Higher High-density Lipoprotein Concentrations Research Articles

The association between adolescent depression and dyslipidemia

BackgroundChildren and adolescents with major depressive disorder (MDD) are at increased risk for premature cardiovascular disease (CVD). Whether adolescents with MDD manifest evidence of dyslipidemia, a key risk factor for CVD, is unknown. MethodsYouth recruited through an ambulatory psychiatry clinic and the community, were categorized following diagnostic interview as MDD or as healthy controls [HC]. CVD risk factors including high density lipoprotein (HDL), low density lipoprotein (LDL), and triglyceride concentrations were collected. Depression severity was measured using the Center for Epidemiological Studies Depression Scale for Children. The associations of diagnostic group as well as depressive symptom severity with lipid concentrations were examined using multiple regression analyses. Models were adjusted for age, sex, and standardized Body Mass Index. ResultsParticipants (n = 243) were 68 % female with a mean age of 15.04 ± 1.81 years. MDD and HC participants had comparable levels of dyslipidemia (MDD: 48 %, HC: 46 %, p > .7) and hypertriglyceridemia (MDD: 34 %, HC: 30 %, p > .7). Among depressed adolescents, greater depressive symptoms were associated with higher total cholesterol concentrations in unadjusted models only. Greater depressive symptoms were associated with higher HDL concentrations and a lower triglyceride-to-HDL ratio, after adjusting for covariates. LimitationsCross-sectional design. ConclusionsAdolescents with clinically significant depressive symptoms manifested similar levels of dyslipidemia as healthy youth. Future studies examining the prospective trajectories of depressive symptoms and lipid concentrations are needed to determine the point at which dyslipidemia emerges in the course of MDD, and the mechanism of the association that imparts increased CVD risk for depressed youth.

Impact of macronutrient supplements for children born preterm or small for gestational age on developmental and metabolic outcomes: A systematic review and meta-analysis.

BackgroundNutritional supplements may improve development of infants born small (preterm or small for gestational age [SGA]) but may increase the risk of later metabolic disease. We conducted a systematic review and meta-analysis to assess the effects of macronutrient supplements for infants born small on later development and metabolism.Methods and findingsWe searched OvidMedline, Embase, Cochrane CENTRAL, and Cochrane Database of Systematic Reviews from inception to April 1, 2019, and controlled-trials.com, clinicaltrials.gov, and anzctr.org.au. Randomised or quasirandomised trials were included if the intention was to increase macronutrient intake to improve growth or development of infants born small and assessed post-discharge outcomes. Co-primary outcomes were cognitive impairment and metabolic risk, evaluated in toddlers (<3 years), childhood (3 to 8 years), and adolescence (9 to 18 years). Two reviewers independently extracted data. Quality was assessed using the Cochrane Risk of Bias tool, and data were pooled using random-effect models.Twenty-one randomised and one quasirandomised trial of variable methodological quality involving 3,680 infants were included. In toddlers born small, supplementation did not alter cognitive impairment (relative risk [RR] 1.00; 95% confidence interval [CI] 0.67 to 1.49; P = 0.99), and there were no differences in cognitive scores (mean difference [MD] 0.57; 95% CI −0.71 to 1.84; P = 0.38) or motor scores (MD 1.16; 95% CI −0.32 to 2.65; P = 0.12) between supplemented and unsupplemented groups. However, fewer supplemented children had motor impairment (RR 0.76; 95% CI 0.62 to 0.94; P = 0.01). In subgroup analyses, supplementation improved cognitive scores in boys (MD 5.60; 95% CI 1.07 to 10.14; P = 0.02), but not girls born small (MD −2.04; 95% CI −7.04 to 2.95; P = 0.42), and did not alter cognitive or motor scores in the subgroup of children born SGA. In childhood, there was no difference in cognitive impairment (RR 0.81; 95% CI 0.26 to 2.57; P = 0.72) or cognitive scores (MD 1.02; 95% CI −1.91 to 3.95; P = 0.50) between supplemented and unsupplemented groups. There were also no differences in blood pressure, triglyceride, and low-density lipoprotein (LDL) concentrations (all P > 0.05). However, supplemented children had lower fasting glucose (mmol/L: MD −0.20; 95% CI −0.34 to −0.06; P = 0.005) and higher high-density lipoprotein (HDL) concentrations (mmol/L: MD 0.11; 95% CI 0.02 to 0.19; P = 0.02). In subgroup analyses, there was no evidence of differences in blood pressure between supplemented and unsupplemented groups in boys or girls born small, or in SGA children. In adolescence, there was no difference between supplemented and unsupplemented groups in blood pressure, triglycerides, LDL and HDL concentrations, fasting blood glucose, insulin resistance, and fasting insulin concentrations (all P > 0.05). Limitations include considerable unexplained heterogeneity, low to very low quality of the evidence, and limited data beyond early childhood.ConclusionsIn this systematic review and meta-analysis of randomised trials, we found no evidence that early macronutrient supplementation for infants born small altered later cognitive function, although there was some evidence that supplementation may decrease motor impairment in toddlers. Contrary to the findings from observational studies, evidence from randomised trials suggests that early macronutrient supplementation for infants born small improves some metabolic outcomes in childhood.PROSPERO registrationCRD42019127858.

Longitudinal Analysis of Sleep Duration and Cardiometabolic Risk in Young Children.

The aim of this study is to determine if sleep duration in early childhood is associated with cardiometabolic risk (CMR) in later childhood as assessed by a CMR cluster score [sum of age- and sex-standardized z-scores of waist circumference (WC), systolic blood pressure, triglycerides, glucose, and (inverse) high-density lipoprotein (HDL)]. Secondary objectives included examining sleep duration and the individual CMR factors and BMI z-score. A prospective cohort study was conducted using data from the TARGet Kids! practice-based research network in Toronto, Canada. Children (n = 597) with parent-reported 24-hour sleep duration in early childhood (12-36 months) and a follow-up visit (36-96 months) with all five CMR factors were included in the analysis. Multivariable linear regression was used to assess the relationship between early childhood sleep duration and later childhood CMR, adjusting for relevant covariates. Average 24-hour sleep duration in early childhood [mean age: 28.1 (6.6) months] was 11.8 (1.4) hours, with 87% meeting or exceeding total sleep recommendations for their age. Sleep duration in early childhood was not associated with the CMR cluster score in later childhood. Shorter sleep duration was associated with higher HDL concentrations [adjusted β = -0.028 (95% confidence interval: -0.049 to -0.007), p = 0.009]. Further research is needed to determine if early childhood sleep duration is associated with HDL in later childhood. Future studies, which investigate sleep quality in addition to sleep duration, may be helpful.

Optimal serum cholesterol concentrations are associated with accelerated bone loss in African ancestry men.

We tested if serum lipid and lipoprotein cholesterol levels are associated with longitudinal measures of bone mineral density (BMD) in 1289 African ancestry men. After 6years of mean follow-up, men with clinically optimal levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), or triglycerides at baseline experienced the greatest BMD loss, independent of potential confounding factors (all p < 0.05). Studies of lipid and lipoprotein cholesterol associations with bone mineral density (BMD) and bone loss have been inconclusive, and longitudinal data are sparse. Therefore, the aim of this study was to test if fasting serum lipid and lipoprotein cholesterol levels are associated with areal and volumetric BMD and BMD change. We determined the association of serum triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol concentrations with cross-sectional and longitudinal (mean follow-up, 6.1years) measures of BMD in a cohort of 1289 in African ancestry men (mean age, 56.4years). Fasting serum triglycerides, HDL, and LDL were measured at baseline concurrent with BMD assessments. Dual-energy X-ray absorptiometry was used to quantify integral hip BMD, and peripheral quantitative computed tomography at the radius and tibia was used to quantify volumetric BMD. Men were categorized as optimal, borderline, or high risk for triglyceride, HDL, and LDL concentrations based on Adult Treatment Panel III guidelines. Lower serum triglyceride or LDL and higher HDL concentrations were associated with lower trabecular BMD at baseline (all p < 0.05). Similarly, men classified as having optimal levels of LDL, HDL, or triglycerides at baseline experienced the greatest integral BMD loss at the hip and trabecular BMD loss at the tibia (all p < 0.05), independent of potential confounding factors. We found that clinically optimal serum lipid and lipoprotein cholesterol concentrations were associated with accelerated bone loss among Afro-Caribbean men. Further studies are needed to better understand the mechanisms involved and potential clinical significance of these findings.

Elevated high-density lipoprotein cholesterol and cardiovascular mortality in maintenance hemodialysis patients

High-density lipoprotein (HDL) confers protection against atherosclerosis by several different mechanisms. Although in the general population, increasing levels of HDL are associated with reduced cardiovascular (CV) mortality, this association is not well known in patients with chronic disease states such as end-stage renal disease. We hypothesize that the association of serum HDL concentration and its ratio to total cholesterol with all-cause and CV mortality in hemodialysis patients is different from the general population. A 3-year (July 2004 to June 2007) cohort of 33 109 chronic hemodialysis patients was studied in the USA in the dialysis clinics where lipid profile was measured in at least 50% of all outpatients of the clinic during a given calendar quarter. Cox proportional hazard models were adjusted for demographics and case-mix variables and cubic splines were plotted. Higher HDL concentrations up to 50 mg/dL were associated with better overall survival, while HDL at 60 mg/dL and above was associated with a rise in all-cause and CV mortality. All-cause and CV mortality hazard ratio was 1.28 (1.20-1.38) and 1.08 (1.01-1.16) for HDL <30 mg/dL and 1.05 (1.00-1.10) and 1.08 (1.00-1.16) for HDL ≥ 60 mg/dL, respectively (reference: HDL: 30-<60 mg/dL). In contrast to the general population, low total cholesterol to HDL ratio was associated with higher mortality in hemodialysis patients. A U-shaped association between HDL cholesterol level and all-cause and CV mortality exists in hemodialysis patients with HDL between 50 and <60 mg/dL exhibiting the best survival. The underlying mechanisms responsible for these seemingly paradoxical associations await further investigation.

Albusin B modulates lipid metabolism and increases antioxidant defense in broiler chickens by a proteomic approach

The present study was designed to investigate the effect of albusin B on lipid metabolism and antioxidant defense in broiler chickens by a proteomic approach. The bacteriocin, albusin B of Ruminococcus albus 7, expressed by yeast was applied in this study. Three dietary treatments, consisting of the basal diet (control), basal diet + albusin B (2.5 g kg⁻¹), and basal diet + nosiheptide (2.5 mg kg⁻¹) were randomly fed to 90 broiler chickens from 1 to 35 days of age, respectively. After 35 days of supplementation, the growth performance, lipid metabolism and antioxidant proteins in the jejunum and liver, intestinal protein profile, and plasma lipid profile were analyzed. Broilers with albusin B supplementation had greater body weight than the control broilers. Compared with the control broilers, lower triglyceride and higher high-density lipoprotein concentration in the blood were observed in both broilers with albusin B and nosiheptide supplementation. In addition, albusin B suppressed the mRNA expression of fatty acid binding protein 2 and ATP binding cassette transporter G 5 in the jejunum. In the jejunal protein profiles, four antioxidant proteins were upregulated by albusin B and nosiheptide treatments. The jejunal antioxidant gene expression had a concordant pattern. Hepatic genes related to lipid metabolism, 3-hydroxy-3-methyl-glutaryl CoA reductase, and superoxide dismutase were upregulated by albusin B supplementation. Albusin B supplementation modulated lipid metabolism and activated systemic antioxidant defense, which might partially contribute to the performance of broiler chickens.

Analysis of LIPC ‐514C&gt;T and APOA5 ‐1131T&gt;C polymorphisms in Mexican Mestizos and Mexican Amerindians

Description of frequencies and haplotypes in Mexican Mestizo (MM) and Mexican Amerindian (MA) populations, of two SNPs implicated in lipid metabolism, which have been associated to lipid levels in white populations. For this purpose we analyzed DNA extracted from blood samples of 372 MA and 300 MM that participated in the Mexican Genome Diversity Project by allelic discrimination, we also constructed haplotypes and identified tag SNPs.ResultsThe frequency for LIPC rs1800588 was 0.430 in MM and 0.262 in MA, whereas for APOA5 rs662799 the frequency was 0.168 in MM and 0.262 in MA. Three haplotypes (&gt;5%) were identified on the LIPC region on MM, one of them including the rs1800588 (8.3%). Six haplotypes (&gt;5%) were identified on the APOA5 region. The rs662799 SNP was included in haplotypes showing similar frequencies in MM and MA (14% and 14.8% respectively). The APOA5 rs662799 is in high LD with tag SNPs that are present in BUD13 and ZNF259. The LIPC rs1077834, that has been associated to higher high density lipoprotein concentrations in white populations, showed high linkage desequilibrium with our SNP of interest.ConclusionsThe genetic information obtained from this study will be useful in future studies where associations between lipid metabolism phenotypes, environmental factors, and disease onset need to be determine in Mexican population. Source of research support CONACYT.

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.

A prospective study of TaqIB polymorphism in the gene coding for cholesteryl ester transfer protein and risk of myocardial infarction in middle-aged men

Background: Molecular variations in the gene coding for the cholesteryl ester transfer protein (CETP) such as the TaqIB polymorphism are associated with higher plasma high-density lipoprotein (HDL) concentration. However, whether this polymorphism is associated with risk of myocardial infarction (MI) is uncertain. Methods and results: In a prospective cohort of 14 916 apparently healthy men enrolled in the Physicians’ Health Study, allelic status for the TaqIB polymorphism in the CETP gene was determined among 384 participants who subsequently developed a first MI (cases) and among an equal number of age and smoking-matched participants who remained free of cardiovascular disease during follow-up (controls). Overall, the B2B2 genotype was present in 17% of the study participants and was associated with higher HDL cholesterol levels (mean mg/dl [±S.D.], 45±11 for the B1B1 genotype, 48±13 for the B1B2 genotype and 50±12 for the B2B2 genotype; P=0.01). However, the risk of developing MI did not differ significantly across these three genotypes. After adjustment for coronary risk factors (but not HDL), the relative risks for future MI were 1.12(95% CI 0.74−1.70) for the B1B2 genotype and 0.95(95% CI 0.54–1.66) for the B2B2 genotype, compared with the B1B1 genotype. In subgroup analysis of individuals with low HDL levels, B2B2 genotype appeared to have a lower risk of MI compared with the B1B1 genotype. However, participants with high HDL were at lower risk of developing MI regardless of their CETP genotype. Conclusions: In this prospective study of apparently healthy middle-aged US men, carriers of the B2 allele of the TaqIB in the CETP gene had higher HDL concentrations, but did not have lower risk of MI. Co ndensed abstract: In a cohort of apparently healthy middle-aged US men, the relation between CETP genotype and MI risk was prospectively examined in a nested case-control study. Afier adjusting for coronary risk factors (but not HDL), the 9-year risk of developing MI did not differ significantly by genotype. Comparing to the B1B1 genotype, the relative risks for future MI were 1.12 (95% CI 0.74−1.70) for the B1B2 genotype and 0.95 (95% CI 0.54–1.66) for the B2B2 genotype.

Weight set-point theory and the high-density lipoprotein concentrations of long-distance runners

Long-distance runners have higher high-density lipoprotein (HDL)-cholesterol concentrations and lower adiposity than sedentary men. Most cross-sectional studies claim that the runners' elevated HDL-cholesterol is not due to the runners' leanness. However, when cross-sectional studies use analysis of covariance (ANCOVA) to adjust for adiposity, or when they compare runners with lean sedentary men, they make an incorrect tacit assumption. They assume that the relationship between change in adiposity and change in HDL-cholesterol in men who have lost fat by running is the same as the cross-sectional difference in HDL-cholesterol between naturally fat and lean sedentary men. Regression slopes for HDL-cholesterol versus adiposity during and at the end of 1 year of running in 35 initially sedentary men suggest this assumption is incorrect; the increase in HDL-cholesterol that accompanies weight loss ( −4.28 ± 1.01 mg 100 mL per kg/m 2 ) is considerably greater than the increase in HDL-cholesterol that is associated with lower adiposity crosssectionally ( −0.78 ± 0.46 mg 100 mL per kg/m 2 ). These results suggest the following theory: long-distance runners have the HDL metabolism of men who are below their sedentary set-point weight rather than the HDL metabolism of men who are naturally lean without exercising or dieting. This theory was applied to data from 23 published comparisons between long-distance runners and sedentary men. The differences were highly correlated ( r = .80) with the theory's predictions (ie, the HDL-cholesterol differences predicted by applying the regression slope for change in HDL-cholesterol v change in adiposity to the average differences in adiposity between the runners and sedentary men). These analyses suggest that comparing long-distance runners to a reference population suitably matched for adiposity, and adjusting for adiposity by ANCOVA may each seriously underestimate the contribution of the runners' leanness to their HDL concentrations. These results suggest that the elevated HDL-cholesterol concentrations of long-distance runners is primarily a phenomenon of reduced adiposity.

Cholesterol, Lipoproteins, and Triglyceride Before, During, and After an Ultramarathon Road Race

Endurance-trained individuals generally have lower cholesterol and triglyceride and higher high-density lipoprotein concentrations than do their sedentary counterparts. It is not clear how much of the reported differences in lipid values are attributable to an acute residual influence of the most recent exercise session. Five endurance-trained men had their total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride (TG) determined before, during an ultramarathon road race (after 20, 30, and 50 miles) and 30 minutes and 18 hours after the race. Only LDL was significantly changed during the race (lower after 30 and 50 miles), however, a significant decline in TC (14%), LDL (16%), and TG (26%) concentrations were observed 18 hours after the ultramarathon road race. These findings concur with others demonstrating that exercise can have an acute influence (the day after exercise) on changing blood lipid concentrations. Factors influential to inducing acute postexercise changes and potential implications are discussed.

Elevated high-density lipoprotein cholesterol in endurance athletes is related to enhanced plasma triglyceride clearance

We compared the clearance rate (K 2) of plasma triglycerides (TG) following the intravenous (IV) infusion of a fat emulsion in 13 male endurance athletes (age 33 ± 5.6 years, mean ± SD) and 12 sedentary men (33 ± 5.6 years). The athletes had lower fasting triglycerides (TG) (75 ± 30.4 mg/dL v 125 ± 52.5 mg/dL) and higher high-density lipoprotein (HDL) cholesterol concentrations (64 ± 16.2 mg/dL v 42 ± 9.4 mg/dL) than the sedentary subjects ( P < .01 for all). The higher HDL concentrations were due to increases in both the HDL 2 and HDL 3 subfractions. K 2 in the athletes was 92% higher than that in the sedentary men (4.8 ± 2.3 %/min v 2.5 ± 0.7 %/min, P < .01), but there was no difference in postheparin lipoprotein lipase activity (LPLA) between the groups ( P > .05). K 2 was positively correlated with LPLA ( r = .51) and inversely related to fasting TG concentrations ( r = −.73, P < .01 for both). Furthermore, K 2 was directly related to HDL ( r = .75), HDL 2 ( r = .72), and HDL 3 ( r = .60) cholesterol concentrations ( P < .01 for all). These data suggest that the low TG levels in endurance athletes result at least in part from increased TG removal and that the elevated HDL concentrations of endurance athletes are related to enhanced fat clearance.

Apolipoprotein (apo) A-I production and mRNA abundance explain plasma apoA-I and high density lipoprotein differences between two nonhuman primate species with high and low susceptibilities to diet-induced hypercholesterolemia.

Earlier studies have shown that African green monkeys develop a more modest hypercholesterolemia, higher high density lipoprotein (HDL) concentrations, and less atherosclerosis than cynomolgus monkeys fed diets with the same cholesterol content. In the present study, cynomolgus monkeys were fed less cholesterol than was fed to African green monkeys to induce equivalent hypercholesterolemia in both species. African green monkeys still had 2-fold higher plasma HDL cholesterol concentrations and 2.7-fold higher plasma apolipoprotein (apo) A-I concentrations. Therefore, the higher HDL concentration in African green monkeys appears to result from factors that act independently of dietary cholesterol intake or total plasma cholesterol concentration. Two aspects of HDL production were examined to determine the metabolic basis of the species difference in HDL concentration. The rate of hepatic apoA-I secretion, as estimated by the accumulation of apoA-I in the medium during recirculating liver perfusion, was 5-fold higher in livers of African green monkeys. In addition, the concentration of apoA-I mRNA was 2-fold higher in the liver and 3.7-fold higher in the intestine of African green monkeys. Taken together, these findings indicate that differences in apoA-I production in the liver and small intestine are large enough to be responsible for the differences in the plasma concentrations of HDL and apoA-I between these species. Factors which regulate apoA-I secretion, including modulation of tissue apoA-I mRNA concentrations, are important determinants of plasma HDL concentrations and may contribute to the relative resistance of African green monkeys to dietary cholesterol-induced hypercholesterolemia and atherosclerosis. ApoA-I mRNA was also detected at low levels in the kidney and testis of African green and cynomolgus monkeys but not in the adrenal or brain. The tissue distribution and abundance of apoA-I mRNA in peripheral tissues was very different than that seen for apoE mRNA. Kidney and testis apoA-I mRNAs were the same size as liver apoA-I mRNA when examined by Northern blot analysis. Testis apoA-I mRNA appeared to be functionally active as judged by its presence in cytoplasmic polyribosomes. The low levels of apoA-I expression in kidney and testis are unlikely to contribute significantly to the plasma apoA-I pool but might function in some aspect of local lipid metabolism within these tissues.

Addendum

Although the concentration of high density lipoprotein (HDL) cholesterol is a sensitive index of coronary heart disease (CHD) risk in Caucasians there is little evidence for differences in HDL levels between populations with low and high prevalence of CHD. This study compares the concentrations of apolipoprotein AI, the major HDL protein, in South Pacific Islanders of different ethnic origin. In two rural populations on Ouvea, the mean AI levels were 94 and 91 mg/dl, respectively, for Melanesian and Polynesian men. These values are substantially lower than in a group of Australian men (120 20 mg/dl). A further comparison between rural and urbanized Polynesian males in Western Samoa showed that urbanization led to higher AI levels (117 mg/dl in the town versus 94 mg/dl in the village). A survey of factors that influence HDL levels suggests that the higher AI levels were due to changes in diet, including fat and alcohol consumption. The prevalence of probable CHD in Western Samoan men aged 40–69, determined by electrocardiography, was about half that reported in an Australian survey. Thus the lower AI levels in the Western Samoan men appeared not to be related to the prevalence of CHD which was less than among Australians who have higher HDL concentrations.

HDL levels in pacific islanders

Although the concentration of high density lipoprotein (HDL) cholesterol is a sensitive index of coronary heart disease (CHD) risk in Caucasians there is little evidence for differences in HDL levels between populations with low and high prevalence of CHD. This study compares the concentrations of apolipoprotein AI, the major HDL protein, in South Pacific Islanders of different ethnic origin. In two rural populations on Ouvea, the mean AI levels were 94 and 91 mg/dl, respectively, for Melanesian and Polynesian men. These values are substantially lower than in a group of Australian men (120 20 mg/dl). A further comparison between rural and urbanized Polynesian males in Western Samoa showed that urbanization led to higher AI levels (117 mg/dl in the town versus 94 mg/dl in the village). A survey of factors that influence HDL levels suggests that the higher AI levels were due to changes in diet, including fat and alcohol consumption. The prevalence of probable CHD in Western Samoan men aged 40–69, determined by electrocardiography, was about half that reported in an Australian survey. Thus the lower AI levels in the Western Samoan men appeared not to be related to the prevalence of CHD which was less than among Australians who have higher HDL concentrations.

Quantitation of high density lipoproteins

AbstractThe demand for high density lipoprotein (HDL) quantitation has dramatically increased with the renewed awareness of the importance of HDL as a negative risk factor for coronary heart disease. HDL is usually estimated by specific precipitation of the non‐HDL apoB‐containing lipoproteins by polyanions and divalent cations followed by measurement of cholesterol in the supernatant. A common procedure involves precipitation with sodium heparin at 1.3 mg/ml and MnCl2 at 0.046 M (final concentrations). This method is appropriate for serum but less than ideal for plasma because of incomplete precipitation and sedimentation of the apoB‐containing lipoproteins. A two‐fold increase in Mn2+ to 0.096 M improves precipitation of the apoB‐associated lipoproteins from plasma without excessive precipitation of HDL. This modified heparin‐Mn2+ procedure gives results nearly identical to the results with the ultracentrifugal reference method (cholesterol in the d&gt;1.063 fraction corrected for losses and the presence of apoB‐associated cholesterol). The dextran sulfate 500‐Mg2+ and the sodium phosphotungstate‐Mg2+ procedures give results consistently 2–4 mg/dl lower than does the reference method. In contrast, a heparin‐Ca2+ method gives results 5–8 mg/dl higher than does the reference method. Immunochemical analysis of apoA‐I in the precipitate and apoB in the supernatant indicates that lower values for the phosphotungstate‐Mg2+ procedure is due to partial precipitation of the A‐I‐containing lipoproteins, while higher values by the heparin‐Ca2+ method are due to incomplete precipitation of the apoB‐containing lipoproteins. Quantitation of the principal apoproteins of HDL, A‐I and A‐II, represent an important additional index of HDL concentrations and composition. Quantitation of plasma A‐I and A‐II concentrations by radial immunodiffusion indicates that women generally have higher HDL concentrations than men (women, A‐I, 135±25, A‐II, 36±6; men, A‐I, 120±20, A‐II, 33±5; mean±S.D., in mg/dl). A‐I and A‐II do not increase with age in men but show a slight increase with age in women. Estrogen increases HDL cholesterol and protein and may in part account for the higher HDL in women. The lighter density HDL subclass has a higher A‐I/A‐II ratio than the denser HDL subclass, with women generally having significantly more of the lighter HDL subclass. Density‐gradient ultracentrifugation in CsCl2 gradients indicates that HDL contains subpopulations of differing hydrated density which vary in the A‐I/A=II ratio. Immunoassay of A‐I and A‐II when used in combination with HDL cholesterol analysis is a powerful tool for studies of HDL structure, epidemiology and metabolism.