NMR-derived data, DHA supplementation reduced VLDL TG (P = 0.009) and total TG concentrations (P = 0.006). Plasma IL-10 increased with DHA supplementation to a greater extent than placebo (P = 0.021), but no other significant changes were observed in glucose metabolism, insulin sensitivity, blood pressure, or markers of inflammation with DHA. In summary, DHA supplementation resulted in potentially beneficial changes in some markers of cardiometabolic risk, whereas other markers were unchanged.

NMR identifies atherogenic lipoprotein abnormalities in early diabetic nephropathy that are unrecognized by conventional analysis

Lipoprotein abnormalities are likely contributors to the high risk of cardiovascular disease in the chronic kidney disease (CKD) population, although information is limited. Specifically, little is known about lipoprotein abnormalities during the early stages of diabetic kidney disease. The aim of this study was to investigate the relationship between lipoproteins and early manifestations of CKD in the 517 Type 2 diabetes mellitus (T2DM) patients who participated in the Insulin Resistance Atherosclerosis Study (IRAS). Lipoprotein abnormalities were measured by conventional lipid analysis, nuclear magnetic resonance (NMR) spectroscopy, gel gradient electrophoresis (GE), immunoprecipitation (IP), and ELISA. We grouped the cases into albumin to creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) quartiles. In the conventional lipid analysis, triglycerides (TG) correlated directly with ACR and inversely with eGFR quartiles (p = 0.01), while LDL, HDL cholesterol did not correlate with change in ACR or eGFR. ACR was directly associated with apoB, total VLDL, medium VLDL, IDL and small LDL particle concentrations (p < or = 0.03), and inversely with large LDL particles (p = 0.01) and LDL size (p = 0.008). Estimated GFR quartiles were inversely associated with total VLDL, small VLDL, IDL, and medium HDL particles (p < or = 0.01). In subjects with T2DM, mild albuminuria and reduction in eGFR were associated with numerous atherogenic lipoprotein abnormalities that were detected by the combination of NMR spectroscopy, gel gradient electrophoresis, immunoprecipitation and ELISA but not by the standard clinical lipid analysis.