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• TyG-related indices has the utility for risk assessment and prevention of CVD. • TyG-BMI, TyG-WC and TyG-WHtR are significantly associated with new-onset CVD in non-diabetic populations. • TyG-WC and TyG-WHtR have remarkable predictability in non-diabetic populations. Cardiovascular disease (CVD) risk assessment is a crucial component of public health. We aimed to determine the predictive value of the triglyceride-glucose (TyG) index and TyG-related indices for new-onset CVD. This prospective study included 7,808 participants aged 40-69 years from the Ansung-Ansan cohort database. Our analysis was stratified by diabetes status. The hazard ratio (HR) with a 95% confidence interval (CI) for incident CVD was computed using multiple Cox proportional-hazards regression models. To evaluate the predictive performance of these indices for new-onset CVD, we calculated the Harrell's C-index (95% CI). In this study, a total of 6,890 participants did not have diabetes at baseline, while 918 participants had diabetes. In participants without diabetes, compared to the lowest tertile, fully adjusted HR and 95% CI for new-onset CVD in the highest tertile were as follows: TyG (HR 1.42, 95% CI 1.06–1.90), TyG-body mass index (BMI) (HR 1.92, 95% CI 1.19–3.10), TyG-waist circumference (WC) (HR 2.37, 95% CI 1.61–3.49), and TyG-waist-to-height ratio (WHtR) (HR 2.20, 95% CI 1.47–3.28). However, no significant associations were observed between TyG, modified TyG indices, and new-onset CVD in participants with diabetes. Notably, the C-indice of TyG-WC and TyG-WHtR were significantly higher than those of TyG and TyG-BMI in participants without diabetes. TyG-BMI, TyG-WC, and TyG-WHtR were associated with an increased risk of new-onset CVD in participants without diabetes. Furthermore, TyG-WC and TyG-WHtR showed better predictive performances for new-onset CVD than TyG and TyG-BMI in participants without diabetes. [ABSTRACT FROM AUTHOR]

• Hypertriglyceridemia-induced acute pancreatitis recurrence rate is high. • High triglyceride (TG) level post attack is closely associated with recurrence. • Controlling TG below 5.65 mmol/L may be an effective strategy to prevent recurrence. • Glucose should be controlled below 7.0 mmol/L for preventing recurrence. • Long-term TG lowering drugs treatment decreases recurrence. Data on recurrent hypertriglyceridemia-induced acute pancreatitis (HTG-AP) are scarce. To investigate the incidence and risk factors for recurrence of HTG-AP, and the effect of triglyceride (TG) lowering drugs post index attack on recurrence. This study was a prospective cohort study of adult patients with first episode of HTG-AP from December 2019 to February 2021 who were followed until recurrence or death, or February 2022. The cumulative incidence function and Fine and Gray's competing-risk model were applied to the analyses. A total of 317 patients were enrolled, and the 12-month and 18-month cumulative recurrence incidences were 8% and 22%, respectively. The cumulative recurrence incidence was 2 times higher in patients whose serum TG levels post index attack were ≥5.65 mmol/L (subdistribution hazard ratio [SHR], 2.00; 95% confidence interval [CI], 1.05–3.80; P = 0.034) compared to patients with TG <5.65 mmol/L. The recurrence rate was 3.3 times higher in patients whose glucose levels post index attack were ≥7.0 mmol/L (SHR, 3.31; 95% CI, 1.56–7.03; P = 0.002) than in patients with glucose <7.0 mmol/L). Compared to TG lowering drugs for less than 1 month post index attack, treatment for longer than 12 months decreased the incidence of recurrence by 75% (SHR, 0.25; 95% CI, 0.08–0.80; P = 0.019). The HTG-AP recurrence incidence is high and closely associated with high levels of TGs and glucose post index attack. Long-term TG lowering drugs treatment significantly decreases this recurrence. [ABSTRACT FROM AUTHOR]

• Managing high TG levels in familial partial lipodystrophy (FPLD) is challenging. • The antisense oligonucleotide volanesorsen can reduce apolipoprotein C-III and TG. • In BROADEN, volanesorsen decreased TG and maintained reduced levels in FPLD. • Volanesorsen reduced hepatic fat fraction, suggesting hepatosteatosis improvement. • Volanesorsen was well tolerated, with a manageable safety profile in FPLD. Volanesorsen, an antisense oligonucleotide, is designed to inhibit hepatic apolipoprotein C-III synthesis and reduce plasma apolipoprotein C-III and triglyceride concentrations. The present study assessed efficacy and safety of volanesorsen in patients with familial partial lipodystrophy (FPLD) and concomitant hypertriglyceridemia and diabetes. BROADEN was a randomized, placebo-controlled, phase 2/3, 52-week study with open-label extension and post-treatment follow-up periods. Patients received weekly subcutaneous volanesorsen 300 mg or placebo. The primary endpoint was percent change from baseline in fasting triglycerides at 3 months. Secondary endpoints included relative percent change in hepatic fat fraction (HFF), visceral adiposity, and glycated hemoglobin levels. Forty patients (11 men, 29 women) were enrolled, majority of whom were aged <65 years (mean, 47 years) and White. Least squares mean (LSM) percent change in triglycerides from baseline to 3 months was −88% (95% CI, −134 to −43) in the volanesorsen group versus –22% (95% CI, −61 to 18) in the placebo group, with a difference in LSM of −67% (95% CI, –104 to –30; P =0.0009). Volanesorsen induced a significant LSM relative reduction in HFF of 53% at month 12 versus placebo (observed mean [SD]: 9.7 [7.65] vs. 18.0 [8.89]; P =0.0039). No statistically significant changes were noted in body volume measurements (fat, liver, spleen, visceral/subcutaneous adipose tissue) or glycated hemoglobin. Serious adverse events in patients assigned to volanesorsen included 1 case each of sarcoidosis, anaphylactic reaction, and systemic inflammatory response syndrome. In BROADEN, volanesorsen significantly reduced serum triglyceride levels and hepatic steatosis in patients with FPLD. [ABSTRACT FROM AUTHOR]

• The prevalence of hypertriglyceridemia-associated acute pancreatitis (HTG-AP) was 3%. • HTG-AP patients had a worse clinical course than biliary-AP patients. • The quality of the follow-up post hospital discharge was suboptimal in HTG-AP patients. Hypertriglyceridemia (HTG) is known as the third most common cause of acute pancreatitis (AP). To study the prevalence and outcomes of HTG-AP as well as the quality of the follow-up post HTG-AP hospitalization in Canada. This retrospective multicenter study was performed in patients admitted with AP (ICD 10 code K85) in quaternary care hospitals between 2012 and 2018. For every case of HTG-AP (TG ≥ 5.6 mmol/L on admission), two controls of biliary-AP were selected and matched for sex and age at the time of admission. Out of 1490 admitted AP patients, 40 (3%) had HTG-AP. The average TG concentration was higher in patients admitted to the ICU compared to those who were not (27.34 mmol/L vs 13.02 mmol/L). Compared to biliary-AP group, the HTG-AP patients had more frequent severe Balthazar grade (45% vs 25%) with longer duration of hospitalisation (nine versus five days) and more frequent ICU admission (38% vs 8%). Furthermore, only 35% of HTG-AP patients were referred to specialized clinics and 42.5% were left with no follow-up. Only 17% of newly discovered HTG-AP patients were started on fibrate at discharge. In comparison to biliary-AP, HTG-AP patients had a worse clinical course of pancreatitis. Furthermore, the quality of the follow-up post HTG-AP hospitalization was suboptimal. This could be explained by of the lack of knowledge of health care providers concerning the proper diagnosis and management of chylomicronemia syndromes, leading to this condition to be frequently missed or underdiagnosed. [ABSTRACT FROM AUTHOR]

• Patients with no apo B-containing lipoproteins can develop severe complications. • We have followed three such patients for >40 years. • All three patients are clinically and particularly neurologically stable. • A liver biopsy in one patient showed minimal pathology. • Adhering to high dose fat soluble vitamins was associated with favorable outcomes. Complete deficiency of apolipoprotein (apo) B-containing lipoproteins can result from both abetalipoproteinemia (ABL) and homozygous hypobetalipoproteinemia (HoHBL), caused by bi-allelic loss-of-function variants in the MTTP and APOB genes encoding microsomal triglyceride transfer protein and apolipoprotein (apo) B, respectively. Both conditions are associated with failure to assemble and secrete apo B-containing lipoproteins from intestine and liver, resulting in absence of chylomicrons, very low-density lipoproteins and remnants, and low-density lipoproteins. Because absorption and transport of fat soluble vitamins requires intact production of apo B-containing lipoproteins, untreated patients develop fat soluble vitamin deficiencies, with associated clinical features including atypical retinitis pigmentosa, osteopenia, neuromyopathy and coagulopathy. Other features include acanthocytosis on the peripheral blood film, fat malabsorption and hepatosteatosis. We describe two patients with ABL and one with HoHBL who have each been on high dose oral fat soluble vitamin replacement under the care of the same physician for more than four decades. Each patient has remained clinically stable. A recent liver biopsy from an ABL patient showed mild macrovesicular steatosis, patchy microvesicular steatosis and mild fibrosis. These observations add to our understanding of the long term trajectory of ABL and HoHBL, and emphasize the importance of compliance to treatment and follow up. [ABSTRACT FROM AUTHOR]

Background: The genetic substrate of severe hypertriglyceridemia (sHTG) in Latin America is insufficiently understood., Objective: To identify genetic variants in genes related to triglyceride (TG) metabolism among adults with sHTG from Colombia., Methods: In individuals with plasma TG≥880 mg/dL at least once in their lifetime, we amplified and sequenced all exons and intron/exon boundaries of the genes LPL, APOC2, APOA5, GPIHBP1 and LMF1. For each variant we ascertained its location, zygosity, allelic frequency and pathogenicity classification according to American College of Medical Genetics (ACMG) criteria., Results: The study included 166 participants (62 % male, mean age 50), peak TG levels ranged between 894 and 11,000 mg/dL. We identified 92 variants: 19 in LPL, 7 in APOC2, 11 in GPIHBP1, 38 in LMF1, and 17 in APOA5. Eighteen of these variants had not been reported. We identified a new pathogenic variant in LMF1 (c.41C>A; p.Ser14*), a new likely pathogenic variant in LMF1 (c.1527 C > T; p.Pro509=, also expressed as c.1447C>T; p.Gln483*), and a known pathogenic variant in LMF1 (c.779G>A; p.Trp260*). Four participants were heterozygous for variant c.953A>G; p.Asn318Ser in LPL, a known risk factor for hypertriglyceridemia. Participants with variants of unknown significance (VUS) in LMF1 had significantly higher peak TG than those with VUS in other genes. Peak TG were 4317 mg/dL in participants with a history of pancreatitis, and 1769 mg/dL in those without it (p = 0.001)., Conclusion: Our study identified variants associated with sHTG among Latinos, and showed that genetic variation in LMF1 may be frequently associated with sHTG in this population., Competing Interests: Declaration of competing interest This study was funded by PTC Therapeutics through an investigator-initiated grant, but the sponsor had no incidence in the design or execution of the study, or on the decision to publish., (Copyright © 2024. Published by Elsevier Inc.)

• The role of ANGPTL3 and ANGPTL8 in high levels of HDL-C and triglyceride is unknown. • Plasma level of ANGPTL3 was increased in both high levels of HDL-C and triglyceride. • Plasma level of ANGPTL8 was increased in high levels of HDL-C and not in severe HTG. • ANGPTL3 and ANGPTL8 might play distinct roles in these 2 extremes of dyslipidemia. The role of ANGPTL3 and ANGPTL8 in lipid regulation in patients with very high levels of HDL-cholesterol and triglyceride is unknown. We examined plasma levels of ANGPTL3 and ANGPTL8 in subjects with hyperalphalipoproteinemia (HALP) and in those with severe hypertriglyceridemia (HTG). Plasma ANGPTL3 and ANGPTL8 levels were measured by ELISA in 320 subjects, consisting of HALP subjects with HDL-cholesterol ≥100 mg/dl (n=90) and healthy controls (n=90) and subjects with triglyceride ≥886 mg/dl (n=89) and control subjects (n=51). The mean plasma ANGPTL3 level was significantly higher in the HALP group compared to that of the controls (297 ± 112 ng/mL vs. 230 ± 100 ng/mL, p<0.001). Similarly, the mean plasma ANGPTL8 level was also higher in the HALP group (30 ± 11 ng/mL vs. 20 ± 8 ng/mL, p<0.001). Both ANGPTL3 and ANGPTL8 levels positively correlated with HDL-cholesterol levels. In the severe HTG group, plasma ANGPTL3 level was significantly higher than those in the control group (223 ± 105 ng/mL vs. 151 ± 60 ng/mL, p<0.001), but not ANGPTL8 (23 ± 20 ng/mL vs. 31 ± 23 ng/mL in controls, p=0.028). Only ANGPTL3, but not ANGPTL8, levels positively correlated with triglyceride levels. Plasma level of ANGPTL3 was increased in both HALP and severe HTG whereas an increase in plasma level of ANGPTL8 was found only in HALP, and not in severe HTG, suggesting that both ANGPTL3 and ANGPTL8 might play distinct roles in lipid regulation on these two extremes of dyslipidemia. [Display omitted] [ABSTRACT FROM AUTHOR]

• Hypertriglyceridemia during hospitalization has 2.3 times higher mortality in COVID. • This association is independent of age, gender, obesity, diabetes, and hypertension. • Non-surviving COVID-19 patients had higher peak triglyceride during hospitalization. • Peak triglyceride associates with CRP and leukocyte count during hospitalization. • Hypertriglyceridemia at admission was not associated with mortality. Alteration in blood triglyceride levels have been found in patients with coronavirus disease 2019 (COVID-19). However, the association between hypertriglyceridemia and mortality in COVID-19 patients is unknown. To investigate the association between alteration in triglyceride level and mortality in hospitalized COVID-19 patients. We conducted a retrospective study of 600 hospitalized patients with COVID-19 diagnosis (ICD10CM:U07.1) and/or SARS-CoV-2 positive testing results between March 1, 2020 and December 21, 2020 at a tertiary academic medical center in Milwaukee, Wisconsin. De-identified data, including demographics, medical history, and blood triglyceride levels were collected and analyzed. Of the 600 patients, 109 patients died. The triglyceride value on admission was considered the baseline and the peak was defined as the highest level reported during the entire period of hospitalization. Hypertriglyceridemia was defined as greater than 150 mg/dl. Logistic regression analyses were performed to evaluate the association between hypertriglyceridemia and mortality. There was no significant difference in baseline triglyceride levels between non-survivors (n = 109) and survivors (n = 491) [Median 127 vs. 113 mg/dl, p = 0.213]. However, the non-survivors had significantly higher peak triglyceride levels during hospitalization [Median 179 vs. 134 mg/dl, p < 0.001]. Importantly, hypertriglyceridemia independently associated with mortality [odds ratio=2.3 (95% CI: 1.4–3.7, p = 0.001)], after adjusting for age, gender, obesity, history of hypertension and diabetes, high CRP, high leukocyte count and glucocorticoid treatment in a multivariable logistic regression model. Hypertriglyceridemia during hospitalization is independently associated with 2.3 times higher mortality in COVID-19 patients. Prospective studies are needed to independently validate this retrospective analysis. [ABSTRACT FROM AUTHOR]

Severe hypertriglyceridemia (HTG), characterized by triglycerides (TG) permanently over 10 mmol/L, may correspond to familial chylomicronemia syndrome (FCS), a rare disorder. However, hypertriglyceridemic patients more often present multifactorial chylomicronemia syndrome (MCS), characterized by highly variable TG. A few nonsense variants of LMF1 gene were reported in literature in FCS patients. In this study, we described a woman with an intermittent severe HTG. NGS analysis and the sequencing of a long range PCR product revealed a homozygous deletion of 6507 base pairs in LMF1 gene, c.730-1528_898-3417del, removing exon 6, predicted to create an in-frame deletion of 56 amino acids, p.(Thr244_Gln299del). Despite an exon 6 homozygous deletion of LMF1 , the patient's highly variable lipid phenotype was suggestive of MCS diagnosis. • Deleterious variations in the LMF1 gene leading to hyperchylomicronemia are rare. • No copy number variation was previously reported in the LMF1 gene. • The study describes the first deletion in the LMF1 gene, removing exon 6. • This deletion is associated with a multifactorial chylomicronemia syndrome phenotype. [ABSTRACT FROM AUTHOR]

The etiology of hypertriglyceridemia (HTG) and, consequently, HTG-induced acute pancreatitis (HTG-AP), is complex. Herein, we explore a possible gene–environment interaction between APOA5 c.553G>T (p.185Gly>Cys, rs2075291), a common variant associated with altered triglyceride levels, and pregnancy in HTG-AP. We enrolled 318 Chinese HTG-AP patients and divided them into 3 distinct groups: Group 1, male patients (n = 183); Group 2, female patients whose disease was unrelated to pregnancy (n = 105); and Group 3, female patients whose disease was related to pregnancy (n = 30). APOA5 rs2075291 genotype status was determined by Sanger sequencing. A total of 362 healthy Han Chinese subjects were used as controls. Data on body mass index, peak triglyceride level, age of disease onset, episode number, and clinical severity of HTG-AP were collected from each patient. Multiple comparisons, between patient groups, between patient groups and controls, or within each patient group, were performed. A robust association of APOA5 rs2075291 with HTG-AP in general, and HTG-AP during pregnancy in particular, was demonstrated. The minor T allele showed a stronger association with Group 3 patients than with either Group 1 or Group 2 patients. This stronger association was due mainly to the much higher frequency of TT genotype in Group 3 patients (20%) than that (<6%) in Group 1 and Group 2 patients. Moreover, the TT genotype was associated with a significantly higher peak triglyceride level in Group 3 patients compared with the GG genotype. Our findings provide evidence for an interaction between APOA5 rs2075291 and pregnancy in HTG-AP. • APOA5 c.553G>T has been previously associated with altered triglyceride levels. • Here, we report for the first time an association of APOA5 c.553G>T with hypertriglyceridemia-induced acute pancreatitis (HTG-AP). • We provide evidence that APOA5 c.553G>T interacts with pregnancy in causing HTG-AP. • Our findings provide novel insights into the complex etiology of HTG-AP. [ABSTRACT FROM AUTHOR]

Background The LMF1 (lipase maturation factor 1) gene encodes a protein involved in lipoprotein lipase and hepatic lipase maturation. Homozygous mutations in LMF1 leading to severe hypertriglyceridemia (SHTG) are rare in the literature. A few additional rare LMF1 variants have been described with poor functional studies. Objective The aim of this study was to assess the frequency of LMF1 variants in a cohort of 385 patients with SHTG, without homozygous or compound heterozygous deleterious mutations identified in lipoprotein lipase (LPL), apolipoprotein A5 (APOA5), apolipoprotein C2 (APOC2), glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) genes, and to determine their functionality. Methods LMF1 coding variants were screened using denaturing high-performance liquid chromatography followed by direct sequencing. In silico studies of LMF1 variants were performed, followed by in vitro functional studies using human embryonic kidney 293T (HEK-293T) cells cotransfected with vectors encoding human LPL and LMF1 c DNA. LPL activity was measured in cell culture medium after heparin addition using human VLDL-TG as substrate. Results Nineteen nonsynonymous coding LMF1 variants were identified in 65 patients; 10 variants were newly described in SHTG. In vitro, p.Gly172Arg, p.Arg354Trp, p.Arg364Gln, and p.Arg537Trp LMF1 variants decreased LPL activity, and the p.Trp464Ter variant completely abolished LPL activity. We identified a young girl heterozygote for the p.Trp464Ter variant and a homozygote carrier of the p.Gly172Arg variant with a near 50% decreased LPL activity in vitro and in vivo. Conclusion The study confirms the rarity of LMF1 variants in a large cohort of patients with SHTG. LMF1 variants are likely to be involved in multifactorial hyperchylomicronemia. Partial LMF1 defects could be associated with intermittent phenotype as described for p.Gly172Arg homozygous and p.Trp464Ter heterozygous carriers. Highlights • LMF1 variants leading to SHTG are rare in literature. • We identified 19 LMF1 nonsynonymous coding variants in 385 patients with severeHTG. • Ten of these variants are newly described. • Five of these variants have a functional impact on LPL activity in vitro. • Functional variants in LMF1 contribute to the occurrence of SHTG. [ABSTRACT FROM AUTHOR]

Background Adult patients with severe hypertriglyceridemia (SHTG) are at increased risk of developing acute pancreatitis and cardiovascular disease. Omega-3 carboxylic acids (OM3-CA) are approved for treatment as an adjunct to diet to reduce triglyceride (TG) concentrations in patients with SHTG. Objective The aim of the study was to assess efficacy and safety of the intermediate dose of OM3-CA (2 g daily), compared with olive oil 2 g daily, in reducing serum TG and lipid concentrations in patients with SHTG. Methods A randomized, double-blind, olive oil–controlled, parallel-group trial involving 162 adults with qualifying serum TG concentrations of at least 500 mg/dL (5.65 mmol/L) and <2500 mg/dL (28.25 mmol/L; <2000 mg/dL [22.60 mmol/L] in Canada). The treatment period after randomization was 12 weeks. Blood samples for measurement of fasting serum lipid concentrations were taken at baseline, 6, 10, and 12 weeks. Results Treatment with OM3-CA 2 g daily led to a significant reduction in TG concentrations (median of differences, −14.2% [95% confidence interval: −26.2%, −2.8%; P = .017]) and non-high-density lipoprotein cholesterol concentrations (median of differences, −9.0% [95% confidence interval: −14.8%, −2.8%; adjusted P = .018]) from baseline to the Week 12 endpoint, when compared with olive oil 2 g daily. These treatment effects were more pronounced in patients with qualifying TG concentrations >885 mg/dL (10 mmol/L). Conclusion An intermediate dose of OM3-CA (2 g daily) significantly lowers TG and non-high-density lipoprotein cholesterol concentrations in patients with SHTG and may benefit individuals at risk of acute pancreatitis and cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background The prevalence of dyslipidemia, particularly hypercholesterolemia, has been reported to increase after pregnancy and menopause in Korea. This suggests the importance of the management of dyslipidemia in women for preventing cardiovascular diseases. Objective This study aimed to examine the association of breastfeeding with 5 subtypes of dyslipidemia in Korean women aged over 20 years, by using the nationally representative Korea National Health and Nutrition Examination Survey 2010–2014. Methods Ordinary least square regression and ordered logistic regression analyses were used to determine the association between breastfeeding duration and dyslipidemia. Results The likelihood of having low-density lipoprotein cholesterol (LDL-C) disorder decreased by 16% in the group that breastfed for more than 24 months (odds ratio, 0.84; 95% confidence interval, 0.75–0.95) compared with the group that did not breastfeed. The likelihood of having non–high-density lipoprotein cholesterol (non-HDL-C) disorder was significantly reduced by 25% when the breastfeeding duration was more than 24 months (odds ratio, 0.75; 95% confidence interval, 0.64–0.87). The tendency toward developing disorders of total cholesterol (TC), LDL-C, and non-HDL-C decreased as the duration of breastfeeding increased, particularly among women aged 30–39 years. Conclusion Breastfeeding duration was negatively correlated with dyslipidemia in terms of TC, LDL-C, non-HDL-C, and triglycerides. Long-term breastfeeding was associated with the prevalence of dyslipidemia-TC, LDL-C, non-HDL-C, and TG disorders, in particular. [ABSTRACT FROM AUTHOR]

Background Familial hypercholesterolemia (FH) in children is under-detected. Plasma biomarkers associated with low-density lipoprotein receptor (LDLR) function could help identifying FH children. Objectives We aim to assess the clinical value of inducible degrader of the LDLR (IDOL), soluble LDLR (sLDLR), and proprotein convertase subtilisin/kexin type 9 (PCSK9) plasma concentrations in children with FH compared with control children (CCh). Methods This was a cross-sectional study performed in a Lipid Unit from a University hospital. The participants were 177 children distributed into FH (n = 77) and CCh (n = 100). Main outcomes were changes in IDOL, sLDLR, and PCSK9 plasma concentrations between children groups; secondary outcomes were the association between IDOL, sLDLR, and PCSK9 and lipid profile determined by 2-dimensional nuclear magnetic resonance. Results The IDOL levels were higher in FH compared with CCh ( P = .007). The PCSK9 levels were elevated in FH ( P < .001). The sLDLR levels had no significant differences between groups. IDOL was significantly positively associated to total and LDL cholesterol and ApoB100 but not to LDL particle number. However, a robust correlation with Lp(a) ( P = .001) was observed. PCSK9 had the strongest correlation with LDL-associated parameters including particle number. sLDLR was associated with triglyceride levels ( P < .001) and triglyceride-rich particles and inversely to LDL size. Conclusions The IDOL and PCSK9 plasma levels are significantly higher in FH children. Interestingly, sLDLR was associated with atherogenic dyslipidemia components. IDOL concentrations show a robust association with Lp(a) levels. To study the role of plasma biomarkers associated with LDLR expression in FH is warranted. [ABSTRACT FROM AUTHOR]

Background Despite abundant evidence indicating that higher triglyceride (TG) levels are associated with increased risks of hyperuricemia (HUA), it is unclear whether TG levels can independently predict the incidence of HUA. Objective The aim of the study was to investigate whether TG is an independent risk factor of HUA in a cohort study. Methods We explored the relationship between TG levels and HUA in a dynamic cohort established in 2009. During the 6 years of follow-up, 5442 subjects without HUA were studied. We divided subjects into 4 groups based on baseline TG levels and used the Cox hazard regression model to estimate HUA risk by TG quartile, after adjustment for potential confounding factors. Kaplan–Meier survival analysis compared the risk of HUA incidence among individuals in each TG quartile. Results The incidence of HUA in this cohort was 25.9%. The hazard ratios (95% confidence intervals) for HUA in the second, third, and fourth TG quartiles, compared with the first quartile, were 1.19 (1.01–1.40), 1.33 (1.13–1.57), and 1.62 (1.37–1.92), respectively. The Kaplan–Meier survival analysis suggested that higher TG levels predicted higher incidences of HUA in a dose-dependent relationship. Stratification analyses showed that the association between TG levels and the presence of HUA was more pronounced in individuals aged <50 years, of obese, with normal estimated glomerular filtration rate, and with hypertension. Conclusion Our findings suggest that TG level is a significant and independent risk factor for HUA. [ABSTRACT FROM AUTHOR]

Background Hyperlipidemia has unique adverse effects on pregnant women and their offspring. The underlying genetic factors related to lipid levels in pregnant populations need more studies. Objective This study aimed to investigate the relationship between 6 single-nucleotide polymorphisms (SNPs) and plasma lipid levels during pregnancy. Methods A total of 2060 pregnant women were recruited. Fasting plasma lipids were measured in the third trimester of pregnancy. Six SNPs (rs1260326 in GCKR , rs1800775 in CETP , rs515135 in APOB , rs1800588 in LIPC , rs964184 in ZPR1 , and and rs4420638 in APOC1 of each participant were genotyped using TaqMan allelic discrimination assays. The relationships between the 6 loci and plasma lipids were analyzed using a multiple linear regression method. Results Two variants, rs1260326 (β = 0.220, 95% confidence interval [CI] = 0.148–0.291; P = 2.048 × 10 −9 ) and rs964184 (β = 0.172, 95% CI = 0.085–0.258; P = 1.083 × 10 −4 ) were significantly associated with triglyceride levels. Another 2 variants, rs1800775 (β = −0.033, 95% CI = −0.065 to −0.002; P = .040) and rs1800588 (β = 0.079, 95% CI = 0.046–0.112; P = 3.137 × 10 −6 ), were associated with high-density lipoprotein cholesterol. In addition, rs1800775 (β = −0.086, 95% CI = −0.156 to −0.012; P = .024) was associated with total cholesterol. No selected SNPs were associated with plasma low-density lipoprotein cholesterol levels in this study. Conclusions Loci found by genome-wide association studies to be associated with plasma lipid levels in the general population were also related to lipid levels in the third trimester of pregnancy. This finding implies that changes to lipid profiles during gestation may be associated with SNPs of lipid-related genes. Variants of lipid-related genes are important predictors for estimating lipid concentrations during the pregnancy. [ABSTRACT FROM AUTHOR]

Background Increased serum triglyceride and apolipoprotein B (apoB) levels and decreased high-density lipoprotein cholesterol (HDL-C) levels are risk factors for cardiovascular diseases. The major types of dyslipidemia in Chinese population are hypertriglyceridemia and low HDL-C. Objective This study aimed to evaluate the effect of HDL-C, triglyceride, and apoB levels on the risk of coronary heart disease (CHD) in a Chinese population undergoing coronary angiography. Methods This was a cross-sectional study. A total of 1941 consecutive patients who were referred to coronary angiography for the evaluation of suspected CHD were recruited. Lipid parameters were measured after an overnight fast. Patients were diagnosed with CHD and without CHD based on the findings of the coronary angiography. Results There were 1363 angiography confirmed CHD patients and 578 non-CHD patients. In nonstatin users, the major types of dyslipidemia were hypertriglyceridemia combined with low HDL-C, isolated low HDL-C, and isolated hypertriglyceridemia, accounting for 21.60%, 19.70%, and 14.99%, respectively. In statin users, a low to moderate-intensity statin was effective in lowering low-density lipoprotein cholesterol (LDL-C). The proportion of reaching an LDL-C goal <2.6 mmol/L and <1.8 mmol/L in statin users was 83.20% and 55.19%, respectively. In nonstatin users, the triglyceride and apoB levels were higher and the HDL-C levels were lower in CHD patients compared with non-CHD patients after the adjustment of age, sex, body mass index, diabetes, smoking, and alcohol drinking ( P = .002, .007, and .005, respectively). After adjusting for age, sex, body mass index, diabetes, hypertension, smoking and alcohol drinking, the quartiles of triglyceride, HDL-C, and apoB were associated with CHD ( P for trend = .001, .005, and .003, respectively). Conclusion Serum triglyceride, HDL-C, and apoB levels were independently associated with CHD in a Chinese population undergoing coronary angiography with a relatively low level of LDL-C and a high prevalence of hypertriglyceridemia and low HDL-C. [ABSTRACT FROM AUTHOR]

Background The metabolic syndrome (MetS) is highly prevalent and associated with an increased risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Lifestyle recommendations to treat MetS often include the replacement of saturated fats (SFAs) and monosaccharides with unsaturated fat. However, it is unclear whether metabolic parameters will improve more when the saturated fat in American Heart Association (AHA) diets is replaced with higher concentrations of monounsaturated or polyunsaturated fatty acids (MUFA or PUFA). Objective To test the hypothesis that an AHA diet enriched in MUFA improves lipoprotein lipids, insulin resistance, inflammation, and endothelial function to a greater extent than a diet enriched in PUFA in middle-aged men and women with MetS. Methods A prospective, open-label, parallel group design with randomization to a hypocaloric MUFA or PUFA-enriched diet after weight stabilization on an AHA step I diet. Participants consumed 3 MUFA-enriched or PUFA-enriched muffins daily with additional supplementation as required to ensure 25%–50% increases in dietary fat intake from these sources at the expense of SFA and the opposing unsaturated fat. Changes in MetS components were measured at baseline and after 6 months of dietary intervention. Results Thirty-nine participants (mean age, 60.8 years; 79% African-American, 60% women) with MetS completed the 6-month study. Compared to baseline, assignment to either MUFA (n = 23) or PUFA (n = 16) both were associated with weight loss (MUFA: −2.3 ± 1 kg, P = .06; PUFA: −4.6 ± 2 kg; P = .002), but PUFA was also associated with reductions in triglycerides (TG) (−30 ± 18 mg/dL, P = .02), systolic blood pressure (BP) (−7 ± 3 mm Hg, P = .01), diastolic BP (DBP) (−4 ± 2 mm Hg, P = .01) and improved flow mediated dilation (FMD) (7.1% ± 1.8% vs 13.6% ± 2%, absolute increase; P = .0001). When compared to MUFA treatment, PUFA intervention was associated with reduced TG ( P = .04) and DBP ( P = .07) as well as increased FMD ( P = .04) even after adjustment for changes in weight. There was no effect on total cholesterol, low-density lipoprotein cholesterol, glucose, high-sensitivity C-reactive protein (hs-CRP), or other inflammatory proteins. Overall, 25% (4 of 16) assigned to PUFA and 13% (3 of 23) to MUFA converted to non-MetS status. Conclusion Substitution of SFA with PUFA in patients with MetS is associated with greater reductions in TG and improvement in endothelial function than MUFA that is independent of weight loss. These preliminary findings raise the possibility that PUFA may be the unsaturated fat of choice to reduce cardiometabolic risk in patients with MetS. [ABSTRACT FROM AUTHOR]

Background Humans with familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD) have extremely low or undetectable high-density lipoprotein cholesterol (HDL-C) levels and by early adulthood develop many manifestations of the disorder, including corneal opacities, anemia, and renal disease. Objective To determine if infusions of recombinant human LCAT (rhLCAT) could reverse the anemia, halt progression of renal disease, and normalize HDL in FLD. Methods rhLCAT (ACP-501) was infused intravenously over 1 hour on 3 occasions in a dose optimization phase (0.3, 3.0, and 9.0 mg/kg), then 3.0 or 9.0 mg/kg every 1 to 2 weeks for 7 months in a maintenance phase. Plasma lipoproteins, lipids, LCAT levels, and several measures of renal function and other clinical labs were monitored. Results LCAT concentration peaked at the end of each infusion and decreased to near baseline over 7 days. Renal function generally stabilized or improved and the anemia improved. After infusion, HDL-C rapidly increased, peaking near normal in 8 to 12 hours; analysis of HDL particles by various methods all revealed rapid sequential disappearance of preβ-HDL and small α-4 HDL and appearance of normal α-HDL. Low-density lipoprotein cholesterol increased more slowly than HDL-C. Of note, triglyceride routinely decreased after meals after infusion, in contrast to the usual postprandial increase in the absence of rhLCAT infusion. Conclusions rhLCAT infusions were well tolerated in this first-in-human study in FLD; the anemia improved, as did most parameters related to renal function in spite of advanced disease. Plasma lipids transiently normalized, and there was rapid sequential conversion of small preβ-HDL particles to mature spherical α-HDL particles. [ABSTRACT FROM AUTHOR]

Background High triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) are important cardiovascular risk factors. The exact prognostic value of the TG/HDL-C ratio, a marker for cardiovascular events, is currently unknown among Iranians so this study sought to determine the optimal cutoff point for the TG/HDL-C ratio in predicting cardiovascular disease events in the Iranian population. Method The Isfahan Cohort Study (ICS) is an ongoing, longitudinal, population-based study that was originally conducted on adults aged ≥35 years, living in urban and rural areas of three districts in central Iran. After 10 years of follow-up, 5431 participants were re-evaluated using a standard protocol similar to the one used for baseline. At both measurements, participants underwent medical interviews, physical examinations, and fasting blood measurements. “High-risk” subjects were defined by the discrimination power of indices, which were assessed using receiver operating characteristic (ROC) analysis; the optimal cutoff point value for each index was then derived. Results The mean age of the participants was 50.7 ± 11.6 years. The TG/HDL-C ratio, at a threshold of 3.68, was used to screen for cardiovascular events among the study population. Subjects were divided into two groups (“low” and “high” risk) according to the TG/HDL-C concentration ratio at baseline. A slightly higher number of high-risk individuals were identified using the European cutoff points of 63.7% in comparison with the ICS cutoff points of 49.5%. The unadjusted hazard ratio (HR) was greatest in high-risk individuals identified by the ICS cutoff points (HR = 1.54, 95% CI [1.33–1.79]) vs European cutoff points (HR = 1.38, 95% [1.17–1.63]). There were no remarkable changes after adjusting for differences in sex and age (HR = 1.58, 95% CI [1.36–1.84] vs HR = 1.44, 95% CI [1.22–1.71]) for the ICS and European cutoff points, respectively. Conclusion The threshold of TG/HDL ≥3.68 is the optimal cutoff point for predicting cardiovascular events in Iranian individuals. [ABSTRACT FROM AUTHOR]

Background New, safer, and more effective agents to treat hyperlipidemia and thereby prevent cardiovascular events are under research. Objective To evaluate the lipid-lowering effects and safety of a natural hypolipidemic compound, coenzyme A (CoA) capsule, in Chinese patients with moderate dyslipidemia, compared with pantethine. Methods Overall, 216 subjects (124 males and 92 females; age, 18–75 years) with moderate dyslipidemia (triglyceride [TG], 2.3–6.5 mmol/L) were randomly divided into 2 groups administered CoA 400 U/d (n = 111) or pantethine 600 U/d (n = 105). Blood lipoproteins, liver and renal function, blood glucose, and complete blood count were measured at baseline and after 4- and 8-week treatment. Results TG reduction was 26.0% with CoA and 17.4% with pantethine after 4 weeks and 33.3% and 16.5% after 8 weeks; compared with baseline, the reduction was significant ( P < .01) in both groups. The difference between the 2 groups was significant at both 4 weeks ( P = .0413) and 8 weeks ( P < .001). Compared with baseline, total cholesterol and non–high-density lipoprotein cholesterol (non–HDL-C) were reduced, whereas HDL-C was increased with CoA after 8 weeks (all P < .05). Compared with pantethine, total cholesterol ( P = .026) and non–HDL-C ( P = .005) were significantly reduced after 8 weeks of CoA treatment. There was no statistical difference in low-density lipoprotein cholesterol or HDL-C between the 2 groups ( P > .05) and no difference in blood glucose, hepatic or renal function, myopathy, or gastrointestinal tract symptoms. Conclusions CoA can improve TG and other lipoprotein parameters to a greater extent than pantethine in moderate dyslipidemia, with no obvious adverse effects. [ABSTRACT FROM AUTHOR]

Background Fetal organs require much lipid for growth, but the cord blood had low TG concentrations, compared to adult serum. We investigated the association between the concentration of apolipoprotein A-V (apoA-V) and lipid profile in cord blood and neonatal serum. Objective ApoA-V was identified as an important determinant of plasma triglyceride concentrations. We sought to determine the association between serum apoA-V concentrations and lipoprotein profile in preterm infants and its early postnatal change. Methods Sixty-three neonates (35 males and 28 females; 15 term and 48 preterm) were included. Serum lipoprotein profile and apoA-V concentrations were determined at birth and 1 month. Results Cord blood apoA-V concentrations in appropriate-for-gestational age infants were extremely low (13.1 ± 3.4 ng/mL in term infants, 4.4 ± 0.9 ng/mL in preterm infants) compared with adult values, and those of small-for-gestational age infants were further low (6.4 ± 4.2 ng/mL, 2.2 ± 1.3 ng/mL, respectively). During the first month, serum apoA-V concentration markedly increased, and the concentration of preterm appropriate-for-gestational age infants caught up, whereas that of preterm small-for-gestational age infants did not. At birth, apoA-V concentration positively correlated with gestational age (r = 0.354, P = .0069) but not with birth weight Z-score. ApoA-V concentration had a positive association with very low–density lipoprotein triglyceride concentrations (r = 0.646, P < .0001), and the relationships still remained at 1 month (r = 0.283, P = .0348). Conclusions ApoA-V in neonates was unique in its serum concentration and in the association with lipoprotein profile. [ABSTRACT FROM AUTHOR]

Background Although of interest, few data exist on the clinical characteristics of Japanese patients with an extremely high triglyceride level (≥1000 mg/dL). Objective We assessed the clinical characteristics of Japanese patients with an extremely high triglyceride level. Methods We investigated the presence of coronary artery disease, history of pancreatitis, the presence of fatty liver, and the potential causes of elevated triglyceride in Japanese subjects with an extremely high level of fasting triglyceride (≥1000 mg/dL) among 70,368 subjects whose serum triglyceride was measured for any reason at Kanazawa University Hospital from April 2004 to March 2014. Results We identified 215 (0.31%) subjects (mean age, 46 years; male, 170, mean body mass index, 25 kg/m 2 ) with severe hypertriglyceridemia. Among them, 4 (1.9%) subjects were classified as type I, 97 (45.1%) subjects were type IV, and 114 (53.0%) subjects were type V hyperlipidemia, according to Fredrickson's classification. Among 215 subjects, 116 subjects (54.0%) drank alcohol, 58 (27.0%) showed heavy intake (≥60 g/d), and 64 (29.8%) subjects had diabetes. In total, 59 (27.4%) subjects had transient severe hypertriglyceridemia caused by corticosteroids (N = 19), antidepressant (N = 18), l -asparaginase and steroids for acute lymphoid leukemia (N = 15), hormone replacement therapy for breast cancer (N = 9), β-blocker (N = 5), hypothyroidism (N = 4), pregnancy (N = 4), and panhypopituitarism (N = 2). As many as 119 (55.3%) subjects exhibited fatty liver. Moreover, 12 (5.6%) and 17 (7.9%) subjects had a history of pancreatitis and coronary artery disease, respectively. Conclusions A variety of situations can cause severe hypertriglyceridemia. We suggest that potential secondary causes should be carefully assessed for such patients. [ABSTRACT FROM AUTHOR]

Background: One-hour plasma glucose (1-h PG) level of ≥ 155 mg/dL during an oral glucose tolerance test (OGTT) predicts the development of type 2 diabetes mellitus among individuals with normal glucose tolerance (NGT). In addition, high triglyceride (TG) and low high-density lipoprotein-cholesterol (HDL-C) levels are risks factors for development of diabetes mellitus in the future. Objective: To examine the association between 1-h PG levels and serum lipid profiles in individuals with NGT. Methods: We enrolled 736 individuals with NGT who underwent a 75-g OGTT. They were divided into 2 groups, those with 1-h PG levels < 155 mg/dL (n = 543) and those with 1-h PG levels ≥ 155 mg/dL (n = 193). Multivariate linear regression analyses were performed to assess correlations between 1-h PG levels and lipid profiles. Results: The multiple linear regression analyses showed that 1-h PG levels negatively correlated with HDL-C in individuals with NGT who had 1-h PG levels ≥ 155 mg/dL as well as those with 1-h PG levels < 155 mg/dL (β = −0.137, P = .001 and β = −0.214, P = .003, respectively). In addition, 1-h PG levels positively correlated with log-transformed TG/HDL-C ratio in both groups (β = 0.098, P = .032 and β = 0.152, P = .035, respectively). Moreover, even after adjusting for confounding parameters, TG was higher and HDL-C was lower in individuals with NGT who had 1-h PG levels ≥ 155 mg/dL compared with those who had 1-h PG levels < 155 mg/dL. Conclusion: HDL-C levels and TG/HDL-C ratios closely correlate with 1-h PG levels in individuals with NGT. [Copyright &y& Elsevier]

Background: Type 2 diabetes is associated with early development of endothelial dysfunction. Patients present with typical dyslipidemia (predominantly high levels of triglycerides [TG] and low levels of high-density lipoprotein cholesterol [HDL-C]) or mixed hypercholesterolemia (high levels of low-density lipoprotein cholesterol [LDL-C] and TG with low HDL-C). Normal levels include LDL-C < 100 mg/dL, TG < 135 mg/dL, and HDL-C > 40 mg/dL for men and >50 mg/dL for women. Objective: To determine the effects of 8 weeks’ administration of fenofibrate on inflammatory markers, metabolic parameters, and endothelial dysfunction. Methods: We administered micronized fenofibrate (Laboratories Fourneir S.A Dijon, France) daily for 8 weeks to 40 dyslipidemic, type 2 diabetes patients with equal numbers in each arm of the typical or mixed dyslipidemia groups. Noninvasive endothelial function assessments were performed and serum inflammatory markers obtained before and after treatment. Results: The typical group demonstrated significantly greater TG reduction and HDL-C increment, ie, 56% vs, 21.3% (P < .005) and 21% vs. 7.6% (P = .001), respectively, compared with the mixed group. There was greater LDL-C reduction within the mixed group compared with the typical group 21.0% vs. 2.2% (P < .05). Endothelial dysfunction was present in both groups at baseline. After treatment, the typical group demonstrated significant improvement in resting brachial diameter (3.9 mm [interquartile range {IQR} 3.3-4.7] to 4.2 mm [IQR 3.4-4.8], P = .001) compared with no change within the mixed group (3.6 mm [IQR 3.1-5.4] to 3.7 mm [IQR 3.1-5.3], P = .26). Flow-mediated diameter improved significantly in both groups. The mixed group had significantly greater levels of hs-CRP at baseline but no changes throughout the study. The mixed group demonstrated an increase in vascular adhesion molecule-1 from 706 ng/mL (IQR 566-1195) to 845 ng/mL (637-1653; P = .01), a reduction of tumor necrosis factor-α from 7.0 pg/mL (IQR 1.0-43.5) to 2.5 pg/mL (IQR 1.5-13.5; P = .04) throughout the study. Conclusions: We effectively compared 8 weeks of fenofibrate therapy in type 2 diabetics with contrasting lipid abnormalities. The typical dyslipidemia group showed significantly greater lipid improvements compared with the mixed dyslipidemia group. Both groups had improvements in endothelial functions that were independent of the lipid levels. We concluded that fibrate therapy in type 2 diabetics is beneficial, especially those with typical dyslipidemia and extends beyond its lipid lowering properties. [Copyright &y& Elsevier]

Background: Apolipoprotein A-V (ApoA-V) has been shown to play an important role in the metabolism of plasma triglyceride (TG) levels. However, data for the relationship between serum ApoA-V and TG level and the association between ApoA-V levels and the risk of coronary artery disease (CAD) are inconsistent. Objective: To investigate plasma ApoA-V level and its association with TG in patients with CAD determined by angiography. Methods: Three hundred forty subjects who underwent coronary angiography (CAG) were classified into a CAD group (n = 211) and a non-CAD group (n = 129) according to the results of their CAG. Serum ApoA-V levels were determined by enzyme-linked immunosorbent assays. Results: Patients in the CAD group had greater ApoA-V levels than controls (192.0 ± 114.6 ng/mL vs 164.4 ± 107.5 ng/mL, P < .05). The concentration of ApoA-V was positively correlated to TG level (r = 0.229, P < .01). This correlation was more intense in non-CAD group (r = 0.306, P < .01) than in CAD group (r = 0.172, P < .05). ApoA-V was positively associated with Gensini score. However, the contribution of ApoA-V to Gensini score and CAD risk disappeared after adjustment for the TG level. Conclusion: The positive correlation between serum ApoA-V and TG differs in strength between control and CAD patients. The correlation between ApoA-V and CAD is confounded by the effect of TG. We speculate that the increase of ApoA-V may be a consequence of compensation for the increased demand for plasma TG hydrolysis. [Copyright &y& Elsevier]

Objective: We evaluated factors that caused differences between calculated low-density lipoprotein cholesterol (C-LDL-C) and direct-measured LDL-C (D-LDL-C) and compared them in subjects with diabetes mellitus (DM) or taking lipid-lowering medications. Methods: 21,452 subjects (9,177 women, 12,275 men; 8.1% with DM and 8.5% on lipid-lowering medications) were included in the analysis. Participants were classified into 3 groups, i.e., group 1: the subjects without DM and not on lipid-modifying drugs (n = 18,287), group 2: without DM and on lipid-modifying drugs (n = 1,423), and group 3: with DM (n = 1,742). LDL-C concentrations were either directly measured by a homogenous method or calculated by Friedewald formula. Results: There was a significant correlation between C-LDL-C and D-LDL-C (r = 0.966, P < .001). The absolute values of the differences between two LDL-C values were 7.0 ± 6.2 mg/dl and 6.6 ± 7.3% (6.6 ± 5.9 mg/dl and 6.0 ± 6.5%, 8.8 ± 6.7 mg/dl and 9.1 ± 9.7%, and 10.1 ± 7.3 mg/dl and 10.7 ± 10.1% in group 1, 2, and 3 respectively, P < .001). The subjects with the absolute value of the differences of LDL-C ≥10% was 20.2% (17.3%, 31.3%, and 41.1% in group 1, 2, and 3 respectively, P < .001). In the multiple logistic regression analysis, high triglyceride (≥150 mg/dl), low high-density lipoprotein cholesterol (HDL-C) (<40 mg/dl), male gender, obesity (body mass index ≥25 kg/m2), DM and taking lipid-lowering drugs were significant associated with high LDL-differences (the absolute value of the differences ≥10% or ≥10 mg/dl). Conclusion: D-LDL-C was generally higher by 5 mg/dl or 5% than C-LDL-C. The differences C-LDL-C and D-LDL-C were higher in subjects with DM and on lipid-lowering medications. Male gender, high triglyceride, low HDL-C, and obesity were also associated with the greater differences between C-LDL-C and D-LDL-C. [ABSTRACT FROM AUTHOR]

Objective: Our objective was to develop a simple algorithm that could be applied in routine clinical practice to diagnose type III hyperlipoproteinemia based on plasma total cholesterol, triglyceride and apolipoprotein (Apo) B. Methods: Analysis of plasma lipid, lipoprotein lipid, and apolipoprotein data from 1771 patients in a tertiary care lipid clinic, from whom all data had been collected prospectively by standardized methods. Of the 1771, based on the Fredrickson classification, 16 had type I hyperlipoproteinemia, 736 type IIa hyperlipoproteinemia, 371 type IIb hyperlipoproteinemia, 38 type III hyperlipoproteinemia, 509 type IV hyperlipoproteinemia, and 101 type V hyperlipoproteinemia. Results: Mean plasma ApoB was highest in type IIb (1.53 ± 0.36 g/L), borderline high (1.1 ± 0.23 g/L) in type IV, normal in type III and type V (1.04 ± 0.21 g/L and 0.96 ± 0.40 g/L, respectively) and low in type I (0.48 ± 0.16 g/L). In type III hyperlipoproteinemia, very low–density lipoprotein ApoB (ie, d<1.006 g/mL) accounted for 42.3% of total ApoB, a value that was substantially higher than in any of the other dyslipoproteinemias. The total cholesterol (TC)/ApoB ratio was similar in the uncommon dyslipoproteinemias—type I, III, and V hyperlipoproteinemia (10.5 ± 4.8, 8.7 ± 1.8, 10.3 ± 7.7, respectively)—and much higher than in the common dyslipoproteinemias—type IIa, IIb, and type IV hyperlipoproteinemia (5.0 ± 0.4, 4.6 ± 0.4, 4.9 ± 1.1, respectively). Notwithstanding that the TC/ApoB area under the curve-receiver operating characteristic (AUC-ROC) was very high (0.93), it did not discriminate among the uncommon dyslipoproteinemias. However, the triglyceride (TG)/ApoB ratio was much higher in type I (42.4 ± 28.8) and type V (25.6 ± 30.2) than in type III (5.8 ± 3.2). All cases of type III had a TC/ApoB ratio >6.2 and a TG/ApoB ratio of <10.0. Using these cutpoints, there were also no false positives. Based on the TC/ApoB ratio and the TG/ApoB ratio, the AUC-ROC was 0.99. Conclusions: These data indicate that type III hyperlipoproteinemia can be reliably diagnosed based on plasma cholesterol, TG, and ApoB. [Copyright &y& Elsevier]

Abstract: Background: Niacin and ω-3 fatty acids (ω-3 FA) are both nutrients that reduce serum triglyceride and raise high-density lipoprotein cholesterol (HDL-C) levels when used at pharmacological doses. The possibility that these two agents, given in combination, might have additive effects on these lipid parameters has not been examined previously. In addition, the combination might prevent the rise in low-density lipoprotein (LDL)-C levels frequently seen with ω-3 FA treatment. Objective: To determine the effect of therapy of niacin and ω-3 FA alone and in combination versus placebo on lipid parameters in subjects with atherogenic dyslipidemia. Methods: In a pilot parallel group study, we studied 29 patients with atherogenic dyslipidemia who were assigned to either dual placebo (n = 7), ω-3 FA (3.4 g/d; n = 8), crystalline niacin (3 g/d; n = 7), or the combination (n = 7) for 12 weeks. Fasting lipid profiles were assessed before and after treatment. Results: Changes in serum triglyceride levels from baseline were 10%, −2%, −17%, and −52%, respectively, while HDL-C concentrations rose by 4%, 10%, 18%, and 33%, respectively. Both of these results were statistically significantly different for combination therapy compared to changes with placebo and ω-3 FA monotherapy (analysis of variance with Tukey’s post-hoc test). No statistically significant changes were seen for LDL-C. Addition of ω-FA to niacin had no effect on niacin-induced flushing. Conclusion: From this small pilot study, we conclude that combined therapy with niacin and ω-3 FA has beneficial effects on triglyceride and HDL-C levels, and use of these two agents in combination prevents the ω-3 FA-induced rise in LDL-C. Larger studies of this combination therapy are clearly warranted in patient populations with atherogenic dyslipidemia to assess not only lipid effects, but also potential coronary heart disease benefits. [Copyright &y& Elsevier]

Abstract: High-density lipoproteins (HDL) contain approximately 25% of the cholesterol and <5% of the triglyceride in the plasma of human blood. However, the dynamic exchange of lipids and lipid-binding proteins is not revealed by simply considering the mass of material at any point in time. HDL are the most complex of lipoprotein species with multiple protein constituents, which facilitate cholesterol secretion from cells, cholesterol esterification in plasma, and transfer of cholesterol to other lipoproteins and to the liver for excretion. They also play a major role in triglyceride transport by providing for activation of lipoprotein lipase, exchange of triglyceride among the lipoproteins, and removal of triglyceride rich remnants of chylomicrons and very-low–density lipoproteins after lipase action. In addition, antioxidative enzymes and phospholipid transfer proteins are important components of HDL. Many of the proteins of HDL are exchangeable with other lipoproteins, including chylomicrons and very-low–density lipoproteins. The constantly changing content of lipids and apolipoproteins in HDL particles generate a series of structures that can be analyzed by using separation techniques that depend on size or charge of the particles. Interaction of these various structures can be very different with cell surfaces depending on the size or apolipoprotein content. A series of different transport proteins preferentially exchange lipids with specific structures among the HDL but interact poorly or not at all with others. The role of these differing forms of HDL and their interactions with cells and other lipoprotein species in plasma is the subject of intense study stimulated by the potential for reducing atherogenesis. The strength of this is only partially indicated by the correlation of higher total levels of the HDL particles with reduced incidence of vascular disease in various clinical trials and epidemiological studies. [Copyright &y& Elsevier]