Medium High-density Lipoprotein Particles Research Articles

New perspectives on the high-density lipoprotein system and its role in the prevention and treatment of atherosclerotic cardiovascular disease.

The causal role of high-density lipoprotein (HDL) in atherosclerotic cardiovascular disease (CVD) remains debated. Considering recent evidence, the purpose of this review is to a provide a focused update and new perspectives on HDL and CVD. A Mendelian randomization study demonstrated an increased risk of CVD when HDL-cholesterol was predominantly transported in larger HDL particles and a decreased risk of CVD when HDL-cholesterol was predominantly transported in smaller HDL particles. Moreover, another Mendelian randomization study demonstrated that concentration and content of medium HDL particles is associated with CVD. A Mendelian randomization study that utilized stratified analyses demonstrated that individuals with HDL-cholesterol 50 mg/dl or less were at increased risk of CVD. Lastly, the AEGIS-II trial demonstrated that CSL112, a human apolipoprotein A-I that increases cholesterol efflux, did not significantly reduce cardiovascular events in patients at very high risk. Exploratory analyses showed that patients treated with CSL112 had numerically lower rates of cardiovascular events. Qualitative markers of HDL may be causally related to CVD. There is a need for ongoing research into HDL therapeutics that promote the biological properties of HDL. The optimal cohort or disease state that will benefit from these therapies needs to be identified.

Cross-sectional associations between cardiorespiratory fitness and NMR-derived metabolic biomarkers in children – the PANIC study

ObjectiveCardiorespiratory fitness has been inversely associated with cardiovascular risk across the lifespan. Some studies in adults suggest that higher cardiorespiratory fitness is associated with cardioprotective metabolite profile, but the evidence in children is lacking. Therefore, we investigated the cross-sectional association of cardiorespiratory fitness with serum nuclear magnetic resonance derived metabolic biomarkers in children.MethodsA population sample of 450 children aged 6–8 years was examined. Cardiorespiratory fitness was assessed by a maximal exercise test on a cycle ergometer and quantified as maximal power output normalised for lean body mass assessed by dual-energy X-ray absorbtiometry. Serum metabolites were assessed using a high throughput nuclear magnetic resonance platform. The data were analysed using linear regression analyses adjusted for age and sex and subsequently for body fat percentage (BF%) assessed by DXA.ResultsCardiorespiratory fitness was directly associated with high density lipoprotein (HDL) cholesterol (β=0.138, 95% CI=0.042 to 0.135, p=0.005), average HDL particle diameter (β=0.102, 95% CI=0.004 to 0.199, p=0.041), and the concentrations of extra-large HDL particles (β=0.103, 95% CI=0.006 to 0.201, p=0.038), large HDL particles (β=0.122, 95% CI=0.025 to 0.220, p=0.014), and medium HDL particles (β=0.143, 95% CI=0.047 to 0.239, p=0.004) after adjustment for age and sex. Higher cardiorespiratory fitness was also associated with higher concentrations of ApoA1 (β=0.145, 95% CI=0.047 to 0.242, p=0.003), glutamine (β=0.161, 95% CI=0.064 to 0.257, p=0.001), and phenylalanine (β=0.187, 95% CI=0.091 to 0.283, p<0.001). However, only the direct associations of cardiorespiratory fitness with the concentrations of HDL cholesterol (β=0.114, 95% CI=0.018 to 0.210, p=0.021), medium HDL particles (β=0.126, 95% CI=0.030 to 0.223, p=0.010), ApoA1 (β=0.126, 95% CI=0.030 to 0.223, p=0.011), glutamine (β=0.147, 95% CI=0.050 to 0.224, p=0.003), and phenylalanine (β=0.217, 95% CI=0.122 to 0.311, p<0.001) remained statistically significant after further adjustment for BF%.ConclusionsHigher cardiorespiratory fitness was associated with a cardioprotective biomarker profile in children. Most associations were independent of BF% suggesting that the differences in serum metabolites between children are driven by cardiorespiratory fitness and not adiposity.

High-Density Lipoprotein and Long-Term Incidence and Progression of Aortic Valve Calcification: The Multi-Ethnic Study of Atherosclerosis.

Aortic valve calcification (AVC) shares pathological features with atherosclerosis. Lipoprotein components have been detected in aortic valve tissue, including HDL (high-density lipoprotein). HDL measures have inverse associations with cardiovascular disease, but relationships with long-term AVC progression are unclear. We investigated associations of HDL cholesterol, HDL-particle number and size, apoC3-defined HDL subtypes, and, secondarily, CETP (cholesteryl ester transfer protein) mass and activity, with long-term incidence and progression of AVC. We used linear mixed-effects models to evaluate the associations of baseline HDL indices with AVC. AVC was quantified by Agatston scoring of up to 3 serial computed tomography scans over a median of 8.9 (maximum 11.2) years of follow-up in the Multi-Ethnic Study of Atherosclerosis (n=6784). After adjustment, higher concentrations of HDL-C (high-density lipoprotein cholesterol), HDL-P (HDL particles), large HDL-P, and apoC3-lacking HDL-C were significantly associated with lower incidence/progression of AVC. Neither small or medium HDL-P nor apoC3-containing HDL-C was significantly associated with AVC incidence/progression. When included together, a significant association was observed only for HDL-C, but not for HDL-P. Secondary analyses showed an inverse relationship between CETP mass, but not activity, and AVC incidence/progression. In exploratory assessments, inverse associations for HDL-C, HDL-P, large HDL-P, and apoC3-lacking HDL with AVC incidence/progression were more pronounced for older, male, and White participants. ApoC3-containing HDL-C only showed a positive association with AVC in these subgroups. In a multiethnic population, HDL-C, HDL-P, large HDL-P, and apoC3-lacking HDL-C were inversely associated with long-term incidence and progression of AVC. Further investigation of HDL composition and mechanisms could be useful in understanding pathways that slow AVC.

High-Density Lipoprotein Particle Subclasses in Statin-Treated Patients with Peripheral Artery Disease Predict Long-Term Survival.

Low-density lipoprotein-cholesterol reduction showed a strong reduction of cardiovascular (CV) event rates in CV disease. However, the residual risk of future CV events remains high, which especially extends to peripheral arterial disease (PAD). Nuclear magnetic resonance (NMR) spectroscopy offers a novel method for analysis of the lipoprotein spectrum. This study investigates lipoprotein subclasses using NMR spectroscopy and assesses implications for long-term survival in PAD. NMR spectroscopy was performed by Nightingale Inc., in 319 patients with stable PAD and well-controlled CV risk factors. Patients were followed-up for 10 years. During that period, 123 patients (38.5%) died, of those 68 (21.3%) were defined as CV deaths. Outcome data were analyzed by the Kaplan-Meier method and multivariable Cox-regression for lipoprotein particles. Small and medium high-density lipoprotein-particles (S-HDL-P and M-HDL-P) showed a significant inverse association with all-cause mortality in Cox-regression analyses after multivariable adjustment (S-HDL-P, hazard ratio [HR]: 0.71, 95% confidence interval [CI]: 0.57-0.88; M-HDL-P, HR: 0.72, 95% CI: 0.58-0.90) for each increase of one standard deviation. In contrast, cholesterol-rich X-large HDL-particles (XL-HDL-P) showed a positive association with all-cause mortality (HR: 1.51, 95% CI: 1.20-1.89). Only the association between XL-HDL-P and CV death sustained multivariable adjustment (HR: 1.49, 95% CI: 1.10-2.02), whereas associations for S-HDL-P and M-HDL-P were attenuated (HR: 0.76, 95% CI: 0.57-1.01; HR: 0.80, 95% CI: 0.60-1.06). This study shows a novel association for a beneficial role of S-HDL-P and M-HDL-P but a negative association with higher cholesterol-rich XL-HDL-P for long-term outcome in well-treated patients with PAD. Thus, these results provide evidence that NMR-measured HDL particles identify patients at high CV residual risk beyond adequate lipid-lowering therapy.

Associations of Endogenous Hormones With HDL Novel Metrics Across the Menopause Transition: The SWAN HDL Study.

Novel metrics of high-density lipoprotein (HDL) (subclasses, lipid content, and function) may improve characterization of the anti-atherogenic features of HDL. In midlife women, changes in these metrics vary by time relative to the final menstrual period (FMP), supporting a contribution of estradiol (E2) and follicle-stimulating hormone (FSH). We tested associations of endogenous E2 and FSH with novel HDL metrics and assessed whether these associations varied by time relative to FMP. This study was a longitudinal analysis from the Study of Women's Health Across the Nation (SWAN) HDL study, using a community-based cohort of 463 women, baseline mean age 50.2 (2.7) years. The main outcome measures were HDL cholesterol efflux capacity (HDL-CEC), HDL phospholipids (HDL-PL), HDL triglycerides (HDL-Tg), HDL particles (HDL-P), HDL size, and HDL cholesterol (HDL-C). In multivariable analyses, E2 was positively associated with HDL size, large HDL-P, HDL-CEC, and HDL-Tg, but negatively with medium HDL-P (P values < 0.05). The positive association between E2 and HDL-Tg was stronger 2 years post-FMP than before, (interaction P = 0.031). FSH was positively related to total and medium HDL-P, but negatively to HDL size, large HDL-P, and HDL-CEC per particle (P values < 0.05). Associations of higher FSH with greater total HDL-P and smaller HDL size were only evident at/after menopause (interaction P values < 0.05). Some of the associations linking E2 and FSH with novel HDL metrics were vulnerable to time relative to menopause onset. Whether a late initiation of hormone therapy relative to menopause could have a detrimental effect on lipid content of HDL particles should be tested in the future.

P1650HIGH-DENSITY LIPOPROTEIN PARTICLES AND THEIR RELATIONSHIP TO POSTTRANSPLANTATION DIABETES IN RENAL TRANSPLANT RECIPIENTS

Abstract Background and Aims It is established that high concentrations of High-Density Lipoprotein (HDL) are associated with low risk of type 2 diabetes and posttransplantation diabetes mellitus (PTDM). However, HDL particles vary by size, density, and biological action. The aim of our study was to determine the association between different HDL particles with the development of PTDM in renal transplant recipients (RTRs). Method We included 351 stable outpatient adult RTR with a functioning graft ≥1 year from the Tranplantlines Food and Nutrition Study(NCT02811835). HDL particle concentration and size were measured by 1H-NMR spectroscopy using a Vantera® NMR Clinical Analyzer (LabCorp, Raleigh, NC). HDL size was weighted averages derived from the sum of the diameter of each subclass multiplied by its relative mass percentage. Estimated ranges of HDL diameter for the HDL subclasses were as follows: large HDL particles, 9.6–13 nm; medium HDL particles, 8.1–9.5 nm; and small HDL particles, 7.4–8.0 nm. PTDM was defined according the American Diabetes Association’s diagnostic criteria for diabetes. Multivariable-adjusted Cox proportional-hazards regression analyses were performed to assess the prospective association of HDL particles with PTDM. Results During 5.2 (IQR, 4.1–5.8) years of follow-up, 39 (11%) RTR developed PTDM. In a multivariable Cox regression analysis, higher HDL cholesterol was associated with a lower risk of PTDM development, after adjustment for age, sex and BMI (hazard ratio[HR] 0.55, 95% CI 0.36-0.83 per 1SD mg/dL; P=0.005). Moreover, among different HDL indices; HDL size, and large HDL were inversely associated with PTDM, after adjustment for age, sex, and BMI ([ HR 0.48, 95% CI 0.31-0.76 per 1SD nm; P=0.002], and [HR 0.63, 95% CI 0.47-0.84 per 1SD µmol/L; P=0.002], respectively ). However medium HDL and small HDL were not associated with risk of developing PTDM ([ HR 0.88, 95% CI 0.64-1.23 per 1SD µmol/L; P=0.48], and [HR 1.14, 95% CI 0.85-1.52 per µmol/L; P=0.37], respectively ). In additional models, the association remained significant for HDL cholesterol, HDL size, and large HDL after adjustment for other confounders including, the lifestyle, use of medication, kidney function and transplantation-specific parameters. In the last model after adjustment for age, sex, BMI, triglycerides, systolic blood pressure, and fasting plasma glucose, association were similar for HDL cholesterol, HDL size, and large HDL ([ HR 0.61, 95% CI 0.40-0.94 per 1SD mg/dL; P=0.024], [HR 0.58, 95% CI 0.36-0.93 per 1SD nm; P=0.025], and [HR 0.68, 95% CI 0.50-0.93 per 1SD µmol/L; P=0.017]. Conclusion In this study, we found that higher concentrations of HDL cholesterol, large HDL, and higher HDL size were associated with a lower risk of developing PTDM in RTRs, independent of established risk factors for PTDM development.

Impact of obeticholic acid on the lipoprotein profile in patients with non-alcoholic steatohepatitis

Obeticholic acid (OCA), a farnesoid X receptor agonist, increases total and low-density lipoprotein cholesterol (LDL-C) in patients with non-alcoholic steatohepatitis. In the present study, we aimed to evaluate the impact of OCA therapy on lipoprotein sub-particles. This study included 196 patients (99 OCA group and 97 placebo group) who were enrolled in the FLINT trial and had samples available for lipid analysis and liver biopsies at enrollment and end-of-treatment (EOT) at 72 weeks. Very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) particles were evaluated at baseline, 12 and 72 weeks after randomization, and 24 weeks following EOT. Baseline lipoprotein profiles were similar among OCA and placebo groups. OCA did not affect total VLDL particle concentrations, but OCA vs. placebo treatment was associated with decreased large VLDL particle concentration at 12 weeks (baseline-adjusted mean: 6.8 vs. 8.9 nmol/L; p = 0.002), mirrored by an increase in less atherogenic, small VLDL particle concentration (33.9 vs. 28.0 nmol/L; p = 0.02). After 12 weeks, total LDL particle concentration was higher in the OCA group than the placebo group (1,667 vs. 1,329 nmol/L; p <0.0001), characterized by corresponding increases in both less atherogenic, large-buoyant LDL (475 vs. 308 nmol/L; p ≤0.001) and more atherogenic small-dense LDL particles (1,015 vs. 872 nmol/L; p = 0.002). The changes in LDL particle concentrations were similar between treatment groups (OCA and placebo) 24 weeks following EOT due to improvement in the OCA cohort. Compared to placebo, a reduction in total HDL particle concentration, particularly large and medium HDL particles, was noted in the OCA-treated patients, but this resolved after drug discontinuation. OCA therapy is associated with increases in small VLDL particles, large and small LDL particles, and a reduction in HDL particles at 12 weeks. These lipoprotein concentrations reverted to baseline values 24 weeks after drug discontinuation. Non-alcoholic steatohepatitis is a chronic liver disease that is associated with an increased risk of developing cirrhosis and cardiovascular disease. Recently, obeticholic acid (OCA), a farnesoid X receptor agonist, improved liver disease but led to an increase in cholesterol. However, the impact of OCA on cholesterol is not well understood. In the present study, we show that OCA therapy is associated with a detrimental increase in lipoprotein levels, which improves after drug discontinuation. ClinicalTrials.gov numbers: NCT01265498.

Abstract 13272: High Density Lipoprotein Subclasses Predict Non-Cardiovascular Disease, Non-Cancer Chronic Inflammatory-Related Death and Hospitalization More Strongly than Cardiovascular Disease Events in the Multi-Ethnic Study of Atherosclerosis

In vitro studies have demonstrated that high density lipoprotein particles (HDL-P) antagonize inflammatory processes. We studied the predictive value of HDL-P and inflammatory markers for incident cardiovascular disease (CVD) and non-CVD, non-cancer, chronic inflammatory-related events. Methods: In the Multi-Ethnic Study of Atherosclerosis, we studied 6475 men and women free of overt CVD, baseline age 45-84 years, who had fasting venous samples for lipid profile, lipoprotein particles, and inflammatory markers Interleukin-6 (IL-6), hs-CRP and D-dimer at baseline. Median follow-up was 10.1 years. Poisson regression models predicted non-CVD, non-cancer, chronic inflammatory-related events (death and hospitalization), based on diagnostic codes, n=1054) and CVD events due to coronary heart disease, myocardial infarction, coronary artery disease requiring revascularization, stroke, peripheral arterial disease, congestive heart failure and CVD or unwitnessed death (adjudicated, n=756). Adjustment was for age, race, gender, clinic, heart rate, smoking, body mass index, blood pressure, blood pressure and lipid lowering medication, diabetes mellitus, plus all lipid, lipoprotein particle and inflammatory variables. Results: Non-CVD, non-cancer, chronic inflammatory-related events were inversely associated with the sum of small+medium HDL-P independent of covariates (relative risk (RR) per standard deviation (95% confidence limits), RR: 0.85 (0.79-0.91, P &lt; 0.0001). Non-CVD, non-cancer, chronic inflammatory-related events were positively associated with IL-6, RR:1.19 (1.11-1.27, P &lt; 0.0001) and D-dimer, RR: 1.10 (1.05-1.16, P &lt; 0.0001). CVD was associated with small+medium HDL-P, RR: 0.90 (0.82-0.99, P &lt; 0.03) and IL-6, RR:1.15 (1.06-1.25 P &lt; 0.0001). hsCRP was unrelated to either outcome after adjustment for other inflammatory markers. Conclusion: The long-term inverse association of small+medium HDL-P with non-CVD, non-cancer, chronic inflammatory-related death and hospitalization was stronger than with fatal and non-fatal CVD in subjects initially free of overt CVD. These findings provide clinical evidence that small+medium HDL-P have anti-inflammatory properties and may rethink the importance of HDL-P beyond CVD.

Serum paraoxonase-1 activity is more closely related to HDL particle concentration and large HDL particles than to HDL cholesterol in Type 2 diabetic and non-diabetic subjects

ObjectivesWe determined relationships of the anti-oxidative enzyme, paraoxonase-1 (PON-1), with high density lipoprotein (HDL) subfractions, and tested whether these relationships are stronger than those with HDL cholesterol and apolipoprotein A-I (apoA-I) in subjects with and without type 2 diabetes mellitus (T2DM). Design and methodsSerum PON-1 (arylesterase activity) and HDL subfractions (nuclear magnetic resonance spectroscopy) were determined in 67 T2DM patients and in 56 non-diabetic subjects. ResultsPON-1 activity, HDL cholesterol and apoA-I were decreased in T2DM (all p<0.05). The HDL particle concentration was unaltered, but large HDL particles, medium HDL particles and HDL particle size were decreased, whereas small HDL particles were increased in T2DM (all p<0.05). PON-1 was more closely related to HDL cholesterol than to apoA-I (p=0.001). In turn, the positive relationship of PON-1 with the HDL particle concentration and with large HDL particles was stronger than that with HDL cholesterol (both p<0.01). The inverse relationship of PON-1 with T2DM was only modestly attenuated by HDL cholesterol or HDL particle characteristics. ConclusionsPON-1 activity is more closely related to the HDL particle concentration or large HDL particles than to HDL cholesterol. Impaired PON-1 activity in T2DM is not to a considerable extent explained by altered HDL subfraction levels.

Relationships between cholesterol efflux and high-density lipoprotein particles in patients with type 2 diabetes mellitus

High-density lipoprotein (HDL) encompasses a heterogeneous population of lipoproteins with differences in functionality. The impact of HDL heterogeneity on its ability to support HDL-mediated cholesterol efflux has not been previously studied in patients with type 2 diabetes mellitus (T2DM). To examine the relationships between various HDL subtypes and cholesterol efflux from macrophages in patients with T2DM. Lipoprotein molecular profiles of 44 patients were studied by NMR spectroscopy. Cholesterol efflux was expressed as percentage efflux of radioactivity from lipid-laden THP-1 macrophages preincubated with (3)H-cholesterol and then incubated with serum depleted of apolipoprotein Bto provide an HDL-enriched acceptor medium. There was a predominance of small HDL particles (59%) and small putatively atherogenic low-density lipoprotein particles (56%). Neither HDL-C nor ApoA-I concentrations showed statistically significant correlations with percentage cholesterol efflux, but a significant positive relationship was found with the total HDL particle concentration (r= 0.41, P= .005) contributed to largely by medium HDL particles (r= 0.41, P= .006). The correlation between medium-sized HDL particle concentration remained significantly associated with cholesterol efflux when assessed with the use of a linear regression model that included all the HDL lipoprotein subclass concentrations as well as apolipoprotein A-I. Importantly, no statistically significant association was observed between the number of small HDL particles and cholesterol efflux. Hemoglobin A1c showed a significant inverse correlation with cholesterol efflux (r= -0.31, P= .04). In patients with moderately controlled type 2 diabetes mellitus, cholesterol efflux from macrophages incubated with apolipoprotein B-depleted plasmas correlated significantly and positively with the concentration of total and medium-sized HDL and not with that of the smallest particles.

Sex and Ethnic Disparities in High-Density Lipoprotein Subclasses∗

Synopsis: Several epidemiological studies have shown race and sex differences in conventional lipoprotein parameters. Descriptive studies on these differences in novel lipid subfractions, high-density lipoprotein (HDL) subclasses in particular, are very scant. Previous studies were performed only on biracial groups and in high-risk populations. Purpose: To determine the variances of the HDL subfractions in an ethnically diverse healthy adult population and to ascertain their impact on cardiovascular outcomes. Methods: Multi-Ethnic study of Atherosclerosis (MESA) is a population based study (n = 6814) of white (38%), black (28%), Chinese (22%), and Hispanic (12%) subjects, aged 45–84 years, with no self-reported cardiovascular disease. This is a post-hoc analysis of the NHLBI limited access dataset of MESA subjects who had data on lipid subclasses available (n = 6697). Individual lipoprotein subclasses were measured on frozen plasma specimens (−70 °C) using nuclear magnetic resonance spectroscopy. The end points analyzed were all-cause mortality, all CVD events and composite cardiovascular events. Chinese were arbitrarily selected as a reference cohort (lowest cardiovascular event rate). Multivariate analysis of variance was used to adjust for age, body mass index, hypertension, diabetes, any lipid-lowering medication and smoking. Results: Men had a greater incidence of cardiovascular events compared with women. Similarly, white subjects had more events compared with the other ethnic groups. The distribution of outcomes and the HDL subclasses across the various groups is detailed in the figure. Women had increased levels of HDL cholesterol and total HDL particles as well as significantly higher levels of large and medium HDL particles compared to men. Chinese subjects had greater levels of small HDL among all the racial groups. HDL size was greater among African-American subjects, and they had greater levels of large HDL compared with the other groups. Overall, interpretation of the HDL subclass distribution pattern reveals that the concentration of small HDL particles was inversely related to the number of cardiovascular outcomes across all the different ethnic groups. Conclusions: There were clear sex and race differences in HDL subclasses in this multiethnic cohort. These differences might provide a different atherogenic profile that is not apparent in a standard lipid panel. The current analysis might suggest a potential protective effect of small HDL on cardiovascular events.

Atherogenic Lipoprotein Particle Size and Concentrations and the Effect of Pravastatin in Children with Familial Hypercholesterolemia

To determine lipoprotein particle concentrations and size in children with familial hypercholesterolemia (FH) and investigate the effect of pravastatin therapy on these measures. Lipoprotein particle concentrations and sizes were examined by nuclear magnetic resonance (NMR) spectroscopy in 144 children with FH and 45 unaffected siblings. The effect of pravastatin therapy (20 to 40 mg) on lipoprotein particle concentration and size were compared with placebo after 1 year of treatment, using analysis of covariance. Compared with the unaffected siblings, the children with FH had significantly higher concentrations of very-low-density lipoprotein (VLDL) particles (115.6 nmol/L vs 51.2 nmol/L; P < .001) and low-density lipoprotein (LDL) particles (1726.8 nmol/L vs 955.3 nmol/L; P < .001), and lower concentrations of high-density lipoprotein (HDL) particles (23.2 micromol/L vs 26.9 micromol/L; P < .001). Compared with placebo, pravastatin therapy decreased the concentration of VLDL particles by 35.9 nmol/L (P < .001), of total LDL particles by 342.7 nmol/L (P < .001), of large LDL particles by 189.5 nmol/L (P < .001), and of small LDL particles by 156.2 nmol/L (P = .152), but increased the concentration of total HDL particles by 2.2 micromol/L (P < .001), of large HDL particles by 1.0 micromol/L (P = .006), and of medium HDL particles by 1.1 micromol/L (P = .003). VLDL particle size increased by 1.0 nm (P = .032). Compared with their healthy siblings, children with FH have an atherogenic lipoprotein profile based on their lipoprotein distribution and lipoprotein particle diameter. Pravastatin therapy can improve, but not fully restore, these lipoprotein abnormalities toward normal levels in these children.

The relationship between physical activity and lipoprotein subclasses in postmenopausal women

This study's objective was to determine if the association between physical activity and lipids and lipoprotein subclasses in postmenopausal women varies by hormone therapy (HT) use. The cross-sectional relationship between physical activity and lipid and lipoprotein subclass relationship was examined before group randomization in 485 postmenopausal (mean age 56.9 [2.9] y) white and African American women from the Woman On the Move through Activity and Nutrition study. This study is a randomized clinical trial designed to test whether a lifestyle intervention will reduce subclinical cardiovascular disease measures. Hormone therapy users (n = 286) were significantly (P < 0.05) younger, less likely to be African American, reported higher levels of physical activity, large very low-density lipoprotein particles (VLDL-P), and medium high-density lipoprotein particles (HDL-P), had a larger mean HDL-P size, and lower levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, small HDL-P, and small VLDL-P than nonusers (n = 196). Physical activity was significantly associated with favorable lipoprotein and lipid levels, regardless of HT use. Some relationships were found to vary significantly by HT use. In nonusers, mean HDL-P and LDL particles (LDL-P) size was significantly larger (P = 0.01 and 0.05, respectively) and total and small LDL-P were significantly lower (both P = 0.02) as activity increased. These relationship were not found in HT users. Physical activity was significantly related to some lipoprotein subclasses regardless of HT; however, several key lipoprotein subclasses were associated with higher levels of activity only among non-HT users.

Lipoprotein particles, insulin, adiponectin, C-reactive protein and risk of coronary heart disease among men with metabolic syndrome

We tested the hypotheses whether nuclear magnetic resonance (NMR) determined lipoprotein particles, insulin and adiponectin, and C-reactive protein (CRP) and white blood cell (WBC) count as markers of inflammation predicted risk of coronary heart disease (CHD) death among 428 men age 35–57 years with metabolic syndrome (MetSyn) in a matched case control study within the multiple risk factor intervention trial. Blood samples collected at entry into the study and stored at −60 °C were obtained from central storage for blood analyte analysis. Two hundred and fourteen men with MetSyn who died of CHD were matched with 214 men with MetSyn who did not die of CHD during 18 years of follow-up. Cases were matched to controls on age, study group, number of factors present in the MetSyn, and presence or absence of a nonfatal CVD event during the trial. Mortality follow-up was determined using the National Death Index. Higher levels of high density lipoprotein particles (HDL-P), especially medium-sized HDL-P [hazard ratio (95% confidence interval) 0.45 (0.25–0.83, P < 0.01), quartile 1 as compared to quartile 4], were associated with lower risk of CHD death. Low density lipoprotein (LDL) particles were not associated with increased risk of CHD. Elevated LDL cholesterol (LDL-C), smoking and WBC count were, but levels of adiponectin, insulin and CRP were not significantly related to CHD death. In multivariate models adjusting for smoking and LDL-C, medium HDL-P and WBC count remained independent predictors of CHD death. Number of HDL particles, especially medium-sized HDL particles and WBC count were independent predictors of CHD death among men with MetSyn.