Major Modifiable Risk Factor Research Articles

Recruitment data of the HAPPCAP‐AD (Human‐APPlication Combined Approach for Prevention of Alzheimer’s Disease): a feasibility study

AbstractBackgroundPhysical inactivity, obesity, type 2 diabetes [T2D], hypertension, smoking, and depression, are six major modifiable risk factors for Alzheimer’s disease (AD). While several multi‐domain intervention studies have been completed, mostly in older adults, targeting one or more modifiable risk factor, results have been inconsistent. We designed novel, “real‐life”, feasibility study of a personalized 18‐months intervention for prevention of cognitive decline in middle‐aged individuals at very high AD risk due the presence of at least two modifiable risk factors plus parental family history of AD. Our aims are to explore: 1) The feasibility of our novel approach; 2) Whether our intervention improves AD risk factors and whether greater adherence is associated with larger improvement; and 3) Whether our intervention improves cognition.MethodStudy’s participants are 40‐65 years old cognitively normal offspring of individuals with AD. Participants must have at least two of the six major modifiable AD risk factors. Recruitment goal was 100 participants. Participants were randomized at a 2:1 ratio to the intervention:control arms of the study. The 18‐months intervention combines a smartphone application (app) with study team guidance through phone‐calls, which include advice for risk factors improvement, interactive follow‐up using an app, and feedback on risk factors management for its modification.ResultSince study was launch in 2019, 500 individuals have completed an online eligibility questionnaire. We have achieved the recruitment goal, and 100 participants have been enrolled, with 67 in the intervention group and 33 in the control group. Groups are well‐matched for baseline demographics and AD risk factors (intervention vs control: age‐ 57.3[SE = 0.64]vs.57.0[SE = 0.99]; sex ‐ [% males]30%vs.33%; years of education‐ 17.7[SE = 0.77] vs.17.0[SE = 0.64]; BMI‐ 30.5[SE = 0.63]vs.29.6[SE = 0.59]; % physical inactivity ‐84vs.82; % T2D‐ 15vs.12; % hypertension‐ 27vs.30; % depression‐ 16vs.15; and MMSE‐ 29[SE = 0.17]vs. 29.2[SE = 0.16]; all p>0.05), except for percentage of smokers which was significantly higher in the intervention arm (12vs.3). Additional analyses will be ready by AAIC 2023.ConclusionResults of this study will provide feasibility data on the adherence to the human‐app approach, characteristics of those who adhere, on whether the approach improves risk factors, and will provide initial data on intervention efficacy for cognition.

Socioeconomic variation in modifiable risk factors for dementia

AbstractBackgroundMost studies on modifiable risk factors for dementia are in relatively affluent populations, but dementia risk is higher among those who are more materially deprived. We aimed to consider whether this is accounted for by potentially modifiable risk factors, and compare the overall population attributable fraction (PAF) in the least and most socioeconomically deprived participants within the UK Biobank (UKB).MethodThe UKB is a cohort study with 502,656 volunteer participants registered between 2006‐2010, aged 40‐60 years at baseline, and followed for up to 16.8 years. Material deprivation was quantified using the Townsend Deprivation Index grouped into quintiles, with higher scores meaning higher deprivation. We assessed interactions between Townsend quintiles (using least deprived as reference), and each modifiable risk factor. To estimate the PAFs of 12 modifiable risk factors (diabetes, hypertension, depression, hearing loss, obesity, traumatic brain injury, less education, social isolation, physical inactivity, air pollution, and smoking), we first estimated hazard ratios (HRs) (adjusted for age, gender, and ethnicity) stratified by Townsend. HRs were then converted to relative risk for PAF calculation.Results6,624 incident cases of dementia developed in 1.6%(95%CI = 1.5‐1.7)(n = 11679/10369) of participants in the most deprived group, compared to 1.2%(95%CI = 1.1‐1.3)(n = 1174/98074) in the least deprived group. The mean age at dementia diagnosis were 72.7 years(SD,6.3){in most deprived}, and 73.8 years(SD,5.1){in least deprived}. The combined PAF(95%CI) for dementia was 40.3%(40.0‐40.6){most deprived}, versus 27.2%(27.0‐27.5){least deprived}. The most deprived, compared to the least deprived, had higher PAFs for: (a)Midlife hypertension: 7.7%(7.6‐7.9) vs 4.1%(3.9‐4.2); (b)Less education: 5.8%(5.6‐5.9) vs 3.4%(3.2‐3.6); (c)Diabetes: 4.4%(4.3‐4.6) vs 3.1%(3.0‐3.2); (d)Physical inactivity: 3.5%(3.4‐3.6) vs 0.7%(0.6‐0.7);) (e)Social isolation: 3.4%(3.3‐3.5) vs 1.0%(1.0‐1.1); (f)Midlife obesity: 2.1%(2.0‐2.2) vs 1.2%(1.2‐1.3); and (g)Smoking 1.8%(1.7‐1.9) vs 0.5%(0.5‐0.6). Air pollution had a PAF of 1.8%(1.7‐1.9) in the least deprived, and 0.0% in the most deprived. The remaining risk factor PAFs did not differ between the most and least deprived.ConclusionsIn this volunteer cohort, which is relatively wealthy, a higher proportion of dementia cases were attributable to major modifiable risk factors in more socioeconomically disadvantaged participants. Targeted interventions particularly addressing midlife hypertension, education, physical activity and social isolation might mitigate known inequalities in dementia risk according to socioeconomic status.

Late, but not too late, is better than never: late‐life literacy is not associated with lower prevalence of dementia and cognitive impairment no dementia

AbstractBackgroundEducation is a major modifiable risk factor for dementia and is usually considered an early‐life intervention. However, low‐ and middle‐income countries usually have high rates of illiteracy among older adults, and some became literate after childhood. Therefore, we aimed to investigate whether there were any associations between the age of literacy with the prevalence of cognitive impairment no dementia (CIND) and dementia, compared to illiteracy, regardless of the educational attainment.MethodWe used baseline data from the Brazilian Longitudinal Study of Aging (ELSI‐Brazil), a population‐based nationally representative cohort of people aged 50 years or older, and the first Health and Retirement Studies (HRS) partner study in South America. For this study, we restricted our analysis to those aged 60 years or older, who had been classified as cognitively normal, CIND, or dementia. Participants were stratified into five groups: four according to their age when started schooling (early‐life literacy (EL) (<11 years), adolescent literacy (AdL) (11‐19 years), adulthood literacy (AhL) (20‐59 years) and late‐life literacy (LL) (≥60 years)) and illiteracy (IL). CIND and dementia classification prevalence ratios (PR) according to literacy status were assessed using Poisson regression, and adjusted for sociodemographic (age, sex/gender, educational attainment, race/ethnicity) and clinical confounders (memory complain, depressive symptoms, heavy drinking, smoking status, hypertension, and diabetes).ResultOur final sample comprised 5,244 older adults (mean age 70.1±7.8 years, mean education 4.6±4.4 years, 60% female, 55% Black/Brown, 6% with dementia and 8% with CIND) (Table 1). Fifteen percent of the sample started their literacy after childhood, and 21% remained illiterate. EL and (PR = 0.22, 95%CI = 0.09;0.53) and AdL (PR = 0.42, 95%CI = 0.18;0.98) groups had lower dementia prevalence compared to IL group (Table 2). However, there was no prevalence difference between IL and those who started literacy after adolescence.ConclusionWe found a lower prevalence of dementia among participants with early‐life and adolescent literacy compared to illiteracy. Adulthood and late‐life literacy were not associated with lower dementia prevalence. Literacy after childhood might have same beneficial impact if it is not started too later in life. Further studies should be conducted to better understand the impact of late‐life literacy interventions on reducing dementia risk.

HPB P13 A Systematic Review of the Methodology Used in Nutritional Effectiveness Trials for Pancreatoduodenectomy Patients

Abstract Background Malnutrition is highly prevalent amongst pancreatoduodenectomy (PD) patients and remains a major modifiable risk factor for postoperative morbidity and mortality. As a result, there is a need to identify optimal nutritional therapies but this has typically been difficult due to multiple methodological issues including lack of suitable control group and outcome. Therefore, the aim of this review is to report and compare the administration of different nutritional therapies as well as reporting of nutritional outcomes in randomised controlled trials (RCTs) of PD patients. Methods A systematic review of randomised controlled trials (RCTs) studies reporting the effect of different nutritional interventions after PD was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Embase and Medline databases were searched. The search identified 21 suitable studies for inclusion. Results There were 5 different feeding routes reported, with oral diet (14 studies, 67%) and parenteral nutrition (9 studies, 43%) being the most common. There was widespread variation in when oral diet was started, ranging between postoperative day (POD) 1 and 7. Regarding enteral tube feeding, multiple different feed types were used and feed administration was highly variable, for both rate and duration. In terms of outcome types, 17 (81%) studies reported biochemical outcomes with serum albumin being the most common (12 studies, 57%) and 12 (57%) reported anthropometric outcomes with body mass index the most common (7 studies, 33%). Conclusions Amongst the published RCTs investigating the effect of different nutritional routes after PD, widespread variation in the methodology was evident. This has implications for both interpretation of results and for design of future nutritional trials. Multiple biochemical and anthropometric outcomes were reported but quality of life measures, such as the SF-36 recommended by a recently published core outcome set, were not used.

Effect of supportive periodontal therapy on tooth loss in regular and irregular compliant smokers and non-smokers: A Systematic Review

Aim: The aim of this systematic review is to analyze and compare tooth loss (TL) rates between regular and irregular compliant patients having different smoking habits. Materials and Methods: Electronic and manual literature searches were conducted by one author in several databases, including Medline (PubMed), Embase, Google Scholar. A total of 156 publications were screened. Three reviewers analyzed the articles and extracted the data. A total of 33 studies met the inclusion criteria. Results: A total of 30 articles were eligible for qualitative analysis, and only 3 for quantitative analysis. Compliance and smoking case definition as well as recall intervals during supportive periodontal therapy (SPT) differed widely between studies. A total of 10 publications reported significant differences in TL rates between regular (RC) and irregular compliant (IC) patients, while 25 publications reported significant differences in TL rates between smokers and non-smokers. Conclusion: Regular attendance to SPT visits and non-smoking patients are associated with fewer TL rates. Smoking is considered a major modifiable risk factor for TL.

The effect of implementing a guideline-based approach to achieve target LDL-C levels in very high risk patients. The PENELOPE study one year follow-up results

Abstract Background/introduction Hyperlipidemia is a major modifiable risk factor for developing cardiovascular disease. Lowering LDL-C reduces the risk for coronary heart disease (1,2). The PENELOPE study implemented an ESC-guideline-based, stepwise strategy of lipid-lowering therapy (LLT) to achieve target LDL-C levels in very high-risk patients, with a mean duration of 61 days. Purpose This paper demonstrates the legacy effect after one year. Methods Nine hundred and ninety-nine (999) patients with a myocardial infarction and a history of atherosclerotic cardiovascular disease and/or diabetes mellitus were included in PENELOPE for stepwise intensified LLT (high intensity statin (HIST) monotherapy, HIST + ezetimibe, HIST + ezetimibe + PCSK9i) until reaching target LDL-C level (≤1.8mmol/L). The primary objective was to assess the prevalence of maintained LDL-C ≤1.8 mmol/L and therapy-adherence after one year. Results For the one year follow up visit, 738 patients (73%) were available. Thirty patients had died, 45 were lost to follow up and from 178 patients no signed informed reconsent was obtained. The per protocol cohort included six hundred and seventy-one (671) patients. In this cohort, a non-participation bias cannot be excluded. After one year, in four-hundred forty-nine (449) patients target LDL-C level (66,9%) was maintained. Mean LDL-C level after one year was 1.67 mmol/L and the adherence rate to LLT was 94,5%. The major treatment regimens were statin monotherapy (61,7%), statin + ezetimibe (28,3%) and PCK9i + ezetimibe (+ statin) (5,8%). Maintained target (LDL-C ≤1.8mmol/L) was 64%, 77% and 82%, respectively. The large percentage loss of patients on target after one year could be explained by the cut-off at 1.8 mmol/L (only 0.28 mmol/L increase in mean LDL-C level), the short-term effect of heart rehabilitation and a treatment change in 20,4% of patients. Therapy adherence was high and did not differ between treatment regimen. Conclusion Using an ESC-guideline-based flowchart with quick, stepwise intensification of LLT leads to a 99% success rate (LDL-C ≤1.8mmol/L) within 3 months and 67% after one year. The mean LDL-C level increases with 0.28 mmol/L.

Abstract 13901: Deep Learning-Based Digital Biomarker to Diagnose Hypertension and Stratify Cardiovascular Risk From the Electrocardiogram

Background/Aim: Hypertension affects nearly half of US adults and is a major modifiable risk factor for cardiovascular disease (CVD). Guidelines recommend serial blood pressure (BP) measurement under controlled conditions or ambulatory BP monitoring, but BP is often measured intermittently under suboptimal conditions, leading to underdiagnosis and undertreatment. We developed a deep learning model (HTN-AI) to identify hypertension and stratify risk of hypertension-associated CVD from 12-lead ECGs. Methods: HTN-AI is a convolutional neural network trained to detect prevalent hypertension or elevated baseline BP (systolic ≥ 140 mmHg or diastolic ≥ 90 mmHg) using 747,992 ECGs from 106,879 adults receiving primary or cardiology care at Massachusetts General Hospital (MGH). Associations between HTN-AI-predicted risk of hypertension and CVD (all-cause mortality, heart failure [HF], myocardial infarction [MI], stroke, and aortic dissection) were assessed in 56,730 primary care patients at Brigham and Women’s Hospital (BWH) with cumulative incidence analysis and cause-specific hazard regression. Results: In an MGH test sample and the BWH sample, HTN-AI discriminated prevalent hypertension or elevated baseline BP (AUC 0.791 and 0.762, respectively). Quintiles of HTN-AI risk stratified cumulative incidence of mortality (Figure), HF, MI, stroke, and aortic dissection (p < 0.001 for all). HTN-AI risk was significantly associated with age- and sex-adjusted risk of incident mortality (HR per SD: 1.85 [95% CI: 1.77-1.92], p<0.001), HF (3.55 [3.25-3.88], p<0.001), MI (2.33 [2.20-2.47], p<0.001), stroke (1.74 [1.64-1.86], p<0.001), and aortic dissection (1.80 [1.41-2.31], p<0.001). Conclusion: A deep learning model, HTN-AI, discriminates patients with hypertension and stratifies risk of incident CVD using 12-lead ECGs. HTN-AI has the potential to facilitate diagnosis of hypertension and serve as a novel digital biomarker for hypertension-associated CVD.

Blood Management for the Orthopaedic Surgical Patient.

Prevention and management of anemia and blood loss in the orthopaedic patient undergoing surgery is a major concern for healthcare providers and patients. Although transfusion technology can be lifesaving, there are risks to blood products that have led to increased awareness of blood management and development of hospital patient blood management programs. Use of patient blood management can be effective in addressing preoperative anemia, a major modifiable risk factor in patients undergoing surgery. In this informational article, evidence-based practice guidelines for perioperative blood management are addressed. A case scenario is introduced focusing on a patient whose religious preference is Jehovah's Witness having "no blood wishes" undergoing elective orthopaedic surgery. Orthopaedic nurses can facilitate optimal patient blood management through multidisciplinary collaboration.

Risk factors associated with elevated intraocular pressure: a population-based study in a rural community of Bangladesh

ObjectiveHigh intraocular pressure (IOP) is one of the major modifiable risk factors for glaucoma. The objective was to examine socio-demographic and clinical factors related to IOP.Methods and analysisThis study was...

Effects of obesity, and of weight loss following bariatric surgery, on methylation of DNA from the rectal mucosa and in cell-free DNA from blood.

DNA methylation is an epigenetic mechanism through which environmental factors including nutrition and inflammation influence health. Obesity is a major modifiable risk factor for many common diseases including cardiovascular diseases and cancer. In particular, obesity-induced inflammation resulting from aberrantly-methylated inflammatory genes may drive risk of several non-communicable diseases including colorectal cancer (CRC). This study is the first to investigate the effects of weight loss induced by bariatric surgery (BS) on DNA methylation in the rectum and in cell-free DNA (cfDNA) from blood. DNA methylation was quantified in rectal mucosal biopsies and cfDNA from serum of 28 participants with obesity before and 6 months after BS, as well as in 12 participants without obesity (control group) matched for age and sex from the Biomarkers Of Colorectal cancer After Bariatric Surgery (BOCABS) Study. DNA methylation of LEP, IL6, POMC, LINE1, MAPK7 and COX2 was quantified by pyrosequencing. BMI decreased significantly from 41.8 kg/m2 pre-surgery to 32.3 kg/m2 at 6 months after BS. Compared with the control group, obesity was associated with lower LEP methylation in both the rectal mucosa and in cfDNA from serum. BS normalised LEP methylation in DNA from the rectal mucosa but not in cfDNA. BS decreased methylation of some CpG sites of LINE1 in the rectal mucosal DNA and in cfDNA to levels comparable with those in participants without obesity. Methylation of POMC in rectal mucosal DNA was normalised at 6 months after BS. BS reversed LINE1, POMC and LEP methylation in the rectal mucosa of patients with obesity to levels similar to those in individuals without obesity. These findings support current evidence of effects of BS-induced weight loss on reversibility of DNA methylation in other tissues. The DNA methylation changes in the rectal mucosa shows promise as a biomarker for objective assessment of effects of weight loss interventions on risk of cancer and other diseases.

Abstract 077: Protein Biomarkers Of Hypertension

Background: Hypertension is a major modifiable riskfactor for cardiovascular disease. The discovery of novel protein biomarkers ofhypertension can provide information on disease pathophysiology and highlightpromising therapeutic targets. Methods: We measured plasma levels of 2925proteins in 740 participants (mean age 51.7 ±11.3 years; 46% women) in the Framingham HeartStudy using the Olink Explore proximity extension assay. Linear mixed modelswere used to explore the associations of plasma proteins with systolic anddiastolic blood pressure (BP) and prevalent hypertension. We definedhypertension as having elevated BP (systolic ≥ 140 mmHg or diastolic ≥90 mmHg) or current use of antihypertensive medication. We adjusted all themodels for age, sex, batch effects, eGFR (estimated glomerular filtration rate),pack-years of smoking, and lung function status (normal/obstructive/restrictive). Sensitivity analysis was performed by excluding individuals treated withantihypertensive medication. Using overrepresentation analysis, we annotatedthe proteins associated with hypertension. We adjusted for multiple tests using the Benjamini-Hochberg method and a false discovery rate of < 0.05 wasused to define statistical significance. Results: We observed differential expression of 526proteins (465 upregulated, 61 downregulated) in participants with prevalenthypertension (N=257) vs. normal BP (N= 483). Systolic BP was associated with571 proteins and diastolic BP was associated with 662 proteins. We observed 507protein associations with systolic BP and 626 protein associations withdiastolic BP after exclusion of treated individuals (N=177). Functionalannotation of proteins associated with hypertension showed enrichment of genesassociated with fatty acid transport, regulation of MAPK cascade, response tointerleukin-1 and inflammatory response. Discussion: This study elucidates protein signaturesassociated with BP and hypertension. Hypertension is enriched in pathwaysrelated to fatty acid transport and inflammatory response. These results mayprovide information on the pathogenesis ofhypertension and highlight promising therapeutic targets.

Development and piloting of a primary school-based salt reduction programme: Formative work and a process evaluation in rural and urban Malawi.

Excess salt intake is a major modifiable risk factor for cardiovascular disease. Promoting salt reduction as part of routine school-health programming may be a pragmatic way to address this risk factor early in the life course but has not been tested in sub-Saharan Africa (SSA). Here we describe the formative work with stakeholders and process evaluation of pilot work to develop a school-based salt reduction programme for children aged 11-14 years, in preparation for a cluster-randomised trial in rural/urban Malawi. Collection of observational data and documentary evidence (meeting minutes/field notes) from the earliest key stakeholder engagement with Malawi Ministries of Health, Education, Local Government and Rural Development and Malawi Institute of Education, and non-governmental stakeholders; and a series of semi-structured interviews and focus groups (with head teachers (n = 2); teachers (n = 4); parents (n = 30); and learners (n = 40)). Data was analysed thematically and conceptualised through a Normalization Process Theory lens. Formative work illustrated a range of administrative, technical, and practical issues faced during development of the programme; including allocation of stakeholder roles and responsibilities, harmonisation with pre-existing strategies and competing priorities, resources required for programme development, and design of effective teaching materials. While participants were positive about the programme, the process evaluation identified features to be refined including perceived challenges to participation, recommended adaptations to the content and delivery of lessons, and concerns related to quantity/quality of learning resources provided. This study demonstrates the importance of comprehensive, sustained, and participatory stakeholder engagement in the development of a novel school health programme in SSA; and highlights the factors that were critical to successfully achieving this. We also demonstrate the value of detailed process evaluation in informing development of the programme to ensure that it was feasible and relevant to the context prior to evaluation through a cluster-randomised trial.

Will the use of anabolic androgenic steroids become a significant cardiovascular risk factor in the future?

Introduction and purpose: Cardiovascular diseases are the leading cause of mortality in many European countries. Major modifiable risk factors include dyslipidemia, hypertension, smoking and diabetes. The aim of our study is to draw attention to the possible impact of the use of anabolic androgenic steroids on increased cardiovascular risk.
 Brief description of the state of knowledge: Currently, an increasing proportion of the population uses anabolic-androgenic steroids (AAS). This situation applies not only to athletes, but also to amateurs. The use of AAS may be associated with numerous complications. These include an increased risk of cardiovascular disease. The literature describes the effect of AAS use on the occurrence of dyslipidemia, insulin resistance, hypertension and metabolic syndrome. All these metabolic disorders result in increased cardiovascular risk. To prevent complications, it seems best to withdraw AAS gradually under medical supervision to minimize withdrawal effects.
 Conclusion: The use of AAS may cause cardiovascular disease, but additional long-term studies are needed to prove this. It is necessary to sensitize patients and doctors to the problem of AAS abuse in society, because this issue can become a significant risk factor for cardiovascular diseases in near future.

Smoking and risk of colorectal cancer according to KRAS and BRAF mutation status in a Japanese prospective Study.

Although smoking is a major modifiable risk factor for many types of cancer, evidence for colorectal cancer is equivocal in Asian populations. Recent Western studies have proposed that the association between smoking and colorectal cancer is restricted to specific tumor molecular subtypes. However, no studies have evaluated the association according to tumor molecular subtypes in Asian populations. In a Japanese prospective population-based cohort study of 18 773 participants, we collected tumor tissues from incident colorectal cancer cases and evaluated KRAS (Kirsten rat sarcoma viral oncogene homolog) and BRAF (v-raf murine sarcoma viral oncogene homolog B) mutation status using target sequencing. Multivariable-adjusted Cox proportional hazard model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for associations of smoking with the risk of overall colorectal cancer and its subtypes defined by KRAS and BRAF mutation status. Among 339 cases, KRAS and BRAF mutations were identified in 164 (48.4%) and 16 (4.7%) cases, respectively. The multivariable-adjusted HR for ever smoking compared with never smoking was 1.24 [95% CI: 0.93-1.66], 1.75 [1.14-2.68], 0.87 [0.59-1.29], 1.24 [0.93-1.67] and 1.22 [0.38-3.93] for overall, KRAS wild-type, KRAS-mutated, BRAF wild-type and BRAF-mutated colorectal cancer, respectively. The statistically significant heterogeneity was indicated between KRAS mutation status (Pheterogeneity = 0.01) but not between BRAF mutation status. This study is the first to demonstrate that smokers have an approximately 2-fold higher risk of KRAS wild-type colorectal cancer than never smokers in an Asian population. Our findings support that smoking is a risk factor for colorectal cancer, especially for its subtype without KRAS mutations, in Asian populations.

Outcomes With Peripheral Venoarterial Extracorporeal Membrane Oxygenation for Suspected Acute Myocarditis: 10-Year Experience From the Extracorporeal Life Support Organization Registry.

Acute myocarditis can result in severe hemodynamic compromise requiring venoarterial extracorporeal membrane oxygenation (VA-ECMO). Outcomes and factors associated with mortality among myocarditis patients are not well described in the modern ECMO era. We queried the Extracorporeal Life Support Organization registry from 2011 to 2020 for adults with suspected acute myocarditis undergoing peripheral VA-ECMO support. The primary outcome was in-hospital mortality and was compared to all-comers receiving VA-ECMO in the registry over the same period. Secondary outcomes were rates of bridging to advanced therapies and ECMO complications. We used multivariable logistic regression to examine factors associated with in-hospital mortality. Among 850 patients with suspected acute myocarditis receiving peripheral VA-ECMO, the mean age was 41 years, 52% were men, 39% Asian race, and 14.8% underwent extracorporeal cardiopulmonary resuscitation. During the study period, in-hospital mortality steadily declined and was 58.3% for all all-comers receiving VA-ECMO compared with 34.9% for patients with myocarditis (P<0.001). After multivariable modeling, risk factors for mortality were earlier year of support, older age, higher weight, Asian race, need for extracorporeal cardiopulmonary resuscitation, sepsis, and lower mean arterial pressure and pH prior to ECMO initiation. ECMO complications including bleeding, limb ischemia, infections and ischemic stroke were more common among nonsurvivors and significantly declined during the study period. Compared with all-comers supported with VA-ECMO, in-hospital mortality for patients with acute myocarditis is significantly lower, with nearly two-thirds of patients surviving to discharge. Major modifiable risk factors for mortality were ongoing cardiopulmonary resuscitation requiring ECMO and markers of illness severity prior to ECMO.

Alcohol Consumption and Measures of Sarcopenic Muscle Risk: Cross-Sectional and Prospective Associations Within the UK Biobank Study

Alcohol intake is a major modifiable risk factor for many diseases. Alcohol can also damage skeletal muscle health during ageing which in turn increases risk of sarcopenia, frailty and falls but this relationship is understudied. The aim of this study was to model the relationship between a full range of alcohol consumption and components of sarcopenic risk, skeletal muscle mass and function, in middle-aged and younger older-aged men and women. A cross-sectional analyses was undertaken of 196,561 white participants from the UK Biobank with longitudinal analysis also in 12,298 of these participants, with outcome measures for the latter repeated after around four years. For the cross-sectional analysis fractional polynomial curves were fitted in models of measures of skeletal muscle mass, appendicular lean mass/body mass index (ALM/BMI), fat-free mass as a percentage of body weight (FFM%) and grip strength, all predicted from alcohol consumption with models fitted for men and women separately. Alcohol consumption at baseline was based on the mean of up to five dietary recalls, typically over 16 months. Linear regression was used for longitudinal analyses to model the effects of alcohol consumption groups on these measures. All models were adjusted for covariates. In the cross-sectional analysis, modelled values of the muscle mass measures all showed a peak at medium levels of alcohol consumption and a steep decline with increasing alcohol consumption. Modelled differences in muscle mass from zero consumption of alcohol to 160 g/d ranged from 3.6 to 4.9% for ALM/BMI for men and women, respectively, and 3.6 to 6.1% for FFM%. Grip strength consistently increased with alcohol consumption. No association between alcohol consumption and muscle measures were seen in the longitudinal results. Our results suggest that higher levels of alcohol consumption could have detrimental effects on muscle mass in middle- and older-aged men and women.

Evaluation of transitions from early hypertension to hypertensive chronic kidney disease, coronary artery disease, stroke and mortality: a Thai real-world data cohort.

Systemic arterial hypertension (HT) is a major modifiable risk factor for cardiovascular disease (CVDs), associated with all-cause death (ACD). Understanding its progression from the early state to late complications should lead to more timely intensification of treatment. This study aimed to construct a real-world cohort profile of HT and to estimate transition probabilities from the uncomplicated state to any of these long-term complications; chronic kidney disease (CKD), coronary artery disease (CAD), stroke, and ACD. This real-world cohort study used routine clinical practice data for all adult patients diagnosed with HT in the Ramathibodi Hospital, Thailand from 2010 to 2022. A multi-state model was developed based on the following: state 1-uncomplicated HT, 2-CKD, 3-CAD, 4-stroke, and 5-ACD. Transition probabilities were estimated using Kaplan-Meier method. A total of 144,149 patients were initially classified as having uncomplicated HT. The transition probabilities (95% CI) from the initial state to CKD, CAD, stroke, and ACD at 10-years were 19.6% (19.3%, 20.0%), 18.2% (17.9%, 18.6%), 7.4% (7.1%, 7.6%), and 1.7% (1.5%, 1.8%), respectively. Once in the intermediate-states of CKD, CAD, and stroke, 10-year transition probabilities to death were 7.5% (6.8%, 8.4%), 9.0% (8.2%, 9.9%), and 10.8% (9.3%, 12.5%). In this 13-year cohort, CKD was observed as the most common complication, followed by CAD and stroke. Among these, stroke carried the highest risk of ACD, followed by CAD and CKD. These findings provide improved understanding of disease progression to guide appropriate prevention measures. Further investigations of prognostic factors and treatment effectiveness are warranted.

(Zu-)Hören mit alterndem Gehirn – eine kognitive Herausforderung

Hearing impairment has been recently identified as a major modifiable risk factor for cognitive decline in later life and has been becoming of increasing scientific interest. Sensory and cognitive decline are connected by complex bottom-up and top-down processes, a sharp distinction between sensation, perception, and cognition is impossible. This review provides a comprehensive overview on the effects of healthy and pathological aging on auditory as well as cognitive functioning on speech perception and comprehension, as well as specific auditory deficits in the 2 most common neurodegenerative diseases in old age: Alzheimer disease and Parkinson syndrome. Hypotheses linking hearing loss to cognitive decline are discussed, and current knowledge on the effect of hearing rehabilitation on cognitive functioning is presented. This article provides an overview of the complex relationship between hearing and cognition in old age.

Mendelian Randomization and Transcriptome-Wide Association Analysis Identified Genes That Were Pleiotropically Associated with Intraocular Pressure.

Intraocular pressure (IOP) is a major modifiable risk factor for glaucoma. However, the mechanisms underlying the controlling of IOP remain to be elucidated. To prioritize genes that are pleiotropically associated with IOP. We adopted a two-sample Mendelian randomization method, named summary-based Mendelian randomization (SMR), to examine the pleiotropic effect of gene expression on IOP. The SMR analyses were based on summarized data from a genome-wide association study (GWAS) on IOP. We conducted separate SMR analyses using Genotype-Tissue Expression (GTEx) and Consortium for the Architecture of Gene Expression (CAGE) expression quantitative trait loci (eQTL) data. Additionally, we performed a transcriptome-wide association study (TWAS) to identify genes whose cis-regulated expression levels were associated with IOP. We identified 19 and 25 genes showing pleiotropic association with IOP using the GTEx and CAGE eQTL data, respectively. RP11-259G18.3 (PSMR = 2.66 × 10-6), KANSL1-AS1 (PSMR = 2.78 × 10-6), and RP11-259G18.2 (PSMR = 2.91 × 10-6) were the top three genes using the GTEx eQTL data. LRRC37A4 (PSMR = 1.19 × 10-5), MGC57346 (PSMR = 1.19 × 10-5), and RNF167 (PSMR = 1.53 × 10-5) were the top three genes using the CAGE eQTL data. Most of the identified genes were found in or near the 17q21.31 genomic region. Additionally, our TWAS analysis identified 18 significant genes whose expression was associated with IOP. Of these, 12 and 4 were also identified by the SMR analysis using the GTEx and CAGE eQTL data, respectively. Our findings suggest that the 17q21.31 genomic region may play a critical role in the regulation of IOP.

Role of Hypertension and Obesity as Risk Factors for IHD

Background: Hypertension and obesity are two major modifiable risk factors for CAD, most of the time there will be more than two risk factors in an IHD. Obesity itself cause insulin resistance to initiate type -2 DM. is the most common and significant RFs for IHD, and proper BP management is the cornerstone of both direct and indirect prevention. Overweight and obesity account for more than 80% of CHD patients. Obesity is sometimes viewed as a "minor" CHD RF; however, it is a widely effective risk-factor approach. A range of "major" risk factors have been proven to be significantly influenced by weight loss, including HTN, hyperlipidemia and insulin resistance/T2DM. Aim: To assess arterial hypertension and obesity as risk factors of IHD. Methods: This cross-sectional study which was done retrospectively by collecting data from database of "Scientific Research Institute of Cardiology and Internal Diseases" Almaty city, Kazakhstan during 2020. IHD confirmed by history, physical exam, angiography and other lab findings. Result: The research involved a total of 649 participants. The mean age of study population was 64.2±9.24 (P = 0,000). Mean of SBP and DBP were 180.73±34.9; 99.48±14.28 mmHg respectively. Number of females with normal BMI 50(21.6%), overweight 93(40.10%), obesity class – 1, 59(25.4%), obesity class – 2, 23(9.90%) and obesity class – 3, 7(3%), (P = 0.486). Number of males with underweight BMI 1(0.20%), normal BMI 96(23%), overweight 190(45.6%), obesity class – 1, 89(21.3%), obesity class – 2, 29(7%) and obesity class – 3, 12(2.9%). (P = 0.486). The Mean BMI in both genders was (28.72±11.79). Conclusion: The burden of CVDs and their related risk factors are significant in Almaty, posing a major public health concern. For accurate management and implementation of preventive measures in this area, effective strategies in management, education, and healthcare centers are needed.