Risk Of Disease Research Articles

Type 2 diabetes prevention: genetic association analysis of dried fruit intake and disease risk.

Prior research has suggested an inverse correlation between dried fruit intake and type 2 diabetes mellitus (T2DM), yet the causal link remains uncertain. This study seeks to investigate the potential causal impact of dried fruit intake on T2DM, covering cases both with and without various complications, as well as glycaemic traits, using a two-sample Mendelian randomisation (MR) approach. Using MR analysis with genome-wide association study summary statistics, the primary analysis investigated the causal relationship between dried fruit intake and T2DM, both with and without complications, as well as glycaemic traits, employing the inverse variance weighted method. Supplementary analyses were conducted using MR-Egger and the weighted median method. Heterogeneity and intercept tests were utilised to evaluate the robustness of the study outcomes. The results show a significant association between dried fruit intake and T2DM without complications, as well as fasting insulin. Sensitivity analyses confirmed the robustness of the results and the independence from multicollinearity. However, no association was found between dried fruit intake and T2DM with various complications or other glycaemic traits. The significant association between dried fruit intake and T2DM without complications and fasting insulin persisted even after adjusting for BMI. This study offers genetic evidence endorsing the protective effects of dried fruit intake against T2DM, specifically for cases without complications, and in regulating fasting insulin. These findings suggest that dried fruit intake might serve as a primary preventive strategy for T2DM.

Calculating potential impact fractions to assess the impact of tobacco control policies

Abstract This presentation will provide a straightforward and accessible method for evaluating the effectiveness of various tobacco control policies in reducing the smoking-associated disease burden. To estimate numbers and proportions of potentially avoidable disease cases under different policy intervention scenarios (such as cigarette tax/price increases, comprehensive marketing ban, and plain packaging), this approach entails the calculation of age- and sex-specific potential impact fractions, representing the percentage change in disease risk following changes in exposure to smoking. The approach can account for lag and latency periods between reductions in smoking prevalence and declines in disease excess risks. The future disease burden is estimated by combining data on the incidence or mortality of the disease of interest, published effect sizes of tobacco control policies, and national smoking prevalence data. Intervention scenarios are compared against a status quo scenario that assumes the continuation of recent smoking trends. The presentation will outline the approach, using the example of smoking-associated cancer, and discuss model assumptions, required data, and sensitivity analyses. This straightforward modelling framework enables the comparison of different health policy measures’ impacts, providing valuable insights for policymakers and public health officials regarding the potential public health impact of tobacco control policy measures.

Interactive effects of outdoor fine particulate matter and metabolic, behavioural, and psychosocial risk factors on cardiovascular disease: analysis of the PURE-China cohort study

Abstract Background Long-term PM2.5 exposure has been associated with an elevated risk of cardiovascular disease (CVD) and its associated risk factors.[1–4] There is a paucity of studies investigating the interactive effects of PM2.5 exposure and a comprehensive list of risk factors including metabolic, behavioural, and psychosocial risk factors on CVD risk.[5] Purpose This study aims to examine the interactive effects of PM2.5 exposure and metabolic, behavioural, and psychosocial risk factors on incident CVD. Methods The Prospective Urban Rural Epidemiology (PURE)-China cohort study is a population-based cohort study recruiting participants aged 35–70 years from 115 communities in 12 provinces of China between 2005 and 2009, and followed up until August 31, 2021.[6] Participants’ metabolic, behavioural, and psychosocial risk factor information was recorded. PM2.5 concentrations were extracted from a 1x1 km2 global model.[7,8] For this analysis, we included participants aged 35–70 years at baseline without a history of CVD, with at least one follow-up visit. The primary outcome was a composite of major cardiovascular events (CVD deaths, myocardial infarction, stroke, and heart failure). Additive interaction was measured by relative excess risk due to interaction (RERI), the proportion of disease attributable to interaction (AP), and the synergy index (SI).[9,10] To comply with the additive interaction method, we classified concentrations of PM2.5 into low and high levels by the median of 3-year average PM2.5 concentration (45.7 μg/m3, IQR: 33.7-74). Cox proportional hazard models were used to assess the associations of metabolic, behavioural, and psychosocial risk factors on incident CVD by PM2.5 concentrations. Results The PURE-China study recruited 47 931 participants, of which 39 329 are eligible for this analysis. During the median follow-up period of 11.9 years (IQR: 9.6-12.6), 1462 and 2155 major CVD events had occurred in the low and high PM2.5 group respectively. There was a synergistic interaction between PM2.5 and the systolic blood pressure (SBP) for CVD: RERI: 0.363, 95% CI: 0.196-0.531; AP: 0.098, 95% CI: 0.081-0.115; SI: 1.155, 95% CI: 1.132-1.177; high LDL cholesterol: RERI: 0.219, 0.003-0.436; AP: 0.135, 0.008-0.263; SI: 1.549, 0.947-2.533. A significant synergistic interaction was also identified between PM2.5 and household air pollution (RERI: 0.457, 0.292-0.622; AP: 0.277, 0.184-0.37; SI: 3.362, 1.409-8.019). Interactions between PM2.5 and low grip strength on CVD were significantly synergistic, but antagonistic between PM2.5 and low physical activity (RERI: -0.248, -0.485--0.012; AP: -0.174, -0.349-0.001; SI: 0.633, 0.412-0.971). Conclusion Addictive interaction was between PM2.5 and SBP, high LDL cholesterol, household air pollution, low grip strength and low physical activity on incident CVD, indicating the benefit of coordinated control strategies for metabolic, physical, and environmental risk factors for the prevention of CVD.

Factors associated with use of active transport in users of HEVS Program of Ministry of Sports

Abstract Background Sedentary behavior and physical inactivity are associated with an increased risk of chronic disease and mortality. Studies have shown the benefits of active transport to reduce NCDs. In Colombia, studies have been developed to determine the factors associated with the use of active transport, in cities such as Bogota but not nationally, therefore, this study seeks to determine the factors associated with the use of active transport in users of the National Program of Habits and Healthy Lifestyle (HEVS) led by the Ministry of Sport of Colombia in partnership with municipal sports and departmental. Methods The research presented a quantitative approach on a retrospective basis. The population consisted of 75,086 users of the HEVS program in 2019, over 18 years old (average = 44.04 and D.E. = 15.75 years old) of which 87.7% were women. For the statistical analysis a forward logistic regression model was carried out, with the dependent variable: active transport use (0 = no active transport use and 1 = active transport use). Results 41.6% of 75086 participants reported using active transport, corresponding to 31,211. Regular users, who attend physical activity programs 3 times a week, report a higher probability of using active transport OR = 1.38 (95% CI 1.31 to 1.45), compared to those who attend less than 3 times a week. Being female represents a greater probability of using active transport compared to men, OR = 1.39 (95% CI 1.32 to 1.47), those who add salt to food are also more likely to use active transport than those who do not add, OR = 2.04 (95% CI 1.92 to 2.26) and in terms of physical activity, those who meet the minimum recommendations in minutes a week use active transport more likely than those who do not comply, OR = 1.49 (95% CI 1.4 to 1.6). Conclusions Using active transport is associated with greater compliance with weekly physical activity recommendations. Women are more likely to use active transport just like people who add salt to food. Key messages • In order to reduce NCDs in the Colombian population, walking or cycling is proposed because it is associated with a greater probability of compliance with weekly physical activity recommendations. • Formulating public policies in Colombia that encourage the use of active transport would contribute to meeting weekly physical activity requirements.

Dapagliflozin versus empagliflozin and major adverse cardiovascular events in type 2 diabetes: a nationwide cohort study

Abstract Background Large randomized clinical trials have shown that sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of adverse kidney and cardiovascular outcomes in patients with heart failure, chronic kidney disease, or type 2 diabetes mellitus (T2DM) at high risk of atherosclerotic cardiovascular disease. Whether these effects might differ between individual SGLT2-inhbitors remain unclear given the lack of head-to-head comparisons. Purpose To examine the association between treatment with dapagliflozin versus empagliflozin and the long-term rate of major adverse cardiovascular events (MACE) in patients with T2DM. Methods Using nationwide registries, all Danish residents with T2DM, who initiated treatment with dapagliflozin or empagliflozin from 2015 to 2020, were identified. Only treatment with dapagliflozin or empagliflozin was considered in the present analysis, since approximately 3% initiated treatment with other SGLT2-inhibitors (i.e., canagliflozin and ertugliflozin). Patients were followed from date of the first claimed prescription of dapagliflozin or empagliflozin until the outcome of interest, emigration, death, or end of study (December 31, 2021). The primary outcome was a composite endpoint of major adverse cardiovascular events (i.e., time to first heart failure hospitalisation, acute myocardial infarction (AMI), stroke, or all-cause mortality). The primary outcome was compared between the dapagliflozin and empagliflozin group, overall and in prespecified subgroups of interest, with multivariable Cox proportional hazards regression models. Results In total, 61,031 patients with T2DM initiated treatment with dapagliflozin (N=21,028; 34.5%) or empagliflozin (N=40,003; 65.5%). The median age of study population was 62.6 years (25th-75th percentile, 54.2-70.8 years), and 62.6% were men. There were no clinically significant differences between the dapagliflozin and empagliflozin group with respect to age, sex, and clinical characteristics. The median follow-up was 3.1 years (25th-75th percentile, 1.9-4.5 years). The adjusted long-term hazard ratios of the primary outcome, overall and in prespecified subgroups of interest, are displayed in the Figure. Compared with empagliflozin, treatment with dapagliflozin was not associated with a significantly different rate of the primary outcome (HR 1.02 [95% CI, 0.97-1.07]). The observed association was consistent across clinically relevant subgroups, including in patients with and without heart failure, chronic kidney disease, and atherosclerotic cardiovascular disease. Conclusion In a large, nationwide cohort of patients with T2DM, treatment with dapagliflozin was associated with a similar rate of major adverse cardiovascular outcomes compared with empagliflozin, and this association was consistent across clinically relevant subgroups. These findings suggest that the benefits of SGLT2-inhibitors can be characterized as a class-effect.

2.K. Scientific session: Promoting organizational health literacy in healthcare organizations and beyond in Europe

Abstract Organizational health literacy (OHL) has been defined as the degree to which healthcare organizations equitably enable/empower people, through organizational structures, policies, and processes, to find, understand, appraise, and use information and services to make health-related decisions and actions for themselves and others. By adopting an OHL approach, healthcare organizations enhance health service delivery by simplifying interaction with health systems by making information and services more comprehensible. An OHL approach not only reduces health literacy demands of patients, but also of workforce and the resident population of the community that they serve. The workshop focuses on two theory-based initiatives that focus at promoting OHL in Europe: (1) the Organizational Health Literacy for All (OHL-ALL) initiative, which developed a practice-oriented OHL approach for organizations promoting equity explicitly to support people in vulnerable positions with or at risk for diabetes or other non-communicable diseases, and (2) the World Health Organization (WHO) Action Network on Measuring Population and Organizational Health Literacy (M-POHL) which aims at initiating and facilitating the (self-) assessment of OHL in healthcare organization by developing, providing, and disseminating OHL assessment tools. Both initiatives strive to support organizational change and workforce responsiveness. While the first initiative goes beyond health literacy responsiveness of healthcare organizations intending to offer guidance for organizations on how to give all individuals the best possible opportunities to achieve their optimal health and well-being, the second initiative specifically focuses on OHL in healthcare organizations using a settings approach with a focus on health care, prevention, and health promotion. The initiatives enrich and complement each other. The workshop consists of five short presentations, followed by a discussion among the presenters and the audience. The first presentation focuses on the development of the theory-informed and coherent OHL approach of the OHL-ALL initiative. The second presentation provides an overview of the M-POHL initiative and its innovative tools. Then three presentations will showcase results, experiences, and outcomes from European countries on assessing OHL in different healthcare settings. Expected impact: Theory-based guidance for implementing organizational development will be provided. Results from the M-POHL initiative will contribute to greatly needed insights into OHL needs and opportunities of healthcare organizations. The insights from these real-world assessments and implementation can inform future public health practice, policy, and research. Key messages • An OHL approach contributes to better equity. It helps meet health literacy needs of patients, health and care workforce and the resident population of the community that are served. • New tools have been developed to support management and health and care workforce in assessing and improving OHL responsiveness, to better serve patient communities.

The prognostic value of metabolic dysfunction associated steatotic liver disease in acute myocardial infarction

Abstract Background Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are at increased risk of incident cardiovascular disease. However, the clinical characteristics and prognostic importance of MASLD in patients presenting with acute myocardial infarction (AMI) have yet to be examined. Methods This study compared the characteristics, and outcomes of patients with and without MASLD presenting with AMI at a tertiary centre in Singapore. MASLD was defined as hepatic steatosis, with at least one of five metabolic criteria. Hepatic steatosis was determined using the Hepatic Steatosis Index. Propensity score matching was performed to adjust for age and sex. Kaplan-Meier curve was constructed for long-term all-cause mortality. Cox regression analysis was used to investigate independent predictors of long-term all-cause mortality. Results In this study of 4446 patients with AMI, 2223 patients with MASLD were matched with patients without MASLD using propensity scores. The mean follow-up duration was 3.4 ± 24 years. The MASLD group had higher rates of obesity, diabetes, and chronic kidney disease than their counterparts. Patients with MASLD had early excess all-cause mortality (6.8% vs 3.6%, p<0.001) at 30 days, with unfavorable mortality rates sustained in the long-term (18.3% vs 14.5%, p=0.001) compared to those without MASLD. After adjustment, MASLD remained independently associated with higher long-term all-cause mortality (HR 1.338, 95% CI 1.115-1.604). Conclusion MASLD embodies a higher burden of metabolic dysfunction and is an independent predictor of long-term mortality in the AMI population. Its early identification may be beneficial for risk stratification and provide therapeutic targets for secondary preventive strategies in AMI.Kaplan Meier curve of long-term all-caus

Clinical profile and outcomes of patients with chronic kidney disease on chronic hemodialysis hospitalized for acute coronary syndrome in a tertiary public hospital in the Philippines

Abstract Introduction Acute coronary syndrome (ACS) and end-stage renal disease (ESRD) are both prevalent globally. Of the many risk factors for ACS, chronic kidney disease (CKD) remains to be of great concern because the interplay of cardiac and renal disease is inherently complicated. Cardiovascular mortality rates are 10-30 times higher in the ESRD population. The risk for cardiovascular disease in CKD extends beyond the traditional risk factors. Purpose The guidelines for ACS may not be applicable to the ESRD population because the landmark ACS trials mostly excluded ESRD patients. Due to the gaps in knowledge regarding ACS in ESRD, our study sought to explore the clinical profile and outcomes of these patients in the our institution. Methods We did a retrospective cohort study among ESRD patients presenting with ACS in our institution from May 2021 to November 2023. The data was analyzed using univariate and bivariate statistics using PRISM software. Results A total of 48 patients with ESRD were admitted for ACS in this study - 8 with STEMI and 40 with NSTEMI. The mean age was 61 years old and 33 (68.8%) were male. The average length of hospital stay was 12 days. The most common comorbidities were hypertension (91.7%), heart failure (83.3%), and diabetes mellitus (60.4%). The most common cause of ESRD in our cohort is concomitant hypertensive and diabetic kidney disease (45.8%) with an average length of hemodialysis at 31 months. The most common chief complaints were chest pain (39.6%), dyspnea (29.2%), and decreased sensorium (10.4%). On admission, 18 (37.5%) presented with systolic BP >160mmHg, 7 (14.6%) presented with shock, and 4 (8.3%) presented with cardiac arrest. On electrocardiogram, 21 (43.8%) had left ventricular hypertrophy while 34 (70.8%) had cardiomegaly on chest radiography. On two-dimensional echocardiogram, the average left ventricular ejection fraction was 46% and 27 (90%) had segmental wall motion abnormalities. The most common angiographic finding was 3-vessel coronary artery disease (50%). Only 5 patients (10.4%) had an LDL-C greater than 55mg/dL. Among those with STEMI, 6 (75%) presented with Kilip II or more. While among those with NSTEMI, 27 (67.5%) had a TIMI risk score >2. Almost all patients received dual-antiplatelet therapy, high dose statin, and beta-blocker. The mortality rate was 43.8% with acute coronary syndrome being the most common cause of death. Conclusion Our study did not show significant associated predictors of mortality possibly due to the low sample size. Despite this, our study portrays that patients admitted for ACS with ESRD present with higher risk features reflected by derangement in vital signs, abnormal laboratories, significant imaging abnormalities, high prognostication scores, and high in-hospital morbidity.Predictors of Mortality

Associations of smoking status with long-term cardiovascular events in different arterial territories: the EPIC Norfolk prospective population cohort

Abstract Background Smoking cessation is associated with a reduced risk of cardiovascular disease (CVD) events, mainly in ischemic heart disease (IHD) and stroke. However, the impact of smoking status (never, former or current smoking) on long-term CVD events across different arterial territories remains understudied. Knowledge of such associations is important, as it may assist in risk communication and smoking cessation motivation. We therefore investigated associations between smoking status and territory-specific CVD events in a large cohort with ≥20 years follow-up. Methods We included participants without baseline CVD from the European Prospective Investigation of Cancer (EPIC) Norfolk prospective population cohort. The strengths of associations between smoking, former smoking and never smoking with the first occurrence of a CVD event were evaluated using a competing risk-adjusted regression model. CVD events were defined as hospitalisation or death due to IHD, ischemic stroke, haemorrhagic stroke, peripheral arterial disease (PAD) or aortic aneurysm (AA). Patients were followed-up until the first event, non-CVD death (competing risk) or end of study (15-03-2018). The model was adjusted for sex, age, systolic blood pressure, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), diabetes, renal function and body mass index. We compared former and current smoking (at baseline) with never smoking. Results We included 23,581 participants (56% women) with a median baseline age of 58 years [interquartile range (IQR) 51-66]. During median follow up of 21.3 years (IQR 19.0-22.8), 26.4% experienced ≥1 CVD event. The first event of occurrence was IHD in 17.3%, ischemic stroke in 3.6%, haemorrhagic stroke in 1.4%, PAD in 3.1% and AA in 1.4%. Current (vs. never) smoking was associated with IHD [adjusted hazard rate (aHR) 1.53, 95% confidence interval (CI) 1.36-1.72], PAD (aHR 1.29, 95%CI 1.07-1.56) and AA (aHR 4.81, 95%CI 3.54-6.54). Current smoking was not significantly associated with ischemic stroke (aHR 1.20, 95% CI 0.95-1.52) and haemorrhagic stroke (aHR 1.18, 95% CI 0.81-1.70). In former (vs. never) smoking individuals, the association with AA remained statistically significant but less pronounced [aHR 1.69, 95%CI 1.29-2.23]. Conversely, former smoking was not associated with IHD (aHR 1.07, 95%CI 0.99-1.16) or PAD (aHR 1.09, 95%CI 0.95-1.26) (Figure 1). Conclusion After 20-years of follow-up, former smokers, compared to never-smokers, remain at considerably higher risk for CVD events, particularly for aortic aneurysm. This knowledge may assist in treatment decisions and risk communication.

Effect of interleukin 1b inhibition with canakinumab on inflammation and viral persistence in people with human immunodeficiency virus

Abstract Introduction Effectively treated people with HIV (PWH) have elevated risk of cardiovascular disease (CVD). Inflammatory markers are predictive of CVD and mortality among PWH. The role of the myeloid system in driving inflammation and atherosclerosis has been recently recognized. Canakinumab (a monoclonal antibody to IL-1β) reduces inflammation and CVD events among people with elevated hsCRP after myocardial infarction without HIV. We evaluated the impact of IL-1β inhibition using canakinumab on HIV parameters, inflammation, HIV persistence markers, arterial inflammation, and hematopoietic activity in PWH. Methods PWH on effective ART who had CVD or were at risk for CVD were randomized 2:1 to receive 150 mg of canakinumab subcutaneously or matched placebo at weeks 0 and 12. Arterial inflammation and bone marrow metabolic activity were assessed using F18 FDG PET/CT at baseline and week 18. T cell and monocyte activation were evaluated using multiparameter spectral cytometry. The viral reservoir was quantified using Tat/rev Induced Limiting Dilution Assay (TILDA), HIV DNA and cell-associated RNA. The primary endpoints were change in CD4 and CD8 count. We assessed group effects over time using linear mixed effects models. Results 33 individuals were randomized (median age of 60 years old (IQR 57.5, 64.5) and 94% male); 25 received canakinumab and 8 received placebo. There were no significant differences at baseline. As expected, IL-1β increased among those treated with canakinumab at weeks 4- 24 (p<0.01 for each) and returned to baseline at week 36. There was one death from sepsis in an individual aged 84 with CVD and poorly controlled diabetes who received canakinumab. There were no significant changes in CD4 count, CD8 count, platelet count, creatinine, AST, or ALT by group. Treatment was not associated with a greater reduction in arterial inflammation in the most diseased segment compared to placebo (-6.9%; 95% CI -30.4 to 24.5%; p=0.62). However, bone marrow metabolic activity decreased in the canakinumab group versus placebo (-14.4%, 95% CI -26.5% to -0.2%; p=0.047). Treatment was associated with increased CD163 expression on monocytes at weeks 24 (p=0.03) and 36 (p<0.001), and lower caspase activity at week 36 (p=0.02). There was expansion of anti-inflammatory CD16+ patrolling monocytes that co-express CD163+CX3CR1+ and a decrease in pro-inflammatory CD16+ patrolling monocytes that are Caspase1+CCR2+. Treatment was not associated with differences in hsCRP, IL-6, IL-16, IL-18, MCP-1, sCD14, sCD163, T cell subsets, NK cell subsets, or viral persistence markers. Conclusion Among treated PWH, targeted inhibition of IL-1β using canakinumab results in decreased bone marrow metabolic activity and a shift toward anti-inflammatory monocyte populations. These findings shed light on mechanisms underlying how targeted IL-1β inhibition using canakinumab prevents CVD events by altering monocyte populations and reducing systemic inflammation.

Is chronic kidney disease predictive of coronary artery bypass grafting after acute coronary syndrome? A systematic review and meta-analysis

Abstract Background Coronary artery bypass grafting (CABG) provides superior long-term outcomes to percutaneous coronary intervention (PCI) for multi-vessel coronary artery disease. People with chronic kidney disease (CKD) are at increased risk of multi-vessel coronary artery disease, and experience greater morbidity and mortality following acute coronary syndrome (ACS). Purpose To determine whether CKD affects choice of revascularisation strategy after ACS. Methods We searched EMBASE, MEDLINE, SCOPUS, CENTRAL and the NIHR’s website of funded studies to identify articles referring to ACS and invasive coronary management in high-income countries over the past 12 years until 29th September 2023. Full text articles were included if data on rates of CABG were reported in people with and without CKD who were revascularised following ACS. CKD was defined as one or more recording of an estimated glomerular filtration rate (eGFR) <60mls/min/1.73m2, however proxies for this were accepted. Risk of bias was assessed via ROBINS-E. Random effect meta-analyses estimated the odds ratios for CKD and CABG, stratified by ACS type and receipt of dialysis. Certainty of evidence was assessed according to GRADE. Results Initial searches generated 15,138 articles, of which 13 observational studies were included in this review (8,021,743 participants). Amongst people revascularised following ACS, those with CKD were more likely to receive CABG than those without kidney disease (OR for the average exposure effect 1.47 (95% CI 1.30-1.66)). The likelihood of CABG in people with CKD receiving dialysis and those with CKD not receiving dialysis were similar as the 95% confidence intervals demonstrate (ORs 1.25 (95% CI 1.00-1.57) and 1.41 (1.19-1.67) respectively). The effect of CKD on increased likelihood of CABG appeared greater following ST-elevation myocardial infarction (STEMI) than non-ST elevation ACS (NSTE-ACS) (OR 1.53 (95% CI 1.27-1.83) versus 1.10 (0.98-1.25) respectively, p=0.003). Certainty of the evidence was low for receipt of CABG in people with CKD not receiving dialysis, and moderate for all other outcomes. Conclusion In high-income countries, CKD is associated with increased receipt of CABG amongst people revascularised following ACS. This finding is likely explained by the greater prevalence of multi-vessel coronary artery disease in this population. It is however unclear why the association between CKD and receipt of CABG is stronger in those with STEMI compared to NSTE-ACS, and whether this accurately reflects differential need between the two groups.Figure 1Figure 2

Association of Altitude with Mortality among Patients with Hypertension - A Cohort Study

Abstract Background Available evidence falls short in assessing the risk of all-cause mortality and cardiovascular disease (CVD) mortality among individuals with hypertension residing at various altitudes. This study’s objective was to investigate the correlation between residential altitude and the rates of all-cause mortality and CVD mortality among hypertensive patients. Methods This prospective cohort study encompassed 67,275 hypertensive individuals aged 35 years and above in the year 2018. Participants were categorized into four distinct groups based on their residence altitude: those living below 500 meters, between 500 and 1499 meters, 1500 to 2500 meters, and above 2500 meters. The study spanned a mean follow-up duration of 4.78 years. The associations between residential altitude and the risks of all-cause and CVD mortality were analyzed using Cox proportional hazards regression models. Results Among the 67,275 hypertensive patients included in the study (mean age of 63.9 years, with 45.3% being male), 8,768 deaths were recorded, of which 5,666 were attributed to CVD. Following multivariate adjustment, when compared to the group residing at altitudes below 500 meters, the groups living at altitudes of 500-1499 meters, 1500-2500 meters, and above 2500 meters exhibited significantly elevated risks of all-cause mortality [hazard ratio, HR = 1.45 (95% CI: 1.36-1.54), 1.35 (95% CI: 1.36), and 1.41 (95% CI: 1.28-1.54), respectively] and CVD mortality [HR = 1.47 (95% CI: 1.35-1.58), 1.42 (95% CI: 1.33-1.52), and 1.46 (95% CI: 1.31-1.62), respectively]. For each 500-meter increment in altitude, the risk of all-cause and CVD mortality increased by 10% and 11%, respectively. Subgroup analyses and sensitivity assessments consistently supported this association. Conclusions This study’s findings indicate a substantial connection between long-term residential high-altitude exposure and increased risks of all-cause mortality and CVD mortality among individuals with hypertension. Key messages • Increased altitude of residence increases the risk of subsequent all-cause and CVD mortality in hypertensive patients. • This study highlights that relevant guidelines and healthcare providers should consider altitude as an important factor in reducing the burden of hypertension and CVD.

Associations of omega-3 fatty acid subclasses with cardiovascular diseases in 500,000 individuals

Abstract Increased blood levels of omega-3 fatty acids have consistently been shown to be associated with reduced risk of cardiovascular diseases (CVD). However, large scale placebo-controlled trials of omega-3 supplementation have had discordant results: in 2018 REDUCE-IT reported a 25% risk reduction, whereas in 2020 STRENGTH reported no risk reduction. The two trials had both different placebos (mineral vs corn oil) and omega-3 formulations (EPA vs DHA+EPA). There is not yet a consensus on what explains these results. Here we describe the profiling of omega-3 fatty acid subclasses, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) with nuclear magnetic resonance (NMR), and test their associations with incident CVD in 500,000 individuals from UK Biobank. We utilized 500 MHz NMR spectrometers to analyze total omega-3 and its subclasses in EDTA plasma samples and employed biomarker-specific quantification algorithms to measure their absolute concentrations. In this study, we developed a novel algorithm to quantify EPA, complementing previously described algorithms for omega-3 and DHA. Correlation (r^2) of this novel NMR-based quantification and gas chromatography-based measurements was 0.77 for EPA. On average, DHA comprised 44.5% of the total omega-3 concentration, EPA accounted for 22.2%, and other subclasses constituted 34.3% in the cohort. We computed age and sex adjusted associations of omega-3, DHA, and EPA with 10-year risk of CVD among individuals who were not taking cholesterol lowering medication. We discovered protective associations: for DHA a hazard ratio of 0.85 (0.86-0.89, 95% confidence interval) per standard deviation versus 0.96 (0.95-0.98) for EPA, and 0.95 (0.93-0.97) for total omega-3 (Figure). Since DHA (used in the STRENGTH trial with a null result) has a significantly stronger epidemiological association than EPA, these results from a large-scale observational study do not support the hypothesis that the differential use of DHA and EPA in the REDUCE-IT and STRENGTH trials explains their divergent results.Figure

High altitude exercise stress echocardiograph for identification of susceptibility to acute mountain sickness

Abstract Background Acute high-altitude exposure increases the risk of acute mountain disease (AMS) and high-altitude pulmonary edema. After the initial exposure to high altitude, mountain climbers are worried about whether they will develop AMS. At high altitudes, there are no accurate indicators to predict the near future occurrence of AMS. Objectives To investigate whether treadmill exercise stress echocardiography at high altitude can predict the occurrence of AMS, and to find out some powerful factors associated with the susceptibility to AMS. Methods 36 healthy lowlanders were taken by bus from sea level to an altitude of 3600 m the next morning, during which they rested overnight at an altitude of 2150 m. Treadmill exercise stress echocardiography was performed immediately upon arrival at 2150 m, and the 2018 Lake Louise Questionnaire Score was performed the next day when arrived at the altitude of 3600 m. Heart rate (HR) and blood pressure (BP) were monitored during stress echocardiography. Left ventricular (LV) ejection fraction and E/e’ were calculated at rest and immediately after exercise. Other right ventricular systolic function parameters and pulmonary artery pressure (PAP) were calculated at the same time, which included tricuspid regurgitation velocity (TRV), tricuspid annular peak systolic excursion (TAPSE), systolic PAP (SPAP), right ventricular (RV) dimension by 2D, RV fraction of area change (FAC), right ventricular outflow tract velocity time integral (RVOT VTI). Pulmonary vascular resistance (PVR) was calculated according to the formula: TRV/RVOT VTI*10+0.16. Mean PAP (mPAP) was calculated as the formula: sPAP*0.61+2. All subjects ascended to 3600m within 24 hours by bus. AMS was identified by 2018 Lake Louise Questionnaire Score. Univariable and multivariable logistic regression analysis assessed independent factors associated with AMS. Results At the altitude of 3600m, 13 of 36 subjects had AMS, which defined as AMS (+) group. And the rest was AMS (-) group. There were no significant differences in HR, BP, SO2 and LV systolic and diastolic function between the two groups (P > 0.05). No significant differences were noted at rest except for TV s' (P < 0.05). Immediately after exercise, TRV, TAPSE, SPAP, mPAP, PVR, and RV area at the end of systole were much higher in AMS (+) group (all P < 0.05). While FAC and TVs’/SPAP were much lower in AMS (+) group (P < 0.05). By multivariable logistic regression model, mPAP immediately after exercise was significantly correlated with AMS occurrence (OR =1.332, 95% CI: 0.669-0.993, P= 003). The cutoff value of mPAP to predict AMS was 32 mmHg (AUC: 0.831, specificity: 86.7%, sensitivity: 76.9%). Conclusions The mPAP immediately after exercise upon arrival at an altitude of 2150 m is a strong predictor of near future AMS, and treadmill exercise stress echocardiography is a simple and non-invasive tool to help mountain climbers avoid more severe mountain sickness.

Effect of green coffee on miR-133a, miR-155 and inflammatory biomarkers in obese individuals

ObjectivesMetabolic syndrome is a cluster of conditions that increases the risk of atherosclerotic cardiovascular diseases. The current study was a randomized, double blind, placebo-controlled study that aimed to determine the impact of green coffee (GC) in obese patients with metabolic syndrome through analysis of miRNA-155, miRNA-133a and the inflammatory biomarkers such as resistin, TNF-α, total sialic acid, homocysteine, high sensitivity C-reactive protein (hs-CRP), and the anti-inflammatory cytokine, adiponectin.MethodsOne hundred-sixty obese patients were randomly supplemented either with GC capsules (800 mg) or placebo daily for six months. Both groups were advised to take a balanced diet. Blood samples were collected at baseline and after six months of supplementation.ResultsGC supplementation for 6 months reduced BMI (p = 0.002), waist circumference (p = 0.038), blood glucose (p = 0.002), HbA1c% (p = 0.000), Insulin (p = 0.000), systolic blood pressure (p = 0.005), diastolic BP (p = 0.001) compared with placebo. GC significantly decreased total cholesterol (TC, p = 0.000), LDL-C (p = 0.001), triglycerides (TG, p = 0.002) and increased HDL-C (p = 0.008) compared with placebo group. In addition, GC significantly (p ≤ 0.005) reduced total sialic acid, homocysteine, resistin, TNF-α, hs-CRP and the oxidative stress marker malondialdehyde (MDA), but increased serum adiponectin (p = 0.000) compared to placebo group. There was a significant reduction in the gene expression of miR-133a (p = 0.000) in GC group as compared with baseline levels and with the control placebo group (p = 0.001) after 6 months.ConclusionGC administration modulated metabolic syndrome by decreasing BMI, high BP, blood glucose, dyslipidemia, miRNA-133a and inflammatory biomarkers that constitute risk factors for cardiovascular diseases.ClinicalTrials.gov registration No. is NCT05688917.Graphical

Albuminuria is associated with progression of diastolic dysfunction in patients at risk for cardiovascular disease

Abstract Background The number of the patients with heart failure with preserved ejection fraction (HFpEF) is increasing as society ages, which indicates that the number of pre-HFpEF patients is increasing even more. To combat this sociomedical burden, it is critical to establish cost-effective and simple biomarkers to identify the high-risk population at early phase of the disease. Recent studies demonstrated the association between albuminuria and incident heart failure, but the prognostic impact of albuminuria on diastolic dysfunction, an early phenotype of HFpEF, has not been elucidated. Purpose To examine the impact of albuminuria on the diastolic function over time in the patients with cardiovascular risks. Methods One hundred and fifty-eight patients with at least one cardiovascular risk factor without history of heart failure were followed up for 5 years. Echocardiogram was conducted at baseline, year 3, and year 5. Diastolic dysfunction was defined as E/e’ >14. Albuminuria was defined as urine albumin-to-creatinine ratio (UACR) 30 ≧mg/gCre. The patients with ejection fraction <40% and those had diastolic dysfunction at baseline were excluded from the study. The relationship between albuminuria at baseline and diastolic function at year 3 and 5 were investigated. Results Among 158 subjects, 27 showed albuminuria at baseline and the prevalence of hypertension, dyslipidemia, and diabetes was not significantly different between patients with and without albuminuria. The baseline E/e’ tended to be higher in patients with albuminuria, although the difference was not statistically significant (Fig1: E/e’ = 10.0±2.4 vs. 9.4±2.2, p = 0.08) . However, the patients with albuminuria showed a steeper increase in E/e’ than those without albuminuria, and the significant difference was observed at year 3, that was even greater at year 5 (Fig1: E/e’ = 11.1±2.8 vs 10.0±2.6, p = 0.04 in year 3, E/e’ = 12.5±4.1 vs 10.3±2.9, p = 0.002 in year 5, respectively). Furthermore, log UACR at baseline showed significant correlation with E/e’ at year 5 (p = 0.02, r = 0.21) and normo-, micro-, and macroalbuminuria (UACR<30, 30-300, and >300mg/gCre, respectively) at baseline showed elevated E/e’ at year 5 in this order ( p = 0.01 for UACR<30 vs. 30-300mg/gCre, and p = 0.04 for UACR<30 vs. >300mg/gCre, reapectively ). The prevalence of incident diastolic dysfunction increased greater in patients with albuminuria throughout the follow-up period and the difference reached statistical significance at year 5 (Fig2: 18.5% vs. 9.2%, p = 0.28 for year 3, and 25.9% vs. 8.4%, p = 0.009 for year 5, respectively). Conclusion In the patients with cardiovascular risk factors, albuminuria was associated with development and progression of diastolic dysfunction over subsequent 5 years. Future prospective study is warranted to investigate the effectiveness of albuminuria-directed care to prevent development of HFpEF.

Climate change and gastroenteritis projections in Albanian children

Abstract Background Human health can be affected by climate in direct and indirect ways. Increasing temperatures may affect ecosystems, water safety, and exposure to waterborne diseases. This is the first work in Albania aiming to demonstrate the link between gastroenteritis rate and climate in the country. This research was supported by UNICEF Albania through the WASH Global Thematic Fund, but it doesn’t necessarily represent UNICEF’s position. Methods Epidemiological surveillance reports of the period 2006-2022 were used for the yearly incidence of gastroenteritis in children 0-14 years old. Years 2020 and 2021 were not included because of pandemic confounding potential. Historic data for calculating the average summer temperatures were retrieved from timeanddate.com repository. Pearson coefficient is calculated to quantify the associations and linear regression is applied to project the increased rate in the future. Results There was a statistical association between gastroenteritis rate and summer temperatures during the study period (Pearson coefficient=0.78, p = 0.001). There was a tendency that in years with hotter summers higher incidence of gastroenteritis was reported by the health system. For each degree (Celsius) increase in the average summer day temperatures, the risk of gastroenteritis in children is expected to increase by 644/100 000 (CI 95%: 317 - 972). An excess rate of 966/100 000 is expected in the case of Intergovernmental Panel on Climate Change medium scenario projection of 1.5o C average temperature increase. That implies more than 4830 additional new cases every year in children 0-14 years old, attributed to climate change in the future in Albania. Conclusions The analysis demonstrated excess gastroenteritis risk may be related to higher summer temperatures observed in Albania. The expected gastroenteritis risk increase in a warmer future should be addressed by improvements in sanitation, education of parents and epidemiological intelligence. Key messages • A warmer climate is expected to affect the health by increasing the risk for diarrheic diseases. • Children will be the most at-risk population category.

Incidence and risk of autoimmune disease in patients with a previous diagnosis of myocarditis - a nationwide Danish register-based cohort study

Abstract Introduction Myocarditis is a severe condition with an acute onset characterized by myocardial inflammation. The aetiology is heterogenous ranging from viral infections to autoimmune diseases (AD). However, it is currently unknown if patients with a first-time diagnosis of myocarditis are at higher risk of developing an autoimmune disease (AD) at a later stage. Purpose To estimate the risk of developing AD in patients with a first-time diagnosis of myocarditis during 20 years of follow-up. Methods Data source and study design: Nationwide register-based cohort study using data from Danish national administrative registers containing data on ICD-10 codes of diagnoses, prescription of pharmaceuticals, as well as date of birth and death on all Danish citizens. Study population: All Danish patients with a diagnosis of myocarditis from 2002-2020. Patients with previous diagnosis of AD were excluded. A control population without a diagnosis of myocarditis nor AD was sex and aged matched 1:5. Endpoints: Receiving a diagnosis of AD out of 35 recognized AD, and all-cause mortality. Statistics: Cumulative incidence of AD diagnosis was calculated by use of Aalen-Johansen estimation and all-cause mortality rate by Kaplan-Meier estimation. Hazard ratio (HR) by multivariate Cox regression modelling, standardized to sex, age, and comorbidities. Standardized relative (RR) and absolute (AR) risk derived from Cox regression by estimated Average Treatment Effect. Continuous variables are presented as median [1st quartile, 3rd quartile]. Results Study population: Myocarditis cohort: n=2,684. Control cohort: n=13,420. Median follow-up time: 9.5 years [5.4, 14.6]. Median age: 46 years [28, 67]. 69.5 % were of male sex. Comorbidities including hypertension, heart failure, and ischemic heart disease were significantly more common in patients with myocarditis. Autoimmune disease: At 20 years of follow-up, the cumulative incidence of AD diagnosis was 14.1% in the myocarditis cohort, and 5.8% in the control cohort. Adjusted HR for AD diagnosis in myocarditis vs. control cohorts was 2.65 (95% CI 2.19-3.17). Adjusted RR at 1 and 20 years of follow-up was 2.26 (95% CI 2.13-3.11) and 2.47 (95% CI 2.03-2.90), respectively. Figure 1 (left) shows AR of developing an AD at 20 years of follow-up, stratified by sex and age group. Mortality: Kaplan-Meier all-cause mortality was 40.5% in the myocarditis cohort, and 28.5% in the control cohort. Adjusted HR: 1.84 (95% CI 1.67-2.03). Adjusted RR at 1 and 20 years of follow-up: 1.77 (95% CI 1.60-1.93) and 1.31 (95% CI 1.25-1.36), respectively. Figure 1 (right) shows stratified AR of all-cause mortality at 20 years of follow-up. Conclusions Patients with a diagnosis of myocarditis had a significantly higher risk of developing AD in addition to significantly higher all-cause mortality compared to patients without previous myocarditis diagnosis. These findings suggest underlying and subsequent AD should be considered in patients with myocarditis.20-year AR of AD and all-cause mortalityICD-10 codes of AD investigated

Rapid response Task Force: addressing the detection of Aedes albopictus in Lisbon, Portugal

Abstract Issue The invasive Aedes albopictus mosquitoes are spreading in southern Europe and pose a heightened risk of mosquito-borne diseases, like Dengue and Chikungunya. On September 2023, A. albopictus was first identified in Lisbon through community-based surveillance and a multidisciplinary national Task Force (TF) was convened. Description of the problem The TF included experts in epidemiology, entomology, environmental health, laboratory diagnosis, prevention and control and communication. The objectives were to i) confirm A.albopictus presence in Lisbon and adjust the risk assessment, ii) raise awareness and prevent mosquitoes’ spread, iii) revise national guidelines on arboviruses surveillance and control. During September-December 2023, the National Network for Vectors Surveillance (REVIVE) and the Hygiene and Tropical Medicine Institute sampled mosquito-prone habitats within 2km-radius of the detection point using QGIS software. They used snowball sampling to identify any new foci. They placed ovitraps for ongoing surveillance and conducted morphological analysis and xenomonitoring for pathogen DNA and RNA detection at the national reference laboratory. Results By November 2023, A.albopictus was detected in two new foci. No mosquitoes tested positive for arboviruses, and no autochthonous cases of mosquito-borne diseases were identified. The TF developed national guidelines for vector prevention and control and awareness for arboviruses and trained municipality workers. To raise awareness, we communicated with experts and the public through existing channels and media. As of April 2024, no new foci have been detected. Lessons Community-based surveillance and REVIVE approach were crucial for invasive A.albopictus detection and monitoring in Lisbon. Rapid multidisciplinary TF coordination may have been key for timely vector control.

LE8 score in relation to cardiovascular disease and mortality in individuals with diabetes

Abstract Background Evidence regarding the potential health effects of Life’s Essential 8 (LE8) score among individuals with type 2 diabetes (T2D) is limited. Purpose We aimed to examine the associations of LE8 score with risk of cardiovascular disease (CVD) and mortality, among individuals with T2D. Methods We prospectively followed 19,915 Chinese participants with T2D at baseline or diagnosed during follow-up (Kailuan Study: 2006-2020), who were free of CVD at diagnosis of diabetes. Diet, lifestyle, and health conditions were repeatedly assessed every 2 years. The LE8 score (range, 0-100), was calculated based on 8 components: diet quality, physical activity, smoking status, sleep health, BMI, blood lipids, blood glucose, and blood pressure. We used time-varying cox models to model the associations. Results During a median follow-up of 11.5 years in participants with T2D, there were 3,295 incident CVD cases and 3,123 deaths. Higher LE8 score was associated with lower risk of CVD incidence and total mortality among participants with diabetes. The multivariate-adjusted hazard ratios and 95%CIs for the highest quintile of LE8 score compared with the lowest quintile were 0.56 (0.53, 0.59) for CVD incidence, 0.57 (0.53, 0.62) for heart disease incidence, 0.53 (0.49, 0.57) for stroke incidence, and 0.73 (0.69, 0.78) for total mortality (all p trend<0.001). Furthermore, compared with participants with stable or decreased LE8 score after diabetes diagnosis, those with increased LE8 score had 17%-42% lower risk of CVD incidence, heart disease incidence, stroke incidence, and total mortality. These associations persisted in subgroup analysis stratified by age, sex, BMI, smoking status, alcohol intake, family history of diabetes and CVD, and follow-up time. Conclusions Higher LE8 score was associated with a substantially lower risk of CVD incidence and total mortality among adults with T2D. These findings further support the tremendous benefit of adhering to a high CVH, defined as the LE8 in reducing the subsequent burden of cardiovascular complications and improving overall health in individuals with T2D.Main TableMain Figure