Higher High-density Lipoprotein Cholesterol Research Articles

HDL-C criterion of the metabolic syndrome and future diabetes and atherosclerosis in midlife women: The SWAN Study

ObjectiveHigh-density lipoprotein cholesterol (HDL-C) is one of 5 components [high blood pressure, glucose, triglycerides, waist circumference, low HDL-C], 3 of which, needed to diagnose metabolic syndrome (MetS). Evolving research shows that higher HDL-C is not necessarily cardioprotective in midlife women, supporting a need to re-evaluate HDL-C's contribution to risks related to MetS. We tested whether risk of future diabetes and higher carotid intima-media thickness (cIMT) differ by HDL-C status in midlife women diagnosed with MetS based on the other 4 components. Methods: Midlife women were classified into 3 groups1) no MetS, 2) MetS with HDL-C ≥ 50 mg/dL (MetS hiHDL), and 3) MetS with HDL-C < 50 mg/dL (MetS loHDL). cIMT was measured 13.8 ± 0.6 years post baseline. Incident diabetes was assessed yearly. ResultsAmong 2773 women (1350 (48 %) of them had cIMT), 2383 (86 %) had no MetS, 117 (4 %) had MetS hiHDL, 273 (10 %) had MetS loHDL. Compared with no MetS, both MetS- hiHDL and loHDL groups had higher cIMT and diabetes risk. Risk of having high cIMT did not differ between MetS loHDL vs. hiHDL groups. Adjusting for levels of MetS criteria other than HDL-C at baseline explained the associations of each of the two MetS groups with cIMT. Conversely, after adjustment, associations of MetS hiHDL and MetS loHDL with incident diabetes persisted. ConclusionsIn midlife women, HDL-C status matters for predicting risk of incident diabetes but not higher cIMT beyond other MetS components.

The association between serum high-density lipoprotein and hemoglobin A1c in T2DM: Evidence from a nationwide cross-sectional study in diabetic patients

IntroductionThe prevalence of Type 2 Diabetes Mellitus (T2DM) is expected to rise, increasing the risk of cardiovascular disease. This study explores the relationship between high-density lipoprotein cholesterol (HDL) and glycemic control in T2DM patients, measured by hemoglobin A1c (HbA1c). While HDL is known to confer cardiovascular benefits, its impact on glycemic control remains unclear. MethodsThis cross-sectional study analyzed 30,195 Thai adults with T2DM data from the 2018 Thailand DM/HT database. Well-controlled HbA1c was defined as less than 53 mmol/mol (7 %). The study utilized multivariable linear, piecewise linear, and logistic regression analyses to investigate the relationship between HDL levels and glycemic control. ResultsThe impact of HDL on HbA1c levels was nonlinear, showing a U-shaped relationship among the study participants with an HDL inflection point of 59 mg/dl. In females, a U-shaped relationship was also observed at the same inflection point, where increased HDL above this level was associated with a rise in HbA1c (Adjusted β = 0.205, P < 0.001). In contrast, a linear model better explained the consistent negative relationship between HDL and HbA1c in males (Adjusted β = –0.076, P < 0.001). Furthermore, in the poorly controlled HbA1c group, a significant U-shaped pattern was observed with an inflection point at 59 mg/dl. ConclusionThis study found a nonlinear, gender-specific relationship between HDL and HbA1c in T2DM patients. Males with higher HDL are more likely to achieve glycemic control, while a U-shaped relationship is observed in females. Further research is needed to understand the differing correlation between well-controlled and poorly controlled groups.

Association of KLF14 rs4731702 gene polymorphism with metabolic phenotype in young patients with type 1 diabetes.

To explore the potential association between the KLF14 rs4731702 polymorphism and metabolic syndrome traits among patients diagnosed with type 1 diabetes (T1D). The study group included 350 patients with T1D and 250 healthy control subjects. The analysis focused on the genotyping of KLF14 rs4731702 single nucleotide polymorphism (SNP), as well as evaluating serum concentrations of inflammatory markers, blood pressure, lipid profiles, and the quantitative status of CD4 + CD25highFOXP3+ T cells. Patients with T1D carrying the T allele of KLF14 rs4731702 SNP had higher high-density lipoprotein cholesterol, lower low-density lipoprotein cholesterol, as well as lower glycated haemoglobin and serum concentration of proinflammatory markers than C allele carriers. They also developed hypertension less often than carriers of the C allele. The analysis of CD4 + CD25highFOXP3+ regulatory T-cell status based on KLF14 genotype showed that, in T1D patients, those with the TT genotype had the highest frequency of these cells compared to carriers of the CC and CT genotypes. Our study suggests that the T allele of the KLF14 rs4731702 SNP might confer a protective effect against the development of obesity, hypertension, dyslipidaemia, and chronic inflammatory state in patients diagnosed with T1D.

Paraoxonase 1: evolution of the enzyme and of its role in protecting against atherosclerosis.

To review the discoveries which led to the concept that serum paraoxonase 1 (PON1) is inversely related to atherosclerotic cardiovascular disease (ASCVD) incidence, how this association came to be regarded as causal and how such a role might have evolved. Animal models suggest a causal link between PON1 present on HDL and atherosclerosis. Serum PON1 activity predicts ASCVD with a similar reliability to HDL cholesterol, but at the extremes of high and low HDL cholesterol, there is discordance with PON1 being potentially more accurate. The paraoxonase gene family has its origins in the earliest life forms. Its greatest hydrolytic activity is towards lactones and organophosphates, both of which can be generated in the natural environment. It is active towards a wide range of substrates and thus its conservation may have resulted from improved survival of species facing a variety of evolutionary challenges. Protection against ASCVD is likely to be the consequence of some promiscuous activity of PON1, but nonetheless has the potential for exploitation to improve risk prediction and prevention of ASCVD.

Assessing High-Density Lipoprotein: Shifting Focus from Quantity to Quality in Cardiovascular Disease Risk Assessment

High-density lipoprotein cholesterol (HDL) has long been regarded as a protective factor against cardiovascular disease (CVD). However, recent research challenges this notion, suggesting that HDL functionality rather than its quantity may be a more accurate predictor of CVD risk. While epidemiological studies have traditionally found that higher HDL levels are associated with reduced CVD risk, intervention trials aiming to elevate HDL levels have yielded inconsistent results. Moreover, observational studies have reported that unusually high HDL levels are associated with increased mortality rates. These discrepancies underscore the complexity of the role of HDL in CVD. Reverse cholesterol transport, facilitated by HDL, plays a crucial role in preventing atherosclerosis by removing cholesterol from peripheral tissues. Additionally, HDL exhibits anti-inflammatory properties by inhibiting endothelial adhesion molecules and suppressing pro-inflammatory cytokines. Recent studies have highlighted the importance of HDL particle number, size, and functionality in assessing CVD risk. For instance, increased HDL particle number and larger particle size have been associated with reduced CVD risk, independent of HDL cholesterol levels. Furthermore, HDL’s cholesterol efflux capacity has emerged as a promising biomarker for predicting CVD risk, with higher efflux capacity correlating with lower CVD incidence and mortality. This article reviews the latest findings regarding the role of HDL in CVD risk assessment, emphasizing the need to focus on HDL quantity and HDL quality.

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...

Milk protein concentrate supplementation improved appetite, metabolic parameters, adipocytokines, and body composition in dieting women with obesity: a randomized controlled trial

BackgroundDairy consumption is associated with many health benefits. However, to our knowledge, no clinical trials examined the effects of milk protein concentrate (MPC) on metabolic health in overweight and obese adults. This study investigated the effect of supplementation with MPC on glycaemic status, lipid profile, biomarkers of inflammation, and anthropometric measurements in women with obesity under a weight loss diet.MethodsThis is a single-blind, open-labelled, parallel-group, randomized trial. Forty-four healthy women with obesity were randomized into a control (n = 22) or MPC (n = 22) group. Participants in the MPC group were supplemented with 30 g of MPC per day for 8 weeks. Both groups were on a calorie-restricted diet plan with 800 Kcal lower intakes than their needs. Blood samples, dietary intake, and body composition were assessed before and after the intervention.ResultsMPC group had a significantly lower body mass index (P = 0.009), waist circumference (P = 0.013), fat mass (P = 0.021), appetite score (P = 0.002), fasting blood sugar (P < 0.001), insulin (P = 0.027), low-density lipoprotein cholesterol (P = 0.025), and leptin (P = 0.014) levels and higher high-density lipoprotein cholesterol (P = 0.001) and adiponectin (P = 0.032) compared to the control group after supplementation. Lean body mass, total cholesterol, and triglyceride did not differ significantly (P > 0.05).ConclusionDaily intake of 30 g of MPC for 8 weeks may improve several anthropometric and metabolic markers in women with obesity under a hypocaloric diet.

Confounding association between plasma HDL-C levels and increased fracture risk: A correspondence.

This article explores the association between fractures, particularly in the elderly, and elevated plasma high-density lipoprotein cholesterol (HDL-C) levels. The study challenges the conventional idea of HDL-C as "good cholesterol" by revealing its potential role as a risk factor for fractures. Factors contributing to fractures in the elderly, such as diminishing bone strength due to aging-related tissue breakdown, are discussed. Sedentary lifestyles, low bone mineral density (BMD), and habits like smoking and alcohol consumption compound fracture susceptibility. The study delves into mechanisms linking elevated HDL-C to fractures, using data from the ASPREE-Fracturesub-study of the ASPREE trial involving Australian and American participants aged 65 and above. The study showed that over a 4-year period, elevated HDL-C levels in healthy older people were linked to a 14% higher fracture risk. This revelation expands the understanding of fracture risk factors beyond the established norms. The article emphasizes the need to reconsider HDL-C's traditional role as an indicator of cardiovascular health, particularly in light of medications like Statins and Anacetrapib that raise HDL-C levels. It calls for further exploration into the relationship between HDL-C, fractures at varying sites, and different age groups. Practical implications involve incorporating fracture risk associated with high HDL-C into clinical considerations, alongside advocating lifestyle changes for optimal HDL-C levels. In summary, this study prompts a reevaluation of HDL-C's implications in clinical practice, demanding further investigation into the intricacies of this relationship.

Association between very high HDL-C levels and mortality: A systematic review and meta-analysis

Recent research has raised questions about the assumed cardiovascular (CV) benefits of high-density lipoprotein cholesterol (HDL-C) and the potential for adverse outcomes with extremely high levels. We conducted a meta-analysis to investigate the association between very high HDL-C levels (≥80 mg/dL) and mortality outcomes in individuals without coronary artery disease (CAD). We systematically searched PubMed, Embase, and Cochrane databases for studies comparing very high HDL-C levels to normal levels (40-60 mg/dL) in CAD-free individuals. We assessed heterogeneity using I2 statistics with a random-effects model. Our analysis included 1,004,584 individuals from 8 studies, of whom 133,646 (13.3 %) had very high HDL-C levels. All-cause mortality did not significantly differ between groups (p = 0.55), nor did cancer mortality (p = 0.45). Cardiovascular mortality showed no change in those with very high HDL-C (HR 1.05; 95 % CI 0.94-1.17; p = 0.37). Fatal and non-fatal coronary heart disease events were less frequent in the very high HDL-C group (HR 0.79; 95 % CI 0.73-0.86; p < 0.00001). Subgroup dose-response analysis revealed that very high HDL-C levels increased cardiovascular death in women above 116 mg/dL (HR 1.47; 95 % CI 1.01-2.15) and in men above 94 mg/dL (HR 1.29; 95 % CI 1.01-1.65) (p_nonlinearity <0.01). These findings suggest that very high HDL-C levels are not protective against cardiovascular mortality and may, in fact, increase CV mortality risk specially in men.

Dietary intake of branched-chain amino acids (BCAAs), serum BCAAs, and cardiometabolic risk markers among community-dwelling adults.

To investigate the associations between dietary/serum branched-chain amino acids (BCAAs) and cardiometabolic risk markers. In a cohort of 2791 participants, diet and cardiometabolic risk markers were measured twice at baseline in overall participants and after 1-year in a subset of 423 participants. We assessed serum BCAAs at baseline and arterial stiffness after 1-year. The cross-sectional associations between dietary/serum BCAAs and cardiometabolic risk markers were analyzed using baseline measurements by linear regression, while the 1-year longitudinal association were analyzed using repeated measurements by linear mixed-effects regression. Higher BCAA intake from poultry was associated with lower triglycerides (β=-0.028, P = 0.027) and higher high-density lipoprotein cholesterol (HDL-C, β = 0.013, P = 0.006), while BCAAs in red and processed meat or fish were inversely associated with low-density lipoprotein cholesterol (β = 0.025, P = 0.001) and total cholesterol (β = 0.012, P = 0.033), respectively. BCAAs in whole grains and nuts were associated with higher HDL-C (β = 0.011, P = 0.016), and lower TG (β=-0.021, P = 0.041) and diastolic blood pressure (β=-0.003, P = 0.027). Also, BCAAs from soy or vegetables and fruits were inversely associated with arterial stiffness (β=-0.018, P = 0.047) and systolic blood pressure (β=-0.011, P = 0.003), respectively. However, BCAAs in refined grains were positively associated with triglycerides (β = 0.037, P = 0.014). Total serum BCAAs were unfavorably associated with multiple cardiometabolic risk markers (all P < 0.05). Dietary BCAAs in poultry, whole grains and nuts, soy, and vegetables and fruits may be favorably, while BCAAs in red and processed meat, fish, and refined grains were unfavorably associated with cardiometabolic health. Serum BCAAs showed a detrimental association with cardiometabolic risk markers.

An ensemble-based machine learning model for predicting type 2 diabetes and its effect on bone health

BackgroundDiabetes is a chronic condition that can result in many long-term physiological, metabolic, and neurological complications. Therefore, early detection of diabetes would help to determine a proper diagnosis and treatment plan.MethodsIn this study, we employed machine learning (ML) based case-control study on a diabetic cohort size of 1000 participants form Qatar Biobank to predict diabetes using clinical and bone health indicators from Dual Energy X-ray Absorptiometry (DXA) machines. ML models were utilized to distinguish diabetes groups from non-diabetes controls. Recursive feature elimination (RFE) was leveraged to identify a subset of features to improve the performance of model. SHAP based analysis was used for the importance of features and support the explainability of the proposed model.ResultsEnsemble based models XGboost and RF achieved over 84% accuracy for detecting diabetes. After applying RFE, we selected only 20 features which improved the model accuracy to 87.2%. From a clinical standpoint, higher HDL-Cholesterol and Neutrophil levels were observed in the diabetic group, along with lower vitamin B12 and testosterone levels. Lower sodium levels were found in diabetics, potentially stemming from clinical factors including specific medications, hormonal imbalances, unmanaged diabetes. We believe Dapagliflozin prescriptions in Qatar were associated with decreased Gamma Glutamyltransferase and Aspartate Aminotransferase enzyme levels, confirming prior research. We observed that bone area, bone mineral content, and bone mineral density were slightly lower in the Diabetes group across almost all body parts, but the difference against the control group was not statistically significant except in T12, troch and trunk area. No significant negative impact of diabetes progression on bone health was observed over a period of 5-15 yrs in the cohort.ConclusionThis study recommends the inclusion of ML model which combines both DXA and clinical data for the early diagnosis of diabetes.

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.

Ethnic Disparities in the Risk Factors, Morbidity, and Mortality of Cardiovascular Disease in People With Diabetes.

Cardiovascular disease (CVD) is the leading cause of death in people with diabetes. Compared with European Americans, African Americans have more favorable lipid profiles, as indicated by higher high-density lipoprotein cholesterol, lower triglycerides, and less dense low-density lipoprotein particles. The less atherogenic lipid profile translates to lower incidence and prevalence of CVD in African Americans with diabetes, despite higher rates of hypertension and obesity. However, African Americans with CVD experience worse clinical outcomes, including higher mortality, compared with European Americans. This mini-review summarizes the epidemiology, pathophysiology, mechanisms, and management of CVD in people with diabetes, focusing on possible factors underlying the "African American CVD paradox" (lower CVD incidence/prevalence but worse outcomes). Although the reasons for the disparities in CVD outcomes remain to be fully elucidated, we present a critical appraisal of the roles of suboptimal control of risk factors, inequities in care delivery, several biological factors, and psychosocial stress. We identify gaps in current knowledge and propose areas for future investigation.

#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.

Association of physical activity and screen time with cardiovascular disease risk in the Adolescent Brain Cognitive Development Study

BackgroundAccording to the Physical Activity Guidelines Advisory Committee Scientific Report, limited evidence is available on sedentary behaviors (screen time) and their joint associations with physical activity (steps) for cardiovascular health in adolescence. The objective of this study was to identify joint associations of screen time and physical activity categories with cardiovascular disease (CVD) risk factors (blood pressure, hemoglobin A1c, cholesterol) in adolescence.MethodsThis study analyzed data from the Adolescent Brain Cognitive Development (ABCD) Study, comprising a diverse sample of 4,718 U.S. adolescents aged 10–15 years between 2018 and 2021. Steps were measured by a Fitbit wearable device and levels were categorized as low (1,000–6,000), medium (> 6,000–12,000), and high (> 12,000) averaged daily step counts. Self-reported recreational screen time hours per day were classified as low (0–4), medium (> 4–8), and high (> 8) hours per day. CVD risk factors including blood pressure, hemoglobin A1c, and cholesterol (total and HDL) were measured.ResultsThe analytical sample averaged 6.6 h of screen time per day and 9,722 steps per day. In models including both screen time and steps, the high screen time category was associated with a 4.27 higher diastolic blood pressure percentile (95% CI 1.83–6.73) and lower HDL cholesterol (B= -2.85, 95% CI -4.77 to -0.94 mg/dL) compared to the low screen time category. Medium (B = 3.68, 95% CI 1.24–6.11) and low (B = 7.64, 95% CI 4.07–11.20) step categories were associated with higher diastolic blood pressure percentile compared to the high step category. The medium step category was associated with lower HDL cholesterol (B= -1.99, 95% CI -3.80 to -0.19 mg/dL) compared to the high step category. Findings were similar when screen time and step counts were analyzed as continuous variables; higher continuous step count was additionally associated with lower total cholesterol (mg/dL).ConclusionsCombinations of low screen time and high steps were generally associated with favorable cardiovascular health markers including lower diastolic blood pressure and higher HDL cholesterol, which can inform future adolescent health guidelines.

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 lecithin cholesterol acyltransferase (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 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 to dampen hepatocarcinogenesis. LCAT and HDL-C represent potential prognostic and therapeutic biomarkers for targeting cholesterol homeostasis as a strategy for treating HCC. Significance: Estrogen mediates the sex differences in hepatocellular carcinoma development by reducing cholesterol biosynthesis through activation of an LCAT/HDL-C axis, providing strategies for improving liver cancer prevention, prognosis, and treatment.

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

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.

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.