scholarly journals Quantile-Dependent Expressivity and Gene-Lifestyle Interactions Involving High-Density Lipoprotein Cholesterol

2020 ◽  
pp. 1-19 ◽  
Author(s):  
Paul T. Williams
Keyword(s):  
High Density Lipoprotein ◽  
Genetic Risk Score ◽  
Phenotypic Expression ◽  
Density Lipoprotein ◽  
Genetic Effect ◽  
Hdl Cholesterol ◽  
High Density ◽  
Interactive Effects ◽  
Effect Sizes ◽  
Low Hdl

<b><i>Background:</i></b> The phenotypic expression of a high-density lipoprotein (HDL) genetic risk score has been shown to depend upon whether the phenotype (HDL-cholesterol) is high or low relative to its distribution in the population (quantile-dependent expressivity). This may be due to the effects of genetic mutations on HDL-metabolism being concentration dependent. <b><i>Method:</i></b> The purpose of this article is to assess whether some previously reported HDL gene-lifestyle interactions could potentially be attributable to quantile-dependent expressivity. <b><i>Summary:</i></b><i></i>Seventy-three published examples of HDL gene-lifestyle interactions were interpreted from the perspective of quantile-dependent expressivity. These included interactive effects of diet, alcohol, physical activity, adiposity, and smoking with genetic variants associated with the <i>ABCA1</i>, <i>ADH3</i>,<i> ANGPTL4</i>, <i>APOA1</i>,<i> APOA4</i>,<i> APOA5</i>, <i>APOC3</i>,<i> APOE</i>,<i> CETP</i>,<i> CLASP1</i>,<i> CYP7A1</i>, <i>GALNT2</i>, <i>LDLR</i>,<i> LHX1</i>,<i> LIPC</i>,<i> LIPG</i>,<i> LPL</i>,<i> MVK-MMAB</i>,<i> PLTP</i>,<i> PON1</i>, <i>PPARα</i>,<i> SIRT1</i>,<i> SNTA1</i>,<i></i>and<i> UCP1</i>genes. The selected examples showed larger genetic effect sizes for lifestyle conditions associated with higher vis-à-vis lower average HDL-cholesterol concentrations. This suggests these reported interactions could be the result of selecting subjects for conditions that differentiate high from low HDL-cholesterol (e.g., lean vs. overweight, active vs. sedentary, high-fat vs. high-carbohydrate diets, alcohol drinkers vs. abstainers, nonsmokers vs. smokers) producing larger versus smaller genetic effect sizes. <b><i>Key Message:</i></b> Quantile-dependent expressivity provides a potential explanation for some reported gene-lifestyle interactions for HDL-cholesterol. Although overall genetic heritability appears to be quantile specific, this may vary by genetic variant and environmental exposure.

High-Density Lipoprotein Cholesterol (HDL-C) Levels Independently Correlates With Cardiac Arrhythmias and Atrial Fibrillation

2018 ◽  
Vol 35 (5) ◽  
pp. 438-444 ◽  
Author(s):  
Farzin Brian Boudi ◽  
Nicholas Kalayeh ◽  
Mohammad Reza Movahed
Keyword(s):  
Acute Coronary Syndrome ◽  
High Density Lipoprotein ◽  
Medical Center ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
High Density ◽  
St Segment Elevation ◽  
Coronary Syndrome ◽  
Cholesterol Levels ◽  
Low Hdl

Objective: Acute coronary syndrome is frequently complicated by rhythm disturbances, yet any association between high-density lipoprotein (HDL) cholesterol levels and arrhythmias in the setting of non-ST-segment elevation myocardial infarction (non-STEMI) is uncertain. The goal of this study was to evaluate any association between HDL-cholesterol levels and arrhythmias in the setting of non-STEMI. Methods: Retrospective data from Phoenix Veterans Affair Medical Center records were utilized for our study. A total of 6881 patients were found who presented during 2000 to 2003 with non-STEMI with available fasting lipid panels collected within the first 24 hours of admission. Patients were followed for the development of rhythm disturbances up to 6 years after initial presentation, with a mean follow up of 1269 days. Results: We found that high triglycerides/HDL and low-density lipid/HDL ratios were predictive of arrhythmias. However, low HDL levels had strongest association with highest odds ratio (OR) for development of arrhythmias (for HDL <31 mg/dL, OR = 3.72, 95% confidence interval [CI] = 2.55-5.44, P < .05) in patients with diabetes and (for HDL < 31 mg/dL, OR = 3.69, 95% CI = 2.85-4.71, P < .05) in patients without diabetes. Using multivariate analysis adjusting for comorbidities, low HDL level remained independently associated with arrhythmias. Conclusions: Patients with low HDL levels during hospitalization with non-STEMI have a greater risk of developing cardiac rhythm disturbances independent of other risk factors. These data suggest a possible protective role of HDL in preventing arrhythmias in the setting of acute coronary syndrome.

scholarly journals Low HDL (High-Density Lipoprotein) Cholesterol and High White Blood Cell Counts

2020 ◽  
Author(s):  
Mads Harsløf ◽  
Kasper M. Pedersen ◽  
Børge G. Nordestgaard ◽  
Shoaib Afzal
Keyword(s):  
Blood Cell ◽  
High Density Lipoprotein ◽  
White Blood Cell ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
High Density ◽  
Cell Counts ◽  
Blood Cell Counts ◽  
Low Hdl ◽  
White Blood Cell Counts

Objective: Animal studies suggest that HDL (high-density lipoprotein) regulates proliferation and differentiation of hematopoietic stem cells. Using a Mendelian randomization approach, we tested the hypothesis that low HDL cholesterol is associated with high white blood cell counts. Approach and Results: We included 107 952 individuals aged 20 to 100 years from the Copenhagen General Population Study with information on HDL cholesterol, white blood cell counts, and 9 genetic variants associated with HDL cholesterol. In multivariable-adjusted observational analyses, HDL cholesterol was inversely associated with white blood cell counts. On a continuous scale, a 1-mmol/L (39 mg/dL) lower HDL cholesterol was associated with 5.1% (95% CI, 4.7%–5.4%) higher leukocytes, 4.5% (95% CI, 4.0%–4.9%) higher neutrophils, 5.7% (95% CI, 5.3%–6.1%) higher lymphocytes, 5.7% (95% CI, 5.3%–6.2%) higher monocytes, 14.8% (95% CI, 13.9%–15.8%) higher eosinophils, and 3.9% (95% CI, 3.1%–4.7%) higher basophils. In age- and sex-adjusted genetic analyses using the inverse-variance weighted analysis, a 1-mmol/L (39 mg/dL) genetically determined lower HDL cholesterol was associated with 2.2% (95% CI, 0.3%–4.1%) higher leukocytes, 4.3% (95% CI, 1.6%–7.1%) higher lymphocytes, 4.3% (95% CI, 2.6%–6.1%) higher monocytes, and 4.8% (95% CI, 1.2%–8.5%) higher eosinophils. Overall, the genetic associations were robust across sensitivity analyses and replicated using summary statistics from the UK Biobank with up to 350 470 individuals. Conclusions: Genetic and hence lifelong low HDL cholesterol was associated with high peripheral blood leukocytes, including high lymphocytes, monocytes, and eosinophils. The concordance between observational and genetic estimates and independent replication suggest a potential causal relationship.

Six methods for isolating high-density lipoprotein compared, with use of the reference method for quantifying cholesterol in serum.

1985 ◽  
Vol 31 (5) ◽  
pp. 746-750 ◽  
Author(s):  
D A Wiebe ◽  
S J Smith
Keyword(s):  
High Density Lipoprotein ◽  
Density Lipoprotein ◽  
Reference Method ◽  
Hdl Cholesterol ◽  
High Density ◽  
Constant Bias ◽  
Low Hdl ◽  
High Concentrations ◽  
Routine Procedures ◽  
Polyethylene Glycol 6000

Abstract Using 90 serum specimens, we compared six routine procedures for high-density lipoprotein (HDL) isolation to determine the biases, if any, of each. Use of the Reference Method for cholesterol (Duncan et al., Centers for Disease Control, Atlanta, GA) and automated dispensing equipment helped ensure the accuracy of the cholesterol measurements and minimized errors from sample and reagent manipulations. Regression analysis of the results showed significant differences between most HDL isolation methods, except for those involving precipitation with heparin-MnCl2 (1.0 mol/L) or polyethylene glycol 6000, which yielded comparable results with a slope close to one and a zero intercept. The dextran sulfate (Mr 500 000)-MgCl2 method had the largest proportional and constant bias with respect to those two methods. All the methods produced comparable results in the clinically important low HDL-cholesterol range (250 to 350 mg/L), but biases were significant at high concentrations. We conclude that these increased biases in the upper ranges of HDL-cholesterol concentrations are the result of increased heterogeneity of HDL and the different mechanisms involved in forming the insoluble complexes between lipoproteins and the various precipitation reagents.

scholarly journals High Density Lipoprotein Cholesterol Efflux Capacity and Atherosclerosis in Cardiovascular Disease: Pathophysiological Aspects and Pharmacological Perspectives

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 574
Author(s):  
Maria Pia Adorni ◽  
Nicoletta Ronda ◽  
Franco Bernini ◽  
Francesca Zimetti
Keyword(s):  
High Density Lipoprotein ◽  
Cholesterol Efflux ◽  
Current Knowledge ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
High Density ◽  
Current Evidence ◽  
Endocrine Disorders ◽  
Lifestyle Modifications ◽  
Cholesterol Efflux Capacity

Over the years, the relationship between high-density lipoprotein (HDL) and atherosclerosis, initially highlighted by the Framingham study, has been revealed to be extremely complex, due to the multiple HDL functions involved in atheroprotection. Among them, HDL cholesterol efflux capacity (CEC), the ability of HDL to promote cell cholesterol efflux from cells, has emerged as a better predictor of cardiovascular (CV) risk compared to merely plasma HDL-cholesterol (HDL-C) levels. HDL CEC is impaired in many genetic and pathological conditions associated to high CV risk such as dyslipidemia, chronic kidney disease, diabetes, inflammatory and autoimmune diseases, endocrine disorders, etc. The present review describes the current knowledge on HDL CEC modifications in these conditions, focusing on the most recent human studies and on genetic and pathophysiologic aspects. In addition, the most relevant strategies possibly modulating HDL CEC, including lifestyle modifications, as well as nutraceutical and pharmacological interventions, will be discussed. The objective of this review is to help understanding whether, from the current evidence, HDL CEC may be considered as a valid biomarker of CV risk and a potential pharmacological target for novel therapeutic approaches.

“Isolated” Low High-Density Lipoprotein Cholesterol

1997 ◽  
Vol 31 (1) ◽  
pp. 89-97 ◽  
Author(s):  
Vickie M Wilt ◽  
John G Gums
Keyword(s):  
High Density Lipoprotein ◽  
High Density Lipoprotein Cholesterol ◽  
Lifestyle Modification ◽  
Density Lipoprotein ◽  
Additional Treatment ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Estrogen Replacement ◽  
Review Articles ◽  
Low Hdl

OBJECTIVE: To present information on the function, structure, and importance of high-density lipoprotein cholesterol (HDL-C) and to evaluate the current literature regarding the controversy of managing patients with an “isolated” low HDL-C concentration. DATA SOURCE: A MEDLINE search was performed (1966–June 1996) to identify English-language clinical and review articles pertaining to HDL-C. Some articles were identified through the bibliography of selected articles. STUDY SELECTION: All articles were considered for possible inclusion in the review. Pertinent information, as judged by the authors, was selected for discussion. DATA EXTRACTION: Important historical lipid studies, recent review articles, and clinical trials involving therapy for HDL-C were evaluated. DATA SYNTHESIS: The structure, function, and measurement of HDL-C and the state of an isolated low HDL-C are discussed for background. Lifestyle modification measures to increase HDL-C, medications to avoid, estrogen replacement, and lipid-altering agents used to raise an isolated low HDL-C are presented. CONCLUSIONS: An isolated low HDL-C concentration poses a risk for coronary heart disease. The management of this state is controversial. The first step in management is in agreement with experts and includes lifestyle modification (e.g., weight reduction, diet, smoking cessation, aerobic exercise). Estrogen replacement therapy and discontinuance of drugs that secondarily lower HDL-C are additional treatment options. The use of lipid-altering agents has been used in some patients. Nicotinic acid appears to be an effective agent for an isolated low HDL-C. A large clinical trial evaluating the effect of treating an isolated low HDL-C for primary and secondary prevention of coronary events is needed.

scholarly journals Is There Any Association Between Uric Acid to High-density Lipoprotein Cholesterol Ratio and Erectile Dysfunction?

2021 ◽  
Author(s):  
Dilay Karabulut ◽  
Mustafa Gürkan Yenice
Keyword(s):  
Uric Acid ◽  
Erectile Dysfunction ◽  
High Density Lipoprotein ◽  
Roc Curve ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
High Density ◽  
Roc Curve Analysis ◽  
Cholesterol Ratio ◽  
Group 3

Objective: Elevated uric acid (UA) and low levels of high-density lipoprotein (HDL) cholesterol are associated with cardiovascular events and mortality. Erectile dysfunction (ED) has been considered an early marker of cardiovascular disease (CVD). Therefore, this study aimed to investigate the uric acid/ HDL ratio (UHR) as a nowel marker in patients with ED. Materials and Methods: The study included 147 patients with a mean age of 50 years (range 32-76 years). Retrospective analyses were performed on the patients who were admitted to urology outpatient clinics. The laboratory parameter results were retrieved from the hospital medical records, and the UHR value was calculated. Patients were categorized into three groups according to the International Index of Erectile Function (IIEF) score. UHR was compared between groups, and its predictive value was evaluated using regression analysis and ROC curve analysis. Results: Age was found to be significantly different in all three groups (Groups 1-2, p=0.001; Groups 1-3, p=0.000; Groups 2-3, p=0.001). It was observed that the degree of ED increased with age. The values of UA and HDL were similar in all groups (p>0.05). In contrast, the UHR value was statistically significantly higher 0.15 (0.083-0.288, p =0.047) in the moderate-severe ED (Group 3). ROC curve analyses revealed that UHR predicted severe ED (IIEF 5-11) with 42.9% sensitivity and 87.3% specificity (AUC:0.66, CI 95% 0.538-0.781, p=0.019). Conclusion: UHR may serve as a severe ED indicator in patients admitted to the cardiology outpatient clinic since it has a significant association with a low IIEF score.

scholarly journals Prevalence and Predictors of Dyslipidemia in Children and Adolescents in Yazd Greater Area, Yazd, Iran

2021 ◽  
Keyword(s):  
High Density Lipoprotein ◽  
Children And Adolescents ◽  
Lifestyle Modification ◽  
Age Groups ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Cluster Sampling ◽  
Cross Sectional

Background: Dyslipidemia, a genetic and multifactorial disorder of lipoprotein metabolism, is defined by elevations in levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non–HDL-C), triglyceride, or some combination thereof, as well as lower levels of high-density lipoprotein (HDL) cholesterol. Objectives: This study aimed to investigate the prevalence and predictors of dyslipidemia in children and adolescents in the Yazd Greater Area, Yazd, Iran. Methods: This cross-sectional study was conducted as a part of the national project implemented in Yazd Greater Area, Yazd, Iran. The sampling was performed using a multi-stage cluster sampling method on three age groups of girls and boys (6-9, 10-14, and 15-18 years old). Out of the total 1,035 children and adolescents who participated in this study, only 784 participants remained in the study until the end. Data collection was performed using lifestyle questionnaires including Kiddie-SADS-Present and Lifetime Version. Results: The prevalence of high triglyceride was estimated at 1.4% and 4.2% in 6-9 and 10-18 years old children and adolescents, respectively. The prevalence of high cholesterol, LDL, and HDL was 3.2%, 3.2%, and 25.6%, respectively. The prevalence of dyslipidemia in the total population of children and adolescents in terms of demographic variables was 64.6% and 57.3% in boys and girls, respectively (P=0.038). Gender and increase in body mass index were significantly associated with dyslipidemia with OR=1.35; 95% CI: 1.01-1.81 and OR=13.781; 95% CI: 3.78- 46.43, respectively. However, after adjustment for other factors, only an increase in BMI was significantly associated with dyslipidemia (OR=16.08; 95% CI: 4.49-57.59). Conclusions: Overweight and obese adolescents had a higher concentration of serum blood triglycerides, compared to other adolescents. Weight control, lifestyle modification, and diet are three ways to reduce lipid disorders in adolescents.

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