Higher High-density Lipoprotein Cholesterol Research Articles

Genetic variants in the adenosine triphosphate-binding cassette transporter A1 and risk of age-related macular degeneration

Genetic variants in ABCA1 are associated with higher concentrations of high-density lipoprotein (HDL) cholesterol. Higher HDL cholesterol concentrations are observationally and genetically associated with higher risk of age-related macular degeneration (AMD). However, whether amino acid-changing genetic variants in ABCA1 associated with high HDL cholesterol concentrations confer a higher risk of AMD in the general population is currently unknown. We tested this hypothesis. The study included 80,972 individuals (1,370 AMD cases) from the Copenhagen General Population Study (CGPS) and 9,584 individuals (142 AMD cases) from the Copenhagen City Heart Study (CCHS) with 10 to 18 years of follow-up. We created an HDL cholesterol weighted allele score based on amino acid-changing ABCA1 variants with a minor allele frequency above 0.001 and divided it into tertiles. The study included 55% women. Mean age was 58 years. The ABCA1 allele score for the third versus the first tertile was associated with HRs (95% confidence intervals (CIs)) of 1.30 (1.14–1.49) for all-cause AMD, 1.26 (1.06–1.50) for nonneovascular AMD, and 1.31 (1.12–1.53) for neovascular AMD in a multivariable adjusted model. On a continuous scale, higher concentrations of genetically determined HDL cholesterol were associated with higher risk of all-cause AMD, nonneovascular AMD, and neovascular AMD in an age- and sex adjusted model and in a multivariable adjusted model. In conclusion, amino acid-changing genetic variants in ABCA1 associated with higher HDL cholesterol concentrations were also associated with higher risk of AMD, suggesting a role for ABCA1 in AMD pathogenesis.

When "Good" Cholesterol Turns Bad: New research reveals the risks of very high HDL cholesterol levels.

When "Good" Cholesterol Turns Bad: New research reveals the risks of very high HDL cholesterol levels.

THE PLASMA HDL-SUBFRACTION PROFILE IN HYPERTENSIVE PATIENTS WITH HIGH HDL-CHOLESTEROL LEVELS

Objective: The evaluation of cardiovascular risk (CVR) in arterial hypertension includes the estimation of high density lipoprotein (HDL-C). Although HDL-C is considered as a favorite CVR factor, the exact role that HDL-C subfraction profile play in the pathogenesis of atherosclerosis, especially in higher than usual HDL-C levels (>60 mg/dl) is currently under investigation. The aim of this study was to evaluate the plasma HDL subfraction profile of high HDL-C levels in hypertensive patients compared to normotensive subjects. Design and method: We studied 74 hypertensive patients (60 + 13 years, 62 females) and 24 normotensives, apparently healthy subjects (49 + 14 years, 22 females) with HDL-C equal or above 55 mg/dl. Cholesterol, HDL-C, and TG were determined enzymatically while LDL-C was calculated using the Friedewald formula. Plasma HDL particles were separated and determined electrophorically using Lipoprint System HDL Subfractions Kit. Aortic stiffness (c-f PWV) and central BP (cBP) were evaluated by carotid-femoral pulse wave velocity (Complior apparatus). Results: We found that hypertensive patients had increased age, BMI, office systolic and diastolic BP, PWV compared to normotensives. Regarding HDL, 10 HDL fractions were separated: fractions 1-3 were denoted as Large-HDL (L-HDL), fractions 4-7 constituted the Intermediate-HDL (I-HDL), and fractions 8-10 were denoted as Small-HDL (S-HDL) subfraction. Although HDL-C levels were similar between groups (76 + 13 vs. 81 + 17 mg/dl, p = 0.10), the percent distribution (%) of L-HDL was lower in hypertensives compared to normotensives (29.8±4.7% vs. 36.6±6.3%, p<0.001), % I-HDL was similar while % S-HDL was increased (27.3±3.7% vs. 20.4±4.4%, p<0.001). We found a significant negative correlation between L-HDL and SBP (rho = -0.48, p = 0.01) as well as cBP (rho = -0.52, p = 0.008) in younger hypertensive females before menopause (n = 26, 49 + 5 years). Conclusions: L-HDL particles, the most antiatherogenic HDL-C subfraction, were reduced in hypertensive patients with high HDL-C levels compared to normotensive subjects, suggesting that these patients are probably less protected against CV disease compared to normotensive subjects with similar HDL-C and LDL-C levels. Therefore, plasma HDL-subfraction profile might replace the HDL-C evaluation as a better biomarker of CVR in hypertensive patients, especially females before menopause.

Coronary Artery Disease with Elevated Levels of HDL Cholesterol Is Associated with Distinct Lipid Signatures.

Levels of high-density lipoprotein cholesterol (HDL-C) are inversely associated with the incidence of coronary artery disease (CAD). However, the underlying mechanism of CAD in the context of elevated HDL-C levels is unclear. Our study aimed to explore the lipid signatures in patients with CAD and elevated HDL-C levels and to identify potential diagnostic biomarkers for these conditions. We measured the plasma lipidomes of forty participants with elevated HDL-C levels (men with >50 mg/dL and women with >60 mg/dL), with or without CAD, using liquid chromatography-tandem mass spectrometry. We analyzed four hundred fifty-eight lipid species and identified an altered lipidomic profile in subjects with CAD and high HDL-C levels. In addition, we identified eighteen distinct lipid species, including eight sphingolipids and ten glycerophospholipids; all of these, except sphingosine-1-phosphate (d20:1), were higher in the CAD group. Pathways for sphingolipid and glycerophospholipid metabolism were the most significantly altered. Moreover, our data led to a diagnostic model with an area under the curve of 0.935, in which monosialo-dihexosyl ganglioside (GM3) (d18:1/22:0), GM3 (d18:0/22:0), and phosphatidylserine (38:4) were combined. We found that a characteristic lipidome signature is associated with CAD in individuals with elevated HDL-C levels. Additionally, the disorders of sphingolipid as well as glycerophospholipid metabolism may underlie CAD.

Genetic Associations Between Modifiable Risk Factors and Alzheimer Disease

An estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course. However, robust evidence for most of these risk factors is lacking. Effective interventions should target risk factors in the causal pathway to dementia. To comprehensively disentangle potentially causal aspects of modifiable risk factors for Alzheimer disease (AD) to inspire new drug targeting and improved prevention. This genetic association study was conducted using 2-sample univariable and multivariable mendelian randomization. Independent genetic variants associated with modifiable risk factors were selected as instrumental variables from genomic consortia. Outcome data for AD were obtained from the European Alzheimer & Dementia Biobank (EADB), generated on August 31, 2021. Main analyses were conducted using the EADB clinically diagnosed end point data. All analyses were performed between April 12 and October 27, 2022. Genetically determined modifiable risk factors. Odds ratios (ORs) and 95% CIs for AD were calculated per 1-unit change of genetically determined risk factors. The EADB-diagnosed cohort included 39 106 participants with clinically diagnosed AD and 401 577 control participants without AD. The mean age ranged from 72 to 83 years for participants with AD and 51 to 80 years for control participants. Among participants with AD, 54% to 75% were female, and among control participants, 48% to 60% were female. Genetically determined high-density lipoprotein (HDL) cholesterol concentrations were associated with increased odds of AD (OR per 1-SD increase, 1.10 [95% CI, 1.05-1.16]). Genetically determined high systolic blood pressure was associated with increased risk of AD after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.22 [95% CI, 1.02-1.46]). In a second analysis to minimize bias due to sample overlap, the entire UK Biobank was excluded from the EADB consortium; odds for AD were similar for HDL cholesterol (OR per 1-SD unit increase, 1.08 [95% CI, 1.02-1.15]) and systolic blood pressure after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.23 [95% CI, 1.01-1.50]). This genetic association study found novel genetic associations between high HDL cholesterol concentrations and high systolic blood pressure with higher risk of AD. These findings may inspire new drug targeting and improved prevention implementation.

Risk Factors for Premature Coronary Heart Disease in Women Compared to Men: Systematic Review and Meta-Analysis.

Background and Aim: We aimed to systematically examine literature on the prevalence of known modifiable and nonmodifiable risk factors for premature coronary heart disease (PCHD) in women compared with men. Materials and Methods: PubMed, CINAHL, Embase, and Web of Science databases were searched. Review protocol is registered in PROSPERO (CRD42020173216). Quality was assessed using the National Heart, Lung, and Blood Institute tool. Review Manager 5.3 was used for meta-analysis. Effect sizes were expressed as odds ratio (OR) and mean differences/standardized mean differences (SMD) with 95% confidence intervals (CIs) for categorical and continuous variables. Results: In this PCHD cohort (age <65 years), the mean age of presentation in women was 3 years older than men. Women had higher total cholesterol (SMD 0.11; 95% CI 0.00 to 0.23) and higher high-density lipoprotein cholesterol (SMD 0.49; 95% CI 0.29 to 0.69). Women were more likely to have hypertension (OR 1.51, 95% CI 1.42 to 1.60), diabetes mellitus (OR 1.78, 95% CI 1.55 to 2.04), obesity (OR 1.33, 95% CI 1.24 to 1.42), metabolic syndrome (OR 3.73, 95% CI 1.60 to 8.69), stroke (OR 1.63, 95% CI 1.51 to 1.77), peripheral vascular disorder (OR 1.67, 95% CI 1.43 to 1.96), and depression (OR 2.29, 95% CI 1.96 to 2.67). Women were less likely to be smokers (OR 0.60, 95% CI 0.55 to 0.66), have reported alcohol intake (OR 0.36, 95% CI 0.33 to 0.40), and reported use of illicit drug (OR 0.32, 95% CI 0.16 to 0.62). Conclusions: Risk factor profile in PCHD has a clear sex difference that supports early, aggressive, holistic, but sex-specific, approach to prevention.

HDL-cholesterol concentration and its association with coronary artery calcification: a systematic review and meta-analysis

BackgroundCoronary artery calcification (CAC) is a potential risk marker of coronary atherosclerosis that has high specificity and sensitivity. However, the association between high-density lipoprotein cholesterol (HDL-C) concentration and CAC incidence and progression is controversial.MethodsPubMed, Embase, Web of Science, and Scopus were systematically searched to identify relevant observational studies up to March 2023 and assessed the methodological quality using Newcastle-Ottawa Scale (NOS) scale. Random-effects meta-analysis was used to estimate pooled odds ratios (OR) and 95% confidence interval considering heterogeneity across studies.ResultsOf the 2,411 records, 25 cross-sectional (n = 71,190) and 13 cohort (n = 25,442) studies were included in the systematic review. Ten cross-sectional and eight cohort studies were not eligible and were omitted from the meta-analysis. A total of 15 eligible cross-sectional studies (n = 33,913) were included in the meta-analysis and pooled results revealed no significant association between HDL-C and CAC > 0, CAC > 10, or CAC > 100 [pooled OR: 0.99 (0.97, 1.01)]. Meta-analysis of the 5 eligible prospective cohort studies (n = 10,721) revealed no significant protective effect of high HDL-C against CAC > 0 [pooled OR: 1.02 (0.93, 1.13)].ConclusionsAccording to this analysis of observational studies, high HDL-C levels were not found to predict protection against CAC. These results suggest HDL quality rather than HDL quantity is important for certain aspects of atherogenesis and CAC.Registration numberCRD42021292077.

Association of lipid metabolism with pneumonia risk in under-five children in China

ObjectiveThe relationship between lipid metabolism and pneumonia in under-five children remains unclear. The aim of the study was to explore the association of several lipids, lipoproteins and apolipoproteins with the risk of childhood pneumonia, and to initially reveal the mechanisms involved. MethodsThere were 1000 children with confirmed severe pneumonia and 1000 healthy controls (18–59 months old) in the study. Serum levels of several lipids, lipoproteins and apolipoproteins were measured. The occurrence of hypoxaemia and serum level of C-reactive protein were recorded. Multivariate logistic regression and spearman correlation analysis were adopted to assess the correlation between these variables to achieve the research objective. ResultsFirst, higher triglycerides, total cholesterol, LDL cholesterol, VLDL cholesterol and apolipoprotein B levels were associated with the elevated risk of severe pneumonia (OR: 1.407, 95%CI: 1.336∼1.480; OR: 1.947, 95%CI: 1.741∼2.175; OR: 1.153, 95%CI: 1.116∼1.189; OR: 1.310, 95%CI: 1.222∼1.404; OR: 1.075, 95%CI: 1.003∼1.151). Higher HDL cholesterol and apolipoprotein A1 levels were associated with a decreased risk of the disease (OR: 0.903, 95%CI: 0.873∼0.933; OR: 0.921, 95%CI: 0.891∼0.952). Second, higher triglycerides level was associated with an increased risk of hypoxemia in these children (OR: 1.142, 95%CI: 1.072∼1.215). Third, serum HDL cholesterol level was linearly associated with C-reactive protein level in these children (ρ = -0.343, P < 0.001). ConclusionAbnormal levels of several lipids, lipoproteins and apolipoproteins were related to severe childhood pneumonia. The findings that triglycerides and HDL cholesterol were respectively implicated in hypoxaemia and inflammation might partly explain the mechanisms linking lipid metabolism to severe pneumonia.

Association between Obesity and Cardiovascular Disease Risk Factors in Different Age Groups of Adolescents: An Analysis of Data from the Korean National Health and Nutritional Examination Survey.

We investigated the association between obesity and cardiovascular disease risk factors (CVDRFs) in adolescents. We performed a cross-sectional study using the data from 8149 adolescents, aged 10-18 years, included in the Korean National Health and Nutrition Examination Survey (2011-2020). Using the body mass index, we defined "overweight" (≥85th to <95th percentile) and "obese" (≥95th percentile). We analyzed the associations between obesity and CVDRFs (high blood pressure, abnormal lipid profiles, and high fasting glucose levels) by sex and age groups (early [10-12 years], middle [13-15 years], and late [16-18 years] adolescence). When analyzing all the subjects, being overweight was correlated with high blood pressure and abnormal all-lipid profiles in boys and high triglyceride and low high-density lipoprotein cholesterol levels in girls, while obesity was associated with all CVDRFs in both boys and girls. Analyzing separately in the age subgroups, the correlation between obesity and CVDRFs tended to be shown earlier in boys than in girls, and obesity tended to be associated with CVDRFs earlier than being overweight. The association between obesity and CVDRFs may begin to be shown at different periods of youth, depending on the degree of obesity, CVDRF variables, and sex.

Nut and seed consumption is inversely associated with metabolic syndrome in females but not males: findings from the 2005–2018 NHANES data

PurposeTo assess the association between nut and seed consumption, both combined and separately, and metabolic syndrome and its components, including fasting glucose, triglycerides, high-density lipoprotein (HDL) cholesterol, central obesity, and blood pressure.MethodsThis cross-sectional analysis used data from 22,687 adults (aged ≥ 18 years) involved in seven cycles (2005–2018) of the National Health and Nutrition Examination Survey (NHANES). Habitual nut and seed intakes were estimated by the Multiple Source Method using data from two 24-h dietary recalls. Metabolic syndrome was ascertained using biochemical data and self-reported medication use. Sex-specific effect estimates were obtained using logistic and linear regressions adjusting for lifestyle and socioeconomic confounders.ResultsCompared to non-consumers, female, but not male, habitual consumers of either nuts or seeds had lower odds of having metabolic syndrome (OR: 0.83, 95% CI 0.71, 0.97). Both nut intake alone and seed intake alone were inversely associated with high fasting glucose and low HDL-cholesterol in females compared to non-consumers. When restricted to habitual consumers only, the combined intake of nuts and seeds at 6 g/day was associated with the lowest triglycerides and highest HDL-cholesterol in females. Combined consumption of nuts and seeds up to one ounce-equivalent (15 g) per day, but not in higher intake levels, was inversely associated with metabolic syndrome, high fasting glucose, central obesity, and low HDL-cholesterol in females.ConclusionsNut and seed consumption, both separately or combined, below 15 g/day was inversely associated with metabolic syndrome and its component conditions in females but not males.

Impact of short- and long-term exposure to air pollution on lipid profile in adults aged 20 to 69 years in Tehran Province, Iran

There are inconsistent findings concerning the impact of air pollution on different lipid measures and there is a lack of data for the highly polluted Middle East and North Africa (MENA) region. To assess the association between short-term exposure to five major air pollutants including PM10, NO2, SO2, O3, and CO, and lipid profiles as well as long-term exposure to these pollutants and incident dyslipidemia. A total of 5,821 participants (3,387 women) aged 20–69 years at baseline were followed from 2001 to 2018, every three years. The mixed-effects model evaluated the impact of air pollutants on blood lipids including TC, TG, HDL-C, LDL-C, and non-HDL-C. The proportional hazards Weibull model estimated the long-term impacts of air pollutants on incident dyslipidemia. Applying the Bonferroni correction, the significance level of 0.0014 (0.05/35) and 0.0033 (0.05/15) was set for short- and long-term scenarios, respectively. In the short term, SO2 and CO had consistent unfavorable effects on lipid profiles, including TC, TG, LDL-C, non-HDL-C, and HDL-C (only for CO). Moreover, short-term exposure to O3 and NO2 had negative associations with TG, LDL-C, HDL-C, and TC (only NO2) and positive associations with HDL-C. Generally, in a long-term manner, CO was associated with a higher incidence of high TC, high TG, and low HDL-C; NO2 and O3 were associated with a lower incidence of high TG and low HDL-C; 1- and 2-year exposure to PM10 was associated with lower incidence of low HDL-C and 3-year exposure to PM10 was associated with lower high TC and high non-HDL-C. In conclusion, given the robust unfavorable impact of CO on lipid profiles in both short- and long-term periods, more interventions should be conducted to reduce the impact of CO exposure.

Favorable Effect of High-Density Lipoprotein Cholesterol on Gastric Cancer Mortality by Sex and Treatment Modality.

Studies on the effects of high-density lipoprotein cholesterol (HDL-C) on gastric cancer mortality are few, and the results are inconsistent. In this study, we investigated the effects of HDL-C on gastric cancer mortality and conducted sub-group analysis by sex and treatment modality. Newly diagnosed patients with gastric cancer (n = 22,468) who underwent gastric cancer screening between January 2011 and December 2013 were included and followed up until 2018. A validation cohort (n = 3379) that had newly diagnosed gastric cancer from 2005 to 2013 at a university hospital, was followed up until 2017. HDL-C was inversely related with mortality; adjusted hazard ratio (aHR) 0.90 (95% confidence interval [CI], 0.83-0.98) for HDL-C of 40-49 mg/dL, 0.86 (0.79-0.93) for HDL-C of 50-59 mg/dL, 0.82 (0.74-0.90) for HDL-C of 60-69 mg/dL, and 0.78 (0.69-0.87) for HDL-C ≥ 70 mg/dL compared to HDL-C < 40 mg/dL. In the validation cohort, HDL-C was also inversely associated with mortality; aHR 0.81 (0.65-0.99) for HDL-C of 40-49 mg/dL, 0.64 (0.50-0.82) for HDL-C of 50-59 mg/dL, and 0.46 (0.34-0.62) for HDL-C ≥ 60 mg/dL compared to HDL-C < 40 mg/dL. The two cohorts demonstrated that higher HDL-C was associated with a low risk of mortality in both sexes. In validation cohort, this association was observed in both gastrectomy and endoscopic resection (p for trend < 0.001) as more remarkable in endoscopic resection group. In this study, we explored that an increased HDL-C reduced mortality in both sexes and curative resection group.

Longitudinal association of hypertension and dyslipidemia with cognitive function in community-dwelling older adults: the SONIC study

The associations among cognitive function, hypertension, and dyslipidemia in older adults are controversial. Therefore, we investigated the associations among cognitive decline, hypertension, dyslipidemia, and their combination in community-dwelling older people in their 70s, 80s, and 90s in the long-term observational Septuagenarians, Octogenarians, Nonagenarians, Investigation with Centenarians (SONIC) study. We administered the Montreal Cognitive Assessment Japanese version (MoCA-J) by trained geriatricians and psychologists, and conducted blood testing and blood pressure (BP) measuring by medical staff involving 1186 participants. We performed multiple regression analysis to assess the relationships among hypertension, dyslipidemia, their combination, and lipid and BP levels with cognitive function at the 3-year follow-up after adjusting for covariate factors. At the baseline, the percentage of the combination of hypertension and dyslipidemia was 46.6% (n = 553), hypertension was 25.6% (n = 304), dyslipidemia was 15.0% (n = 178), and that without hypertension or dyslipidemia was 12.7% (n = 151). Conducting multiple regression analysis, no significant correlation was found between the combination of hypertension and dyslipidemia and MoCA-J score. In the group with the combination, high high-density lipoprotein cholesterol (HDL) levels resulted in higher MoCA-J scores at the follow-up (β = 0.06; P < 0.05) and high diastolic BP (DBP) also resulted in higher MoCA-J scores (β = 0.08; P < 0.05). The results suggest that high HDL and DBP levels of individuals with HT & DL and high SBP levels of individuals with HT were associated with cognitive function in community-dwelling older adults.In the SONIC study, which is an epidemiological study of Japanese older persons aged 70 years or older, a disease-specific examination suggested that high HDL and DBP levels of individuals with hypertension & dyslipidemia and high SBP levels of individuals with hypertension were associated with maintaining cognitive function in community-dwelling older adults

Effect of Omega-3 on lipid profile in type 2 diabetic patients

Diabetic complication is a major health concern , especially uncontrolled lipid profile, contributing to cardiac, renal and multisystem disorders. To evaluate the effect of 2 months supplementation of Omega-3 on lipid profile in type 2 diabetic patients and in comparison with the control. This non-randomized clinical trial was conducted at Al-Wafa'a Center for Diabetes Management and Research in Mosul City in the period from 1st of February 2012 to the 1st of July 2012. A total number of 84 patients (42 males and 42 females) diagnosed with type 2 diabetes mellitus (T2DM) for 2-5 years and were treated with metformin (dose of 500 mg twice daily) + glibenclamide (dose of 2.5 mg once daily) with no other liver or renal disorders, the patients were divided into two groups: First group included 50 patients with age ranged from 37 to 61 years, the patients were given Omega-3 capsules (1000 mg twice daily) for two months (Omega-3 group). The second group included the remaining 34 diagnosed diabetic patients, matched with the first group by age, sex , and BMI and considered as (control group). Fasting blood samples were taken from the first group at the beginning then after two months of Omega-3 use and from the control group once. The sera obtained from all participants in this study were used to measure lipid profile parameters by using the commercial kits, serum low-density lipoprotein cholesterol (LDL-c) was calculated using Friedewald equation. Atherogenic index (AI) was recognized by simple equation and BMI measured by dividing weight in (kg) by square of height in (meter). There was a significant reduction of serum triglycarides (TG) level and atherogenic index but no significant changes in total cholesterol (TC), high density lipoprotein-cholesterol HDL-c, nor in LDL-c level after 2 months therapy with Omega-3 and in comparison with the control group. The use of Omega-3 supplementation for two months in type 2 diabetic patients resulted in significant reduction in the serum TG level and atherogenic index but there was no effect on the other lipid profile parameters. This may be of therapeutic importance in lowering of the cardiovascular risk factors in patients with T2DM.

Exogenous exposures shape genetic predisposition to lipids, Alzheimer's, and coronary heart disease in the MLXIPL gene locus.

Associations of single nucleotide polymorphisms (SNPs) of the MLXIPL lipid gene with Alzheimer's (AD) and coronary heart disease (CHD) and potentially causal mediation effects of their risk factors, high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG), were examined in two samples of European ancestry from the US (22,712 individuals 587/2,608 AD/CHD cases) and the UK Biobank (UKB) (232,341 individuals; 809/15,269 AD/CHD cases). Our results suggest that these associations can be regulated by several biological mechanisms and shaped by exogenous exposures. Two patterns of associations (represented by rs17145750 and rs6967028) were identified. Minor alleles of rs17145750 and rs6967028 demonstrated primary (secondary) association with high TG (lower HDL-C) and high HDL-C (lower TG) levels, respectively. The primary association explained ~50% of the secondary one suggesting partly independent mechanisms of TG and HDL-C regulation. The magnitude of the association of rs17145750 with HDL-C was significantly higher in the US vs. UKB sample and likely related to differences in exogenous exposures in the two countries. rs17145750 demonstrated a significant detrimental indirect effect through TG on AD risk in the UKB only (βIE = 0.015, pIE = 1.9 × 10-3), which suggests protective effects of high TG levels against AD, likely shaped by exogenous exposures. Also, rs17145750 demonstrated significant protective indirect effects through TG and HDL-C in the associations with CHD in both samples. In contrast, rs6967028 demonstrated an adverse mediation effect through HDL-C on CHD risk in the US sample only (βIE = 0.019, pIE = 8.6 × 10-4). This trade-off suggests different roles of triglyceride mediated mechanisms in the pathogenesis of AD and CHD.

Evaluation of low-density lipoprotein cholesterol equations by cross-platform assessment of accuracy-based EQA data against SI-traceable reference value.

Low-density lipoprotein cholesterol (LDLC) is the primary cholesterol target for the diagnosis and treatment of cardiovascular disease (CVD). Although beta-quantitation (BQ) is the gold standard to determine LDLC levels accurately, many clinical laboratories apply the Friedewald equation to calculate LDLC. As LDLC is an important risk factor for CVD, we evaluated the accuracy of Friedewald and alternative equations (Martin/Hopkins and Sampson) for LDLC. We calculated LDLC based on three equations (Friedewald, Martin/Hopkins and Sampson) using the total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDLC) in commutable serum samples measured by clinical laboratories participating in the Health Sciences Authority (HSA) external quality assessment (EQA) programme over a 5years period (number of datasets, n=345). LDLC calculated from the equations were comparatively evaluated against the reference values, determined from BQ-isotope dilution mass spectrometry (IDMS) with traceability to the International System of Units (SI). Among the three equations, Martin/Hopkins equation derived LDLC had the best linearity against direct measured (y=1.141x-14.403; R2=0.8626) and traceable LDLC (y=1.1692x-22.137; R2=0.9638). Martin/Hopkins equation (R2=0.9638) had the strongest R2 in association with traceable LDLC compared with the Friedewald (R2=0.9262) and Sampson (R2=0.9447) equation. The discordance with traceable LDLC was the lowest in Martin/Hopkins (median=-0.725%, IQR=6.914%) as compared to Friedewald (median=-4.094%, IQR=10.305%) and Sampson equation (median=-1.389%, IQR=9.972%). Martin/Hopkins was found to result in the lowest number of misclassifications, whereas Friedewald had the most numbers of misclassification. Samples with high TG, low HDLC and high LDLC had no misclassification by Martin/Hopkins equation, but Friedewald equation resulted in ∼50% misclassification in these samples. The Martin/Hopkins equation was found to achieve better agreement with the LDLC reference values as compared to Friedewald and Sampson equations, especially in samples with high TG and low HDLC. Martin/Hopkins derived LDLC also enabled a more accurate classification of LDLC levels.

Novel Metabolic Subtypes in Pregnant Women and Risk of Early Childhood Obesity in Offspring

The in utero metabolic milieu is associated with offspring adiposity. Standard definitions of maternal obesity (according to prepregnancy body mass index [BMI]) and gestational diabetes (GDM) may not be adequate to capture subtle yet important differences in the intrauterine environment that could be involved in programming. To identify maternal metabolic subgroups during pregnancy and to examine associations of subgroup classification with adiposity traits in their children. This cohort study included mother-offspring pairs in the Healthy Start prebirth cohort (enrollment: 2010-2014) recruited from University of Colorado Hospital obstetrics clinics in Aurora, Colorado. Follow-up of women and children is ongoing. Data were analyzed from March to December 2022. Metabolic subtypes of pregnant women ascertained by applying k-means clustering on 7 biomarkers and 2 biomarker indices measured at approximately 17 gestational weeks: glucose, insulin, Homeostatic Model Assessment for Insulin Resistance, total cholesterol, high-density lipoprotein cholesterol (HDL-C), triglycerides, free fatty acids (FFA), HDL-C:triglycerides ratio, and tumor necrosis factor α. Offspring birthweight z score and neonatal fat mass percentage (FM%). In childhood at approximately 5 years of age, offspring BMI percentile, FM%, BMI in the 95th percentile or higher, and FM% in the 95th percentile or higher. A total of 1325 pregnant women (mean [SD] age, 27.8 [6.2 years]; 322 [24.3%] Hispanic, 207 non-Hispanic Black [15.6%], and 713 [53.8%] non-Hispanic White), and 727 offspring with anthropometric data measured in childhood (mean [SD] age 4.81 [0.72] years, 48% female) were included. We identified the following 5 maternal metabolic subgroups: reference (438 participants), high HDL-C (355 participants), dyslipidemic-high triglycerides (182 participants), dyslipidemic-high FFA (234 participants), and insulin resistant (IR)-hyperglycemic (116 participants). Compared with the reference subgroup, women in the IR-hyperglycemic and dyslipidemic-high FFA subgroups had offspring with 4.27% (95% CI, 1.94-6.59) and 1.96% (95% CI, 0.45-3.47) greater FM% during childhood, respectively. There was a higher risk of high FM% among offspring of the IR-hyperglycemic (relative risk, 8.7; 95% CI, 2.7-27.8) and dyslipidemic-high FFA (relative risk, 3.4; 95% CI, 1.0-11.3) subgroups; this risk was of greater magnitude compared with prepregnancy obesity alone, GDM alone, or both conditions. In this cohort study, an unsupervised clustering approach revealed distinct metabolic subgroups of pregnant women. These subgroups exhibited differences in risk of offspring adiposity in early childhood. Such approaches have the potential to refine understanding of the in utero metabolic milieu, with utility for capturing variation in sociocultural, anthropometric, and biochemical risk factors for offspring adiposity.

Abstract 6459: Developed and persistent dyslipidemia is associated with increased risk of gastric cancer in a prospective study

Abstract Background: Increasing evidence suggests that metabolic disorders are a risk factor for gastric cancer. However, there is a lack of evidence on whether changes and persistence of metabolic disorders affect the subsequent gastric cancer occurrence. Therefore, this study aimed to evaluate the effects of changes or persistence in metabolic syndrome and its components' status on the incidence of gastric cancer among Korean population. Methods: This study comprised 59,671 individuals from the Health Examinees Study who had baseline surveys from 2004 to 2012 and repeated measurements from 2012 to 2016; and were followed up until 2018. Metabolic syndrome and its components were defined according to the National Cholesterol Education Program Adult Treatment Panel III and modified based on Korean population criteria. Participants were categorized into free, developed, recovered, and persistent metabolic syndrome and its components. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for gastric cancer incidence using multivariable cox proportional hazard models with age as a time scale. Results: During the mean follow-up of 9.4 years, 312 subjects were newly diagnosed with gastric cancer. Compared with the metabolic syndrome-free group, the persistent group had a higher incidence of gastric cancer (HR 1.37, 95% CI 1.02-1.84). Among individual components, the developed-high triglycerides group had the highest gastric cancer incidence (HR 1.52, 95% CI 1.12-2.05), followed by the persistent group (HR 1.40, 95% CI 1.04-1.90) compared to the free group. The low HDL-cholesterol persistent group (HR 1.45, 95% CI 1.08-1.93) showed a higher incidence than in the free group. In the subgroup analysis, we found association between high triglycerides developed and gastric cancer in men, while for women, the associations were significant between high triglycerides and low HDL-cholesterol persistent groups and gastric cancer incidence. Conclusions: In this prospective cohort study, we found that developed or persistent dyslipidemia, assessed as abnormal triglycerides and low HDL-cholesterol, were associated with an increased incidence of gastric cancer. These findings suggest that effective management of dyslipidemia may reduce gastric cancer risk. Keywords: Gastric cancer, Dyslipidemia, Metabolic syndrome, Prospective cohort Citation Format: Dan Huang, Woo-Kyoung Shin, Katherine De la Torre, Sukhong Min, Aesun Shin, Jong-Koo Lee, Hyung-Ho Kim, Daehee Kang. Developed and persistent dyslipidemia is associated with increased risk of gastric cancer in a prospective study. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6459.

Clinical relevance of serum lipids in the carcinogenesis of oral squamous cell carcinoma

BackgroundDyslipidaemia is associated with cancers. However, the specific expression of serum lipids in oral potentially malignant disorders (OPMD) and oral squamous cell carcinoma (OSCC) remains unclear, and it remains unknown whether serum lipids are associated with the development of OPMD and OSCC. This study investigated the serum lipid profiles of OPMD and OSCC patients, and the association of serum lipids with the occurrence of OPMD and OSCC.MethodsA total of 532 patients were recruited from the Affiliated Hospital of Stomatology, Nanjing Medical University. Serum lipid parameters including total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A (Apo-A), apolipoprotein B (Apo-B), and lipoprotein (a) (Lpa) were analysed, and clinicopathological data were collected for further analysis. Furthermore, a regression model was used to evaluate the relationship between serum lipids and the occurrence of OSCC and OPMD.ResultsAfter adjusting for age and sex, no significant differences were observed in serum lipid or body mass index (BMI) between OSCC patients and controls (P > 0.05). HDL-C, Apo-A, and Apo-B levels were lower in OSCC patients than in OPMD patients (P < 0.05); HDL-C and Apo-A levels were higher in OPMD patients than in controls (P < 0.05). Furthermore, female OSCC patients had higher Apo-A and BMI values than males. The HDL-C level was lower in patients under 60 years of age than in elders (P < 0.05); and age was related to a higher risk of developing OSCC. Female patients with OPMD had higher TC, HDL-C, and Apo-A levels than males (P < 0.05); OPMD patients over 60 years of age had higher HDL-C than youngers (P < 0.05), whereas the LDL-C level was lower in elders (P < 0.05). The HDL-C and BMI values of the patients with oral leukoplakia (OLK) with dysplasia were more elevated than those of the oral lichen planus group, and the LDL-C, and Apo-A levels in patients with OLK with dysplasia were decreased (P < 0.05). Sex, high HDL-C and Apo-A values were associated with the development of OPMD.ConclusionSerum lipids exhibited certain differences according to the occurrence and development of OSCC; high levels of HDL-C and Apo-A might be markers for predicting OPMD.

Changes in high-density lipoprotein cholesterol with risk of Cardiovascular Disease among initially high-density lipoprotein-high participants

BackgroundHigh-density lipoprotein cholesterol’s (HDL-C) long-held status as a cardiovascular disease (CVD) preventative has been called into question. Most of the evidence, however, focused on either the risk of death from CVD, or on single time point level of HDL-C. This study aimed to determine the association between changes in HDL-C levels and incident CVD in individuals with high baseline HDL-C levels (≥ 60 mg/dL).Methods77,134 people from the Korea National Health Insurance Service-Health Screening Cohort were followed for 517,515 person-years. Cox proportional hazards regression was used to evaluate the association between change in HDL-C levels and the risk of incident CVD. All participants were followed up until 31 December 2019, CVD, or death.ResultsParticipants with the greatest increase in their HDL-C levels had higher risks of CVD (adjusted hazard ratio [aHR], 1.15; 95% confidence interval [CI], 1.05–1.25) and CHD (aHR 1.27, CI 1.11–1.46) after adjusting for age, sex, household income, body mass index, hypertension, diabetes mellitus, dyslipidemia, smoking, alcohol consumption, moderate-to-vigorous physical activity, Charlson comorbidity index, and total cholesterol than those with the lowest increase in HDL-C levels. Such association remained significant even among participants with decreased low-density lipoprotein cholesterol (LDL-C) levels for CHD (aHR 1.26, CI 1.03–1.53).ConclusionsIn people with already high HDL-C levels, additional increases in HDL-C levels may be associated with an increased risk of CVD. This finding held true irrespective of the change in their LDL-C levels. Increasing HDL-C levels may lead to unintentionally elevated risk of CVD.