Particle Cholesterol Research Articles

Description of Discordance Between LDL Cholesterol, Non-HDL Cholesterol, and LDL Particle Number Among Patients of a Lipid Clinic

Background: While LDL cholesterol measures the cholesterol content within an LDL particle (LDL-P), it may not reflect LDL-P concentrations. If discordance exists, LDL-P may better predict cardiovascular events compared to LDL-C and non-HDL cholesterol (non-HDL-C). In primary prevention patients, discordance has been associated with diabetes, ethnicity, gender, metabolic syndrome, and smoking history. 
 Objective: To describe discordance in patients of a lipid clinic by exploring associations between patient characteristics and discordance among LDL-C, non-HDL-C, or LDL-P. Secondarily to compare proportion of patients with baseline concordance versus discordance who have ASCVD events, diagnoses of new onset diabetes or death.
 Methods: A retrospective, single-center cohort study at a large academic medical center was conducted. Patients establishing care from January 2009 through December 2012 with complete initial labs were included. Logistic regression models were used to explore associations between discordance and patient characteristics.
 Results: Of 603 patients screened, the final cohort included 166 patients with 104 (62.7%) discordant. LDL-P was the most common discordant value. Discordance was associated with gender, smoking status, use of lipid lowering medications, and achieving patient specific LDL-C goals. In terms of any event observed after initial measurements, no significant differences were detected between discordant and concordant groups.
 Conclusion: Within a lipid clinic population, discordance was associated with male gender, smoking status, lipid-lowering therapy, and being at patient specific LDL-C goal. While associations were found in our population, clinicians should consider measuring LDL-P to fully assess presence or extent of discordance.
 Conflict of Interest
 We declare no conflicts of interest or financial interests that the authors or members of their immediate families have in any product or service discussed in the manuscript, including grants (pending or received), employment, gifts, stock holdings or options, honoraria, consultancies, expert testimony, patents and royalties. 
 
 Type: Original Research

Low-density lipoprotein 4: a novel predictor of coronary artery disease severity

Background: Hyperlipidemia is a well established risk factor for coronary artery disease (CAD). Severe CAD has been observed in patients with normal levels of total and low-density lipoprotein (LDL) cholesterol. Small dense LDL particle subtypes (LDL3 and LDL4) have been observed to be more oxidizable and atherogenic. We aimed to identify the role of cholesterol particle subtypes in predicting CAD severity.Methods: Blood samples were obtained immediately before cardiac catheterization in 179 consecutive patients with suspected CAD. Detailed lipid profiling was performed using a VAP cholesterol test. CAD severity was categorized angiographically as no/minor CAD (<20% luminal diameter stenosis [LDS]), moderate CAD (20% to 74% LDS) and severe CAD (>75% LDS of any major coronary vessel).Results: Patients with severe CAD had significantly higher LDL4 and triglycerides, and lower total HDL, HDL2, HDL3, LDL2 and LDL3 compared to patients with no/minor CAD (p < .05 for all). Multivariate analysis showed high LDL4 as an independent predictive of severe CAD. ROC analysis showed an area under the curve of 0.62 (p < .0001) with a cut-point of >16.9 mg/dL to predict severe CAD with a sensitivity of 53% and specificity of 79%.Conclusion: Elevated LDL4 levels are associated with severe CAD. Further large-scale investigations are required to evaluate the utility of LDL4 in predicting CAD severity.

Effects of gender and menopause on the cholesterol and triglyceride particle number of lipoprotein subclasses as separated by high performance liquid chromatography

Effects of gender and menopause on the cholesterol and triglyceride particle number of lipoprotein subclasses as separated by high performance liquid chromatography

High density lipoproteins and type 2 inflammatory biomarkers are negatively correlated in atopic asthmatics

Blood eosinophil counts and serum periostin levels are biomarkers of type 2 inflammation. Although serum levels of HDL and apoA-I have been associated with less severe airflow obstruction in asthma, it is not known whether serum lipids or lipoprotein particles are correlated with type 2 inflammation in asthmatics. Here, we assessed whether serum lipids and lipoproteins correlated with blood eosinophil counts or serum periostin levels in 165 atopic asthmatics and 163 nonasthmatic subjects with and without atopy. Serum lipids and lipoproteins were quantified using standard laboratory assays and NMR spectroscopy. Absolute blood eosinophils were quantified by complete blood counts. Periostin levels were measured using the Elecsys® periostin assay. In atopic asthmatics, blood eosinophils negatively correlated with serum HDL cholesterol and total HDL particles measured by NMR spectroscopy (HDLNMR). Serum periostin levels negatively correlated with total HDLNMR In contrast, blood eosinophil counts positively correlated with serum triglyceride levels. This study demonstrates for the first time that HDL particles were negatively correlated, whereas serum triglycerides were positively correlated, with blood eosinophils in atopic asthmatics. This supports the concept that serum levels of HDL and triglycerides may be linked to systemic type 2 inflammation in atopic asthma.

Cholesterol Efflux Capacity, High-Density Lipoprotein Particle Number, and Incident Cardiovascular Events: An Analysis From the JUPITER Trial (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin).

Recent failures of drugs that raised high-density lipoprotein (HDL) cholesterol levels to reduce cardiovascular events in clinical trials have led to increased interest in alternative indices of HDL quality, such as cholesterol efflux capacity, and HDL quantity, such as HDL particle number. However, no studies have directly compared these metrics in a contemporary population that includes potent statin therapy and low low-density lipoprotein cholesterol. HDL cholesterol levels, apolipoprotein A-I, cholesterol efflux capacity, and HDL particle number were assessed at baseline and 12 months in a nested case-control study of the JUPITER trial (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin), a randomized primary prevention trial that compared rosuvastatin treatment to placebo in individuals with normal low-density lipoprotein cholesterol but increased C-reactive protein levels. In total, 314 cases of incident cardiovascular disease (CVD) (myocardial infarction, unstable angina, arterial revascularization, stroke, or cardiovascular death) were compared to age- and gender-matched controls. Conditional logistic regression models adjusting for risk factors evaluated associations between HDL-related biomarkers and incident CVD. Cholesterol efflux capacity was moderately correlated with HDL cholesterol, apolipoprotein A-I, and HDL particle number (Spearman r= 0.39, 0.48, and 0.39 respectively; P<0.001). Baseline HDL particle number was inversely associated with incident CVD (adjusted odds ratio per SD increment [OR/SD], 0.69; 95% confidence interval [CI], 0.56-0.86; P<0.001), whereas no significant association was found for baseline cholesterol efflux capacity (OR/SD, 0.89; 95% CI, 0.72-1.10; P=0.28), HDL cholesterol (OR/SD, 0.82; 95% CI, 0.66-1.02; P=0.08), or apolipoprotein A-I (OR/SD, 0.83; 95% CI, 0.67-1.03; P=0.08). Twelve months of rosuvastatin (20 mg/day) did not change cholesterol efflux capacity (average percentage change -1.5%, 95% CI, -13.3 to +10.2; P=0.80), but increased HDL cholesterol (+7.7%), apolipoprotein A-I (+4.3%), and HDL particle number (+5.2%). On-statin cholesterol efflux capacity was inversely associated with incident CVD (OR/SD, 0.62; 95% CI, 0.42-0.92; P=0.02), although HDL particle number again emerged as the strongest predictor (OR/SD, 0.51; 95% CI, 0.33-0.77; P<0.001). In JUPITER, cholesterol efflux capacity was associated with incident CVD in individuals on potent statin therapy but not at baseline. For both baseline and on-statin analyses, HDL particle number was the strongest of 4 HDL-related biomarkers as an inverse predictor of incident events and biomarker of residual risk. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681.

Brief Report: Progression of Atherosclerosis in HIV-Infected Individuals-Prospective Data From an Asian Cohort.

The magnitude and risk factors of progression of atherosclerosis in Asian HIV-infected individuals were unknown. This study aimed to evaluate: (1) the rate of progression of atherosclerosis in HIV-infected individuals, and (2) metabolic and inflammatory parameters that may predict atherosclerosis progression in HIV-infected individuals in an Asian cohort. A prospective, longitudinal study was performed among adults attending an HIV Metabolic clinic in Hong Kong. Carotid intima media thickness (cIMT) was measured at baseline and 24 months. Body composition, metabolic, and inflammatory biomarkers [including homeostasis model assessment of insulin resistance, LDL (low-density lipoprotein) cholesterol particle size, high-sensitive C reactive protein, adiponectin] associated with cIMT change were analyzed; their predictive performances were estimated using receiver operating characteristic analyses. Sixty-one HIV-infected individuals (mean ± SD age 49.8 ± 11.4 years, 89% men, 97% Chinese, diabetes 39%, hypertension 30%, and dyslipidemia 85%) were recruited. Annual rate of change of cIMT was +0.0075 (0.0000-0.0163) mm/yr, and 19% developed new plaque at 24 months. Two patients died during the study period, 1 because of sudden cardiac death. Using receiver operating characteristic analyses, combination of lower limb fat percentage, LDL cholesterol subclass pattern B, and lower adiponectin level, but not Framingham score, predicted greater cIMT progression in HIV-infected individuals. Asian HIV-infected individuals had atherosclerosis progression. Limb fat percentage, LDL cholesterol particle size, and adiponectin level may identify at-risk Asian HIV-infected individuals for early intervention.

Association of Air Pollution Exposures With High-Density Lipoprotein Cholesterol and Particle Number: The Multi-Ethnic Study of Atherosclerosis.

The relationship between air pollution and cardiovascular disease may be explained by changes in high-density lipoprotein (HDL). We examined the cross-sectional relationship between air pollution and both HDL cholesterol and HDL particle number in the MESA Air study (Multi-Ethnic Study of Atherosclerosis Air Pollution). Study participants were 6654 white, black, Hispanic, and Chinese men and women aged 45 to 84 years. We estimated individual residential ambient fine particulate pollution exposure (PM2.5) and black carbon concentrations using a fine-scale likelihood-based spatiotemporal model and cohort-specific monitoring. Exposure periods were averaged to 12 months, 3 months, and 2 weeks prior to examination. HDL cholesterol and HDL particle number were measured in the year 2000 using the cholesterol oxidase method and nuclear magnetic resonance spectroscopy, respectively. We used multivariable linear regression to examine the relationship between air pollution exposure and HDL measures. A 0.7×10-6 m-1 higher exposure to black carbon (a marker of traffic-related pollution) averaged over a 1-year period was significantly associated with a lower HDL cholesterol (-1.68 mg/dL; 95% confidence interval, -2.86 to -0.50) and approached significance with HDL particle number (-0.55 mg/dL; 95% confidence interval, -1.13 to 0.03). In the 3-month averaging time period, a 5 μg/m3 higher PM2.5 was associated with lower HDL particle number (-0.64 μmol/L; 95% confidence interval, -1.01 to -0.26), but not HDL cholesterol (-0.05 mg/dL; 95% confidence interval, -0.82 to 0.71). These data are consistent with the hypothesis that exposure to air pollution is adversely associated with measures of HDL.

Cholesterol delivery to the adrenal glands estimated by adrenal venous sampling: An in vivo model to determine the contribution of circulating lipoproteins to steroidogenesis in humans

Cholesterol, required for adrenal steroid hormone synthesis, is at least in part derived from circulating lipoproteins. The contribution of high-density lipoproteins (HDL) and low-density lipoproteins (LDL) to adrenal steroidogenesis in humans is unclear. The aim of the study was to determine the extent to which HDL and LDL are taken up by the adrenal glands using samples obtained during adrenal venous sampling (AVS). AVS was successfully performed in 23 patients with primary aldosteronism. Samples were drawn from both adrenal veins and inferior vena cava (IVC). HDL cholesterol (HDL-C) and lipoprotein particle profiles were determined by nuclear magnetic resonance spectroscopy. Apolipoprotein (apo) A-I and apoB were assayed by immunoturbidimetry. Plasma HDL-C and HDL and LDL particle concentrations (HDL-P and LDL-P) were not lower in samples obtained from the adrenal veins compared with the IVC (HDL-C, P=.59; HDL-P, P=.06; LDL-P, P=.93). ApoB was lower in adrenal venous plasma than in IVC (P=.026; P<.05 for right adrenal vein). In 13 patients with an aldosterone producing adenoma (APA), apoB was also lower (P=.045) and LDL-P tended to be lower (P=.065) in the APA adrenal vein compared with the IVC. ApoA-I was not lower in adrenal venous plasma compared with the IVC, neither in the whole group (P=.20) nor in the APA subgroup (P=.075). These invivo observations suggest that circulating LDL may contribute to adrenal steroidogenesis in humans as inferred from adrenal venous-IVC apoB concentration differences. AVS is a feasible method to investigate the relationships between lipoproteins and steroidogenesis.

High‐Density Lipoprotein Cholesterol Concentrations and Particle Size Are Modified by Dietary Zinc in Men

ObjectiveTo measure biomarkers of lipid metabolism in response to a marginal zinc depletion, repletion, and supplementation in healthy male subjects.MethodsEighteen male subjects between ages of 18–45 consumed a controlled diet (80% carbohydrate, 10% fat, 10% protein) with two levels of dietary zinc. Phase I: Low zinc: 6 mg/day with 1.5 mg of phytate (2 weeks); Phase II: Zinc repletion: 10 mg/day with no phytate (4 weeks). Thereafter, a 25 mg/day zinc supplement was administered with an ad libitum diet for 3 weeks (Phase III). Targeted analysis of lipids and lipoprotein particle size were performed using standard methodology.ResultsPlasma zinc levels remained unchanged during Phases I and II in all subjects; they increased by 17.4 ± 3.8% (mean ± SE) at the end of supplementation (phase III). Apo‐A1 decreased significantly from 119.2 ± 13.2 mg/dL (mean ± SD) to 110.2 ± 13.2 mg/dL (p=0.003) at the end of the low zinc period. Apo‐A1 remained low at the end of phase II, but returned back to baseline after supplementation. A similar pattern was observed in HDL‐c and HDL‐L (large buoyant HDL particles) levels across the three phases. Plasma triglyceride levels increased during the 6‐week high‐carbohydrate diet, but were not modified by shifts in dietary zinc. Based on our previous observation of higher DNA strand breaks in the low zinc metabolic period and literature reports linking cancer to low HDL‐c levels, we performed a correlation analysis of DNA strand breaks and HDL subspecies. Our results show that the percent changes in HDL‐L and DNA strand breaks from phase I to II are negatively correlated (r=−0.45; p=0.05).ConclusionResults from our studies show that low zinc combined with a high carbohydrate diet increased biomarkers of dyslipidemia, but provision of adequate dietary zinc or a zinc supplement for a short period of time mitigated the increase in these biomarkers.Support or Funding InformationHarvest Plus

Discordance between Circulating Atherogenic Cholesterol Mass and Lipoprotein Particle Concentration in Relation to Future Coronary Events in Women

It is uncertain whether measurement of circulating total atherogenic lipoprotein particle cholesterol mass [non-HDL cholesterol (nonHDLc)] or particle concentration [apolipoprotein B (apo B) and LDL particle concentration (LDLp)] more accurately reflects risk of incident coronary heart disease (CHD). We evaluated CHD risk among women in whom these markers where discordant. Among 27533 initially healthy women in the Women's Health Study (NCT00000479), using residuals from linear regression models, we compared risk among women with higher or lower observed particle concentration relative to nonHDLc (highest and lowest residual quartiles, respectively) to individuals with agreement between markers (middle quartiles) using Cox proportional hazards models. Although all 3 biomarkers were correlated (r ≥ 0.77), discordance occurred in up to 20.2% of women. Women with discordant high particle concentration were more likely to have metabolic syndrome (MetS) and diabetes (both P < 0.001). Over a median follow-up of 20.4 years, 1246 CHD events occurred (514725 person-years). Women with high particle concentration relative to nonHDLc had increased CHD risk: age-adjusted hazard ratio (95% CI) = 1.77 (1.56-2.00) for apo B and 1.70 (1.50-1.92) for LDLp. After adjustment for clinical risk factors including MetS, these risks attenuated to 1.22 (1.07-1.39) for apo B and 1.13 (0.99-1.29) for LDLp. Discordant low apo B or LDLp relative to nonHDLc was not associated with lower risk. Discordance between atherogenic particle cholesterol mass and particle concentration occurs in a sizeable proportion of apparently healthy women and should be suspected clinically among women with cardiometabolic traits. In such women, direct measurement of lipoprotein particle concentration might better inform CHD risk assessment.

Sex-Based Differences in Cardiometabolic Biomarkers.

Few data are available comparing cardiovascular disease (CVD) biomarker profiles between women and men in the general population. We analyzed sex-based differences in multiple biomarkers reflecting distinct pathophysiological pathways, accounting for differences between women and men in CVD risk factors, body composition, and cardiac morphology. A cross-sectional analysis was performed using data from the Dallas Heart Study, a multiethnic population-based study. Associations between sex and 30 distinct biomarkers representative of 6 pathophysiological categories were evaluated using multivariable linear regression adjusting for age, race, traditional CVD risk factors, kidney function, insulin resistance, MRI and dual-energy x-ray absorptiometry measures of body composition and fat distribution, and left ventricular mass. After excluding participants with CVD, the study population included 3439 individuals, mean age 43 years, 56% women, and 52% black. Significant sex-based differences were seen in multiple categories of biomarkers, including lipids, adipokines, and biomarkers of inflammation, endothelial dysfunction, myocyte injury and stress, and kidney function. In fully adjusted models, women had higher levels of high-density lipoprotein cholesterol and high-density lipoprotein particle concentration, leptin, d-dimer, homoarginine, and N-terminal pro B-type natriuretic peptide, and lower levels of low-density lipoprotein cholesterol, adiponectin, lipoprotein-associated phospholipase A2 mass and activity, monocyte chemoattractant protein-1, soluble endothelial cell adhesion molecule, symmetrical dimethylarginine, asymmetrical dimethylarginine, high-sensitivity troponin T, and cystatin C. Biomarker profiles differ significantly between women and men in the general population. Sex differences were most apparent for biomarkers of adiposity, endothelial dysfunction, inflammatory cell recruitment, and cardiac stress and injury. Future studies are needed to characterize whether pathophysiological processes delineated by these biomarkers contribute to sex-based differences in the development and complications of CVD.

Association of Comprehensive Lipoprotein Profiling with Coronary Artery Disease in Allogeneic Stem Cell Transplant (Allo-SCT) Survivors

INTRODUCTION:Premature vascular disease is a leading cause of late mortality in allogeneic stem cell transplantation (SCT) survivors but the underlying mechanism is not understood. Dyslipidemia is a strong and targetable risk factor for coronary artery disease (CAD) in the general population and its relevance (higher prevalence and high attributable risk in epidemiologic studies of arterial disease) has also been recognized in SCT survivors over the last decade. However, we have previously shown that Framingham risk scores, which rely upon traditional lipid cholesterol measures, are insensitive in determining the presence of CAD. Here, we present the first comprehensive lipoprotein analysis in well-annotated asymptomatic SCT survivors, simultaneously assessed for vascular health using cardiac CT to identify CAD.PATIENTS & METHODS:We performed a cross-sectional analysis of 67 survivors who underwent allo-SCT between 1993 and 2012 for hematologic malignancies and survived for at least three years. All subjects received total body irradiation (TBI) based conditioning followed by a 3-4 log ex vivo T cell depleted graft. The median age at transplant was 39 years (range 17-69). The median duration of follow up was 11 years (range 3-22). Sixty percent were male. Seventy percent had some chronic GVHD, but only 23% required immunosuppression at 3 years post transplant. All subjects had a cardiac CT performed and CAD was defined by the presence of either luminal stenosis by angiography or coronary calcification. Cardiovascular clinical data (hypertension, diabetes, dyslipidemia, smoking, CRP, body mass index) and 10- year Framingham risk scores were also collected. Comprehensive lipoprotein analysis was performed on fasting plasma samples using nuclear magnetic resonance (NMR) with the Vantera clinical analyzer (LipoScience Inc., Raleigh, NC). Digitized spectral data signals undergo algorithmic processing to identify and quantify concentrations of lipoproteins and, potentially, small molecule metabolites from a single sample. 13 subjects with history of lipid lowering therapy or absence of plasma sample were excluded. 24 lipoprotein metabolites were measured including particle cholesterol content (_C), particle count (_P), size [small (S_), medium (M_), large (L_), large + medium (LM_)] and average size (_Z). Due to natural variability in the amount of cholesterol per particle, HDL_C/LDL_C and HDL_P/LDL_P levels often are discordant. HDL_P/LDL_P provides a more clinically reliable measure of HDL/LDL quantity than HDL_C/LDL_C.RESULTS:CAD was confirmed in 45% of survivors; 89% of lesions were non-obstructive and 28% of plaques were non-calcified. Lipoprotein analysis on 54 subjects showed no significant association between HDL or LDL particle cholesterol content, particle count or size distribution. Interestingly, measures of Triglyceride and VLDL were significantly higher in survivors with CAD vs no CAD [VLDL_P median 90.4 vs 54.0 nmol/L (p= 0.009), M_VLDL_P 40.2 vs 23.1 nmol/L (p= 0.03), LM_VLDL_P 44.5 vs 26.1 nmol/L (p= 0.04), and total triglycerides (TG) 172 vs 133 mg/dL (p= 0.03)] (Figure 1).CONCLUSION:In allo-SCT long term survivors, elevated triglyceride and VLDL counts were associated with early CAD even when traditional targetable measures of dyslipidemia (HDL and LDL) were normal. Future efforts will integrate traditional cardiac risk factors with metabolic markers (lipoproteins, insulin resistance and growth hormone deficiency) to better understand premature coronary artery disease in SCT recipients. [Display omitted] DisclosuresBattiwalla:NIH/NHLBI: Employment.

Solubility and solubilizing capabilities of aqueous solutions of Extractum Taraxaci e radix cum herba aqu. siccum in light of selected values of general Hildebrand-Scatchard-Fedors theory of solubility

Summary Introduction: The general Hildebrand-Scatchard theory of solubility supplemented by Fedors’ solubility parameter − δ 1 2 $- \delta ^{{1 \over 2}} $ was used to estimate the real solubility by −log x2 (log of the mole fraction) of phytochemicals contained in Ext. Taraxaci e radix cum herba aqu. siccum. Surface activity of aqueous solution of extracts was determined and quantified – solubilizing capabilities of solutions of cexp. ≥cmc in relation to cholesterol particle size of Ø=1.00 mm, as well as of ketoprofen were defined. Objective: The calculated value −log x2 collated with the polarity of extraction medium εM allows to estimate the optimal solubility of phytochemicals that determine the viscosity of the aqueous extract of dandelion and above all its surface activity and the ability to solubilize lipophilic therapeutic agents (ketoprofen). Methods: Viscosity of water model solutions of dandelion extracts and exhibition solutions after the effective micellar solubilization of cholesterol and ketoprofen was measured using Ubbelohde viscometer in accordance with the Polish Standard. The surface tension of aqueous solutions of extract and exhibition solutions after solubilization of cholesterol and ketoprofen was measured according to the Polish Standard with stalagmometric method. Results: The calculated factual solubility, and mainly the determined and calculated hydrodynamic size mean, that despite the complex structure of the micelle, it solubilizes cholesterol (granulometric grain of diameter Ø=1.00 mm) and ketoprofen (state of technological fragmentation) in equilibrium conditions. Equilibrium solubilization of ketoprofen also occurs in an environment of model gastric juice (0.1 mol HCl). Conclusions: The obtained results indicate that after the administration (and/or dietary supplementation) with Ext. Taraxaci e radix cum herba aqu. siccum, the physiological parameters of gastric juice would not be measured and its presence (phytosurfactant) in the body of the duodenum (bile A) increases abilities of solubilizing lipophilic therapeutic agents and cholesterol accounting for its use in the treatment of liver diseases and cholesterol gall bladder stones.

Sex differences in lipid profiles and treatment utilization among young adults with acute myocardial infarction: Results from the VIRGO study

Young women with acute myocardial infarction (AMI) have higher mortality risk than similarly aged men. An adverse lipid profile is an important risk factor for cardiovascular outcomes after AMI, but little is known about whether young women with AMI have a higher-risk lipid pattern than men. We characterized sex differences in lipid profiles and treatment utilization among young adults with AMI. A total of 2,219 adults with AMI (1,494 women) aged 18-55 years were enrolled from 103 hospitals in the United States (2008-2012). Serum lipids and lipoprotein subclasses were measured 1 month after discharge. More than 90% of adults were discharged on a statin, but less than half received a high-intensity dose and 12% stopped taking treatments by 1 month. For both men and women, the median of low-density lipoprotein (LDL) cholesterol was reduced to <100 mg/dL 1 month after discharge for AMI, but high-density lipoprotein (HDL) cholesterol remained <40 mg/dL. Multivariate regression analyses showed that young women had favorable lipoprotein profiles compared with men: women had higher HDL cholesterol and HDL large particle, but lower total cholesterol-to-HDL cholesterol ratio and LDL small particle. Young women with AMI had slightly favorable lipid and lipoprotein profiles compared with men, suggesting that difference in lipid and lipoprotein may not be a major contributor to sex differences in outcomes after AMI. In both men and women, statin remained inadequately used, and low HDL cholesterol level was a major lipid abnormality.

Metabolic abnormalities in patients with inflammatory rheumatic diseases.

Patients with rheumatoid arthritis (RA) experience an increased cardiometabolic risk factor burden that is substantially driven by systemic inflammation. This occurs less consistently in patients with ankylosing spondylitis (AS). Psoriatic arthritis most strongly associates with excess adiposity and metabolic risk. RA patients also often have systemic inflammation-induced proinflammatory high-density lipoprotein (HDL) cholesterol particles and lean/muscle mass loss in association with increased adiposity, a condition termed rheumatoid cachexia, which further enhances cardiovascular risk. The presence of proinflammatory HDL and lean mass loss was also reported in patients with AS. Individualized aerobic and resistance exercise programs can improve body composition and metabolic risk factor profiles in RA and AS. Future studies should assess how long-term lifestyle changes can be effectuated and if these can influence cardiovascular events in inflammatory rheumatic diseases. Herein, we review the current evidence on metabolic abnormalities in inflammatory arthritis. We propose management strategies and a research agenda.

Evaluation of Non-HDL Cholesterol and Total Cholesterol/HDL-C Ratio, LDL-C/HDL-C Ratio as Cumulative Marker of Cardiovascular Disease risk in Type 2 Diabetes Mellitus Patients

Background: Cardiovascular disease (CVD) is the leading cause of death worldwide with an estimated 17.3 million deaths from CVDs in 2008, representing 30% of all global deaths. The main cause of CVD development is atherosclerosis and among the various factors for developing increased cardiovascular risk in diabetes; lipid abnormalities, the dyslipidemia is the major contributor. The common type of dyslipidemia in diabetes is characterized by elevated triglyceride (TG), low levels of high density lipoprotein cholesterol (HDL-C) and typically has a preponderance of smaller, denser low density lipoprotein cholesterol (LDL-C) particles, which possibly increases atherogenicity even if the absolute concentration of LDL cholesterol (LDL-C) is not significantly increased. Materials & Methods: Total of 100 diagnosed type 2 diabetes mellitus ambulatory patients of both sexes were taken as cases. Their age ranged between 30 to 70 years. 100 healthy subjects, with their age ranging between 30 to 70 years were selected as control group. Serum sample was used for the estimation of study parameters such as FBS, PPBS, Total Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol. Results: In this study, total cholesterol, triglycerides, LDL-C, Non-HDL-C, TC/HDL-C and LDL-C/HDL-C were found to be statistically significantly increased in type 2 diabetes mellitus patients when compared to controls. HDL-C was significantly decreased in type 2 diabetes mellitus patients when compared to controls ( p -value 0.001). Conclusion: In this study, type 2 diabetes mellitus is associated with dyslipidemia with increased levels of TC, TG, LDL-C, Non-HDL-C, TC/HDL-C and LDL-C/HDL-C ratio, but a lower levels of HDL-C compared to that of controls. Increased levels of Non-HDL-C, TC/HDL-C and LDL-C/HDL-C ratio which indicates increased impending cardiovascular disease risk in type 2 diabetes mellitus.

Corn oil intake favorably impacts lipoprotein cholesterol, apolipoprotein and lipoprotein particle levels compared with extra-virgin olive oil.

Corn oil (CO) and extra-virgin olive oil (EVOO) are rich sources of unsaturated fatty acids (UFA), but UFA profiles differ among oils, which may affect lipoprotein levels. The objective of this study was to assess the effects of CO versus EVOO intake on fasting lipoprotein and subfraction cholesterol levels, apolipoprotein (apo) A1, apo B, and low-density lipoprotein particle concentrations in men and women. As part of a weight maintenance diet, men and women were provided with food items prepared with 54 g per day of CO or EVOO (21-day treatment, 21-day washout) in a randomized, double-blind, controlled-feeding, crossover trial. Fasting lipoprotein cholesterol and related variables were determined with density gradient ultracentrifugation. Among the 54 completers, CO reduced total cholesterol, low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apo B and LDL particle concentration to a greater extent compared with EVOO intake. Changes in LDL-C and VLDL-C contributed to the larger reduction in non-HDL-C with CO compared with EVOO intake (-0.39 mmol/l vs -0.04 mmol/l; P<0.001). The larger reduction in LDL-C by CO intake was attributable to changes (P<0.05) caused by CO vs EVOO in large LDL1+2-C (-0.22 mmol/l) and intermediate-density lipoprotein cholesterol (-0.12 mmol/l). HDL-C responses did not differ between treatments, but apo A1 increased more with EVOO compared with CO intake (4.6 versus 0.7 mg/dl, respectively, P=0.016). CO intake reduced atherogenic lipoprotein cholesterol and particle concentrations to a larger extent than did EVOO, which may have implications for cardiovascular disease risk.

Mendelian randomization analysis in three Japanese populations supports a causal role of alcohol consumption in lowering low-density lipid cholesterol levels and particle numbers

Background and aimsWhile alcohol consumption is known to increase plasma high-density lipoprotein (HDL) cholesterol levels, its relationship with low-density lipoprotein (LDL) cholesterol levels is unclear. Aldehyde dehydrogenase 2 (ALDH2) is a rate-controlling enzyme in alcohol metabolism, but a large number of Japanese people have the inactive allele. Here, we conducted a Mendelian randomization analysis using the ALDH2 genotype to clarify a causal role of alcohol on circulating cholesterol levels and lipoprotein particle numbers. MethodsThis study was conducted in three independent general Japanese populations (men, n = 2289; women, n = 1940; mean age 63.3 ± 11.2 years). Alcohol consumption was assessed using a questionnaire. Lipoprotein particle numbers were determined by nuclear magnetic resonance spectroscopy. ResultsAlcohol consumption increased linearly in proportion to the number of subjects carrying the enzymatically active *1 allele in men (p < 0.001). The *1 allele was also positively associated with HDL cholesterol level (adjusted mean ± standard error, *1*1: 60 ± 0.5, *1*2: 56 ± 0.6, *2*2: 55 ± 1.3 mg/dl, p < 0.001) and inversely associated with LDL cholesterol level (116 ± 0.9, 124 ± 1.1, 130 ± 2.6 mg/dl, p < 0.001). The *1 allele was also positively associated with HDL particle numbers (per-allele: 2.60 ± 0.32 μmol/l, p < 0.001) and inversely associated with LDL particle numbers (−67.8 ± 19.6 nmol/l, p = 0.001). Additional Mendelian randomization analysis failed to clarify the involvement of cholesteryl ester transfer protein in alcohol-related changes in lipoprotein cholesterol levels. No significant association was observed in women, presumably due to their small amount of alcohol intake. ConclusionsAlcohol consumption has a causal role in not only increasing HDL cholesterol levels but also decreasing LDL cholesterol levels and particle numbers.

Variant rs10911021 that associates with coronary heart disease in type 2 diabetes, is associated with lower concentrations of circulating HDL cholesterol and large HDL particles but not with amino acids.

AimsAn intergenic locus on chromosome 1 (lead SNP rs10911021) was previously associated with coronary heart disease (CHD) in type 2 diabetes (T2D). Using data from the UCLEB consortium we investigated the relationship between rs10911021 and CHD in T2D, whether rs10911021 was associated with levels of amino acids involved in the γ-glutamyl cycle or any conventional risk factors (CRFs) for CHD in the T2D participants.MethodsFour UCLEB studies (n = 6531) had rs10911021 imputation, CHD in T2D, CRF and metabolomics data determined using a nuclear magnetic resonance based platform.ResultsThe expected direction of effect between rs10911021 and CHD in T2D was observed (1377 no CHD/160 CHD; minor allele OR 0.80, 95 % CI 0.60–1.06) although this was not statistically significant (p = 0.13). No association between rs10911021 and CHD was seen in non-T2D participants (11218 no CHD/1274 CHD; minor allele OR 1.00 95 % CIs 0.92–1.10). In T2D participants, while no associations were observed between rs10911021 and the nine amino acids measured, rs10911021 was associated with HDL-cholesterol (p = 0.0005) but the minor “protective” allele was associated with lower levels (−0.034 mmol/l per allele). Focusing more closely on the HDL-cholesterol subclasses measured, we observed that rs10911021 was associated with six large HDL particle measures in T2D (all p < 0.001). No significant associations were seen in non-T2D subjects.ConclusionsOur findings are consistent with a true association between rs10911021 and CHD in T2D. The protective minor allele was associated with lower HDL-cholesterol and reductions in HDL particle traits. Our results indicate a complex relationship between rs10911021 and CHD in T2D.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-016-0435-0) contains supplementary material, which is available to authorized users.

Nonenzymatic Mechanism of Statins in Modulating Cholesterol Particles Formation

Statin drugs are leading medication prescribed for treatment of dyslipidemic patients aimed at preventing both primary and secondary incidences of atherosclerosis-related cardiovascular events. Statin drugs competitively inhibit HMG-CoA reductase enzyme activity, thereby inhibiting cell-mediated cholesterol synthesis and reducing the low-density lipoprotein (LDL) cholesterol concentration of plasma. Conversely, the mechanism by which statins increase high-density lipoprotein (HDL) cholesterol concentration of plasma is not well understood. The plaque array method was used to examine the effect of statins on invitro cholesterol particle formation. We observed that statins induced high-density cholesterol particle formation in buffer solution with or without the addition of human serum. Besides, simvastatin and lovastatin in their inactive pro-drug forms modulate formation of LDL and HDL cholesterol particles, indicating a novel nonenzymatic mechanism of statins. In a pilot study, screening of serum samples in the assay showed variation among patient samples in response to different statins. Specifically, screening of 50 serum samples with high cholesterol and statin treatment, compared with standard LDL-based measurement of statin efficacy, showed a good correlation for simvastatin (88%) and atorvastatin (84%). Taken together, our data indicate that statins, in addition to inhibiting enzyme-mediated cholesterol synthesis, have the capability to nonenzymatically modulate formation of LDL and HDL cholesterol particles invitro. Similar interactions occurring in serum may provide a means to alter cholesterol particle formation invivo.