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Background: High intakes of trans-fatty acids (TFAs), especially industrially produced TFAs, can lead to unfavorable lipid and lipoprotein concentrations and an increased risk of cardiovascular disease. It is unknown how this relation might change in a population after significant reductions in TFA intake.Objective: This study, which used a new analytical method for measuring plasma TFA concentrations, clarified the association between plasma TFA and serum lipid and lipoprotein concentrations before and after the US FDA enacted TFA food-labeling regulations in 2006.Methods: Data were selected from the NHANES of 1999-2000 and 2009-2010. Findings on 1383 and 2155 adults, respectively, aged ≥20 y, were evaluated. Multivariable linear regressions were used to examine the associations between plasma TFA concentration and lipid and lipoprotein concentrations. The outcome measures were serum concentrations of total cholesterol (TC), LDL cholesterol, HDL cholesterol, and triglycerides and the ratio of TC to HDL cholesterol.Results: The median plasma TFA concentration decreased from 80.6 μmol/L in 1999-2000 to 37.0 μmol/L in 2009-2010. Plasma TFA concentration continued to be associated with serum lipid and lipoprotein concentrations after significant reductions in TFA intake in the population. For example, by comparing the lowest with the highest quintiles of TFA concentration in 1999-2000, adjusted mean (95% CI) LDL-cholesterol concentrations increased from 118 mg/dL (112, 123 mg/dL) to 135 mg/dL (130, 141 mg/dL) (P-trend < 0.001). The corresponding values for 2009-2010 were 102 mg/dL (97.4, 107 mg/dL) and 129 mg/dL (125, 133 mg/dL) for LDL cholesterol (P-trend < 0.001). Differences between the highest and lowest quintiles were consistent across age groups, sexes, races/ethnicities, and other covariates.Conclusions: Despite a 54% reduction in plasma TFA concentrations in US adults from 1999-2000 to 2009-2010, concentrations remained significantly associated with serum lipid and lipoprotein concentrations. There does not appear to be a threshold under which the association between plasma TFA concentration and lipid profiles might become undetectable. [ABSTRACT FROM AUTHOR]

Background and Aims: A relationship exists between dietary copper intake and hypertriglyceridemia in the United States (US). However, children and adolescents have there is limited research data for children and adolescents, who have not been thoroughly investigated. This study aimed to carefully evaluate this relationship., Methods and Results: This cross-sectional study included 3982 children and adolescents who participated in the US National Health and Nutrition Examination Survey 1999-2006. The outcome variable was hypertriglyceridemia, defined as a triglyceride (TG) concentration >150 mg/dL. Multivariate and binary logistic regression models were applied in this study. The median (Q1-Q3) copper intake and TG levels were 0.98 (0.71-1.32) mg/d and 72.00 (53.00-100.00) mg/dL, respectively. The smoothing curve showed an inverted L-shaped relationship between copper intake and the prevalence of hypertriglyceridemia in American children and adolescents. A binary logistic regression model was developed to evaluate the relationship between copper intake and the prevalence of hypertriglyceridemia, and the inflection point was 0.76 mg/d. The odds of developing hypertriglyceridemia significantly increased with increasing levels of copper intake (odds ratio (OR), 2.00; 95% confidence interval (CI): 1.39-2.86) in participants with copper intake >0.76 mg/d (P for log likelihood ratio test = 0.032). The association between high copper intake and increased hypertriglyceridemia risk was significantly stronger in participants with a high body mass index (BMI; ≥23 kg/m 2 ) (OR: 2.09; 95% CI: 1.42-3.07) than in those with a low BMI (tertile 1-2) (p for interaction = 0.048). Moreover, the increase in copper intake in adolescents aged 13-18 years significantly increased the prevalence of hypertriglyceridemia (OR: 1.95; 95% CI: 1.38-2.76; p for interaction = 0.001)., Conclusion: Higher dietary copper intake increases the prevalence of hypertriglyceridemia, especially among US adolescents with a BMI ≥23 kg/m 2 ., Competing Interests: Declaration of competing interest The authors have no competing interests to declare that are relevant to the content of this article., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Cardiovascular disease is one of the leading causes of death among reproductive-age women. In this study, we examine trends in the prevalence of dyslipidemia, hypertension, and related clinicians' advice among reproductive-age women. We conducted trend analysis of these factors among non-pregnant women aged 20-49 years (n = 5,768) using National Health and Nutrition Examination Survey (NHANES) data obtained between 1999 and 2008. Multiple linear regression and logistic regression analyses were used to examine linear trends over a 10-year period after adjusting for covariates. A downward trend was observed for the proportion of women with abnormal levels of low density lipoprotein (LDL; P = 0.038) and high density lipoprotein (HDL; P = 0.008) cholesterol from 1999 to 2008. In contrast, no significant changes were observed in the prevalence of abnormal total cholesterol ( P = 0.948) and triglyceride levels ( P = 0.300), or hypertension ( P = 0.632). Based on the self-reported data, upward trends were observed in the rates of cholesterol checking ( P = 0.002), high cholesterol ( P = 0.012), receiving clinicians' advice to use lipid-lowering agents ( P < 0.001) and patients' compliance with their advice ( P < 0.001). Although rates of self-reported hypertension did not change over time ( P = 0.120), receiving clinicians' advice to use antihypertensive medications ( P = 0.003) and patients' compliance with these medications ( P = 0.015) also increased significantly. Overall improvements in LDL and HDL cholesterol over this time period could be due to increases in related awareness, receiving advice to use medications, and patients' compliance with this advice. Use of antihypertensive medication has also increased among reproductive-age women in the US. [ABSTRACT FROM AUTHOR]

A 12-hour fasting lipid profile was obtained from 88 otherwise healthy obese (BMI ≥ 95%) adolescents (age 16 ± 1 years, BMI 36 ± 1 kg/m², 55 males, 33 females, 57% Hispanic, 23% African American, 19% Caucasian, 1% Asian American). About 56% of the obese adolescents exhibited lipid abnormalities based on cutoff points established by American Heart Association (AHA) guidelines, and about 57% exhibited lipid abnormalities based on percentile values established by the Lipid Research Clinic Pediatric Prevalence Study. Isolated low high-density lipoprotein-cholesterol (HDL-C) was the most common abnormality (43% based on AHA, 36% based on the Lipid Research Clinic Pediatric Prevalence Study) among the obese adolescents with lipid disorders. While there was no significant statistical difference (SSD) between genders in the levels of total cholesterol and low-density lipoprotein-cholesterol (LDL-C), triglyceride (TG) levels were significantly higher (P = .003) in males (120 ± 11 mg/dL) than in females (81 ± 7 mg/dL), and levels of HDL-C were significantly higher (P = .006) in females (42 ± 2 mg/dL) than in males (35 ± 1 mg/dL). There was no SSD between races in total cholesterol and LDL-C levels. TG levels were significantly lower in African-American participants (81 ± 9 mg/ dL) compared with levels in Caucasian participants (117 ± 15 mg/dL, P ≤ .05) and with levels in Hispanic participants (112 ± 11 mg/dL, P = .03). HDL-C levels were significantly higher in African-American participants (43 ± 3 mg/dL) compared with levels in Hispanic participants (36 ± 1 mg/dL, P = .03), but there was no SSD when compared with HDL-C levels in Caucasian participants (37 ± 2 mg/dL). [ABSTRACT FROM AUTHOR]

Summary: Background: Hypertriglyceridemic waist (HTGW) phenotype is a marker of atherogenesis whose association with cardiovascular diseases is unclear. Objective: To determine the association of abdominal obesity, hypertriglyceridemia and HTGW with risk of type 2 diabetes in American adults. Methods: Data (n =1914) From the 2003–2004 United States National Health and Nutrition Examination Surveys (NHANESs) were used in this investigation. The risk of type 2 diabetes associated with HTGW was estimated using odds ratio from the logistic regression model, adjusting for race/ethnicity, age, body mass index (BMI), hypertension, HDL-cholesterol (HDL-C), smoking and alcohol intake. Results: There was a gender and racial/ethnic difference in the association of adiposity phenotypes with type 2 diabetes. In men, abdominal obesity, hypertriglyceridemia and HTGW were associated with 1.59 (95% CI: 1.09–2.79), 2.27 (95% CI: 1.42–3.62), and 2.85 (95% CI: 2.10–2.10) increased odds of type 2 diabetes. The analogous values in women were 2.50 (95% CI: 1.82–4.79), 2.14 (95% CI: 1.30–3.53), and 2.58 (95% CI: 1.48–4.24), respectively. HTGW was associated with 1.24 (95% CI: 1.05–2.39) and 3.94 (95% CI: 2.85–3.90) increased risks of type 2 diabetes. The corresponding risks in White women and Black women were 1.36 (95% CI: 1.23–2.91) and 5.62 (95% CI: 1.04–9.42), respectively. Conclusion: Hypertriglyceridemic waist phenotype is more strongly associated with type 2 diabetes than both hypertriglyceridemia and abdominal obesity alone. Well designed public health strategies to enhance lifestyle modification program to reduce the prevalence of HTGW may be a way to decrease racial/ethnic disparities for type 2 diabetes in the United States. [Copyright &y& Elsevier]

Abstract: Background: We tested whether single nucleotide polymorphisms (SNPs) in the PPARα gene (PPARA) are associated with variations in levels of plasma apolipoprotein CIII (apoCIII) levels, as well as other lipids and lipoproteins, in African-Americans and Caucasians. Methods and results: We initially identified an intronic SNP (rs4253728) in PPARA that was associated with plasma apoCIII level (p <0.05) in a subset of 435 individuals from the total study population (n =944; 335 African-Americans and 609 Caucasians). This SNP was then genotyped in a second subset of 476 individuals (total 911 subjects with available data), and a previously described PPARA coding SNP (L162V) which was shown to be in moderate linkage disequilibrium with the intronic SNP (r 2 =0.18) was genotyped in 928 subjects from the same study population. The minor allele frequencies for both SNPs were significantly lower in African-Americans compared with Caucasians (7.2% vs. 27.3% for rs4253728, 1.5% vs. 6.1% for L162V, both p <0.0001). African-Americans had significantly lower levels of TG and apoCIII compared with Caucasians after adjusting for age, sex, body mass index (BMI), waist circumference and other baseline characteristics. However, racial differences in TG levels were attenuated after adjusting for apoCIII levels. The minor alleles for both PPARA SNPs were associated with higher TG and apoCIII levels. Race modified the associations of L162V with TG (p for interaction=0.0056) and apoCIII (p for interaction=0.0011). Levels of both TG and apoCIII were lower in African-American but not Caucasian homozygotes for the major allele compared with carriers of the minor allele. Similar results were obtained for the intronic SNP, but the findings were no longer significant in a model that also contained L162V. Conclusions: Two PPARA SNPs, L162V and rs4253728 (intronic), are less prevalent in African-Americans than in Caucasians and in African-Americans only are associated with higher apoCIII and TG levels. [Copyright &y& Elsevier]

Background: It is unknown whether higher triglyceride results in higher mortality from diabetes, i.e., diabetes mortality. This study aimed to investigate the association of fasting triglyceride with diabetes mortality., Methods: This study included 26,582 US adults from the National Health and Nutrition Examination Surveys from 1988 to 2014. Diabetes mortality outcomes were ascertained by linkage to the National Death Index records. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of triglyceride for diabetes mortality., Results: Higher levels of fasting triglyceride were associated with higher levels of glucose, glycated hemoglobin, insulin, and homeostatic model assessment for insulin resistance at baseline. A 1-natural-log-unit increase in triglyceride (e.g., from 70 to 190 mg/dL) was associated with a 115% higher multivariate-adjusted risk of diabetes diagnosis (odds ratio, 2.15; 95% CI, 2.00-2.33). During 319,758 person-years of follow-up with a mean follow-up of 12.0 years, 582 diabetes deaths were documented. Compared with people with triglyceride in the lowest quintile, people with triglyceride in the highest quintile had an 85% higher risk of diabetes mortality (HR, 1.85; 95% CI, 1.25-2.73). A 1-natural-log-unit increase in triglyceride was associated with a 40% higher multivariate-adjusted risk of diabetes mortality. The positive association between triglyceride and diabetes mortality was also presented in sub-cohorts of participants with or without diabetes., Conclusions: This study demonstrated that higher fasting triglyceride was associated with a higher diabetes mortality risk., (© 2021. The Author(s).)

Background: The relationship between triglyceride (TG) level and the mortality risk of all-cause and cardiovascular disease is not entirely consistent among adults., Methods: The present analysis included adult participants from National Health and Nutrition Examination Surveys (NHANES) between the periods 1999-2014. The levels of TG were categorized into < 150, 150-199, 200-250 and ≥ 250 mg/dL respectively. Multivariate Cox regression analysis, stratified analysis and generalized additive model were conducted to reveal the correlation between TG and mortality risk. Results were presented in hazard ratio (HRs) and 95% confidence intervals (CIs)., Results: There were 18,781 (9130 males, mean age was 45.64 years) participants being included in the analysis. The average follow-up period was 8.25 years, where 1992 (10.61%) cases of all-cause and 421 (2.24%) cardiovascular death have occurred. In the multivariate Cox model, every 1 mg/dL raise in TG has significantly associated with all-cause mortality (HR: 1.08, 95% CI: 1.02, 1.15) but not cardiovascular mortality (HR: 1.10, 95% CI: 0.97, 1.24). When using TG <  150 mg/dL as reference, TG ≥ 250 mg/dL associated with death from all-cause (HR = 1.34, 95% CI: 1.12, 1.60; P = 0.0016 but not cardiovascular death (HR = 1.26, 95% CI: 0.85, 1.88; P = 0.2517). According to smoothing spline plots, the risk of all-cause was the lowest when TG was approximately 135 mg/dL., Conclusion: TG might have a dose-independent association with all-cause mortality among adults in United States.

Background: Statistical methods to study the joint effects of environmental factors are of great importance to understand the impact of correlated exposures that may act synergistically or antagonistically on health outcomes. This study proposes a family of statistical models under a unified partial-linear single-index (PLSI) modeling framework, to assess the joint effects of environmental factors for continuous, categorical, time-to-event, and longitudinal outcomes. All PLSI models consist of a linear combination of exposures into a single index for practical interpretability of relative direction and importance, and a nonparametric link function for modeling flexibility., Methods: We presented PLSI linear regression and PLSI quantile regression for continuous outcome, PLSI generalized linear regression for categorical outcome, PLSI proportional hazards model for time-to-event outcome, and PLSI mixed-effects model for longitudinal outcome. These models were demonstrated using a dataset of 800 subjects from NHANES 2003-2004 survey including 8 environmental factors. Serum triglyceride concentration was analyzed as a continuous outcome and then dichotomized as a binary outcome. Simulations were conducted to demonstrate the PLSI proportional hazards model and PLSI mixed-effects model. The performance of PLSI models was compared with their counterpart parametric models., Results: PLSI linear, quantile, and logistic regressions showed similar results that the 8 environmental factors had both positive and negative associations with triglycerides, with a-Tocopherol having the most positive and trans-b-carotene having the most negative association. For the time-to-event and longitudinal settings, simulations showed that PLSI models could correctly identify directions and relative importance for the 8 environmental factors. Compared with parametric models, PLSI models got similar results when the link function was close to linear, but clearly outperformed in simulations with nonlinear effects., Conclusions: We presented a unified family of PLSI models to assess the joint effects of exposures on four commonly-used types of outcomes in environmental research, and demonstrated their modeling flexibility and effectiveness, especially for studying environmental factors with mixed directional effects and/or nonlinear effects. Our study has expanded the analytical toolbox for investigating the complex effects of environmental factors. A practical contribution also included a coherent algorithm for all proposed PLSI models with R codes available.

Objective: Aimed to find the cut-off point of handgrip strength and it's association with MetS., Results: The relative handgrip strength was negatively associated with the prevalence of MetS. Of note, the odds ratios (ORs) with 95% confidence intervals (CIs) across tertiles of relative handgrip strength were 1 (reference), 0.45 (0.33, 0.62), and 0.13 (0.08, 0.20) in male participants after adjusting for demographic factors, calorie intake, and physical activity. Similar results were observed in female participants. The cutoff values of relative handgrip strength for male and female participants were 0.52 and 0.40, respectively., Conclusions: Findings of this study suggest that a strong relationship exists between handgrip strength and prevalence of MetS in US adults, regardless of sex., Methods: A total of 5 056 participants in the National Health and Nutrition Examination Survey were analysed in this study. Handgrip strength was measured by using a handgrip dynamometer. MetS was defined in accordance with the criteria of the scientific statement of the American Heart Association in 2009. Multivariable binary logistic regression was used to explore the association between handgrip strength and MetS.

Background: Recent court decisions have thrown into question the Food and Drug Administration's rules limiting manufacturer promotion of prescription drugs for unapproved uses. We assessed how providing pro forma disclosures or more descriptive evidence context about the data supporting an off-label claim affected physicians' beliefs about drug efficacy., Methods and Results: In online and mailed surveys, we randomized national samples of board-certified, clinically active cardiologists, internists, and endocrinologists to receive 1 of 3 information scenarios about a hypothetical drug derived verbatim from excerpts on the website for Vascepa, a prescription fish oil for which Food and Drug Administration specially permitted off-label promotion after a manufacturer lawsuit. The scenarios presented information about the approved on-label indication (severe hypertriglyceridemia), off-label claim + pro forma disclaimers (suggestive but not conclusive evidence for use as an add-on to a statin for patients reaching low-density lipoprotein goal but with persistent moderate hypertriglyceridemia), and off-label claim + evidence context (eg, reports on 3 trials failing to demonstrate cardiovascular benefit of other triglyceride-lowering drugs for such patients). Among 686 respondents (48% response rate), 29% reported receiving off-label information about Vascepa (ie, use as an add-on to a statin) from the manufacturer, and 16% had prescribed it off-label for this purpose. Off-label prescribing was 5 times higher among physicians who received such off-label information (38% versus 7%, P <0.001). For the hypothetical drug, the proportion of physicians endorsing the unproven claim that the drug reduced cardiovascular risk was similar among those randomized to the on-label and off-label claim + pro forma disclaimers scenarios (35% versus 37% [95% CI, -6% to 11%]), but substantially lower among those randomized to the off-label claim + evidence context scenario (21% [95% CI, -24% to 7%])., Conclusions: Physicians who received company information about the unapproved use of Vascepa were more likely to report prescribing it off-label. Supplementing off-label claims with evidence context improved the prescribers' knowledge and reduced enthusiasm for the unproven, off-label indication of reducing cardiovascular risk.

Objective: Traditionally, the absence of insulin resistance risk factors (IRRFs) was considered a low risk for insulin resistance (IR). However, IR also existed in certain individuals without IRRFs; thus this study aims to explore predictors of IR targeted at the population without IRRFs., Design: Cross-sectional survey., Setting: National Health and Nutrition Examination Survey., Participants: Participants without regular IRRFs (IRRF-Free, n=2478) and a subgroup without optimal IRRFs (IRRF-Optimal, n=1414) were involved in this study., Primary and Secondary Outcome Measure: IRRFs and the optimal cut-off value of triglyceride (TG) to predict IR., Results: Overall, the prevalence of IR was 6.9% and 5.7% in the IRRF-Free group and the IRRF-Optimal group, respectively. TG and waist circumference were independently associated with the prevalence of IR in both the groups (OR=1.010 to 10.20; p<0.05 for all), where TG was positively associated with IR. The area under the receiver operating characteristic curve of TG was 0.7016 (95% CI: 0.7013 to 0.7018) and 0.7219 (95% CI: 0.7215 to 0.7222), and the optimal cut-off value of TG to predict IR was 79.5 mg/dL and 81.5 mg/dL in the IRRF-Free group and the IRRF-Optimal group, respectively., Conclusion: There is an association between TG and IR even in the normal range of TG concentration. Therefore, normal TG could be used as an important indicator to predict the prevalence of IR in the absence of IRRFs., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale & Objective: A large residual risk for atherosclerotic cardiovascular disease (ASCVD) remains in the setting of chronic kidney disease (CKD) despite treatment with statins. We sought to evaluate the associations of lipid and apolipoprotein levels with risk for ASCVD in individuals with CKD., Study Design: Prospective cohort study., Settings & Participants: Adults aged 21 to 74 years with non-dialysis-dependent CKD at baseline enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study in 7 clinical study centers in the United States., Predictor: Baseline total cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C), very low-density lipoprotein cholesterol (VLDL-C), triglycerides, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo-B), HDL-C, and apolipoprotein AI (Apo-AI) values stratified into tertiles., Outcome: A composite ASCVD event of myocardial infarction or ischemic stroke., Analytic Approach: Multivariable Cox proportional hazards regression to estimate the risk for ASCVD for each tertile of lipoprotein predictor., Results: Among 3,811 CRIC participants (mean age, 57.7 years; 41.8% white), there were 451 ASCVD events during a median follow-up of 7.9 years. There was increased ASCVD risk among participants with VLDL-C levels in the highest tertile (HR, 1.28; 95% CI, 1.01-1.64), Apo-B levels in the middle tertile (HR, 1.30; 95% CI, 1.03-1.64), HDL-C levels in the middle and lowest tertiles (HRs of 1.40 [95% CI, 1.08-1.83] and 1.77 [95% CI, 1.35-2.33], respectively), and Apo-AI levels in the middle and lowest tertiles (HRs of 1.77 [95% CI, 1.02-1.74] and 1.77 [95% CI, 1.36-2.32], respectively). LDL-C level was not significantly associated with the ASCVD outcome in this population (HR, 1.00 [95% CI, 0.77-1.30] for the highest tertile)., Limitations: Associations based on observational data do not permit inferences about causal associations., Conclusions: Higher VLDL-C and Apo-B levels, as well as lower HDL-C and Apo-AI levels, are associated with increased risk for ASCVD. These findings support future investigations into pharmacologic targeting of lipoproteins beyond LDL-C, such as triglyceride-rich lipoproteins, to reduce residual risk for ASCVD among individuals with CKD., (Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: The triglyceride (TG) response to a high-fat meal (postprandial lipemia, PPL) affects cardiovascular disease risk and is influenced by genes and environment. Genes involved in lipid metabolism have dominated genetic studies of PPL TG response. We sought to elucidate common genetic variants through a genome-wide association (GWA) study in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN)., Methods: The GOLDN GWAS discovery sample consisted of 872 participants within families of European ancestry. Genotypes for 2,543,887 variants were measured or imputed from HapMap. Replication of our top results was performed in the Heredity and Phenotype Intervention (HAPI) Heart Study (n = 843). PPL TG response phenotypes were constructed from plasma TG measured at baseline (fasting, 0 hour), 3.5 and 6 hours after a high-fat meal, using a random coefficient regression model. Association analyses were adjusted for covariates and principal components, as necessary, in a linear mixed model using the kinship matrix; additional models further adjusted for fasting TG were also performed. Meta-analysis of the discovery and replication studies (n = 1715) was performed on the top SNPs from GOLDN., Results: GOLDN revealed 111 suggestive (p < 1E-05) associations, with two SNPs meeting GWA significance level (p < 5E-08). Of the two significant SNPs, rs964184 demonstrated evidence of replication (p = 1.20E-03) in the HAPI Heart Study and in a joint analysis, was GWA significant (p = 1.26E-09). Rs964184 has been associated with fasting lipids (TG and HDL) and is near ZPR1 (formerly ZNF259), close to the APOA1/C3/A4/A5 cluster. This association was attenuated upon additional adjustment for fasting TG., Conclusion: This is the first report of a genome-wide significant association with replication for a novel phenotype, namely PPL TG response. Future investigation into response phenotypes is warranted using pathway analyses, or newer genetic technologies such as metabolomics., (Copyright © 2015 Elsevier Inc. All rights reserved.)