Higher High-density Lipoprotein Cholesterol Levels Research Articles

HDL-cholesterol confers sensitivity of immunotherapy in nasopharyngeal carcinoma via remodeling tumor-associated macrophages towards the M1 phenotype

BackgroundThe sustained effectiveness of anti-programmed cell death protein-1/programmed death-ligand 1 treatment is limited to a subgroup of patients with advanced nasopharyngeal carcinoma (NPC), and the specific biomarker determining the response...

The serum metabolomic profiles of atrial fibrillation patients treated with direct oral anticoagulants or vitamin K antagonists

AimsLong-term oral anticoagulation is the primary therapy for preventing ischemic stroke in patients with atrial fibrillation (AF). Different types of oral anticoagulant drugs can have specific effects on the metabolism of patients. Here we characterize, for the first time, the serum metabolomic and lipoproteomic profiles of AF patients treated with anticoagulants: vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs). Materials and methodsSerum samples of 167 AF patients (median age 78 years, 62 % males, 70 % on DOACs treatment) were analyzed via high resolution 1H nuclear magnetic resonance (NMR) spectroscopy. Data on 25 metabolites and 112 lipoprotein-related fractions were quantified and analyzed with multivariate and univariate statistical approaches. Key findingsOur data provide evidence that patients treated with VKAs and DOACs present significant differences in their profiles: lower levels of alanine and lactate (odds ratio: 1.72 and 1.84), free cholesterol VLDL-4 subfraction (OR: 1.75), triglycerides LDL-1 subfraction (OR: 1.80) and 4 IDL cholesterol fractions (ORs ∼ 1.80), as well as higher levels of HDL cholesterol (OR: 0.48), apolipoprotein A1 (OR: 0.42) and 7 HDL cholesterol fractions/subfractions (ORs: 0.40–0.51) are characteristic of serum profile of patients on DOACs' therapy. SignificanceOur results support the usefulness of NMR-based metabolomics for the description of the effects of oral anticoagulants on AF patient circulating metabolites and lipoproteins. The higher serum levels of HDL cholesterol observed in patients on DOACs could contribute to explaining their reduced cardiovascular risk, suggesting the need of further studies in this direction to fully understand possible clinical implications.

The impact of duration and severity of obesity exposure on cardiometabolic health

PurposeDuration and severity of exposure to excess adipose tissue are important risk factors for complications, but are generally not examined in conjunction. We developed a metric considering both factors to examine the relationship between obesity-related complications and parameters of cardiometabolic health in patients undergoing a metabolic bariatric procedure (MBS).Materials & MethodsData from patients screened for primary MBS between 2017 and 2021 were analyzed. The Obesity Exposure score (OBES), based on self-reported years of life with a BMI ≥ 25 kg/m2, was calculated with increased weighting applied for higher BMI categories. Multivariate logistic regression analysis was performed, adjusting for multiple potential confounders.ResultsIn total, 2441 patients were included (76% female, age 42.1 ± 11.9 years, BMI 42.0 ± 4.9 kg/m2). OBES was positively related to myocardial infarction, atrial fibrillation and renal function loss (per 10 OBES-units: OR 1.31, 95%CI [1.11–1.52], p = 0.002; OR 1.23, 95% CI [1.06–1.44], p = 0.008; and OR 1.26, 95% CI [1.04–1.51], p = 0.02). OBES was negatively associated with obstructive sleep apnea syndrome (OSAS) (OR 0.90, 95% CI [0.83–0.98], p = 0.02). In patients without obesity-related complications, OBES was related to lower HbA1c and higher HDL-cholesterol levels (ß -0.5 95% CI [-0.08-.0.02] p < 0.001 and ß 0.02 [0.00–0.04] p = 0.01).ConclusionOBES was related to myocardial infarction, atrial fibrillation and renal function loss in patients applying for MBS. OBES was negatively related to OSAS, possibly because undiagnosed years were not taken into account. In the absence of obesity-related complications, OBES was not related to metabolic blood markers. Our data may aid in improving perioperative risk assessments.Graphical

The associations of psychopathology and metabolic parameters with serum bilirubin levels in patients with acute-episode and drug-free schizophrenia: a 5-year retrospective study using an electronic medical record system

BackgroundThe oxidative system plays an important role in the pathogenesis of schizophrenia. Inconsistent associations were found between hyperbilirubinemia and psychopathology as well as glycolipid metabolism in patients with schizophrenia at different episodes. This current study aimed to examine these associations in patients with acute-episode and drug-free (AEDF) schizophrenia.MethodsThis is a retrospective study using 5 years of data from May 2017 to May 2022 extracted from the electronic medical record system of Chaohu Hospital of Anhui Medical University. Healthy controls (HCs) from the local medical screening center during the same period were also included. Participants’ data of the bilirubin levels [total bilirubin (TB), conjugated bilirubin (CB), unconjugated bilirubin (UCB)], glycolipid metabolic parameters and the score of the Brief Psychiatric Rating Scale (BPRS) were collected.ResultsA total of 1468 case records were identified through the initial search. After screening, 89 AEDF patients and 100 HCs were included. Compared with HCs, patients had a higher CB level, and lower levels of glycolipid metabolic parameters excluding high density lipoprotein-cholesterol (HDL-C) (all P < 0.001). Binary logistic regression analyses revealed that high bilirubin levels in the patients were independently associated with higher total and resistance subscale scores of BPRS, a higher HDL-C level, and lower total cholesterol and triglyceride levels (all P < 0.05).ConclusionBilirubin levels are elevated in patients with AEDF schizophrenia. Patients with high bilirubin levels have more severe psychopathology and relatively optimized glycolipid metabolism. In clinical practice, regular monitoring of bilirubin levels in this patient population should be carried out.

Serum high-density lipoprotein cholesterol levels predict early recurrence and prognosis of intrahepatic cholangiocarcinoma after surgical resection

IntroductionDysregulation in lipid metabolism contributes to the occurrence and development of various cancers. The connection between changes in lipid metabolism and the development of intrahepatic cholangiocarcinoma remains uncertain. Our objective was to investigate the significance of blood lipid levels in patients with intrahepatic cholangiocarcinoma who have undergone surgery. MethodsNinety-seven ICC patients who underwent surgery were retrospectively enrolled. After 92.2 months of follow-up, the Kaplan-Meier analysis and Cox proportional hazard model were used to calculate overall survival and recurrence-free survival. ResultsThe median age of this cohort was 56 years, and 79 (81.4 %) of them were male. Eighty-eight (90.7 %) patients presented with tumor recurrence and 73 (75.3 %) died. In multivariate analyses, high-density lipoprotein cholesterol level (<0.91 vs. ≥ 0.91 mmol/L, hazard ratio [HR] = 2.55; 95 % CI: 1.38–4.71), lymph node metastasis (Yes vs. No, HR = 2.58; 95 % CI: 1.28–5.19), etiology factor (chronic HBV infection vs. others, HR = 0.5; 95 % CI: 0.28–0.88) and multiple tumor lesions (Yes vs. No, HR = 1.85; 95 % CI: 1.01–3.39) were independent predictors of overall survival. However, only high-density lipoprotein cholesterol level (HR = 1.86; 95 % CI: 1.19–2.92) emerged as the independent factor for recurrence-free survival. High-density lipoprotein cholesterol level (HR = 2.07; 95 % CI: 1.26–3.41), etiology factor (HR = 0.49; 95 % CI: 0.29–0.84), and multiple tumor lesions (HR = 2.00; 95 % CI: 1.14–3.51) were independent predictors of early recurrence. For patients who did not experience the spread of cancer to the lymph nodes, there was a significant correlation between the level of high-density lipoprotein cholesterol and their overall survival, recurrence-free survival, and early recurrence. For patients with low pre-operation high-density lipoprotein cholesterol levels, high post-operation high-density lipoprotein cholesterol levels were associated with better prognosis. ConclusionsLow serum high-density lipoprotein cholesterol level might serve as a sign of poor clinical outcomes (overall survival and recurrence-free survival) and early recurrence among intrahepatic cholangiocarcinoma patients. Strengthening the monitoring and intervention of intrahepatic cholangiocarcinoma patients with poor prognosis might be critical for improving the prognosis.

#1672 High level of HDL-C is associated with a higher risk of ESRD and all-cause mortality in patients with DM and CKD

Abstract Background and Aims Previous studies have regarded high-density lipoprotein cholesterol (HDL-C) as ‘good cholesterol’; however, recent research has unveiled a higher incidence of adverse events among individuals with extremely elevated HDL-C levels. Method Two cohorts of subjects were analyzed in this study. In the first cohort, a total of 375 participants with DKD who underwent renal-biopsy between January 2008 and September 2020, from West China Hospital T2DM-DKD cohort, were enrolled for the longitudinal observational study. Additionally, 3,262 participants with DM and chronic kidney disease (CKD) from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were included. Kaplan-Meier curves and Cox proportional hazard models were used to analyze the association between HDL-C concentration and the incidence of end-stage renal disease (ESRD) as well as all-cause mortality. Results Patients were divided into three groups based on HDL-C levels. After a median follow-up of 36 months, 44% of the patients developed ESRD in T2DM-DKD cohort. Patients in Group 3 (HDL-C ≥1.55 mmol/L) exhibited a higher risk of ESRD compared to Group 1 (HDL-C &amp;lt;1.03 mmol/L). After adjusting for confounders, Group 3 patients still had a significantly higher risk of ESRD (adjusted HR: 1.68, 95% CI: 1.03, 2.71). Analysis of HDL subfractions revealed that a higher HDL3/HDL2 ratio was associated with a lower risk of ESRD. Furthermore, in the NHANES cohort, higher HDL-C levels were linked to a higher risk of all-cause mortality during a median follow-up of 75 months as the result of the weighted Kaplan-Meier curves (p = 0.02). Notably, in patients with CKD stages 1-2, Group 3 participants had a significantly higher hazard ratio (HR: 1.61, 95% CI: 1.19, 2.19) after adjusting for confounders. Conclusion This study challenges the notion of HDL-C as ‘good cholesterol’ in patients with DKD, as higher HDL-C levels were associated with increased risks of ESRD and all-cause mortality. Additionally, the study highlights the potential protective effect of a higher HDL3/HDL2 ratio against ESRD. These findings contribute to reevaluating the role of HDL-C and its subfractions in DKD patients.

#1439 Risk factors and significance of a reduction of serum albumin after start of PD

Abstract Background and Aims A reduction in the serum level of albumin following the initiation of peritoneal dialysis (PD) has been reported to associate with impaired survival. Our aim was to identify pre-PD risk factors of drop of serum albumin, and to estimate how a decrease in albumin level affects PD patients’ survival prognosis. Method We included all adult patients who had been on PD for at least half a year in the Helsinki area in Finland during the years 2004 to 2019. Patients who had a dialysis history longer than 1 year before transferal to PD were excluded. We analysed the serum albumin level at start of PD and the last available albumin level before 6 months after start of PD. A 20% reduction of serum albumin was considered significant. Logistic regression was used to assess the association between risk factors (age, sex, primary kidney disease, comorbidities, laboratory variables) and a 20% drop of serum albumin. Cox regression was employed to study the effect of albumin drop on survival with adjustment for confounders. Results Of 379 patients, 80 (21%) showed a reduction of serum albumin of at least 20% after start of PD. High age, high albumin level at start of PD, high level of HDL cholesterol and low level of ionized calcium all associated independently with the risk of an albumin drop in the logistic regression analysis. The albumin level at start (hazard ratio 0.94 per one g/l increment, 95% CI 0.89-0.98) and a 20% or larger drop of albumin level (HR 2.3, 95% CI 1.4-3.9) were connected to impaired survival irrespective of each other. Other independent predictors of worse survival were high age, peripheral vascular disease, a history of stroke, and diabetes. Conclusion A drop of serum albumin after start of PD is frequent and associates with impaired survival. Drop of albumin is more common among elderly patients and those with high values HDL cholesterol or low levels of ionized calcium.

Higher high-density lipoprotein cholesterol levels increased vertebral osteoporotic fracture, but reduced hip fracture in men based on the National Health Insurance Service-National Health Screening Cohort

BACKGROUND CONTEXTLipids are currently known to play an important role in bone metabolism. PURPOSEThis study aimed to investigate the effect of high-density lipoprotein cholesterol (HDL-C) on osteoporotic fractures beyond its beneficial effects on the cardiovascular system. STUDY DESIGN/SETTINGThis was a retrospective, observational study that used data from the National Health Insurance Service-Health Screening cohort database. PATIENT SAMPLEThis study included 318,237 participants who were 50 years or older and with HDL-C levels of 10 to 200 mg/dL. OUTCOMES MEASURESPhysiologic measure—Diagnosis of osteoporotic fracture during the follow-up period. METHODSThe study participants were categorized into four quartiles according to baseline HDL-C levels. The Cox proportional hazards model was used to assess osteoporotic fracture risk according to HDL-C levels. RESULTSAfter full adjustment and with the Q1 group as the reference group, estimates of hazard ratios (HRs; 95% confidence intervals [CIs]) for any osteoporotic fracture in men were 1.03 (0.94–1.12), 1.02 (0.93–1.11), and 1.07 (0.98–1.18) for the Q2, Q3, and Q4 groups, respectively. After classifying osteoporotic fractures according to the body location, the fully adjusted HRs for vertebral and hip fractures in the men's Q4 groups were 1.16 (1.02–1.31) and 0.74 (0.57–0.96), respectively. In women, fully adjusted HRs (95% CIs) of the female Q4 group for any osteoporotic, vertebral, and hip fractures were 1.03 (0.95–1.11), 0.96 (0.86–1.07), and 1.06 (0.80–1.41), respectively. CONCLUSIONIn this study, HDL-C levels were positively associated with vertebral fractures in both men and women but inversely related to hip fractures in men. Therefore, monitoring the lipid profiles of patients with osteoporosis may be beneficial for the prevention of osteoporotic fractures.

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.

HDL CHOLESTEROL AND CARDIOVASCULAR EVENTS ON HYPERTENSIVE PATIENTS

Objective: Evaluate cardiovascular events on hypertensive patients and their HDL-cholesterol levels Design and method: Retrospective single-center study including first visits of adult patients in a hypertension clinic of a tertiary hospital during 2015 and their follow-up until 2020. Patients without follow-up and/or information about HDL cholesterol levels were excluded. Information on demographics, comorbidities, blood pressure control (&lt;140/90mmHg), number of drugs, and cardiovascular events were analyzed. Subjects were divided in 3 groups: Group 1 - HDL &lt;40mg/dL; Group 2- 40-80 mg/dL and Group 3 - &gt;80mg/dL. Results: Of the 104 initial participants we included 71, 43 female (60.6%) with mean age 55.9 years (18-87), which were monitorized on average for 42.5 months (3-60). Patients were taking on average 2.67 different anti-hypertensive drugs and, by the end of follow-up, 53 (74.6%) had controlled blood pressure. The sample included 26 (36.6%) smokers, 18 (25.3%) patients with diabetes, 9 (12.7%) with obstructive sleep apnea SAOS, 6 (8.5%) with chronic kidney disease and there were 30 (42.3%) patients with BMI &gt; 30 HDL cholesterol mean levels were 50.98 mg/dL (24-95). Group 1 included 19 (26.8%) patients, of these 15 (78.9%) had controlled blood pressure, and 3 presented cardiovascular events during the follow-up (2 acute myocardial infarction and 1 cerebrovascular event). Within group 2 there were 47 (66.2%) patients, 36 (76.6%) with controlled blood pressure and 2 cardiovascular events occurred (acute myocardial infarction). There were no cardiovascular events on group 3, which included 5 (7%) patients, 2 of those with controlled blood pressure. Conclusions: Some studies established a U shaped risk of cardiovascular events on the lower and higher end of HDL cholesterol. The first relation is well established, however the optimal higher level of HDL cholesterol is not defined. On our study the majority of patients presented controlled blood pressure and HDL-C within target levels. There was a small number of patients with HDL cholesterol &gt;80mg/dL and no events occurred, which is a limitation to make any conclusions. On the other hand we verified that the patients with low levels of HDL cholesterol had more events.

Abstract 1040: Investigating The Role Of Lipoproteins In Macrophage Er Stress

Atherosclerosis, a major cause of cardiovascular disease (CVD), is an inflammatory disease defined by the progressive buildup of lipid-laden macrophages and cholesterol-filled plaques. Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) play critical roles in the pathogenesis of atherosclerosis due to their roles in transporting cholesterol between tissues and cell types, including macrophages. Epidemiological studies have shown that high levels of HDL-cholesterol (HDL-C) are correlated with decreased CVD. However, HDL-C raising therapeutics failed to show clinical benefits, suggesting that HDL function may be a better indicator of CVD risk. Recent studies from our lab demonstrated that HDL modified by reactive aldehydes has impaired cardioprotective functions in macrophages. Other studies have also shown that oxidized LDL triggers ER stress in vascular cells and macrophages, a process that can be blunted by the presence of HDL. Therefore, we tested the hypothesis that HDL modified by reactive aldehydes triggers ER stress in macrophages, with the goal of identifying mechanisms by which dysfunctional HDL contributes to atherosclerosis progression. Primary murine macrophages were incubated with native or modified forms of lipoproteins and ER stress markers (XBP1, BiP, p-eIF2a, ATF6) were assessed by immunoblot analysis or semi-quantitative PCR. Through a comprehensive and extensive analysis, our findings led us to discover three novel findings in primary murine macrophages: (i) oxLDL alone was unable to induce ER stress; (ii) co-incubation with oxLDL or HDL in the presence of thapsigargin (an inducer of ER stress) resulted in increased and prolonged expression of ER stress markers as compared to cells treated with thapsigargin alone; and (iii) neither HDL nor HDL modified by reactive aldehydes was able blunt the ER stress induced by thapsigargin in the presence or absence of oxLDL. In summary, our highly systematic approach to assess the role of lipoproteins in mediating ER stress in primary macrophages generated convincing data that refutes previously-published findings, thus resulting in an inability to make definitive conclusions on the role of HDL modification in ER stress.

VISCERAL FAT TISSUE AS A SIGNIFICANT CARDIOVASCULAR RISK FACTOR IN CORRELATION WITH SUBCLINICAL ORGAN DAMAGE IN POSTMENOPAUSAL WOMEN

Objective: Postmenopausal women are a special group of the cardiological patients. Every effort should be made to search for subclinical organ damage in this group, the presence of which correlates with the amount of visceral fat tissue. Design and method: We examined 156 postmenopausal women. The average age of them was 65,3 years old. 41% of them had type 2 diabetes; 46% of them were taking statins. Pulse wave velocity (PWV), systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI) and lipid profile were evaluated. Visceral fat tissue, body weight and fat mass were performed by Tanita MC980 MA Plus analyzer. We assessed cardiovascular risk according to: SCORE2 and SCORE2- OP scales. Statistical calculations were performed in the StatSoft Statistica 10: ?Spearmana was taken to analyze the correlation of statistically significant values. Results: We revealed following results [∗for p&lt;= 0,05; ∗∗for p&lt;0,001]. People with higher body weight characterized by higher SBP and DBP. Lower fat mass and BMI resulted with lower DBP. The lower fat mass, BMI and the amount of visceral fat tissue, the higher HDL cholesterol level. People with higher fat mass, BMI and the amount of visceral fat tissue were more likely to have type 2 diabetes.Patients with higher amount of visceral fat tissue characterized by greater aortic stiffness and more often required lipid-lowering therapy. The amount of visceral fat tissue correlated with age of the patients and their cardiovascular risk assessed by SCORE2/SCORE2OP scales. Conclusions: The amount of visceral fat tissue should be taken into account in assessing the patient‘s cardiovascular risk and occurrence of cardiological subclinical organ damage. Weight loss must be considered as an important factor in the reducing of blood pressure. The likelihood of developing type 2 diabetes is correlated with higher BMI and fat mass. Reduction of BMI, fat mass and the amount of visceral fat tissue results with better lipid profile. Greater amount of visceral fat tissue results in more frequent need of starting lipid-lowering therapy.

Association of High-Density Lipoprotein Cholesterol with Sarcopenia in Chinese Community-Dwelling Middle-Aged and Older Adults: Evidence from 4-Year Longitudinal Study

Introduction: There is inconsistent evidence on the associations between high-density lipoprotein cholesterol (HDL-C) and risk of sarcopenia. The aim of the study was 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 colorimetric 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-year 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). The restricted cubic spline curves showed a J-shaped association between HDL-C and risk of sarcopenia in females. HDL-C was negatively associated with muscle mass (β = −0.23, 95% CI = −0.27 to −0.20) and hand grip strength (β = −0.05, 95% CI = −0.19 to 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.

Using propensity score matching analysis to compare between cardiometabolic risk factors and physical activity type in Korean adults: findings from a nationwide population-based survey

PurposeWe aimed to assess the effects of different exercise modalities on cardiometabolic risk factors within a comprehensive, representative sample of the Korean population.MethodsWe categorized 13,971 adult participants into aerobic exercise (AE), resistance exercise (RE), combined aerobic and resistance exercise (TE), insufficient exercise, and inactive groups. Multivariable regressions were conducted to compare the incidence of chronic diseases across the groups before and after propensity score matching (PSM).ResultsThe TE and RE groups had significantly lower waist circumference (WC), mean blood pressure (BP), glucose and insulin-related indices, and white blood cell count (WBC) measures, with TE showing the most significant differences. The TE group had significantly lower triglyceride levels and higher high-density lipoprotein-cholesterol levels. Post-PSM, the TE group had the lowest risk for metabolic syndrome, hypertension, and diabetes, closely followed by the RE group when compared with the inactive group. In a subgroup analysis, RE consistently exhibited benefits including lower body mass index, WC, BP, total cholesterol, glucose and insulin-related indices, and WBC count when compared with AE. RE may be associated with reduced incidence of cardiometabolic diseases compared to AE alone.ConclusionTE appears to be associated with significant reduction in cardiometabolic risk in Korean adults. RE possibly provides a more favorable cardiometabolic effect than AE.

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.

Abstract P265: Housing Instability and Cardiometabolic Health in the Rural South: Findings From Alabama Subcohort of the Rural Study

Introduction: Housing instability may be an important determinant contributing to cardiometabolic health. However, studies have focused largely on urban contexts. Further, there may be race- and sex-related differences in housing instability, which may help explain racial and sex disparities in cardiometabolic health. We examined the association between housing instability and cardiometabolic health among rural adults and analyzed potential race and sex differences. Methods: Data are from the Risk Underlying Rural Areas Longitudinal subcohort (mean [SD] age, 48.8 [11.0] years; 70.1% women; 79.8% Black) sampled in two rural Counties in Alabama (n=903). Housing stability (range: 0-10) was defined using the Rollins Index with higher scores indicating greater housing instability. We examined multiple measures of cardiometabolic health including BMI, HDL and LDL cholesterol, triglycerides, current smoking status (yes/no), and coronary artery calcification (CAC &gt; 0). Multivariable linear and logistic regression models adjusted for age, education, and income were used to examine continuous and categorical measures of cardiometabolic health, respectively. We further examined differences by self-reported race and sex in the association between housing instability and cardiometabolic health. Results: In the overall sample, mean (SD) housing instability was 1.1 (1.6). The prevalence of housing instability (Rollins Index ≥ 1) was higher for Black participants compared to White participants (60.5% vs. 27.4%, p&lt;.0001). Housing instability did not differ by sex (52.9% women vs. 57.4% men, p=0.187). In multivariable-adjusted models, greater housing instability was associated with presence of CAC among Black participants (OR 1.12; 95% CI: 1.00, 1.26) but with lower prevalence of CAC among White participants (OR 0.49; 95% CI: 0.25, 0.90). Housing instability was also associated with higher HDL cholesterol levels (b=1.04; 95% CI: 0.08, 2.01) among Black participants and higher triglyceride levels among White participants (b=29.40; 95% CI: 0.49, 58.31). Housing instability was not associated with BMI in either group and was associated with higher prevalence of current smoking among Black participants only (OR 1.20; 95% CI: 1.07, 1.34). We did not observe statistically significant associations between housing instability and cardiometabolic health in sex-stratified analyses. Conclusion: Housing instability may be a social determinant of cardiometabolic health; however, findings were mixed and appear to vary for Black adults compared to White adults. Future research should utilize a longitudinal design to assess how changes in housing stability may affect cardiometabolic health over time.

Neurological, Metabolic, and Psychopathological Correlates of Lifetime Suicidal Behaviour in Major Depressive Disorder without Current Suicide Ideation

Plain Language SummaryAlthough thinking of suicide for some period of time (suicide ideation) is traditionally viewed as necessary to attempt suicide in the future, many people who engage in suicide behaviour do not report specific suicidal thoughts during clinical interviews. We wanted to know how to predict suicide in these subjects; therefore, we investigated a number of promising characteristics in two different age groups of depressed patients (sample 1: n = 230; age: 18–65 years; sample 2: n = 258; age >60 years) who were negatively tested for the presence of suicide ideation. As expected, SB was not rare in these groups. Among younger patients, suicide attempts were a little more frequent than in the other group (15 vs. 9%); they more often involved men, those who had been victims of sexual abuse in childhood, those who had negative thoughts about themselves or were predisposed to bipolar disorder. On the other hand, in old age, suicide risk was correlated with neurological problems, foremost alterations in language and movement disorders, and cholesterol levels. Thanks to this information, to determine suicide risk is still possible even when intent to die is not reported.

Association of the ESR1 (rs9340799), OLR1 (rs3736234), LIPC (rs2070895), VDR (rs2228570), and CETP (rs708272) Polymorphisms With Risk of Coronary Artery Disease in Iranian Patients.

Coronary artery disease (CAD) is a devastating illness and a leading cause of death worldwide, primarily caused by atherosclerosis resulting from a genetic-environmental interaction. This study aimed to investigate the relationship between the ESR1 (rs9340799), OLR1 (rs3736234), LIPC (rs2070895), VDR (rs2228570), and CETP (rs708272) polymorphisms, lipid profile parameters, and CAD risk in a southeast Iranian population. A total of 400 subjects (200 CAD patients with hyperlipidemia and 200 healthy controls) were enrolled in this case-control study. Five selected polymorphisms were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. For all single nucleotide polymorphisms (SNPs), the population under study was in the Hardy-Weinberg equilibrium. The T-risk allele frequency of rs2228570 was associated with an increased risk of CAD. The TT and CT genotypes of rs2228570 had also been associated with the risk of CAD. Additionally, the TT genotype was associated with higher serum low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) levels. The GG genotype of the rs3736234 was associated with higher body mass index (BMI) and triglyceride (TG) levels, and the AA genotype of the rs708272 was associated with higher HDL-c levels. Based on these findings, we propose that the VDR (rs2228570) polymorphism was associated with serum HDL-c and LDL-c levels and may serve as potential risk factors for CAD within the Iranian population. Moreover, rs3736234 and rs708272 influence the concentrations of TG and HDL-c, respectively. These findings provided insights into the complex interplay between genetic variations, cardiovascular risk, and lipid metabolism.

Drug target Mendelian randomization supports apolipoprotein C3-lowering for lipoprotein-lipid levels reductions and cardiovascular diseases prevention

Background and aimsInhibitors of apolipoprotein C-III (apoC3) are currently approved for the reduction of triglyceride levels in patients with Familial Chylomicronemia Syndrome. We used drug target Mendelian randomization (MR) to assess the effect of genetically predicted decrease in apoC3 blood protein levels on cardiometabolic traits and diseases. MethodsWe quantified lifelong reductions in apoC3 blood levels by selecting all genome wide significant and independent (r2<0.1) single nucleotide polymorphisms (SNPs) in the APOC3 gene region ±1 Mb, from three genome-wide association studies (GWAS) of apoC3 blood protein levels (deCODE, n = 35,378, Fenland, n = 10,708 and ARIC, n = 7213). We included the largest GWASes on 18 cardiometabolic traits and 9 cardiometabolic diseases as study outcomes. ResultsA one standard deviation lowering in apoC3 blood protein levels was associated with lower triglycerides, apolipoprotein B, low-density lipoprotein cholesterol, alanine aminotransferase, and glomerular filtration rate as well as higher high-density lipoprotein cholesterol levels. ApoC3 lowering was also associated with lower risk of acute pancreatitis (odds ratio [OR] = 0.91 95% CI = 0.82 to 1.00), aortic stenosis (OR = 0.82 95% CI = 0.73 to 0.93), and coronary artery disease (OR = 0.86 95% CI = 0.80 to 0.93), and was associated with increased parental lifespan (0.06 95% CI = 0.03–0.09 years). These results were concordant across robust MR methods, the three protein datasets and upon adjustment for APOA1, APOA4 and APOA5 using a multivariable MR framework. ConclusionsThese results provide evidence that apoC3 lowering could result in widespread benefits for cardiometabolic health and encourage the launch of trials on apoC3 inhibition for coronary artery disease prevention.

Association between high-density lipoprotein cholesterol and type 2 diabetes mellitus: dual evidence from NHANES database and Mendelian randomization analysis.

Low levels of high-density lipoprotein cholesterol (HDL-C) are commonly seen in patients with type 2 diabetes mellitus (T2DM). However, it is unclear whether there is an independent or causal link between HDL-C levels and T2DM. This study aims to address this gap by using the The National Health and Nutrition Examination Survey (NHANES) database and Mendelian randomization (MR) analysis. Data from the NHANES survey (2007-2018) with 9,420 participants were analyzed using specialized software. Logistic regression models and restricted cubic splines (RCS) were used to assess the relationship between HDL-C and T2DM incidence, while considering covariates. Genetic variants associated with HDL-C and T2DM were obtained from genome-wide association studies (GWAS), and Mendelian randomization (MR) was used to evaluate the causal relationship between HDL-C and T2DM. Various tests were conducted to assess pleiotropy and outliers. In the NHANES study, all groups, except the lowest quartile (Q1: 0.28-1.09 mmol/L], showed a significant association between HDL-C levels and reduced T2DM risk (all P < 0.001). After adjusting for covariates, the Q2 [odds ratio (OR) = 0.67, 95% confidence interval (CI): (0.57, 0.79)], Q3 [OR = 0.51, 95% CI: (0.40, 0.65)], and Q4 [OR = 0.29, 95% CI: (0.23, 0.36)] groups exhibited average reductions in T2DM risk of 23%, 49%, and 71%, respectively. In the sensitivity analysis incorporating other lipid levels, the Q4 group still demonstrates a 57% reduction in the risk of T2DM. The impact of HDL-C levels on T2DM varied with age (P for interaction = 0.006). RCS analysis showed a nonlinear decreasing trend in T2DM risk with increasing HDL-C levels (P = 0.003). In the MR analysis, HDL-C levels were also associated with reduced T2DM risk (OR = 0.69, 95% CI = 0.52-0.82; P = 1.41 × 10-13), and there was no evidence of pleiotropy or outliers. This study provides evidence supporting a causal relationship between higher HDL-C levels and reduced T2DM risk. Further research is needed to explore interventions targeting HDL-C levels for reducing T2DM risk.