Altered HDL metabolism in metabolic disorders: insights into the therapeutic potential of HDL

2019 ◽  
Vol 133 (21) ◽  
pp. 2221-2235 ◽  
Author(s):  
Nicholas Hui ◽  
Philip J. Barter ◽  
Kwok-Leung Ong ◽  
Kerry-Anne Rye
Keyword(s):  
Metabolic Disorders ◽  
Therapeutic Potential ◽  
Stable Coronary Artery Disease ◽  
Density Lipoprotein ◽  
Metabolic Abnormalities ◽  
Cvd Risk ◽  
Coronary Syndrome ◽  
Hdl Function ◽  
Increased Risk ◽  
The Impact

Abstract Metabolic disorders are associated with an increased risk of cardiovascular disease (CVD), and are commonly characterized by a low plasma level of high-density lipoprotein cholesterol (HDL-C). Although cholesterol lowering medications reduce CVD risk in these patients, they often remain at increased risk of CVD. Therapeutic strategies that raise HDL-C levels and improve HDL function are a potential treatment option for reducing residual CVD risk in these individuals. Over the past decade, understanding of the metabolism and cardioprotective functions of HDLs has improved, with preclinical and clinical studies both indicating that the ability of HDLs to mediate reverse cholesterol transport, inhibit inflammation and reduce oxidation is impaired in metabolic disorders. These cardioprotective effects of HDLs are supported by the outcomes of epidemiological, cell and animal studies, but have not been confirmed in several recent clinical outcome trials of HDL-raising agents. Recent studies suggest that HDL function may be clinically more important than plasma levels of HDL-C. However, at least some of the cardioprotective functions of HDLs are lost in acute coronary syndrome and stable coronary artery disease patients. HDL dysfunction is also associated with metabolic abnormalities. This review is concerned with the impact of metabolic abnormalities, including dyslipidemia, obesity and Type 2 diabetes, on the metabolism and cardioprotective functions of HDLs.

scholarly journals Obesity-Related Changes in High-Density Lipoprotein Metabolism and Function

2020 ◽  
Vol 21 (23) ◽  
pp. 8985
Author(s):  
Julia T. Stadler ◽  
Gunther Marsche
Keyword(s):  
High Density Lipoprotein ◽  
Virgin Olive Oil ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
High Density ◽  
Atherogenic Dyslipidemia ◽  
Hdl Function ◽  
Increased Risk ◽  
And Function ◽  
The Impact

In obese individuals, atherogenic dyslipidemia is a very common and important factor in the increased risk of cardiovascular disease. Adiposity-associated dyslipidemia is characterized by low high-density lipoprotein cholesterol (HDL-C) levels and an increase in triglyceride-rich lipoproteins. Several factors and mechanisms are involved in lowering HDL-C levels in the obese state and HDL quantity and quality is closely related to adiponectin levels and the bioactive lipid sphingosine-1-phosphate. Recent studies have shown that obesity profoundly alters HDL metabolism, resulting in altered HDL subclass distribution, composition, and function. Importantly, weight loss through gastric bypass surgery and Mediterranean diet, especially when enriched with virgin olive oil, is associated with increased HDL-C levels and significantly improved metrics of HDL function. A thorough understanding of the underlying mechanisms is crucial for a better understanding of the impact of obesity on lipoprotein metabolism and for the development of appropriate therapeutic approaches. The objective of this review article was to summarize the newly identified changes in the metabolism, composition, and function of HDL in obesity and to discuss possible pathophysiological consequences.

scholarly journals Profile of copper-associated DNA methylation and its association with incident acute coronary syndrome

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Pinpin Long ◽  
Qiuhong Wang ◽  
Yizhi Zhang ◽  
Xiaoyan Zhu ◽  
Kuai Yu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Acute Coronary Syndrome ◽  
Methylation Level ◽  
Meta Analysis ◽  
Regulation Of Gene Expression ◽  
Density Lipoprotein ◽  
Blood Leukocytes ◽  
Coronary Syndrome ◽  
A Genome ◽  
Increased Risk

Abstract Background Acute coronary syndrome (ACS) is a cardiac emergency with high mortality. Exposure to high copper (Cu) concentration has been linked to ACS. However, whether DNA methylation contributes to the association between Cu and ACS is unclear. Methods We measured methylation level at > 485,000 cytosine-phosphoguanine sites (CpGs) of blood leukocytes using Human Methylation 450 Bead Chip and conducted a genome-wide meta-analysis of plasma Cu in a total of 1243 Chinese individuals. For plasma Cu-related CpGs, we evaluated their associations with the expression of nearby genes as well as major cardiovascular risk factors. Furthermore, we examined their longitudinal associations with incident ACS in the nested case-control study. Results We identified four novel Cu-associated CpGs (cg20995564, cg18608055, cg26470501 and cg05825244) within a 5% false discovery rate (FDR). DNA methylation level of cg18608055, cg26470501, and cg05825244 also showed significant correlations with expressions of SBNO2, BCL3, and EBF4 gene, respectively. Higher DNA methylation level at cg05825244 locus was associated with lower high-density lipoprotein cholesterol level and higher C-reactive protein level. Furthermore, we demonstrated that higher cg05825244 methylation level was associated with increased risk of ACS (odds ratio [OR], 1.23; 95% CI 1.02–1.48; P = 0.03). Conclusions We identified novel DNA methylation alterations associated with plasma Cu in Chinese populations and linked these loci to risk of ACS, providing new insights into the regulation of gene expression by Cu-related DNA methylation and suggesting a role for DNA methylation in the association between copper and ACS.

scholarly journals Gestational Diabetes Mellitus and Infant Adiposity at Birth: A Systematic Review and Meta-Analysis of Therapeutic Interventions

2021 ◽  
Vol 10 (4) ◽  
pp. 835
Author(s):  
Manoja P. Herath ◽  
Jeffrey M. Beckett ◽  
Andrew P. Hills ◽  
Nuala M. Byrne ◽  
Kiran D. K. Ahuja
Keyword(s):  
Diabetes Mellitus ◽  
Adipose Tissue ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Fat Mass ◽  
Metabolic Disorders ◽  
Later Life ◽  
Therapeutic Interventions ◽  
Increased Risk ◽  
The Impact

Exposure to untreated gestational diabetes mellitus (GDM) in utero increases the risk of obesity and type 2 diabetes in adulthood, and increased adiposity in GDM-exposed infants is suggested as a plausible mediator of this increased risk of later-life metabolic disorders. Evidence is equivocal regarding the impact of good glycaemic control in GDM mothers on infant adiposity at birth. We systematically reviewed studies reporting fat mass (FM), percent fat mass (%FM) and skinfold thicknesses (SFT) at birth in infants of mothers with GDM controlled with therapeutic interventions (IGDMtr). While treating GDM lowered FM in newborns compared to no treatment, there was no difference in FM and SFT according to the type of treatment (insulin, metformin, glyburide). IGDMtr had higher overall adiposity (mean difference, 95% confidence interval) measured with FM (68.46 g, 29.91 to 107.01) and %FM (1.98%, 0.54 to 3.42) but similar subcutaneous adiposity measured with SFT, compared to infants exposed to normal glucose tolerance (INGT). This suggests that IGDMtr may be characterised by excess fat accrual in internal adipose tissue. Given that intra-abdominal adiposity is a major risk factor for metabolic disorders, future studies should distinguish adipose tissue distribution of IGDMtr and INGT.

scholarly journals Evaluating the effects of alcohol and tobacco use on cardiovascular disease using multivariable Mendelian randomization

2019 ◽  
Author(s):  
Daniel B. Rosoff ◽  
George Davey Smith ◽  
Nehal Mehta ◽  
Toni-Kim Clarke ◽  
Falk W. Lohoff
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Alcohol Use ◽  
Tobacco Use ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Density Lipoprotein ◽  
Genome Wide Association Studies ◽  
Cvd Risk ◽  
Increased Risk

ABSTRACTAlcohol and tobacco use, two major modifiable risk factors for cardiovascular disease (CVD), are often consumed together. Using large publicly available genome-wide association studies (results from > 940,000 participants), we conducted two-sample multivariable Mendelian randomization (MR) to simultaneously assess the independent effects of alcohol and tobacco use on CVD risk factors and events. We found genetic instruments associated with increased alcohol use, controlling for tobacco use, associated with increased high-density-lipoprotein-cholesterol (HDL-C), decreased triglycerides, but not with coronary heart disease (CHD), myocardial infarction (MI), nor stroke; and instruments for increased tobacco use, controlling for alcohol use, associated with decreased HDL-C, increased triglycerides, and increased risk of CHD and MI. Exploratory analysis found associations with HDL-C, LDL-C, and intermediate-density-lipoprotein metabolites. Consistency of results across complementary methods accommodating different MR assumptions strengthened causal inference, providing strong genetic evidence for the causal effects of modifiable lifestyle risk factors on CVD risk.

scholarly journals Could Omega 3 Fatty Acids Preserve Muscle Health in Rheumatoid Arthritis?

Nutrients ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 223
Author(s):  
Kassandra Lanchais ◽  
Frederic Capel ◽  
Anne Tournadre
Keyword(s):  
Rheumatoid Arthritis ◽  
Insulin Resistance ◽  
Fatty Acids ◽  
Density Lipoprotein ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Cvd Risk ◽  
Cardiometabolic Diseases ◽  
Increased Risk ◽  
Muscle Health

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by a high prevalence of death due to cardiometabolic diseases. As observed during the aging process, several comorbidities, such as cardiovascular disorders (CVD), insulin resistance, metabolic syndrome and sarcopenia, are frequently associated to RA. These abnormalities could be closely linked to alterations in lipid metabolism. Indeed, RA patients exhibit a lipid paradox, defined by reduced levels of total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol whereas the CVD risk is increased. Moreover, the accumulation of toxic lipid mediators (i.e., lipotoxicity) in skeletal muscles can induce mitochondrial dysfunctions and insulin resistance, which are both crucial determinants of CVD and sarcopenia. The prevention or reversion of these biological perturbations in RA patients could contribute to the maintenance of muscle health and thus be protective against the increased risk for cardiometabolic diseases, dysmobility and mortality. Yet, several studies have shown that omega 3 fatty acids (FA) could prevent the development of RA, improve muscle metabolism and limit muscle atrophy in obese and insulin-resistant subjects. Thereby, dietary supplementation with omega 3 FA should be a promising strategy to counteract muscle lipotoxicity and for the prevention of comorbidities in RA patients.

scholarly journals Depression and cardiovascular risk—association among Beck Depression Inventory, PCSK9 levels and insulin resistance

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
C. Macchi ◽  
C. Favero ◽  
A. Ceresa ◽  
L. Vigna ◽  
D. M. Conti ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Risk Factor ◽  
Beck Depression Inventory ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Model Assessment ◽  
Cvd Risk ◽  
Assessment Index ◽  
Increased Risk ◽  
Homeostatic Model Assessment

Abstract Background Depression and cardiovascular disease (CVD) are among the most common causes of disability in high-income countries, depression being associated with a 30% increased risk of future CV events. Depression is twice as common in people with diabetes and is associated with a 60% rise in the incidence of type 2 diabetes, an independent CVD risk factor. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of low-density lipoprotein cholesterol, has been related to a large number of CV risk factors, including insulin resistance. Aim of this study was to investigate whether the presence of depression could affect PCSK9 levels in a population of obese subjects susceptible to depressive symptoms and how these changes may mediate a pre-diabetic risk. Results In 389 obese individuals, the Beck Depression Inventory (BDI-II) was significantly associated with PCSK9 levels. For every one-unit increment in BDI-II score, PCSK9 rose by 1.85 ng/mL. Depression was associated also with the HOMA-IR (homeostatic model assessment index of insulin resistance), 11% of this effect operating indirectly via PCSK9. Conclusions This study indicates a possible mechanism linking depression and insulin resistance, a well-known CV risk factor, providing evidence for a significant role of PCSK9.

scholarly journals Association between the Non-high-Density Lipoprotein Cholesterol to High-Density Lipoprotein Cholesterol Ratio and the Risk of Coronary Artery Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Jiayin You ◽  
Zhenhao Wang ◽  
Guoping Lu ◽  
Zhenyue Chen
Keyword(s):  
Coronary Artery Disease ◽  
High Density Lipoprotein ◽  
High Density Lipoprotein Cholesterol ◽  
Density Lipoprotein ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Gensini Score ◽  
Coronary Syndrome ◽  
Increased Risk ◽  
Artery Disease

Background. The purpose of this study was to evaluate the association between the non-high-density lipoprotein cholesterol (non-HDL-C) to high-density lipoprotein cholesterol (HDL-C) ratio and the risk of coronary artery disease (CAD). We also explored the potential role of non-HDL-C/HDL-C in the prognosis of CAD. Methods. We analyzed 930 consecutive patients with chest discomfort who underwent coronary angiography. Of these, 680 were diagnosed with CAD; the remaining 250 patients were normal. Multivariate logistic regression and receiver operating characteristic (ROC) curves were employed to evaluate the association between non-HDL-C/HDL-C and CAD. The effect of non-HDL-C/HDL-C on the progression of major adverse cardiovascular events (MACEs) was also explored. Results. Increased non-HDL-C/HDL-C was associated with an increased risk of CAD (OR: 1.291; 95% CI: 1.039-1.561; P=0.013). The results of stratified analyses by CAD subtype showed a correlation between high non-HDL-C/HDL-C and increased risk of acute coronary syndrome (OR: 1.661; 95% CI: 1.259-2.207; P<0.001), high Gensini score (OR: 1.408; 95% CI: 1.021-1.935; P=0.039), and multivessel disease (OR: 1.487; 95% CI: 1.128-1.992; P=0.007). Moreover, the areas under the ROC for the predictive value of non-HDL-C/HDL-C for CAD, acute coronary syndrome, high Gensini score, and multivessel disease were 0.604, 0.658, 0.642, and 0.636, respectively. Non-HDL-C/HDL-C in CAD patients was significantly correlated with the risk of long-term MACEs (P=0.004). Conclusions. The findings of this study indicated that non-HDL-C/HDL-C plays an important role in the risk and progression of CAD. These findings need verification by further large-scale prospective studies.

scholarly journals Impact of bleeding during dual antiplatelet therapy in patients with coronary artery disease

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ying-Chang Tung ◽  
Lai-Chu See ◽  
Shu-Hao Chang ◽  
Jia-Rou Liu ◽  
Chi-Tai Kuo ◽  
...  
Keyword(s):  
Antiplatelet Therapy ◽  
Dual Antiplatelet Therapy ◽  
East Asian ◽  
Asian Population ◽  
Adverse Outcomes ◽  
Research Database ◽  
Coronary Syndrome ◽  
Asian Patients ◽  
Increased Risk ◽  
The Impact

AbstractThis nationwide retrospective cohort study used the National Health Insurance Research Database of Taiwan to compare the impact of bleeding on clinical outcomes in patients with acute myocardial infarction (AMI) versus chronic coronary syndrome (CCS). Between July 2007 and December 2010, patients with AMI (n = 15,391) and CCS (n = 19,724) who received dual antiplatelet therapy after coronary stenting were identified from the database. AMI was associated with increased risks of MI (AMI vs. CCS: 0.38 vs. 0.16 per 100 patient-months; p < 0.01), all-cause death (0.49 vs. 0.32 per 100 patient-months; p < 0.01), and BARC type 3 bleeding (0.22 vs. 0.13 per 100 patient-months; p < 0.01) at 1 year compared with CCS, while the risk of BARC type 2 bleeding was marginally higher in the CCS patients than in the AMI patients (1.32 vs. 1.4 per 100 person-months; p = 0.06). Bleeding was an independent predictor of MI, stroke, and all-cause death in this East Asian population, regardless of the initial presentation. Among the patients with bleeding, AMI was associated with a higher risk of ischemic events at 1 year after bleeding compared with CCS (MI: 0.34 vs. 0.25 per 100 patient-months; p = 0.06; ischemic stroke: 0.22 vs. 0.13 per 100 patient-months; p = 0.02). The 1-year mortality after bleeding was comparable between the two groups after propensity score weighting. In conclusion, bleeding conferred an increased risk of adverse outcomes in East Asian patients with AMI and CCS.

scholarly journals P6419Machine learning in critical care: the role of diabetes and age in acute coronary syndromes

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E Cenko ◽  
M Van Der Schaar ◽  
J Yoon ◽  
Z Vasiljevic ◽  
S Kedev ◽  
...  
Keyword(s):  
Medical Treatment ◽  
Primary Endpoint ◽  
Left Ventricular ◽  
Adverse Outcomes ◽  
Secondary Endpoint ◽  
Coronary Syndrome ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Patients With Diabetes ◽  
The Impact

Abstract Background Patients with diabetes and non-ST elevation acute coronary syndrome (NSTE-ACS) have an increased risk of mortality and adverse outcomes following percutaneous coronary intervention (PCI). Purpose We aimed to investigate the impact of early, within 24 hours PCI compared with only routine medical treatment on clinical outcomes in a large international cohort of patients with NSTE-ACS and diabetes. Methods We identified 1,250 patients with diabetes and NSTE-ACS from a registry-based population between October 2010 and April 2016. The primary endpoint was 30-day all-cause mortality. The secondary endpoint was the composite outcome of 30-day all-cause mortality and left ventricular dysfunction (ejection fraction <40%). We undertook analyses to explore the heterogeneity of treatment effects using meta-classification (MC) algorithms followed by propensity score matching and inverse-probability-of-treatment weighting (IPTW) from a landmark of 24 hours from hospitalization. Results Of 1,250 NSTE-ACS first-day survivors with diabetes (median age 67 years; 59%, men), 470 (37.6%) received early PCI and 780 routine medical treatment. The overall 30-day all-cause mortality rates were higher in the routine medical treatment than the early PCI group (6.3% vs. 2.5%). The prediction results of the MC algorithms accounted for only one interaction term that was statistically significant: age ≥65 years. After propensity-matched analysis as well as IPTW, early PCI was associated with reduced 30-day all-cause mortality in the older age (OR: 0.35; 95% CI: 0.14 to 0.92 and 0.43; 95% CI: 0.21 to 0.86, respectively), whereas younger age had no association with the primary endpoint. Similar results were also obtained for the secondary endpoint. Conclusions Among patients with diabetes hospitalized for NSTE-ACS, an early, within 24 hours, PCI strategy is associated with reduced odds of 30-day mortality only for patients aged 65 years or over. MC algorithms provide accurate identification of treatment effect modifiers.

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