Reduced HDL-cholesterol Levels Research Articles

Association of Metabolic Syndrome With Neuroimaging and Cognitive Outcomes in the UK Biobank.

Metabolic syndrome (MetS) has been linked to dementia. In this study, we examined the association of MetS with neuroimaging and cognition in dementia-free adults, offering insight into the impact of MetS on brain health prior to dementia onset. We included 37,395 dementia-free adults from the UK Biobank database. MetS was defined as having at least three of the following components: larger waist circumference; elevated levels of triglycerides, blood pressure, HbA1c; or reduced HDL cholesterol levels. Multivariable-adjusted linear regression was used to assess associations of MetS with structural neuroimaging and cognitive domains. MetS was associated with lower total brain (standardized β: -0.06; 95% CI -0.08, -0.04), gray matter (β: -0.10; 95% CI -0.12, -0.08) and hippocampal (for left side, β: -0.03, 95% CI -0.05, -0.01; for right side, β: -0.04, 95% CI -0.07, -0.02) volumes, and greater white matter hyperintensity (WMH) volume (β: 0.08; 95% CI 0.06, 0.11). Study participants with MetS performed poorer on cognitive tests of working memory (β: -0.10; 95% CI -0.13, -0.07), verbal declarative memory (β: -0.08; 95% CI -0.11, -0.05), processing speed (β: -0.06; 95% CI -0.09, -0.04), verbal and numerical reasoning (β: -0.07; 95% CI -0.09, -0.04), nonverbal reasoning (β: -0.03; 95% CI -0.05, -0.01), and on tests of executive function, where higher scores indicated poorer performance (β: 0.05; 95% CI 0.03, 0.08). More MetS components were also associated with less brain volume, greater WMH, and poorer cognition across all domains. MetS was associated poorer brain health in dementia-free adults, characterized by less brain volume, greater vascular pathology, and poorer cognition. Further research is necessary to understand whether reversal or improvement of MetS can improve brain health.

Comparison of Metabolic Syndrome (MetS) Risk and Nutritional Status According to Menopause Age and the Impact of Socioeconomic Status on MetS Prevalence in Postmenopausal Women: A Cross-Sectional Study Based on the 8th Korea National Health and Nutrition Examination Survey (KNHANES).

The increased life expectancy and the occurrence of premature menopause prolong the mean postmenopausal phase in women's lifespans. Although the roles of poor socioeconomic status (SES), anthropometric characteristics, and nutritional status in premature menopause and the health of postmenopausal women are well understood, the differences in nutritional status and metabolic syndrome (MetS) prevalence in postmenopausal women depending on their menopause age are less explored. Furthermore, the association between SES and MetS risk in postmenopausal women is not studied. Thus, this study aimed to compare distinct nutritional status and MetS risk between women with premature menopause and natural menopause. Additionally, the association among SES, health-related lifestyle behaviors (HLBs), and MetS risk in postmenopausal women was studied. This study included 31,799 postmenopausal women from the 8th National Health and Nutrition Examination Survey (KNHANES). The relationship between disease prevalence and nutrient intake of the subjects was analyzed using analysis of variance (GLM), and Scheffé test was performed. Multiple logistic regression analysis was used to evaluate the association among SES, HLBs, and MetS as well as premature menopause. Women with premature menopause showed poor SES, anthropometric characteristics, and HLBs compared with women with natural menopause. Additionally, premature menopausal women had markedly lower intakes of protein, polyunsaturated fatty acid, n-3 fatty acid, and β-carotene, but higher intakes of energy, carbohydrate, saturated fatty acid, and sugar than women with natural menopause (p < 0.0001). Premature menopausal women showed significantly higher MetS prevalence by having hypertriglyceridemia (p < 0.0001), hypertension (p = 0.0145), and reduced HDL cholesterol levels (p < 0.0001) relative to natural menopausal women. Furthermore, our findings indicate a substantial link among SES, HLBs, and the risk of premature menopause. In postmenopausal women, deteriorating SES and HLBs appear to influence the prevalence of MetS. Notably, our study reveals that higher intakes of protein, calcium, phosphate, and iron are correlated with a lower risk of developing MetS. These observations suggest that proactive nutritional education for premature menopausal women is necessary to improve MetS risk and their nutritional status. Also, SES-dependent interventions regarding nutrition and HLBs in postmenopausal women will be significant to lower MetS risk, MetS-derived chronic disease, and mortality in postmenopausal women.

Causal effect of severe and non-severe malaria on dyslipidemia in African Ancestry individuals: A Mendelian randomization study.

Dyslipidemia is becoming prevalent in Africa, where malaria is endemic. Observational studies have documented the long-term protective effect of malaria on dyslipidemia; however, these study designs are prone to confounding. Therefore, we used Mendelian randomization (MR, a method robust to confounders and reverse causation) to determine the causal effect of severe malaria (SM) and the recurrence of non-severe malaria (RNM) on lipid traits. We performed two-sample MR using genome wide association study (GWAS) summary statistics for recurrent non-severe malaria (RNM) from a Benin cohort (N=775) and severe malaria from the MalariaGEN dataset (N=17,000) and lipid traits from summary-level data of a meta-analyzed African lipid GWAS (MALG, N=24,215) from the African Partnership for Chronic Disease Research (APCDR) (N=13,612) and the Africa Wits-IN-DEPTH partnership for genomics studies (AWI-Gen) dataset (N=10,603). No evidence of significant causal association was obtained between RNM and high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol and triglycerides. However, a notable association emerged between severe malarial anaemia (SMA) which is a subtype of severe malaria and reduced HDL-C levels, suggesting a potential subtype-specific effect. Nonetheless, we strongly believe that the small sample size likely affects our estimates, warranting cautious interpretation of these results. Our findings challenge the hypothesis of a broad causal relationship between malaria (both severe and recurrent non-severe forms) and dyslipidemia. The isolated association with SMA highlights an intriguing area for future research. However, we believe that conducting larger studies to investigate the connection between malaria and dyslipidemia in Africa will enhance our ability to better address the burden posed by both diseases.

Predictive value of early postoperative blood lipid metabolism for anastomotic leakage after esophageal cancer surgery.

To explore the clinical value of assessing early postoperative blood lipid metabolism levels in predicting anastomotic leakage (AL) after esophageal cancer (EC) surgery. The clinical data of EC patients who underwent surgery at the Northern Jiangsu People's Hospital from May 2021 to May 2023 were retrospectively studied. Totally, 28 patients who developed AL were included in the AL group, while 110 patients who did not develop AL were included in the non-AL group. Outcomes compared between the two groups included clinical baseline data, total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels. Logistic regression analysis was performed to identify independent risk factors for postoperative AL. The predictive value of early postoperative blood lipid metabolism levels for AL was evaluated using Receiver Operating Characteristic (ROC) curves. The AL group exhibited significantly elevated levels of TC and LDL-C but significantly reduced HDL-C levels compared to the non-AL group (all P<0.05). However, there was no significant difference in triglyceride levels between the two groups (P>0.05). Logistic regression analysis revealed that low BMI (P=0.012; OR: 4.409; 95% CI: 1.391-13.976), comorbid hypertension (P=0.011; OR: 5.891; 95% CI: 1.492-23.259), comorbid diabetes (P=0.022; OR: 4.522; 95% CI: 1.238-16.521), low HDL-C (P=0.007; OR: 19.965; 95% CI: 2.293-173.809), and high LDL-C (P=0.012; OR: 4.321; 95% CI: 1.388-13.449) were independent risk factors for developing AL after EC surgery. The combined prediction model using TC, HDL-C, and LDL-C yielded an area under the curve (AUC) of 0.876, with a sensitivity of 79.09%, specificity of 85.71%, and overall accuracy of 80.44%, significantly outperforming individual lipid measurements. The combined assessment of TC, HDL-C, and LDL-C can effectively predict the occurrence of AL after EC surgery. For EC patients with relatively low BMI, hypertension, diabetes, relatively low HDL-C, and relatively high LDL-C, prioritizing weight management, hypertension and diabetes control, and lipid management can significantly reduce the risk of AL post-surgery.

Dyslipidemia in the Russian Federation: population data, associations with risk factors

Aim. To study the prevalence of dyslipidemias and their association with various risk factors in the Russian population of men and women aged 35-74 years in 2020-2022.Material and methods. This work was carried out as part of the Epidemiology of Cardiovascular Diseases and their Risk Factors in Regions of Russian Federation-3 (ESSE-RF3) study. The sample included 28731 men and women aged 35-74 years living in 15 Russian regions. Hypercholesterolemia (HC) was diagnosed with total cholesterol (TC) ≥5,0 mmol/l, while elevated low-density lipoprotein cholesterol (LDL-C) was considered ≥3,0 mmol/l, hypertriglyceridemia — with triglyceride levels ≥1,7 mmol/l, reduced high-density lipoprotein cholesterol (HDL-C) &lt;1,0 mmol/l in men and &lt;1,2 mmol/l in women. Associations were assessed using logistic regression after adjustment for socio-demographic characteristics, drinking status, presence of hypertension (HTN) and stroke.Results. The prevalence of hypertriglyceridemia in the Russian Federation in 2020-2022 was 58,8%, hypertriglyceridemia — 32,2%. The incidence of lipid-lowering therapy increased with age from 1% in the group of 35-44 years to 16% in the group of 65-74 years. On average, only 7,6% of study participants received lipid-lowering therapy. Significant associations of HC with HTN, obesity and alcohol abuse were identified. Similar results were obtained for elevated LDL-C levels, with the exception of alcohol abuse. In turn, a reduced HDL-C level was significantly associated with the lack of higher education, marriage, physical activity, smoking and the presence of diseases.Conclusion. The prevalence of lipid disorders in the Russian Federation in 2020-2022 remained at a high level. These disorders occurred more often in women, and they were better informed about their cholesterol levels and more often received lipid-lowering therapy. HTN, obesity, and some behavioral and social risk factors were associated with dyslipidemia.

Functional characterization of missense variants affecting the extracellular domains of ABCA1 using a fluorescence-based assay

Excess cholesterol originating from nonhepatic tissues is transported within HDL particles to the liver for metabolism and excretion. Cholesterol efflux is initiated by lipid-free or lipid-poor apolipoprotein A1 interacting with the transmembrane protein ABCA1, a key player in cholesterol homeostasis. Defective ABCA1 results in reduced serum levels of HDL cholesterol, deposition of cholesterol in arteries, and an increased risk of early onset CVD. Over 300 genetic variants in ABCA1 have been reported, many of which are associated with reduced HDL cholesterol levels. Only a few of these have been functionally characterized. In this study, we have analyzed 51 previously unclassified missense variants affecting the extracellular domains of ABCA1 using a sensitive, easy, and low-cost fluorescence-based assay. Among these, only 12 variants showed a distinct loss-of-function phenotype, asserting their direct association with severe HDL disorders. These findings emphasize the crucial role of functional characterization of genetic variants in pathogenicity assessment and precision medicine. The functional rescue of ABCA1 loss-of-function variants through proteasomal inhibition or by the use of the chemical chaperone 4-phenylbutyric acid was genotype specific. Genotype-specific responses were also observed for the ability of apolipoprotein A1 to stabilize the different ABCA1 variants. In view of personalized medicine, this could potentially form the basis for novel therapeutic strategies.

Deteriorative Effect of a Combination of Hypertriglyceridemia and Low High-Density Lipoprotein Cholesterolemia on Target Lesion Revascularization after Everolimus-Eluting Stent Implantation.

This study aimed to investigate the association between a combination of elevated triglyceride (TG) and reduced high-density lipoprotein cholesterol (HDL-C) levels and target lesion revascularization (TLR) following everolimus-eluting stent (EES) implantation. The adverse impact of clinical, lesion, and procedural characteristics on TLR in patients with elevated TG and reduced HDL-C levels was also assessed. We retrospectively collected data on 3,014 lesions from 2,022 consecutive patients, who underwent EES implantation at Koto Memorial Hospital. Atherogenic dyslipidemia (AD) is defined as a combination of non-fasting serum TG ≥ 175 mg/dL and HDL-C ＜40 mg/dL. AD was observed in 212 lesions in 139 (6.9%) patients. The cumulative incidence of clinically driven TLR was significantly higher in patients with AD than in those without AD (hazard ratio [HR] 2.31, 95% confidence interval [CI] 1.43-3.73, P=0.0006). Subgroup analysis showed that AD increased the risk of TLR with the implantation of small stents (≤ 2.75 mm). Multivariable Cox regression analysis showed that AD was an independent predictor of TLR in the small EES stratum (adjusted HR 3.00, 95% CI 1.53-5.93, P=0.004), whereas the incidence of TLR was similar in the non-small-EES stratum, irrespective of the presence or absence of AD. Patients with AD had a higher risk of TLR after EES implantation, and this risk was greater for lesions treated with small stents.

Dietary inflammatory index in relation to severe coronary artery disease in Iranian adults.

Limited findings are available on the relationship between dietary inflammation index (DII) and severe coronary artery disease (CAD). Considering the high prevalence of CAD and its complications, we examined the relationship between DII and CAD. This cross-sectional study was conducted on 275 adults who underwent elective angiography. Severe coronary artery disease was measured by the gensini scoring system. DII was measured by a valid semi-quantitative 168-item food frequency questionnaire (FFQ). Blood samples were collected after 12 h of fasting to measure serum lipid profile and quantitative C-reactive protein (q-CRP) levels. Binary logistic regression was used to calculate the odds (OR) and 95% confidence interval (CI). People in the last tertile of the DII had a higher chance of suffering from severe coronary artery disease (OR: 3.71; 95% CI: 1.97-6.98), hypercholesterolemia (OR: 2.73; 95% CI: 5.03-1.48), reduced HDL-cholesterol levels (OR: 3.77; 95% CI: 9.34-1.52), and hypertension (OR: 1.93; 95% CI: 3.49-1.06) compared to people in the first tertile. After adjusting for confounding factors, the relationship remained significant. A direct and significant relationship was observed between the DII and increased q-CRP levels, which disappeared after adjusting for confounding factors in the adjusted model (OR: 2.02; 95% CI: 0.86-4.73). This cross-sectional study showed a direct and linear relationship between following an anti-inflammatory diet and decreasing the chance of severe CAD. Therefore, it seems necessary to implement community-based educational programs to promote healthy nutrition in order to prevent CADs.

Association between vitamin D deficiency and lipid profiles in overweight and obese adults: a systematic review and meta-analysis

ObjectiveThe association between vitamin D deficiency and lipid profiles in adults with overweight or obesity remains unclear and inconsistent. The aim of our study was to determine the relationship between lipid profiles and vitamin D deficiency in the overweight and obese adults.MethodsFour databases, including PubMed, the Web of Science, EMBASE and the Cochrane Library, were used to identify all studies on vitamin D status and lipid levels, including the serum levels of triglycerides (TGs), total cholesterol (TC), low-density lipoprotein cholesterol (LDL), and high-density lipoprotein cholesterol (HDL). The Weighted mean difference (WMD) with 95% confidence intervals (CIs) using random-effects models was used to assess the association between the lipid profile and vitamin D deficiency.ResultsTwenty-one articles that included a total of 7952 adults with overweight or obesity (BMI ≥ 25 kg/m2) were included. The overall results revealed that compared with the controls, individuals with vitamin D deficiency showed higher levels of TG (WMD = 15.01; 95%CI, 2.51–27.52) and TC (WMD = 8.61; 95%CI, 1.31–15.92). Moreover, vitamin D deficiency was related to an increased level of LDL (WMD = 6.12; 95%CI, 0.02–12.23). HDL level was inversely associated with the vitamin D deficiency status (WMD = -2.57; 95%CI, -4.26, -0.88).ConclusionsAmong the adults with overweight or obesity, the vitamin D deficient group displayed impaired lipid profiles, including increased TG, TC and LDL levels and reduced HDL level.

To Compare the Pattern of Serum Non HDL, HDL Levels in Type 2 Diabetes Subjects With and Without Ischemic Heart Disease

Individuals with DM may have several forms of dyslipidemia. Because of the additive cardiovascular risk of hyperglycemia and hyperlipidemia, lipid abnormalities should be assessed aggressively and treated as part of comprehensive diabetes care. The most common pattern of dyslipidemia is hypertriglyceridemia and reduced HDL cholesterol levels. DM itself does not increase levels of LDL, but the small dense LDL particles found in type 2 DM are more atherogenic because they are more easily glycated and susceptible to oxidation. Low HDL cholesterol as an independent risk factor for CHD Strong epidemiological evidence links low levels of serum HDL cholesterol to increased CHD morbidity and mortality. High HDL-cholesterol levels conversely convey reduced risk. Epidemiological data taken as a whole signify that a 1 percent decrease in HDL cholesterol is associated with a 2–3 percent increase in CHD risk. Epidemiological studies consistently show low HDL cholesterol to be an independent risk factor for CHD. Objective: To compare the pattern of serum non HDL, HDL levels in type 2 diabetes subjects with and without Ischemic Heart Disease. A descriptive study was carried out. Source of Data: Primary observed data of subjects with type 2 diabetes admitted to Medicine wards for ischemic heart disease. Control group of Type 2DM without IHD. Statistical Tests: Chi square test, students T test Bar and Pie chart. Related statistical techniques using SPSS version 21.0. Results: Among the 100 subjects chosen for the study, 59 subjects were males (59%) and remaining 41 subjects were females (41%). Majority of the subjects were in the age group of 50-69 years (60%). Mean non HDL value among non IHD was 67.1+14.6 and among IHD cases were at higher level i.e 176.4+18.7. p value showed statistical significance. Conclusion: UACR is statistically different among subjects with IHD compared to subjects without IHD. Hence subjects with Type 2 DM with IHD have been found to have higher total ....

Association of HDL subfractions with cardiovascular risk in Hungarian general and Roma populations

Abstract Background High-density lipoprotein (HDL) cholesterol levels are inversely associated with cardiovascular risk (CVR). However, HDL cholesterol is not a homogeneous lipid and can be subdivided into subfractions, which are not uniformly associated with CVR. Among Roma populations, the prevalence of reduced HDL cholesterol levels and, consequently, that of cardiovascular diseases is very high. However, it is not known how this reduction affects the different HDL subfractions and whether changes in their representation are associated with changes in CVR. Methods The study aimed to investigate whether there is a difference in the HDL subfraction profile between the Hungarian general (HG) and Roma populations and to determine the association of the different subfractions with the CVR estimated by the Framingham Risk Score (FRS) and the Systematic COronary Risk Evaluation (SCORE) algorithms. HDL cholesterol was separated using the Lipoprint system, which separates 10 subfractions into three classes: large HDL (HDL-L), medium HDL (HDL-I), and small HDL (HDL-S). Analyses were carried out on samples of 100 control subjects (50 Hungarian general and 50 Roma individuals with normal lipid profiles) and 277 individuals with reduced HDL-C levels. Results Our results show that Roma has reduced levels of the overall HDL subfraction profile, with significant decreases in HDL-6, and -7. Regardless of the estimation method, elevated levels (in mmol/L) of HDL-1 to 3 and HDL-L were significantly associated with reduced risk. A higher representation (in %) of HDL-1 to 3 subfractions have a significant risk-reducing, while HDL-8 to 10 have a risk-increasing effect estimated by FRS. Conclusions The results of our study show that levels of CVR protective HDL subfractions are significantly lower in Roma individuals and their reduced levels are associated with increased CVR, suggesting that the distribution of HDL subfractions contributes to the overall unfavourable CVR profile of Roma. Key messages • Levels of HDL-6 and -7 subfractions were significantly lower in the Roma population than in the Hungarian general one. • The HDL subfraction profile of the Roma population is associated with a higher cardiovascular risk among them.

Elevated triglycerides and reduced high-density lipoprotein cholesterol are independently associated with the onset of advanced chronic kidney disease: a cohort study of 911,360 individuals from the United Kingdom

BackgroundIncreased total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and decreased high-density lipoprotein cholesterol (HDL-C) concentrations, are established risk factors for cardiovascular morbidity and mortality; but their impact on the risk of advanced chronic kidney disease (CKD) is unclear. This study evaluates the association between the different lipid profiles and the onset of advanced CKD using a general population sample.MethodsThis observational study used records of 911,360 individuals from the English Clinical Practice Research Datalink (from 2000 to 2014), linked to coded hospital discharges and mortality registrations. Cox models were used to examine the independent association between the equal quarters of TC, TG, LDL-C, and HDL-C and the risk of advanced CKD, after adjustment for sex and age, and potential effect mediators.ResultsDuring a median follow-up of 7.5 years, 11,825 individuals developed CKD stages 4–5. After adjustment for sex and age, the hazard ratios (HRs) and confidence intervals (CIs) for CKD stages 4–5 comparing the 4th vs. 1st quarters of TG and 1st vs. 4th quarters of HDL-C were 2.69 (95% CI, 2.49–2.90) and 2.61 (95% CI, 2.42–2.80), respectively. Additional adjustment for potential effect mediators reduced the HRs to 1.28 (95% CI, 1.15–1.43), and 1.27 (95% CI, 1.14–1.41), respectively. There was no evidence of fully adjusted associations with CKD stages 4–5 for levels of either TC or LDL-C.ConclusionsElevated TG and reduced HDL-C levels are independently associated with the onset of advanced CKD. Future studies, such as in basic science and randomized trials, are needed to understand whether associations between TG and HDL-C and the development of CKD are causal.

SNPs in apolipoproteins contribute to sex-dependent differences in blood lipids before and after a high-fat dietary challenge in healthy U.S. adults

BackgroundThe effect of genetic polymorphisms on fasting blood lipid levels have been widely studied but the effects of these within the context of a high-fat meal challenge remain less characterized. The current study aimed to investigate the association of SNPs in lipoprotein-related genes with blood lipid profiles in healthy adults in the U.S.MethodsSubjects (n = 393) between 18–66 years of age with BMIs ranging from 18.5–45 kg/m2 were enrolled the cross-sectional Nutritional Phenotyping Study. Among them, 349 subjects (men: 48%; women: 52%) gave consent for genotyping. SNPs in APOA5, APOB, APOC3, APOE, and LDLR were assessed. The association between lipid markers and genotypes was tested separately for each SNP with analysis of variance (ANOVA), adjusted for sex, age, and BMI. We also examined two-factor interactions between SNPs and sex, age, or BMI.ResultsWomen carrying the C allele of rs3135506 in APOA5 or men carrying the C allele of rs429358 in APOE had reduced HDL-cholesterol levels during fasting and postprandially. The C allele in APOE was also correlated to increased LDL-C levels. The TT genotype of rs2854116 in APOC3 was associated with elevated total cholesterol. Additive effect of the risk alleles of APOA5 and APOE or APOC3 and APOE was detected. Nevertheless, the tested SNPs had little impact on the postprandial triglyceride responses to the high-fat challenge meal. We found no significant effects of SNPs in APOB (rs1042034) or LDLR (rs2228671) on triglycerides, cholesterol, or free fatty acid levels.ConclusionsIn healthy adults, fasting and postprandial cholesterol levels are strongly correlated with the tested APOA5, APOE, and APOC3 genotypes. Sex contributes to the genetic impact of the tested SNPs on lipid profiles.Trial registrationClinicalTrials.gov, NCT02367287. Registered February 20, 2015, https://clinicaltrials.gov/ct2/show/NCT02367287.

The profile of HDL-C subfractions and their association with cardiovascular risk in the Hungarian general and Roma populations

High-density lipoprotein cholesterol (HDL-C) is not a homogenous lipid fraction, but it can be further divided into subfractions. It is well-known that the Roma population has a high prevalence of reduced HDL-C levels and cardiovascular diseases (CVDs). However, it is unknown how this reduction affects different HDL subfractions, and whether changes in their quantity/representation are associated with an increased cardiovascular risk among them. In the present study, the HDL subfraction profile of the Hungarian general (HG) and the Roma populations were compared, and the subfractions showing a significant difference between the two populations were identified. The association of HDL subfractions with CVD risk estimated by the Framingham risk score (FRS) and the Systematic COronary Risk Evaluation (SCORE) algorithms were also defined. The present study is the first to find a significant association between HDL subfractions and cardiovascular risk estimated by FRS and SCORE. Ten HDL subfractions were investigated on small but carefully selected samples comprising 100 control subjects (with normal lipid profile) and 277 case subjects (with reduced HDL-C levels) from HG and Roma populations of a complex health survey. The level of HDL-1 to 3 subfractions and HDL-L showed a significant inverse association with cardiovascular risk estimated by both SCORE and FRS algorithms, whereas HDL-4 to 6 and HDL-I only for FRS. A higher representation (in %) of HDL-1 to 3 has a significant risk-reducing effect, while HDL-8 to 10 has a risk-increasing effect estimated by FRS. Our results confirmed that reduced levels of HDL-6 and -7 expressed in mmol/L were significantly associated with Roma ethnicity.

Association of Serum 25(OH)D with Metabolic Syndrome in Chinese Women of Childbearing Age.

Objective: To analyze the associations between serum 25(OH)D levels and the risk of metabolic syndrome (MetS) and its components, and the related genetic and non-genetic factors in non-diabetic women of childbearing age in China. Methods: Subjects were randomly selected from the 2015 Chinese Adult Chronic Disease and Nutrition Surveillance. The data of sociodemographic characteristics and lifestyle factors were obtained through questionnaire survey. Anthropometry was measured by trained interviewers, and fasting blood was collected to test 25-hydroxyvitamin D [25(OH)D], total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), and other related parameters. Generalized linear mode and multivariate logistic analysis were performed to analyze the associations between serum 25(OH)D and MetS and its components, adjusting for the possible confounders. Results: Body mass index (BMI), serum alanine aminotransferase (ALT), hypersensitive C-reactive protein (hs-CRP), 25(OH)D, phosphorus (P), and parathyroid hormone (PTH) levels were associated with the number of MetS’s components. G allele carriers of GC rs2282679 had higher diastolic blood pressure (DBP) and FBG levels compared with the TT genotypes, while higher genetic risk score (GRS) seemed to be associated with reduced HDL-C level. The odds ratio (OR) for MetS in lowest group of 25(OH)D was 1.533 (0.980–2.399) after adjusting for season, district, area type, latitude, age, BMI, PTH, P, ALT, CRE, interleukin-6 (IL-6), and hs-CRP, compared with the median group, but the association was not significant. An insufficient 25(OH)D concentration (<14.22 ng/mL) was significantly related to the risk of elevated waist circumference (WC) (OR = 1.612 (1.014–2.561)) and TG (OR = 2.210 (1.318–3.706)), and reduced HDL-C (OR = 1.639 (1.206–2.229)) after adjusting for the confounders among these women. Moreover, these relationships were not affected by vitamin D metabolism-related gene polymorphisms. Conclusion: After comprehensively considering various influencing factors, significant associations between insufficient serum 25(OH)D and MetS‘s components, including elevated WC, TG, and reduced HDL-C, were observed. However, MetS, hypertension, and hyperglycemia were not found independently associated with 25(OH)D levels.

Correlation between circulating microRNA and lipid indicesin patients with ischemic heart disease and type 2 diabetes mellitus

The aim of the study was to investigate circulating miRNAs-27a, -221 levels and their correlations with lipid indices in patients with ischemic heart disease (IHD) and type 2 diabetes mellitus. Materials and methods. The study included 58 patients with stable IHD and type 2 diabetes mellitus, 22 IHD patients without diabetes and 19 healthy controls. MicroRNAs-27a-3р and 221-3р were determined in blood plasma by real time polymerase chain reaction. U6 small nuclear RNA was used for normalization. Results. The lowest levels of circulating miRNAs-27a and -221 were in IHD patients with diabetes. The decrease in the levels of both microRNAs in patients with diabetes was significant not only in comparison with the control group (P = 0.024, P = 0.006), but also with patients without diabetes (P = 0.011, P = 0.001). In IHD patients without diabetes, microRNAs-27a and -221 levels did not change significantly. In IHD patients with diabetes, microRNA-221 showed a significant positive correlation with high-density lipoprotein cholesterol (HDL-C) (R = 0.382, P = 0.003). MicroRNA-27a was correlated negatively with triglycerides (TG) (R = -0.284, P = 0.051) and positively – with HDL-C (R = 0.257, P = 0.078) at a borderline significance level. The lower level of microRNA-27a (the 1st tertile) was associated with significantly increased TG level in comparison with the 3rd tertile (P = 0.004), and significantly decreased HDL-C level in comparison with the 2nd (P = 0.001) and the 3rd (P = 0.023) tertiles. Patients with lower microRNA-221 level (the 1st tertile) had significantly reduced HDL-C level in comparison with the 3rd tertile(P = 0.007). Conclusions. The results have demonstrated the significant decrease in circulating microRNAs-27a and -221 levels in IHD patients with type 2 diabetes mellitus and no change in both microRNAs in patients without diabetes. In IHD patients with diabetes, the lower expression of microRNA-27a was associated with the significant elevation of TG and the significant decrease in HDL-C. The lower microRNA-221 level was associated only with the significant decrease in HDL-C.

Association of Lipids’ Metabolism with Vitamin D Receptor (rs10735810, rs222857) and Angiotensinogen (rs699) Genes Polymorphism in Essential Hypertensive Patients

BACKGROUND: Cardiovascular (CV) diseases are the most spread cause of mortality in the world. Essential arterial hypertension (EAH), as a major risk factor for the development of CV diseases, is a multifactorial disease involving environmental and genetic factors together with risk-conferring behaviors. AIM: The purpose of this study was to analyze lipid metabolism changes in patients with EAH depending on the Vitamin D receptor (VDR rs2228570 (aka rs10735810)) and angiotensinogen (AGT rs699) genes polymorphism. MATERIALS AND METHODS: The single-stage study involved 100 patients suffering from Stage 2 EAH, 1–3 degrees of blood pressure increase, high and very high CV risks, 21% (21) men, and 79% (79) women. The average age of patients was 59.86 ± 6.22 years old. The control group included 60 practically healthy individuals of an appropriate age and sex distribution. To examine the VDR gene (rs10735810, rs2228570) and AGT gene (rs699) polymorphism, a qualitative real-time polymerase chain reaction was made. The lipid metabolism was studied by determining the blood plasma content of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TGs). RESULTS: Т allele of AGT gene is associated with reduced HDL-C level in men and increased TGs level in women. The EAH risk increases 4.5 times as much among the ТС-genotype carriers and lowered HDL-C level (odds ratio [OR] = 6.43; p = 0.01). The EAH risk increases as far as the HDL-C level reduction, irrespective of the VDR gene alleles condition 1.83 times (OR = 2.37; OR 95% confidence interval [CI]: 1.02–5.51; p = 0.04) and 1.9 times (OR=2.43; OR 95% CI: 0.99–5.97; p = 0.04). HDL-C reduction and LDL-C elevation in women increase the EAH risk 2.4 times (OR = 3.27; p = 0.01) and 1.24 times (OR = 3.67; p = 0.01), respectively. CONCLUSIONS: The EAH risk increases with a reduced HDL-C level in the TC genotype carriers of the AGT gene and irrespective of VDR gene polymorphic variants.

Butyrylcholinesterase-Protein Interactions in Human Serum.

Measuring various biochemical and cellular components in the blood is a routine procedure in clinical practice. Human serum contains hundreds of diverse proteins secreted from all cells and tissues in healthy and diseased states. Moreover, some serum proteins have specific strong interactions with other blood components, but most interactions are probably weak and transient. One of the serum proteins is butyrylcholinesterase (BChE), an enzyme existing mainly as a glycosylated soluble tetramer that plays an important role in the metabolism of many drugs. Our results suggest that BChE interacts with plasma proteins and forms much larger complexes than predicted from the molecular weight of the BChE tetramer. To investigate and isolate such complexes, we developed a two-step strategy to find specific protein–protein interactions by combining native size-exclusion chromatography (SEC) with affinity chromatography with the resin that specifically binds BChE. Second, to confirm protein complexes′ specificity, we fractionated blood serum proteins by density gradient ultracentrifugation followed by co-immunoprecipitation with anti-BChE monoclonal antibodies. The proteins coisolated in complexes with BChE were identified by mass spectroscopy. These binding studies revealed that BChE interacts with a number of proteins in the human serum. Some of these interactions seem to be more stable than transient. BChE copurification with ApoA-I and the density of some fractions containing BChE corresponding to high-density lipoprotein cholesterol (HDL) during ultracentrifugation suggest its interactions with HDL. Moreover, we observed lower BChE plasma activity in individuals with severely reduced HDL levels (≤20 mg/dL). The presented two-step methodology for determination of the BChE interactions can facilitate further analysis of such complexes, especially from the brain tissue, where BChE could be involved in the pathogenesis and progression of AD.

Predictive value of a reduction in the level of high-density lipoprotein-cholesterol in patients with non-small-cell lung cancer undergoing radical resection and adjuvant chemotherapy: a retrospective observational study

BackgroundCancer patients often exhibit chemotherapy-associated changes in serum lipid profiles, however, their prognostic value before and after adjuvant chemotherapy on survival among non-small-cell lung cancer (NSCLC) patients is unknown.MethodsNSCLC patients undergoing radical resection and subsequent adjuvant chemotherapy from 2013 to 2017 at Sun Yat-sen University Cancer Center were retrospectively reviewed. Fasted serum lipid levels were measured before and after chemotherapy. The optimal lipid cut-off values at baseline and fluctuation were determined using X-tile™. The fluctuations in serum lipid levels and disease-free survival (DFS) were assessed.ResultsSerum cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglyceride, apolipoprotein (Apo) A-I, and ApoB all significantly increased after adjuvant chemotherapy. X-tile determined 1.52 mmol/L of HDL-C and 0.74 g/L of ApoB as the optimal cut-off values before chemotherapy. Patients with HDL-C ≥ 1.52 mmol/L (median DFS: not reached vs. 26.30 months, P = 0.0005) and a decreased HDL-C level after adjuvant chemotherapy (median DFS: 80.43 vs. 26.12 months, P = 0.0204) had a longer DFS. An HDL-C level that increased by ≥ 0.32 mmol/L after chemotherapy indicated a worse DFS. A high baseline ApoB level were associated with a superior DFS. In the univariate analysis and the multivariate Cox analyses, a high baseline HDL-C level and a HDL-C reduction after adjuvant chemotherapy were independent indicators for superior DFS. High baseline HDL-C was related to N0-1 stage (χ2 = 6.413, P = 0.011), and HDL-C fluctuation was significantly correlated with specific chemotherapy regimens (χ2 = 5.002, P = 0.025).ConclusionsAdjuvant chemotherapy increased various lipid levels in resected NSCLC patients. A higher HDL-C level before chemotherapy and a reduced HDL-C level after adjuvant chemotherapy were independent predictors of longer DFS in patients with curable NSCLC.

HDL and type 2 diabetes: the chicken or the egg?

HDL is a complex macromolecular cluster of various components, such as apolipoproteins, enzymes and lipids. Quality evidence from clinical and epidemiological studies led to the principle that HDL-cholesterol (HDL-C) levels are inversely correlated with the risk of CHD. Nevertheless, the failure of many cholesteryl ester transfer protein inhibitors to protect against CVD casts doubts on this principle and highlights the fact that HDL functionality, as dictated by its proteome and lipidome, also plays an important role in protecting against metabolic disorders. Recent data indicate that HDL-C levels and HDL particle functionality are correlated with the pathogenesis and prognosis of type 2 diabetes mellitus, a major risk factor for CVD. Hyperglycaemia leads to reduced HDL-C levels and deteriorated HDL functionality, via various alterations in HDL particles' proteome and lipidome. In turn, reduced HDL-C levels and impaired HDL functionality impact the performance of key organs related to glucose homeostasis, such as pancreas and skeletal muscles. Interestingly, different structural alterations in HDL correlate with distinct metabolic abnormalities, as indicated by recent data evaluating the role of apolipoprotein A1 and lecithin-cholesterol acyltransferase deficiency in glucose homeostasis. While it is becoming evident that not all HDL disturbances are causatively associated with the development and progression of type 2 diabetes, a bidirectional correlation between these two conditions exists, leading to a perpetual self-feeding cycle.