Higher High-density Lipoprotein Cholesterol Concentrations Research Articles

Association of HDL cholesterol with all-cause and cardiovascular mortality in primary hypercholesterolemia

Background and aimsRecent reports have shown that subjects with high high-density lipoprotein cholesterol (HDLc) levels are paradoxically at increased risk for all-cause and cardiovascular mortality. The aim was to study the association of HDLc concentration with mortality in subjects with high cholesterol. MethodsWe analyzed total mortality, cardiovascular mortality, and non-cardiovascular mortality in a cohort of 2992 subjects with primary hypercholesterolemia, who were followed for 10.2 years (range 1–25 years), with a total of 30,602 subject-years of follow-up. ResultsDuring follow-up, 168 subjects died, with 52 (13.7 %), 105 (4.80 %), and 11 (2.60 %) in the low, normal, and high HDLc groups, respectively (p < 0.001). The risk of death was 2.89 times higher (95 % confidence interval (CI), 1.50–5.57, p < 0.001) in subjects in the low HDLc group compared to those in the high HDLc group and 1.48 times higher (95 % CI 0.80–2.76, p = 0.214) in the normal HDLc group compared to the high HDLc group. However, HDLc concentration and HDLc groups based on HDLc concentration were not independently associated with mortality in Cox regression analysis. Cardiovascular and non-cardiovascular mortalities showed similar results. ConclusionsAll types of mortality were lower in subjects with primary hypercholesterolemia and with high HDLc in univariate analysis. Elevated HDLc was not associated with total, cardiovascular, and non-cardiovascular mortality when adjusted for major cardiovascular risk factors.

A multitissue transcriptomic analysis reveals a potential mechanism whereby Brevibacillus laterosporus S62-9 promotes broiler growth

Brevibacillus laterosporus S62-9 has been shown to improve broiler growth performance and immunity. In the present study, we aimed to evaluate the effects of B. laterosporus S62-9 on the immunity and lipid metabolism of broilers by means of transcriptomic analysis. A total of 160 1-day-old broilers were randomly allocated to a S62-9 group, the diet of which was supplemented with 106 CFU/g B. laterosporus S62-9 daily, and a control group, which was not. After 42 d of feeding, the broilers in the S62-9 group had higher body mass (7.2%) and feed conversion ratio (5.19%) than the control group. Supplementation with B. laterosporus S62-9 resulted in lower serum total cholesterol and low-density lipoprotein-cholesterol concentrations and higher high-density lipoprotein-cholesterol concentrations. An analysis of the fatty acid composition of the broiler's thigh muscles revealed that the proportions of the unsaturated fatty acids myristoleic acid (C14:1) and arachidonic acid (C20:1) were higher for birds in the S62-9 group. Transcriptomic analysis also showed an upregulation of immunity-related genes in the S62-9 group. Gene Ontology functional enrichment analysis showed that the mitogen-activated protein kinase pathway was enriched in the liver, the defense response was enriched in the duodenum, and immunoglobulin-related entries were enriched in the jejunum of the S62-9 group. Furthermore, the expression of key genes involved in unsaturated fatty acid synthesis (SCD, encoding stearoyl-CoA desaturase) and fatty acid metabolism (HACD2, encoding 3-hydroxyacyl-CoA dehydratase 2) was upregulated in the liver, and the expression of genes associated with fat biosynthesis and accumulation, such as PLIN1, encoding perilipin 1, and FABP4, encoding fatty acid binding protein 4, was upregulated in the ileum of the birds in the S62-9 group. In summary, supplementation with B. laterosporus S62-9 could improve immune defense and the fatty acid metabolism of broiler chickens, thereby enhancing their disease resistance and promoting growth and development.

Association of the polymorphisms of the cholesteryl ester transfer protein gene with coronary artery disease: a meta-analysis.

This meta-analysis aimed to assess the association of the polymorphisms of cholesterol ester transfer protein (CETP) rs708272 (G>A), rs5882 (G>A), rs1800775 (C>A), rs4783961 (G>A), rs247616 (C>T), rs5883 (C>T), rs1800776 (C>A), and rs1532624 (C>A) with coronary artery disease (CAD) and the related underlying mechanisms. A comprehensive search was performed using five databases such as PubMed, EMBASE, Web of Science, Cochrane Library and Scopus to obtain the appropriate articles. The quality of the included studies was assessed by the Newcastle-Ottawa Scale. The statistical analysis of the data was performed using STATA 17.0 software. The association between CETP gene polymorphisms and risk of CAD was estimated using the pooled odds ratio (OR) and 95% confidence interval (95% CI). The association of CETP gene polymorphisms with lipids and with CETP levels was assessed using the pooled standardized mean difference and corresponding 95% CI. P < 0.05 was considered statistically significant. A total of 70 case-control studies with 30,619 cases and 31,836 controls from 46 articles were included. The results showed the CETP rs708272 polymorphism was significantly associated with a reduced risk of CAD under the allele model (OR = 0.846, P < 0.001), the dominant model (OR = 0.838, P < 0.001) and the recessive model (OR = 0.758, P < 0.001). AA genotype and GA genotype corresponded to higher high-density lipoprotein cholesterol (HDL-C) concentrations in the blood compared with GG genotype across the studied groups (all P < 0.05). The CETP rs5882 and rs1800775 polymorphisms were not significantly associated with CAD under the allele model (P = 0.802, P = 0.392), the dominant model (P = 0.556, P = 0.183) and the recessive model (P = 0.429, P = 0.551). Similarly, the other mentioned gene polymorphisms were not significantly associated with CAD under the three genetic models. The CETP rs708272 polymorphism shows a significant association with CAD, and the carriers of the allele A are associated with a lower risk of CAD and higher HDL-C concentrations in the blood compared to the non-carriers. The CETP rs5882, rs1800775, rs4783961, rs247616, rs5883, rs1800776, and rs1532624 are not significantly associated with CAD. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023432865, identifier: CRD42023432865.

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.

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 between snus use and lipid status in Swedish men

Snus is a common tobacco product in Sweden, but the cardiovascular risk profile for snus users is less known than for cigarette smokers. We examined the association of snus use with lipid status, particularly in comparison to non-tobacco use and cigarette smoking, using data from 5930 men in the Northern Sweden MONICA study. Tobacco use was self-reported in 1986 to 2014 (24.4% used snus) and blood samples were collected at the same time. Harmonized analyses on non-high-density lipoprotein (non-HDL) cholesterol, HDL cholesterol, and triglycerides were conducted in 2016 to 2018. Three hundred eighty-one snus users had also been examined more than once, allowing us to study the effect of discontinued use (achieved by 21.0%). In multivariable linear regression models, snus use was associated with higher HDL cholesterol and triglyceride concentrations compared to non-tobacco use (p values ≤ 0.04), and it was associated with higher HDL cholesterol concentrations and lower triglyceride concentrations compared to cigarette smoking (p values ≤ 0.02). Snus use was not associated with non-HDL cholesterol concentrations, irrespective of the comparison group (p values ≥ 0.07). There was no indication that higher intensity of snus use led to a worse lipid profile, given that high-consumers had higher HDL cholesterol concentrations than low-consumers (p value = 0.02), or that discontinuation of snus use led to a better lipid profile, given that continued users had lower triglyceride concentrations than discontinued users (p value = 0.03). Further studies are needed to confirm or refute our findings.

Abstract P551: Genetic Variants in the Adenosine Triphosphate-Binding Cassette Transporter A1 and Risk of Age-Related Macular Degeneration

Objective: Genetic variants in the adenosine triphosphate-binding cassette transporter A1( ABCA1 ) is 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. Methods: We genotyped all amino acid changing ABCA1 variants with a minor allele frequency above 0.002, measured plasma HDL cholesterol and other plasma lipids, and used Cox regression to assess risk of AMD. We created an HDL cholesterol weighted allele score and tested the association with risk of AMD on a continuous scale and in tertiles. Further, we performed mediation analyses. Main outcome measures: 1,554 AMD events. Median follow-up of 10 years. Results: Of 90,344 study participants, 55% were women. Median age was 58 (interquartile range: 47-67) years. On a continuous scale, higher concentrations of genetically determined HDL cholesterol were associated with higher risk of all-cause AMD, dry AMD, and wet AMD both in an age- and sex adjusted model and in a multivariable adjusted model (See Figure). 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 dry AMD, and 1.31 (1.12-1.53) for wet AMD in a multivariable adjusted model. 6-8% of the effect was mediated through HDL cholesterol. There was no interaction between weighted allele score tertiles and confounding factors on risk of AMD. Conclusions: Amino acid changing genetic variants in ABCA1 which were associated with higher HDL cholesterol concentrations, were also associated with higher risk of AMD, both on a weighted allele score continuously and when divided into tertiles.

Glycemic index and heart disease , ,

A diet high in carbohydrates with high glycemic indexes (GI) and glycemic load were linked to risk of coronary heart disease development in women in a large prospective study. Two cross-sectional studies showed that low-GI diets are associated with high HDL-cholesterol concentrations, especially in women. In a tightly controlled study of patients with type 2 diabetes, serum total cholesterol, LDL cholesterol, and apolipoprotein B concentrations fell more significantly after a low-GI diet than after a high-GI diet. In the same study, plasminogen activator inhibitor-1 concentrations were reduced by 58% after the low-GI diet. Insulin-stimulated glucose uptake by adipocytes was significantly higher in patients undergoing coronary artery bypass graft surgery after 4 wk of consuming a low-GI diet than after consuming a high-GI diet. The effects of low-GI diets may be mediated by changes in postprandial fatty acid concentrations or by hormonal signals from adipocytes, but a possible association of low-GI diets with some other dietary factor such as chromium must not be excluded. Proof of the clinical value of low-GI diets awaits prospective trials, which should include short-term observations covering periods of metabolic stress induced by surgery as well as long-term trials with clinical endpoints.

Atherogenic dyslipidemia and associated risk factors among hypertensive patients of five health facilities in Northeast Ethiopia.

One of the major risk factors for cardiovascular disease is atherogenic dyslipidemia. There was, however, little information available in Ethiopia. Therefore, the purpose of this study was to estimate the prevalence of atherogenic dyslipidemia and related risk factors in Northeast Ethiopian hypertension patients. A systematic random sampling technique was used to perform a cross-sectional study at an institution with 384 chosen participants. A structured questionnaire was used to collect the socio-demographic, anthropometric, lifestyle, and clinical characteristics of the respondents. Student's t-test, Mann-Whitney test, and Pearson's Chi-square test were employed to compare groups based on the type of data. Furthermore, Bivariate and multivariable logistic regression analyses were performed to identify factors independently associated with dyslipidemia. Crude and adjusted odds ratios and their corresponding 95% Confidence Intervals (CI) were computed. In all cases, statistical significance was declared at p <0.05. The majority (93.2%; 95%CI: 90.6-95.6) of patients had at least one atherogenic dyslipidemia. The prevalence of elevated total cholesterol (TC), elevated triglyceride (TG), raised low-density lipoprotein cholesterol (LDL-c), and reduced high-density lipoprotein cholesterol (HDL-c) were 47.7%, 50.3%, 44.3%, and 59.6%, respectively. Being≥ 40 years were at higher risk for having elevated levels of TC (AOR: 3.22, 95% CI: 2.40-4.32), TG (AOR: 2.30, 95% CI: 1.61-3.79), and LDL-c (AOR: 4.68, 95% CI: 2.0-10.95) than those who were below 40years. Obese participants were more likely to have high concentrations of TC (AOR: 2.57, 95%CI: 2.10-3.22), LDL-c (AOR: 3.13, 95% CI: 1.97-5.10), HDL-c (AOR: 2.71, 95% CI: 1.77-4.58), and TG (AOR: 2.23, 95%CI: 1.79-4.16). This study revealed that a high prevalence of atherogenic dyslipidemia. Thus, to prevent atherogenic dyslipidemia, it is crucial to create routine blood lipid testing programs and carry out suitable intervention programs focused on risk factor reduction.

Serum opacity factor rescues fertility among female Scarb1−/− mice by reducing HDL-free cholesterol bioavailability

Human female infertility, 20% of which is idiopathic, is a public health problem for which better diagnostics and therapeutics are needed. A novel cause of infertility emerged from studies of female mice deficient in the HDL receptor gene (Scarb1). These mice are infertile and have high plasma HDL cholesterol (C) concentrations, due to elevated HDL-free cholesterol (FC), which transfers from HDL to all tissues. Previous studies have indicated that oral delivery of probucol, an HDL-lowering drug, to female Scarb1−/− mice reduces plasma HDL-C concentrations and rescues fertility. Additionally, serum opacity factor (SOF), a bacterial virulence factor, disrupts HDL structure, and bolus SOF injection into mice reduces plasma HDL-C concentrations. Here, we discovered that delivering SOF to female Scarb1−/− mice with an adeno-associated virus (AAVSOF) induces constitutive SOF expression, reduces HDL-FC concentrations, and rescues fertility while normalizing ovary morphology. Although AAVSOF did not alter ovary-FC content, the ovary-mol% FC correlated with plasma HDL-mol% FC in a fertility-dependent way. Therefore, reversing the abnormal plasma microenvironment of high plasma HDL-mol% FC in female Scarb1-/- mice rescues fertility. These data provide the rationale to search for similar mechanistic links between HDL-mol% FC and infertility and the rescue of fertility in women by reducing plasma HDL-mol% FC.

High-Density Lipoprotein and Long-Term Incidence and Progression of Aortic Valve Calcification: The Multi-Ethnic Study of Atherosclerosis.

Aortic valve calcification (AVC) shares pathological features with atherosclerosis. Lipoprotein components have been detected in aortic valve tissue, including HDL (high-density lipoprotein). HDL measures have inverse associations with cardiovascular disease, but relationships with long-term AVC progression are unclear. We investigated associations of HDL cholesterol, HDL-particle number and size, apoC3-defined HDL subtypes, and, secondarily, CETP (cholesteryl ester transfer protein) mass and activity, with long-term incidence and progression of AVC. We used linear mixed-effects models to evaluate the associations of baseline HDL indices with AVC. AVC was quantified by Agatston scoring of up to 3 serial computed tomography scans over a median of 8.9 (maximum 11.2) years of follow-up in the Multi-Ethnic Study of Atherosclerosis (n=6784). After adjustment, higher concentrations of HDL-C (high-density lipoprotein cholesterol), HDL-P (HDL particles), large HDL-P, and apoC3-lacking HDL-C were significantly associated with lower incidence/progression of AVC. Neither small or medium HDL-P nor apoC3-containing HDL-C was significantly associated with AVC incidence/progression. When included together, a significant association was observed only for HDL-C, but not for HDL-P. Secondary analyses showed an inverse relationship between CETP mass, but not activity, and AVC incidence/progression. In exploratory assessments, inverse associations for HDL-C, HDL-P, large HDL-P, and apoC3-lacking HDL with AVC incidence/progression were more pronounced for older, male, and White participants. ApoC3-containing HDL-C only showed a positive association with AVC in these subgroups. In a multiethnic population, HDL-C, HDL-P, large HDL-P, and apoC3-lacking HDL-C were inversely associated with long-term incidence and progression of AVC. Further investigation of HDL composition and mechanisms could be useful in understanding pathways that slow AVC.

Association Between High-Density Lipoprotein Cholesterol Levels and Adverse Cardiovascular Outcomes in High-risk Populations

Previous studies have shown lower cardiovascular risk with higher high-density lipoprotein cholesterol (HDL-C) levels. However, recent data in the general population have shown increased risk of adverse outcomes at very high HDL-C concentrations. To study the association between very high HDL-C levels (>80 mg/dL) and mortality in patients with coronary artery disease (CAD) and to investigate the association of known HDL-C genotypes with high HDL-C level outcomes. This prospective, multicenter, cohort study, conducted from 2006 to present in the UK and from 2003 to present in Atlanta, Georgia, recruited patients with CAD from the UK Biobank (UKB) and the Emory Cardiovascular Biobank (EmCAB), respectively. Patients without confirmed CAD were excluded from the study. Data analyses were conducted from May 10, 2020, to April 28, 2021. High HDL-C levels (>80 mg/dL). The primary outcome was all-cause death. The secondary outcome was cardiovascular death. A total of 14 478 participants (mean [SD] age, 62.1 [5.8] years; 11 034 men [76.2%]) from the UKB and 5467 participants (mean [SD] age, 63.8 [12.3] years; 3632 men [66.4%]) from the EmCAB were included in the study. Over a median follow-up of 8.9 (IQR, 8.0-9.7) years in the UKB and 6.7 (IQR, 4.0-10.8) years in the EmCAB, a U-shaped association with outcomes was observed with higher risk in those with both low and very high HDL-C levels compared with those with midrange values. Very high HDL-C levels (>80 mg/dL) were associated with increased risk of all-cause death (hazard ratio [HR], 1.96; 95% CI, 1.42-2.71; P < .001) and cardiovascular death (HR, 1.71; 95% CI, 1.09-2.68; P = .02) compared with those with HDL-C levels in the range of 40 to 60 mg/dL in the UKB after adjustment for confounding factors. These results were replicated in the EmCAB. These associations persisted after adjustment for the HDL-C genetic risk score within the UKB. Sensitivity analyses demonstrated that the risk of all-cause mortality in the very high HDL-C group was higher among men than women in the UKB (HR, 2.63; 95% CI, 1.75-3.95; P < .001 vs HR, 1.39; 95% CI, 0.82-2.35; P = .23). Results of this cohort study suggest that very high HDL-C levels are paradoxically associated with higher mortality risk in individuals with CAD. This association was independent of the common polymorphisms associated with high HDL-C levels.

Abstract 499: Serum Opacity Factor Therapy Alters Plasma, Erythrocyte And Tissue Cholesterol Content In The Dysfunctional High Density Lipoprotein Scarb1 -/- Mouse Model

Aim: In humans, very high plasma HDL-cholesterol concentrations are associated with increased all cause- and atherosclerotic cardiovascular disease (ASCVD)-mortality. The HDL receptor-deficient mouse (Scarb1 -/- ) is a robust model of this phenotype having high free cholesterol (FC) bioavailability due to too many FC-rich HDL particles. Clinically, plasma LDL and HDL are quantified according to total cholesterol = FC + cholesteryl esters (CE), which likely contribute to ASCVD pathophysiology differently. Despite higher HDL, Scarb1 -/- mice have more ASCVD on a Western diet, and increased mol% FC in ovaries, erythrocytes, heart, lung, female liver and macrophages, tissues that are associated with female infertility, impaired cell maturation, cardiac dysfunction and atherosclerosis. Bacterial serum opacity factor (SOF) reduces plasma cholesterol ~ 40% by diverting HDL-cholesterol to the hepatic LDLR. Hypothesis: Adeno-associated virus delivery of SOF (AAV SOF ) normalizes plasma and tissue FC accretion and reverses the pathologies associated with Scarb1 -/- mice. Methods: The lipid compositions of plasma, HDL, erythrocytes, and tissues of Scarb1 -/- mice treated with AAV SOF at 12-13 weeks of age for three weeks were compared with age- and sex-matched wild type (WT) C57BL6 and Scarb1 -/- mice. Results: As hypothesized, AAV SOF reduced plasma and HDL-FC and CE, as well as mol% FC in Scarb1 -/- mice towards WT levels. Erythrocyte FC levels also fell, but mol% FC remained elevated. Some changes were sex-specific: AAV SOF reduced the elevated FC only in female livers to WT levels. AAV SOF reduced FC and CE in lungs of females to WT levels, but not among males; the mol% FC remained high in both sexes. In steroidogenic tissues, adrenals, ovaries and testis, AAV SOF treatment increased FC. Unexpectedly, in Scarb1 -/- mice, AAV SOF increased mol% FC and FC in heart beyond already elevated levels. Conclusions: These findings support the hypothesis that plasma and HDL cholesterol levels determine tissue cholesterol levels that drive the pathologies specific to Scarb1 -/- mice. This evolving model of the role of HDL-FC in RCT provides a rationale for human studies to determine the utility of HDL-FC bioavailability as a risk factor for ASCVD and other pathologies.

Dietary calcium intake in relation to blood lipids and lipoproteins profiles: A systematic review and meta-analysis of epidemiologic studies

AimsFindings of prior investigations on the association between calcium intake and lipid profiles were inconsistent. We performed a systematic review and meta-analysis on epidemiologic studies to evaluate the relationship of dietary calcium intake with blood lipids and lipoproteins. Data synthesisA systematic search up to April 2021 was performed in different electronic databases, including MEDLINE (PubMed), Scopus, Web of Science (ISI), and Google Scholar for epidemiological studies that considered dietary calcium intake as the exposure and reported risk of dyslipidemia or blood lipids and lipoproteins concentrations (as mean ± SD or mean ± SE or median (Inter Quartile Range) as the outcomes of interest in adult populations from both genders (18 years or older), regardless of their health status. Nineteen cross-sectional studies were included in the analysis. Combining estimates from 11 studies (including 33,304 subjects) revealed that individuals in the highest category of calcium intake, compared to the lowest one, had 5.94 mg/dL lower circulating triglyceride (TG) concentration (weighted mean difference (WMD): −5.94; 95% CI: −8.27, −3.62), 4.02 mg/dL lower circulating low-density lipoprotein cholesterol (LDL-c) levels (WMD: −4.02; 95% CI: −7.08, −0.95), and 1.56 mg/dL higher blood high-density lipoprotein cholesterol (HDL-c) (WMD: 1.56; 95% CI: 0.81, 2.30). Although meta-analysis on 13 studies (including 38,714 participants) did not reveal a significant relationship between dietary calcium intake and odds of dyslipidemia or hyperlipidemia in the whole population, the highest vs. lowest level of calcium intake was related to 42% decreased odds of low blood HDL-c levels in females (95% CI: 0.40, 0.84) and 41% increased odds in males (95% CI: 1.21, 1.65). ConclusionsThis meta-analysis demonstrated that individuals with the highest dietary calcium intake might have lower blood TG, LDL-c, and higher HDL-c concentrations as compared to those with the lowest calcium intake. However, the linkage between dietary calcium intake with odds of hyperlipidemia or dyslipidemia was not significant. Because of the cross-sectional nature of included studies, causality could not be proven. Further prospective studies are needed to affirm these findings.

Very High High-Density Lipoprotein Cholesterol Levels and Cardiovascular Mortality

Previous studies have shown reduced cardiovascular risk with increasing high-density lipoprotein cholesterol (HDL-C) levels. However, recent data in the general population have shown increased risk of adverse outcomes at very high concentrations of HDL-C. Thus, we aimed to study the gender-specific relation between very high HDL-C levels (>80, >100mg/100ml) and adverse cardiovascular outcomes and the genetic basis in the general population enrolled in the United Kingdom Biobank. A total of 415,416 participants enrolled in the United Kingdom Biobank without coronary artery disease were included in this prospective cohort study, with a median follow-up of 9years. A high HDL-C level >80mg/100ml was associated with increased risk of all-cause death (Hazard ratio [HR] 1.11, confidence interval [CI] 1.03 to 1.20, p=0.005) and cardiovascular death (HR 1.24, CI 1.05 to 1.46, p=0.01) after adjustment for age, gender, race, body mass index, hypertension, smoking, triglycerides, LDL-C, stroke history, heart attack history, diabetes, eGFR, and frequent alcohol use (defined as ≥3 times/week) using Cox proportional hazard and Fine and Gray's subdistribution hazard models, respectively. In gender-stratified analyses, such associations were only observed in men (all-cause death HR 1.79, CI 1.59 to 2.02, p <0.0001; cardiovascular death HR 1.92, CI 1.52 to 2.42, p <0.0001), but not in women (all-cause death HR 0.97, CI 0.88 to 1.06, p=0.50; cardiovascular death HR 1.04, CI 0.83 to 1.31, p=0.70). The findings persisted after adjusting for the genetic risk score comprised of known HDL-C-associated single nucleotide polymorphisms. Very high HDL-C levels are associated with an increased risk of all-cause death and cardiovascular death among men but not in women in the general population free of coronary artery disease.

Metformin versus insulin therapy for gestational diabetes: Effects on offspring anthropometrics and metabolism at the age of 9 years: A follow-up study of two open-label, randomized controlled trials.

AimsTo compare anthropometrics, and lipid and glucose metabolism in the 9‐year‐old offspring of mothers treated with metformin or insulin for gestational diabetes mellitus (GDM).Materials and MethodsThis was a Finnish two‐centre, 9‐year follow‐up study of two open‐label, randomized controlled trials comparing the effects observed in the offspring of mothers who received metformin and insulin treatment for GDM. Measurements included anthropometrics, blood pressure, lipoproteins, and oral glucose tolerance tests. This study was registered with ClinicalTrials.gov, number NCT02417090.ResultsAt the age of 9 years 172 children (55% of the original study cohort, 82 from the metformin and 90 from the insulin group) participated in the study. No differences were found between the 9‐year‐old offspring groups in anthropometric variables, including body mass index and waist‐to‐height ratio. The offspring in the metformin group had higher high‐density lipoprotein (HDL) cholesterol concentrations (1.72 vs. 1.54 mmol/L; P = 0.039) but lower low‐density lipoprotein cholesterol (2.39 vs. 2.58 mmol/L; P = 0.046) and apolipoprotein B concentrations (0.63 vs. 0.67 g/L; P = 0.043) than the offspring in the insulin group. The difference in HDL cholesterol concentration was found to be significant only in boys (P = 0.003). The 2‐hour glucose value in the oral glucose tolerance test was 0.6‐mmol/L lower in boys from the metformin group than in those from the insulin group (P = 0.015).ConclusionsMetformin treatment for GDM is associated with similar offspring growth and glucose metabolism but a more favourable lipid profile at the age of 9 years as compared to insulin treatment.

Impact of Fatty Acids on Obesity-Associated Diseases and Radical Weight Reduction

PurposeFatty acids (FA), particularly polyunsaturated (PUFA) ones, are involved in the regulation of glycemic control, lipid metabolism, and inflammation. The aim of the study was to assess patient FA profile in relation to obesity, lipid and carbohydrate metabolism disturbances, and weight loss.Materials and MethodsThe studied group consisted of 51 patients with extreme obesity, 23 of whom achieved radical weight reduction within 1 year after a laparoscopic sleeve gastrectomy (LSG). FA levels were determined using gas chromatography with flame ionization detection.ResultsPatients with extreme obesity and higher serum PUFA content have lower serum levels of SFA and MUFA (especially myristic, palmitic, lignoceric acids and palmitoleic, oleic acids), as well as lower triglyceride and higher HDL-cholesterol concentrations and it was not influenced by CEPT Taq1B variant. At baseline, the fatty acid profile of patients with type II diabetes differ from patients with dyslipidemia. In patients who had lost weight, significantly lower levels of selected saturated FA and major trans-fatty acid, elaidic, were found. Moreover, the proportion of PUFA was increased.ConclusionIn extreme obesity, higher PUFA exert their favorable effects on serum lipids. Significant weight reduction after the bariatric surgery is associated with beneficial changes in the fatty acid profile.Graphical

Association of Serum High-Density Lipoprotein Cholesterol with High Blood Pressures at Checkup: Results of Kanagawa Investigation of Total Checkup Data from the National Database-9 (KITCHEN-9).

Background: although high-density lipoprotein has cardioprotective effects, the association between serum high-density lipoprotein cholesterol (HDL-C) and hypertension is poorly understood. Therefore, we investigated whether high and low concentrations of HDL-C are associated with high blood pressure (HBP) using a large healthcare dataset. Methods: in a community-based cross-sectional study of 1,493,152 Japanese people (830,669 men and 662,483 women) aged 40–74 years who underwent a health checkup, blood pressures automatically measured at healthcare center were investigated in nine HDL-C groups (20–110 mg/dL or over). Results: crude U-shaped relationship were observed between the nine HDL-C and blood pressures in both men and women. Logistic regression analysis showed left-to-right inverted J-shaped relationships between HDL-C and odds ratios for HBP (≥140/90 mmHg and/or pharmacotherapy), with lower limits of 90–99 mg/dL in both sexes, which were unchanged after adjusting for confounding factors. However, further adjustment for body mass index and serum triglyceride concentration revealed positive linear associations between HDL-C and HBP, although blunt U-shaped associations remained in nonalcohol drinkers. Conclusion: both low and extremely high HDL-C concentrations are associated with HBP. The former association might be dependent on excess fat mass concomitant with low HDL-C, whereas the latter association may be largely dependent on frequent alcohol consumption.

Postprandial dyslipidemia after a standardized high-fat meal in BMI-matched healthy individuals, and in subjects with prediabetes or type 2 diabetes

A relationship between postprandial hyperlipidemia and glucose homeostasis/cardiovascular diseases has been suggested. We investigated postprandial plasma lipid patterns after a standardized high-fat meal and their association with glucose homeostasis and subclinical atherosclerosis. Using matching by BMI, 32 healthy individuals with normal glucose tolerance (NGT), 21 subjects with impaired glucose tolerance (IGT), and 20 subjects with drug-naïve type 2 diabetes (T2D) were enrolled. Plasma concentrations of triglycerides (TGs), apolipoprotein-B (ApoB), ApoB48, ApoB100, glucose, and insulin at baseline and 1, 2, 3, 4, 5, 6, and 8h after a standardized meal (1041.03kcal with 70.99g of fat) were measured. Body composition, abdominal visceral fat area, and resting energy expenditure (REE) were measured using dual energy X-ray absorptiometry, computed tomography, and indirect calorimetry, respectively. The intima-media thickness (IMT) of the carotid artery and the ankle-brachial index (ABI) were used to detect subclinical atherosclerosis. Baseline data and area under the curve (AUC) of plasma concentrations of TGs, ApoB, and ApoB48 in the IGT and T2D groups were higher than in the NGT group. The peak TG concentrations after the meal was observed at 5h in subjects with IGT and T2D, while healthy subjects showed the highest concentrations at 4h. In multivariable analysis, high abdominal visceral fat area and low HDL-cholesterol concentrations were independently associated with the AUCTG and AUCApoB after adjusting for confounders including baseline TG and the REE. High LDL-cholesterol and high HbA1c concentrations were also associated with the AUCApoB. Furthermore, high AUCTG and AUCApoB values were independent factors for an increased carotid IMT and a low ABI after adjusting for relevant variables. Abdominal visceral obesity and low HDL-cholesterol concentrations were associated with increased post load excursions of TGs and ApoB in this series. These elevated concentrations of TGs and ApoB were linked with subclinical atherosclerosis.

Different associations between HDL cholesterol and cardiovascular diseases in people with diabetes mellitus and people without diabetes mellitus: a prospective community-based study

Experimental studies have found that the functionality of HDL cholesterol may be lost in the presence of diabetes mellitus (DM). We aimed to elucidate whether DM modified the association between HDL-cholesterol concentrations and cardiovascular disease (CVD) outcomes. Included were 91,354 Chinese adults (8244 participants with DM and 83,110 participants without DM) free of CVD or cancer at baseline (2006) and without use of lipid-lowering drugs at baseline and during follow-up. The primary endpoint of interest was a composite of CVDs (myocardial infarction, ischemic stroke, and hemorrhagic stroke). Cumulative average HDL-cholesterol concentrations were calculated from all available HDL-cholesterol measures at baseline (2006) and during the follow-up period (2008, 2010, 2012, and 2014). During a mean of 10.4 y of follow-up, there were 5076 CVD events identified. There was a significant interaction between DM and HDL-cholesterol concentrations on CVD risk (Pinteraction=0.003). The association between HDL-cholesterol concentrations and CVD followed a U-shaped curve in individuals without DM (Pnonlinearity<0.001). The adjusted HR of CVD was 1.26 (95% CI: 1.07, 1.48) for HDL-cholesterol concentrations<1.04 mmol/L and 1.76 (95% CI: 1.53, 2.03) for HDL-cholesterol concentrations>2.07 mmol/L, relative to the lowest-risk group (HDL-cholesterol concentrations of 1.30-1.42 mmol/L). In participants with DM, higher HDL-cholesterol concentrations were associated with a higher risk of CVD, in a dose-response manner (Pnonlinearity=0.44; Ptrend<0.001). The adjusted HR of CVD was 1.62 (95% CI: 1.19, 2.20) for HDL-cholesterol concentrations>2.07 mmol/L, relative to HDL-cholesterol concentrations of 1.30-1.42 mmol/L. High HDL-cholesterol concentrations were paradoxically associated with high risk of composite CVD outcomes in individuals with or without DM. However, low HDL-cholesterol concentrations failed to predict future CVD risk in individuals with DM.