Higher High-density Lipoprotein Cholesterol Concentrations Research Articles

Gender specific association of ABCA1 gene R219K variant in coronary disease risk through interactions with serum triglyceride elevation in Turkish adults

ATP binding cassette transporter A1 (ABCA1) controls the reverse cholesterol transport. Some ABCA1 variants are correlated with serum high-density lipoprotein cholesterol (HDL-C) and other lipid concentrations. We aimed to explore the relationship of ABCA1 gene with both the lipid profile and coronary heart disease (CHD) risk. Selected 627 individuals of the Turkish Adult Risk Factor Study were genotyped for ABCA1 R219K polymorphism using PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) method. Student's t-test, one-way ANOVA, Chi-square test, linear and logistic regression was used for statistical analysis. We demonstrated a gender-specific effect of the R219K polymorphism on plasma lipids and CHD. In men, while homozygosity of the K allele was associated with increased plasma low-density lipoprotein cholesterol (LDL-C) (p<0.05) and total cholesterol concentrations (p<0.05), carriage of this allele was associated with higher HDL-C concentrations (p<0.05) after adjustment for associated risk factors, but not with CHD. In women, however, without being related to HDL-C levels, each 219K allele was associated with 10% higher triglycerides (TG) concentrations (p<0.05). R219K heterozygosity in women independently doubled (95% CI 1.00; 3.80) the odds ratio for CHD risk in regression models, after adjustment for several variables. Interaction of TG elevation (>140 mg/dL) with CHD was demonstrated in female 219RK genotype carriers. R219 allele of the ABCA1 gene independently confers CHD risk in heterozygote Turkish women, not via reduced HDL-C, but interacting with elevated TG expressed by the 219K allele, but not in men.

Controlling for apolipoprotein A-I concentrations changes the inverse direction of the relationship between high HDL-C concentration and a measure of pre-clinical atherosclerosis

BackgroundThe independent effect of high density lipoprotein cholesterol (HDL-C) concentration to confer cardiovascular disease protection has been questioned. We investigated whether the inverse association between HDL-C concentration and a measure of preclinical atherosclerosis was modified by other risk factors. MethodsCross-sectional data were analysed from an occupational cohort of 12,031 men who had measurements of cardiovascular risk factors and a cardiac computed tomography (CT) estimation of coronary artery calcium (CAC) score, a measure of pre-clinical atherosclerosis. Logistic regression was used to describe associations between both HDL-C and Apo-A-I concentrations and their ratio as exposures, and CAC scores >0, ≥20 and ≥100, as outcomes. Results1351 (11.2%), 665 (5.5%) and 230 (1.9%) of participants had a CAC score >0, ≥20 and ≥100, respectively. Adjusting for age, glucose, triglyceride, LDL-C, systolic blood pressure, waist circumference, prior cerebrovascular accident, prior coronary artery disease, prior hypertension, alcohol consumption, smoking status and exercise, a negative association existed between HDL-C and CAC score. (E.g. odds ratio (OR) for top compared to bottom HDL-C quartile for CAC >0 = 0.78 [95%CI 0.64, 0.94], p = 0.01). Further adjustment for Apo A-I changed the direction of the association between HDL-C and CAC score >0 (OR for top compared to bottom quartiles 1.61 [95%CI 1.18, 2.21], p = 0.003). Sensitivity analyses showed that point estimates for ORs were very similar regardless of CAC score threshold (CAC >0, ≥20 and ≥100). ConclusionControlling for Apo A-I concentrations changes the inverse direction of relationship between high HDL-C concentration and a measure of pre-clinical atherosclerosis.

Omega-3 fatty acids, polymorphisms and lipid related cardiovascular disease risk factors in the Inuit population

BackgroundTissue concentrations of fatty acids (FAs) and genetic variations are well-known factors which affect the cardiovascular disease (CVD) risk. The objective was to examine whether the genetic variability of 20 candidate genes and red blood cells (RBCs) percentage of total n-3 polyunsaturated fatty acids (PUFA), a biomarker of dietary n-3 PUFA intake, modulate lipid related CVD risk factors in the Inuit population.MethodsData from the Qanuippitaa Nunavik Health Survey (n = 553) were analysed via multivariate regression models with 40 known polymorphisms, RBCs percentage of n-3 PUFA, and the interaction term to take into account the effect on plasma lipid and apolipoporotein levels.ResultsIndividuals being heterozygotes for CETP C-4502T (rs183130) or G-971A (rs4783961) together with higher n-3 PUFA had lower triacylglycerol (TG) concentrations compared to homozygotes for the minor allele. Further, effects of a stronger beneficial association between n-3 PUFA in RBCs and plasma lipid parameters- including lower total cholesterol (TC), lower low-density lipoprotein cholesterol (LDL-C) or higher high-density lipoprotein cholesterol (HDL-C) concentrations- were associated with AGT M235T (rs699) TT genotype, CETP G-971A (rs4783961) AG genotype, T allele carriers of CETP C-4502T (rs183130), and T allele carriers of CETP Ile405Val (rs5882). In contrast, higher n-3 PUFA in RBCs were associated with adverse lipid profiles- including increased LDL-C, increased apolipoprotein B100 or decreased HDL-C concentrations- in G allele carriers of the APOA5 -3 A/G (rs651821), C allele carriers of APOA5 T-1131C (rs662799), G carriers of APOC3 SstI (rs5128) and G carriers of APOA4 Asn147Ser (rs5104).ConclusionOverall, these results suggest that percentage of total n-3 PUFA of RBCs are associated with lipids related CVD risk factors conferred by genetic variations in the Inuit population.

Association Between Lipids, Lipoproteins Composition of HDL Particles and Triglyceride-Rich Lipoproteins, and LCAT and CETP Activity in Post-renal Transplant Patients

High-density lipoprotein (HDL) remodeling within the plasma compartment and the association between lecithin-cholesterol acyltransferase (LCAT) and cholesterol ester transfer protein (CETP) activity, and lipid, lipoprotein concentrations and composition were investigated. The aim was to examine the high sensitivity of C-reactive protein (hsCRP), lipid, apolipoprotein B (apoB), apoAI, total apoAII, apoAIInonB, apoB-containing apoAII (apoB:AII), total apoCIII, apoCIIInonB, apoB-containing apoCIII (apoB:CIII) concentration and LCAT and CETP activity to gain an insight into the association between them and LCAT and CETP, 57 post-renal transplant (Tx) patients with and without statin therapy and in 15 healthy subjects. Tx patients had moderate hypertriglyceridemia, hypercholesterolemia, and dyslipoproteinemia, disturbed triglyceride-rich lipoproteins (TRLs) and HDL composition, decreased LCAT, and slightly increased hsCRP but no CETP activity. Spearman’s correlation test showed the association between lipids and lipoproteins and LCAT or CETP, and multiple ridge stepwise forward regression showed that immunosuppressive therapy in Tx patients can disturb HDL and TRLs composition. The results suggest that inhibition or activation of LCAT is due, in part, to HDL-associated lipoprotein. Lipoprotein composition of apoAI, apoAIInonB, and apoCIIInonB in HDL particle and apoB:AII TRLs can contribute to decrease LCAT mass in Tx patients. Tx patients without statin and with lower triglycerides but higher HDL cholesterol concentration and disturbed lipoprotein composition of ApoAI and apoAII in HDL particle can decrease LCAT, increase LDL cholesterol, aggravate renal graft, and accelerate atherosclerosis and chronic heart diseases.

Epigenome-Wide Analysis in Familial Hypercholesterolemia Identified New Loci Associated with High-Density Lipoprotein Cholesterol Concentration

This study aims to assess whether epigenetic changes may account for high-density lipoprotein cholesterol (HDL-C) level variability in familial hypercholesterolemia (FH), a recognized human model to study cardiovascular disease risk modulators. A genome-wide DNA methylation analysis (Infinium HumanMethylation27 BeadChip, Illumina) was performed on peripheral blood DNA samples obtained from men with FH with low (n = 10) or high (n = 11) HDL-C concentrations. The initial association with one of the top differentially methylated loci located in the promoter of the TNNT1 gene was replicated in a cohort of 276 FH subjects using pyrosequencing. According to the Ingenuity Pathway Analysis software, the HDL-C differentially methylated loci identified were significantly associated with pathways related to lipid metabolism and cardiovascular disease. TNNT1 DNA methylation levels were positively correlated with mean HDL particle size, HDL-phospholipid, HDL-apolipoprotein AI, HDL-C and TNNT1 expression levels. These results suggest that epigenome-wide changes account for interindividual variations in HDL particle metabolism and that TNNT1 is a new candidate gene for dyslipidemia.

FABP 2 gene polymorphism and metabolic syndrome in elderly people of Croatian descent

Metabolic syndrome (MetS) is a multifactorial disorder in which dyslipidemia plays an important role. Fatty acid-binding protein 2 (FABP 2) is responsible for transport of free fatty acids in the intestinal endothelium cells. FABP2-genetic variants might affect plasma lipid concentrations and intracellular lipid transport. The aim of this study was to investigate the association between FABP2 Ala54Thr genetic polymorphism and metabolic syndrome and some biochemical and anthropological parameters in elderly subjects. This cross-sectional study included 140 men and 176 women older than 70 years. Fasting serum concentration of glucose, lipid parameters, total proteins and C-reactive protein were determined by standardized methods. Presence (MetS(+)) or absence (MetS(-)) of MetS was determined according to criteria of the International Diabetes Federation. FABP2 genetic polymorphism Ala54Thr (rs1799883) was genotyped with PCR-RFPL. The genotype frequencies for Ala/Ala, Ala/Thr and Thr/Thr genotype were 60, 36 and 6 in MetS(-), and 131, 70 and 13 in MetS(+), respectively, without statistical significance (P = 0.567). Ala/Ala genotype was a subgroup of non-carriers, while Ala/Thr and Thr/Thr genotypes were Thr54-carriers. Median triglyceride concentration was significantly lower in carriers then in non-carriers for whole MetS(+) group (P = 0.050); there were no significant difference between men with MetS (P = 0.144), but there was a difference between women with MetS (P = 0.020). T-test showed that mean HDL cholesterol concentrations in MetS(+) group for Thr54-carriers was significantly higher in whole group (P = 0.001), and for both genders (men P = 0.039; women P = 0.004) as compared to non-carriers. FABP2 genetic polymorphism is associated with lower triglyceride and higher HDL-cholesterol concentrations in elderly subjects with MetS. This genetic variation might be a useful marker for understanding dyslipidemia in MetS.

Serum paraoxonase-3 concentration in HIV-infected patients. Evidence for a protective role against oxidation

We investigated the influence of the HIV infection on serum paraoxonase-3 (PON3) concentration and assessed the relationships with lipoprotein-associated abnormalities, immunological response, and accelerated atherosclerosis. We studied 207 HIV-infected patients and 385 healthy volunteers. Serum PON3 was determined by in-house ELISA, and PON3 distribution in lipoproteins was investigated by fast-performance liquid chromatography (FPLC). Polymorphisms of the PON3 promoter were analyzed by the Iplex Gold MassArray(TM) method. PON3 concentrations were increased (about three times) in HIV-infected patients with respect to controls (P < 0.001) and were inversely correlated with oxidized LDL levels (P = 0.038). Long-term use of nonnucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy was associated with a decrease of PON3 concentrations. In a multivariate linear regression analysis, these relationships were still strong when the main confounding covariates were considered. PON3 was mainly found in HDL in HIV-infected patients, but a substantial amount of the protein was detected in LDL particles. This study reports for the first time an important increase in serum PON3 concentrations in HIV-infected patients that is associated with their oxidative status and their treatment with NNRTI. Long-term, prospective studies are needed to confirm the possible influence of this enzyme on the course of this disease and its possible utility as an analytical biomarker.

Comparison of native and capric acid-enriched mustard oil effects on oxidative stress and antioxidant protection in rats

The present study evaluated the effect of mustard oil enriched in capric acid, a medium-chain fatty acid, on antioxidant enzyme activities in liver and brain and on the levels of malondialdehyde (MDA) in liver, brain and plasma in rats; the effect of adding cholesterol to the diet was also investigated. Charles Foster male albino rats weighing 80-100 g were fed one of four diets for 30 d (six rats per group). In the absence of added dietary cholesterol, the addition of capric acid to the diet resulted in lower plasma total cholesterol, non-HDL-cholesterol and TAG concentrations, higher HDL-cholesterol concentrations, higher antioxidant enzyme activities in liver and brain and lower MDA concentrations in liver, brain and plasma. Adding cholesterol to the diet increased plasma total cholesterol, non-HDL-cholesterol and TAG concentrations, decreased HDL-cholesterol concentration, decreased the activities of antioxidant enzymes and increased tissue and plasma MDA concentrations. Including capric acid in the diet of rats receiving cholesterol at least partly prevented the effects of the increased cholesterol. It is concluded that compared with native mustard oil, capric acid-enriched mustard oil improves blood lipids, enhances antioxidant protection and reduces lipid peroxidation.

Blood lipid and lipoprotein concentrations and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition

ObjectiveTo examine the association between serum concentrations of total cholesterol, high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol, triglycerides, apolipoprotein A-I (apoA), apolipoprotein B and the incidence of colorectal...

Association of interleukin-6 gene -572 C > G polymorphism with dietary intake of n-3 fatty acids on plasma HDL-c level in Chinese male adults.

Heterogeneity in circulating lipid concentrations in response to different dietary fat intakes may be due, in part, to gene polymorphism of cytokine related to inflammation. The objective was to determine whether dietary n-3 PUFAs intake influenced the effects of IL-6 -572 polymorphism on plasma lipids and apolipoproteins. This cross-sectional study included 195 men and 386 women aged 40-65 y. DNA was isolated from white blood cell to determine the IL-6 -572 C-G polymorphisms by the polymerase chain reaction-logation detection reaction (PCR-LDR) method. Dietary fatty acids were assessed by measuring erythrocyte membrane fatty acids, and fasting plasma was collected to determine blood lipids and apoproteins. The frequency of the G allele was 0.214. There were no significant differences in plasma lipids across genotypes (all p > 0.05). When men and women were grouped into tertiles by the erythrocyte membrane n-3 PUFAs composition; in the lowest group, men with G allele had 18% higher HDL-cholesterol concentrations than did C/C genotype (p < 0.05). Similar effects were observed for apo A. Adjusting for age, BMI and total PUFA did not alter this association. The interaction was not significant in women. Dietary n-3 PUFA intake influenced the effects of IL-6 -572 genotype on HDL-c concentrations in males.

Call to Action: Cardiovascular Disease in Asian Americans

In 2009, President Obama signed an Executive Order calling for strategies to improve the health of Asian Americans and to seek data on the health disparities in Asian American subgroups.1 Data on Asian American subgroups are scarce and many health disparities remain unknown. The purpose of this Advisory is to highlight the gaps in existing research on cardiovascular disease (CVD) among Asian Americans, and to serve as a call to action on behalf of the American Heart Association to address these areas of need. Asian Americans are the fastest growing racial/ethnic group in the United States, representing 25% of all foreign-born people in the United States.2 They are projected to reach nearly 34 million by 2050.3 Several major Federal surveys (eg, the American Community Survey, the National Health Interview Survey, and the Behavioral Risk Factor Surveillance Survey) only recently started to classify Asian Americans into 7 subgroups: Asian Indian, Chinese, Filipino, Korean, Japanese, Vietnamese, and Other Asian. The first six of these subgroups together constitute >90% of Asian Americans in the United States.4 Although some data are available on Asian subgroups from these major federal surveys, in general, these data are not available for public use because of the privacy concerns resulting from the small sample sizes within subgroups. This situation limits their utility for health-related research. Because health surveys and questionnaires almost universally combine persons of Asian ancestry into a single group, the heterogeneity within this classification is masked. Socioeconomic and cultural factors have been found to be associated with CVD and its risk factors, which is why it is important to understand these differences among Asian subgroups. The Table shows the number of persons in each group based on the most recent US Census data available (American Community Survey, 2008), with the recognition that …

Association of the low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio and concentrations of plasma lipids with high-density lipoprotein subclass distribution in the Chinese population

BackgroundTo evaluate the relationship between the low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio and HDL subclass distribution and to further examine and discuss the potential impact of LDL-C and HDL-C together with TG on HDL subclass metabolism.ResultsSmall-sized preβ1-HDL, HDL3b and HDL3a increased significantly while large-sized HDL2a and HDL2b decreased significantly as the LDL-C/HDL-C ratio increased. The subjects in low HDL-C level (< 1.03 mmol/L) who had an elevation of the LDL-C/HDL-C ratio and a reduction of HDL2b/preβ1-HDL regardless of an undesirable or high LDL-C level. At desirable LDL-C levels (< 3.34 mmol/L), the HDL2b/preβ1-HDL ratio was 5.4 for the subjects with a high HDL-C concentration (≥ 1.55 mmol/L); however, at high LDL-C levels (≥ 3.36 mmol/L), the ratio of LDL-C/HDL-C was 2.8 in subjects, and an extremely low HDL2b/preβ1-HDL value although with high HDL-C concentration.ConclusionWith increase of the LDL-C/HDL-C ratio, there was a general shift toward smaller-sized HDL particles, which implied that the maturation process of HDL was blocked. High HDL-C concentrations can regulate the HDL subclass distribution at desirable and borderline LDL-C levels but cannot counteract the influence of high LDL-C levels on HDL subclass distribution.

High Pre-β1 HDL Concentrations and Low Lecithin: Cholesterol Acyltransferase Activities Are Strong Positive Risk Markers for Ischemic Heart Disease and Independent of HDL-Cholesterol

We hypothesized that patients with high HDL-cholesterol (HDL-C) and ischemic heart disease (IHD) may have dysfunctional HDL or unrecognized nonconventional risk factors. Individuals with IHD (Copenhagen University Hospital) and either high HDL-C (n = 53; women >or=735 mg/L; men >or=619 mg/L) or low HDL-C (n = 42; women <or=387 mg/L; men <or=341 mg/L) were compared with individuals without IHD (Copenhagen City Heart Study) matched by age, sex, and HDL-C concentrations (n = 110). All participants had concentrations within reference intervals for LDL-C (<1600 mg/L) and triglyceride (<1500 mg/L), and none were treated with lipid-lowering medications. Pre-beta(1) HDL and phospholipid transfer protein concentrations were measured by using commercial kits and lecithin:cholesterol acyltransferase (LCAT) activity by using a proteoliposome cholesterol esterification assay. Pre-beta(1) HDL concentrations were 2-fold higher in individuals with IHD vs no IHD in both the high [63 (5.7) vs 35 (2.3) mg/L; P < 0.0001] and low HDL-C [49 (5.0) vs 27 (1.5) mg/L; P = 0.001] groups. Low LCAT activity was also associated with IHD in the high [95.2 (6.7) vs 123.0 (5.3) micromol x L(-1) x h(-1); P = 0.002] and low [93.4 (8.3) vs 113.5 (4.9) micromol x L(-1) . h(-1); P = 0.03] HDL-C groups. ROC curves for pre-beta(1) HDL in the high-HDL-C groups yielded an area under the curve of 0.71 (95% CI: 0.61-0.81) for predicting IHD, which increased to 0.92 (0.87-0.97) when LCAT was included. Similar results were obtained for low HDL-C groups. An inverse correlation between LCAT activity and pre-beta(1) HDL was observed (r(2) = 0.30; P < 0.0001) in IHD participants, which was stronger in the low HDL-C group (r(2) = 0.56; P < 0.0001). IHD was associated with high pre-beta(1) HDL concentrations and low LCAT levels, yielding correct classification in more than 90% of the IHD cases for which both were measured, thus making pre-beta(1) HDL concentration and LCAT activity level potentially useful diagnostic markers for cardiovascular disease.

Dietary n−3 and n−6 polyunsaturated fatty acid intake interacts with FADS1 genetic variation to affect total and HDL-cholesterol concentrations in the Doetinchem Cohort Study

The delta-5 and delta-6 desaturases, encoded by the FADS1 and FADS2 genes, are rate-limiting enzymes in polyunsaturated fatty acid (PUFA) biosynthesis. Single nucleotide polymorphisms in the FADS gene cluster region have been associated with both PUFA concentrations in plasma or erythrocyte membrane phospholipids and cholesterol concentrations in recent genome-wide association studies. We examined whether genetic variations in the FADS gene cluster region interact with dietary intakes of n-3 (omega-3) and n-6 (omega-6) PUFAs to affect plasma total, HDL-, and non-HDL-cholesterol concentrations. Dietary intakes of n-3 and n-6 PUFAs, plasma concentrations of total and HDL cholesterol, and rs174546, rs482548, and rs174570 in the FADS gene cluster region were measured in 3575 subjects in the second survey of the Doetinchem Cohort Study. Significant associations between rs174546 genotypes and total and non-HDL-cholesterol concentrations were observed in the group with a high intake of n-3 PUFAs (> or =0.51% of total energy; P = 0.006 and 0.047, respectively) but not in the low-intake group (P for interaction = 0.32 and 0.51, respectively). The C allele was associated with high total and non-HDL-cholesterol concentrations. Furthermore, the C allele was significantly associated with high HDL-cholesterol concentrations in the group with a high intake of n-6 PUFAs (> or =5.26% of total energy, P = 0.004) but not in the group with a low intake (P for interaction = 0.02). Genetic variation in the FADS1 gene potentially interacts with dietary PUFA intakes to affect plasma cholesterol concentrations, which should be investigated further in other studies.

Eating Competence of Elderly Spanish Adults Is Associated with a Healthy Diet and a Favorable Cardiovascular Disease Risk Profile1–3

Eating competence (EC), a bio-psychosocial model for intrapersonal approaches to eating and food-related behaviors, is associated with less weight dissatisfaction, lower BMI, and increased HDL-cholesterol in small U.S. studies, but its relationship to nutrient quality and overall cardiovascular risk have not been examined. Prevención con Dieta Mediterránea (PREDIMED) is a 5-y controlled clinical trial evaluating Mediterranean diet efficacy on the primary prevention of cardiovascular diseases (CVD) in Spain. In a cross-sectional study, 638 PREDIMED participants (62% women, mean age 67 y) well phenotyped for cardiovascular risk factors were assessed for food intake and EC using validated questionnaires. Overall, 45.6% were eating-competent. EC was associated with being male and energy intake (P < 0.01). After gender and energy adjustment, participants with EC compared with those without showed higher fruit intake and greater adherence to the Mediterranean diet (P < 0.05) and tended to consume more fish (P = 0.076) and fewer dairy products (P = 0.054). EC participants tended to have a lower BMI (P = 0.057) and had a lower fasting blood glucose concentration and serum LDL-:HDL-cholesterol ratio (P < 0.05) and a higher HDL-cholesterol concentration (P = 0.025) after gender adjustment. EC participants had lower odds ratios (OR) of having a blood glucose concentration >5.6 mmol/L (0.71; 95% CI 0.51–0.98) and HDL-cholesterol <1.0 mmol/L (0.70; 95% CI 0.68–1.00). The OR of actively smoking, being obese, or having a serum LDL-cholesterol concentration ≥3.4 mmol/L were <1.0, but the 95% CI included the 1.0 (P > 0.1). Our findings support further examination of EC as a strategy for enhancing diet quality and CVD prevention. J. Nutr. 140: 1322–1327, 2010.

Cholesterol Efflux Potential and Antiinflammatory Properties of High-Density Lipoprotein After Treatment With Niacin or Anacetrapib

To examine the effects of treatments with niacin or anacetrapib (an inhibitor of cholesteryl ester transfer protein) on the ability of high-density lipoprotein (HDL) to promote net cholesterol efflux and reduce toll-like receptor-mediated inflammation in macrophages. A total of 18 patients received niacin, 2 g/d, for 4 weeks; 20 patients received anacetrapib, 300 mg/d, for 8 weeks; and 2 groups (n=4 and n=5 patients) received placebo. HDL samples were isolated by polyethylene glycol precipitation or ultracentrifugation, tested for the ability to promote cholesterol efflux in cholesterol-loaded THP-I or mouse peritoneal macrophages, or used to pretreat macrophages, followed by lipopolysaccharide exposure. HDL cholesterol levels were increased by 30% in response to niacin and by approximately 100% in response to anacetrapib. Niacin treatment increased HDL-mediated net cholesterol efflux from foam cells, primarily by increasing HDL concentration, whereas anacetrapib treatment increased cholesterol efflux by both increasing HDL concentration and causing increased efflux at matched HDL concentrations. The increased efflux potential of anacetrapib-HDL was more prominent at higher HDL cholesterol concentrations (>12 microg/mL), which was associated with an increased content of lecithin-cholesterol acyltransferase (LCAT) and apolipoprotein E and completely dependent on the expression of ATP binding cassette transporters (ABCA1 and ABCG1). Potent antiinflammatory effects of HDL were observed at low HDL concentrations (3 to 20 microg/mL) and were partly dependent on the expression of ABCA1 and ABCG1. All HDL preparations showed similar antiinflammatory effects, proportionate to the HDL cholesterol concentration. Niacin treatment caused a moderate increase in the ability of HDL to promote net cholesterol efflux, whereas inhibition of cholesteryl ester transfer protein via anacetrapib led to a more dramatic increase in association with enhanced particle functionality at higher HDL concentrations. All HDLs exhibited potent ability to suppress macrophage toll-like receptor 4-mediated inflammatory responses, in a process partly dependent on cholesterol efflux via ABCA1 and ABCG1.

An elevated apolipoprotein B/AI ratio is independently associated with microalbuminuria in male subjects with impaired fasting glucose

Background and aims The ratio of apolipoprotein B/AI (apo B/AI) has been used as a marker to predict the risk of coronary artery disease. Recent studies have suggested an association between apolipoprotein B level and microalbuminuria in diabetic subjects. This study was performed to assess a possible association between the apo B/AI ratio and microalbuminuria in male subjects with impaired fasting glucose (IFG). Methods and results In 1266 patients with fasting serum glucose level in the pre-diabetic range, urine albumin-to-creatinine ratio (UACR, μg mg −1) was measured from single morning voided urine. The presence of microalbuminuria was defined as a UACR between 30 and 299 μg mg −1. Participants were stratified into four groups by apo B/AI quartiles, from the lowest to the highest. Apo B/AI was higher with increasing body mass index, higher serum triglyceride and serum low-density lipoprotein cholesterol, systolic and diastolic blood pressure values, but lower with higher high-density lipoprotein cholesterol concentrations. After adjusting for these and other confounding factors, an increased apo B/AI ratio was independently associated with the presence of microalbuminuria. In receiver operating characteristic (ROC) curve analyses, apo B/AI ratio showed the highest correlation with the presence of microalbuminuria among the variables, although statistically not different. Conclusion These findings indicate that apo B/AI ratio shows significant association with microalbuminuria in Korean male subjects with IFG.

Nicotinic acid improves reverse cholesterol transport in dogs

Nicotinic acid (NA) improves plasma lipids but the involved mechanisms have not been fully elucidated. A higher HDL‐cholesterol (HDL‐C) concentration has been observed in humans, and the role of cholesteryl ester transfer protein (CETP) in this raise remains to be determined. With this aim, we assessed the NA effect on the reverse cholesterol transport (RCT) in the dog, which is a CETP‐devoid species. RCT was assessed through stable isotope endogenous labeling of HDL‐C and apoAI moieties. NA treatment lowered triglyceride (TG) plasma concentration (p &lt; 0.01) due to a diminution in VLDL‐TG (p &lt; 0.05). Cholesterol plasma concentration was reduced (p &lt; 0.0001) as a result of lowered concentration of both LDL‐C (p &lt; 0.05) and HDL‐C (p &lt; 0.0001). Kinetic studies showed a higher cholesterol esterification rate (p &lt; 0.05) that was in accordance with a rise in cholesterol efflux as measured in vitro (p &lt; 0.05). Cholesterol turnover was accelerated via selective uptake of both HDL and cholesterol esters that explain the HDL‐C reduction (p &lt; 0.05 for both). In conclusion, this study shows that, in CETP‐devoid species as dogs, NA would lower HDL due to a higher catabolism, which would reflect a more active RCT. Moreover, in humans or in other CETP species, NA could also raise HDL‐C as a result of a reduction in plasma TG. Since it has been shown a higher HDL‐C concentration after NA treatment, this second effect should be predominant in human.

Lipoproteínas de alta densidad y riesgo cardiovascular: revisión de las evidencias y de las dudas

High-density lipoproteins (HDL) transport cholesterol from the periphery to the liver. Cross-sectional studies relating low HDL-cholesterol (HDL-c) concentrations to a higher prevalence of cardiovascular disease (CVD) date back to the 1950s. Subsequent populationbased studies established that low HDL-c levels are an independent predictor of CVD, a finding that is recognized in clinical guidelines for cardiovascular prevention. Many publications, although not all, have established an inverse correlation between the incidence of ischemic stroke, whether fatal or non-fatal, and HDL-c. Cholesteryl ester transfer protein (CETP) facilitates the exchange of triglyceride (for cholesteryl ester) from very low density lipoprotein (VLDL) particles to HDL particles. Some families with genetic CETP alterations have high HDL-c concentrations and a lower incidence of CVD. Some observational studies, but not all, have shown that persons with functional CETP anomalies have high HDL-c levels and a lower incidence of CVD. This observation has prompted interest in CETP inhibition as an intervention to reduce coronary heart disease.

Plasma lecithin:cholesterol acyltransferase activity modifies the inverse relationship of C-reactive protein with HDL cholesterol in nondiabetic men

Lecithin:cholesterol acyltransferase (LCAT) is instrumental in high-density lipoprotein (HDL) maturation, but high LCAT levels do not predict low cardiovascular risk. LCAT may affect antioxidative or anti-inflammatory properties of HDL. We determined the relationship of plasma high-sensitivity C-reactive protein (CRP) with LCAT activity and evaluated whether LCAT activity modifies the decreasing effect of HDL cholesterol (HDL-C) on CRP, as an estimate of its anti-inflammatory properties. Plasma HDL-C, apolipoprotein (apo) A-I and LCAT activity (exogenous substrate method) were measured in 260 nondiabetic men without cardiovascular disease. CRP was correlated inversely with HDL-C and apo A-I, and positively with LCAT activity ( P < 0.01 to 0.001). Multivariate regression analysis demonstrated that age- and smoking-adjusted plasma CRP levels were associated negatively with HDL-C ( β = − 0.224, P < 0.001) and positively with LCAT activity ( β = 0.119, P = 0.034), as well as with the interaction between HDL-C and LCAT activity ( β = 0.123, P = 0.026). There was also an interaction between apo A-I and LCAT activity on CRP ( β = 0.159, P = 0.005). These relationships remained similar after adjustment for apo B-containing lipoproteins. In conclusion, the inverse relationship of HDL-C with CRP is attenuated by LCAT activity at higher HDL-C levels. It is hypothesized that LCAT could mitigate HDL's anti-inflammatory or antioxidative properties at higher HDL-C concentrations.