Nuclear Magnetic Resonance Lipoprotein Research Articles

Abstract 12864: Nuclear Magnetic Resonance Lipoprotein Particle Subclasses Associate With Chronic Inflammatory Related Diseases Differently Than Cardiovascular Diseases: The Multi-Ethnic Study of Atherosclerosis

Introduction: Chronic inflammatory related disease (ChrIRD) is a novel outcome capturing non-cancer, non-cardiovascular clinical events driven by subclinical inflammation. Derangements in triglyceride-rich, low-density, and high-density lipoprotein particle (TRLp, LDLp, HDLp) subclass concentrations known to associate with inflammation and future cardiovascular disease have not been extensively evaluated in ChrIRD. Hypothesis: Lipoprotein particle subclasses may predict future ChrIRD in a similar direction and magnitude as with CVD. Methods: We measured 17 lipoprotein subclass particle concentrations by NMR spectroscopy in the Multi-Ethnic Study of Atherosclerosis (MESA). MESA is a US cohort including 6,759 White (38.6%), Chinese (11.9%), Black (27.6%), and Hispanic (22%) men and women initially aged 45-84 years and free of CVD. Participants were contacted at least annually to ascertain clinical events. Incident CVD (MI, Stroke, PAD, CV Death) and ChrIRD death/hospitalization risk per-quartile of lipoprotein marker levels were evaluated using disease-specific multivariable Cox regression models adjusted for traditional risk factors. Results: Disparate risk associations with ChrIRD and CVD were observed (Figure). Elevated small HDLp, total LDLp, and small TRLp, and were inversely associated with ChrIRD events. Additionally, larger TRLp size was associated higher ChrIRD risk. Metrics of HDL, LDL, and TRL associations with incident CVD as expected. In contrast, Very large TRLp was inverse with both clinical outcomes (HR [95% CI] CVD: 0.83 [0.75-0.96] ptrend=0.09, ChrIRD: 0.85 [0.69-0.99], ptrend =0.02). Conclusions: TRL, LDL, and HDL particles differentially associate with CVD and ChrIRD. Established predictors of CVD, including total TRL and LDL particles, small LDL, and large /medium TRL, may be inert or even protective in development of ChrIRD events due to distinct pathophysiologic contributions that warrant further investigation.

Nut consumption is associated with a shift of the NMR lipoprotein subfraction profile to a less atherogenic pattern among older individuals at high CVD risk

BackgroundScientific evidence has accumulated on the beneficial effects of nut consumption on cardiovascular risk and cholesterol reduction, but few studies have examined the effects of nuts on advanced measures of lipoprotein atherogenicity determined by nuclear magnetic resonance (NMR) spectroscopy. We analyzed associations between the amount and type of of nuts consumed and advanced measures of lipoprotein atherogenity and insulin resistance in older individuals at high cardiovascular risk.MethodsThe present observational study was carried out within the framework of the Prevención con Dieta Mediterránea (PREDIMED) trial. Cross-sectional and longitudinal analyses after 1-year of follow-up were conducted in 196 men and women recruited in the PREDIMED-Reus (Spain) center. Dietary intake was assessed using a validated semi-quantitative food questionnaire. Baseline and 1-year fasting plasma lipoprotein and metabolite profiling were performed in plasma using NMR spectra Vantera® Clinical Analyzer. Associations by tertiles of nut consumption between baseline and 1-year changes and advanced measures of lipoprotein atherogenicity, branched chain amminoacids, and measures of insulin resistance were tested by multivariable-adjusted ANCOVA models.ResultsCompared to paticipants in the bottom tertile, those in the top tertile of total nut consumption showed higher levels of large HDL particles and HDL-cholesterol, lower levels of branched-chain amino acids (BCAA) and GlycA, and reduced lipoprotein insulin resistance and diabetes risk index. Participants in the top tertile of walnut consumption disclosed lower levels of very large VLDL, total LDL particles, LDL-cholesterol, and GlycA. Participants in the top tertile of non-walnut nut consumption displayed higher levels of total HDL particles, HDL-cholesterol and apoliporotein A1, lower BCAA and GlycA, and reduced lipoprotein insulin resistance. Participants in the top tertile of 1-year changes in walnut consumption showed increases in medium-sized HDL particles in comparison to the bottom tertile.ConclusionsIn older individuals at high cardiovascular risk, increasing nut consumption was associated with a shift of the NMR lipoprotein subfraction profile to a less atherogenic pattern, as well as lower circulating concentrations of BCAA and decreased insulin resistance. These results provide novel mechanistic insight into the cardiovascular benefit of nut consumption.Trial registration ISRCTN35739639; registration date: 05/10/2005; recruitment start date 01/10/2003.

Association of inflammatory markers and lipoprotein particle subclasses with progression of coronary artery calcium: The multi-ethnic study of atherosclerosis

Background and aimsAtherosclerosis is a complex phenomenon manifesting several features typical of chronic inflammation and disorders of lipid metabolism. We assessed association of nuclear magnetic resonance (NMR) lipid variables and inflammatory markers with incident coronary artery calcium (CAC) and CAC progression among participants with baseline CAC ≥0. MethodsMESA is a longitudinal cohort study of 6,814 participants (aged 45–85). 3,115 had CAC = 0 and 2,896 had CAC>0 at baseline. Repeat CAC measurements were obtained (mean duration of follow up, 6.5 years). ResultsIL-6 (log pg/mL) and fibrinogen (50 mg/dL) were associated with a higher relative risk (RR) of incident CAC (HU) (RR = 1.09, p=0.010 & RR 1.05, p=0.004, respectively). Small LDL (100 nmol/L) (RR = 1.03, p<0.001) and log large VLDL (log nmol/L) (RR = 1.06, p=0.001) were associated with higher risks, whereas large HDL (μmol/L) was associated with an inverse risk of incident CAC (RR = 0.97, p< 0.001) in a model adjusted for follow up time, age, gender and race. Among participants with baseline CAC>0, progression of CAC was positively associated with hsCRP (log mg/L) (β = 1.99), IL-6 (log pg/mL) (β = 2.9), fibrinogen (50 mg/dL) (β = 1.0), large VLDL (log nmol/L) (β = 2.2), and small LDL (100 nmol/L) (β = 0.36) (all p values < 0.05) in a model adjusted for scanner type, age, gender and race. Relationships with inflammatory markers and NMR lipoprotein particles lost significance after adjustment for traditional risk factors and statin use. Traditional risk factors were strongly associated with both CAC incidence and progression with the exception of cholesterol parameters not associated with CAC progression in adjusted model. ConclusionsInflammatory markers and lipoprotein particles were associated with CAC incidence and progression in minimally adjusted models, but not after adjustment for traditional risk factors.

Predictive utilities of lipid traits, lipoprotein subfractions and other risk factors for incident diabetes: a machine learning approach in the Diabetes Prevention Program

IntroductionAlthough various lipid and non-lipid analytes measured by nuclear magnetic resonance (NMR) spectroscopy have been associated with type 2 diabetes, a structured comparison of the ability of NMR-derived biomarkers and...

Nuclear magnetic resonance lipoproteins are associated with carotid atherosclerosis in type 1 diabetes and pre-eclampsia.

Persistence of lipoprotein abnormalities in type 1 diabetes (T1D) and/or pre-eclampsia could be associated with cardiovascular disease (CVD). We assessed differences in the advanced lipoprotein profiles according to the presence of both conditions and their differential association with atherosclerosis. We recruited 112 women without CVD and last pregnancy ≥5 years previously, divided into four groups (n = 28 per group): (a) T1D and previous pre-eclampsia; (b) T1D without pre-eclampsia; (c) pre-eclampsia without T1D; and (d) controls (without T1D/pre-eclampsia). Groups were matched by several risk factors, and diabetes duration and retinopathy in T1D. Carotid intima-media thickness (IMT) and the presence of plaque (IMT ≥1.5 mm) were assessed by ultrasonography. The lipoprotein profile was evaluated by nuclear magnetic resonance (NMR) spectroscopy. The participants were 44.9 ± 7.8 years old. Carotid plaque presence was 20.5%, with a higher prevalence in T1D and/or pre-eclampsia vs controls (P < .05). High-density lipoprotein (HDL)-related variables differed among groups, mainly driven by an increase in T1D (P < .05), whereas triglyceride-related variables were increased in pre-eclampsia [medium very low-density lipoprotein (VLDL) particles and triglyceride enrichment in HDL and low-density lipoprotein (LDL)]. Overall, in multivariate-adjusted models, LDL-related variables were the most strongly associated with atherosclerosis (P < .05). In age- and statin-adjusted models, previous pre-eclampsia showed an independent association with triglyceride-related variables (plaque: medium-VLDL-particles, OR 1.550 [1.013-2.374]; HDL-cholesterol/HDL-triglycerides ratio, OR 0.411 [0.175-0.967]). Regarding T1D, HDL-parameters were also differentially associated (maximum-IMT: HDL-cholesterol/HDL-particles ratio, β = -.258, P = .036). NMR lipoproteins were differentially and independently associated with atherosclerosis in T1D/pre-eclampsia. Further studies are needed to ascertain the role of NMR parameters as CVD biomarkers in this high-risk population.

Increased atherogenic lipoprotein profile in children with non-alcoholic steatohepatitis.

Non-alcoholic fatty liver disease (NAFLD) has been shown to be an independent risk factor for cardiovascular disease. In adults, histologic severity of non-alcoholic steatohepatitis (NASH) is associated with a more atherogenic profile. To assess cardiovascular disease risk by lipoprotein profile in children with NAFLD and compare to histologic assessment of severity. Nuclear magnetic resonance lipoprotein profile including lipoprotein particle sizes, apolipoproteins and the lipoprotein insulin resistance (LP-IR) index was measured in serum samples collected from 76 children at the time of a clinically indicated liver biopsy for NAFLD. Liver histology was scored using the NASH Clinical Research Network criteria and grouped into NASH or non-NASH. Children with NASH had higher apolipoprotein B to apolipoprotein AI, ApoB/ApoAI (0.56 [IQR, 0.45-0.70] vs 0.66 [IQR, 0.56-0.79], P = .02) and higher LP-IR index (61 ± 21.9 vs 68 ± 17.3, P = .05) compared to children with non-NASH. Severity of hepatocyte ballooning was associated with higher ApoB/ApoAI ratios (P = .01), while high-density lipoprotein size was inversely associated with hepatic fat accumulation (P = .04). While dyslipidaemia is common among children with NAFLD, this data suggests severity of the histologic features is closely associated with severity of cardiometabolic risk. Further studies are needed to understand the role of treatment of NASH in children to prevent future cardiometabolic disease.

Habitual Fish Consumption, n-3 Fatty Acids, and Nuclear Magnetic Resonance Lipoprotein Subfractions in Women.

BackgroundSupplementation with omega‐3 (n‐3) fatty acid or dietary fish may protect against atherosclerosis, but the potential mechanisms are unclear. Prior studies found modest triglyceride‐lowering effects and slight increases in LDL (low‐density lipoprotein) cholesterol. Limited evidence has examined n‐3 effects on more detailed lipoprotein biomarkers.Methods and ResultsWe conducted a study of 26 034 healthy women who reported information on fish and n‐3 intake from a 131‐item food‐frequency questionnaire. We measured plasma lipids, apolipoproteins, and nuclear magnetic resonance spectroscopy lipoproteins and examined their associations with dietary intake of fish, total n‐3, and the n‐3 subtypes (eicosapentaenoic, docosahexaenoic, and α‐linolenic acids). Top‐ versus bottom‐quintile intake of fish and n‐3 were significantly associated with lower triglyceride and large VLDL (very‐low‐density lipoprotein) particles. Fish intake, but not total n‐3, was positively associated with total cholesterol, LDL cholesterol, apolipoprotein B, and larger LDL size, but only α‐linolenic acid was associated with lower LDL cholesterol. Total n‐3, docosahexaenoic acid, and α‐linolenic acid intake were also positively associated with larger HDL (high‐density lipoprotein) size and large HDL particles. High eicosapentaenoic acid intake was significantly associated with only a decreased level of VLDL particle concentration and VLDL triglyceride content. The n‐3 fatty acids had some similarities but also differed in their associations with prospective cardiovascular disease risk patterns.ConclusionsHigher consumption of fish and n‐3 fatty acids were associated with multiple measures of lipoproteins that were mostly consistent with cardiovascular prevention, with differences noted for high intake of eicosapentaenoic acid versus docosahexaenoic acid and α‐linolenic acid that were apparent with more detailed lipoprotein phenotyping. These hypothesis‐generating findings warrant further study in clinical trials.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000479.

Lipoprotein particles in patients with pediatric Cushing disease and possible cardiovascular risks.

Background:Cardiovascular (CV) complications are the most significant cause of mortality in adults with Cushing disease (CD); little is known about CV risk factors in children with CD. Measurement of lipoprotein particles by nuclear magnetic resonance (NMR) spectroscopy is a novel technology to assess CV risk. The objective of the current study is to analyze the NMR lipid profile in pediatric CD patients before and 1 year after remission.Methods:NMR lipid profile was obtained via the Vantera NMR analyzer, using frozen serum samples from 33 CD patients (mean age 13.8 ± 4.0 years) evaluated between 1997 and 2017 at the National Institutes of Health (NIH) Clinical Center (CC).Results:GlycA, triglyceride-rich particles (TRLP medium and very small sizes), LDL particles (LDLP total and large size), HDL particles (HDLP total, medium and small sizes), total cholesterol, LDL cholesterol, HDL cholesterol, GlycA inflammatory biomarker, Apolipoprotein B and Apolipoprotein A1 concentrations showed statistically significant changes after remission of CD (p<0.05).Conclusion:In our study population, most of the lipid variables improved post-CDremission, with the exception of HDL and apoA1, indicating that NMR lipoprotein profile may be a helpful tool in assessing the cardiovascular risk in pediatric patients with CD.

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.

Phlebotomy tube interference with nuclear magnetic resonance (NMR) lipoprotein subclass analysis

BackgroundLipoprotein subclass analysis by nuclear magnetic resonance (NMR) can be used in risk assessment of atherosclerotic cardiovascular disease (ASCVD). There is little information in the literature regarding phlebotomy tube interferences with NMR testing. MethodsPooled human serum was exposed to phlebotomy tubes manufactured by Becton Dickinson (BD), Greiner Bio-One, or Sarstedt. Serum was analyzed on the Axinon lipoFIT by NMR assay and by conventional lipid assays performed on a Roche Cobas 8000 system. The effect of incomplete fill volume was also assessed. ResultsAnalytical interference in NMR lipoprotein subclass results was observed across many different tube types. The 5 mL Greiner Bio-One Z Serum Sep Clot Activator tube correlated the best with non-gel containing serum tubes from BD and Greiner Bio-One. BD Serum Separator Tubes (SSTs) displayed strong interferences across several NMR analytes that were enhanced with decreased tube fill volumes. Interferences were also observed with different sizes of Greiner Bio-One Z Serum Sep Clot Activator tubes. Interference was generally not observed with conventional lipid testing, although minor interference was found for some tubes with lipoprotein(a) [Lp(a)]. ConclusionsNMR lipoprotein subclass analysis should be standardized by both tube type and tube size to prevent risk of analytical interference.

Relationship between noninvasive scores of nonalcoholic fatty liver disease and nuclear magnetic resonance lipoprotein abnormalities: A focus on atherogenic dyslipidemia

Nonalcoholic fatty liver disease (NAFLD) is an emerging, highly prevalent, cardiovascular risk factor, and lipoprotein proatherogenic disturbances likely explain a large part of this risk. However, information regarding associations between detailed nuclear magnetic resonance (NMR) lipoprotein changes and noninvasive NAFLD scores is lacking. The objective of the study was to investigate the NMR-assessed atherogenic lipoprotein profile according to noninvasive NAFLD status. Lipoprotein profiles by NMR spectroscopy and NAFLD status by fatty liver index (FLI) and Gholam's models. We assessed 173 participants (55% males), mean age 60.8±7.8years, 87% overweight/obese, 53% with diabetes. An FLI <30, 30 to 60, and >60 was found in 32, 50, and 91 participants, respectively. Individuals with FLI >60 had lower high-density lipoprotein (HDL)-cholesterol (P<.001), higher triglyceride (P<.001), and similar non-HDL-cholesterol (P=.912) concentrations. In NMR analysis, FLI was related with very-low-density lipoprotein (VLDL) and HDL parameters in a dose-dependent manner. VLDL particle number (P<.001) and VLDL size (39.1±0.99, 39.7±0.96, 40.8±1.19nm, P<.001) increased with increased FLI (<30, 30-60, and >60, respectively). Conversely, although total HDL particle number did not differ by FLI (P=.377), larger HDL particles (P<.001), amount of cholesterol within HDL particles (P<.001), and HDL size (median [p25-p75]: 8.23 [8.08-8.41], 8.12 [8.03-8.29], 8.04 [7.93-8.16]nm, P<.001) decreased as FLI increased. FLI >60 (vs <60) was associated with a higher proportion of small LDL particles (P=.010) and lower LDL size (19.85±0.34 vs 19.98±0.25nm; P=.005). Similar findings were found for Gholam's model. Simple and noninvasive NAFLD scores are useful to detect many of the proatherogenic changes (especially in VLDL and HDL), beyond conventional lipids parameters that are common in individuals with this high-risk condition.

Nuclear magnetic resonance lipoprotein abnormalities in newly-diagnosed type 2 diabetes and their association with preclinical carotid atherosclerosis

Background and AimsAtherogenic dyslipidemia is common in type 2 diabetes (T2DM) and predicts cardiovascular disease, but information on the association of its components with atherosclerosis is scarce. We aimed to assess differences in the lipoprotein profile in newly-diagnosed T2DM and matched control individuals and their associations with preclinical carotid atherosclerosis. MethodsIn a case-control study, we evaluated lipoprotein profiles by nuclear magnetic resonance (NMR) spectroscopy and determined carotid intima-media thickness (IMT) and plaque presence (IMT ≥1.5 mm) by B-mode ultrasonography. ResultsWe assessed 96 T2DM patients (median age 63 years, 44% women, 19% smokers, 54% hypertension, 38% dyslipidemia) and 90 non-diabetic controls matched for age, sex, and cardiovascular risk factors. In T2DM VLDL-particles (mainly large and enriched in cholesterol and triglycerides) were increased, and large HDL-particles (enriched in triglycerides and depleted in cholesterol) were reduced (p < 0.05; all comparisons). Regarding associations with preclinical atherosclerosis, VLDL triglyceride content (odds ratio [OR], 8.975; 95% confidence interval [CI], 2.330–34.576), total number of VLDL particles (OR, 2.713; CI, 1.601–4.598) and VLDL size (OR, 2.044; CI, 1.320–3.166), and the ratio cholesterol/triglycerides in HDL (OR, 0.638; CI, 0.477–0.852) were associated with plaque burden (≥3 plaques) independently of confounders, including conventional lipid levels. ConclusionNMR-assessed advanced lipoprotein profile identifies lipid abnormalities associated with newly-diagnosed T2DM and preclinical atherosclerosis that are not captured by the traditional lipid profile. At this early stage of diabetes, NMR lipoproteins could be useful to identify candidates for a more comprehensive cardiovascular risk prevention strategy.

Superiority of lipoprotein particle number to detect associations with arterial thickness and stiffness in obese youth with and without prediabetes

The nuclear magnetic resonance (NMR) lipoprotein profile provides additional cardiovascular risk information beyond traditional lipids in high-risk adults. Similar studies have not been conducted in youth. To evaluate the relationship between the NMR profile and preclinical vascular measures in youth. We studied 96 obese youth with prediabetes (mean age= 18.1±3.6years, 63% female, 78% African American) and 118 obese normoglycemic controls (mean age= 18.0±3.1years, 75% female, 62% African American) cross sectionally. Traditional lipids (triglycerides, total, high-density lipoprotein [HDL], and low-density lipoprotein [LDL] cholesterol), NMR particle size (particle concentration [P] and size) and vascular thickness (carotid IMT) and stiffness (pulse wave velocity [PWV]) were measured. Independent associations between lipoproteins with carotid IMT and PWV after adjustment for group, age, race, sex, BMI z score, blood pressure, HOMA-IR, and A1c were studied. NMR analysis revealed youth with prediabetes exhibited a more atherogenic profile with higher levels of small LDL-P and HDL-P and lower levels of intermediate and large HDL-P (P<.03). In addition, lower intermediate HDL-P was associated with a higher carotid IMT, whereas higher small HDL-P was associated with a higher PWV (P<.01). Traditional lipids were not significantly different between groups and were not associated with either vascular outcome. NMR lipoprotein subclasses have improved sensitivity compared to traditional lipids to detect lipoprotein abnormalities in normoglycemic and prediabetic obese youth and are independently associated with preclinical vascular thickness and stiffness. NMR lipids may enhance cardiovascular risk assessment in youth.

Lipoprotein heterogeneity may help to detect individuals with insulin resistance.

The triacylglycerol (TG)-to-HDL-cholesterol ratio has been shown to detect insulin resistance. However, the added predictive value of a more comprehensive assessment of lipoprotein composition is unknown. We analysed cross-sectional data from 882 non-diabetic participants in the Insulin Resistance Atherosclerosis Study (IRAS). Lipoproteins were measured by nuclear magnetic resonance (NMR) spectroscopy. Determined by the frequently sampled intravenous glucose tolerance test, insulin resistance was defined as the lowest sex-specific quartile of insulin sensitivity. The AUC of the receiver operating characteristic curve of HDL-cholesterol and TG levels for detecting insulin resistance was similar to that of the TG-to-HDL-cholesterol ratio (0.676 vs 0.673; p = 0.685), but smaller than the AUC of NMR-detected lipoproteins (0.676 vs 0.745; p < 0.001). NMR lipoproteins added discriminative value to HDL-cholesterol and TG levels (net reclassification improvement of 40.0%; p < 0.001; and integrated discrimination improvement of 9.5%; p < 0.001), with net benefit within predicted probabilities of between 10% and 50% by Vickers' decision-curve analysis. We also demonstrated additive value to demographic variables, BMI and levels of fasting glucose, TG, and HDL-cholesterol (net reclassification improvement of 14.0%; p < 0.001; and integrated discrimination improvement of 4.5%; p < 0.001). NMR lipoproteins, which can be measured in the fasting state, add information to the TG and HDL-cholesterol ratio across a broad range on insulin resistance. Depending on the other risk factors of insulin resistance that are incorporated, NMR lipoproteins permit the correct reclassification of an additional 14-40% of individuals.

Outcomes of Biomarker Feedback on Physical Activity, Eating Habits, and Emotional Health: From the Americans in Motion-Healthy Intervention (AIM-HI) Study

The purpose of this article was to test whether physical activity, healthy eating, and emotional well-being would improve if patients received feedback about biomarkers that have been shown to be responsive to changes in weight and fitness. Patients were randomized to limited feedback (weight, body mass index [BMI], and blood pressure at 4 and 10 months) or enhanced feedback (weight, BMI, blood pressure, homeostatic insulin resistance, and nuclear magnetic resonance lipoprotein profiles at 2, 4, 7, and 10 months). Repeated measures mixed effects multivariate regression models were used to determine whether BMI, fitness, diet, and quality of life changed over time. Major parameters were similar in both groups at baseline. BMI, measures of fitness, healthy eating, quality of life, and health state improved in both patient groups, but there was no difference between patient groups at 4 or 10 months. Systolic blood pressure improved in the enhanced feedback group, and there was a difference between the enhanced and limited feedback groups at 10 months (95% confidence interval, -6.011 to -0.5113). Providing patients with enhanced feedback did not dramatically change outcomes. However, across groups, many patients maintained or lost weight, suggesting the need for more study of nondiet interventions.

Particle numbers of lipoprotein subclasses and arterial stiffness among middle-aged men from the ERA JUMP study

We examined the association between serum lipoprotein subclasses and the three measures of arterial stiffness i.e. (i) carotid-femoral pulse wave velocity (cfPWV) which is a gold standard measure of central arterial stiffness, (ii) brachial-ankle PWV (baPWV) which is emerging as a combined measure of central and peripheral arterial stiffness, and (iii) femoral-ankle PWV (faPWV) which is a measure of peripheral arterial stiffness. Among a population-based sample of 701 apparently healthy Caucasian, Japanese American and Korean men aged 40–49 years, concentrations of lipoprotein particles were assessed by nuclear magnetic resonance (NMR) spectroscopy, and PWV was assessed with an automated waveform analyzer (VP2000, Omron, Japan). Multiple linear regressions were performed to analyze the association between each NMR lipoprotein subclasses and PWV measures, after adjusting for cardiovascular risk factors and other confounders. A cut-off of p<0.01 was used for determining significance. All PWV measures had significant correlations with total and small low-density lipoprotein particle number (LDL-P) (all p<0.0001) but not LDL-cholesterol (LDL-C) (all p>0.1), independent of race and age. In multivariate regression analysis, no NMR lipoprotein subclass was significantly associated with cfPWV (all p>0.01). However, most NMR lipoprotein subclasses had significant associations with both baPWV and faPWV (p<0.01). In this study of healthy middle-aged men, as compared to cfPWV, both baPWV and faPWV had stronger associations with particle numbers of lipoprotein subclasses. Our results may suggest that both baPWV and faPWV are related to arterial stiffness and atherosclerosis, whereas cfPWV may represent arterial stiffness alone.

Effectiveness of 2 methods of promoting physical activity, healthy eating, and emotional well-being with the americans in motion--healthy interventions approach.

An increasing number of Americans are putting their health at risk from being overweight. We undertook a study to compare patient-level outcomes of 2 methods of implementing the Americans In Motion-Healthy Interventions (AIM-HI) approach to promoting physical activity, healthy eating, and emotional well-being. We conducted a randomized trial in which 24 family medicine practices were randomized to (1) an enhanced practice approach in which clinicians and office staff used AIM-HI tools to make personal changes and created a healthy environment, or (2) a traditional practice approach in which physicians and staff were trained and asked to use the tools with patients. Of the 610 patients enrolled, 331 were in healthy practices, and 279 were in traditional practices. At 0, 4, and 10 months we assessed blood pressure, body mass index, fasting blood glucose and insulin levels, nuclear magnetic resonance lipoprotein profiles, fitness, dietary intake, physical activity, and emotional well-being. Outcome data were analyzed using linear, mixed-effects multivariate models, adjusting for practices as a random effect. Regardless of patient group, 16.2% of patients who completed a 10-month visit (n = 378 patients, 62% of enrollees) and 10% of all patients enrolled lost 5% or more of their body weight; 16.7% of patients who completed a 10-month visit (10.3% of all enrollees) had a 2-point or greater increase in their fitness level; and 29.2% of 10-month completers (18.0% of all enrollees) lost 5% or more of their body weight and/or increased their fitness level by 2 or more points. There were no significant differences in these outcomes between groups. There was no difference between the 2 groups in the primary and most secondary outcomes. Both patient groups were able to show significant before-after improvements in selected patient-level outcomes.

Advanced lipoprotein measures and recurrent preterm birth

Lipoproteins are associated with atherogenic and inflammatory processes, and these processes may be related to adverse pregnancy outcomes. We therefore examined whether variations in lipoprotein particle size and concentration are associated with preterm birth (PTB) <35 weeks' gestation. This is a case-control ancillary study to a randomized trial of omega-3 fatty acid supplementation to prevent recurrent PTB. We measured standard lipids and used nuclear magnetic resonance (NMR) spectroscopy to characterize 17 lipoprotein particles from plasma collected at the baseline randomization visit (16-21weeks' gestation) in 128 cases (PTB <35 weeks' gestation) and 132 term controls. Logistic regression models controlled for study center, race/ethnicity, number of prior PTB, smoking, and treatment group,as well as total low-density lipoprotein (LDL), high-density lipoprotein, and triglyceride concentrations when examining LDLNMR, high-density lipoproteinNMR, and very LDL (VLDL)NMR, respectively. Only 1 of the 17 NMR lipoproteins was associated with recurrent PTB. We observed an increased odds of recurrent PTB of 1.04 (95% confidence interval, 1.01-1.08; P= .02) per nanometer increase in VLDLNMR particle size and an odds ratio of 3.00 (confidence interval, 1.40-6.43; P= .005) for the third tertile of VLDLNMR particle size compared with the first tertile. In women with prior PTB, variations in midpregnancy lipoproteins were not associated with recurrent PTB overall, however the association observed with VLDLNMR particle size is suggestive that PTBmay be amenable to lifestyle, nutritional, or pharmacologic interventions.

The association of alanine aminotransferase within the normal and mildly elevated range with lipoproteins and apolipoproteins: the Insulin Resistance Atherosclerosis Study

Markers of liver injury, such as alanine aminotransferase (ALT), have been associated with atherogenic lipoprotein changes. We examined the extent to which this association was explained by insulin resistance, adiposity, glucose tolerance and chronic inflammation. In this analysis we included 824 non-diabetic participants (age 40-69 years) in the Insulin Resistance Atherosclerosis Study. No participants reported excessive alcohol intake or treatment with lipid-lowering medications. Lipoproteins and apolipoproteins were measured by conventional methods and lipoprotein heterogeneity by nuclear magnetic resonance (NMR) spectroscopy. ALT had a positive relationship with triacylglycerols, LDL-to-HDL-cholesterol ratio and apolipoprotein B (ApoB) after adjusting for demographic variables (p < 0.001 for all three relationships). ALT was also associated with the following NMR lipoproteins: positively with large VLDL (p < 0.001), intermediate-density lipoprotein (IDL) (p < 0.001) and small LDL subclass particles (p < 0.001), and VLDL particle size (p < 0.001); and negatively with large LDL subclass particles (p < 0.05) and LDL (p < 0.001) and HDL particle sizes (p < 0.01). ALT remained associated with IDL and small LDL subclass particles and ApoB after adjusting for glucose tolerance, adiposity, directly measured insulin sensitivity and C-reactive protein. ALT is associated with a wide range of atherogenic lipoprotein changes, which are partially explained by insulin resistance, adiposity, glucose tolerance and chronic inflammation. Because of the significant variability in the relationship between ALT and liver fat, further studies are needed to assess the extent of the lipoprotein changes using a direct measure of liver fat.

Abstract 19075: Impact of LDL Apheresis on Lipoprotein Particle Concentrations

Background: Low-density lipoprotein (LDL) apheresis via dextran-sulfate-cellulose absorption lowers LDL cholesterol (LDL-C) levels (&gt;60%) by removing apoB containing lipoproteins due to their positive charge. Although HDL is negatively charged LDL apheresis also causes small but significant reductions in HDL-C levels (10-15%). LDL particle number (LDL-P) has been associated more strongly with clinical atherosclerotic outcomes than LDL-C; however, the impact of LDL apheresis on lipoprotein particle concentrations as determined by nuclear magnetic resonance (NMR) has not been reported. Objective: To determine the effects of LDL apheresis on lipoprotein particle concentrations and to compare changes in lipoprotein particle concentrations to conventional serum lipid levels. Methods: Comprehensive NMR lipoprotein analysis was performed on serum obtained from five subjects prior to and following three occasions of LDL apheresis performed at two-week intervals. Three subjects had homozygous familial hypercholesterolemia (FH) and two had coronary artery disease (CAD) and mixed dyslipidemia with LDL-C &gt; 200 mg/dL (one subject had pre-treatment triglyceride (TG) levels &gt; 400 mg/d) prior to and following LDL apheresis Results: Mean LDL-P concentration was 2957+1024 nmol/L, HDL particle number (HDL-P) was 27+9 μ mol/L and TG was 224+208 mg/dL. LDL apheresis treatment reduced LDL-P by 67% (p &lt; 0.0001) and decreased TG (43%, p = 0.153) to a lesser extent. All reductions were significant in subjects with pre-treatment TG levels &lt; 400 mg/dL. The mean HDL-P increased slightly with treatment (29+7 mg/dL, p = 0.533), but the effect was not significant. There were no treatment-dependent changes in the size distribution of LDL particles, whereas HDL particle size shifted toward an increase in medium HDL-P in FH subjects. Conclusion: This is the first report on the effects of LDL apheresis on serum concentrations of lipoprotein particles as determined by NMR. LDL apheresis promoted dramatic reductions in both LDL-C and LDL-P, whereas HDL-P was unchanged to slightly increased despite a significant decrease in HDL-C.