Enhanced Muscle Strength in Dyslipidemic Mice and Its Relation to Increased Capacity for Fatty Acid Oxidation.

Dyslipidemia is commonly linked to skeletal muscle dysfunction, accumulation of intramyocellular lipids, and insulin resistance. However, our previous research indicated that dyslipidemia in apolipoprotein E and low-density lipoprotein receptor double knock-out mice (ApoE/LDLR -/-) leads to improvement of exercise capacity. This study aimed to investigate in detail skeletal muscle function and metabolism in these dyslipidemic mice. We found that ApoE/LDLR -/- mice showed an increased grip strength as well as increased troponins, and Mhc2 levels in skeletal muscle. It was accompanied by the increased skeletal muscle mitochondria numbers (judged by increased citrate synthase activity) and elevated total adenine nucleotides pool. We noted increased triglycerides contents in skeletal muscles and increased serum free fatty acids (FFA) levels in ApoE/LDLR -/- mice. Importantly, Ranolazine mediated inhibition of FFA oxidation in ApoE/LDLR -/- mice led to the reduction of exercise capacity and total adenine nucleotides pool. Thus, this study demonstrated that increased capacity for fatty acid oxidation, an adaptive response to dyslipidemia leads to improved cellular energetics that translates to increased skeletal muscle strength and contributes to increased exercise capacity in ApoE/LDLR -/- mice.

Acute and Long Term Effects of a Nutraceutical Combination on Lipid Profile, Glucose Metabolism and Vascular Function in Patients with Dyslipidaemia with and Without Cigarette Smoking.

INTRODUCTION: Lifestyle changes present a fundamental role in cardiovascular prevention. Nutraceuticals also supplementing diet could help in controlling the cardiometabolic risk. AIM: (1) to evaluate acute effects of a combination of nutraceuticals (cNUT) on vascular function, BP, metabolism in dyslipidaemic patients before and after smoking; (2) to evaluate 12 weeks effects of the cNUT on lipid profile, insulin resistance and vascular function in patients with hypercholesterolemia not on statins. METHODS: After 14 d run-in period, 33 patients assumed a cNUT [patented formula containing: berberine (531.25 mg), red yeast rice powder (220 mg, 3.3 mg monacolin K) and leaf extract of Morus alba (200 mg) (LopiGLIK®, Akademy Pharma)]. To evaluate acute effects, cNUT or cNUT + smoking (in smoking subjects) on the morning of the first day of the study and then 26 patients prolonged 12 weeks effects. RESULTS: In non smokers, cNUT improved FMD (p = 0.041 for treatment). In smokers, FMD decreased after smoking, this was counteracted by intake of cNUT. In smokers, DBP increased after smoking a cigarette (p = 0.042 for treatment), counteracted by the cNUT intake. In non smokers, thermogenesis was increased after cNUT administration (p < 0.0001 for treatment). After 12 weeks of cNUT, FMD significantly increased (p < 0.05) and SBP (p = 0.04), total cholesterol and LDL cholesterol (p = 0.03) decreased. CONCLUSIONS: Our study suggests benefits of cNUT on cardiovascular prevention in hypercolesterolemic patients, non statin treated, that goes beyond the cholesterol and insulin resistance reduction protecting the subject from negative effects induced by smoking too.

Increasing the Power of Polyphenols through Nanoencapsulation for Adjuvant Therapy against Cardiovascular Diseases.

Polyphenols play a therapeutic role in vascular diseases, acting in inherent illness-associate conditions such as inflammation, diabetes, dyslipidemia, hypertension, and oxidative stress, as demonstrated by clinical trials and epidemiological surveys. The main polyphenol cardioprotective mechanisms rely on increased nitric oxide, decreased asymmetric dimethylarginine levels, upregulation of genes encoding antioxidant enzymes via the Nrf2-ARE pathway and anti-inflammatory action through the redox-sensitive transcription factor NF-κB and PPAR-γ receptor. However, poor polyphenol bioavailability and extensive metabolization restrict their applicability. Polyphenols carried by nanoparticles circumvent these limitations providing controlled release and better solubility, chemical protection, and target achievement. Nano-encapsulate polyphenols loaded in food grade polymers and lipids appear to be safe, gaining resistance in the enteric route for intestinal absorption, in which the mucoadhesiveness ensures their increased uptake, achieving high systemic levels in non-metabolized forms. Nano-capsules confer a gradual release to these compounds, as well as longer half-lives and cell and whole organism permanence, reinforcing their effectiveness, as demonstrated in pre-clinical trials, enabling their application as an adjuvant therapy against cardiovascular diseases. Polyphenol entrapment in nanoparticles should be encouraged in nutraceutical manufacturing for the fortification of foods and beverages. This study discusses pre-clinical trials evaluating how nano-encapsulate polyphenols following oral administration can aid in cardiovascular performance.

Hemoglobin and adult height loss among Japanese workers: A retrospective study.

Height loss starting in middle age is reported to be associated with increased all-cause and cardiovascular mortality later in life. However, the mechanisms underlying this association are unclear. Hypoxia and oxidative stress, which are known causes of cardiovascular disease, could be reduced by hemoglobin. Therefore, hemoglobin could be inversely associated with height loss. However, high body mass index (BMI) is a known risk factor for intervertebral disc disorder, a known cause of height loss in adults. High BMI might confound the association between hemoglobin and height loss. Therefore, we performed analyses stratified by BMI status. To clarify the association between hemoglobin and height loss, we conducted a retrospective study of Japanese workers (6,471 men and 3,180 women) aged 40-74 years. Height loss was defined as being in the highest quintile of height decrease per year. In men overall and men with BMI <25 kg/m2, hemoglobin was significantly inversely associated with height loss; but no association was observed for men with high BMI (BMI ≥25 kg/m2) and for women. For men, after adjusting for known cardiovascular risk factors, adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for height loss with each 1 standard deviation (SD) increase in hemoglobin (1.0 g/dL for men and 0.8g/dL for women) were 0.89 (0.83, 0.95) for men overall, 0.82 (0.75, 0.89) for men who do not have high BMI, and 1.01 (0.92, 1.12) for men with high BMI. For women, the corresponding values were 0.97 (0.89, 1.06), 0.98 (0.89, 1.09), and 0.93 (0.75, 1.15) respectively. Hemoglobin is significantly inversely associated with height loss in men who do not have high BMI, but not in men with high BMI or women. These results help clarify the mechanisms underlying height loss, which has been reported to be associated with a higher risk of mortality in adults.

Asociación entre indicadores antropométricos y dislipidemia en adolescentes y adultos jóvenes de la ciudad de Caracas / Association between anthropometric indicators and dyslipidemia in adolescents and young adults in the city of Caracas

Tradicionalmente se han utilizado algunos índices antropométricos para el diagnóstico de exceso de peso en niños y adolescentes que han mostrado algunas desventajas por lo que se han postulado otros indicadores. En ese sentido, se plantea estimar el nivel de asociación entre indicadores antropométricos y la presencia de dislipidemia en adolescentes y adultos jóvenes. Se realizó una investigación observacional, descriptiva y de corte transversal en 123 adolescentes (68,2% mujeres, edad promedio 14,5 años) y 122 adultos jóvenes (70,5% mujeres, edad promedio 21 años) de la ciudad de Caracas. Se calcularon Índices de Masa Corporal (IMC), Índice Cintura­Talla (ICT), Índice de Masa Corporal Abdominal (IMCA) e Índice de Masa Tri-Ponderal (IMT). Se obtuvo una muestra de sangre por punción venosa, en ayuno de 12 a 14 horas, a partir de la cual se cuantificó Colesterol Total, Lipoproteína de alta densidad y Triglicéridos. Se calculó la concentración de Lipoproteína de baja densidad por la fórmula de Friedewald, así como el índice LDL-C/HDL-C y el índice LogTg/HDL. Para el análisis e interpretación de los datos se utilizó estadística descriptiva univariante y multivariante. Los resultados revelaron que los índices antropométricos IMCA e IMT no mostraron mejor desempeño en predecir dislipidemia que los indicadores IMC, Circunferencia de Cintura (CC) e ICT en adolescentes y adultos jóvenes. Los indicadores antropométricos de adiposidad abdominal, CC e ICT, tendieron a presentar mayores OR, ABC, sensibilidad y especificidad independientemente del grupo de estudio. En general, la capacidad de los indicadores antropométricos evaluados en predecir la presencia de dislipidemia en adultos jóvenes fue adecuada, situación que no se presentó en los adolescentes(AU)

Traditionally, some anthropometric indices have been used for the diagnosis of excess weight in children and adolescents, which have shown some disadvantages for which other indicators have been postulated. In this sense, it is proposed to estimate the level of association between anthropometric indicators and the presence of dyslipidemia in adolescents and young adults. An observational, descriptive cross-sectional investigation was carried out in 123 adolescents (68,2% women, media age 14,5 years) and 122 young adults (70,5% women, media age 21 years) from the city of Caracas. Body Mass Indices (BMI), Waist-Height Ratio (WHR), Abdominal Body Mass Index (BMAI) and Tri-Ponderal Mass Index (TMI) were calculated. A blood sample was obtained by venipuncture, fasting for 12 to 14 hours, from which Total Cholesterol, High Density Lipoprotein and Triglycerides were quantified. The low-density lipoprotein concentration was calculated by the FriedEwald formula, as well as the LDL-C / HDL-C index and the LogTg / HDL index. Univariate and multivariate descriptive statistics were used for the analysis and interpretation of the data. The results revealed that the BMI and TMI anthropometric indices did not show better performance in predicting dyslipidemia than the BMI, Waist Circumference (WC) and WHR indicators in adolescents and young adults. The anthropometric indicators of abdominal adiposity, WC and WHR, tended to present higher OR, AUC, sensitivity and specificity regardless of the study group. In general, the capacity of the anthropometric indicators evaluated to predict the presence of dyslipidemia in young adults was adequate, a situation that did not occur in adolescents(AU)

The interplay of sleep duration, working hours, and obesity in Korean male workers: The 2010-2015 Korea National Health and Nutrition Examination Survey.

The purpose of this study was to clarify the odds ratio for association between working hours and obesity in Korean male wage workers and investigate the role of sleep duration. This study is a cross-sectional one using large-scale national data from the Korea National Health and Nutrition Examination Survey collected between 2010 and 2015 to evaluate 2,592 male wage workers (between the ages of 19 and 60 years). Obesity was defined as 25kg/m2 or more and working hours per week were categorized into <40, 40-49, 50-59, and ≥60 hours. Multiple regression analysis was performed to examine the odds ratio for association between working hours and obesity, after controlling for age, education, income, marital status, smoking, drinking, physical activity, daily energy intake, sleep duration, hypertension, diabetes, dyslipidemia, work schedule, and job category. Next, to study the mediating effect of sleep duration on the association between working hours and obesity, an analysis was performed using the Baron and Kenny method and the Sobel test. Results showed that workers with 50 to 59 hours had 1.4 times higher odds (odds ratio [OR] = 1.4, confidence interval [CI]: 1.11-1.85) of obesity and workers with 60 hours or more had 1.4 times higher odds (OR = 1.4, CI: 1.06-1.90) of obesity than workers with less than 40 hours. Sleep was found to have a mediating effect on the association between working time and body mass index. Therefore, the results of this analysis suggest that practitioners should identify potential factors such as working time and sleeping time when preventing work-related obesity.

Bempedoic Acid: a cholesterol lowering agent with a novel mechanism of action.

INTRODUCTION: Dyslipidemia is a common condition that increases the risk of heart diseases and stroke. High levels of low-density lipoprotein-cholesterol (LDL-C) are correlated with a higher risk for heart disease. A drug class known as 'statins' is the gold standard for LDL-C-lowering, but its use in some patients is limited by its adverse effects of myalgias and myopathies. Use of other LDL-C-lowering agents is frequently limited by cost and degree of efficacy. Additionally, many high-risk atherosclerotic cardiovascular disease patients fail to meet LDL-C goals despite maximally tolerated statin therapy with or without the addition of a non-statin agent. AREAS COVERED: This review covers the pharmacology, pharmacokinetics, clinical trials, and clinical implications of bempedoic acid. A PubMed search was conducted using the terms bempedoic, bempedoic acid, Nexletol, ETC-1002, and adenosine triphosphate citrate lyase inhibitor. Additional data were obtained from the prescribing information and relevant guidelines. All clinical trials were included. EXPERT OPINION: Bempedoic acid has not been shown to cause myalgias or myopathies and is likely to be competitively affordable compared to other LDL-C-lowering agents. Bempedoic acid has been shown to be superior compared to placebo and provides additional LDL-C lowering on top of maximally tolerated statin therapy or combined with ezetimibe alone.

Fasting Blood Glucose, Cholesterol, and Risk of Primary Liver Cancer: The Kailuan Study.

PURPOSE: The influence of fasting blood glucose (FBG) and cholesterolemia primary liver cancer (PLC) in china was analyzed via a large prospective cohort study based on a community population, and the combined effects between them were investigated. MATERIALS AND METHODS: Overall, 98,936 staff from the Kailuan Group who participated in and finished physical examinations between 2006 and 2007 were included in the cohort study. Their medical information was collected and they were followed up after examination. The correlations of serum FBG or total cholesterol (TC) with PLC were analyzed. Then, we categorized all staff into four groups: normal FBG/non-hypocholesterolemia, normal FBG/hypocholesterolemia, elevated FBG/non-hypocholesterolemia, elevated FBG/hypocholesterolemia, and normal FBG/non-hypocholesterolemia was used as a control group. The combined effects of elevated FBG and hypocholesterolemia with PLC were analyzed using the Age-scale Cox proportional hazard regression model. RESULTS: During 1,134,843.68 person-years follow-up, a total of 388 PLC cases occurred. We found the elevated FBG and hypocholesterolemia increase the risk for PLC, respectively. Compared with the non-hypocholesterolemia/normal FBG group, the risk of PLC was significantly increased in the non-hypocholesterolemia/elevated FBG group (hazard artio [HR], 1.19; 95% confidence interval [CI], 0.88 to 1.62) and hypocholesterolemia/normal FBG group (HR, 1.53; 95% CI, 1.19 to 1.97), and in the hypocholesterolemia/elevated FBG group (HR, 3.16; 95% CI, 2.13 to 4.69). And, a significant interaction effect was found of FBG and TC on PLC. All results were independent from the influence of liver disease. CONCLUSION: Elevated serum FBG and hypocholesterolemia are risk factors for PLC, especially when combined. Thus, for the prevention and treatment of PLC, serum FBG and TC levels should be investigated.

Association of LDLc to HDLc ratio with carotid plaques in a community-based population with a high stroke risk: A cross-sectional study in China.

BACKGROUND AND AIMS: The association between low-density lipoprotein cholesterol (LDLc) to high-density lipoprotein cholesterol (HDLc) ratio (LDLc/HDLc) and carotid plaques remains controversial. We conducted a cross-sectional study to evaluate whether LDLc/HDLc is associated with carotid plaques in individuals with a high-stroke-risk. METHODS AND RESULTS: The study initially enrolled 5529 residents aged 40 years or older from Yangzhou, China in 2013-2014. All participants received a questionnaire interview, physical examination, and laboratory tests. Risk factors for stroke included hypertension, diabetes mellitus, dyslipidemia, atrial fibrillation, smoking, less exercise, overweight/obesity, and family stroke history. Subjects with at least three of the risk factors or a history of stroke/transient ischemic attack (TIA) were defined as a high-stroke-risk population. Carotid ultrasonography was only conducted for this high-stroke-risk population. Logistic regression was used to examine the association of LDLc/HDLc with the presence of carotid plaques. Final analysis included 839 high-stroke-risk subjects and 40.6% were identified to have carotid plaques. Subjects with the highest tertiles group of LDLc/HDLc had a higher proportion of carotid plaques than the other two groups (47.1% vs. 34.6% and 40.4%, P < 0.001). With each unit increase of LDLc/HDLc, the chance of having carotid plaques increased by 65% (OR 1.65, 95%CI 1.31-2.08) after adjusted for potential confounders. Among most subgroups, a higher LDLc/HDLc was significantly correlated with the presence of carotid plaques. CONCLUSION: Higher LDLc/HDLc was significantly associated with the presence of carotid plaques in the Chinese population with a high risk of stroke.

Repercussões metabólicas: quais, como e por que investigar? / Metabolic repercussions: which ones, how and why investigate?

A síndrome dos ovários policísticos (SOP) é frequentemente acompanhada de distúrbio metabólico, principalmente dos carboidratos e dos lipídeos, aumentando o risco de síndrome metabólica. Por essa razão, alguns investigadores ainda denominam a SOP de síndrome metabólica-reprodutiva. O objetivo deste capítulo é descrever as principais repercussões metabólicas, bem como como investigá-las e saber como suas consequências podem ser deletérias para a saúde da mulher. Esta é uma revisão narrativa mostrando a implicação do metabolismo dos carboidratos e dos lipídeos nas dislipidemias, bem como da síndrome metabólica sobre o sistema reprodutor, e o risco cardiovascular da mulher com SOP. Conclui-se que o manejo adequado dos distúrbios metabólicos na SOP é benéfico a curto e a longo prazo tanto para o sistema reprodutor quanto para o cardiovascular.(AU)

Nutritional Intervention Reduces Dyslipidemia, Fasting Glucose and Blood Pressure in People Living with HIV/AIDS in Antiretroviral Therapy: A Randomized Clinical Trial Comparing Two Nutritional Interventions.

Antiretroviral therapy (ART) increases the risk of cardiometabolic diseases in people living with HIV/AIDS (PLWHA). However, there is a lack of evidence regarding the effectiveness of a nutritional intervention on several cardiometabolic parameters in this population. Therefore, this study aimed to evaluate the effectiveness of two nutritional interventions on several cardiometabolic parameters in PLWHA treated with ART. A parallel randomized clinical trial was performed with PLWHA treated with ART. The participants (n = 88) were divided into two intervention groups: (1) nutritional counseling (n = 44) and (2) individualized dietary prescription (n = 44). The follow-up period was 30 weeks. A reduction in low-density lipoprotein (LDL) was the primary outcome. Secondary outcome variables were reductions in total cholesterol (TC), triglycerides (TG), fasting plasma glucose (FPG), systolic and diastolic blood pressures (SBP and DBP, respectively), waist circumference (WC), body mass index (BMI), and increases in high-density lipoproteins (HDL). A multiple linear regression was used to analyze the effectiveness of the interventions, adjusted for sociodemographic, lifestyle, and clinical characteristics. Sixty-two PLWHA completed the trial (nutritional counseling, n = 32; individualized dietary prescription, n = 30). At follow-up, we observed in the nutritional counseling group significant reductions in SBP (p = 0.036) and DBP (p = 0.001). Significant reductions in FPG (p = 0.008) and DBP (p = 0.023) were found in the individualized dietary prescription group. In the fully adjusted models, significant reductions in LDL, SBP, DBP, and BMI were found in the individualized dietary prescription group. In conclusion, the two investigated nutritional interventions were effective in reducing some cardiometabolic risk factors in PLWHA. However, after adjustments for covariates, the individualized dietary prescription showed significant reductions in the primary outcome and, also, in more cardiometabolic risk factors than the nutritional counseling.

Differential risk factors and morbidity/mortality pattern in type 2 diabetes: A study among two Mendelian populations with different ancestry (India).

BACKGROUND AND AIMS: Association studies of type 2 diabetes mellitus (T2DM) with risk factors have shown variable results. Moreover, population-specific comparative investigations are negligible. Therefore, the present study aimed to evaluate the association of dyslipidemia and obesity with impaired fasting glucose (IFG) and T2DM among two ethnically, geographically and culturally different populations in India. METHODS: This was a cross-sectional study among Jats and Meiteis, each inhabiting a separate geographical region. A total of 2371 individuals, age ≥30 years were recruited through household survey. Obesity variables were captured using anthropometric measurements while fasting blood (2.5 mL) was drawn to measure lipid and glucose levels using enzymatic assay by spectrophotometer. Participants were categorized under normal, IFG and T2DM groups, indicative of diabetes progression stages. Statistical analysis was performed using SPSS 16.0 version. RESULTS: Significant differential distribution of lipid and obesity variables among IFG and T2DM in both populations were observed. Odds ratio revealed high TC and all obesity variables except BMI posed significant increased risk for T2DM among Jats. Abnormal TG, VLDL, WC, and WHtR posed significant increased risk for T2DM among Meiteis. Age-cohort wise prevalence of T2DM showed increasing trend at ≥60 years among Jats and decreasing trend at ≥60 years among Meiteis, suggesting a potential higher morbidity in the former and mortality in latter because of T2DM. CONCLUSIONS: The present study observed a differential association of risk factors for T2DM among Jats and Meiteis. This study emphasize the need to implement community-specific intervention programs for prevention, treatment and management of T2DM.

Integrins α4ß1 and αVß3 are Reduced in Endothelial Progenitor Cells from Diabetic Dyslipidemic Mice and May Represent New Targets for Therapy in Aortic Valve Disease.

Diabetes reduces the number and induces dysfunction in circulating endothelial progenitor cells (EPCs) by mechanisms that are still uncovered. This study aims to evaluate the number, viability, phenotype, and function of EPCs in dyslipidemic mice with early diabetes mellitus and EPC infiltration in the aortic valve in order to identify possible therapeutic targets in diabetes-associated cardiovascular disease. A streptozotocin-induced diabetic apolipoprotein E knock-out (ApoE-/-) mouse model was used to identify the early and progressive changes, at 4 or 7 days on atherogenic diet after the last streptozotocin or citrate buffer injection. Blood and aortic valves from diabetic or nondiabetic ApoE-/- animals were collected.EPCs were identified as CD34 and vascular endothelial growth factor receptor 2 positive monocytes, and the expression levels of α4ß1, αVß3, αVß5, ß1, αLß2, α5 integrins, and C-X-C chemokine receptor type 4 chemokine receptor on EPC surface were assessed by flow cytometry. The number of CD34 positive cells in the aortic valve, previously found to be recruited progenitor cells, was measured by fluorescence microscopy. Our results show that aortic valves from mice fed 7 days with atherogenic diet presented a significantly higher number of CD34 positive cells compared with mice fed only 4 days with the same diet, and diabetes reversed this finding. We also show a reduction of circulatory EPC numbers in diabetic mice caused by cell senescence and lower mobilization. Dyslipidemia induced EPC death through apoptosis regardless of the presence of diabetes, as shown by the higher percent of propidium iodide positive cells and higher cleaved caspase-3 levels. EPCs from diabetic mice expressed α4ß1 and αVß3 integrins at a lower level, while the rest of the integrins tested were unaffected by diabetes or diet. In conclusion, reduced EPC number and expression of α4ß1 and αVß3 integrins on EPCs at 4 and 7 days after diabetes induction in atherosclerosis-prone mice have resulted in lower recruitment of EPCs in the aortic valve.

Gender differences in the modifiable risk factors associated with the presence of prediabetes: A systematic review.

BACKGROUND: Prediabetes is a risk state for the future development of type 2 diabetes. Previously, it was evident that the risk factors for diabetes differ by gender. However, conclusive evidence regarding the gender difference in modifiable risk factors associated with the presence of pre-diabetes is still lacking. AIMS: To systematically identify and summarize the available literature on whether the modifiable risk factors associated with prediabetes displays similar relationship in both the genders. METHODS: A systematic search was performed on electronic databases i.e. PubMed, EBSCOhost, and Scopus using "sex", "gender", "modifiable risk factors" and "prediabetes" as keywords. Reference list from identified studies was used to augment the search strategy. Methodological quality and results from individual studies were summarized in tables. RESULTS: Gender differences in the risk factor association were observed among reviewed studies. Overall, reported association between risk factors and prediabetes apparently stronger among men. In particular, abdominal obesity, dyslipidemia, smoking and alcohol drinking habits were risk factors that showed prominent association among men. Hypertension and poor diet quality may appear to be stronger among women. General obesity showed stringent hold, while physical activity not significantly associated with the risk of prediabetes in both the genders. CONCLUSIONS: Evidence suggests the existence of gender differences in risk factors associated with prediabetes, demands future researchers to analyze data separately based on gender. The consideration and the implementation of gender differences in health policies and in diabetes prevention programs may improve the quality of care and reduce number of diabetes prevalence among prediabetic subjects.

Increased cancer risk in polycystic ovary syndrome: An (un)sympathetic connection?

Women with polycystic ovary syndrome (PCOS) have been shown to have a higher incidence of cancer. It is suggested that several factors, including hyperinsulinemia, dyslipidemia, raised estrogen levels, chronic inflammation, and reduced apoptosis are responsible for this association. However, in this paper we propose the hypothesis that increased sympathetic activity may represent an important factor that interconnects PCOS and cancer. This hypothesis is based on two facts: a) in women with PCOS is found sympathetic hyperactivity and b) recent data showing a stimulatory effect of the sympathetic system on cancer initiation, progression, and development of metastases. If our hypothesis is correct, then new preventive approaches might be used to reduce cancer risk in women with PCOS.

Association Between Dyslipidemia and Dry Eye Syndrome Among the Korean Middle-Aged Population.

PURPOSE: Dry eye syndrome (DES) is a common eye disease caused by tear deficiency or excessive tear evaporation. Because the tear film layers play a major role in the pathogenesis of the evaporative dry eye, some previous articles have suggested the possible mechanism of dyslipidemia and DES. However, the previous results were inconsistent and few studies were conducted to find the independent relationship between dyslipidemia and DES. Therefore, we investigated the association of dyslipidemia with DES in middle-aged Korean adults. METHODS: This study was conducted on 2272 participants (854 men and 1418 women) enrolled in the Study Group for Environmental Eye Disease (2013-2017) after excluding people who have taken lipid-lowering medication. Participants with total cholesterol ≥240 mg/dL or high-density lipoprotein cholesterol <40 mg/dL or low-density lipoprotein cholesterol ≥160 mg/dL or triglycerides ≥200 mg/dL are defined as having dyslipidemia. Using the ocular surface disease index, we measured the DES severity and defined DES as an ocular surface disease index score ≥13. RESULTS: Men with dyslipidemia had an odds ratio of 1.29 (95% confidence interval, 0.97-1.71) for DES in an unadjusted model compared with those without DES. After adjusting for age, body mass index, hypertension, diabetes, occupations, smoking and drinking status, exercise, contact lens use, computer use, study cohorts, and calendar year of examinations, the adjusted odds ratio for DES was 1.40 (1.03-1.90) in men. However, there was no significant association between dyslipidemia and DES in women, even after stratifying by menopausal status. CONCLUSIONS: Our findings suggest that dyslipidemia may be associated with the prevalence of DES in Korean men, but not in women.

Excess weight mediates changes in HDL pool that reduce cholesterol efflux capacity and increase antioxidant activity.

BACKGROUND AND AIM: Obesity-related decline in high-density lipoprotein (HDL) functions such as cholesterol efflux capacity (CEC) has supported the notion that this lipoprotein dysfunction may contribute for atherogenesis among obese patients. We investigated if potentially other HDL protective actions may be affected with weight gain and these changes may occur even before the obesity range in a cross-sectional analysis. METHODS AND RESULTS: Lipid profile, body mass index (BMI), biochemical measurements, and carotid intima-media thickness (cIMT) were obtained in this cross-sectional study with 899 asymptomatic individuals. Lipoproteins were separated by ultracentrifugation and HDL physical-chemical characterization, CEC, antioxidant activity, anti-inflammatory activity, HDL-mediated platelet aggregation inhibition were measured in a randomly-selected subgroup (n = 101). Individuals with increased HDL-C had an attenuated increase in cIMT with elevation of BMI (interaction effect ß = -0.054; CI 95% -0.0815, -0.0301). CEC, HDL-C, HDL size and HDL-antioxidant activity were negatively associated with cIMT. BMI was inversely correlated with HDL-mediated inhibition of platelet aggregation (Spearman's rho -0.157, p < 0.03) and CEC (Spearman's rho -0.32, p < 0.001), but surprisingly it was directly correlated with the antioxidant activity (Spearman's rho 0.194, p = 0.052). Thus, even in non-obese, non-diabetic individuals, increased BMI is associated with a wide change in protective functions of HDL, reducing CEC and increasing antioxidant activity. In these subjects, decreased HDL concentration, size or function are related to increased atherosclerotic burden. CONCLUSION: Our findings demonstrate that in non-obese, non-diabetic individuals, the increasing values of BMI are associated with impaired protective functions of HDL and concomitant increase in atherosclerotic burden.

Effects of 1 year of exercise training versus combined exercise training and weight loss on body composition, low-grade inflammation and lipids in overweight patients with coronary artery disease: a randomized trial.

BACKGROUND: Dyslipidaemia and low-grade inflammation are central in atherogenesis and linked to overweight and physical inactivity. Lifestyle changes are important in secondary prevention of coronary artery disease (CAD). We compared the effects of combined weight loss and interval training with interval training alone on physical fitness, body composition, dyslipidaemia and low-grade inflammation in overweight, sedentary participants with CAD. METHODS: Seventy CAD patients, BMI 28-40 kg/m2 and age 45-75 years were randomised to (1) 12 weeks' aerobic interval training (AIT) at 90% of peak heart rate three times/week followed by 40 weeks' AIT twice weekly or (2) a low energy diet (LED) (800-1000 kcal/day) for 8-10 weeks followed by 40 weeks' weight maintenance including AIT twice weekly and a high-protein/low-glycaemic load diet. Effects of the intervention were evaluated by physical fitness, body weight and composition. Dyslipidaemia was described using both biochemical analysis of lipid concentrations and lipoprotein particle subclass distribution determined by density profiling. Low-grade inflammation was determined by C-reactive protein, soluble urokinase-type plasminogen activator receptor and tumour necrosis factor α. Effects on continuous outcomes were tested by mixed-models analysis. RESULTS: Twenty-six (74%) AIT and 29 (83%) LED + AIT participants completed the study. At baseline subject included 43 (78%) men; subjects averages were: age 63 years (6.2), body weight 95.9 kg (12.2) and VO2peak 20.7 mL O2/kg/min (4.9). Forty-six (84%) had pre-diabetes (i.e. impaired fasting glucose and/or impaired glucose tolerance). LED + AIT reduced body weight by 7.2 kg (- 8.4; - 6.1) and waist circumference by 6.6 cm (- 7.7; - 5.5) compared to 1.7 kg (- 0.7; - 2.6) and 3.3 cm (- 5.1; - 1.5) after AIT (within-group p < 0.001, between-group p < 0.001 and p = 0.018, respectively). Treatments caused similar changes in VO2peak and lowering of total cholesterol, triglycerides, non-HDL cholesterol and low-grade inflammation. A shift toward larger HDL particles was seen following LED + AIT while AIT elicited no change. CONCLUSIONS: Both interventions were feasible. Both groups obtained improvements in VO2peak, serum-lipids and inflammation with superior weight loss and greater central fat loss following LED + AIT. Combined LED induced weight loss and exercise can be recommended to CAD patients. Trial registration NCT01724567, November 12, 2012, retrospectively registered (enrolment ended in April 2013).

Relationship between blood lipid and arterial stiffness in hypertension.

PURPOSE: To explore the relationship between blood lipids and pulse wave velocity (PWV). METHODS: We retrospectively selected subjects who had undergone treatment in an outpatient or inpatient clinic. The subjects were sub-grouped into four groups: Group A (no history of hypertension and dyslipidemia), Group B (a history of dyslipidemia but not hypertension), Group C (a history of hypertension but not dyslipidemia) and Group D (a history of both hypertension and dyslipidemia). We determined brachial-ankle pulse wave velocity (baPWV), atherogenic index of plasma (AIP), non-high-density lipoprotein (non-HDL-C), total cholesterol/high density lipoprotein (TC/HDL-C) and atherogenic indices (AI) for hypertension and non-hypertension and dyslipidemia and non-dyslipidemia patients. RESULTS: A total of 380 subjects were included. Uric acid, systolic pressure, diastolic pressure, pulse pressure and mean arterial pressure were significantly different among the groups. The prevalence of coronary arterial disease and diabetes mellitus, age, body mass index, heart rate, blood glucose, creatinine, urea, smoking history and alcohol consumption did not differ among groups. The baPWV was significantly different between both hypertension/nonhypertension and dyslipidemia/non-dyslipidemia patients. In hypertension patients (in Group C and D), partial correlation analysis showed that ΔbaPWV correlated with TC, HDL-C, AI, AIP and TC/HDL-C but not LDL-C, triglyceride (TG) or non-HDL-C. CONCLUSION: Hypertension and/or dyslipidemia may be risk factors for arterial stiffness. In hypertension patients, TC, HDL-C, AIP, AI and TC/HDL-C might correlate to arterial stiffness and pathological increases in these levels may indicate risk factors for arterial stiffness.

Mendelian randomization analysis rules out disylipidaemia as colorectal cancer cause.

Dyslipidemia and statin use have been associated with colorectal cancer (CRC), but prospective studies have shown mixed results. We aimed to determine whether dyslipidemia is causally linked to CRC risk using a Mendelian randomization approach and to explore the association of statins with CRC. A case-control study was performed including 1336 CRC cases and 2744 controls (MCC-Spain). Subjects were administered an epidemiological questionnaire and were genotyped with an array which included polymorphisms associated with blood lipids levels, selected to avoid pleiotropy. Four genetic lipid scores specific for triglycerides (TG), high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), or total cholesterol (TC) were created as the count of risk alleles. The genetic lipid scores were not associated with CRC. The ORs per 10 risk alleles, were for TG 0.91 (95%CI: 0.72-1.16, p = 0.44), for HDL 1.14 (95%CI: 0.95-1.37, p = 0.16), for LDL 0.97 (95%CI: 0.81-1.16, p = 0.73), and for TC 0.98 (95%CI: 0.84-1.17, p = 0.88). The LDL and TC genetic risk scores were associated with statin use, but not the HDL or TG. Statin use, overall, was a non-significant protective factor for CRC (OR 0.84; 95%CI: 0.70-1.01, p = 0.060), but lipophilic statins were associated with a CRC risk reduction (OR 0.78; 95%CI 0.66-0.96, p = 0.018). Using the Mendelian randomization approach, our study does not support the hypothesis that lipid levels are associated with the risk of CRC. This study does not rule out, however, a possible protective effect of statins in CRC by a mechanism unrelated to lipid levels.