ResearchPad - dyslipidemia https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Epidemiological characteristics of obstructive sleep apnea in a hospital-based historical cohort in Lebanon]]> https://www.researchpad.co/article/elastic_article_14697 The objective of our study was to characterize and analyze the associations between OSA (obstructive sleep apnea) and other clinical variables in adult patients referred for sleep evaluation by polysomnography at a referral center in Beirut, Lebanon, in terms of sociodemographic features, symptoms presentation and comorbidities, and evaluate the burden of comorbidities associated with this disease. All individuals with suspected Sleep Apnea referred (January 2010-September 2017) for a one-night polysomnography were included. Demographics, self-reported symptoms and comorbidities were documented. The relationship between OSA severity and the presence of symptoms and comorbidities were evaluated using multivariate logistic regression. Overall, 663 subjects were assessed. Of these, 57.3% were referred from chest physicians, and sleep test results were abnormal in 589 subjects (88.8%) of whom 526 patients (89.3%) fulfilled diagnostic criteria for OSA; 76.3% were men and women were on average older. OSA was severe in 43.2% and more severe in men. Almost all patients were symptomatic with ~2–4 symptoms per patient and women presented with symptoms that are more atypical. Comorbidities were significantly higher in women. In the multivariate analysis, age, male sex, obesity, symptoms of snoring, excessive daytime somnolence and witnessed apneas were associated with OSA severity. Only age and obesity were associated with self-reported diagnosis of hypertension and diabetes. This is the first study in Lebanon to explore the characteristics of patients with polysomnography-diagnosed OSA. High prevalence of severe OSA and low referral rates in the medical community support promoting awareness for an earlier diagnosis and more personalized approach in this country.

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<![CDATA[Prediction of hypertension, hyperglycemia and dyslipidemia from retinal fundus photographs via deep learning: A cross-sectional study of chronic diseases in central China]]> https://www.researchpad.co/article/elastic_article_14561 Retinal fundus photography provides a non-invasive approach for identifying early microcirculatory alterations of chronic diseases prior to the onset of overt clinical complications. Here, we developed neural network models to predict hypertension, hyperglycemia, dyslipidemia, and a range of risk factors from retinal fundus images obtained from a cross-sectional study of chronic diseases in rural areas of Xinxiang County, Henan, in central China. 1222 high-quality retinal images and over 50 measurements of anthropometry and biochemical parameters were generated from 625 subjects. The models in this study achieved an area under the ROC curve (AUC) of 0.880 in predicting hyperglycemia, of 0.766 in predicting hypertension, and of 0.703 in predicting dyslipidemia. In addition, these models can predict with AUC>0.7 several blood test erythrocyte parameters, including hematocrit (HCT), mean corpuscular hemoglobin concentration (MCHC), and a cluster of cardiovascular disease (CVD) risk factors. Taken together, deep learning approaches are feasible for predicting hypertension, dyslipidemia, diabetes, and risks of other chronic diseases.

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<![CDATA[Access to and price trends of antidiabetic, antihypertensive, and antilipidemic drugs in outpatient settings of the Universal Coverage Scheme in Thailand]]> https://www.researchpad.co/article/5c76fe51d5eed0c484e5b8a2

Under the Universal Coverage Scheme (UCS) with payment per capita for outpatient (OP) services, hospitals’ financial risks will rise if access to essential drugs increases. This study examined trends in access to and price of essential drugs for noncommunicable diseases (NCDs) and an overall purchasing price index (PPI) for an OP drug basket from public hospitals. To examine drug access, OP prescription data from 2010–2012 were obtained from the UCS. Access to thirteen drugs for diabetes, hypertension, and dyslipidemia was examined for trend using a time-series analysis. To calculate the PPI, drugs in the same dataset in 2010 that each contributed at least 0.2% of the total OP drug expenditure (N = 118 items) were selected together with drugs expected for near future growth (N = 48 items). The PPI was constructed from purchasing prices in 16 hospitals using a standard method developed by the International Labour Organization. Based on 166 drug items accounting for 75% of OP drug expenditures, the overall PPI continually declined by 6.8% from 2010 to 2012. Access to the 13 selected NCD drugs, accounting for 22% of the total OP drug expenditure increased from 22 to 30 per 1,000 population for antidiabetics, 27 to 47 for antihypertensive agents, and 32 to 53 for antilipidemics from 2010–2012. Growth in the study drug recipients was relatively higher than that in the population and diagnosed patients. Due to generic market competition, metformin, glipizide, amlodipine, losartan, simvastatin, atorvastatin, and fenofibrate prices decreased by 6–22%. Antiretrovirals and risperidone prices decreased by more than 10% due to price negotiation by the UCS. Access to essential drugs for diabetes, hypertension and dyslipidemia has increased. A decline in the PPI could contain essential drug expenditure when the demand for the drugs increased. Generic market competition and price negotiation by the UCS led to price reduction.

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<![CDATA[Should clinicians pay more attention to the potential underdiagnosis of osteoporosis in patients with ankylosing spondylitis? A national population-based study in Taiwan]]> https://www.researchpad.co/article/5c648d58d5eed0c484c82627

Objectives

There are limited studies describing the association between ankylosing spondylitis (AS) and osteoporosis. We conducted a nationwide retrospective cohort study to investigate this epidemiologic evidence.

Methods

Data were obtained from the Taiwan National Health Insurance Research Database (NHIRD). Of 10,290 participants, 2,058 patients with AS and 8,232 patients without AS were enrolled from the NHIRD between 2000 to 2013. Cumulative incidences of osteoporosis were compared between 2 groups. Cox regression model was used to estimate the hazard ratio (HR) of developing osteoporosis after controlling for demographic and other co-morbidities, and subgroup analyses were conducted to examine the risk factors for osteoporosis in AS patients.

Results

The incidence rate ratio (IRR) of osteoporosis in AS patients was 2.17 times higher than that non-AS group (95% confidence interval [CI], 1.83–2.57). The adjusted HRs of osteoporosis for AS patients after controlling for demographic characteristics and comorbid medical disorders was 1.99 (95% CI 1.68–2.36). Among AS group, after adjustment for major comorbidities, old age (≥65 years, HR 4.32, 95% CI 3.01–6.18), female sex (HR 2.48, 95% CI 1.87–3.28), dyslipidemia (HR 1.44, 95% CI 1.01–2.06) were risk factors associated with osteoporosis.

Conclusions

This cohort study demonstrated that patients with AS had a higher risk of developing osteoporosis, especially in those aged over 65, female sex and with dyslipidemia in this patient group.

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<![CDATA[Relationship between dementia and ankylosing spondylitis: A nationwide, population-based, retrospective longitudinal cohort study]]> https://www.researchpad.co/article/5c5ca317d5eed0c48441f12e

Among a variety of comorbidities of ankylosing spondylitis (AS), the association between dementia and AS by using an extensive dataset from the Korean National Health Insurance System was evaluated in this study. We extracted 15,547 newly diagnosed AS subjects among the entire Korean population and excluded wash-out patients (n = 162) and patients that were inappropriate for cohort match (n = 1192). Finally, 14,193 subjects were chosen as the AS group, and through 1:5 age- and sex-stratified matching, 70,965 subjects were chosen as the control group. We evaluated patient demographics, household incomes, and comorbidities, including hypertension, diabetes, and dyslipidemia. The prevalence of overall dementia (1.37%) and Alzheimer’s dementia (AD) (0.99%) in the AS group was significantly higher than in the control group (0.87% and 0.63%), respectively. The adjusted hazard ratio of the AS group for overall dementia (1.758) and AD (1.782) showed statistical significance also. On the other hand, the prevalence of vascular dementia did not differ significantly between the two groups. Subgroup analyses revealed the following risk factors for dementia in the AS group: male gender, greater than 65 years in age, fair income (household income greater than 20% of the median), urban residency, no diabetes, and no hypertension. From the nationwide, population-based, retrospective, longitudinal cohort study, AS patients showed a significantly higher prevalence of overall dementia and Alzheimer’s dementia. Comprehensive patient assessment using our subgroup analysis could help to prevent dementia in patients suffering from AS.

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<![CDATA[Evidence of association of circulating epigenetic-sensitive biomarkers with suspected coronary heart disease evaluated by Cardiac Computed Tomography]]> https://www.researchpad.co/article/5c521864d5eed0c484797f48

Circulating biomarkers available in clinical practice do not allow to stratify patients with coronary heart disease (CHD) prior the onset of a clinically relevant event. We evaluated the methylation status of specific genomic segments and gene expression in peripheral blood of patients undergoing Cardiac Computed Tomography (CCT) for CHD (n = 95).

We choose to investigate cholesterol metabolism. Methylation and gene expression of low density lipoprotein receptor (LDLR), sterol regulatory element-binding factor 2 (SREBF2) and ATP-binding cassette transporter 1 (ABCA1) were evaluated by qRT-PCR. Calcium score (CACS), stenosis degree, total plaque volume (TPV), calcified plaque volume (CPV), non-calcified plaque volume (NCPV) and plaque burden (PB) were assessed in all CHD patients (n = 65). The percentage of methylation at the specific analyzed segment of LDLR promoter was higher in CHD patients vs healthy subjects (HS) (n = 30) (p = 0.001). LDLR, SREBF2 and ABCA1 mRNAs were up-regulated in CHD patients vs HS (p = 0.02; p = 0.019; p = 0.008). SREBF2 was overexpressed in patients with coronary stenosis ≥50% vs subjects with stenosis <50% (p = 0.036). After adjustment for risk factors and clinical features, ABCA1 (p = 0.005) and SREBF2 (p = 0.010) gene expression were identified as independent predictors of CHD and severity. ROC curve analysis revealed a good performance of ABCA1 on predicting CHD (AUC = 0.768; p<0.001) and of SREBF2 for the prediction of disease severity (AUC = 0.815; p<0.001). Moreover, adjusted multivariate analysis demonstrated SREBF2 as independent predictor of CPV, NCPV and TPV (p = 0.022; p = 0.002 and p = 0.006) and ABCA1 as independent predictor of NCPV and TPV (p = 0.002 and p = 0.013).

CHD presence and characteristics are related to selected circulating transcriptional and epigenetic-sensitive biomarkers linked to cholesterol pathway. More extensive analysis of CHD phenotypes and circulating biomarkers might improve and personalize cardiovascular risk stratification in the clinical settings.

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<![CDATA[Dyslipidemia, subclinical inflammation, hepatic cholestasis and endothelial dysfunction in schoolchildren with excess fat: A study from the United Arab Emirates]]> https://www.researchpad.co/article/5c3fa58bd5eed0c484ca59b8

Background

The impact of obesity on cardiovascular health of young children is still to be fully illustrated. This study measured biomarkers for glycemic control, lipid metabolism, systemic inflammation, endothelial dysfunction, and hepatic cholestasis in schoolchildren. Its main purpose was to determine whether metabolic derangements could be detected in young children with excess fat.

Method

This cross-sectional study involved 967 children in the second, sixth, and tenth grades (median age, 7.3, 11.3, and 15.4 years, respectively). Using the International Obesity Task Force interpretation (IOTF) of body-mass-index (BMI), children were stratified as thin (<5th centiles), normal (5th to <85th centiles), overweight (85th to <95th centiles), obese (95th to <98th centiles), or extremely-obese (≥98th centiles). Waist circumference was also measured. Several metabolic determinations were then used as surrogate biomarkers for cardiovascular risks.

Results

Prevalence of BMI≥85th centile among the second graders was 13.1%, sixth graders 42.2%, and tenth graders 33.8%. BMI≥85th centile was associated with a tendency for higher hemoglobin A1c (p≥0.160) and higher blood glucose (p≥0.197). For the second graders, BMI≥85th centile was associated with higher high-sensitivity C-reactive protein (hs-CRP, p<0.001), higher tumor necrosis factor-α (TNF-alpha, p<0.001), higher interleukin-6 (IL-6, p<0.001), higher soluble intercellular cytoadhesive molecule-1 (sICAM-1), higher triglycerides (p≤0.024), and lower high-density lipoprotein (HDL, p<0.001). Additionally, for the sixth and tenth graders, BMI≥85th centile was associated with higher gamma-glutamyl transferase (GGT, p<0.001). In the sixth graders, BMI≥85th centile was insignificantly changed with sICAM-1 or the soluble vascular cytoadhesive molecule-1 (sVCAM-1).

Conclusions

The studied children with excess fat had increased risks for developing systemic inflammation, dyslipidemia, endothelial dysfunction, cholestasis, and diabetes. These results suggest that metabolic biomarkers should be included in the routine assessment of children with an overweight problem.

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<![CDATA[Maternal dyslipidemia and risk for preterm birth]]> https://www.researchpad.co/article/5c269774d5eed0c48470f93b

Maternal lipid profiles during pregnancy are associated with risk for preterm birth. This study investigates the association between maternal dyslipidemia and subsequent preterm birth among pregnant women in the state of California. Births were identified from California birth certificate and hospital discharge records from 2007–2012 (N = 2,865,987). Preterm birth was defined as <37 weeks completed gestation and dyslipidemia was defined by diagnostic codes. Subtypes of preterm birth were classified as preterm premature rupture of membranes (PPROM), spontaneous labor, and medically indicated, according to birth certificate data and diagnostic codes. The association between dyslipidemia and preterm birth was tested with logistic regression. Models were adjusted for maternal age at delivery, race/ethnicity, hypertension, pre-pregnancy body mass index, insurance type, and education. Maternal dyslipidemia was significantly associated with increased odds of preterm birth (adjusted OR: 1.49, 95%CI: 1.39, 1.59). This finding was consistent across all subtypes of preterm birth, including PPROM (adjusted OR: 1.54, 95%CI: 1.34, 1.76), spontaneous (adjusted OR: 1.51, 95%CI: 1.39, 1.65), and medically indicated (adjusted OR: 1.454, 95%CI: 1.282, 1.649). This study suggests that maternal dyslipidemia is associated with increased risk for all types of preterm birth.

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<![CDATA[Liver steatosis and dyslipidemia after HCV eradication by direct acting antiviral agents are synergistic risks of atherosclerosis]]> https://www.researchpad.co/article/5c26972cd5eed0c48470ed67

Aim

We comprehensively analyzed how hepatitis C virus (HCV) eradication by interferon (IFN)-free direct-acting-antiviral-agents (DAAs) affects liver steatosis and atherogenic risk.

Methods

Patients treated with IFN-free-DAAs who underwent transient elastography before and at 24-weeks post-treatment, including controlled attenuation parameter (CAP), and achieved sustained viral response (SVR) were enrolled. The association between changes in liver steatosis, lipid-metabolism, and genetic and clinical factors was analyzed.

Results

A total of 117 patients were included. The mean CAP and low-density lipoprotein cholesterol (LDL-C) levels were significantly elevated at SVR24. However, baseline LDL-C and CAP values were significantly negatively correlated with changes in these values after HCV eradication, indicating that in patients with high baseline values, the values generally decreased after HCV eradication. Mean small-dense LDL-C (sdLDL-C), which has greater atherogenic potential, was significantly elevated only in patients with both dyslipidemia (LDL-C >140 mg/dL) and liver steatosis (CAP >248 dB/m) at SVR24. Those patients had significant higher baseline BMI, LDL-C, and total-cholesterol levels.

Conclusions

Generally, successful HCV eradication by IFN-free-DAAs decreases CAP and LDL-C in patients with high baseline values. However, elevated LDL-C was accompanied with elevated sdLDL-C only in patients with liver steatosis and dyslipidemia at SVR24; therefore, those patients may require closer monitoring.

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<![CDATA[Interactions among genes involved in reverse cholesterol transport and in the response to environmental factors in dyslipidemia in subjects from the Xinjiang rural area]]> https://www.researchpad.co/article/5b0436a4463d7e0f0e6b97b0

Gene-gene and gene-environment interactions may be partially responsible for dyslipidemia, but studies investigating interactions in the reverse cholesterol transport system (RCT) are limited. We explored these interactions in a Xinjiang rural population by genotyping five SNPs using SNPShot technique in APOA1, ABCA1, and LCAT, which are involved in the RCT (690 patients, 743 controls). We conducted unconditional logistical regression analysis to evaluate associations and generalized multifactor dimensionality reduction to evaluate interactions. Results revealed significant differences in rs670 and rs2292318 allele frequencies between cases and controls (P<0.025). rs670 G allele carriers were more likely to develop dyslipidemia than A allele carriers (OR = 1.315, OR 95% CI: 1.067–2.620; P = 0.010). rs2292318 T allele carriers were more likely to develop dyslipidemia than A allele carriers (OR = 1.264, OR 95% CI: 1.037–1.541; P = 0.020). Gene-gene interaction model APOA1rs670-ABCA1rs1800976-ABCA1rs4149313-LCATrs1109166 (P = 0.0107) and gene-environment interaction model ABCA1rs1800976-ABCA1rs4149313-LCATrs1109166-obesity-smoking were optimal dyslipidemia predictors (P = 0.0107) and can interact (4). Differences in A-C-A-C-A and G-G-G-T-G haplotype frequencies were observed (P<0.05). Serum lipid profiles could be partly attributed to RCT gene polymorphisms. Thus, dyslipidemia is influenced by APOA1, ABCA1, LCAT, environmental factors, and their interactions.

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<![CDATA[Significant association of RNF213 p.R4810K, a moyamoya susceptibility variant, with coronary artery disease]]> https://www.researchpad.co/article/5989db52ab0ee8fa60bdc7db

Background

The genetic architecture of coronary artery disease has not been fully elucidated, especially in Asian countries. Moyamoya disease is a progressive cerebrovascular disease that is reported to be complicated by coronary artery disease. Because most Japanese patients with moyamoya disease carry the p.R4810K variant of the ring finger 213 gene (RNF213), this may also be a risk factor for coronary artery disease; however, this possibility has never been tested.

Methods and results

We genotyped the RNF213 p.R4810K variant in 956 coronary artery disease patients and 716 controls and tested the association between p.R4810K and coronary artery disease. We also validated the association in an independent population of 311 coronary artery disease patients and 494 controls. In the replication study, the p.R4810K genotypes were imputed from genome-wide genotyping data based on the 1000 Genomes Project. We used multivariate logistic regression analyses to adjust for well-known risk factors such as dyslipidemia and smoking habits. In the primary study population, the frequency of the minor variant allele was significantly higher in patients with coronary artery disease than in controls (2.04% vs. 0.98%), with an odds ratio of 2.11 (p = 0.017). Under a dominant model, after adjustment for risk factors, the association remained significant, with an odds ratio of 2.90 (95% confidence interval: 1.37–6.61; p = 0.005). In the replication study, the association was significant after adjustment for age and sex (odds ratio = 4.99; 95% confidence interval: 1.16–21.53; p = 0.031), although it did not reach statistical significance when further adjusted for risk factors (odds ratio = 3.82; 95% confidence interval: 0.87–16.77; p = 0.076).

Conclusions

The RNF213 p.R4810K variant appears to be significantly associated with coronary artery disease in the Japanese population.

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<![CDATA[Manifold implications of obesity in ischemic heart disease among Japanese patients according to covariance structure analysis: Low reactivity of B-type natriuretic peptide as an intervening risk factor]]> https://www.researchpad.co/article/5989db5aab0ee8fa60bdf619

Background/Objectives

Obesity is believed to be one of the major risk factors for cardiovascular disease in Western countries. However, the effects of obesity should be continuously examined in the Japanese population because the average bodily habitus differs among countries. In this study, we collectively examined the significance of obesity and obesity-triggered risk factors including the low reactivity of B-type natriuretic peptide (BNP), for ischemic heart disease (IHD) in Japanese patients.

Methods and results

The study patients consisted of 1252 subjects (IHD: n = 970; non-IHD: n = 282). Multiple logistic regression analysis revealed that dyslipidemia, hypertension, diabetes, and the low reactivity of BNP were significant risk factors for IHD, but body mass index (BMI) was not. A theoretical path model was proposed by positioning BMI at the top of the hierarchical model. Exploratory factor analysis revealed that BMI did not play a causative role in IHD (P = NS). BMI was causatively linked to other risk factors (P<0.001 for hypertension; P<0.001 for dyslipidemia; P<0.001 for HbA1c; P<0.001 for LogBNP), and these factors played a causative role in IHD (P<0.001 for hypertension; P<0.001 for dyslipidemia; P<0.001 for HbA1c; P<0.001 for LogBNP). The intrinsic power of the low reactivity of BNP induced by high BMI on the promotion of IHD was fairly potent.

Conclusion

This study demonstrated that obesity per se is not a strong risk factor for IHD in Japanese patients. However, several important risk factors triggered by obesity exhibited a causative role for IHD. The low reactivity of BNP is a substantial risk factor for IHD.

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<![CDATA[Adipose Hypothermia in Obesity and Its Association with Period Homolog 1, Insulin Sensitivity, and Inflammation in Fat]]> https://www.researchpad.co/article/5989da69ab0ee8fa60b926b8

Visceral fat adiposity plays an important role in the development of metabolic syndrome. We reported previously the impact of human visceral fat adiposity on gene expression profile of peripheral blood cells. Genes related to circadian rhythm were highly associated with visceral fat area and period homolog 1 (PER1) showed the most significant negative correlation with visceral fat area. However, regulation of adipose Per1 remains poorly understood. The present study was designed to understand the regulation of Per1 in adipose tissues. Adipose Per1 mRNA levels of ob/ob mice were markedly low at 25 and 35 weeks of age. The levels of other core clock genes of white adipose tissues were also low in ob/ob mice at 25 and 35 weeks of age. Per1 mRNA was mainly expressed in the mature adipocyte fraction (MAF) and it was significantly low in MAF of ob/ob mice. To examine the possible mechanisms, 3T3-L1 adipocytes were treated with H2O2, tumor necrosis factor-α (TNF-α), S100A8, and lipopolysaccharide (LPS). However, no significant changes in Per1 mRNA level were observed by these agents. Exposure of cultured 3T3-L1 adipocytes to low temperature (33°C) decreased Per1 and catalase, and increased monocyte chemoattractant protein-1 (Mcp-1) mRNA levels. Hypothermia also worsened insulin-mediated Akt phosphorylation in 3T3-L1 adipocytes. Finally, telemetric analysis showed low temperature of adipose tissues in ob/ob mice. In obesity, adipose hypothermia seems to accelerate adipocyte dysfunction.

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<![CDATA[The differing influence of several factors on the development of fatty liver with elevation of liver enzymes between genders with metabolic syndrome: A cross-sectional study]]> https://www.researchpad.co/article/5989db5cab0ee8fa60be02a7

Background

Nonalcoholic fatty liver disease (NAFLD) is known to be strongly associated with obesity, visceral fat, metabolic syndrome (MS), lifestyle, and lifestyle-related diseases in both males and females. However, the prevalence of NAFLD, MS, and clinical backgrounds is different between males and females.

Objective

We conducted a cross-sectional study to examine the differing influence of lifestyle-related factors and visceral fat on fatty liver (FL) with elevation of liver enzymes between males and females with MS.

Methods

We enrolled 42,134 persons who underwent a regular health check-up, and after excluding subjects who fulfilled excluding criteria, the remaining subjects were 2,110 persons with MS. We examined the differing influence of lifestyle-related factors and visceral fat on FL with elevation of alanine aminotransferase (ALT) (ALT elevation was defined as ALT level of ≥31 IU/l in the present study).

Results

The odds rations for FL with ALT elevation were as follows: WC, 1.83 (95% confidence interval (CI) 1.36–2.46); dyslipidemia, 1.89 (95% CI 1.34–2.68); hemoglobin A1c, 1.36 (95% CI 1.00–1.85); visceral fat type MS (V-type MS), 5.78 (95% CI 4.29–7.80); and light drinker, 0.56 (95% CI 0.41–0.78) in males with MS and BMI, 2.18 (95% CI 1.43–3.33); WC, 1.85 (95% CI 1.27–2.70); diastolic blood pressure, 1.69 (95% CI 1.16–2.45); triglyceride, 2.22 (95% CI 1.56–3.17); impaired glucose tolerance, 1.66 (95% CI 1.11–2.47); and V-type MS, 3.83 (95% CI 2.57–5.70) in females with MS. The prevalence of FL with ALT elevation and ALT was significantly higher in V-type MS than in the subcutaneous fat type MS in both males and females with MS (P < 0.001).

Conclusion

Although V-type MS and WC is a common significant predictor of an increased prevalence of FL with ALT elevation in both males and females with MS, gender, lifestyle-related factors, and MS type in individuals with MS should be considered for the development of FL with ALT elevation.

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<![CDATA[Associations between body fat variability and later onset of cardiovascular disease risk factors]]> https://www.researchpad.co/article/5989db51ab0ee8fa60bdc2e5

Objective

There is current debate regarding whether body weight variability is associated with cardiovascular events. Recently, high body fat percentage (BF%) has been shown to be a cardiovascular risk factor. We therefore hypothesized that BF% variability would present a stronger cardiovascular risk than body weight variability.

Methods

A single-center retrospective cohort study of medical check-up examinees aged 20 years or older at baseline (2005) was performed. Examinees were followed in 2007, 2009, and 2013–2014. BF% variability in 2005, 2007 and 2009 was calculated as the root-mean square error (RMSE) using a simple linear regression model. Multiple logistic regression models estimated the association between BF%-RMSE and new diagnoses of cardiovascular risk factors occurring between the 2009 and 2013–2014 visits.

Results

In total, 11,281 participants (mean age: 51.3 years old, 48.8% were male) were included in this study. The average BF%-RMSE of our subjects was 0.63, and the average BMI-RMSE was 0.24. The high BF%-RMSE group (76-100th percentile) had a higher incidence of hypertension and a lower incidence of diabetes mellitus than the low BF%-RMSE group (1-25th percentile). This tendency was particularly evident in male participants. BMI-RMSE was not associated with any cardiovascular risks in our study.

Conclusions

This study indicates that body fat variability has contrasting effects on cardiovascular risk factors, while body weight variability has no significant effects.

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<![CDATA[Visceral fat area is a strong predictor of leukocyte cell-derived chemotaxin 2, a potential biomarker of dyslipidemia]]> https://www.researchpad.co/article/5989db51ab0ee8fa60bdc4db

Background

Leukocyte cell-derived chemotaxin 2 (LECT2) is a hepatokine linking obesity to skeletal muscle insulin resistance. Although previous studies reported that obesity was associated with high levels of circulating LECT2 in human, the associations of detailed body fat distribution with LECT2 levels have not been examined. Furthermore, although animal study suggested that exercise decreased circulating LECT2 levels, it remains unknown whether physical fitness is associated with LECT2 levels in human. We therefore examined the relationship of plasma LECT2 levels with various adiposity indices and cardiorespiratory fitness (CRF) in middle-aged and elderly Japanese men. Furthermore, we examined the relationship of LECT2 levels with the presence of metabolic syndrome, hypertension, insulin resistance and dyslipidemia to determine the clinical significance of measuring circulating LECT2.

Materials and methods

This was a cross-sectional study of 143 Japanese men (age: 30–79 years). Participants’ plasma LECT2 levels were measured by an enzyme-linked immunosorbent assay. To assess their abdominal fat distributions, visceral fat area (VFA) and subcutaneous fat area (SFA) were measured using magnetic resonance imaging. CRF was assessed by measuring peak oxygen uptake (V˙O2peak).

Results

All adiposity indices measured in this study were positively correlated with plasma LECT2 levels, while V˙O2peak was negatively correlated with LECT2 levels after adjustment for age. The correlations, except for VFA were no longer significant with further adjustment for VFA. Stepwise multiple linear regression analysis revealed that VFA was the strongest predictor of plasma LECT2 levels. Plasma LECT2 levels differed based on the presence of metabolic syndrome and dyslipidemia, but not hypertension and insulin resistance. Logistic regression analyses revealed that plasma LECT2 levels were significantly associated with dyslipidemia independently of VFA; VFA was not significantly associated with dyslipidemia after adjustment for LECT2.

Conclusion

VFA was the strongest predictor of plasma LECT2 that is a potential biomarker linking visceral obesity to dyslipidemia.

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<![CDATA[Effects of Step-Wise Increases in Dietary Carbohydrate on Circulating Saturated Fatty Acids and Palmitoleic Acid in Adults with Metabolic Syndrome]]> https://www.researchpad.co/article/5989da5fab0ee8fa60b90b90

Recent meta-analyses have found no association between heart disease and dietary saturated fat; however, higher proportions of plasma saturated fatty acids (SFA) predict greater risk for developing type-2 diabetes and heart disease. These observations suggest a disconnect between dietary saturated fat and plasma SFA, but few controlled feeding studies have specifically examined how varying saturated fat intake across a broad range affects circulating SFA levels. Sixteen adults with metabolic syndrome (age 44.9±9.9 yr, BMI 37.9±6.3 kg/m2) were fed six 3-wk diets that progressively increased carbohydrate (from 47 to 346 g/day) with concomitant decreases in total and saturated fat. Despite a distinct increase in saturated fat intake from baseline to the low-carbohydrate diet (46 to 84 g/day), and then a gradual decrease in saturated fat to 32 g/day at the highest carbohydrate phase, there were no significant changes in the proportion of total SFA in any plasma lipid fractions. Whereas plasma saturated fat remained relatively stable, the proportion of palmitoleic acid in plasma triglyceride and cholesteryl ester was significantly and uniformly reduced as carbohydrate intake decreased, and then gradually increased as dietary carbohydrate was re-introduced. The results show that dietary and plasma saturated fat are not related, and that increasing dietary carbohydrate across a range of intakes promotes incremental increases in plasma palmitoleic acid, a biomarker consistently associated with adverse health outcomes.

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<![CDATA[Genomic Determinants of Triglyceride and Cholesterol Distribution into Lipoprotein Fractions in the Rat]]> https://www.researchpad.co/article/5989da32ab0ee8fa60b84e50

The plasma profile of major lipoprotein classes and its subdivision into particular fractions plays a crucial role in the pathogenesis of atherosclerosis and is a major predictor of coronary artery disease. Our aim was to identify genomic determinants of triglyceride and cholesterol distribution into lipoprotein fractions and lipoprotein particle sizes in the recombinant inbred rat set PXO, in which alleles of two rat models of the metabolic syndrome (SHR and PD inbred strains) segregate together with those from Brown Norway rat strain. Adult male rats of 15 PXO strains (n = 8–13/strain) and two progenitor strains SHR-Lx (n = 13) and BXH2/Cub (n = 18) were subjected to one-week of high-sucrose diet feeding. We performed association analyses of triglyceride (TG) and cholesterol (C) concentrations in 20 lipoprotein fractions and the size of major classes of lipoprotein particles utilizing 704 polymorphic microsatellite markers, the genome-wide significance was validated by 2,000 permutations per trait. Subsequent in silico focusing of the identified quantitative trait loci was completed using a map of over 20,000 single nucleotide polymorphisms. In most of the phenotypes we identified substantial gradient among the strains (e.g. VLDL-TG from 5.6 to 66.7 mg/dl). We have identified 14 loci (encompassing 1 to 65 genes) on rat chromosomes 3, 4, 7, 8, 11 and 12 showing suggestive or significant association to one or more of the studied traits. PXO strains carrying the SHR allele displayed significantly higher values of the linked traits except for LDL-TG and adiposity index. Cholesterol concentrations in large, medium and very small LDL particles were significantly associated to a haplotype block spanning part of a single gene, low density lipoprotein receptor-related protein 1B (Lrp1b). Using genome-wide association we have identified new genetic determinants of triglyceride and cholesterol distribution into lipoprotein fractions in the recombinant inbred panel of rat model strains.

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<![CDATA[Apolipoprotein(a) Kringle-IV Type 2 Copy Number Variation Is Associated with Venous Thromboembolism]]> https://www.researchpad.co/article/5989dafeab0ee8fa60bc5d5a

In addition to the established association between high lipoprotein(a) [Lp(a)] concentrations and coronary artery disease, an association between Lp(a) and venous thromboembolism (VTE) has also been described. Lp(a) is controlled by genetic variants in LPA gene, coding for apolipoprotein(a), including the kringle-IV type 2 (KIV-2) size polymorphism. Aim of the study was to investigate the role of LPA gene KIV-2 size polymorphism and single nucleotide polymorphisms (SNPs) (rs1853021, rs1800769, rs3798220, rs10455872) in modulating VTE susceptibility. Five hundred and sixteen patients with VTE without hereditary and acquired thrombophilia and 1117 healthy control subjects, comparable for age and sex, were investigated. LPA KIV-2 polymorphism, rs3798220 and rs10455872 SNPs were genotyped by TaqMan technology. Concerning rs1853021 and rs1800769 SNPs, PCR-RFLP assay was used. LPA KIV-2 repeat number was significantly lower in patients than in controls [median (interquartile range) 11(6–17) vs 15(9–25), p<0.0001]. A significantly higher prevalence of KIV-2 repeat number ≤7 was observed in patients than in controls (33.5% vs 15.5%, p<0.0001). KIV-2 repeat number was independently associated with VTE (p = 4.36 x10-9), as evidenced by the general linear model analysis adjusted for transient risk factors. No significant difference in allele frequency for all SNPs investigated was observed. Haplotype analysis showed that LPA haplotypes rather than individual SNPs influenced disease susceptibility. Receiver operating characteristic curves analysis showed that a combined risk prediction model, including KIV-2 size polymorphism and clinical variables, had a higher performance in identifying subjects at VTE risk than a clinical-only model, also separately in men and women.

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<![CDATA[High Density Lipoprotein Stimulated Migration of Macrophages Depends on the Scavenger Receptor Class B, Type I, PDZK1 and Akt1 and Is Blocked by Sphingosine 1 Phosphate Receptor Antagonists]]> https://www.researchpad.co/article/5989da8bab0ee8fa60b9dda8

HDL carries biologically active lipids such as sphingosine-1-phosphate (S1P) and stimulates a variety of cell signaling pathways in diverse cell types, which may contribute to its ability to protect against atherosclerosis. HDL and sphingosine-1-phosphate receptor agonists, FTY720 and SEW2871 triggered macrophage migration. HDL-, but not FTY720-stimulated migration was inhibited by an antibody against the HDL receptor, SR-BI, and an inhibitor of SR-BI mediated lipid transfer. HDL and FTY720-stimulated migration was also inhibited in macrophages lacking either SR-BI or PDZK1, an adaptor protein that binds to SR-BI's C-terminal cytoplasmic tail. Migration in response to HDL and S1P receptor agonists was inhibited by treatment of macrophages with sphingosine-1-phosphate receptor type 1 (S1PR1) antagonists and by pertussis toxin. S1PR1 activates signaling pathways including PI3K-Akt, PKC, p38 MAPK, ERK1/2 and Rho kinases. Using selective inhibitors or macrophages from gene targeted mice, we demonstrated the involvement of each of these pathways in HDL-dependent macrophage migration. These data suggest that HDL stimulates the migration of macrophages in a manner that requires the activities of the HDL receptor SR-BI as well as S1PR1 activity.

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