Potential Modifiable Risk Factors Research Articles

Sleep disturbance predicts worse cognitive performance in subsequent years: A longitudinal population-based cohort study

BackgroundPoor sleep is a potential modifiable risk factor for later life development cognitive impairment. The aim of this study is to examine if subjective measures of sleep duration and sleep disturbance predict future cognitive decline in a population-based cohort of 60, 66, 72 and 78-year-olds with a maximal follow up time of 18 years. MethodsThis study included participants from the Swedish National Study on Ageing and Care – Blekinge, with assessments 2001–2021. A cohort of 60 (n = 478), 66 (n = 623), 72 (n = 662) and 78 (n = 548) year-olds, were assessed at baseline and every 6 years until 78 years of age. Longitudinal associations between sleep disturbance (sleep scale), self-reported sleep duration and cognitive tests (Mini Mental State Examination and the Clock drawing test) were examined together with typical confounders (sex, education level, hypertension, hyperlipidemia, smoking status, physical inactivity and depression). ResultsThere was an association between sleep disturbance at age 60 and worse cognitive function at ages 60, 66 and 72 years in fully adjusted models. The association was attenuated after bootstrap-analysis for the 72-year-olds. The items of the sleep scale most predictive of later life cognition regarded nightly awakenings, pain and itching and daytime naps. Long sleep was predictive of future worse cognitive function. ConclusionSleep disturbance was associated with worse future cognitive performance for the 60-year-olds, which suggests poor sleep being a risk factor for later life cognitive decline. Questions regarding long sleep, waking during the night, pain and itching and daytime naps should be further explored in future research and may be targets for intervention.

Association between hearing loss and development of dementia using formal behavioural audiometric testing within the Mayo Clinic Study of Aging (MCSA): a prospective population-based study

Hearing loss has been identified as a potential major modifiable risk factor for developing dementia. This study examined associations between formal behavioural pure-tone and speech audiometry assessed by an audiologist with development of dementia in the Mayo Clinic Study of Aging (MCSA). The MCSA is a prospective population-based study examining the incidence, prevalence, and risk factors of mild cognitive impairment and dementia in Olmsted County, Minnesota, USA. Participants undergo clinical examinations with neuropsychological testing at enrolment and every 15 months. Participants were 50 years or older at enrolment between Nov 29, 2004, and Dec 23, 2019, who underwent formal behavioural audiometric evaluation by an audiologist due to concerns about hearing loss or as a part of annual comprehensive health assessments. Associations of pure-tone average (PTA) and word recognition scores (WRS) with the development of dementia were evaluated using Cox proportional hazards regression with age as the timescale, and associations with changes in cognitive testing scores over time were evaluated using linear mixed-effects models. Among 1200 eligible participants, the mean age at enrolment was 79 years (SD 9), 593 (49%) were men, and 207 developed dementia during a mean of 7·0 years (SD 3·7) of follow-up. After adjusting for sex, years of education, smoking status, diabetes, hypertension, apolipoprotein E ε4 carriership, and hearing rehabilitation (defined as hearing aid or cochlear implant use), neither PTA (hazard ratio [HR] per 10-decibels hearing level increase of 0·99 (95% CI 0·89-1·12; p=0·91) nor WRS (HR per 10% decrease of 0·98, 95% CI 0·89-1 ·07; p=0·65) was significantly associated with the development of dementia. However, both PTA and WRS were significantly associated with poorer performance in cognitive testing over time: participants with a PTA higher than 25 decibels hearing level or a WRS lower than 100% had significantly worse declines in cognitive testing scores. Informant-based hearing difficulties assessed by the participant's study partner were significantly associated with the development of dementia (HR 1·95, 95% CI 1·45-2·62; p<0·0001). In this prospective population-based study, subjective informant-based hearing difficulties were associated with development of dementia, whereas objective measures on formal behavioural audiometry were predictive of poorer performance on cognitive testing over time but not the development of dementia. Other factors related to central processing might potentiate the effects of peripheral hearing loss detected on behavioural audiometric testing. National Institute of Health, the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Clinic, the GHR Foundation, the Mayo Foundation for Medical Education and Research, the Liston Award, the Schuler Foundation, the Rochester Epidemiology Project medical records linkage system, and the National Institute on Aging.

O035 Elevated liver enzymes in paediatric sleep disordered breathing

Abstract Introduction Paediatric sleep disordered breathing (SDB) is associated with adverse cardiovascular outcomes. Non-alcoholic fatty liver disease (NAFLD) and dyslipidaemia are potential modifiable risk factors for cardiovascular disease, often coexisting in adults with SDB. Increases in lipid outputs from the liver have been identified in obese adults and children with SDB. Whether children with SDB compared to healthy non-snoring controls have evidence of elevated serum lipids and associated liver enzyme changes were assessed. Methods Seventy-five children (SDB=49, controls=26) between the ages of 6-17 years matched for age, gender and BMI underwent overnight polysomnography to measure SDB severity and provided a fasting blood sample to assess lipid and liver panels. Results OAHI was significantly increased in children with SDB compared to healthy non-snoring controls (p &amp;lt; 0.05). Serum potassium, alanine aminotransferase and lactate dehydrogenase were significantly increased in children with SDB, while albumin was significantly decreased (p &amp;lt; 0.05). No differences were found between serum lipid levels. Conclusion The presence of paediatric SDB may increase the risk of developing NAFLD. Further investigation is required to determine whether routine assessment of liver enzymes should be implemented in paediatric SDB. Whether surgical removal of the adenoids and tonsils to treat paediatric SDB can stabilise liver enzyme levels requires further research.

Clinical Application of Gait Retraining in the Injured Runner.

Despite its positive influence on physical and mental wellbeing, running is associated with a high incidence of musculoskeletal injury. Potential modifiable risk factors for running-related injury have been identified, including running biomechanics. Gait retraining is used to address these biomechanical risk factors in injured runners. While recent systematic reviews of biomechanical risk factors for running-related injury and gait retraining have been conducted, there is a lack of information surrounding the translation of gait retraining for injured runners into clinical settings. Gait retraining studies in patients with patellofemoral pain syndrome have shown a decrease in pain and increase in functionality through increasing cadence, decreasing hip adduction, transitioning to a non-rearfoot strike pattern, increasing forward trunk lean, or a combination of some of these techniques. This literature suggests that gait retraining could be applied to the treatment of other injuries in runners, although there is limited evidence to support this specific to other running-related injuries. Components of successful gait retraining to treat injured runners with running-related injuries are presented.

Suboptimal coronary flow after PCI in STEMI patients: clinical implications and predictors

Abstract Background Even in experienced angioplasty centers, percutaneous coronary intervention (PCI) in the acute setting of ST-elevation myocardial infarctions (STEMI) is associated with a low, but still significant rate of suboptimal coronary flow. Identification of its clinical impact and potential modifiable risk factors is important. Purpose To evaluate the clinical impact of suboptimal coronary flow after PCI in STEMI patients and to access potential predictors of suboptimal coronary flow. Methods We retrospectively evaluated 103 hospitalized patients with acute STEMI who were admitted to our center between 2018 and 2019 and underwent PCI. Coronary flow was accessed using the Thrombolysis in myocardial infarction (TIMI) Flow Grading System. Patients were divided into suboptimal patency of the culprit-vessel, defined as TIMI flow ≤2 (group 1, n=8 (7,8%)) and optimal patency of the culprit-vessel defined as TIMI flow 3 (group 2, n=95 (92,2%)). Glomerular filtration rate (GFR) was calculated using the Modification of Diet in Renal Disease (MDRD) formula. Results Mean age 58,15±12,6 years and 85,4% were males. Seventy-eight patients (75,7%) had history of smoking, 45 (43,7%) dyslipidemia, 20 (19,4%) previous acute coronary syndrome, 18 (17,5%) diabetes, 17 (15,5%) were obese and 4 (3,9%) had chronic kidney disease. The revascularization strategy was primary PCI in 55 (54,4%) patients and fibrinolytic therapy with facilitated PCI in 48 (46,6%) patients. Infarct-related artery was the left anterior descending artery in 45 (45,5%) and multivessel disease was present in 38 (38,0%). Angiographic no-reflow after PCI was 3,0%. Intrahospital cardiovascular death occurred in 4 (3,9%) patients and was significantly associated with suboptimal flow (p=0,036) and there was no association with stent thrombosis. Predictors of suboptimal flow were higher blood urea nitrogen, creatinine and GFR at hospital admission (p=0,017 and p=0,012), peak creatinine (p=0,012) and stent length (p=0,038). Suboptimal flow was associated with higher Zwolle score (p=0,010) and ischemic Paris score (p=0,036). Conclusion Failure to achieve optimal culprit-vessel patency after PCI in STEMI patients, although infrequent, is associated with increased hospital cardiovascular death. Longer stents could be and important modified risk factor. Renal dysfunction is an important comorbidity that should be promptly identified and could be partially improved with medical treatment. Funding Acknowledgement Type of funding sources: None.

Healthy dietary indices and noncancer pain: a systematic review of cross-sectional and longitudinal studies.

Pain is a global public health problem given its high prevalence and incidence, long duration, and social and economic impact. There is growing interest in nutrition as potential modifiable risk factor related to pain; however, the associations between healthy dietary patterns and pain have not yet been well established. Thus, we aimed to systematically review and synthesise current cross-sectional and longitudinal evidence on the relationship between a priori healthy dietary patterns and noncancer pain among adults aged ≥18 years. We identified relevant published cross-sectional and longitudinal studies by systematically searching several electronic databases from inception to September 2021. Risk of bias was assessed using the modified Newcastle-Ottawa scale for cohort studies. A total of 14 cross-sectional and 6 longitudinal studies were included in the review. These studies measured different dietary scores/indices, such as different measures of adherence to the Mediterranean diet and the dietary inflammatory index. Pain ascertainment methods and pain measurements used differed across studies. All 20 of the included studies had different study designs and statistical analysis. Of these studies, 10 reported an inverse association between adherence to a healthy dietary pattern and pain, 5 reported mixed results, and 5 reported no associations. Despite notable heterogeneity, 50% of included observational studies reported that adherence to a healthy diet, particularly the Mediterranean diet, is inversely associated with pain. Of note, the cross-sectional design of most studies precludes any causal interpretation. Moreover, limited and inconsistent evidence from longitudinal studies highlights the need for further studies.

Seasonality of Hashimoto Thyroiditis: Infodemiology Study of Google Trends Data

Background Hashimoto thyroiditis (HT) is an autoimmune thyroid disease and the leading cause of hypothyroidism in areas with sufficient iodine intake. The quality-of-life impact and financial burden of hypothyroidism and HT highlight the need for additional research investigating the disease etiology with the aim of revealing potential modifiable risk factors. Objective Implementation of measures against such risk factors, once identified, has the potential to lessen the financial burden while also improving the quality of life of many individuals. Therefore, we aimed to examine the potential seasonality of HT in Europe using the Google Trends data to explore whether there is a seasonal characteristic of Google searches regarding HT, examine the potential impact of the countries’ geographic location on the potential seasonality, and identify potential modifiable risk factors for HT, thereby inspiring future research on the topic. Methods Monthly Google Trends data on the search topic “Hashimoto thyroiditis” were retrieved in a 17-year time frame from January 2004 to December 2020 for 36 European countries. A cosinor model analysis was conducted to evaluate potential seasonality. Simple linear regression was used to estimate the potential effect of latitude and longitude on seasonal amplitude and phase of the model outputs. Results Of 36 included European countries, significant seasonality was observed in 30 (83%) countries. Most phase peaks occurred in spring (14/30, 46.7%) and winter (8/30, 26.7%). A statistically significant effect was observed regarding the effect of geographical latitude on cosinor model amplitude (y = –3.23 + 0.13 x; R2=0.29; P=.002). Seasonal increases in HT search volume may therefore be a consequence of an increased incidence or higher disease activity. It is particularly interesting that in most countries, a seasonal peak occurred in spring and winter months; when viewed in the context of the statistically significant impact of geographical latitude on seasonality amplitude, this may indicate the potential role of vitamin D levels in the seasonality of HT. Conclusions Significant seasonality of HT Google Trends search volume was observed in our study, with seasonal peaks in most countries occurring in spring and winter and with a significant impact of latitude on seasonality amplitude. Further studies on the topic of seasonality in HT and factors impacting it are required.

Meta-Analysis and Validation of a Colorectal Cancer Risk Prediction Model Using Deep Sequenced Fecal Metagenomes.

Simple SummaryColorectal cancer (CRC) is the third most common cancer in the world. The gut microbiome, which includes a collection of microbes, is a potential modifiable risk factor. The study of the microbiome is complex and many issues remain unsolved despite the scientific efforts that have been recently made. The present study aimed to build a CRC predictive model performing a meta-analyses of previously published shotgun metagenomics data, and to validate it in a new study. For that purpose, 156 participants of a CRC screening program were recruited, with an even distribution of CRCs, high-risk colonic precancerous lesions, and a control group with normal colonic mucosa. We have identified a signature of 32 bacterial species that have a good predictive accuracy to identify CRC but not precancerous lesions. This suggests that the identified microbes that were enriched or depleted in CRC are merely a consequence of the tumor. The gut microbiome is a potential modifiable risk factor for colorectal cancer (CRC). We re-analyzed all eight previously published stool sequencing data and conducted an MWAS meta-analysis. We used cross-validated LASSO predictive models to identify a microbiome signature for predicting the risk of CRC and precancerous lesions. These models were validated in a new study, Colorectal Cancer Screening (COLSCREEN), including 156 participants that were recruited in a CRC screening context. The MWAS meta-analysis identified 95 bacterial species that were statistically significantly associated with CRC (FDR < 0.05). The LASSO CRC predictive model obtained an area under the receiver operating characteristic curve (aROC) of 0.81 (95%CI: 0.78–0.83) and the validation in the COLSCREEN dataset was 0.75 (95%CI: 0.66–0.84). This model selected a total of 32 species. The aROC of this CRC-trained model to predict precancerous lesions was 0.52 (95%CI: 0.41–0.63). We have identified a signature of 32 bacterial species that have a good predictive accuracy to identify CRC but not precancerous lesions, suggesting that the identified microbes that were enriched or depleted in CRC are merely a consequence of the tumor. Further studies should focus on CRC as well as precancerous lesions with the intent to implement a microbiome signature in CRC screening programs.

Diet, Gut Microbiome, and Cognitive Decline.

An epidemic of age-associated cognitive decline, most commonly ascribed to neurodegenerative conditions such as Alzheimer's and Parkinson's disease, is causing healthcare costs to soar and devastating caregivers. An estimated 6.5 million Americans are living today with Alzheimer's disease, with 13.8 million cases projected by mid-century. Although genetic mutations are known to cause neurodegeneration, autosomal dominant disease is very rare and most sporadic cases can be attributed, at least in part, to modifiable risk factors. Diet is a potential modifiable risk factor in cognitive decline. Food communicates with the brain through a complex signaling web involving multiple cells, mediators and receptors. Gut-brain communication is modulated by microorganisms including bacteria, archaea, viruses, and unicellular eukaryotes, which together constitute the microbiota. Microbes not only play major roles in the digestion and fermentation of the food, providing nutrients and bioactive metabolites, but also reflect the type and amount of food consumed and food-borne toxic exposures. Food components modify the diversity and abundance of the microbial populations, maintain the integrity of the gut barrier, and regulate the passage of microbes and their metabolites into the blood stream where they modulate the immune system and communicate with body systems including the brain. This paper will focus on selected mechanisms through which interactions between diet and the gut microbiota can modify brain integrity and cognitive function with emphasis on the pathogenesis of the most common dementia, Alzheimer's disease.

Neurological Manifestations of SARS-CoV-2 Infection: Protocol for a Sub-analysis of the COVID-19 Critical Care Consortium Observational Study.

IntroductionNeurological manifestations and complications in coronavirus disease-2019 (COVID-19) patients are frequent. Prior studies suggested a possible association between neurological complications and fatal outcome, as well as the existence of potential modifiable risk factors associated to their occurrence. Therefore, more information is needed regarding the incidence and type of neurological complications, risk factors, and associated outcomes in COVID-19.MethodsThis is a pre-planned secondary analysis of the international multicenter observational study of the COVID-19 Critical Care Consortium (which collected data both retrospectively and prospectively from the beginning of COVID-19 pandemic) with the aim to describe neurological complications in critically ill COVID-19 patients and to assess the associated risk factors, and outcomes. Adult patients with confirmed COVID-19, admitted to Intensive Care Unit (ICU) will be considered for this analysis. Data collected in the COVID-19 Critical Care Consortium study includes patients' pre-admission characteristics, comorbidities, severity status, and type and severity of neurological complications. In-hospital mortality and neurological outcome were collected at discharge from ICU, and at 28-days.Ethics and DisseminationThe COVID-19 Critical Care Consortium main study and its amendments have been approved by the Regional Ethics Committee of participating sites. No further approval is required for this secondary analysis.Trial Registration NumberACTRN12620000421932.

Diet and risk of Barrett's oesophagus: Melbourne collaborative cohort study.

Barrett's oesophagus (BE) is the precursor of oesophageal adenocarcinoma, which has become the most common type of oesophageal cancer in many Western populations. Existing evidence on diet and risk of BE predominantly comes from case-control studies, which are subject to recall bias in measurement of diet. We aimed to investigate the potential effect of diet, including macronutrients, carotenoids, food groups, specific food items, beverages and dietary scores, on risk of BE in over 20000 participants of the Melbourne Collaborative Cohort Study. Diet at baseline (1990-1994) was measured using a food frequency questionnaire. The outcome was BE diagnosed between baseline and follow-up (2007-2010). Logistic regression models were used to estimate OR and 95 % CI for diet in relation to risk of BE. Intakes of leafy vegetables and fruit were inversely associated with risk of BE (highest v. lowest quartile: OR = 0·59; CI: 0·38, 0·94; P-trend = 0·02 and OR = 0·58; CI: 0·37, 0·93; P-trend = 0·02 respectively), as were dietary fibre and carotenoids. Stronger associations were observed for food than the nutrients found in them. Positive associations were observed for discretionary food (OR = 1·54; CI: 0·97, 2·44; P-trend = 0·04) and total fat intake (OR per 10 g/d = 1·11; CI: 1·00, 1·23), the association for fat was less robust in sensitivity analyses. No association was observed for meat, protein, dairy products or diet scores. Diet is a potential modifiable risk factor for BE. Public health and clinical guidelines that incorporate dietary recommendations could contribute to reduction in risk of BE and, thereby, oesophageal adenocarcinoma.

Diurnal variation of clock genes expression and other sleep-wake rhythm biomarkers among acute ischemic stroke patients

There is accumulating evidence about sleep-wake rhythm disturbances as potential modifiable risk factors of both incident and recurrent stroke and less favorable outcomes after stroke. To our best knowledge this is the first study designed to investigate clock genes expression profiles in ischemic stroke patients and their relations to other biological and behavioral sleep-wake rhythm biomarkers, sleep structural and clinical stroke features. Altogether, 27 ischemic stroke patients (20 males) with the median age of 56 years and 25 gender and age matched controls were investigated with neurological and objective examination, scales, polysomnography, actigraphy and 24-h blood sampling for melatonin and clock genes profiles. Median melatonin plasma concentrations at four time points at 7, 11 p.m., 3 a.m. and 12 p.m. did not differ significantly between patients and controls, only early morning melatonin concentration at 7 a.m. was significantly lower and cortisol plasma concentration - significantly higher among stroke patients. All four clock genes (ARNTL (BMAL1), NR1D1 (Rev-erbα/β), PER1, and PER3) showed significant time-of-day variation in both patients' and controls’ groups, except expression of NR1D1 (Rev-erbα/β) at 7 a.m. and PER1 at 12 p.m. differed significantly. In conclusion, acute ischemic stroke patients tended to preserve most of diurnal variation of sleep-wake rhythm molecular patterns. Nevertheless, early morning time point showing higher cortisol and lower melatonin concentrations and lower NR1D1 (Rev-erbα/β) expression, as well as lower PER1 midday expression reflect specific circadian desynchrony features in different loops of the molecular circadian clock system.

Daycare Attendance is Linked to Increased Risk of Respiratory Morbidities in Children Born Preterm with Bronchopulmonary Dysplasia

To test the hypothesis that daycare attendance among children with bronchopulmonary dysplasia (BPD) is associated with increased chronic respiratory symptoms and/or greater health care use for respiratory illnesses during the first 3years of life. Daycare attendance and clinical outcomes were obtained via standardized instruments for 341 subjects recruited from 9 BPD specialty clinics in the US. All subjects were former infants born preterm (<34weeks) with BPD (71% severe) requiring outpatient follow-up between 0 and 3years of age. Mixed logistic regression models were used to test for associations. Children with BPD attending daycare were more likely to have emergency department visits and systemic steroid usage. Children in daycare up to 3years of age also were more likely to report trouble breathing, having activity limitations, and using rescue medications when compared with children not in daycare. More severe manifestations were found in children attending daycare between 6 and 12months of chronological age. In this study, children born preterm with BPD who attend daycare were more likely to visit the emergency department, use systemic steroids, and have chronic respiratory symptoms compared with children not in daycare, indicating that daycare may be a potential modifiable risk factor to minimize respiratory morbidities in children with BPD during the preschool years.

Application of the Amyloid/Tau/Neurodegeneration Framework in Cognitively Intact Adults: The CABLE Study.

The amyloid/tau/neurodegeneration (AT[N]) framework has conceptualized the Alzheimer's disease (AD) continuum as a continuum of disease with evidence of amyloid-related pathologies independent of clinical manifestation. Based on this framework, it is necessary to reveal the distribution and risk factors of AD continuum in the cognitively intact population among different cohorts and races, including the northern Chinese Han population. This study classified cognitively intact Chinese Alzheimer's Biomarker and LifestylE (CABLE) participants through the AT(N) scheme. Gaussian mixture models were used to identify the cutoff values of cerebrospinal fluid biomarkers, which distinguished AD continuum(A+T-N-,A+T+N-,A+T-N+andA+T+N+) from 1,005 participants (mean age 61 years; 40% female). Multivariable logistic regressions and Cochran-Armitage trend tests were used to test neuropsychological performance and risk factors for AD continuum. Approximately one-third of individuals (33.7%) belonged to the AD continuum. Four potential modifiable risk factors, including hypertension, thyroid diseases, social isolation, and minimal depression symptoms, were identified for the AD continuum (OR ranging 1.68-6.90). A trend toward higher prevalence of the AD continuum was associated with a larger number of risk factors (p for trend <0.0001). The risk of AD continuum increased by approximately twofold for each additional modifiable risk factor (OR 1.9, 95% CI 1.65-2.24, p < 0.0001). This study revealed the distribution and potential risk factors of the AD continuum in a cognitively intact Han population in northern China, which filled the gap in the area about the performance of the AT(N) framework in the Asian population. ANN NEUROL 2022;92:439-450.

Blood Pressure Variability and Cognitive Function: a Scoping Review.

To conduct a scoping review of articles which have evaluated BPV and cognitive function. Articles with keywords, titles or abstracts containing the terms 'cognitive' OR 'cognition' OR 'dementia' AND 'blood pressure variability' were identified from CINAHL, Medline, PMC and Web of Science. Methods of acquisition and analysis of BPV and cognitive measurements and their relationship were extracted from selected articles. Of 656 studies identified, 53 articles were selected. Twenty-five evaluated long-term (LTBPV), nine mid-term (MTBPV), 12 short-term (STBPV) and nine very short-term BPV (VSTBPV) with conflicting findings on the relationship between BPV and cognition. Variations existed in devices, period and procedure for acquisition. The studies also utilized a wide range of methods of BPV calculation. Thirteen cognitive assessment tools were used to measure global cognition or domain functions which were influenced by the population of interest. The interpretation of available studies was hence limited by heterogeneity. There is an urgent need for standardization of BPV assessments to streamline research on BPV and cognition. Future studies should also establish whether BPV could be a potential modifiable risk factor for cognitive decline, as well as a marker for treatment response.

Effect of age and sex on the associations between potential modifiable risk factors and both type 2 diabetes and impaired fasting glycaemia among West African adults

BackgroundType 2 diabetes mellitus (T2DM) is becoming one of the leading causes of morbidity and mortality worldwide, including among Africans. Knowledge of the association between traditional risk factors and both diabetes and pre-diabetes, and whether these differ by age and sex, is important for designing targeted interventions. However, little is known about these associations for African populations.MethodsThe study used data from WHO STEPS surveys, comprising 15,520 participants (6,774 men and 8,746 women) aged 25–64 years, from 5 different West African countries, namely Burkina Faso (4,711), Benin (3,816), Mali (1,772), Liberia (2,594), and Ghana (2,662). T-test and chi-square tests were used to compare differences in the prevalence of traditional risk factors for both sexes. Multinomial logistic regression was conducted to ascertain the relative risks (RR) and 95% confidence intervals (CI) for both T2DM and impaired fasting glucose (IFG) relating to each risk factor, including obesity [defined by BMI, waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR)], high blood pressure (HBP), fruit and vegetable consumption, physical inactivity, alcohol consumption, and smoking. Models for each of these traditional risk factors and interactions with age and sex were fitted.ResultsFactors associated with T2DM and IFG were age, obesity [defined by BMI, WC, WHtR, and WHR], HBP, smoking, physical inactivity, and fruit and vegetable consumption (p < 0.05). Analysis of interaction effects showed few significant differences in associations between risk factors and T2DM according to age or sex. Significant interaction with age was observed for HBP*age and T2DM [RR; 1.20, 95% CI: (1.01, 1.42)) (p = 0.04)], WHtR*age and T2DM [RR; 1.23, 95% CI: (1.06, 1.44) (p = 0.007)] and WHR*age and IFG [RR: 0.79, 95% CI: (0.67, 0.94) (p = 0.006)]. Some interactions with age and sex were observed for the association of alcohol consumption and both IFG and T2DM, but no clear patterns were observed.ConclusionThe study found that with very few exceptions, associations between traditional risk factors examined and both IFG and T2DM did not vary by age or sex among the West African population. Policies and public health intervention strategies for the prevention of T2DM and IFG should target adults of any age or sex in West Africa.

Obstructive Sleep Apnea in Heart Failure: Current Knowledge and Future Directions.

Obstructive sleep apnea (OSA) is highly prevalent among patients with asymptomatic left ventricular systolic and diastolic dysfunction and congestive heart failure, and if untreated may contribute to the clinical progression of heart failure (HF). Given the health and economic burden of HF, identifying potential modifiable risk factors such as OSA and whether appropriate treatment improves outcomes is of critical importance. Identifying the subgroups of patients with OSA and HF who would benefit most from OSA treatment is another important point. This focused review surveys current knowledge of OSA and HF in order to provide: (1) a better understanding of the pathophysiologic mechanisms that may increase morbidity among individuals with HF and comorbid OSA, (2) a summary of current observational data and small randomized trials, (3) an understanding of the limitations of current larger randomized controlled trials, and (4) future needs to more accurately determine the efficacy of OSA treatment among individuals with HF.

Genetic Determinants of Body Mass Index and Fasting Glucose Are Mediators of Grade 1 Diastolic Dysfunction.

BackgroundEarly (grade 1) cardiac left ventricular diastolic dysfunction (G1DD) increases the risk for heart failure with preserved ejection fraction and may improve with aggressive risk factor modification. Type 2 diabetes, obesity, hypertension, and coronary heart disease are associated with increased incidence of diastolic dysfunction. The genetic drivers of G1DD are not defined.Methods and ResultsWe curated genotyped European ancestry G1DD cases (n=668) and controls with normal diastolic function (n=1772) from Vanderbilt’s biobank. G1DD status was explored through (1) an additive model genome‐wide association study, (2) shared polygenic risk through logistic regression, and (3) instrumental variable analysis using 2‐sample Mendelian randomization (the inverse‐variance weighted method, Mendelian randomization‐Egger, and median) to determine potential modifiable risk factors. There were no common single nucleotide polymorphisms significantly associated with G1DD status. A polygenic risk score for BMI was significantly associated with increased G1DD risk (odds ratio [OR], 1.20 for 1‐SD increase in BMI [95% CI, 1.08–1.32]; P=0.0003). The association was confirmed by the inverse‐variance weighted method (OR, 1.89 [95% CI, 1.37–2.61]). Among the candidate mediators for BMI, only fasting glucose was significantly associated with G1DD status by the inverse‐variance weighted method (OR, 4.14 for 1‐SD increase in fasting glucose [95% CI, 1.55–11.02]; P=0.005). Multivariable Mendelian randomization showed a modest attenuation of the BMI association (OR, 1.84 [95% CI, 1.35–2.52]) when adjusting for fasting glucose.ConclusionsThese data suggest that a genetic predisposition to elevated BMI increases the risk for G1DD. Part of this effect may be mediated through altered glucose homeostasis.

Modifiable and non-modifiable risk factors associated with early-onset colorectal cancer: Analysis of the National Health Interview Survey.

e15528 Background: The incidence of early-onset colorectal cancer (EO-CRC), colorectal cancer (CRC) diagnosed in individuals younger than 50 years, is rapidly increasing in the United States. However, risk factors for EO-CRC are poorly understood. Identifying potential risk factors using population-based health data is critical to identify at-risk populations and develop cost-effective screening guidelines and other prevention strategies. This study aimed to identify potential modifiable and non-modifiable risk factors associated with EO-CRC. Methods: This cross-sectional study used data from 2004-2018 National Health Interview Survey (NHIS), a nationally representative health information of US population collected through personal household interviews. Individuals who were at an age of 18-49 years and had a history of CRC diagnosis at the time of the interview were identified as patients with EO-CRC, and their demographic, clinical, and behavioral characteristics were compared with those of non-cancer young adult (18-49 years) population. In addition, their non-age-related characteristics (gender, race/ethnicity, region, and body mass index [BMI]) were compared with those of individuals who were diagnosed with CRC at age 50 or older (late-onset CRC; LO-CRC). For both comparisons, bivariate and multivariable logistic regression (proc surveylogistic) analyses were performed. Results: We identified 156 patients with EO-CRC (weighted: 105,300; 46.4% female; mean age = 41.8 [SE = 0.69]), 204,846 with non-cancer (weighted: 126,257,662; 50.7% female; mean age = 33.6 [SE = 0.05]), and 1,972 with LO-CRC (weighted: 920,231; 48.6% female; mean age = 72.6 [SE = 0.28]). Results from the comparison between patients with EO-CRC and non-cancer population showed that higher odds of having EO-CRC were associated with older age (Odds Ratio [OR] = 1.11; 95% CI = 1.08–1.14), living in Midwest (vs. South; OR = 1.64, 95% CI = 1.06 – 2.55), and history of alcohol consumption (vs. lifetime abstainer; OR = 2.09, 95% CI = 1.01 – 4.36). Lower odds of having EO-CRC were associated with being Hispanic or Asian (vs. non-Hispanic White; OR = 0.43, 95% CI = 0.22 – 0.84 and OR = 0.38, 95% CI = 0.16 – 0.92, respectively) and doing vigorous physical activity (vs. no activity; OR = 0.34; 95% CI = 0.21 – 0.55). Gender, BMI, diabetes, and smoking were not significantly different between the two groups. Compared with patients with LO-CRC, those with EO-CRC were more likely to be Hispanic (vs. non-Hispanic White; OR = 2.21, 95% CI = 1.14 – 4.31) and live in Midwest (vs. South; OR = 1.62, 95% CI = 1.02 – 2.58). Gender and BMI were not significantly different between the two groups. Conclusions: In this cross-sectional population-based study, we identified potential modifiable (alcohol consumption and physical activity) and non-modifiable (age, race/ethnicity, and region) risk factors associated with EO-CRC.

Association Between Sugar-Sweetened Beverage Intake and Liver Cancer Risk in the Women’s Health Initiative

ObjectivesIntake of sugar-sweetened beverage (SSB), a postulated risk factor for obesity, diabetes, and cardiovascular disease, may drive insulin resistance and inflammation which are strongly implicated in liver carcinogenesis. However, evidence on the association between SSB intake and liver cancer is scarce. We hypothesized that higher SSB intake would be associated with a greater risk of liver cancer. MethodsWe included 90,504 women aged 50–79 years from the Women’s Health Initiative Observational Study and Clinical Trials excluding Dietary Modification Trial participants. SSB intake was defined as the sum of soft drinks and fruit drinks (1 serving = one 12 fl. oz can or 355 ml), which was assessed by a validated food frequency questionnaire administered at baseline between 1993 and 1998. Incident liver cancers were reported by self-administered questionnaires and further confirmed by medical record review. Cox proportional hazards regression models were used to estimate multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for age, race and ethnicity, education, alcohol intake, smoking status, body mass index, non-steroidal anti-inflammatory drug use, physical activity, total caloric intake, and history of diabetes. ResultsAfter a median of 18.7 years follow-up, 205 women had confirmed liver cancer. Approximately 7.3% of women consumed ≥ 1 serving/day of SSB. Higher SSB intake was associated with a 78% greater risk of liver cancer (HR ≥1/day vs never to < 3/month = 1.78, 95%CI = 1.09–2.95, P linear trend = 0.007) as compared to intake of < 3 servings/month. Non-statistically significant positive associations with liver cancer were observed for fruit drinks (HR ≥1/day vs never to < 3/month = 1.55, 95%CI = 0.88–2.75) and soft drinks (HR ≥1/day vs never to < 3/month = 1.73, 95%CI = 0.76–3.94). Results were similar after further adjustment for coffee/tea intake, or history of liver diseases, or when liver cancer cases diagnosed within the first 2 years of follow-up or those with history of diabetes were excluded. ConclusionsOur findings suggest SSB as a potential modifiable risk factor for liver cancer in postmenopausal women. Studies in men and diverse populations are needed to examine these associations more comprehensively. Funding SourcesThe WHI study is funded by the National Institute of Health.