Higher High-density Lipoprotein Research Articles

Sex-dependent associations of plasma high-density lipoprotein cholesterol and mortality risk in healthy older men and women: two prospective cohort studies

The relationship between high plasma high-density lipoprotein cholesterol (HDL-C) and cause and mortality are not well established in healthy older people. This study examined the associations between HDL-C levels and mortality in initially healthy older men and women. This analysis included participants from the Aspirin in Reducing Events in the Elderly (ASPREE; n=18,668) trial and a matched cohort from the UK Biobank (UKB; n=62,849 ≥65 years). Cox regression was used to examine hazard ratios between HDL-C categories <1.03 mmol/L, 1.03–1.55 mmol/L (referent category), 1.55–2.07 mmol/L, and >2.07 mmol/L and all-cause, cancer, cardiovascular disease (CVD), and “non-cancer non-CVD” mortality. Genetic contributions were assessed using a polygenic score for HDL-C. Among ASPREE participants (aged 75±5 years), 1836 deaths occurred over a mean follow-up of 6.3±1.8 years. In men, the highest category of HDL-C levels was associated with increased risk of all-cause (HR 1.60, 95% CI 1.26–2.03), cancer (HR 1.37, 95% CI 0.96–2.00), and “non-cancer non-CVD” mortality (HR 2.35, 95% CI 1.41–3.42) but not CVD mortality (HR 1.08, 95% CI 0.60–1.94). The associations were replicated among UKB participants (aged 66.9±1.5 years), including 8739 deaths over a mean follow-up of 12.7±0.8 years. There was a non-linear association between HDL-C levels and all-cause and cause-specific mortality. The association between HDL-C levels and mortality was unrelated to variations in the HDL-C polygenic score. No significant association was found between HDL-C levels and mortality in women. Higher HDL-C levels are associated with increased risk from cancer and “non-cancer non-CVD” mortality in healthy older men but no such relationship was observed in women.

Associations between neighborhood socioeconomic deprivation, IFNγ, and high-density lipoprotein particle size: Data from the Washington, D.C. cardiovascular health and needs assessment

IntroductionNeighborhood socioeconomic deprivation is associated with increased cardiovascular risk factors, including inflammation. Inflammation plays an important role in modifying the cardioprotective function of high-density lipoprotein (HDL). Moreover, recent studies suggest that very high HDL is associated with adverse cardiovascular disease (CVD) outcomes. Thus, we sought to explore the relationships between neighborhood socioeconomic deprivation as a marker of chronic stress, inflammation, proprotein convertase subtilisin/kexin type 9 (PCSK9) (a core component of the HDL proteome), HDL characterisitcs, and biological aging as a predictor of CVD and all-cause mortality. MethodsSixty African American subjects were recruited to the NIH Clinical Center as part of a community-based participatory research-designed observational study. Neighborhood deprivation index (NDI), a marker of neighborhood socioeconomic deprivation, was measured using US Census data. HDL characteristics (cholesterol, particle number, size, subspecies) were determined from NMR lipoprotein profiling, and plasma cytokines (IL-1β, IL-6, IL-8, TNFα, IFNγ) were measured using an ELISA-based multiplex technique. Epigenetic clock biomarkers of aging were measured using DNA methylation data obtained from participants' buffy coat samples. We used linear regression modeling adjusted for atherosclerotic cardiovascular disease (ASCVD) risk score, body mass index (BMI), and lipid-lowering medication use to investigate relationships of interest. ResultsNDI directly associated with large HDL particle count (H7P) and IFNγ and trended toward significance with HDL-C and PCSK9. IFNγ and PCSK9 then directly associated with H7P. H7P also directly associated with higher DNA methylation phenotypic age (PhenoAge). ConclusionWe highlight associations between neighborhood socioeconomic deprivation, IFNγ, PCSK9, HDL subspecies, and epigenetic biomarkers of aging. Taken together, our findings suggest indirect pathways linking neighborhood deprivation-related stress and inflammation to HDL and immune epigenetic changes. Moreover, these results add to recent work showing the pathogenicity of high HDL levels and underscore the need to understand how chronic stress-related inflammation and lipoprotein subspecies relate to CVD risk across diverse populations.

Differences in the components of metabolic syndrome by age and sex: a cross-sectional and longitudinal analysis of a cohort of middle-aged and older Japanese adults

BackgroundThe prevalence of metabolic syndrome (MetS) in Japan, a super-aged society, is increasing and poses a major public health issue. Several studies have reported sex differences in the association between age and MetS prevalence. This study aimed to examine the association between age and the prevalence of MetS based on multiple screening criteria and MetS components by sex.MethodsWe used 6 years of individual-level longitudinal follow-up data (June 2012 to November 2018; checkup year: 2012–2017) of middle-aged and older adults aged 40–75 years in Japan (N = 161,735). The Joint Interim Statement criteria, International Diabetes Federation criteria, and another set of criteria excluding central obesity were used as the screening criteria for MetS. The prevalence of MetS and MetS components was cross-sectionally analyzed according to sex and age. A longitudinal association analysis of age, MetS, and MetS components by sex was performed using a multilevel logistic model, adjusted for lifestyle- and regional-related factors.ResultsSex differences were observed in the prevalence and association of MetS and MetS components. In all age groups, the prevalence of central obesity was higher among women, and the prevalence of high blood pressure and fasting glucose was higher among men (P < 0.001). The prevalence of high triglyceride and low high-density lipoprotein cholesterol was higher among women aged > 60 years (P < 0.05). Based on the criteria of the Joint Interim Statement and International Diabetes Federation, the prevalence of MetS was higher among women than in men aged > 55 years (P < 0.001). Men had a higher prevalence of MetS without central obesity than women in all age groups (P < 0.001). The odds ratio for MetS and MetS components with aging was greater among women than in men.ConclusionsMedical management should be based on the prevalence of MetS and its components according to sex and age. In particular, the high prevalence of MetS without central obesity in middle-aged and older Japanese men suggests that the adoption of the Joint Interim Statement criteria, which do not precondition central obesity, should be considered.

P-648 Association of severity of menstrual dysfunction with cardiometabolic risk markers in polycystic ovary syndrome

Abstract Study question Is the severity of menstrual dysfunction related to cardiometabolic risk markers in women with polycystic ovary syndrome (PCOS)? Summary answer PCOS women with amenorrhea, compared to those with oligomenorrhea or eumenorrhea, show a higher prevalence of insulin resistance (IR), prediabetes and hypertriglyceridemia. What is known already PCOS is associated robustly with a wide range of unfavorable cardiometabolic risk markers, including obesity, glucolipid metabolism disorders and metabolic syndrome. Many epidemiological studies have found compared to the women with regular menstrual cycles, women with a history of irregular menstruation increased the risks of metabolic syndrome and coronary heart disease. Recently, the association between the severity of menstrual cyclicity and hyperinsulinemia and IR has been demonstrated, suggesting menstrual history could be a simple but clinically important marker of metabolic dysfunction risk. But evidence linking the severity of menstrual cyclicity with cardiometabolic risk in PCOS women is very limited. Study design, size, duration In this prospective cross-sectional study, one hundred and fifty-four women diagnosed with PCOS by the Rotterdam criteria were recruited from July 2021 to September 2022. The association of menstrual cycle regularity with cardiometabolic risk markers including obesity, hypertension, glycemic abnormalities, dyslipidemia and metabolic syndrome was systematically analyzed. Participants/materials, setting, methods In a university-affiliated hospital, PCOS participants with eumenorrheic (Eumeno, n = 24), oligomenorrhea (Oligo, n = 73) and amenorrhea (Ameno, n = 57) underwent history and physical examination, gonadal steroid hormone measurement, lipid profile, oral glucose tolerance test (OGTT) and homeostasis model assessment of IR. Main results and the role of chance Adjusting for age, BMI and waist circumference, a trend toward an increase of unfavorable cardiometabolic risk markers including obesity, hypertension, prevalence of IR, prediabetes, hypertriglyceridemia and prevalence of metabolic syndrome was observed in Ameno group than in other menstrual categories. A significantly higher prevalence of IR, prediabetes and hypertriglyceridemia was demonstrated in Ameno group compared to the Eumeno or Oligo group. In logistic regression, adjusting for age, BMI, and waist circumference, Ameno women were more likely to have: IR than Eumeno women (odds ratio [OR]: 2.90; 95% CI: 1.01 to 8.31); prediabetes than Eumeno women (OR: 4.06; 95% CI: 1.05 to 15.77) and hypertriglyceridemia than Oligo women (OR: 4.43; 95% CI: 1.74 to 11.26). Moreover, the prevalence of IR, prediabetes and hypertriglyceridemia was still significantly higher in Ameno group than that in the Oligo or Eumeno group when further adjusted for free androgen index in the logistic regression. The proportion of Type 2 Diabetes, high total cholesterol, high low-density lipoprotein (LDL) cholesterol and low high-density lipoprotein (HDL) cholesterol was similar across the three groups. Limitations, reasons for caution Our study was limited by its cross-sectional nature, and another limitation was the cycle regularity question relied on the participant’s interpretation of irregular, although we have acquired the detailed menstrual cycle history and further reviewed at consultation, yet some exposure misclassification might also be present. Wider implications of the findings Our study used menstrual cycle as a readily obtainable marker for identification of PCOS women at greatest risk of IR, prediabetes and hypertriglyceridemia, which would emphasize the importance of menstrual cycle regularity and help refine the current recommendations concerning the screening of PCOS subjects for cardiometabolic diesases. Trial registration number 20210728

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.

Apo CIII Proteoforms, Plasma Lipids, and Cardiovascular Risk in MESA.

Apo CIII (apolipoprotein CIII) is an important regulator of triglyceride metabolism and was associated with cardiovascular risk in several cohorts. It is present in 4 major proteoforms, a native peptide (CIII0a), and glycosylated proteoforms with zero (CIII0b), 1 (CIII1, most abundant), or 2 (CIII2) sialic acids, which may differentially modify lipoprotein metabolism. We studied the relationships of these proteoforms with plasma lipids and cardiovascular risk. Apo CIII proteoforms were measured by mass spectrometry immunoassay in baseline plasma samples of 5791 participants of Multi-Ethnic Study of Atherosclerosis, an observational community-based cohort. Standard plasma lipids were collected for up to 16 years and cardiovascular events (myocardial infarction, resuscitated cardiac arrest, or stroke) were adjudicated for up to 17 years. Apo CIII proteoform composition differed by age, sex, race and ethnicity, body mass index, and fasting glucose. Notably, CIII1 was lower in older participants, men and Black and Chinese (versus White) participants, and higher in obesity and diabetes. In contrast, CIII2 was higher in older participants, men, Black, and Chinese persons, and lower in Hispanic individuals and obesity. Higher CIII2 to CIII1 ratio (CIII2/III1) was associated with lower triglycerides and higher HDL (high-density lipoprotein) in cross-sectional and longitudinal models, independently of clinical and demographic risk factors and total apo CIII. The associations of CIII0a/III1 and CIII0b/III1 with plasma lipids were weaker and varied through cross-sectional and longitudinal analyses. Total apo CIII and CIII2/III1 were positively associated with cardiovascular disease risk (n=669 events, hazard ratios, 1.14 [95% CI, 1.04-1.25] and 1.21 [1.11-1.31], respectively); however, the associations were attenuated after adjustment for clinical and demographic characteristics (1.07 [0.98-1.16]; 1.07 [0.97-1.17]). In contrast, CIII0b/III1 was inversely associated with cardiovascular disease risk even after full adjustment including plasma lipids (0.86 [0.79-0.93]). Our data indicate differences in clinical and demographic relationships of apo CIII proteoforms, and highlight the importance of apo CIII proteoform composition in predicting future lipid patterns and cardiovascular disease risk.

Variations in high density cholesterol levels based on apolipoprotein E variant and exercise type.

In various cross-sectional and longitudinal studies, exercise has been associated with cardiometabolic outcomes, including high-density lipoprotein (HDL) cholesterol. Exercise-induced changes in HDL cholesterol seem to be affected by genetic polymorphisms. In this study, we examined whether variant APOE rs7412 is involved in the association between HDL cholesterol and exercise. From adults assessed in Taiwan Biobank (TWB) between 2008 and 2019, we analyzed data from 57,638 normolipidemic subjects. To examine the association between exercise, APOE rs7412, and HDL cholesterol, a multiple linear regression model was used. A higher HDL was associated with both aerobic exercise (regression coefficient [mg/dL] beta- (β), 1.112; 95% confidence interval (CI); 0.903-1.322) and resistance exercise (β, 2.530; 95% CI, 2.093-2.966). In comparison with the APOE rs7412-CC genotype, the β was 2.589 (95% CI, 2.329-2.848) among those with the CT + TT genotype. Compared to adults who had the CC genotype and did not exercise (the CC/no exercise group), the β-coefficient determined for the different genotype and exercise groups was 1.135 (95% CI, 0.911-1.359) for the CC genotype and aerobic exercise group, 2.753 (95% CI, 2.283-3.322) for the CC genotype and resistance exercise group, 2.705 (95% CI, 2.390-3.020) for the CT + TT genotype and no exercise group, 3.682 (95% CI, 3.218-4.146) for the CT + TT genotype and aerobic exercise group, and 3.855 (95% CI, 2.727-4.982) for the CT + TT genotype and resistance exercise group, respectively. This study demonstrates that self-reported aerobic and resistance exercise both raised HDL levels, yet resistance exercise was associated with a greater increase, particularly among Taiwanese subjects carrying the APOE rs7412-CT+TT genotype.

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.

Association of serum water-soluble vitamin exposures with the risk of metabolic syndrome: results from NHANES 2003-2006.

Existing evidence suggests an association between certain vitamins and metabolic syndrome (MetS), but few epidemiological studies have focused on the effects of multivitamin co-exposure on MetS. This study aims to investigate the associations of the individual or multiple water-soluble vitamins (i.e., vitamin C (VC), vitamin B9 (VB9), and vitamin B12 (VB12)) with co-exposure to MetS, as well as the dose-response relationships among them. A cross-sectional study was conducted by employing the National Health and Examination Surveys (NHANESs) 2003-2006. Multivariate-adjusted logistic regression models were used to explore the association between individual serum water-soluble vitamins and the risk of MetS and its components, including waist circumference, triglyceride, high-density lipoprotein, blood pressure, and fasting plasma glucose. Restricted cubic splines were performed to explore the dose-response relationships among them. The quantile g-computation method was adopted to explore the associations of multiple water-soluble vitamins co-exposure with MetS risk and MetS components. A total of 8983 subjects were involved in the study, of whom 1443 were diagnosed with MetS. The MetS groups had a higher proportion of participants with age ≥60 years, BMI ≥30 kg/m2, and insufficient physical activity. Compared with the lowest quartile, the third (OR=0.67, 95% CI: 0.48, 0.94) and highest quartiles (OR=0.52, 95%CI: 0.35, 0.76) of VC were associated with lower MetS risk. Restricted cubic splines showed negative dose-response relationships among VC, VB9 and VB12, and MetS. Regarding MetS components, higher VC quartiles were associated with lower waist circumference, triglyceride, blood pressure, and fasting plasma glucose, while higher VC and VB9 quartiles were associated with higher high-density lipoprotein (HDL). Co-exposure to VC, VB9, and VB12 was significantly inversely associated with MetS, with ORs (95% CI) of 0.81 (0.74, 0.89) and 0.84 (0.78, 0.90) in the conditional and marginal structural models, respectively. Furthermore, we found that VC, VB9, and VB12 co-exposure were negatively associated with waist circumference and blood pressure, while VC, VB9, and VB12 co-exposure were positively associated with HDL. This study revealed negative associations of VC, VB9, and VB12 with MetS, while the high water-soluble vitamin co-exposure was associated with a lower MetS risk.

Association between second- and third-trimester maternal lipid profiles and adverse perinatal outcomes among women with GDM and non-GDM: a retrospective cohort study

BackgroundLipid metabolism disorder during pregnancy has been reported in women with gestational diabetes mellitus (GDM). However, controversy remains regarding the relationship between maternal changes in lipid profiles and perinatal outcomes. This study investigated the association between maternal lipid levels and adverse perinatal outcomes in women with GDM and non-GDM.MethodsIn total, 1632 pregnant women with GDM and 9067 women with non-GDM who delivered between 2011–2021 were enrolled in this study. Serum samples were assayed for fasting total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels during the second and third trimesters of pregnancy. Adjusted odds ratios (AOR) and 95% confidence intervals (95% CI) were calculated via multivariable logistic regression analysis to determine the association of lipid levels with perinatal outcomes.ResultsThe serum TC, TG, LDL, and HDL levels in the third trimester were significantly higher than those in the second trimester (p < 0.001). Women with GDM had significantly higher levels of TC and TG in the second and third trimesters than those with non-GDM in the same trimesters, while HDL levels decreased in women with GDM (all p < 0.001). After adjusting for confounding factors by multivariate logistic regression, every mmol/L elevation in TG levels of women with GDM in second and third trimesters was associated with a higher risk of caesarean section (AOR = 1.241, 95% CI: 1.103–1.396, p < 0.001; AOR = 1.716, 95% CI: 1.556–1.921, p < 0.001), large for gestational age infants (LGA) (AOR = 1.419, 95% CI: 1.173–2.453, p = 0.001; AOR = 2.011, 95% CI: 1.673–2.735, p < 0.001), macrosomia (AOR = 1.220, 95% CI: 1.133–1.643, p = 0.005; AOR = 1.891, 95% CI: 1.322–2.519, p < 0.001), and neonatal unit admission (NUD; AOR = 1.781, 95% CI: 1.267–2.143, p < 0.001; AOR = 2.052, 95% CI: 1.811–2.432, p < 0.001) cesarean delivery (AOR = 1.423, 95% CI: 1.215–1.679, p < 0.001; AOR = 1.834, 95% CI: 1.453–2.019, p < 0.001), LGA (AOR = 1.593, 95% CI: 1.235–2.518, p = 0.004; AOR = 2.326, 95% CI: 1.728–2.914, p < 0.001), macrosomia (AOR = 1.346, 95% CI: 1.209–1.735, p = 0.006; AOR = 2.032, 95% CI: 1.503–2.627, p < 0.001), and neonatal unit admission (NUD) (AOR = 1.936, 95% CI: 1.453–2.546, p < 0.001; AOR = 1.993, 95% CI: 1.724–2.517, p < 0.001), which were higher than the relative risk of these perinatal outcomes in women with non-GDM. Additionally, every mmol/L increase in second and third-trimester HDL levels of women with GDM was associated with decreased risk of LGA(AOR = 0.421, 95% CI: 0.353–0.712, p = 0.007; AOR = 0.525, 95% CI: 0.319–0.832, p = 0.017) and NUD (AOR = 0.532, 95% CI: 0.327–0.773, p = 0.011; AOR = 0.319, 95% CI: 0.193–0.508, p < 0.001), and the risk reduction was not strong than that of women with GDM.ConclusionsAmong women with GDM, high maternal TG in the second and third trimesters was independently associated with an increased risk of cesarean section, LGA, macrosomia, and NUD. High maternal HDL during the second and third trimesters was significantly associated with decreased risk of LGA and NUD. These associations were stronger than those in women with non-GDM, suggesting the importance of monitoring second and third-trimester lipid profiles in improving clinical outcomes, especially in GDM pregnancies.

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.

SARS-CoV-2 induced HDL dysfunction may affect the host's response to and recovery from COVID-19.

Covid-19 is linked with the development of cardio-metabolic disorders, including dyslipidemia, dysregulation of high-density lipoprotein (HDL), and low-density lipoprotein (LDL). Furthermore, SARS-Co-2 infection is associated with noteworthy changes in lipid profile, which is suggested as a possible biomarker to support the diagnosis and management of Covid-19. This paper adopts the literature review method to obtain information about how Covid-19 affects high-risk group patients and may cause severe and critical effects due to the development of acute lung injury and acute respiratory distress syndrome. A narrative and comprehensive review is presented. Reducing HDL in Covid-19 is connected to the disease severity and poor clinical outcomes, suggesting that high HDL serum levels could benefit Covid-19. SARS-CoV-2 binds HDL, and this complex is attached to the co-localized receptors, facilitating viral entry. Therefore, SARS-CoV-2 infection may induce the development of dysfunctional HDL through different mechanisms, including induction of inflammatory and oxidative stress with activation of inflammatory signaling pathways. In turn, the induction of dysfunctional HDL induces the activation of inflammatory signaling pathways and oxidative stress, increasing Covid-19 severity. Covid-19 is linked with the development of cardio-metabolic disorders, including dyslipidemia in general and dysregulation of high-density lipoprotein and low-density lipoprotein. Therefore, the present study aimed to overview the causal relationship between dysfunctional high-density lipoprotein and Covid-19.

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

Metabolic syndrome as a late effect of childhood hematopoietic stem cell transplantation - A thorough statistical evaluation of putative risk factors.

Metabolic syndrome (MetS) is frequent among survivors of childhood hematopoietic stem-cell transplantation (HSCT), but assessment of risk factors is challenged by survivor and participation bias in long-term follow-up studies. A cohort of 395 pediatric patients transplanted between 1980 and 2018 was investigated. MetS was assessed at follow-up between December 2018 and March 2020. Two composite outcomes ((a) combining MetS and death, (b) combining MetS, death, and nonparticipation) were considered to address the risk of selection bias. Among 234 survivors invited to the follow-up, 96 individuals (median age 27 years) participated. MetS prevalence was 30% among participants. The only significant HSCT risk factor was a variable combining HSCT indication and conditioning with total-body irradiation (TBI) (p = .0011). Compared to acute leukemias (AL) treated with high-grade TBI (8-12 Gy), a lower MetS prevalence was seen for nonmalignant diseases treated with no/low-grade TBI (0-4.5 Gy) (OR = 0.04, 95% confidence interval (CI): 0.00-0.23). Analyses of the composite outcomes indicated overestimation of the effect of high-grade TBI due to selection bias. Scrutiny showed strong residual confounding between HSCT indication and high-grade TBI within AL-patients. The HSCT effect on MetS reflected HSCT effects on high-density-lipoprotein (HDL) and triglycerides. Compared to AL treated with high-grade TBI, nonmalignant diagnoses treated with no/low-grade TBI had higher HDL (+40%, 95% CI: +21% to +62%) and lower triglyceride (-59%, 95% CI: -71% to -42%). The TBI effect on MetS may be overestimated in follow-up studies due to selection bias and confounding. The TBI effect was confined to the potentially modifiable MetS criteria HDL and triglyceride.

The pre-pregnancy fasting blood glucose, glycated hemoglobin and lipid profiles as blood biomarkers for gestational diabetes mellitus: evidence from a multigenerational cohort study

Background Early prevention of gestational diabetes mellitus (GDM) is important to reduce the risk of adverse pregnancy outcomes and post-pregnancy cardiometabolic risk in women and offspring over the life course. This study aimed to investigate some blood biomarkers before pregnancy as GDM predictors. Methods We investigated the prospective association of blood biomarkers before pregnancy and GDM risk among women from the Mater-University of Queensland Study of Pregnancy (MUSP) cohort. A multiple logistic regression model was applied to estimate the odds of experiencing GDM by blood biomarkers. Results Out of 525 women included in this study, the prevalence of GDM was 7.43%. There was an increased risk of experiencing GDM among women who experienced obesity (Odds ratio = OR 2.4; 95% confidence interval = CI 1.6–3.7), had high fasting blood glucose (OR = 2.2; 95% CI = 1.3–3.8), high insulin (OR = 1.1; 95% CI = 1.0–1.2), high insulin resistance (OR = 1.2; 95% CI = 1.0–1.3) and low high-density lipoprotein (OR = 0.2; 95% CI = 0.1–0.7) before pregnancy. Adjustment for potential confounders, such as age, marital status, and BMI did not attenuate these associations substantially. Conclusion The pre-pregnancy fasting blood glucose, insulin, and insulin resistance were independent predictors of GDM. They may be used as early markers for predicting the incidence of GDM.

The relationship between triglyceride, cholesterol and lipoprotein levels, and immune responses to hepatitis B vaccine.

Cholesterol homeostasis disorder and hypertriglyceridemia, as common metabolic conditions, have rarely been reported to affect the immune responses to the hepatitis B vaccine. Our study found that higher high-density lipoprotein (HDL) level showed a significant relationship with positive anti-HBs results (cOR = 1.479, 95% CI: 1.150, 1.901, p = 0.002; aOR = 1.304, 95% CI: 1.006, 1.691, p = 0.045), especially in individuals aged 18- to 40-year-old, female, smoking more than 100 cigarettes in life, and drinking more than 12 times every year. Lower low-density lipoprotein (LDL) level was associated with a negative anti-HBs result among participants aged 18- to 40-year-old, and participants who were obese. Higher level of HDL and lower level of LDL may be protective factors of better immune effect of hepatitis B vaccine. More research should be conducted to investigate the influence of the cholesterol level on the immune responses to the hepatitis B vaccine, and more in-depth research should be performed to uncover the mechanism.

The Association between the Atherogenic Index of Plasma and Cardiometabolic Risk Factors: A Review.

Metabolic syndrome (MetS) is a condition caused by a combination of cardiometabolic risk factors (CMR). MetS leads to type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD), both of which place a burden on not only the patients but also the healthcare system. Diagnostic criteria for MetS vary, and there is no universal tool to detect it. Recently, many studies have found positive associations between the atherogenic index of plasma (AIP) and some CMR factors. Therefore, a comprehensive review was needed to recapitulate these studies and qualitatively estimate the likelihood of AIP being associated with CMR. We aimed to review and summarise observational data on AIP and CMR factors and verify their association. A review of observational studies was conducted by searching "atherogenic index of plasma" in PubMed, One Search, and the Cochrane library. A total of 2068 articles were screened, and 32 were included after excluding paediatric, non-human and interventional studies, and those carried out on cohorts with conditions unrelated to MetS or on lipid-lowering medication. The Newcastle-Ottawa scale was used to assess their quality. Most studies that reported high waist circumference (WC), triglycerides (TG), insulin resistance (IR) and low high-density lipoprotein cholesterol (HDL-C) concentration, also reported high AIP. Few studies investigated blood pressure (BP) and some discrepancies existed between their results. AIP may be associated with WC, TG, IR, and HDL-C. It is unclear if AIP is associated with BP. The current study's results should be used to inform futureward a meta-analysis to be seen quantitatively. It is also recommended that more cohort studies stratified by gender and ethnicity be performed to ascertain if AIP can predict MetS before it manifests.

Prevalence and Predictive Clinical Characteristics of Metabolically Healthy Obesity in Obese Children and Adolescents.

The increasing prevalence of childhood obesity and accompanying comorbidities all over the world constitutes one of the most important public health problems of the changing world. The frequency and causes of the metabolically healthy obesity (MHO) phenotype in children is not clear. The objective is to determine the prevalence of the MHO phenotype in obese Turkish children and adolescents and to identify clinical and biochemical indicators for this phenotype. Eight hundred forty-seven obese children and adolescents, aged 3-18 years with BMI-SDS >+2 SD from the obesity outpatient clinic were included. Demographic, anthropometric, and physical examination information was collected from patient medical files. In addition, obesity-related comorbidities and results of laboratory tests were obtained. For study purposes, obese patients with no cardiometabolic risk factors were accepted as MHO, and those with ≥1 cardiometabolic risk factor were considered metabolically unhealthy obese (MUO). MHO was defined according to Damanhoury's criteria. Out of 847 children (mean age 10.6±3.4 years) who met the study criteria, 289 (34.1%) were diagnosed with MHO. Being younger, prepubertal, having relatively low BMI, low waist/hip ratio, low insulin resistance (HOMA-IR) index, high high-density lipoprotein, low triglyceride, low fasting insulin and glucose levels, low uric acid and low alanine transaminase (ALT) levels were associated with MHO. The MHO phenotype was present in just over a third of this obese pediatric cohort. The most important factors associated with MHO; age, waist-hip ratio, and BMI were determined.

Dyslipidemia Exacerbates Meibomian Gland Dysfunction: A Systematic Review and Meta-Analysis.

An article search was performed in PubMed, EMBASE, and Web of Science. Eleven studies involving dyslipidemia in patients with MGD were identified. Five out of eleven studies were further analyzed with meta-analysis. The preferred reporting items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines were followed. Study-specific estimates (prevalence of dyslipidemia in MGD patients) were combined using one-group meta-analysis in a random-effects model. Meta-analysis revealed that high total cholesterol (TC) and high triglycerides (TG) were significantly associated with MGD prevalence, with odds ratios of 5.245 (95% confidence interval [CI]: 1.582-17.389; p < 0.001) and 3.264 (95% CI: 1.047-10.181; p < 0.001), respectively, but high low-density lipoprotein (LDL) and low high-density lipoprotein (HDL) were not identified. Systematic review found that the percentage of MGD patients with TC ≥ 200 mg/dL ranged from 20.0-77.6%, TG ≥ 150 mg/dL ranged from 8.3-89.7%, whereas, in the aged-match-adjusted controls, TC range of 200 mg/dL or higher and TG range of 150 mg/dL was 6.1-45.1% and 1.1-47.8%, respectively. The severity of MGD was higher with dyslipidemia. Dyslipidemia and higher TC and TG are significant risk factors for MGD.

The factors associated with cognitive function among community-dwelling older adults in Taiwan

BackgroundThis research aimed to investigate the associations of anthropometric measurements, physiological parameters, chronic disease comorbidities, and social and lifestyle factors with cognitive function amongst community-dwelling older adults in Taiwan.MethodsThis was an observational, cross-sectional study involving 4,578 participants at least 65 years old, recruited between January 2008 and December 2018 from the Annual Geriatric Health Examinations Program. Cognitive function was assessed using the short portable mental state questionnaire (SPMSQ). Multivariable logistic regression was done to analyze the factors associated with cognitive impairment. ResultsAmong the 4,578 participants, 103 people (2.3%) with cognitive impairment were identified. Associated factors were age (odds ratio (OR) = 1.16, 95% confidence interval (CI) = 1.13,1.20), male gender (OR = 0.39, 95% CI = 0.21,0.72), diabetes mellitus (DM) (OR = 1.70, 95% CI = 1.03, 2.82), hyperlipidemia (OR = 0.47, 95% CI = 0.25, 0.89), exercise (OR = 0.44, 95% CI = 0.34, 0.56), albumin (OR = 0.37, 95% CI = 0.15, 0.88), and high-density lipoprotein (HDL) (OR = 0.98, 95% CI = 0.97, 1.00). Whereas waistline, alcohol intake in recent six months, and hemoglobin was not significantly associated with cognitive impairment (all p > 0.05).ConclusionsOur findings suggested that people with older age and a history of DM had a higher risk of cognitive impairment. Male gender, a history of hyperlipidemia, exercise, a high albumin level, and a high HDL level seemed to be associated with a lower risk of cognitive impairment amongst older adults.