High-density Lipoprotein Cholesterol Subfractions Research Articles

High-density lipoprotein cholesterol subfraction HDL2 is associated with improved endothelial function in systemic lupus erythematosus

ObjectivePatients with systemic lupus erythematosus (SLE) have increased risk of premature atherosclerosis but the exact mechanisms remains unclear. Flow-mediated dilatation (FMD) is an established non-invasive assessment of vascular endothelial function....

Abstract #1390249: Phenotypes of High-Density Lipoprotein Cholesterol and Presence of Coronary Artery Disease in Asymptomatic Nigerian Type 2 Diabetic Patients

Cardiovascular disease is a major cause of morbidity and mortality in type 2 diabetic (T2DM) patients. Low levels of high-density lipoprotein cholesterol (HDL-C) is the commonest lipid abnormality in Nigerian T2DM patients. The association of HDL-C subfractions (HDL-2 and HDL-3) and the presence of coronary artery disease (CAD) is still unknown among Nigerian T2DM patients. Asymptomatic T2DM patients attending the diabetes clinic of the Nnamdi Azikiwe University Teaching Hospital, Nnewi, Nigeria were identified and recruited for this study. History, physical examination and clinical evaluations were done for study participants. Data obtained were verified and analyzed with appropriate software. Tests for normality were done and comparison of variables in participants with and without CAD done with statistical tests appropriate for non-parametric data. Logistic regression analysis was used to determine the odds at which independent risk factors predicted coronary artery disease. Four hundred study participants consisting of 174 (43.5%) males and 226 (56.5%) females participated in this study. The median (IQR) age of participants was 60(48,65) years. 64(16%) participants had coronary artery disease. The HDL-3 subfraction of HDL-C was significantly lower in those with CAD (Mann-Whiney U=254, p=0.02) with OR=4.6 (95%CI=3.2-7.9, p=0.01) after replacement of significant predictors of CAD in the logistic regression model. There was no significant difference in HDL-2 levels in subjects with CAD compared to those without CAD (Mann-Whitney U=21, p=0.21). The HDL-3 phenotype of HDL-C is a significant predictor of CAD in Nigerian T2DM patients.

Relationship between years since menopause and lipid variation in postmenopausal women: A cross-sectional study

Lipid alteration in postmenopausal women is commonly due to hormonal changes. This study aimed to explore the association between the years since menopause and lipid profiles in postmenopausal women. In this cross-sectional study, a total of 1033 postmenopausal women were recruited from the Women's Hospital of Zhejiang University in China between 2015 and 2022. Each participant was interviewed using questionnaires regarding sociodemographic and reproductive data. Anthropometric measurements, lipid profiles, and reproductive hormone levels were assessed. Participants were divided into 3 groups based on the length of time since menopause: 2, 2 to 5.9, and 6 years. Differences in lipid profiles and reproductive hormones among the groups were compared. Logistic and linear regression analyses were used to examine the relationship between years after menopause and lipid profile. High-density lipoprotein cholesterol (HDL-C) and luteinizing hormone levels were significantly lower in postmenopausal women with time since menopause of ≥6 years than those <2 years (P < .05), whereas low-density lipoprotein cholesterol levels were significantly higher (P < .05). A longer time after menopause was independently associated with lower HDL-C levels (β, -0.059, standard error, 0.023, P = .01) after adjustment for age, body mass index, and other confounders. Compared to women who had menopause for <2 years, those who were postmenopausal for >6 years had lower HDL-C levels after adjustment for age, body mass index, and other covariates (β, -0.123, 95% confidence interval, [-0.221, -0.014], P = .014). Longer time since menopause was associated with an atherogenic lipid profile with appreciably low levels of HDL-C subfraction. Future multicenter studies are necessary to examine postmenopausal population and determine how differences in lipids influence the risk of cardiovascular disease in this group.

The profile of HDL-C subfractions and their association with cardiovascular risk in the Hungarian general and Roma populations

High-density lipoprotein cholesterol (HDL-C) is not a homogenous lipid fraction, but it can be further divided into subfractions. It is well-known that the Roma population has a high prevalence of reduced HDL-C levels and cardiovascular diseases (CVDs). However, it is unknown how this reduction affects different HDL subfractions, and whether changes in their quantity/representation are associated with an increased cardiovascular risk among them. In the present study, the HDL subfraction profile of the Hungarian general (HG) and the Roma populations were compared, and the subfractions showing a significant difference between the two populations were identified. The association of HDL subfractions with CVD risk estimated by the Framingham risk score (FRS) and the Systematic COronary Risk Evaluation (SCORE) algorithms were also defined. The present study is the first to find a significant association between HDL subfractions and cardiovascular risk estimated by FRS and SCORE. Ten HDL subfractions were investigated on small but carefully selected samples comprising 100 control subjects (with normal lipid profile) and 277 case subjects (with reduced HDL-C levels) from HG and Roma populations of a complex health survey. The level of HDL-1 to 3 subfractions and HDL-L showed a significant inverse association with cardiovascular risk estimated by both SCORE and FRS algorithms, whereas HDL-4 to 6 and HDL-I only for FRS. A higher representation (in %) of HDL-1 to 3 has a significant risk-reducing effect, while HDL-8 to 10 has a risk-increasing effect estimated by FRS. Our results confirmed that reduced levels of HDL-6 and -7 expressed in mmol/L were significantly associated with Roma ethnicity.

LDL-C augments whereas HDL-C prevents inflammatory innate immune memory

Recent studies emphasize the importance of low-density lipoprotein cholesterol (LDL-C) in altering the hematopoieticcellcompartmentof bone marrow and of high-density lipoprotein cholesterol (HDL-C) in inhibiting metabolic endotoxemia-induced inflammation. The data suggest that these lipoproteins may exert their inflammatory or anti-inflammatory roles by modulating innate immune memory. Targeting specific LDL-C and HDL-C subfractions could therefore potentially reduce the residual risk in hepatic and cardiometabolic disease.

Abstract 11198: Role of Different Lipid Parameters and Lipoproteins on Coronary Microvascular Dysfunction in the Young

Aim: Young with coronary microvascular dysfunction (CMD) have increased cardiovascular morbidity. Particularly, Asian patients with CMD are considerably younger than their Western peers. Blood lipids are traditionally considered risk factors for myocardial infarction (MI) of the elderly. However, little is known about CMD in the young. The purpose of our study was to test the associations between lipids and lipoprotein particles and CMD in the young. Methods: A cross-sectional study was conducted from 2014 to 2020, 1868 young participants were included. CMD was defined as angina but no obstructive coronary disease. All participants had baseline laboratory testing. Lipid parameters, including total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), small dense low density lipoprotein cholesterol (sd LDL-C), high-density lipoprotein (HDL), non-HDL, TC/HDL ratio, TG/HDL ratio and LDL/HDL ratio were measured. Both low- and high-density lipoprotein cholesterol (LDL-C and HDL-C) subfractions were measured using the Quantimetrix Lipoprint System. Logistic regression analysis was performed to determine associated factors for CMD. Results: Very low-, intermediate-, small dense-, and low- density lipoprotein particles were positively associated with CMD. HDL particles were inversely associated with CMD apart from small HDL. Cholesterol in large HDL was inversely associated with CMD (odds ratio [OR] = 0.75), whereas cholesterol in small HDL was not (OR = 1.08). TG within all lipoproteins, including most HDL particles, were positively associated with CMD. In multiple logistic regression analyses, non-HDL [OR = 1.56 (1.16-1.87)], sd LDL-C [OR = 1.80 (1.21-2.27)], TC [OR = 1.41 (1.25-1.93)], TC/HDL [OR = 1.26 (1.15-1.68)] were significantly associated with CMD. Conclusions: Lipids and lipoproteins showed similar associations with CMD. Within HDL particles, cholesterol concentrations were inversely associated, whereas triglyceride concentrations were positively associated with CMD. Non-HDL, sd LDL-C, TC, and TC/HDL were significantly associated with CMD than others. This result should be considered in future clinical lipid-lowering trials and a routine screening for CMD in the young.

Association of high-density lipoprotein cholesterol subfractions with insulin resistance in Nigerians with type 2 diabetes mellitus

Background: There are conflicting reports on the relationship of each of the two subfractions of high-density lipoprotein cholesterol (HDL-C) with insulin resistance in patients with type 2 diabetes mellitus (T2DM). Information on the relationship between HDL-C subfractions and insulin resistance in Nigerian patients with T2DM is not available in the literature. Aim: The aim of this article is to determine the association between subfractions of HDL-C and insulin resistance in Nigerian patients with T2DM. Materials and Methods: Patients with T2DM who were being managed by the Endocrinology, Diabetes, and Metabolism unit of the Nnamdi Azikiwe University Teaching Hospital (NAUTH), Nnewi, South-East Nigeria were recruited for this study, whereas individuals with normal glucose tolerance (NGT) were recruited from Nnewi town. The study was carried out within a 5-month period. History was taken and physical examination was done on study participants. Fasting venous samples were collected for plasma glucose, plasma total HDL-C, plasma HDL-C phenotypes, serum C-peptide, serum creatinine, and serum alanine transferase estimation. Homeostasis Model Assessment for Insulin Resistance (HOMA2-IRC-peptide) score was determined using plasma glucose and serum C-peptide concentrations. Data were analyzed using appropriate statistical software. Results: A total of 616 participants consisting of 400 participants with T2DM and 216 participants with NGT were recruited for the study. Difference in age, sex, and blood pressure was not statistically significant between participants with T2DM and those with NGT. There were statistically significant differences in body mass index, fasting plasma glucose, C-peptide, HOMA-IR, total HDL-C, and HDL-C subfractions between subjects with T2DM and those with NGT. There was a significant negative correlation between HOMA-IR score and each of HDL2-C (rs= −0.513, P < 0.01), HDL3-C (rs= −0.471, P < 0.01), and HDL2-C/HDL3-C ratio (rs= −0.416, P < 0.01) in subjects with T2DM. Total HDL-C (odds ratio (OR)=3, P = 0.02), HDL2-C (OR=3.87, P = 0.01), and HDL3-C (OR=2.54, P = 0.02) were significant predictors of insulin resistance in individuals with T2DM after univariate and multivariate logistic regressions. Conclusion: This study showed a negative correlation between insulin resistance and each of the HDL-C subfractions in Nigerian patients with T2DM with HDL2-C having the strongest correlation with HOMA-IR score.

Clinical-epidemiological analysis of HDL2 and HDL3 subfractions in adults from Maracaibo city, Venezuela.

To carry out a clinical-epidemiological analysis of high-density lipoprotein cholesterol subfractions (HDL-C) in adults from Maracaibo, Venezuela. A descriptive and cross-sectional study of the database from the Metbolic Syndrome Prevalence in Maracaibo Study was carried out. HDL3 and HDL2 serum concentration, as well as the HDL2/HDL3 ratio, were determined in 359 individuals of both sexes, over 18 years of age. Values obtained were evaluated according to sociodemographic, clinical and biochemical characteristics. Mean population age was 39.4 ± 15.2 years, and 51.5% were female. Differences in HDL-C subfraction levels were only observed in those subjects with low HDL-C levels. Women with hypertriglyceridemia showed significantly lower serum HDL3 and HDL2 concentrations than those with normal triglycerides (p=0.033), as well as a lower HDL3 level and HDL2 / HDL3 ratio in those with higher levels of ultra-sensitive C-reactive protein (us-CRP) (p<0.001). A significantly lower concentration of HDL2 was observed in men with some degree of hypertension (p=0.031), insulin resistance (p=0.050) and metabolic syndrome (p=0.003); while those with elevated us-CRP showed a lower concentration of HDL3 (p=0.011). HDL-C subfractions show varying clinical-epidemiological behavior in adults from Maracaibo. Lower serum levels are observed in men, differences only in those with low HDL-C; and no predominance of any subclass was observed according to sociodemographic, clinical and biochemical characteristics.

2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: The Task Force for diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD)

It has been demonstrated that diabetic dyslipidaemia is the chief bridge between diabetes and incremental risk of cardiovascular disease in patients with diabetes. However, the characteristics of lipoprotein subfractions distribution in patients with type 2 diabetes (T2D) have not been fully investigated. The aim of present study was to evaluate the distributions of lipoprotein subfractions in T2D patients.A total of 920 patients, who have not received lipid-lowering drug treatment previously, were consecutively enrolled in this study. Based on the evidence of diabetes, patients were divided into T2D group (n=204) and non-T2D group (n=716). Both low- and high-density lipoprotein cholesterol (LDL- and HDL-C) subfractions were analysed using the Quantimetrix Lipoprint System. The distributions of lipoprotein subfractions were evaluated in patients with and without T2D.Compared with non-T2D individuals, the T2D group manifested significantly lower large HDL-C concentration/HDL subfraction percentage, smaller mean LDL particle size but higher small HDL-C and LDL-C concentrations as well as small HDL and LDL subfraction percentages. Moreover, the data indicated that the small HDL-C/ LDL-C concentrations, the small and large HDL subfraction percentages along with the mean LDL particle size were independently related to the existence of T2D (95% CI=1.009–1.067, p=0.009; 95% CI=0.938-0.983, p=0.001; 95% CI=1.023–1.135, p=0.005; 95% CI= 1.005–1.048, p=0.014; 95% CI=0.940-0.999, p=0.040; respectively) assessed by logistic regression analysis.The present study indicated that the changes of lipid profile in patients with T2D are characterised by abnormal distributions of lipoprotein subfractions apart from clinically atherogenic dyslipidaemia.

High-density Lipoprotein-cholesterol Subfractions and Coronary Artery Calcium: The ELSA-Brasil Study

Although elevated high-density lipoprotein cholesterol (HDL-C) is considered protective against atherosclerotic cardiovascular disease, no causal relationship has been demonstrated. HDL-C comprises a group of different subfractions that might have different effects on atherosclerosis. Our objective was to investigate the association between HDL-C subfractions with the coronary artery calcium (CAC) score. We included 3,674 (49.8±8.3years, 54% women) participants from the ELSA-Brasil study who had no prior history of CVD and were not currently using lipid-lowering medications. We measured the fasting lipoprotein cholesterol fractions (in mmol/l) by a zonal ultracentrifugation method (VAP). We analyzed the independent predictive values of total HDL-C, HDL2-C, and HDL3-C subfractions and in the HDL2-C/HDL3-C ratio using linear regression to predict Ln(CAC+1) and logistic regression to predict the presence of CAC. Overall 912 (24.8%) of the participants had CAC>0, and 294 (7.7%) had CAC>100. The mean total HDL-C, HDL2-C, and HDL3-C were: 1.42±0.37, 0.38±0.17 and 1.03±0.21mmol/l, respectively. Individuals with CAC>0 had lower levels of total HDL-C as well as of each subfraction (p<0.001). When adjusted for age, gender, smoking, hypertension, alcohol use, physical activity, and LDL-C, we observed an inverse association between HDL-C and its subfractions and CAC (p<0.05). However, by adding triglycerides in the adjustment, neither total HDL-C nor its subfractions remained independently associated with the presence or extent of CAC. In this cross-sectional analysis, neither the total HDL-C nor its subfractions (HDL2-C and HDL3-C, as well as HDL2-C/HDL3-C ratio) measured by VAP are independently associated with the presence or extent of coronary calcification.

Relation of oxidized-low-density lipoprotein and high-density lipoprotein subfractions in non-treated patients with coronary artery disease

BackgroundOxidized-low-density lipoprotein (ox-LDL), as well as high-density lipoprotein (HDL) and its subfractions play important role in the development of coronary artery disease (CAD). MethodsA total of 1417 individuals who received selective coronary angiography (CAG) without lipids-lowering treatments were consecutively enrolled. Patients were divided into CAD (n = 942) and non-CAD group (n = 475). The severity of CAD was assessed by Gensini Scores (GS) system. The correlations of ox-LDL with HDL subfractions were analyzed. ResultsCompared with non-CAD subjects, CAD patients had higher ox-LDL but lower concentrations of HDL cholesterol (p = 0.002) and large HDL subfractions (p = 0.004). And ox-LDL was negatively correlated with large HDL subfractions in patients with severe CAD (p < 0.05). Moreover, ox-LDL was elevated and large HDL subfractions decreased with the increase of the number of stenotic coronary arteries and GS (p < 0.05, respectivelly). ConclusionsThe correlations between ox-LDL and cholesterol level of large HDL particles varied among CAD and non-CAD, and CAD with different severities of atherosclerosis.

Diabetes alters the association between high-density lipoprotein subfractions and carotid intima-media thickness: The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

High-density lipoprotein cholesterol comprises a group of heterogeneous subfractions that might have differential effects on atherosclerosis. Moreover, prior investigations suggest that the presence of diabetes (T2D) modifies the impact of some subfractions on atherosclerosis. In this study, we aimed to evaluate the association between high-density lipoprotein cholesterol subfractions and carotid intima-media thickness in the baseline assessment of the Brazilian Longitudinal Study of Adult Health participants from the São Paulo investigation centre. We evaluated 3930 individuals between 35 and 74 years without previous cardiovascular disease not using lipid-lowering drugs. High-density lipoprotein cholesterol subfractions (HDL2-C and HDL3-C) were measured by vertical ultracentrifugation (vertical auto profile). The relationship between each high-density lipoprotein cholesterol subfraction and carotid intima-media thickness was analysed by multiple linear regression models. Total high-density lipoprotein cholesterol, as well as HDL2-C and HDL3-C, was negatively associated with carotid intima-media thickness after adjustment for demographic data (all p < 0.001) and traditional risk factors (all p < 0.05). When stratified by T2D status, the HDL2-C/HDL3-C ratio showed a negative association with carotid intima-media thickness in participants with T2D ( p = 0.032), even after fully controlling for confounding variables, including total high-density lipoprotein cholesterol. HDL2-C, HDL3-C and HDL2/HDL3-C ratio are inversely associated with carotid intima-media thickness after adjustment for traditional risk factors. Association of the HDL2-C/HDL3-C ratio is modified by the presence of diabetes, being more pronounced in diabetic individuals.

Association between high-density lipoprotein subfractions and low-grade inflammation, insulin resistance, and metabolic syndrome components: The ELSA-Brasil study

High-density lipoprotein cholesterol (HDL-C) can be divided into subfractions, which may have variable effects in atherogenesis. The results about the association between HDL-C subfractions and risk factors for cardiovascular disease are mixed. The objective of this study was to analyze the association between HDL-C subfractions and each metabolic syndrome component, homeostasis model assessment-estimated insulin resistance (HOMA-IR) and C-reactive protein (CRP). Four thousand five hundred thirty-two individuals between 35 and 74years old without previous manifest cardiovascular disease not using fibrates were enrolled. HDL-C subfractions were separated by vertical ultracentrifugation (vertical auto profile-in mg/dL) into HDL2-C and HDL3-C. HDL2-C/HDL3-C ratio, HOMA-IR, and high-sensitivity CRP were also included in the analysis. Mean age of participants was 51±9years, and 54.8% were women. In univariate analysis, HDL-C, HDL2-C, and HDL3-C were all inversely associated with each of the metabolic syndrome defining factors, HOMA-IR values, and serum CRP. We also observed a negative association between HDL2-C/HDL3-C ratio with the variables aforementioned even after adjusting for smoking, alcohol use, physical activity, and HDL-C levels (P<.01). HDL-C and its subfractions (HDL2-C and HDL3-C) are inversely associated with the defining features of metabolic syndrome, insulin resistance, and systemic inflammation. In addition, the HDL2-C/HDL3-C ratio measured by vertical auto profile is significantly associated with the former factors even after comprehensive adjustment for HDL-C and other confounding variables.

Impact of high-density lipoprotein 3 cholesterol subfraction on periprocedural myocardial injury in patients who underwent elective percutaneous coronary intervention

BackgroundPeriprocedural myocardial injury (PMI) is a major complication of percutaneous coronary intervention (PCI) and is associated with atherosclerotic coronary plaque and worse clinical outcomes. High-density lipoprotein cholesterol (HDL-C) is a protective factor for cardiovascular disease. However, the role of HDL-C subfractions, such as HDL2 cholesterol (HDL2-C) or HDL3 cholesterol (HDL3-C), in cardiovascular disease remains unclear. The purpose of the study was to investigate the relationship between HDL2-C and HDL3-C subfractions and the incidence of PMI in patients who underwent elective PCI.MethodsWe enrolled 129 patients who underwent elective PCI for stable angina pectoris. PMI was defined as an increase in high-sensitivity troponin T levels > 5 times the upper normal limit (> 0.070 ng/mL) at 24 h after PCI. Serum HDL-C subfractions (HDL2-C and HDL3-C) were assessed using ultracentrifugation in patients with and those without PMI.ResultsHDL3-C levels were significantly lower in patients with PMI than in those without (15.1 ± 3.0 mg/dL vs. 16.4 ± 2.9 mg/dL, p = 0.016) and had an independent and inverse association with PMI (odds ratio, 0.86; 95% confidence interval, 0.74–0.99; p = 0.038). When divided by the cut-off value of HDL3-C for PMI (14.3 mg/dL), the incidence of PMI was significantly higher in low HDL3-C patients than in high HDL3-C patients (51.2% vs. 30.2%, p = 0.020).ConclusionsHDL3-C was an independent inverse predictor of PMI in patients who underwent elective PCI.

Impact of Smoking Status on Lipoprotein Subfractions: Data from an Untreated Chinese Cohort

ObjectiveCigarette smoking is one of the established risk factors of atherosclerotic cardiovascular disease, however, its impact on lipids is not completely understood, especially in the Chinese population. Therefore, this study evaluated the impact of smoking status (non, former, and current smoking) on the distribution of lipoprotein subfractions in untreated patients with angina-like chest pain. MethodsA total of 877 patients were consecutively enrolled and divided into nonsmoking (n = 518), former smoking (n = 103), and current smoking (n = 256) groups. Both low- and high-density lipoprotein cholesterol (LDL-C and HDL-C) subfractions were measured using the Quantimetrix Lipoprint System. The distributions of lipoprotein subfractions were evaluated among the groups. ResultsCompared with nonsmoking subjects, the current smoking group had significantly lower large/medium HDL-C (both P < 0.001) concentration and large HDL subfraction percentage but higher small HDL-C and medium LDL-C concentrations as well as medium LDL subfraction percentage. Importantly, former smoking subjects showed elevated levels of large HDL-C concentration, large HDL particle percentage, and mean LDL particle size and attenuation in small HDL/LDL percentages and small LDL-C concentration, but these levels did not reach the optimal status compared with those of the non-smoking group (data not shown). ConclusionSmoking has an adverse impact on the lipoprotein subfractions, presented as lower large HDL particles besides higher small HDL and medium LDL particles, whereas smoking cessation could reverse these change to a certain degree.

High-Density Lipoprotein Cholesterol Subfractions in Collegiate Female Volleyball Players

Much of the published data on the lipid profiles of athletes are based on studies of endurance athletes. Data on female volleyball players are rare. The purpose of this study was thus to examine serum high-density-lipoprotein cholesterol (HDL-C) subfractions in collegiate female volleyball players. Twenty-six female collegiate volleyball players were compared with 26 age- and body mass index-matched control subjects. Dietary information was obtained with a food frequency questionnaire. The subjects were all nonsmokers and were not taking any drug known to affect lipid and lipoprotein metabolism. The volleyball players showed significantly higher mean HDL2-C than the control group. There were no significant differences in HDL-C and HDL3-C between the 2 groups. The results indicate that favorable lipid and lipoprotein profiles could be obtained by vigorous volleyball training and significantly higher HDL2-C could be obtained without observing significant differences in HDL-C and HDL3-C.

Subfractions of High-Density Lipoprotein-Cholesterol and Carotid Intima-Media Thickness: The Northern Manhattan Study.

Recent drug trials have challenged the high-density lipoprotein-cholesterol (HDL-C) antiatherosclerotic hypothesis, suggesting that total level of HDL-C may not be the best target for intervention. HDL-C subfractions may be better markers of vascular risk than total levels of HDL-C. The objective of this cross-sectional study was to investigate the relationship between HDL2-C and HDL3-C fractions and carotid intima-media thickness (cIMT) in the population-based Northern Manhattan Study. We evaluated 988 stroke-free participants (mean age, 66±8 years; 60% women; 66% Hispanic, and 34% non-Hispanic) with available data on HDL-C subfractions using precipitation method and cIMT assessed by a high-resolution carotid ultrasound. The associations between HDL-C subfractions and cIMT were analyzed by multiple linear regression models. The mean HDL2-C was 14±8 mg/dL, HDL3-C 32±8 mg/dL, and the mean total HDL-C was 46±14 mg/dL. The mean cIMT was 0.90±0.08 mm. After controlling for demographics and vascular risk factors, HDL2-C and total HDL-C were inversely associated with cIMT (per 2 SDs, β=-0.017, P=0.001 and β=-0.012, P=0.03, respectively). The same inverse association was more pronounced among those with diabetes mellitus (per 2SDs, HDL2-C: β=-0.043, P=0.003 and HDL-C: β=-0.029, P=0.02). HDL3-C was not associated with cIMT. HDL2-C had greater effect on cIMT than HDL3-C in this large urban population. The effect of HDL2-C was especially pronounced among individuals with diabetes mellitus. More research is needed to determine antiatherosclerotic effects of HDL-C subfractions and their clinical relevance.

Effects of menopause, gender and age on lipids and high-density lipoprotein cholesterol subfractions

ObjectiveTo distinguish the effects of menopause, gender and age on serum lipid risk markers for vascular disease, including high-density lipoprotein cholesterol (HDL-C) subfractions 2 and 3 (HDL2-C and HDL3-C). MethodsWe undertook a cross-sectional database analysis of apparently healthy Caucasian pre- and postmenopausal women and men (n=515, 518 and 800, respectively) not taking drugs affecting lipid metabolism (including contraceptive or post-menopausal steroids). Measurements of serum total cholesterol (TC), low-density lipoprotein (LDL-C), triglycerides (TG), HDL-C, HDL2-C, HDL3-C and non-HDL-C concentrations and the TC/HDL-C concentration ratio were considered. ResultsMen had lower TC than postmenopausal women (p<0.001) and similar LDL-C. Compared with premenopausal women, postmenopausal women had a more atherogenic lipid profile with lower HDL2-C (median 0.67 vs 0.60mmol/L, p<0.001) but no difference in HDL3-C (0.96 vs 0.96mmol/L, p=0.8). Compared with either pre or postmenopausal women, men had a more atherogenic profile with lower HDL2-C (0.36mmol/L) and HDL3-C (0.91mmol/L, all p<0.001). With standardization for confounding variables, including standardization to age of menopause (50 years), differences apparent in the non-standardized comparisons were generally sustained, although HDL3-C levels were lower at menopause, HDL2-C ceased to differ and LDL-C was lower in postmenopausal women than men. ConclusionsMale gender is associated with a more atherogenic profile than female gender, with appreciably lower levels of the HDL2-C subfraction. Among women, menopause is associated with a more atherogenic lipid profile, but has less effect than male gender.

High-density lipoprotein subfractions and carotid plaque: The Northern Manhattan Study

ObjectiveThe objective of this cross-sectional analysis was to investigate the relation between two major high-density lipoprotein cholesterol (HDL-C) subfractions (HDL2-C and HDL3-C) and carotid plaque in a population based cohort. MethodsWe evaluated 988 stroke-free participants (mean age 66 ± 8 years; 40% men; 66% Hispanic and 34% Non-Hispanic) with available data on HDL subfractions using precipitation method and carotid plaque area and thickness assessed by a high-resolution 2D ultrasound. The associations between HDL-C subfractions and plaque measurements were analyzed by quantile regression. ResultsPlaque was present in 56% of the study population. Among those with plaque, the mean ± SD plaque area was 19.40 ± 20.46 mm² and thickness 2.30 ± 4.45 mm. The mean ± SD total HDL-C was 46 ± 14 mg/dl, HDL2-C 14 ± 8 mg/dl, and HDL3-C 32 ± 8 mg/dl. After adjusting for demographics and vascular risk factors, there was an inverse association between HDL3-C and plaque area (per mg/dl: beta = −0.26 at the 75th percentile, p = 0.001 and beta = −0.32 at the 90th percentile, p = 0.02). A positive association was observed between HDL2-C and plaque thickness (per mg/dl; beta = 0.02 at the 90% percentile, p = 0.003). HDL-C was associated with plaque area (per mg/dl: beta = −0.18 at the 90th percentile, p = 0.01), but only among Hispanics. ConclusionIn our cohort we observed an inverse association between HDL3-C and plaque area and a positive association between HDL2-C and plaque thickness. HDL-C subfractions may have different contributions to the risk of vascular disease. More studies are needed to fully elucidate HDL-C anti-atherosclerotic functions in order to improve HDL-based treatments in prevention of vascular disease and stroke.

Abstract 37: Association between High-Density Lipoprotein Cholesterol Subfractions and Carotid Intima-Media Thickness

Background Recent trials have challenged the protective effect of HDL in atherosclerosis, implicating the need to shift the focus from total HDL concentration to its function and major subfractions. The objective of this cross-sectional study was to investigate the relation between HDL2 and HDL3 subfractions and carotid intima-media thickness (IMT), an early indicator of atherosclerosis and surrogate marker of ischemic stroke. Methods In NOMAS, a prospective population-based study of the incidence and risk factors of stroke, we evaluated 1041 participants (mean age 68±9 years; 38% men; 62% Hispanic, 19% black, 17% white) with available data on HDL subfractions and carotid IMT assessed by a high-resolution 2D carotid ultrasound. Carotid IMT was a composite measure of the mean IMT in all carotid artery segments. The cross-sectional association between HDL-subfractions and IMT was analyzed by multiple linear regression. Results We mean±SD of total HDL was 46.15±14.25 mg/dl (median = 44.00), HDL2 14.59±8.29 mg/dl (median = 13.00), HDL3 31.06±8.32 mg/dl (median = 32.00). The mean IMT was 0.90±0.08 mm. After controlling for demographics, LDL, triglycerides, and cholesterol-lowering medication, a strong association was observed between total HDL (per SD, beta=-0.008, p= 0.01), HDL2 (per SD, beta=-0.006, p=0.03) and HDL3 (per SD, beta=-0.007 p=0.01) in relation to IMT. A significant interaction was observed between diabetes (vs. non-diabetes) and HDL2 in relation to IMT (p=0.01; -0.018mm). Conclusion The observed strong independent inverse associations between HDL, HDL2 and HDL3 and carotid IMT. HDL2 was only significantly associated with IMT among individuals with diabetes. These observations show novel evidence for a potential role of HDL2 and HDL3 subfractions, providing the opportunity to develop novel HDL-targeted therapies for the prevention of atherosclerosis.