Working towards full eradication of lipid-driven cardiovascular risk?
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ABSTRACT:
SUBMITTER: Nurmohamed NS
PROVIDER: S-EPMC8724506 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The contents of working memory (WM) can influence where we attend-but can it also interfere with what we see? Active maintenance of visual items in WM biases attention towards WM-matching objects, and also enhances early perceptual processing of WM-matching items (e.g., more accurate perceptual discrimination). Here, we asked whether a WM-matching distractor interferes with perceptual processing of a target's features. In a dual-task paradigm, participants maintained a shape in WM across an intervening visual search task, during which they had to reproduce the colour of a designated target item using a continuous-report technique. Importantly, the WM shape could match the target item, a distractor item, or no item in the search array. When the WM shape matched a distractor, we found no evidence of systematic perceptual interference (i.e., swapping or mixing with the distractor colour), but observed only general disruptions in target processing (i.e., decreased target accuracy). These results suggest that when visual attention is inadvertently drawn to a WM-matching distractor, any resultant automatic perceptual processing may be too transient or weak to significantly interfere with perceptual processing of the target's features.
| S-EPMC7529337 | biostudies-literature
Project description:OBJECTIVE:To investigate whether milk polar lipids (PL) impact human intestinal lipid absorption, metabolism, microbiota and associated markers of cardiometabolic health. DESIGN:A double-blind, randomised controlled 4-week study involving 58 postmenopausal women was used to assess the chronic effects of milk PL consumption (0, 3 or 5 g-PL/day) on lipid metabolism and gut microbiota. The acute effects of milk PL on intestinal absorption and metabolism of cholesterol were assessed in a randomised controlled crossover study using tracers in ileostomy patients. RESULTS:Over 4 weeks, milk PL significantly reduced fasting and postprandial plasma concentrations of cholesterol and surrogate lipid markers of cardiovascular disease risk, including total/high-density lipoprotein-cholesterol and apolipoprotein (Apo)B/ApoA1 ratios. The highest PL dose preferentially induced a decreased number of intestine-derived chylomicron particles. Also, milk PL increased faecal loss of coprostanol, a gut-derived metabolite of cholesterol, but major bacterial populations and faecal short-chain fatty acids were not affected by milk PL, regardless of the dose. Acute ingestion of milk PL by ileostomy patients shows that milk PL decreased cholesterol absorption and increased cholesterol-ileal efflux, which can be explained by the observed co-excretion with milk sphingomyelin in the gut. CONCLUSION:The present data demonstrate for the first time in humans that milk PL can improve the cardiometabolic health by decreasing several lipid cardiovascular markers, notably through a reduced intestinal cholesterol absorption involving specific interactions in the gut, without disturbing the major bacterial phyla of gut microbiota. TRIAL REGISTRATION NUMBER:NCT02099032 and NCT02146339; Results.
| S-EPMC7034342 | biostudies-literature
Project description:INTRODUCTION:It has been suggested that long working hours are associated with cardiovascular disease (CVD). Although studies on health inequality caused by income inequality have been performed, income levels of workers have been considered only as an adjusting factor in the relationship between long working hours and CVD. In the present study, we investigated the modifying effects of household income level in the relationship between working hours and estimated risk of CVD. MATERIALS AND METHODS:We analysed a total of 11,602 Koreans who were randomly enrolled in the Korea National Health and Nutrition Examination Survey (2007-2016) with complete data. Nonparametric associations between weekly working hours and estimated risk of CVD were explored according to quartiles of equalised household income by gender, and the size of linear associations among weekly working hours and estimated CVD risk after stratifying for equalised household income by gender was considered. RESULTS:A 4.1% increased risk of CVD was associated with 10 hours or longer per day weekly working hours among males with the highest household income after adjusting for age, equalised household income, occupation, and shift work, but such was not associated among lower income groups. Negative associations between equalised household income and estimated CVD risk were observed only among low household income males. CONCLUSION:Long working hours and household income level can have differential effects on the risk of CVD by socioeconomic status. This study shows that positive income effect may dominate the potential negative effect of long working hours with respect to the risk of CVD in the low-income group.
| S-EPMC6842008 | biostudies-literature
Project description:AimsWe tested whether characteristic changes of the plasma lipidome in individuals with comparable total lipids level associate with future cardiovascular disease (CVD) outcome and whether 23 validated gene variants associated with coronary artery disease (CAD) affect CVD associated lipid species.Methods and resultsScreening of the fasted plasma lipidome was performed by top-down shotgun analysis and lipidome compositions compared between incident CVD cases (n = 211) and controls (n = 216) from the prospective population-based MDC study using logistic regression adjusting for Framingham risk factors. Associations with incident CVD were seen for eight lipid species (0.21≤q≤0.23). Each standard deviation unit higher baseline levels of two lysophosphatidylcholine species (LPC), LPC16∶0 and LPC20∶4, was associated with a decreased risk for CVD (P = 0.024-0.028). Sphingomyelin (SM) 38∶2 was associated with increased odds of CVD (P = 0.057). Five triglyceride (TAG) species were associated with protection (P = 0.031-0.049). LPC16∶0 was negatively correlated with the carotid intima-media thickness (P = 0.010) and with HbA1c (P = 0.012) whereas SM38∶2 was positively correlated with LDL-cholesterol (P = 0.0*10(-6)) and the q-values were good (q≤0.03). The risk allele of 8 CAD-associated gene variants showed significant association with the plasma level of several lipid species. However, the q-values were high for many of the associations (0.015≤q≤0.75). Risk allele carriers of 3 CAD-loci had reduced level of LPC16∶0 and/or LPC 20∶4 (P≤0.056).ConclusionOur study suggests that CVD development is preceded by reduced levels of LPC16∶0, LPC20∶4 and some specific TAG species and by increased levels of SM38∶2. It also indicates that certain lipid species are intermediate phenotypes between genetic susceptibility and overt CVD. But it is a preliminary study that awaits replication in a larger population because statistical significance was lost for the associations between lipid species and future cardiovascular events when correcting for multiple testing.
| S-EPMC3744469 | biostudies-literature
Project description:IntroductionGreater adherence to a Mediterranean diet is linked to lower risk for cardiovascular morbidity/mortality in studies of Mediterranean cohorts, older subjects, and/or those with existing health conditions. No studies have examined the effects of this dietary pattern in younger working populations in the United States. We investigated the effects of Mediterranean diet adherence on cardiovascular disease (CVD) biomarkers, metabolic syndrome and body composition in an occupationally active, non-Mediterranean cohort.MethodsA cross-sectional study in a cohort of 780 career male firefighters, ages 18 years or older, from the United States Midwest. No dietary intervention was performed. A modified Mediterranean diet score (mMDS) was developed for assessment of adherence to a Mediterranean dietary pattern from a previously administered life-style questionnaire that examined pre-existing dietary habits. Clinical data from fire department medical examinations were extracted and analyzed.ResultsObese subjects had significantly lower mMDS, and they reported greater fast/take-out food consumption (p<0.001) and intake of sweetened drinks during meals (p = 0.002). After multivariate adjustment, higher mMDS was inversely related to risk of weight gain over the past 5 years (odds ratio [OR]: 0.57, 95% confidence interval [CI]: 0.39-0.84, p for trend across score quartiles: 0.01); as well as the presence of metabolic syndrome components (OR: 0.65, 95% CI: 0.44-0.94, p for trend across score quartiles: 0.04). Higher HDL-cholesterol (p = 0.008) and lower LDL-cholesterol (p = 0.04) were observed in those with higher mMDS in linear regression after multivariate adjustment for age, BMI and physical activity.ConclusionsIn a cohort of young and active US adults, greater adherence to a Mediterranean-style dietary pattern had significant inverse associations with metabolic syndrome, LDL-cholesterol and reported weight gain, and was significantly and independently associated with higher HDL-cholesterol. Our results support the potential effectiveness of this diet in young, non-Mediterranean working cohorts, and justify future intervention studies.
| S-EPMC3913651 | biostudies-literature
Project description:Platelets are key mediators of atherothrombosis; yet, limited tools exist to identify individuals with a hyperreactive platelet phenotype. Here we derive and validate a Platelet Reactivity ExpreSsion Score (PRESS) integrating platelet aggregation responses and RNA sequencing in multiple cohorts. PRESS performs well in identifying a hyperreactive phenotype in patients with cardiovascular disease (AUC [cross-validation] 0.81, 95% CI 0.68 to 0.94), with similar discrimination in an independent cohort of healthy participants (AUC [validation] 0.77, 95% CI 0.75 to 0.79); accuracy 80%, sensitivity 71%, and specificity 86%. Next, we validate PRESS in multiple cohorts of patients with platelet RNASeq available. Following multivariable adjustment, PRESS was significantly higher in MI (β=1.8, p=0.02), and individuals with a score above the median more frequently develop a future cardiovascular event (adjusted HR 1.90, CI 1.07 to 3.36), p=0.027). Altogether, we provide strong evidence that PRESS is a robust prognostic marker, which could have an essential role in facilitating a personalized approach to cardiovascular risk management.
2024-06-30 | GSE232027 | GEO
Project description:Statins are the cornerstone of the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD). However, even under optimal statin therapy, a significant residual ASCVD risk remains. Therefore, there has been an unmet clinical need for novel lipid-lowering agents that can target low-density lipoprotein cholesterol (LDL-C) and other atherogenic particles. During the past decade, several drugs have been developed for the treatment of dyslipidemia. Inclisiran, a small interfering RNA that targets proprotein convertase subtilisin/kexin type 9 (PCSK9), shows comparable effects to that of PCSK9 monoclonal antibodies. Bempedoic acid, an ATP citrate lyase inhibitor, is a valuable treatment option for the patients with statin intolerance. Pemafibrate, the first selective peroxisome proliferator-activated receptor alpha modulator, showed a favorable benefit-risk balance in phase 2 trial, but the large clinical phase 3 trial (PROMINENT) was recently stopped for futility based on a late interim analysis. High dose icosapent ethyl, a modified eicosapentaenoic acid preparation, shows cardiovascular benefits. Evinacumab, an angiopoietin-like 3 (ANGPTL3) monoclonal antibody, reduces plasma LDL-C levels in patients with refractory hypercholesterolemia. Novel antisense oligonucleotides targeting apolipoprotein C3 (apoC3), ANGPTL3, and lipoprotein(a) have significantly attenuated the levels of their target molecules with beneficial effects on associated dyslipidemias. Apolipoprotein A1 (apoA1) is considered as a potential treatment to exploit the athero-protective effects of high-density lipoprotein cholesterol (HDL-C), but solid clinical evidence is necessary. In this review, we discuss the mode of action and clinical outcomes of these novel lipid-lowering agents beyond statins.
| S-EPMC9353557 | biostudies-literature
Project description:BackgroundLipid-lowering therapy (LLT) is one of the key strategies for reducing the atherosclerotic cardiovascular disease (ASCVD) burden. However, little is known about the percentage of people in need of different LLT regimens to achieve optimal targets of low-density lipoprotein cholesterol (LDL-C), and the corresponding cost and benefit.MethodsWe conducted a simulation study based on the data from the nationwide China PEACE MPP population cohort (2015-2020), from which we included 2,904,914 participants aged 35-75 years from all the 31 provinces in mainland China. Participants were grouped based on their 10-year ASCVD risks, then entered into a Monte Carlo model which was used to perform LLT intensification simulation scenarios to achieve corresponding LDL-C goals in each risk stratification.ResultsAfter standardizing age and sex, the proportions of participants included at low, moderate, high, and very-high risk were 70.8%, 15.6%, 11.5%, and 2.1%, respectively. People who failed to achieve the corresponding LDL-C goals -8.1% at low risk, 19.6% at moderate risk, 53.2% at high risk, and 93.6% at very-high risk (either not achieving the goal or not receiving LLT)-would be in need of the LLT intensification simulation. After the use of atorvastatin 20 mg was simulated, over 99% of the population at low or moderate risk could achieve the LDL-C goals; while 11.3% at high and 24.5% at very-high risk would still require additional non-statin therapy. After the additional use of ezetimibe, there were still 4.8% at high risk and 11.3% at very-high risk in need of evolocumab; and 99% of these two groups could achieve the LDL-C goals after the use of evolocumab. Such LLT intensification with statin, ezetimibe, and evolocumab would annually cost $2.4 billion, $4.2 billion, and $24.5 billion, respectively, and prevent 264,170, 18,390, and 17,045 cardiovascular events, respectively.ConclusionsModerate-intensity statin therapy is pivotal for the attainment of optimal LDL-C goals in China, and around 10-25% of high- or very-high-risk patients would require additional non-statin agents. There is an opportunity to reduce the rising ASCVD burden in China by optimizing LLT.
| S-EPMC8996051 | biostudies-literature
Project description:BackgroundThe tsetse fly Glossina palpalis gambiensis is the main vector of sleeping sickness (Human African Trypanosomiasis - HAT) in West Africa, in particular in littoral Guinea where this disease is currently very active. The Loos islands constitute a small archipelago some 5 km from mainland Guinea, where G. p. gambiensis is well known as a nuisance and potential disease vector by inhabitants of the three main islands, Fotoba, Room, and Kassa. The National Control Program against HAT of Guinea has decided to eradicate tsetse in Loos islands in order to sustainably protect humans and economic activities. After baseline data collection, tsetse control began on the islands in 2006. On each of the three islands a specific combination of control methods was implemented according to the entomological situation found.ResultsStarting densities before control operations were 10, 3 and 1 tsetse/trap/day in Kassa, Room and Fotoba respectively, but by July 2010, tsetse were no longer caught in any of the sentinel traps used for monitoring. The reduction rate was faster where several control methods were implemented as a combination (impregnated traps and targets ITT, selective groundspraying, epicutaneous insecticide treatment of pigs, and impregnated fences around pig pens), whereas it was slower when ITT were used as the only control method.ConclusionsThis 100% suppression is a promising step in the eradication process, but G. p. gambiensis may still occur at very low, undetectable, densities on the archipelago. Next step will consist in assessing a 0.05 probability of tsetse absence to ascertain a provisional eradication status. Throughout these operations, a key factor has been the involvement of local teams and local communities without whom such results would be impossible to obtain. Work will continue thanks to the partners involved until total eradication of the tsetse on Loos islands can be declared.
| S-EPMC3048576 | biostudies-literature
Project description:ObjectivesTo investigate the association between spouse weekly working hours (SWWH) and the estimated 10-years risk of cardiovascular disease (CVD).MethodsThis cross-sectional study was based on the data obtained from the Korean National Health and Nutrition Examination Survey 2007-2012. Data of 16,917 participants (8,330 husbands, 8,587 wives) were used for this analysis. The participants' clinical data were collected to estimate the 10-years risk of CVD, as well as weekly working hours. Multiple logistic regression was conducted to investigate the association between SWWH and the estimated 10-years risk of CVD. We also performed a stratified analysis according to each participant's and their spouse's employment status.ResultsCompared to those whose spouses worked 30 hours per week, estimated 10-years risk of CVD was significantly higher as SWWH increase among those whose spouses worked >30 hours per week. After adjusting for covariates, the odds ratio for high CVD risk was found to increase as SWWH increased, up to 2.52 among husbands and 2.43 among wives. We also found that the association between SWWH and the estimated 10-years risk of CVD varied according to the employment status. Analysis of each component included in the CVD appraisal model showed that SWWH had close relationship with diabetes in men, and smoking habits in women.ConclusionsSpouse's long working hours are associated with individual's risk of CVD in future, especially among husbands.
| S-EPMC5542474 | biostudies-literature