Higher High-density Lipoprotein Cholesterol Research Articles

Estrogen induces LCAT to maintain cholesterol homeostasis and suppress hepatocellular carcinoma development.

Hepatocellular carcinoma (HCC) is an aggressive disease that occurs predominantly in men. Estrogen elicits protective effects against HCC development. Elucidation of the estrogen-regulated biological processes that suppress HCC could lead to improved prevention and treatment strategies. Here, we performed transcriptomic analyses on mouse and human liver cancer and identified LCAT as the most highly estrogen-upregulated gene and a biomarker of favorable prognosis. LCAT upregulation inhibited HCC in vitro and in vivo and mediated estrogen-induced suppression of HCC in an ESR1-dependent manner. LCAT facilitated high-density lipoprotein cholesterol (HDL-C) production and uptake via the LDLR and SCARB1 pathways. Consistently, high HDL-C levels corresponded to a favorable prognosis in HCC patients. The enhanced HDL-C absorption induced by LCAT impaired SREBP2 maturation, which ultimately suppressed cholesterol biosynthesis and dampened HCC cell proliferation. HDL-C alone inhibited HCC growth comparably to the cholesterol-lowering drug lovastatin, and SREBF2 overexpression abolished the inhibitory activity of LCAT. Clinical observations and cross-analyses of multiple databases confirmed the correlation of elevated LCAT and HDL-C levels to reduced cholesterol synthesis and improved HCC patient prognosis. Furthermore, LCAT deficiency mimicked whereas LCAT overexpression abrogated the tumor growth promoting effects of ovariectomy in HCC-bearing female mice. Most importantly, HDL-C and LCAT delayed the development of subcutaneous tumors in nude mice, and HDL-C synergized with lenvatinib to eradicate orthotopic liver tumors. Collectively, this study reveals that estrogen upregulates LCAT to maintain cholesterol homeostasis and dampen hepatocarcinogenesis. LCAT and HDL-C represent potential prognostic and therapeutic biomarkers for targeting cholesterol homeostasis as a strategy for treating HCC.

Risk and Population Attributable Fraction of Stroke Subtypes in Japan.

Associations of major risk factors for stroke with total and each type of stroke, as well as subtypes of ischemic stroke, and their population attributable fractions had not been examined comprehensively. Participants of the Japan Public Health Center-based prospective (JPHC) Study Cohort II without histories of cardiovascular disease and cancer (n = 14,797) were followed from 1993 through 2012. Associations of current smoking, hypertension, diabetes, overweight (body mass index ≥25 kg/m2), non-high-density lipoprotein cholesterol (non-HDLC) categories, low HDLC (<40 mg/dL), urine protein, and history of arrhythmia were examined in a mutually-adjusted Cox regression model that included age and sex. Population attributable fractions (PAFs) were estimated using the hazard ratios and the prevalence of risk factors among cases. Subjects with hypertension were 1.63 to 1.84 times more likely to develop any type of stroke. Diabetes, low HDLC, current smoking, overweight, urine protein, and arrhythmia were associated with risk of overall and ischemic stroke. Hypertension and urine protein were associated with risk of intracerebral hemorrhage, while current smoking, hypertension, and low non-HDLC were associated with subarachnoid hemorrhage. Hypertension alone accounted for more than a quarter of stroke incidence, followed by current smoking and diabetes. High non-HDLC, current smoking, low HDLC, and overweight contributed mostly to large-artery occlusive stroke. Arrhythmia explained 13.2% of embolic stroke. Combined PAFs of all the modifiable risk factors for total, ischemic, and large-artery occlusive strokes were 36.7%, 44.5%, and 61.5%, respectively. Although there are differences according to subtypes, hypertension could be regarded as the most crucial target for preventing strokes in Japan.

Causal relationship between dyslipidemia and risk of facial aging: Insights from Mendelian randomization in East Asian populations.

Emerging observational studies showed an association between dyslipidemia and aging. However, it remains unclear whether this association is causal, particularly in the case of Asians, which are aging more rapidly than other continents. Given the visible manifestations of aging often include changes in facial appearance, the objective of this study is to assess the causal relationship between dyslipidemia and facial aging in East Asian populations. SNPs related to dyslipidemia in East Asian people such as Total cholesterol (TC), High-density-lipoprotein cholesterol (HDL), Low-density-lipoprotein cholesterol (LDL), and Triglyceride (TG) along with outcomes data on facial aging, were extracted from public genome-wide association studies (GWAS). A two-sample Mendelian randomization (MR) analysis was then performed using publicly available GWAS data to investigate the potential causal relationship. The effect estimates were primarily calculated using the fixed-effects inverse variance weighted (IVW) method. Totally, 88 SNPs related to HDL among 70657 East Asian participants in GWAS. Based on the primary causal effects model using MR analyses with the IVW method, high HDL level was demonstrated as significantly related to the risk of facial aging (OR, 1.060; 95% CI, 1.005-1.119, p=0.034), while high TC level (OR, 0.995; 95% CI, 0.920-1.076, p=0.903), high LDL level (OR, 0.980, 95% CI, 0.924-1.041, p=0.515), as well as high TG level (OR, 0.999, 95% CI, 0.932-1.071, p=0.974), showed no significant correlation with facial aging. The two-sample MR analysis conducted in this study revealed a positive causal relationship between high HDL levels and facial aging. In contrast, facial aging demonstrated no significant correlation with high levels of TC, LDL, or TG. Further large-sample prospective studies are needed to validate these findings and to provide appropriate recommendations regarding nutrition management to delay the aging process among old patients in East Asia.

Association of high-density lipoprotein cholesterol with sarcopenia in Chinese community-dwelling middle-aged and older adults: Evidence from 4-year longitudinal study from the CHARLS.

Introduction There is inconsistent evidence on the associations between high-density lipoprotein cholesterol (HDL-C) and risk of sarcopenia. To determine the evidence existing between HDL-C and sarcopenia in Chinese middle-aged and older adults. Methods We used a panel study design of the China Health and Retirement Longitudinal Study (CHARLS), with 7,415 participants (mean age 57.5 years) from 2011, 2013, and 2015. HDL-C was measured by colormetric test of venous serum samples. Sarcopenia was defined as low muscle mass, plus low muscle strength, or low physical performance. Muscle mass was estimated by anthropometric measures. Muscle strength was measured by handgrip strength using dynamometer. Physical performance was measured by 5-time chair stand test, gait speed test, and short physical performance battery. Results With 961 (13.0%) sarcopenia cases, each 1-unit increase (1 SD = 15.4 mg/dL) of HDL-C levels was associated with 42% increased odds of incident sarcopenia [OR = 1.42, 95% confidence interval (CI) = 1.28 - 1.58] at 4 years follow up. Females with high HDL-C levels (HDL-C > 60 mg/dL) had a higher risk of sarcopenia [OR = 2.49, 95% CI = 1.76 - 3.52]. A J-shaped association between HDL-C and risk of sarcopenia in females. HDL-C was negatively associated with muscle mass [ = -0.23, 95% CI = -0.27 - -0.20] and hand grip strength [ = -0.05, 95% CI = -0.19 - 0.09]. Conclusion High HDL-C levels were associated with higher risk of sarcopenia among middle-aged and older Chinese adults, and appropriate control of its high levels informs the management of sarcopenia.

E056 Particularities of the lipid profile in rheumatoid arthritis

Abstract Background/Aims Rheumatoid arthritis (RA), like all autoimmune diseases, is associated with a high cardiovascular risk. This risk is essentially linked to the chronic inflammation and dyslipidaemia engendered by this chronic inflammatory rheumatism. The objective of this work was to study the particularities of the lipid profile in RA. Methods We conducted a retrospective study including patients with RA according to ACR- EULAR 2010 criteria, followed in an internal medicine department between 2015 and 2022. Lipid profile data (total cholesterol (TC), high-density lipoproteins (HDLc), low-density lipoproteins (LDLc), and triglycerides (TG)) were collected. Results Eighty patients with RA were studied. The mean age was 60.79 years [range 30-91]. The sex ratio (F/H) was 4.33, with a clear female predominance. The mean age of disease onset was 46.34 years [extremes: 22-82]. A personal history of dyslipidaemia was noted in 19 patients: hypercholesterolemia, hypertriglyceridemia, and mixed dyslipidaemia were found in 8, 4 and 7 cases. Other comorbidities were arterial hypertension in 35% of cases (n = 28), diabetes in 30% of cases (n = 24), renal insufficiency in 6.25% of cases (n = 5) and a cardiovascular accident in 5% of cases (n = 4). Obesity was present in 15% of patients and smoking in 5%. 69 patients had a lipid panel. Dyslipidaemia was present in 66.7% of cases (n = 46). The mean TC level was 4.47 ± 1.0 mmol/L [range: 2.32 - 6.96 mmol/L], the mean TG level was 2.64 ± 0.81 [range: 0.90 - 4 mmol/L], the mean HDLc level was 1.106 ± 0.394 mmol/L [0.50 - 2] and the mean LDLc level was 1.38 ± 0.565 mmol/L [0.56 - 3.59 mmol/L]. Hypercholesterolemia (21.3%) and hypocholesterolaemia (21.3%) were the most common lipid abnormalities. Hypertriglyceridemia was observed in 10% of cases (n = 8). A low HDLc was observed in 20% of cases (n = 16). Only one patient had a high HDLc, with HDLc= 2 mmol/l. A low LDL was present in 10% of cases (n = 8). Conclusion In our study, hypolipidemia was the most common dyslipidaemia. This confirms the lipid paradox found in RA. Indeed, systemic inflammation is responsible for quantitative and qualitative alterations in lipoproteins. Stabilization of the disease leads to normalization of the lipid balance and improved control of cardiovascular risk. Disclosure I. Fenniche: None. M. Somai: None. I. Rachdi: None. I. Arbaoui: None. F. Daoud: None. S. Kochbati: None. B. Daoud: None. Z. Aydi: None. F. Boussema: None.

Gestational Diabetes and Subsequent Metabolic Dysfunction: An National Health and Nutrition Examination Survey Analysis (2011-2018).

Background: Gestational diabetes mellitus (GDM) complicates ∼10% of pregnancies, with the highest rates among Asian women. Evidence suggests that GDM is associated with an increased risk for future chronic health conditions, yet data for Asian women are sparse. We explored the association between prior GDM and metabolic dysfunction with nationally representative data to obtain Asian-specific estimates. Methods: For this cross-sectional study, data were drawn from the National Health and Nutrition Examination Survey for 7195 women with a prior pregnancy. GDM (yes/no) was defined using the question "During pregnancy, were you ever told by a doctor or other health professional that you had diabetes, sugar diabetes, or gestational diabetes?." Current metabolic dysfunction (yes/no) was based on having at least one of four indicators: systolic blood pressure (SBP, ≥130 mmHg), waist circumference (≥88 cm), high-density lipoprotein (HDL) cholesterol (<50 mg/dL), and glycosylated hemoglobin (HbA1c) (≥6.5%). Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) for the association between prior GDM and metabolic outcomes, overall and by race. Models included sampling weights and demographic and behavioral factors. Results: Overall, women with prior GDM had 46% greater odds of high waist circumference (OR: 1.5; 95% CI: 1.1-2.0) and 200% greater odds (OR: 3.0; 95% CI: 2.1-4.2) of high HbA1c. Prior GDM was not associated with high blood pressure or low HDL cholesterol. In race-specific analyses, prior GDM was associated with increased risk of elevated HbA1c among Asian (OR: 6.6; 95% CI: 2.5-17.2), Mexican American (OR: 3.0; 95% CI: 1.5-5.8), Black (OR: 3.0; 95% CI: 1.7-5.5), and White (OR: 2.6; 95% CI: 1.5-4.6) women. Prior GDM was associated with elevated SBP among Mexican American women and low HDL among Black women. Discussion: Prior GDM is associated with elevated HbA1c among all women, yet is a stronger predictor of elevated HbA1c among Asian women than other women. Race-specific associations between prior GDM and metabolic dysfunction were observed among Mexican American and Black women. Further research is warranted to understand the observed race/ethnic-specific associations.

Trajectories of clinical characteristics, complications and treatment choices in data-driven subgroups of type 2 diabetes.

This study aimed to explore the added value of subgroups that categorise individuals with type 2 diabetes by k-means clustering for two primary care registries (the Netherlands and Scotland), inspired by Ahlqvist's novel diabetes subgroups and previously analysed by Slieker et al. METHODS: We used two Dutch and Scottish diabetes cohorts (N=3054 and 6145; median follow-up=11.2 and 12.3 years, respectively) and defined five subgroups by k-means clustering with age at baseline, BMI, HbA1c, HDL-cholesterol and C-peptide. We investigated differences between subgroups by trajectories of risk factor values (random intercept models), time to diabetes-related complications (logrank tests and Cox models) and medication patterns (multinomial logistic models). We also compared directly using the clustering indicators as predictors of progression vs the k-means discrete subgroups. Cluster consistency over follow-up was assessed. Subgroups' risk factors were significantly different, and these differences remained generally consistent over follow-up. Among all subgroups, individuals with severe insulin resistance faced a significantly higher risk of myocardial infarction both before (HR 1.65; 95% CI 1.40, 1.94) and after adjusting for age effect (HR 1.72; 95% CI 1.46, 2.02) compared with mild diabetes with high HDL-cholesterol. Individuals with severe insulin-deficient diabetes were most intensively treated, with more than 25% prescribed insulin at 10 years of diagnosis. For severe insulin-deficient diabetes relative to mild diabetes, the relative risks for using insulin relative to no common treatment would be expected to increase by a factor of 3.07 (95% CI 2.73, 3.44), holding other factors constant. Clustering indicators were better predictors of progression variation relative to subgroups, but prediction accuracy may improve after combining both. Clusters were consistent over 8 years with an accuracy ranging from 59% to 72%. Data-driven subgroup allocations were generally consistent over follow-up and captured significant differences in risk factor trajectories, medication patterns and complication risks. Subgroups serve better as a complement rather than as a basis for compressing clustering indicators.

Factor modification in the association between high-density lipoprotein cholesterol and liver cancer risk in a nationwide cohort.

The effect modification by smoking and menopausal status in the association between high-density lipoprotein cholesterol (HDL-C) and liver cancer risk has not been reported. This population-based cohort study included 4.486 million cancer-free individuals among those who underwent national cancer screening in 2010 and were followed up until December 2017. We conducted analyses in populations that excluded people with chronic hepatitis B, chronic hepatitis C and liver cirrhosis (Model I) and that included those diseases (Model III). HDL-C level was classified into eight groups at 10-mg/dL intervals. Liver cancer risk by HDL-C was measured using adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). During follow-up, 18 795 liver cancers in Model I and 20 610 liver cancers in Model III developed. In Model I, low HDL-C levels (aHR 1.83; 95% CI 1.65-2.04) and extremely high HDL-C levels (aHR 1.24; 95% CI 1.10-1.40) were associated with an increased liver cancer risk compared with a moderate HDL-C level of 50-59mg/dL. This association was similar in both men and women with larger effect size in men (aHR, 1.91; 95% CI, 1.70-2.15). The hazardous association between low HDL-C and liver cancer risk was remarkable in current smokers (aHR, 2.19; 95% CI, 1.84-2.60) and in pre-menopausal women (aHR, 2.91; 95% CI, 1.29-6.58) compared with post-menopausal women (aHR, 1.45; 95% CI, 1.10-1.93). This association was similarly observed in Model III. Low and extremely high HDL-C levels were associated with an increased liver cancer risk. The unfavourable association between low HDL-C and liver cancer was remarkable in smokers and pre-menopausal women.

Longitudinal study of the impact of the COVID-19 pandemic on diet and physical activity among Latinos of Mexican ancestry

BackgroundThe COVID-19 pandemic caused societal disruption in the United States and most of the world, affecting many aspects of life, including healthcare and health-related behaviors such as diet, food security, and physical activity. Communities with economic and health disparities may have been particularly affected. This study was undertaken to determine how conditions in the early pandemic (January, 2021–February, 2022) affected Latino patients of Mexican Ancestry at high risk of type 2 diabetes mellitus who participated in El Banco por Salud biobank project in Tucson, Arizona.MethodsBaseline, prepandemic measurements were available in 17, 21, and 60 patients with normal hemoglobin A1c (HbA1c), prediabetes, and type 2 diabetes, respectively.ResultsPeople with healthy HbA1c were significantly younger, less obese, and had higher HDL cholesterol. HbA1c was unaffected by the pandemic in any group. Triglycerides, total and HDL cholesterol levels fell in all groups during the pandemic. Physical activity levels in all groups were remarkably low, with most reporting no engagement in any voluntary physical activity. Engagement in physical activity or its enjoyment was lower in patients with diabetes and prediabetes than in younger, less obese patients. Major diet differences were between men and women and were present before the pandemic. Women consumed significantly more vegetables, fruit, and salad than men. The only pandemic-related change in diet was a drop in egg consumption, possibly explaining the fall in total cholesterol.ConclusionSocietal disruption during the COVID-19 pandemic had minimal effects on adverse health-related behaviors, cardiometabolic risk, or changes in glycemic control in a Latino community with diabetes and healthcare disparities in the Southwest US.

Abstract LB415: Association between waist circumference, body mass index, high-density lipoprotein cholesterol level, and risk of chronic myeloid leukemia

Abstract Advances in the treatment of chronic myeloid leukemia (CML) have resulted in increased prevalence. However, a more comprehensive understanding of its pathogenesis and epidemiology is necessary. Recent studies suggested the association between altered lipid metabolism and carcinogenesis, prompting an investigation of the relationship between metabolic disorders and incidence of CML. Thus, we conducted a study to examine the association between waist circumference, body mass index (BMI), high-density lipoprotein cholesterol (HDL-C), and the incidence of CML.Using data from the Korean National Health Insurance Service from 2009 to 2017, a competing risks regression was conducted to examine the hazard ratios of CML in 3,879,560 individuals aged 20 years and above. During a mean of 10.13±1.24 years of follow-up, there were a total of 848 cases of CML, including 539 male and 309 female patients.1) Individuals in the group with a waist circumference equal to or greater than 100cm had the greatest risk of CML (adjusted hazard ratio [aHR], 95% CI = 1.593, 1.058-2.398), compared to those with a waist circumference from 80 to less than 85cm.2) Those with a BMI less than 18.5 showed the lowest incidence of CML ([aHR], 95% CI = 0.509, 0.278–0.931) in comparison to the reference population with a BMI between 18.5 and 22.9.3) Individuals in the highest quartile of HDL-C had the lowest risk of CML ([aHR], 95% CI = 0.795, 0.657–0.961) compared to those in the lowest HDL-C quartile.A large waist circumference was significantly associated with increased risk of CML, whereas a low BMI and high HDL-C were associated with a reduced risk of CML. This suggests that a large waist circumference may be an independent risk factor of CML, whereas a low BMI and high HDL-C may be association with a protective effect against CML. Table 1. Risk of chronic myeloid leukemia by subgroups of waist circumference, bodey mass index, and high-density lipoprotein cholesterol level. Waist circumference (cm) N Case Duration IR (1000,000 PY) HR (95% CI) Model 1 Model 2 Model 3 Model 4 Model 5 &amp;lt;80.0 1,424,747 236 14493864.7 16.2830 0.644 (0.533, 0.778) 0.858 (0.707, 1.041) 0.859 (0.707, 1.045) 0.836 (0.662, 1.055) 0.853 (0.675, 1.078) 80.0 - 84.9 921,040 193 9344290.4 20.6540 0.816 (0.669, 0.995) 0.876 (0.718, 1.069) 0.876 (0.717, 1.069) 0.866 (0.705, 1.063) 0.843 (0.685, 1.037) 85.0 - 89.9 769,528 197 7785119.0 25.3050 1 (Ref.) 1 (Ref.) 1 (Ref.) 1 (Ref.) 1 (Ref.) 90.0 - 94.9 451,608 116 4551043.2 25.4890 1.008 (0.801, 1.267) 0.963 (0.766, 1.212) 0.965 (0.767, 1.215) 0.976 (0.771, 1.234) 1.016 (0.802, 1.286) 95.0 - 99.9 201,541 68 2022854.6 33.6160 1.329 (1.009, 1.751) 1.267 (0.962, 1.670) 1.274 (0.966, 1.681) 1.302 (0.970, 1.747) 1.401 (1.044, 1.880) ≥100 111,096 38 1108876.8 34.2690 1.356 (0.958, 1.919) 1.352 (0.955, 1.915) 1.365 (0.962, 1.938) 1.421 (0.959, 2.105) 1.593 (1.058, 2.398) Model 1 was not adjusted.Model 2 was adjusted for age and sex.Model 3 was adjusted for age, sex, household income, smoking, alcohol consumption, regular exercise, diabetes mellitus, hypertension, dyslipidemia, and chronic kidney disease.Model 4 was adjusted for age, sex, household income, smoking, alcohol consumption, regular exercise, diabetes mellitus, hypertension, dyslipidemia, chronic kidney disease, and BMI (Continuous).Model 5 was adjusted for age, sex, household income, smoking, alcohol consumption, regular exercise, diabetes mellitus, hypertension, dyslipidemia, chronic kidney disease, and BMI (5 level). Body mass index N Case Duration IR (1000,000 PY) HR (95% CI) Model 1 Model 2 Model 3 Model 4 Model 5 &amp;lt;18.5 143,144 11 1421140.8 0.0077 0.410 (0.225, 0.749) 0.496 (0.272, 0.906) 0.505 (0.276, 0.921) 0.586 (0.319, 1.077) 0.509 (0.278, 0.931) 18.5 - 22.9 1,512,449 290 15308105.8 0.0189 1 (Ref.) 1 (Ref.) 1 (Ref.) 1 (Ref.) 1 (Ref.) 23.0 - 24.9 955,515 239 9697732.1 0.0246 1.300 (1.096, 1.543) 1.131 (0.952, 1.343) 1.120 (0.942, 1.331) 0.998 (0.828, 1.203) 1.060 (0.873, 1.287) 25.0 - 29.9 1,130,207 274 11476143.9 0.0239 1.260 (1.068, 1.486) 1.075 (0.910, 1.269) 1.060 (0.895, 1.256) 0.842 (0.675, 1.051) 0.878 (0.699, 1.104) ≥30.0 138,245 34 1402926.2 0.0242 1.280 (0.897, 1.826) 1.234 (0.865, 1.761) 1.218 (0.849, 1.747) 0.786 (0.500, 1.236) 0.765 (0.483, 1.211) Model 1 was not adjusted.Model 2 was adjusted for age and sex.Model 3 was adjusted for age, sex, household income, smoking, alcohol consumption, regular exercise, diabetes mellitus, hypertension, dyslipidemia, and chronic kidney disease.Model 4 was adjusted for age, sex, household income, smoking, alcohol consumption, regular exercise, diabetes mellitus, hypertension, dyslipidemia, chronic kidney disease, and waist circumference (Continuous).Model 5 was adjusted for age, sex, household income, smoking, alcohol consumption, regular exercise, diabetes mellitus, hypertension, dyslipidemia, chronic kidney disease, and waist circumference (5 level). HDL-C level N Case Duration IR (1000,000 PY) HR (95% CI) Model 1 Model 2 Model 3 Model 4 Q1 (Lowest) 1,007,163 277 10156736.52 0.0273 1 (Ref.) 1 (Ref.) 1 (Ref.) 1 (Ref.) Q2 910,627 202 9242549.22 0.0219 0.802 (0.669, 0.961) 0.851 (0.710, 1.021) 0.853 (0.711, 1.023) 0.851 (0.709, 1.021) Q3 979,148 177 9948872.05 0.0178 0.653 (0.540, 0.788) 0.720 (0.596, 0.870) 0.724 (0.598, 0.876) 0.721 (0.596, 0.873) Q4 (Highest) 982,622 192 9957890.96 0.0193 0.708 (0.589, 0.851) 0.789 (0.656, 0.949) 0.798 (0.660, 0.965) 0.795 (0.657, 0.961) Model 1 was not adjusted.Model 2 was adjusted for age and sex.Model 3 was adjusted for age, sex, household income, smoking, alcohol consumption, regular exercise, diabetes mellitus, hypertension, dyslipidemia, chronic kidney disease, and BMI (5 level).Model 4 was adjusted for age, sex, household income, smoking, alcohol consumption, regular exercise, diabetes mellitus, hypertension, dyslipidemia, chronic kidney disease, and dyslipidemia medication. HDL-C high-density lipoprotein cholesterl, IR incidence rate, PY person-years, HR hazard ratio, CI confidence interval. Citation Format: Ka Young Kim, Kyung Do Han, Sung-Eun Lee. Association between waist circumference, body mass index, high-density lipoprotein cholesterol level, and risk of chronic myeloid leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB415.

Evaluation of the Prime Diet Quality Score from Early Childhood Through Mid-Adolescence

BackgroundFew diet quality indices have been developed and validated for use among children and adolescents. Additionally, many available indices require completion of burdensome dietary assessments. ObjectivesWe aimed to calculate and evaluate the performance of a modified version of the food-based Prime Diet Quality Score (PDQS) derived from different diet assessment methods conducted at 4 time points in a single study population from childhood through adolescence. MethodsAmong 1460 child participants in the Project Viva cohort, we calculated the PDQS in early and mid-childhood and early and mid-adolescence using dietary data obtained from food frequency questionnaire (early childhood: parent report), PrimeScreen (mid-childhood: parent report; early adolescence: self-report) and 24-h recall (mid-adolescence: self-report). We evaluated construct and relative validity and internal reliability of the score in each life stage. ResultsThe PDQS showed a range of scores at all life stages and higher scores were associated with intake of many health-promoting macronutrients and micronutrients (e.g., protein, fiber, and vitamins) in early childhood and mid-adolescence. The PDQS performed similarly to the Youth Healthy Eating Index/Healthy Eating Index (Spearman r = 0.63–0.85) in various assessments. Higher PDQS was associated with expected characteristics including more frequent breakfast eating, family dinners, and vigorous physical activity; with less frequent TV viewing and fast food intake; and with more sleep and higher maternal diet scores during pregnancy. Cross-sectional associations of the PDQS with various anthropometric measurements and biomarkers were inconsistent but generally in the expected directions (e.g., higher PDQS associated with lower triglycerides and insulin and higher HDL cholesterol). Internal reliability was consistent with what has been found for other diet quality indices. ConclusionsThe PDQS can be calculated from data collected using different and brief dietary assessment methods and appears to be a valid and useful measure of overall diet quality in children and adolescents.Project Viva was registered at clinicaltrials.gov as NCT02820402.

Discrepant effect of high-density lipoprotein cholesterol on esophageal and gastric cancer risk in a nationwide cohort.

The relationship between high-density lipoprotein cholesterol (HDL-C) and gastroesophageal cancer is not constant. In this population-based cohort study, 4.518 million cancer-free individuals among those who underwent national cancer screening in 2010 were enrolled and followed up until December 2017. HDL-C level was classified into eight groups at 10mg/dL intervals. The risk of gastroesophageal cancers by HDL-C was measured using adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). During 8years of follow-up, 38,362 gastric and 3022 esophageal cancers developed. Low HDL-C level was associated with an increased risk of gastric cancer; aHR was 1.19 (95% CI 1.09-1.30) for HDL-C  < 30mg/dL, 1.07 (95% CI 1.03-1.12) for HDL-C of 30-39mg/dL, and 1.07 (95% CI 1.03-1.12) for HDL-C of 40-49mg/dL comparing to HDL-C of 60-69mg/dL. HDL-C was positively associated with esophageal cancer risk; aHR was 1.30 (1.12-1.51) for HDL-C of 70-79mg/dL, 1.84 (1.53-2.22) for HDL-C of 80-89mg/dL, 2.10 (1.67-2.61) for HDL-C  ≥ 90mg/dL. These site-specific effects of HDL-C were robust in sensitivity analyses. The range of HDL-C for the lowest cancer risk was different by sex and site. The hazardous effect of low HDL-C on gastric cancer was prominent in never and past smokers, and extremely high HDL-C increased gastric cancer risk (aHR 1.19; 95% CI 1.04-1.36) only in current smokers. Unfavorable effect of high HDL-C on gastroesophageal cancer risk was remarkable in smokers. Low HDL-C increased the risk of gastric cancer, wherein high HDL-C was associated with esophageal cancer risk with discrepancies by sex and smoking status.

Running towards higher HDL cholesterol

Running towards higher HDL cholesterol

Unraveling atherosclerotic cardiovascular disease risk factors through conditional probability analysis with Bayesian networks: insights from the AZAR cohort study

This study aimed at modelling the underlying predictor of ASCVD through the Bayesian network (BN). Data for the AZAR Cohort Study, which evaluated 500 healthcare providers in Iran, was collected through examinations, and blood samples. Two BNs were used to explore a suitable causal model for analysing the underlying predictor of ASCVD; Bayesian search through an algorithmic approach and knowledge-based BNs. Results showed significant differences in ASCVD risk factors across background variables’ levels. The diagnostic indices showed better performance for the knowledge-based BN (Area under ROC curve (AUC) = 0.78, Accuracy = 76.6, Sensitivity = 62.5, Negative predictive value (NPV) = 96.0, Negative Likelihood Ratio (LR−) = 0.48) compared to Bayesian search (AUC = 0.76, Accuracy = 72.4, Sensitivity = 17.5, NPV = 93.2, LR− = 0.83). In addition, we decided on knowledge-based BN because of the interpretability of the relationships. Based on this BN, being male (conditional probability = 63.7), age over 45 (36.3), overweight (51.5), Mets (23.8), diabetes (8.3), smoking (10.6), hypertension (12.1), high T-C (28.5), high LDL-C (23.9), FBS (12.1), and TG (25.9) levels were associated with higher ASCVD risk. Low and normal HDL-C levels also had higher ASCVD risk (35.3 and 37.4), while high HDL-C levels had lower risk (27.3). In conclusion, BN demonstrated that ASCVD was significantly associated with certain risk factors including being older and overweight male, having a history of Mets, diabetes, hypertension, having high levels of T-C, LDL-C, FBS, and TG, but Low and normal HDL-C and being a smoker. The study may provide valuable insights for developing effective prevention strategies for ASCVD in Iran.

Cytokeratin-18 as a Non-invasive Biomarker and its Association with Biochemical Parameters in the Diagnosis of Non-alcoholic Fatty Liver Disease

Objective: Nonalcoholic fatty liver disease (NAFLD) is one of the chronic silent diseases in which its therapeutic options and noninvasive markers of disease activity and severity remain limited. We aimed in this study to assess cytokeratin-18 (CK18) as a new non-invasive biomarker to distinguish between NAFLD stages and its correlation with some biochemical parameters.&#x0D; Methods: A case control study was conducted on a sample of 90 subjects aged 12-79 years, categorized into three groups (nonalcoholic steatohepatitis "NASH", steatosis and controls). CK18, fasting blood glucose (FBG), lipid profile parameters, aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine were determined. Low destiny lipoprotein-cholesterol (LDL-C), and body mass index (BMI) were calculated in addition to performing complete blood count (CBC).&#x0D; Results: The results indicate that the mean level of serum CK18 in NASH cases was significantly higher than steatosis and control groups. CK18 has a positive correlation with triglycerides (TG) total cholesterol (TC), ALT, AST, FBG, urea, creatinine, age, BMI, and LDL-C, and a negative correlation with high density lipoprotein-cholesterol HDL-C. Finally, ROC curve showed that the sensitivity of CK18 test is 77.1% and specificity is 96.6%. The cut-off value for CK18 test is 161 U/L.&#x0D; Conclusions: In this study, a significant relationship was observed between CK18, hepatic enzymes, and NAFLD degrees. CK18 has good accuracy, sensitivity, and specificity in diagnosing NASH.

The correlation between serum asprosin and left ventricular diastolic dysfunction in elderly patients with type 2 diabetes mellitus in the community.

Serum asprosin is expected to become a screening indicator in early-stage diabetic heart disease. The relationship between serum asprosin and left ventricular diastolic dysfunction (LVDD) was studied in elderly patients with type 2 diabetes mellitus in the community. A total of 252 elderly patients with type 2 diabetes mellitus were recruited from Zhuoma Community Care Station and Chengbei West Street Community Care Service Center in Changzhi City of Shanxi Province from November 2019 to July 2021. Patients were divided into the LVDD group (n = 195) and the non-LVDD group (n = 57). The t-test, Mann-Whitney U test, and χ2 test were used to compare indicators between the LVDD group and the non-LVDD group. Pearson or Spearman correlation analysis was adopted to evaluate the correlation between serum asprosin and other clinical data. Multivariate logistic regression analysis was applied to analyze the influencing factors on LVDD. Compared with patients without LVDD, patients with LVDD had a higher level of low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FPG), and asprosin, but a lower level of early diastolic movement speed (A) to diastolic movement velocity (E) (E/A). Asprosin was positively associated with waist circumference (WC), body mass index (BMI), creatinine, triglycerides (P < 0.05), and negatively associated with E/A and high density lipoprotein cholesterol HDL-C (P < 0.05). The risk of LVDD increased with elevated asprosin levels after adjustment for age, systolic blood pressure (SBP), BMI, FPG, and LDL-C. Compared with patients in the lowest tertile of serum asprosin (<275.25 pg/mL), a serum level of asprosin between 275.25-355.08 pg/mL [OR (95% CI) is 2.368 (1.169-4.796), P < 0.05] and asprosin >355.08 pg/mL [OR (95% CI) is 2.549 (1.275-5.095), P < 0.05] patients have a higher risk of left ventricular diastolic dysfunction. Serum asprosin was positively associated with left ventricular diastolic dysfunction, and the risk of LVDD increased significantly with increased serum levels of asprosin.

Very high HDL-C associated with increased mortality in men

Very high HDL-C associated with increased mortality in men

Associations of per- and polyfluoroalkyl substances with maternal metabolic and inflammatory biomarkers in early-to-mid-pregnancy

BackgroundPer- and polyfluoroalkyl substances (PFAS) can disrupt metabolism. Early-to-mid pregnancy is characterized by amplified metabolic processes and inflammation to support maternal adaptations and fetal growth. Thus, we cross-sectionally evaluated whether PFAS are individually and jointly associated with these processes in early-to-mid pregnancy. MethodsPregnant Illinois women (n = 452) provided fasted blood samples at median 17 weeks gestation. We quantified serum perfluorononanoic (PFNA), perfluorooctane sulfonic (PFOS), perfluorooctanoic (PFOA), methyl-perfluorooctane sulfonamide acetic acid (Me-PFOSA-AcOH), perfluorohexanesulfonic (PFHxS), perfluorodecanoic (PFDeA), and perfluoroundecanoic (PFUdA) acid. Key outcomes were plasma glucose, insulin, C-peptide, insulin-like growth factor 1 (IGF-1), adiponectin, leptin, triglycerides, free fatty acids, total cholesterol, high-density lipoprotein (HDL) cholesterol, C-reactive protein, tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and interleukin 6. We calculated homeostatic model assessment for insulin resistance (HOMA-IR), low-density lipoprotein (LDL) cholesterol, and very low-density lipoprotein (VLDL). We evaluated associations of PFAS with each metabolic/inflammatory biomarker individually using covariate-adjusted linear regression and jointly using quantile-based g-computation. ResultsIn linear regression, all PFAS (except Me-PFOSA-AcOH) were negatively associated with insulin, HOMA-IR, and leptin, whereas all PFAS were positively associated with HDL cholesterol. We also observed negative associations of some PFAS with TNF-α and MCP-1; positive associations with adiponectin and total cholesterol also emerged. Additionally, PFOS was positively, whereas Me-PFOSA-AcOH was negatively, associated with triglycerides and VLDL. Each 25% increase in the PFAS mixture was associated with −31.3% lower insulin (95%CI: −45.8, −12.9), −31.9% lower HOMA-IR (95%CI: −46.4, −13.4), and −9.4% lower leptin (95%CI: −17.3, −0.8), but 7.4% higher HDL cholesterol (95%CI: 4.6, 10.3). For most outcomes, the major contributors to the PFAS mixture often differed compared to single-PFAS analyses. ImplicationsIndividual and joint PFAS exposures were associated with markers of maternal metabolism and inflammation in pregnancy. Further investigation is needed to elucidate possible mechanisms and consequences of these findings.

Higher testosterone is associated with higher HDL-cholesterol and lower triglyceride concentrations in older women: an observational study

Objective This study aimed to determine whether concentrations of testosterone and its main precursor after menopause, dehydroepiandrosterone (DHEA), are associated with lipoproteins and other lipids in community-dwelling older women. Methods The Sex Hormones in Older Women (SHOW) study was an observational study of 6358 Australian women, aged at least 70 years, with no prior major adverse cardiovascular event who had sex hormones measured by liquid chromatography–tandem mass spectrometry. Associations between hormones and lipids were examined using multilinear regression adjusted for potential confounders. Results The cross-sectional analyses included 3231 participants, median age 74.0 (interquartile range 71.7–77.9) years. Compared with concentrations in the lowest quartile (Q1), testosterone concentrations in the highest quartiles (Q3 and Q4) were positively associated with high-density lipoprotein cholesterol (HDL-C) (p = 0.002 and p < 0.001, respectively) while Q4 testosterone concentrations were positively associated with total cholesterol (p = 0.038). Q2, Q3 and Q4 testosterone concentrations were significantly inversely associated with triglycerides (TG) (p = 0.024, p = 0.003 and p < 0.001, respectively). For DHEA, Q4 concentrations was positively associated with non-HDL-C (p = 0.024). Conclusions In older women, higher endogenous testosterone concentrations are significantly associated with higher HDL-C and lower TG, indicating a less atherogenic profile. These findings suggest a neutral, or potentially protective, cardiovascular disease effect of testosterone in older women.

The metabolic profiles and body composition of non-obese metabolic associated fatty liver disease.

Metabolic-associated fatty liver disease (MAFLD) is a major cause of chronic liver disease worldwide and is generally thought to be closely related to obesity and diabetes. However, it also affects non-obese individuals, particularly in Asian cultures. Healthy physical examination subjects and MAFLD patients were included in the endocrinology department of Jiangsu Provincial Hospital of Traditional Chinese Medicine. MAFLD was defined as fatty liver in imaging without virus infection, drug, alcohol, or other known causes of chronic liver disease. Non-obese MAFLD was defined as MAFLD in non-obese subjects (BMI<25 kg/m2). The final analysis comprised 1047 participants in total. Of 946 MAFLD patients, 162 (17.12%) were diagnosed with non-obese MAFLD. Non-obese MAFLD patients were older, had lower alanine aminotransferase (ALT), triglyceride, and waist circumference, but had higher high density lipoprotein cholesterol (HDL-c) than obese MAFLD patients. Compared with non-obese healthy controls, non-obese MAFLD patients had higher BMI, ALT, gamma-glutamyl transferase (GGT), uric acid (UA), triglycerides (TG), and low density lipoprotein cholesterol (LDL-c). In terms of body composition, body fat mass (BFM), waist-hip ratio (WHR), percent body fat (PBF), visceral fat area (VFA), and fat mass index (FMI) were lower in non-obese healthy controls than non-obese MAFLD patients. A binary logistic regression analysis revealed that non-obese MAFLD was linked with lower GGT and higher HDL-c. In this study cohort, non-obese MAFLD was present at a prevalence of 13.90%. In contrast to non-obese healthy controls, non-obese MAFLD patients exhibited different metabolic profiles, but they also had different body compositions.