Effects of Poly-Bioactive Compounds on Lipid Profile and Body Weight in a Moderately Hypercholesterolemic Population with Low Cardiovascular Disease Risk: A Multicenter Randomized Trial

A dietary supplement (AP, Armolipid Plus) that combines red yeast rice extract, policosanol, berberine, folic acid, coenzyme Q₁₀ and asthaxantine can have beneficial effects on cardiovascular disease (CVD) biomarkers. The aim of this study was to assess whether the intake of AP, in combination with dietary recommendations, reduces serum low density lipoprotein cholesterol (LDL-c) concentrations and other CVD biomarkers in patients with hypercholesterolemia. Eligible patients were recruited from the outpatient clinics of six Spanish hospitals Hospital Virgen del Rocío (Sevilla); Hospital San Jorge (Huesca); Hospital San Pedro (Logroño); Hospital Gregorio Marañón (Madrid), Hospital la Fe (Valencia) and Hospital Universitari Sant Joan (Reus) as recruiting and coordinating center. 102 participants (mean age ± SD; 50.91±11.61; 32 men) with low CVD, with mild-to-moderately elevated LDL-c (between 3.35 mmol/L and 4.88 mmol/L) without hypolipemic therapy were randomized in a double-blind, parallel, controlled, multicenter trial commencing January 2012 and ending December 2012. Among the exclusion criteria were any concomitant chronic disease, triglycerides (TG) >3.97 mmol/L, pregnant or lactating, and history of CVD. At 12 weeks, compared to placebo, AP reduced LDL-c by −6.9%, apolipoprotein (Apo) B-100 by −6.6% and total cholesterol/HDL-c ratio by −5.5%, the ApoB/ApoA1 ratio by −8.6%, while increasing ApoA1 by +2.5% (p<0.05). AP consumption was associated with modest mean weight loss of −0.93 kg (95%CI: -1.74 to -0.12; P = 0.02) compared with control group while dietary composition remained unchanged in the AP group. The AP product was well tolerated. In conclusion, AP, combined with dietary recommendations, reduced LDL-c levels as well as total cholesterol/HDL-c and ApoB/ApoA1 ratios, while increasing Apo A1, all of which are improvements in CVD risk indicators. AP is a product which could benefit patients having moderate hyperlipidemia and excess body weight.

Trial Registration

ClinicalTrials.gov NCT01562080     

Circulating Irisin Concentrations Are Associated with a Favourable Lipid Profile in the General Population

Background/aimsIrisin is a myokine, which is mainly inversely associated with the risk for non-communicable diseases. Irisin improves cellular energy metabolism by uncoupling the mitochondrial respiratory chain resulting in increased energy expenditure using lipids. To date potential associations between irisin concentration and lipid profile are poorly understood. Therefore, this investigation aimed to evaluate potential associations between irisin and lipid levels in the general population.MethodsData of 430 men and 537 women from the population-based Study of Health in Pomerania (SHIP-TREND) with available irisin and lipid concentrations were used. Analyses of variance, linear and logistic regression models adjusted for age, HBA1c, waist circumference, physical activity, smoking, alcohol consumption, systolic blood pressure, ALAT were calculated.ResultsWe detected significantly inverse associations between irisin and circulating levels of total [beta coefficient 0.21 (standard error 0.08), p = 0.01], low-density cholesterol [-0.16 (0.07), p = 0.03] and triglycerides [-0.17 (0.08), p = 0.02] for men. Females without lipid lowering medication had an inverse association between irisin and total cholesterol [-0.12 (0.06), p = 0.05]. Further, male subjects with irisin concentrations in the third tertile had an increased odds for elevated low-density cholesterol [odds ratio 1.96 (95% confidence interval 1.07–3.48), p = 0.03) and triglyceride [1.95 (1.09–3.47), p = 0.02] levels, even after exclusion of subjects with lipid lowering medication. In addition, our data revealed an annual rhythm of serum irisin levels with peak levels arise in winter and summer months.ConclusionThis is the first investigation to report a significant association between circulating irisin and a favourable lipid profile in the general population. This may infer that higher irisin concentrations are associated with a reduced risk for non-communicable diseases.     

Plasma Antioxidants and Human Aging: A Study on Healthy Elderly Tunisian Population

The aging has been described by several theories. It was proposed that free radicals are the major factor involved in this process. This gave birth to the free radical theory of aging. This current theory provides the most popular explanation for how aging occurs at the biochemical/molecular level. Ever since 1956, this theory has received widespread attention and a large body of evidence has been accumulated in support of its hypotheses which were subsequently refined. The free radical theory of aging postulates that age-associated reductions in physiological functions are caused by an irreversible accumulation of oxidative alterations to macromolecules. This accumulation increases with age and is associated with the life expectancy of organisms. Moreover, this theory suggests the existence of an imbalance between reactive oxygen species (ROS)-producing pathways and (ROS)-scavenging pathways, which is responsible for the generation of oxidative stress syndrome. In this article, we evaluate the antioxidant status in a population of healthy elderly Tunisians in comparison with a group of healthy young Tunisian subjects. This study sets out to investigate the age-related changes in glutathione peroxidase (GPx), superoxide dismutase (SOD) activities, and in total antioxidant status (TAS) of human plasma. We have concluded that healthy aging is accompanied with a disturbed antioxidant status.     

Risks and Population Burden of Cardiovascular Diseases Associated with Diabetes in China: A Prospective Study of 0.5 Million Adults

BackgroundIn China, diabetes prevalence is rising rapidly, but little is known about the associated risks and population burden of cardiovascular diseases. We assess associations of diabetes with major cardiovascular diseases and the relevance of diabetes duration and other modifiable risk factors to these associations.ConclusionsAmong Chinese adults, diabetes is associated with significantly increased risks of major cardiovascular diseases. The increasing prevalence and younger age of onset of diabetes foreshadow greater diabetes-attributable disease burden in China.     

The Important Role of Lipid Peroxidation Processes in Aging and Age Dependent Diseases

Any change in the cell membrane structure activates lipoxygenases (LOX). LOX transform polyunsaturated fatty acids (PUFAs) to lipidhydroperoxide molecules (LOOHs). When cells are severely wounded, this physiological process switches to a non-enzymatic lipid peroxidation (LPO) process producing LOO^· radicals. These oxidize nearly all-biological molecules such as lipids, sugars, and proteins. The LOO^· induced degradations proceed by transfer of the radicals from cell to cell like an infection. The chemical reactions induced by LO^· and LOO^· radicals seem to be responsible for aging and induction of age dependent diseases. Alternatively, LO^· and LOO^· radicals are generated by frying of fats and involve cholesterol-PUFA esters and thus induce atherogenesis. Plants and algae are exposed to LOO^· radicals generating radiation. In order to remove LOO^· radicals, plants and algae transform PUFAs to furan fatty acids, which are incorporated after consumption of vegetables into mammalian tissues where they act as excellent scavengers of LOO^· and LO^· radicals. Figure 6 of this article is reprinted from the paper of G. Spiteller: “Peroxyl radicals: Inductors of neurodegenerative and other inflammatory diseases. Their origin and how they transform cholesterol, phospholipids, plasmalogens, polyunsaturated fatty acids, sugars and proteins into deleterious products” published in Free Radic. Biol. Med. 41, 362–387 (2006) Elsevier, 2006 by permission from Elsevier.     

The Role of Lipid Bodies in the Microglial Aging Process and Related Diseases

Lipid bodies (LBs) have long been considered to be organelles merely for the storage of neutral lipids. However, recent studies have shown the significance of LBs in signal transduction, especially in glial cells, including microglia. Microglial cells are the resident mononuclear phagocytes in the central nervous system and have a close relationship with the aging process and neurodegenerative diseases. Evidence suggests that LBs accumulate and are remodeled during the aging process and the development of neuroinflammatory conditions. However, the mechanisms underlying the formation of LBs under these conditions and the mechanism by which LB remodeling influences the progression of neurodegeneration remain to be clarified. In this review, we have summarized the findings from recent studies with the aim of further elucidating these issues.     

p63: A New Link Between Senescence and Aging

Cellular senescence is a distinctive form of cell cycle arrest that has been suggested to modulatethe processes of tumor suppression and aging. Though a detailed understanding of the cellularmachinery regulating this process is emerging, a more thorough understanding of the key playerslinking senescence to organismal aging is needed. The recent discovery that loss of the p53-related protein p63 induces cellular senescence and causes features of accelerated aging providesfurther evidence that cellular senescence is intimately linked with organismal aging, andidentifies p63 as a key regulator of both of these processes.     

Risk of Cardiovascular Disease in a Traditional African Population with a High Infectious Load: A Population-Based Study

Background

To test the inflammatory origin of cardiovascular disease, as opposed to its origin in western lifestyle. Population-based assessment of the prevalences of cardiovascular risk factors and cardiovascular disease in an inflammation-prone African population, including electrocardiography and ankle-arm index measurement. Comparison with known prevalences in American and European societies.

Methodology/Principal Findings

Traditional population in rural Ghana, characterised by adverse environmental conditions and a high infectious load. Population-based sample of 924 individuals aged 50 years and older. Median values for cardiovascular risk factors, including waist circumference, BMI, blood pressure, and markers of glucose and lipid metabolism and inflammation. Prevalence of myocardial infarction detected by electrocardiography and prevalence of peripheral arterial disease detected by ankle-arm index. When compared to western societies, we found the Ghanaians to have more proinflammatory profiles and less cardiovascular risk factors, including obesity, dysglycaemia, dyslipidaemia, and hypertension. Prevalences of cardiovascular disease were also lower. Definite myocardial infarction was present in 1.2% (95%CI: 0.6 to 2.4%). Peripheral arterial disease was present in 2.8% (95%CI: 1.9 to 4.1%).

Conclusions/Significance

Taken together, our data indicate that for the pathogenesis of cardiovascular disease inflammatory processes alone do not suffice and additional factors, probably lifestyle-related, are mandatory.     

Estimated Glomerular Filtration Rate,All-Cause Mortality and Cardiovascular Diseases Incidence in a Low Risk Population: The MATISS Study

Background

Chronic kidney disease (CKD) independently increases the risk of death and cardiovascular disease (CVD) in the general population. However, the relationship between estimated glomerular filtration rate (eGFR) and CVD/death risk in a general population at low risk of CVD has not been explored so far.

Design

Baseline and longitudinal data of 1465 men and 1459 women aged 35-74 years participating to the MATISS study, an Italian general population cohort, were used to evaluate the role of eGFR in the prediction of all-cause mortality and incident CVD.

Methods

Bio-bank stored sera were used to evaluate eGFR at baseline. Serum creatinine was measured on thawed samples by means of an IDMS-calibrated enzymatic method. eGFR was calculated by the CKD-EPI formula.

Results

At baseline, less than 2% of enrolled persons had eGFR < 60 mL/min/1.73m² and more than 70% had a 10-year cardiovascular risk score < 10%. In people 60 or more years old, the first and the last eGFR quintiles (<90 and ≥109 mL/min/1.73m², respectively) were associated to an increased risk for both all-cause mortality (hazard ratio 1.6, 95% confidence interval 1.2-2.1 and 4.3, 1.6-11.7, respectively) and incident CVD (1.6, 1.0-2.4 and 7.0, 2.2-22.9, respectively), even if adjusted for classical risk factors.

Conclusions

These findings strongly suggest that in an elderly, general population at low risk of CVD and low prevalence of reduced renal filtration, even a modest eGFR reduction is related to all-cause mortality and CVD incidence, underlying the potential benefit to this population of considering eGFR for their risk prediction.     

Obesity in Spanish Schoolchildren: Relationship with Lipid Profile and Insulin Resistance

This article reports cross‐sectional data from a total of 1048 children, 6 to 8 years of age, categorized by presence or absence of obesity, who participated in a voluntary survey of cardiovascular risk factors in Spain over the period of 1998 to 2000, to establish the relationship between obesity and its metabolic consequences at this age. The prevalence of obesity and overweight were 9.4% and 15.7%, respectively, in boys and 10.5% and 18.0%, respectively, in girls. We observed that, in both sexes, obese children had higher triglycerides and lower high‐density lipoprotein‐cholesterol levels than non‐obese children. No differences were found in plasma glucose or low‐density lipoprotein‐cholesterol levels between normal and obese children. However, we observed that insulin levels and the homeostasis model assessment for insulin resistance were significantly (p < 0.001) higher in obese children of both sexes but that free fatty acid levels were lower in obese children than in nonobese children, with a statistical significance in girls (0.72 ± 0.30 vs. 0.61 ± 0.16 mEq/liter). In summary, our survey found some metabolic consequences of obesity similar to those found in adults (elevated triglycerides, insulin, and the homeostasis model assessment for insulin resistance, and lower high‐density lipoprotein‐cholesterol). However, other features (glucose, total cholesterol, low‐density lipoprotein‐cholesterol, and free fatty acid levels) were found to behave differently, indicating that the association of obesity with risk factors seems to change as the children age and may depend on the chronology of sexual maturation.     

一个具暂时免疫且总人数可变的传染病动力学模型

建立了一个具常恢复率和接触率依赖于总人数的SIRS传染病动力学模型，讨论了系统平衡点的存在性和稳定性，对双线性传染率的特殊情形，给出了传染病平衡点的全局稳定性结论，推广和改进了已有的相应结果。     

Microbiota: A Missing Link in The Pathogenesis of Chronic Lung Inflammatory Diseases

Chronic respiratory diseases account for high morbidity and mortality, with asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) being the most prevalent globally. Even though the diseases increase in prevalence, the exact underlying mechanisms have still not been fully understood. Despite their differences in nature, pathophysiologies, and clinical phenotypes, a growing body of evidence indicates that the presence of lung microbiota can shape the pathogenic processes underlying chronic inflammation, typically observed in the course of the diseases. Therefore, the characterization of the lung microbiota may shed new light on the pathogenesis of these diseases. Specifically, in chronic respiratory tract diseases, the human microbiota may contribute to the disease’s development and severity. The present review explores the role of the microbiota in the area of chronic pulmonary diseases, especially COPD, asthma, and CF.     

Activation of Blood Coagulation in Two Prototypic Autoimmune Skin Diseases: A Possible Link with Thrombotic Risk

Coagulation activation has been demonstrated in two prototypic autoimmune skin diseases, chronic autoimmune urticaria and bullous pemphigoid, but only the latter is associated with increased thrombotic risk. Two markers of coagulation activation (prothrombin fragment F1+2 and fibrin fragment D-dimer) were measured by immunoenzymatic methods in plasma samples from 30 patients with active chronic autoimmune urticaria, positive for autologous serum skin test, 30 patients with active bullous pemphigoid and 30 healthy subjects. In skin biopsies, tissue factor expression was evaluated by both immunohistochemistry and in situ hybridization. F1+2 and D-dimer levels were higher in active chronic autoimmune urticaria (276.5±89.8 pmol/L and 5.56±4.40 nmol/L, respectively) than in controls (145.2±38.0 pmol/L and 1.06±0.25 nmol/L; P=0.029 and P=0.011) and were much higher in active bullous pemphigoid (691.7±318.7 pmol/L and 15.24±9.09 nmol/L, respectively) (P<0.0001). Tissue factor positivity was evident in skin biopsies of both disorders with higher intensity in bullous pemphigoid. F1+2 and D-dimer, during remission, were markedly reduced in both disorders. These findings support the involvement of coagulation activation in the pathophysiology of both diseases. The strong systemic activation of coagulation in bullous pemphigoid may contribute to increase the thrombotic risk and provides the rationale for clinical trials on anticoagulant treatments in this disease.     

Plasma B-type Natriuretic Peptide as a Predictor of Cardiovascular Events in Subjects with Atrial Fibrillation: A Community-Based Study

Objectives

Atrial fibrillation (AF) is a significant public health issue due to its high prevalence in the general population, and is associated with an increased risk of cardiovascular (CV) events including systemic thrombo-embolism, heart failure, and coronary artery disease. The relationship between plasma B-type natriuretic peptide (BNP) and CV risk in real world AF subjects remains unknown.

Methods

The subject of the study (n = 228; mean age = 69 years) was unselected individuals with AF in a community-based population (n = 15,394; AF prevalence rate = 1.5%). The CV event free rate within each BNP tertile was estimated, and Cox regression analysis was performed to examine the relative risk of the onset of CV events among the tertiles. The prognostic ability of BNP was compared to an established risk score for embolic events (CHADS2 score). In addition, to determine the usefulness of BNP as a predictor in addition to CHADS2 score, we calculated Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI) indices.

Results

During the follow-up period 58 subjects experienced CV events (52 per 1,000 person-years). The event-free ratio was significantly lower in the highest tertile (p < 0.02). After adjustment for established CV risk factors, the hazard ratio (HR) of the highest tertile was significantly higher than that of the lowest tertile (HR = 2.38; p < 0.02). The predictive abilities of plasma BNP in terms of sensitivity and specificity for general CV events were comparable to those of CHADS2 score. Adding BNP to the CHADS2 score only model improved the NRI (0.319; p < 0.05) and the IDI (0.046; p < 0.05).

Conclusion

Plasma BNP is a valuable biomarker both singly or in combination with an established scoring system for assessing general CV risk including stroke, heart failure and acute coronary syndrome in real-world AF subjects.     

Estimation of the Number of Classes in a Population

The problem of estimating M, the number of classes in a population, is formulated as an occupancy problem in which N items are drawn from M urns. Under the assumption of a uniform distribution for the number of classes in the population, the sufficient statistic for M, which is the number of distinct classes observed, does not depend upon the number of repetitions in the sample. Point and interval estimates of M are developed using maximum likelihood and the method of moments. Both techniques give rise to the same basic equation which requires a simple iterative solution. These same techniques are used in the more general situation in which the classes can be further subdivided according to type.     

Behavioral Trait of Morningness-Eveningness in Association with Articular and Spinal Diseases in a Population

Earlier studies have revealed that the more the preference to schedule daily activities towards the evening hours is, the higher the odds for a range of health hazards are. Therefore, we wanted to analyze, whether the behavioral trait of morningness-eveningness is associated with articular and spinal diseases or those with musculoskeletal disorders. Participants (n = 6089), as part of the National FINRISK 2007 Study, were derived from the general population, aged 25 to 74 years, living in Finland. Chronotype was assessed based on six items from the original Horne-Östberg Morningness-Eveningness Questionnaire. Information about risk factors and the diagnoses of articular and spinal diseases were based on the self-reported information. Our results suggest that Evening-types have higher odds for articular and spinal diseases as compared with Morning-types, and this risk is heightened especially regarding spinal disease and backache (odds ratios of 1.8 to 2.1, and 1.6 to 1.8, respectively) and remains significant after controlling for the sex, age, education, civil status, physical activity, alcohol use, and smoking, and additionally for the body-mass index, insufficient sleep, or depressive symptoms.     

Associations of Body Composition Measurements with Serum Lipid,Glucose and Insulin Profile: A Chinese Twin Study

Objectives

To quantitate and compare the associations of various body composition measurements with serum metabolites and to what degree genetic or environmental factors affect obesity-metabolite relation.

Methods

Body mass index (BMI), waist circumference (WC), lean body mass (LBM), percent body fat (PBF), fasting serum high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), total cholesterol (TC), glucose, insulin and lifestyle factors were assessed in 903 twins from Chinese National Twin Registry (CNTR). Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from fasting serum glucose and insulin. Linear regression models and bivariate structural equation models were used to examine the relation of various body composition measurements with serum metabolite levels and genetic/environmental influences on these associations, respectively.

Results

At individual level, adiposity measurements (BMI, WC and PBF) showed significant associations with serum metabolite concentrations in both sexes and the associations still existed in male twins when using within-MZ twin pair comparison analyses. Associations of BMI with TG, insulin and HOMA-IR were significantly stronger in male twins compared to female twins (BMI-by-sex interaction p = 0.043, 0.020 and 0.019, respectively). Comparison of various adiposity measurements with levels of serum metabolites revealed that WC explained the largest fraction of variance in serum LDL-C, TG, TC and glucose concentrations while BMI performed best in explaining variance in serum HDL-C, insulin and HOMA-IR levels. Of these phenotypic correlations, 64–81% were attributed to genetic factors, whereas 19–36% were attributed to unique environmental factors.

Conclusions

We observed different associations between adiposity and serum metabolite profile and demonstrated that WC and BMI explained the largest fraction of variance in serum lipid profile and insulin resistance, respectively. To a large degree, shared genetic factors contributed to these associations with the remaining explained by twin-specific environmental factors.     

Genetics of Plasma Soluble Receptor for Advanced Glycation End-Products and Cardiovascular Outcomes in a Community-based Population: Results from the Atherosclerosis Risk in Communities Study

Plasma soluble Receptor for Advanced Glycation End-products (sRAGE) is a strong marker of vascular outcomes although evidence on the direction of association is mixed. Compared to whites, blacks have lower levels of sRAGE. We hypothesized that genetic determinants of sRAGE would help clarify the causal role of sRAGE and the black-white difference in sRAGE levels. We conducted a genome-wide analysis of sRAGE in whites and blacks from the Atherosclerosis Risk in Communities Study. Median plasma sRAGE levels were lower in blacks than whites (728 vs. 1067 pg/ml; P<0.0001). The T (vs. C) allele of rs2070600, a missense variant in AGER, the gene encoding RAGE, was associated with approximately 50% lower sRAGE levels in both whites (N = 1,737; P = 7.26x10^-16; minor allele frequency (MAF) = 0.04) and blacks (N = 581; P = 0.02; MAF = 0.01). In blacks, the T (vs. C) allele of rs2071288, intronic to AGER, was associated with 43% lower sRAGE levels (P = 2.22x10^-8; MAF = 0.10) and was nearly absent in whites. These AGER SNPs explained 21.5% and 26% of the variation in sRAGE in blacks and whites, respectively, but did not explain the black-white difference in sRAGE. These SNPs were not significantly associated with incident death, coronary heart disease, diabetes, heart failure, or chronic kidney disease in whites (N = 8,130–9,017) or blacks (N = 2,293–2,871) (median follow up ~20 years). We identified strong genetic determinants of sRAGE that did not explain the large black-white difference in sRAGE levels or clearly influence risk of clinical outcomes, suggesting that sRAGE may not be a causal factor in development of these outcomes.