HDL Subclasses Research Articles

High density lipoprotein subfractions and extent of coronary atherosclerotic lesions: From the cordioprev study

Background and aimsThe extent of atherosclerotic coronary heart disease (CHD) is associated with its prognosis, thus discovering potential biomarkers related to worse outcomes could prove valuable. The present work aims to investigate whether lipoprotein subfractions are associated with angiographic CHD severity. Materials and methodsPatients from the CORDIOPREV study exhibiting coronary lesions in angiography were classified into two groups (single-vessel coronary disease (SVD) or multivessel coronary disease (MVD)). High-throughput nuclear magnetic resonance (NMR) spectroscopy determined lipoprotein subfractions concentration and composition. ResultsSVD patients showed a higher concentration of medium and small HDL particles compared with MVD patients. For medium HDL, total lipids, phospholipids, total cholesterol, cholesteryl esters and free cholesterol reflected HDL particle concentration, whereas, for small HDL, total lipids, phospholipids, and free cholesterol mirrored lipoprotein particle concentration. Among traditional cardiovascular risk factors, age, hypertension and T2D were independently associated with angiography severity. In multivariate logistic regression models, medium and small HDL particles remained inversely associated with angiography severity (OR 0.77 (95% CI: 0.64–0.91); OR 0.78 (95% CI: 0.67–0.91), respectively) after adjusting with covariates. ConclusionIn CHD patients mostly on statin treatment, angiography severity is inversely related to small and medium HDL subclasses concentration measured by NMR. These particles are also independent predictors of the presence of MVD, and its use increased the prediction of this entity over traditional risk factors.

Gene-environment interaction analysis of redox-related metals and genetic variants with plasma metabolic patterns in a general population from Spain: The Hortega Study

BackgroundLimited studies have evaluated the joint influence of redox-related metals and genetic variation on metabolic pathways. We analyzed the association of 11 metals with metabolic patterns, and the interacting role of candidate genetic variants, in 1145 participants from the Hortega Study, a population-based sample from Spain. MethodsUrine antimony (Sb), arsenic, barium (Ba), cadmium (Cd), chromium (Cr), cobalt (Co), molybdenum (Mo) and vanadium (V), and plasma copper (Cu), selenium (Se) and zinc (Zn) were measured by ICP-MS and AAS, respectively. We summarized 54 plasma metabolites, measured with targeted NMR, by estimating metabolic principal components (mPC). Redox-related SNPs (N = 291) were measured by oligo-ligation assay. ResultsIn our study, the association with metabolic principal component (mPC) 1 (reflecting non-essential and essential amino acids, including branched chain, and bacterial co-metabolism versus fatty acids and VLDL subclasses) was positive for Se and Zn, but inverse for Cu, arsenobetaine-corrected arsenic (As) and Sb. The association with mPC2 (reflecting essential amino acids, including aromatic, and bacterial co-metabolism) was inverse for Se, Zn and Cd. The association with mPC3 (reflecting LDL subclasses) was positive for Cu, Se and Zn, but inverse for Co. The association for mPC4 (reflecting HDL subclasses) was positive for Sb, but inverse for plasma Zn. These associations were mainly driven by Cu and Sb for mPC1; Se, Zn and Cd for mPC2; Co, Se and Zn for mPC3; and Zn for mPC4. The most SNP-metal interacting genes were NOX1, GSR, GCLC, AGT and REN. Co and Zn showed the highest number of interactions with genetic variants associated to enriched endocrine, cardiovascular and neurological pathways. ConclusionsExposures to Co, Cu, Se, Zn, As, Cd and Sb were associated with several metabolic patterns involved in chronic disease. Carriers of redox-related variants may have differential susceptibility to metabolic alterations associated to excessive exposure to metals.

The Arg82Cys Polymorphism of the Protein Nepmucin Implies a Role in HDL Metabolism.

ContextBlood lipid levels are linked to the risk of cardiovascular disease and regulated by genetic factors. A low-frequency polymorphism Arg82Cys (rs72836561) in the membrane protein nepmucin, encoded by CD300LG, is associated with lower fasting concentration of high-density lipoprotein cholesterol (HDLc) and higher fasting triglycerides. However, whether the variant is linked to postprandial lipids and glycemic status remains elusive.ObjectiveHere, we augment the genetic effect of Arg82Cys on fasting plasma concentrations of HDL subclasses, postprandial lipemia after a standardized high-fat meal, and glycemic status to further untangle its role in HDL metabolism.MethodsWe elucidated fasting associations with HDL subclasses in a population-based cohort study (Oxford BioBank, OBB), including 4522 healthy men and women. We investigated fasting and postprandial consequences on HDL metabolism in recall-by-genotype (RbG) studies (fasting: 20 carrier/20 noncarrier; postprandial: 7 carrier/17 noncarrier), and shed light on the synergistic interaction with glycemic status.ResultsA lower fasting plasma concentration of cholesterol in large HDL particles was found in healthy male carriers of the Cys82 polymorphism compared to noncarriers, both in the OBB (P = .004) and RbG studies (P = .005). In addition, the Cys82 polymorphism was associated with low fasting plasma concentrations of ApoA1 (P = .008) in the OBB cohort. On the contrary, we did not find differences in postprandial lipemia or 2-hour plasma glucose levels.ConclusionTaken together, our results indicate an association between the Arg82Cys variant and a lower concentration of HDL particles and HDLc, especially in larger HDL subclasses, suggesting a link between nepmucin and HDLc metabolism or maturation.

Antioxidant status in hypertensive disorders of pregnancy

ABSTRACT Objective: Pregnancy can be associated with maternal hypertension leading to possible complications in pregnancy outcome. Antioxidant status may be proned to changes during pregnancy with hypertension. The aim of our study was to estimate antioxidant status through high-risk pregnancies. Methods: Seventy-nine pregnant women with high-risk for preeclampsia development were included and 46 of them developed some hypertensive disorder in pregnancy. Superoxide-dismutase (SOD) and paraoxonase 1 (PON1) activities and relative proportion of PON1 activiity on different HDL subclasses were determined in 1st, 2nd, and 3rd trimester and prior to delivery. Results: SOD activity was significantly lower in 2nd and 3rd trimesters when compared to 1st trimester (P˂0.001) whereas PON1 activity was significantly higher in 3rd than in 1st trimester (P˂0.05) in group of hypertensive women. This group had significantly higher SOD and PON1 activities and relative proportion of PON1 on HDL3c subclasses in the 1st trimester, significantly increased PON1 in the 3rd trimester and prior to delivery and significantly higher PON1 activity on HDL3c subclasses (P˂0.05) than nonhypertensive group. In 1st trimester and prior to delivery, total PON1 activity and relative proportion of PON1 on HDL3c subclasses exhibited significant ability to mark out hypertension in pregnancy (P˂0.05). Conclusions: SOD activity decreased whereas total PON1 activity increased during pregnancy with hypertension. Pregnant women with hypertension had higher activities of PON1 and SOD and relative proportion of PON1 on HDL3c subclasses than nonhypertensive ones. PON1 activity and relative proportion of PON1 on HDL3c subclasses exhibited significant association with hypertension in pregnancy.

Overweight and obesity in polycystic ovary syndrome: association with inflammation, oxidative stress and dyslipidaemia.

Polycystic ovary syndrome (PCOS) is associated with altered lipid profile and increased small, dense LDL particles (sdLDL). Considering that paraoxonase 1 (PON1) is an antioxidative enzyme located on HDL particles, the aim of this study was to investigate the connection between oxidative stress (OS) and PON1 activity with lipoprotein subclasses in PCOS depending on obesity. In 115 PCOS patients, lipoprotein subclasses distributions were determined by gradient gel electrophoresis. OS status was assessed by total oxidative status (TOS), advanced oxidation protein products, malondialdehyde (MDA), prooxidant-antioxidant balance (PAB), total antioxidative status (TAS) and superoxide dismutase (SOD) and PON1 activity. Overweight/obese PCOS patients (n 55) had increased OS compared with normal weight patients (n 60). In addition, overweight/obese group had lower HDL size and higher proportion of HDL 3a subclasses (P < 0·05). PAB was in negative correlation with HDL 2a (P < 0·001), whereas MDA and SOD correlated positively with HDL 3 subclasses (P < 0·05). Serum PON1 activity was positively associated with proportions of PON1 activity on HDL 2b (P < 0·05) and 2a (P < 0·01), but negatively with the proportion on HDL 3 particles (P < 0·01). LDL B phenotype patients had increased TAS, SOD and PON1 activity on HDL 2b, but decreased PON1 activity on HDL 3 subclasses. OS is associated with altered lipoprotein subclasses distribution in PCOS patients. Obesity in PCOS affects the profile of HDL subclasses, reflected through the reduced proportion of PON1 activity on HDL 3 subclasses in the presence of sdLDL particles.

Hormone therapy impacts on HDL-CEC but not on HDL subclasses and serum loading capacity: A cohort of transgender individuals.

Background and Aims: Among the HDL atheroprotective function, the most known is the ability of promoting cholesterol efflux from macrophages, termed cholesterol efflux capacity (CEC) and considered a better predictor of cardiovascular disease (CVD) than HDL levels. Moreover, the capacity of serum to load macrophages with cholesterol (cholesterol loading capacity, CLC) represents an index of serum pro-atherogenic potential. As transgender individuals are exposed to lifelong exogenous hormone therapy, we investigated whether HDL-CEC, HDL subclasses and serum CLC are affected by hormone treatment.

Abstract P101: Premenopausal Life’s Simple 7 Score Is Associated With High-density Lipoprotein Metrics Later In Life: The SWAN HDL Study

Objective: In midlife women, higher high-density lipoprotein cholesterol (HDL-C) is not always associated with cardio-protection, suggesting a potential dysfunction of HDL. Novel metrics of HDL may provide further information on its cardio-protective features. The AHA developed the Life’s Simple 7 (LS7) score based on 7 lifestyle factors (cholesterol, BMI, diet, physical activity, smoking, glucose and blood pressure). A higher LS7 indicates a healthier lifestyle and is to cardiovascular health. We aimed to assess if higher premenopausal LS7 score is associated with a protective future HDL metrics profile as measured by greater HDL function (cholesterol efflux capacity), lower HDL-triglycerides (HDL-Tg) and higher HDL-phospholipids (HDL-PL) contents, higher large HDL-particles (HDL-P) and lower small HDL-P levels and larger overall HDL size by nuclear magnetic resonance spectroscopy. Methods: We included 529 women [baseline age 46.4 (2.6) years, 57% (299 of 529) White] from the Study of Women’s Health Across the Nation (SWAN) HDL ancillary study who had premenopausal LS7 score followed by repeated HDL metrics at later visits [time between LS7 score and first HDL measure: 3.9 (1.4) years]. Multivariable linear mixed models were used to analyze the independent association between premenopausal LS7 score and each HDL metric. Results: After adjusting for race, education, and baseline age, menopausal status, economic hardship and high-sensitivity C-reactive protein (Table), higher premenopausal LS7 score was associated with lower HDL-Tg (p&lt;0.0001) and higher HDL-PL (p=0.02), greater total HDL-P (p=0.03), large HDL-P (p=0.0001) and HDL-C (p&lt;0.0001), and larger HDL size (p&lt;0.0001) later in life. Premenopausal LS7 score was not related to HDL function. Conclusion: Higher premenopausal LS7 score was not related to HDL function but related to favorable future HDL contents and subclasses. This indicates that a better premenopausal lifestyle and metabolic health may contribute to a better HDL profile later in life.

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

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

Reduction of small dense LDL and Il-6 after intervention with Plantago psyllium in adolescents with obesity: a parallel, double blind, randomized clinical trial.

Obesity can lead children and adolescents to an increased cardiovascular disease (CVD) risk. A diet supplemented with Plantago psyllium has been shown to be effective in reducing LDL-C and IL-6 in adolescents. However, there are no studies that have explored small-dense LDL (sdLDL) or HDL subclasses. The aim of this study was to evaluate the impact of a fiber dietary intervention on LDL and HDL subclasses in adolescents with obesity. In this parallel, double blind, randomized clinical trial, the participants were assigned to Plantago psyllium or placebo (10g/day for 7 weeks). We randomized 113 participants, and evaluated and analyzed 100 adolescents (50 in each group), 15 to 19 years with a body mass index of 29-34. We measured biochemical markers LDL and HDL subclasses using the Lipoprint system (Quantimetrix) and IL-6 by ELISA. Post-treatment there was a decrease in sdLDL between the groups 2.0 (0-5.0) vs 1 (0-3.0) mg/dl (p = 0.004), IL-6 median 3.32 (1.24-5.96) vs 1.76 (0.54-3.28) pg/ml, p <0.0001. There were no differences in HDL subclasses and no adverse effects were reported in either group.Conclusions: Small dense LDL and IL-6 reduced in adolescents with obesity when consuming Plantago psyllium. This may be an early good strategy for the reduction of cardiovascular disease risk in this vulnerable population.Trial registration: ISRCTN # 14180431. Date assigned 24/08/2020 What is Known: • Supplementing the diet with Plantago psyllium lowers LDL-C levels. What is New: • First evidence that soluble fiber supplementation like Plantago psyllium decreases small dense LDL particles in association with lowered IL-6, reducing the risk of cardiovascular disease in obese adolescents.

Association of proportion of the HDL-cholesterol subclasses HDL-2b and HDL-3 and macrovascular events among patients undergoing hemodialysis

Altered high-density lipoprotein cholesterol (HDL-C) subclass distribution in hemodialysis (HD) patients is well documented. Aim of this study is to investigate the relationship between HDL-C subclass distribution and macrovascular events in patients undergoing HD. A total of 164 prevalent HD patients and 71 healthy individuals in one hospital-facilitated clinic were enrolled from May 2019 to July 2019 and individual HD patients was follow-up for one year. Macrovascular events (cerebral stroke, coronary heart disease) were recorded in the study period. The HDL-2b, HDL-3 proportions and biochemical parameters were measured. Pearson correlation test and logistic regression analysis were used to examine correlation and odds ratio (OR). 144 HD patients completed one-year follow-up. Cohort with macrovascular events revealed significantly lower HDL-2b and higher HDL-3 subclass proportions compared to those without events. By multivariable adjustment, HDL-3 subclass proportion revealed significantly increase risk for these events (OR 1.17, 95% CI 1.02–1.41, P = 0.044). HDL-2b subclass was significantly higher and HDL-3 subclass was significantly lower in the HD cohort under the hs-CRP level of < 3 mg/L compared to higher hs-CRP level. In conclusion, HDL-2b and HDL-3 subclasses distributions were associated with macrovascular events in HD patients. Proinflammatory status influences the distribution of HDL-2b and HDL-3 subclasses in HD patients.

Associations of HDL metrics with coronary artery calcium score and density among women traversing menopause

AbstractThe cardioprotective association of high-density lipoprotein cholesterol (HDL-C) may vary by menopause stage or estradiol level. We tested whether associations of comprehensive HDL metrics (HDL subclasses, phospholipid and triglyceride content, and HDL cholesterol efflux capacity [HDL-CEC]) with coronary artery calcium (CAC) score and density vary by menopause stage or estradiol level in women transitioning through menopause. Participants (N = 294; mean age [SD]: 51.3 [2.9]) had data on HDL metrics and CAC measures at one or two time points during the menopause transition. Generalized estimating equations were used for analyses. Effect modifications by menopause stage or estradiol level were tested in multivariable models. In adjusted models, menopause stage modified the associations of specific HDL metrics with CAC measures. Higher small HDL particles (HDL-P) concentrations (p-interaction = 0.008) and smaller HDL size (p-interaction = 0.02) were associated with greater odds of CAC presence in late perimenopause than in pre/early perimenopause stage. Women in the highest estradiol tertile, but not the lower tertiles, showed a protective association of small HDL-P with CAC presence (p-interaction = 0.007). Lower large HDL-P concentrations (p-interaction = 0.03) and smaller HDL size (p-interaction = 0.03) were associated with lower CAC density in late perimenopause than in postmenopause stage. Associations of HDL phospholipid and triglyceride content and HDL-CEC with CAC measures did not vary by menopause stage or estradiol level. We concluded that HDL subclasses may impact the likelihood of CAC presence and the stability of coronary plaque differently over the menopause transition. Endogenous estradiol levels may contribute to this observation.

CER-001 ameliorates lipid profile and kidney disease in a mouse model of familial LCAT deficiency

ObjectiveCER-001 is an HDL mimetic that has been tested in different pathological conditions, but never with LCAT deficiency. This study was designed to investigate whether the absence of LCAT affects the catabolic fate of CER-001, and to evaluate the effects of CER-001 on kidney disease associated with LCAT deficiency. MethodsLcat−/− and wild-type mice received CER-001 (2.5, 5, 10 mg/kg) intravenously for 2 weeks. The plasma lipid/ lipoprotein profile and HDL subclasses were analyzed. In a second set of experiments, Lcat−/− mice were injected with LpX to induce renal disease and treated with CER-001 and then the plasma lipid profile, lipid accumulation in the kidney, albuminuria and glomerular podocyte markers were evaluated. ResultsIn Lcat−/− mice a decrease in total cholesterol and triglycerides, and an increase in HDL-c was observed after CER-001 treatment. While in wild-type mice CER-001 entered the classical HDL remodeling pathway, in the absence of LCAT it disappeared from the plasma shortly after injection and ended up in the kidney. In a mouse model of renal disease in LCAT deficiency, treatment with CER-001 at 10 mg/kg for one month had beneficial effects not only on the lipid profile, but also on renal disease, by limiting albuminuria and podocyte dysfunction. ConclusionsTreatment with CER-001 ameliorates the dyslipidemia typically associated with LCAT deficiency and more importantly limits renal damage in a mouse model of renal disease in LCAT deficiency. The present results provide a rationale for using CER-001 in FLD patients.

Effects of diet and exercise treatments on distribution and composition of Hdl subclasses in lactating women with overweight and obesity

Rationale: Childbearing decreases HDL cholesterol in the long term, potentially contributing to the increased risk of future cardiovascular disease in parous women. Our aim was to investigate the main effects of dietary and exercise treatments in lactating women with overweight and obesity on distribution and composition of HDL subclasses.

Atherosclerosis: cell biology and lipoproteins.

Lipoproteins have significant role in both the promotion and prevention of atherosclerosis. This brief review will focus on recent reports on relationship between HDL and HDL subclasses and their composition and function, the role of apoC-III in metabolism of triglyceride-rich lipoproteins, the impact of Lipoprotein (a) (Lp(a)) on endothelial cells, and the mechanism of uptake of aggregated LDL by macrophages. The complexity of the protein and lipid content of murine and human HDL and their relationship to its cholesterol efflux capacity have been examined. HDL has also been shown to have both antiatherogenic and proatherogenic properties. The relationship between apoC-III and LPL activity, apoprotein E mediated clearance of triglyceride-rich lipoproteins and the potential importance of apoC-III in the increased risk of cardiovascular disease in type 1 diabetics has been investigated. Oxidized phospholipid in Lp(a) promotes endothelial cells inflammatory and glycolytic responses. TLR4 participates in the uptake of aggregated LDL to contribute to foam cell formation. These studies contribute to our mechanistic understanding of how lipoproteins contribute to atherogenesis and identify potential therapeutic targets.

Cardioprotective Properties of HDL: Structural and Functional Considerations.

As Mendelian Randomization (MR) studies showed no effect of variants altering HDL-cholesterol (HDL-C) levels concerning Cardiovascular Disease (CVD) and novel therapeutic interventions aiming to raise HDL-C resulted to futility, the usefulness of HDL-C is unclear. As the role of HDL-C is currently doubtful, it is suggested that the atheroprotective functions of HDLs can be attributed to the number of HDL particles, and their characteristics including their lipid and protein components. Scientific interest has focused on HDL function and on the causes of rendering HDL particles dysfunctional, whereas the relevance of HDL subclasses with CVD remains controversial. The present review discusses changes in quality as much as in quantity of HDL in pathological conditions and the connection between HDL particle concentration and cardiovascular disease and mortality. Emphasis is given to the recently available data concerning the cholesterol efflux capacity and the parameters that determine HDL functionality, as well as to recent investigations concerning the associations of HDL subclasses with cardiovascular mortality. MR studies or pharmacological interventions targeting HDL-C are not in favor of the hypothesis of HDL-C levels and the relationship with CVD. The search of biomarkers that relate with HDL functionality is needed. Similarly, HDL particle size and number exhibit controversial data in the context of CVD and further studies are needed. There is no room for the old concept of HDL as a silver bullet,as HDL-C cannot be considered a robust marker and does not reflect the importance of HDL particle size and number. Elucidation of the complex HDL system, as well as the finding of biomarkers, will allow the development of any HDL-targeted therapy.

HDL Quality Features Revealed by Proteome-Lipidome Connectivity Are Associated with Atherosclerotic Disease

Background: The protein-lipid composition, namely the “quality” of lipoprotein particles, has been shown to be increasingly associated with cardiovascular disease (CVD). The high heterogeneity of lipoproteins makes it necessary to study the “quality” of each high-resolution subgroup. However, the targeted separation, detection, and exploration of the heterogeneous on omic-scale for lipoprotein remain challenging and rarely touched. Methods: We established a high-resolution proteomics and lipidomics (HiPL) method. Briefly, the lipoprotein particles were separated into nine fractions (Lipo-HiPL) using anion-exchange chromatography (AEC), in which HDL, LDL, and VLDL were fractionated into three more fractions respectively. Furthermore, the HDL subclasses were delicately purified within nine fractions (HDL-HiPL), covering diverse protein-lipid heterogeneity. Then the integration of proteomic and lipidomic analysis of these high-resolution subgroups revealed proteome-lipidome connectivity (PLC) in lipoprotein and HDL particles. Findings: We used the high fat high cholesterol (HFHC)-fed rabbit model before atherosclerotic lesions occurred to evaluate the applicability of our method preliminarily, and then we applied Lipo-HiPL and HDL-HiPL methods to acute coronary syndrome (ACS) patients before and after PCI and standardized drug treatment. We found that LiPL-HiPL method had enough sensitivity to illustrate dramatic changes of lipoproteins in HFHC died rabbits. However, in ACS patients, the HDL-HiPL method with a higher resolution could better reflect the molecular dynamics and PLC features of HDL than Lipo-HiPL. Moreover, the HDL “quality” revealed by PLC related more closely to clinical status in ACS patients than direct proteome and lipidome quantification. Interpretation: Proteome-lipidome connectivity (PLC) as novel HDL “quality” features could be highly associated with atherosclerotic cardiovascular diseases. Funding Statement: This work was supported by a grant from the Ministry of Science and Technology (2017YFA0505500), and grants from the National Natural Science Foundation of China (81561128018, 81670426 and 81870336). Declaration of Interests: None. Ethics Approval Statement: The study was approved by the Medical Ethics Committee of the Second Xiangya Hospital of Central South University. All patients gave written informed consent before blood sample collection. Rabbit studies were performed according to animal protocols approved by the Institutional Animal Care and Use Committee (IACUC) of the University of Michigan.

Physical activity and lipidomics in a population at high risk of type 2 diabetes mellitus

ABSTRACT The aim was to investigate how measurements of the lipidome differ according to the level and intensity of physical activity in a population at high risk of type 2 diabetes (T2DM). A targeted metabolomics platform provided quantitative molecular data on lipid species. Linear regression examined the associations between plasma lipid concentrations, particle size and time spent in objectively measured physical activity intensity domains, in increments of 500 counts per minute (cpm) (up to >4500 cpm (~>5.6METs)). Results are presented as % difference in the concentration (lower/higher) or particle size (smaller/larger) per 10 min of activity within each intensity. Five hundred and nine participants were included. Time spent in the lowest physical activity intensity domain (<500 cpm) was unfavourably associated with VLDL (2%), HDL (−2%) and Apolipoprotein A-1 particle concentrations (−2%) and HDL diameter (−2%). Conversely, time spent in intensities ≥1000 cpm were favourably associated with HDL subclass concentrations; with stronger associations seen at moderate intensities (2000-3999 cpm (~4.5METs)). For Apolipoprotein-B concentration and VLDL particle concentration and size, a negative association was consistently observed at the highest physical activity intensity only. If these associations are causal, HDL subclasses appear sensitive to light-intensities whereas only the high category of physical activity intensity was consistently associated with VLDL subclasses.

The Function and Proteome Alteration of HDL Subclass After Aerobic Exercise

The Function and Proteome Alteration of HDL Subclass After Aerobic Exercise

Abstract MP36: Changes in High-density Lipoprotein (hdl) Subclasses and Particle Size Over the Menopause Transition are Associated With Higher Levels of Complement Proteins C3 and C4. The Study of Women's Health Across the Nation Hdl Ancillary Study

Objective: High density lipoprotein (HDL) is emerging as a key player in modulating inflammation-related response impacting atherosclerosis development. HDL carries multiple proteins with direct roles in complement system activation including C3 and C4. Postmenopausal women have higher levels of C3 than premenopausal women suggesting a role of the menopause transition (MT) in modulating complement proteins. Preliminary work showed significant declines in large HDL particles (HDL-P) and overall HDL particle size, but increases in small HDL-P during the MT. Whether these changes contribute to higher levels of C3 reported after menopause is not known. Our objectives were to test whether C3 and C4 increase around the final menstrual period (FMP) and whether changes in HDL subclasses over the MT associate with C3 and C4 levels in midlife women. Design: We evaluated 558 women (at baseline: age 49.9(2.8) years; 86.6% perimenopausal) who had nuclear magnetic resonance spectroscopy HDL subclasses, C3 and C4 measured up to 5 times over the MT. Piecewise linear mixed-effects models were used to estimate and compare yearly changes in C3 and C4 at 3 time segments relative to the FMP. Linear mixed effect models were used to test associations between changes in each HDL subclass and overall HDL particle size with C3 and C4 separately. Results: Adjusted annual changes in C3 and C4 varied by time segments relative to FMP with significant increases only observed within 1 year before to 2 years after the FMP ( Figure ). These changes were significantly greater than changes in the other 2 time segments. Greater decreases in large and increases in small HDL-P concentrations and decreases in the overall size of HDL-P were independently associated with higher levels of C3 and C4 over time ( Table ). Conclusions: Complement proteins C3 and C4 significantly rise around menopause with C3 showing the steepest rise. Changes in HDL subclasses and overall size over the MT may play role in modulating inflammation responses known to be related to atherosclerosis.

Abstract P401: Associations Between High-density Lipoprotein Subclasses and Coronary Artery Calcification Vary by Menopausal Stage. The Study of Women's Health Across the Nation Hdl Ancillary Study

Objective: Higher levels of high-density lipoproteins cholesterol (HDL-C) may not always be cardio-protective in midlife women. Nuclear magnetic resonance (NMR) spectroscopy HDL subclasses have shown strong associations with CVD risk beyond HDL-C. Preliminary work suggests significant declines in large HDL particles (HDL-P) and overall HDL size, but increases in small HDL-P during the perimenopause stage. Our objective was to assess whether associations between NMR HDL subclasses and risk of coronary artery calcification (CAC) vary by menopausal stage. Design: We assessed 283 women (at baseline : age 51.4 ± 3.0 years; 56.6% Pre-/Early peri-, 8.8% late peri-, 34.6% post-menopausal) who had NMR HDL subclasses and CAC Agatston score measured once (N=48 [17%]) or twice (N=235 [83%]) around menopause. CAC presence was defined as CAC&gt;0. Effect modifications of menopausal stage on associations between HDL subclasses and CAC presence overtime were tested using generalized estimating equation for binary outcome. Final models were adjusted for study site, race and time varying: age, body mass index, physical activity, alcohol consumption, insulin resistance, triglycerides and low-density lipoprotein cholesterol. Results: In final models, menopausal stage modified the associations of small HDL-P (p=.009), large HDL-P (p=.05) and overall HDL size (p=.007) with CAC presence ( Table ). Higher concentration of small HDL-P, lower concentration of large HDL-P, and smaller overall HDL size significantly associated with greater risk of CAC presence during the late-peri stage compared to pre-/early peri-menopausal stage ( Table) . Conclusions: Changes in HDL subclasses during the menopause transition may increase the likelihood of measurable CAC developing in women, particularly during the later peri-menopausal stage. Characterizing associations of HDL composition and function metrics with CVD risk over the menopause transition is critical to better understand the relationship of HDL to coronary disease in midlife women.