Association Of Modifiable Risk Factors Research Articles

Prevalence of Obesity with its Associated Modifiable Risk Factors among Adolescents of Aged 17-24 Years: Cross-Sectional Study

Objective: This study aims to point out the association of modifiable risk factors and the prevalence and riskfactors of overweight and obesity among adolescents aged 17-24 years.Study Design: Cross-sectional descriptive study.Place and Duration of Study: The study was conducted at the Department of Community Medicine, CombinedMilitary Hospital (CMH) College Lahore, Pakistan from April 2022 to May 2022.Methods: A cross-sectional study was performed on a sample size of 108 adult males through nonprobabilityconvenient sampling in CMH Lahore Medical College, Lahore, Pakistan. HbA1c tests were conducted to checkblood sugar. A questionnaire was distributed to collect data. SPSS software was used for the analysis of datausing the Chi-square test.Results: A total of 108 male cadets participated in the study. Mean age was 20.20 years ±1.4 SD. The majority ofparticipants were involved in physical activity and had healthy eating habits. Eighty-nine percent ofrespondents fall in the category of normal body mass index & 6.5% in the category of overweight & obese & 3.7% were underweight. Forty-seven percent of subjects were physically active for ≤ 3 days/week & 57.4% wereengaged for > 3 days/week. Fifty-seven percent of respondents had a screen time of 5-7 hours/day & 11.1% has> 7 hours/day. Among 108 respondents, 37% had snacking habits in between meals 1-2 times/week & 20.4%has 3-4 times/week.Conclusion: This study concludes that apart from non-modifiable risk factors, modifiable risk factors also have a major influence on the prevalence of overweight & obesity. Those who exercise & eat healthy have less risk ofdeveloping obesity as compared to those who have poor physical activity & unhealthy eating habits. How to cite this: Zaib S, Raza T, Ahmad A, Anwar S, Tariq SMH, Mubashar T. Prevalence of Obesity with its Associated Modifiable Risk Factors Among Adolescents of Aged 17-24 Years: Cross Sectional Study. Life and Science. 2024; 5(2): 210-215. doi: http://doi.org/10.37185/LnS.1.1.362

The "Hit and Run" Hypothesis for Alzheimer's Disease Pathogenesis.

Alzheimer's disease (AD) is a devastating neurodegenerative disorder affecting millions worldwide. Emerging research has challenged the conventional notion of a direct correlation between amyloid deposition and neurodegeneration in AD. Recent studies have suggested that amyloid and Tau deposition act as a central nervous system (CNS) innate immune driver event, inducing chronic microglial activation that increases the susceptibility of the AD brain to the neurotoxicity of infectious insults. Although modifiable risk factors account for up to 50% of AD risk, the mechanisms by which they interact with the core process of misfolded protein deposition and neuroinflammation in AD are unclear and require further investigation. This update introduces a novel perspective, suggesting that modifiable risk factors act as external insults that, akin to infectious agents, cause neurodegeneration by inducing recurrent acute neurotoxic microglial activation. This pathological damage occurs in AD pathology-primed regions, creating a "hit and run" mechanism that leaves no discernible pathological trace of the external insult. This model, highlighting microglia as a pivotal player in risk factor-mediated neurodegeneration, offers a new point of view on the complex associations of modifiable risk factors and proteinopathy in AD pathogenesis, which may act in parallel to the thoroughly studied amyloid-driven Tau pathology, and strengthens the therapeutic rationale of combining immune modulation with tight control of risk factor-driven insults.

Association of modifiable risk factors with obstructive sleep apnea: a Mendelian randomization study.

The risk factors involved in obstructive sleep apnea (OSA) have not been clearly identified yet. We attempted to systematically investigate genetically predicted modifiable risk factors and lifestyle behaviors associated with OSA. The association between 34 risk factors and OSA was evaluated using the two-sample Mendelian randomization (MR). Genetic variants for risk factors were acquired from European-descent genome-wide studies. Data sources for OSA were extracted from FinnGen study with 16,761 cases and 201,194 controls. The primary analysis chosen was the inverse-variance weighted method. MR analyses provide evidence of genetically predicted poor overall health rating (odds ratio (OR), 2.82; 95% confidence interval (CI), 1.95-4.08), nap during day (OR, 2.01; 95% CI, 1.37-2.93), high body mass index (BMI) (OR, 1.14; 95% CI, 1.09-1.19), increased body fat mass (OR, 1.83; 95% CI, 1.83-2.05), elevated body water mass (OR, 1.50; 95% CI, 1.31-1.70) and hypertension (OR, 1.81; 95% CI, 1.34-2.45) were associated with higher OSA risk, while high education level (OR, 0.55; 95% CI, 0.40-0.75) correlated with reduced OSA risk. Suggestive evidence was obtained for smoking and waist-to-hip ratio (WHR) with higher OSA odds, and vigorous physical activity, and HDL cholesterol with lower OSA odds. After adjusting for BMI using multivariable MR analysis, the effects of smoking, WHR, vigorous physical activity, and HDL-cholesterol were fully attenuated. This MR study indicates that overall health rating, nap during day, BMI, body fat mass, body water mass, hypertension, and education are causally associated with the risk of OSA, which means that these modifiable risk factors are key targets for OSA prevention.

Sex-related association of modifiable risk factors with hypertension: A national cross-sectional study of NHANES 2007-2018.

Sex difference is commonly observed in hypertension. We aimed to assess sex differences in the associations of modifiable lifestyle and metabolic risk factors with risk of hypertension. National cross-sectional population study. Data from the 2007 to 2018 National Health and Nutrition Examination Survey. 7087 adults aged ≥30 years without a prior history of hypertension. Odds ratios and population attributable fraction (PAF) of hypertension associated with 10 modifiable risk factors: five lifestyle risk factors (current smoking, excess alcohol intake, poor diet, physical inactivity, and unhealthy sleep), and five metabolic risk factors (obesity, diabetes, dyslipidaemia, hyperuricemia, and chronic kidney disease) in women versus men. Compared with women, men had 84% increased risk of prevalence of hypertension. The sex difference in risk for hypertension is more evident in those aged <60 years (p for interaction <.001). For those aged <60 years the combination of lifestyle risk factors accounted for a PAF of 27.2% in men and 48.8% in women, and the combination of metabolic risk factors accounted for a PAF similarly in men (37.4%) and women (38.2%). For those aged ≥60 years, the PAF of lifestyle risk factors was similar between men and women and the metabolic risk factors accounted for a greater proportion in women (33.0% vs. 14.5% in men). Sex differences may exist in the relation and attribution of lifestyle and metabolic risk factors to hypertension, which may have implications for implementing sex-specific strategies to prevent hypertension.

Modifiable Risk Factors for Accelerated Decline in Processing Speed: Results from Three Dutch Population Cohorts

BackgroundSeveral lifestyle, cardiovascular and psychosocial factors are associated with risk of cognitive decline and dementia. We studied the independent associations of a broad set of modifiable risk factors with decline in processing speed in three large population-based cohorts with up to 23 years of follow-up.MethodsWe used data of 9,666 participants from the Doetinchem Cohort Study, the Longitudinal Aging Study Amsterdam, and the Maastricht Aging Study. Decline in processing speed was measured with the letter digit substitution task or the alphabet coding task and modeled using quadratic latent growth curves. Associations of modifiable risk factors with level and rate of decline in processing speed were investigated by estimating associations with level of processing speed at different centering ages.ResultsLatent growth curves showed that decline in processing speed accelerated with age. Smoking, not drinking alcohol and depressive symptoms were associated with a lower level of processing speed in all cohorts. In two of the cohorts, more physical activity, drinking more than two glasses of alcohol per day, higher BMI and diabetes were associated with a lower level of processing speed. Depressive symptoms and diabetes were also associated with faster decline in processing speed.ConclusionSeveral modifiable risk factors are associated with the level of processing speed in older age, while few are also related to the rate of decline.

Association of modifiable risk factors among stroke patients attending a tertiary care hospital at Durg district of Chhattisgarh: a case-control study

Background: Non-communicable diseases (NCDs) are medical conditions or illnesses that are not caused by infectious agents. Modifiable behavioural risk factors, such as tobacco use, physical inactivity, unhealthy diet, stress and the harmful use of alcohol and metabolic risk factors, such as hypertension, diabetes, dyslipidemia, obesity, increase the risk of stroke. Strokes in Asian patients account for more than two-thirds of the overall stroke incidence worldwide. Methods: The Hospital based case-control study was carried out on 88 hospitalized patients with history of first time stroke and Controls were selected from hospital with no history of stroke. For each case gender, age (+5 years) matched control was selected in 1:1 ratio. A predesigned pretested questionnaire was used to collect data. Data were compared between case and control groups using chi-squared test, Students t-tests as appropriate and Uni-variate odds ratio (ORs) for these risks factors were calculated. Results: We recruited 88 cases of stroke and 88 controls for this study. In the current study Hypertension was found to be significantly associated with stroke. The stroke cases had significantly higher proportion of diabetes mellitus and the risk of developing stroke with diabetes mellitus was high and significant. Similarly, stroke was associated with alcohol, family history of stroke and obesity. Risk of developing stroke was not associated with cardiac disease. Conclusions: Hypertension, alcohol, obesity are the biggest risk factors for stroke. This could be helpful in early identification of subjects at risk of stroke and formulation of public health strategy. Additional studies of large patient cohorts will be essential to validate these findings.

Population attributable risk fraction of modifiable risk factors associated with poor self-rated health among children and adolescent; the CASPIAN-V study

BackgroundWe aimed to determine the population attributable risk fraction (PARF) of the risk factors for poor SRH in Iranian children and adolescents. MethodThis was a nationwide cross-sectional study conducted in 2015 among 14,400 students aged 6–18 years, living in 30 provinces of Iran. Data were collected using global school health survey questionnaire. Logistic regression was employed to determine the adjusted association of modifiable risk factors with SRH. We used average PARF to determine the preventable proportion of poor reported SRH. ResultsOf 14,400 recruited students, data on 13,983 subjects were analyzed in current study. The mean (SD) age of participants (n = 13,983) was 12.3 (3.16) years, and 49.3% were female. Poor SRH was reported in 19% of subjects. In total, 77% of poor reported SRH in Iranian children and adolescents could be attributed to insufficient daily sleep duration, physical injury, lack of close friend, dissatisfaction with family relationship, and the lack of a companion to share personal problems. We also found that physical pain had the largest PARF (32.4%) followed by anxiety (26.1%) and un-satisfaction with family relationship (5.2%). ConclusionThe established physical and social support factors of poor SRH were associated with a remarkable proportion of poor SRH in the Iranian pediatric population. Changing the children's risk factor profile to the lowest physical risk factor as well as reducing the anxiety level and preventing from physical painsmay significantly improve the SRH of children and adolescents.

Paternal preconception modifiable risk factors for adverse pregnancy and offspring outcomes: a review of contemporary evidence from observational studies

BackgroundThe preconception period represents transgenerational opportunities to optimize modifiable risk factors associated with both short and long-term adverse health outcomes for women, men, and children. As such, preconception care is recommended to couples during this time to enable them to optimise their health in preparation for pregnancy. Historically, preconception research predominately focuses on maternal modifiable risks and health behaviours associated with pregnancy and offspring outcomes; limited attention has been given to inform paternal preconception health risks and outcomes. This systematic review aims to advance paternal preconception research by synthesising the current evidence on modifiable paternal preconception health behaviours and risk factors to identify associations with pregnancy and/or offspring outcomes.MethodsMedline, Embase, Maternity and Infant care, CINAHL, PsycINFO, Scopus, and ISI Proceedings were searched on the 5th of January 2023, a date limit was set [2012–2023] in each database. A Google Scholar search was also conducted identifying all other relevant papers. Studies were included if they were observational, reporting associations of modifiable risk factors in the preconception period among males (e.g., identified as reproductive partners of pregnant women and/or fathers of offspring for which outcomes were reported) with adverse pregnancy and offspring outcomes. Study quality was assessed using the Newcastle–Ottawa Scale. Exposure and outcome heterogeneity precluded meta-analysis, and results were summarised in tables.ResultsThis review identified 56 cohort and nine case control studies. Studies reported on a range of risk factors and/or health behaviours including paternal body composition (n = 25), alcohol intake (n = 6), cannabis use (n = 5), physical activity (n = 2), smoking (n = 20), stress (n = 3) and nutrition (n = 13). Outcomes included fecundability, IVF/ISCI live birth, offspring weight, body composition/BMI, asthma, lung function, leukemia, preterm birth, and behavioural issues. Despite the limited number of studies and substantial heterogeneity in reporting, results of studies assessed as good quality showed that paternal smoking may increase the risk of birth defects and higher paternal BMI was associated with higher offspring birthweight.ConclusionThe current evidence demonstrates a role of paternal preconception health in influencing outcomes related to pregnancy success and offspring health. The evidence is however limited and heterogenous, and further high-quality research is needed to inform clinical preconception care guidelines to support men and couples to prepare for a health pregnancy and child.

Sex/gender and socioeconomic differences in modifiable risk factors for dementia

Both sex/gender and socioeconomic differences have been reported in the prevalence of modifiable risk factors for dementia. However, it remains unclear whether the associations between modifiable risk factors for dementia and incident dementia differ by sex/gender or socioeconomic status. This study aimed to investigate sex/gender and socioeconomic differences in the associations of modifiable risk factors with incident dementia using a life-course perspective. We used data from the English Longitudinal Study of Ageing (2008/2009 to 2018/2019). A total of 8,941 individuals were included [mean (standard deviation) age, 66.1 ± 9.8 years; 4,935 (55.2%) were women]. No overall sex/gender difference in dementia risk was found. Dementia risk was higher among those who experienced childhood deprivation [hazard ratio (HR) = 1.51 (1.17; 1.96)], lower occupational attainment [HR low versus high = 1.60 (1.23; 2.09) and HR medium versus high = 1.53 (1.15; 2.06)], and low wealth [HR low versus high = 1.63 (1.26; 2.12)]. Though different associations were found among the subgroups, there might be a sex/gender difference in dementia risk only for low cognitive activity, suggesting a higher risk for women [HR = 2.61 (1.89; 3.60)] compared to men [HR = 1.73 (1.20; 2.49)]. No consistent socioeconomic differences in modifiable dementia risk were found. A population-based approach that tackles inequalities in dementia risk profiles directly may be more effective than individual approaches in dementia prevention.

Association of modifiable risk factors with ischaemic stroke subtypes in Asian versus Caucasian populations: A systematic review and meta-analysis.

Ischaemic stroke (IS) is associated with various modifiable risk factors but the association of these risk factors based on TOAST classification, which characterises IS into five subtypes: large artery atherosclerosis (LAA), small vessel occlusion (SVO), cardioembolic disease (CE), other determined aetiology (ODE) and undetermined aetiology (UDE), is unknown. We aimed to summarise the published evidence for the association of modifiable risk factors with IS subtypes based on TOAST classification, specifically focussing on the Asian versus Caucasian population. A comprehensive search for all the published articles was performed in electronic databases including PubMed, EMBASE, Cochrane Library, and Google Scholar from 01st January 1950 to 10th April 2022 based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Odds ratio (OR) with 95% confidence interval (CIs) along with random-effect models was used to calculate summary estimates. In our meta-analysis, 32 studies with a total of 23,404 IS (14,364 in Asian vs. 9040 in Caucasian population), 7121 LAA (5219 in Asian vs. 1902 in Caucasian), 5532 SVO (3604 in Asian vs. 1928 in Caucasian), 3498 CE (1634 in Asian vs. 1864 in Caucasian), 1131 ODE (546 in Asian vs. 585 in Caucasian) and 4519 UDE (2076 in Asian vs. 2443 in Caucasian) were included. Our findings suggest a significant association between LAA and hypertension (OR=1.07, 95% CI=1.02-1.12), smoking (OR=1.11, 95% CI=1.04-1.17), dyslipidemia (OR=1.13, 95% CI=1.06-1.21), diabetes mellitus (OR=1.18, 95% CI=1.11-1.25) and atrial fibrillation (OR=0.55, 95% CI=0.40-0.75). Significantly strong association of hypertension, smoking, dyslipidemia, diabetes mellitus and atrial fibrillation was observed with SVO and CE stroke subtypes. Subgroup analysis based on ethnicity revealed a significant association for dyslipidemia, diabetes mellitus and atrial fibrillation in LAA for both Asians and Caucasians. Hypertension was significantly associated with SVO and ODE subtypes in both Asians and Caucasians; however, only Asian population showed significant association of hypertension in LAA and CE subtypes. The other risk factors did not show any statistical difference between the ethnic groups for the different stroke subtypes. The majority of the risk factors depicted positive association with LAA and SVO, negative with CE and neutral with ODE and UDE. Our findings suggest strong association of smoking, dyslipidemia and diabetes mellitus with LAA and SVO subtypes in the Caucasian population. However, only diabetes mellitus showed significant association with both LAA and SVO subtypes in Asian population as well. Thus, a majority of the traditional modifiable risk factors had a positive association in LAA and SVO, while a negative protective association was observed in CE subtype, among both the Asian and the Caucasian subgroups.

Modifiable risk factors and incidence of gout: Estimation of population attributable fraction in the US

ObjectiveThe burden of gout is substantial in the United States (US). Most gout cases can be attributed to modifiable risk factors, while systematic evidence-based assessment of gout cases and incidence attributable to the risk factors in the US is limited. MethodsThe estimated cases and incidence of gout in the US was obtained from global burden of disease (GBD) study 2019. We calculated the exposure rate of risk factors from National Health and Nutrition Examination Survey (NHANES) 2009–2010, since we estimated an average induction time of 10 years for risk factors and gout. We also conducted a meta-analysis to evaluate the associations of modifiable risk factors and gout in the US population. Furthermore, the population attributable fraction (PAF) was calculated using based on the prevalence of risk factors and relative risk (RR) from the meta-analysis. ResultsThe weighted prevalence of hypertension was 14.37%, and the average body mass index (BMI) and alcohol consumption was 28.50 kg/m2 and 7.14 g/d, respectively. Meta-analysis showed that individuals with hypertension had a higher risk of gout (2.12, 95% CI 1.88 to 2.40). For every five units of increase in BMI, the risk of gout increased by 1.48-fold (95% CI 1.26 to 1.75). The pooled RR was 1.21 (95% CI 1.13 to 1.29) for every 10 g/day increment of alcohol consumption. BMI, hypertension and alcohol consumption accounted for 53.58%, 13.85% and 12.66% of gout cases, respectively. Overall, 65.05% of gout incidence was attributable to the joint effects of these three risk factors. ConclusionHypertension, excess BMI and high alcohol consumption were responsible for approximately 65% of gout incidence in the US in 2019. Reducing the exposure to these factors can effectively reduce the incidence of gout.

Observational and Genetic Associations of Modifiable Risk Factors with Aortic Valve Stenosis: A Prospective Cohort Study of 0.5 Million Participants.

Background: Observational studies have shown that modifiable risk factors are associated with aortic valve stenosis (AVS). However, the causality behind these associations remains largely unknown. Objectives: To explore the associations of modifiable risk factors, including metabolic factors, biochemical measures, education, and lifestyles with AVS and their potential causal associations. Methods: We enrolled 361,930 British white people with genetic data in the UK biobank. Cox proportional risk regression models were used to estimate the hazard ratios between 28 modifiable risk factors and AVS. We used genetic instruments for modifiable risk factors to determine the potential causal relationships using a one-sample Mendelian randomization (MR) approach. Results: A total of 1602 participants developed AVS during an 8.4-year follow-up. Observational analyses showed higher adiposity, blood pressure, heart rate, low-density lipoprotein, urate, C-reactive protein, creatinine, albumin, and glycated hemoglobin, but lower serum vitamin D, and education, unhealthy lifestyle, and poor sleep quality were related to a higher risk of AVS after adjusting for the Bonferroni correction (p < 0.0013). Genetically predicted 1-SD higher levels of body mass index [HR: 1.09, 95% CI: 1.03 to 1.16], body fat percentage (1.17, 1.03 to 1.33), triglyceride (TG) [1.08, 1.00 to 1.16], low-density lipoprotein (LDL) (1.15, 1.08 to 1.21) and serum total cholesterol (TC) (1.13, 1.02 to 1.25) were associated with a higher risk of AVS, respectively. Genetically determined per category higher insomnia (1.32, 1.13 to 1.55) was also associated with AVS. The abovementioned genetic associations with the incident AVS showed an increasing relationship pattern. Conclusions: This study provides strong evidence for the potential causal roles of cardiometabolic factors in developing AVS, highlighting that an idea of metabolic status through a healthy lifestyle may help prevent AVS.

Cardiovascular disease risk factors and cognitive functions in older Russian adults

Abstract Background The prevalence of cardiovascular diseases (CVD) is increasing due to the global trend towards an aging population. CVD and cerebrovascular disease have a negative impact on cognitive health, and CVD risk factors may also be associated with cognitive decline with aging. Purpose To investigate associations of modifiable risk factors for CVD with cognitive functions (CF) in older Russian adults. Methods A random population sample (3153 men and women, aged 55–84 years) was examined in our city in the 3rd wave of the Russian arm of the international project HAPIEE (Health, Alcohol, and Psychosocial Factors in Eastern Europe). We used standardized epidemiological and instrumental methods for assessment of risk factors, history and treatment of CVD. Cognitive tests included the assessment of memory indicators (immediate and delayed recall), semantic verbal fluency (animal naming), attention, concentration and processing speed (letter cancellation task). Associations between CVD risk factors and cognitive indices were analyzed cross-sectionally. Results Mean age in men was of 69.2±7.0 years (n=1198), in women - 69.7±6.9 (n=1955). In both sexes all cognitive domains were positively associated with education and negatively with age (p&amp;lt;0.001 for all cases). In men, after adjusting for health and lifestyle conditions, systolic blood pressure had inverse association with semantic verbal fluency (p=0.015); level of plasma glucose (p=0.003), waist-to-hip ratio (p=0.013) and smoking (p=0.028) were negative associated with letter cancellation task. In multivariate analyses in women, frequency of alcohol consumption (p&amp;lt;0.001 for all CF) and total cholesterol (p=0.042 for memory scores; p=0.001 for letter cancellation task) had positive relationship with CF indices, waist-to-hip ratio (p=0.002 for memory scores, p=0.038 for semantic fluency), level of plasma glucose (p=0.002 for memory scores, p&amp;lt;0.001 for letter cancellation task) and smoking (p&amp;lt;0.001 for letter cancellation task) had inverse relationships with cognition. Conclusion Our results show that metabolic risk factors (systolic blood pressure, plasma glucose, waist-to-hip ratio) and smoking had inverse relationship with CF indices in both sexes, and the level of blood lipids (total cholesterol and high-density lipoprotein cholesterol) and frequency of alcohol consumption (more pronounced in women) had positive associations with cognitive domains. These associations were independent from age. In multivariate analyses, some of these correlations were attenuated, and most associations were at least partly mediated by education. These findings highlight the importance of managing CVD risk factors to prevent cognitive decline. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Russian Foundation for Basic Research (20-313-90016),Russian Academy of Sciences (AAAA-A17-117112850280-2)

Risk Factors and Lifestyles in the Development of Atrial Fibrillation Among Individuals Aged 20-39 Years

Epidemiological evidence on the relationship of modifiable risk factors and lifestyles with incident atrial fibrillation (AF) in young adults remains insufficient. We aimed to identify the determinants of AF among young adults using a nationwide epidemiological database. Medical records of 286,876 individuals (20-39 years) without prior history of cardiovascular disease were extracted from the JMDC Claims Database. We analyzed the association of modifiable risk factors with the incidence of AF. The median (interquartile range) age was 34 (29-37) years, and 54.4% were men. After a mean follow-up of 1,017±836 days, 267 individuals (0.1%) developed AF. Multivariable Cox regression analysis demonstrated that high waist circumference, hypertension, cigarette smoking, and poor sleep quality as well as age and sex were associated with increased incidence of AF. Kaplan-Meier curves showed that number of modifiable components including high waist circumference, hypertension, cigarette smoking, and poor sleep quality clearly stratified the risk of AF development (Log rank test, p<0.001). Age- and sex-adjusted Cox regression analyses showed individuals with one (hazard ratio [HR] 1.56, 95% confidence interval [CI] 1.13-2.18), two (HR 2.03, 95% CI 1.40-2.95), three (HR 3.48, 95% CI 2.19-5.54), and four (HR 10.78, 95% CI 5.26-22.11) components were associated with an increased incidence of AF compared with individuals with no components. In conclusion, high waist circumference, hypertension, cigarette smoking, and poor sleep quality were associated with the development of AF among young adults, suggesting the importance of maintaining these modifiable factors for the primordial prevention of AF in young adults.

Association of Modifiable Risk Factors With Early Discontinuation of Adjuvant Endocrine Therapy

Early discontinuation of adjuvant endocrine therapy (ET) is problematic among breast cancer survivors, with previous studies suggesting that up to 50% of women do not adhere to the recommended full 5 years of ET treatment. To identify the association between early discontinuation of ET in the Trial Assigning Individualized Options for Treatment (TAILORx) and modifiable risk factors, polypharmacy, and types of additional medications such as antidepressants and opioids. This post hoc analysis includes a subgroup of 954 patients with breast cancer in TAILORx, a randomized clinical trial conducted from April 7, 2006, to October 6, 2010. All participants received a diagnosis of hormone receptor-positive, ERBB2-negative, axillary node-negative breast cancer and started ET within a year of study entry. Analyses were conducted in the intent-to-treat population. Statistical analysis took place from January 15, 2020, to April 6, 2021. Participants completed measures on cancer-related health-related quality of life including physical well-being and social well-being prior to initiating ET. Early discontinuation of ET was defined as discontinuation less than 4 years from initiation for reasons other than death or recurrence. Kaplan-Meier estimates were used to calculate discontinuation, and Cox proportional hazards regression joint prediction models were used to analyze the association between rates of adherence to ET with patient-level factors. A total of 954 women (mean [SD] age, 56.6 [8.9] years) were included in this analysis. In a joint model, receipt of chemoendocrine therapy (vs receipt of ET only; hazard ratio [HR], 0.57; 95% CI, 0.35-0.92; P = .02) and age older than 40 years (vs ≤40 years; HR for 41-50 years, 0.39; 95% CI, 0.18-0.85; P = .02; HR for 51-60 years, 0.28; 95% CI, 0.13-0.60; P = .001; HR for 61-70 years, 0.40; 95% CI, 0.18-0.86; P = .02; and HR for >70 years, 0.23; 95% CI, 0.07-0.77; P = .02) were associated with a lower probability of early discontinuation of ET. Adjusted for these factors, a history of depression compared with no history of depression (HR, 1.82; 95% CI, 1.19-2.77; P = .005), worse physical well-being compared with better physical well-being (HR, 2.12; 95% CI, 1.30-3.45; P = .002), and worse social well-being compared with better social well-being (HR, 1.94; 95% CI, 1.20-3.13; P = .006) were individually and significantly associated with a higher probability of early discontinuation of ET. Only antidepressant use at study baseline was associated with early discontinuation (HR, 1.87; 95% CI, 1.23-2.84; P = .003). In this post hoc analysis of a randomized clinical trial, baseline patient-reported health-related quality of life components, such as poor social well-being, poor physical well-being, and comorbid depression, were significant risk factors for early discontinuation of endocrine therapies. These results support systematic screening for patient-reported outcomes and depressive symptoms to identify women at risk for discontinuation of ET. ClinicalTrials.gov Identifier: NCT00310180.

Modifiable risk factors for epilepsy: A two‐sample Mendelian randomization study

IntroductionWe conducted a two‐sample Mendelian randomization study to determine the associations of modifiable risk factors with epilepsy.MethodsFourteen potential risk factors for epilepsy were selected based on a systematic review of risk factors for epilepsy. Single‐nucleotide polymorphisms associated with each exposure at the genome‐wide significance threshold (p < 5×10–8) were proposed as instrumental variables from corresponding genome‐wide association studies. Summary‐level data for epilepsy were obtained from the FinnGen consortium (4,588 cases and 144 780 noncases). Potential causal associations (p < .05) were attempted for replication using UK Biobank data (901 cases and 395 209 controls).ResultsAmong 14 potential risk factors, 4 showed significant associations with epilepsy in FinnGen. All associations were directionally similar in UK Biobank and associated with epilepsy at p ≤ .004 in meta‐analyses of FinnGen and UK Biobank data. The odds ratios of epilepsy were 1.46 (95% CI, 1.18, 1.82) for one unit increase in log odds ratio of having depression, 1.44 (95% CI, 1.13, 1.85) for one standard deviation increase in serum ferritin, 1.12 (95% CI, 1.04, 1.21) for one standard deviation increase in transferrin saturation, and 1.25 (95% CI, 1.09, 1.43) for one standard deviation increase in the prevalence of smoking initiation. There were suggestive associations of serum iron and magnesium with epilepsy. No association was observed for insomnia, blood pressure, alcohol consumption, or serum vitamin B12, 25‐hydroxyvitamin D and calcium levels.ConclusionThis MR study identified several modifiable risk factors for adulthood epilepsy. Reducing prevalence of depression and smoking initiation should be considered as primary prevention strategies for epilepsy.

Longitudinal associations of modifiable risk factors in the first 1000 days with weight status and metabolic risk in early adolescence

Many studies have identified early-life risk factors for childhood overweight/obesity (OwOb), but few have evaluated how they combine to influence later cardiometabolic health. We aimed to examine the association of risk factors in the first 1000 d with adiposity and cardiometabolic risk in early adolescence. We studied 1038 mother-child pairs in Project Viva. We chose 6 modifiable early-life risk factors previously associated with child adiposity or metabolic health in the cohort: smoking during pregnancy (yes compared with no); gestational weight gain (excessive compared with nonexcessive); sugar-sweetened beverage consumption during pregnancy (≥0.5 compared with <0.5 servings/d); breastfeeding duration (<12 compared with ≥12 mo); timing of complementary food introduction (<4 compared with ≥4 mo); and infant sleep duration (<12 compared with ≥12 h/d). We computed risk factor scores by calculating the cumulative number of risk factors for each child. In early adolescence (median: 13.1 y) we measured indicators of adiposity [BMI, fat mass index (FMI), trunk fat mass index (TFMI)]. We also calculated OwOb prevalence and metabolic syndrome (MetS) risk z score of adolescents. Among 1038 adolescents, 71% had >1 early-life risk factor. In covariate-adjusted models, we observed positive monotonic increases in BMI, FMI, TFMI, and MetS z scores with increasing risk factor score. Children with 5‒6 risk factors (compared with 0-1 risk factors) had the highest risk of OwOb [risk ratio (RR): 2.53; 95% CI: 1.63, 3.91] and being in the highest MetS quartile (RR: 2.46; 95% CI: 1.43, 4.21). The predicted probability of OwOb in adolescence varied from 9.4% (favorable levels for all factors) to 63.6% (adverse levels for all factors), and for being in the highest MetS quartile from 9.6% to 56.6%. Early-life risk factors in the first 1000 d cumulatively predicted higher adiposity and cardiometabolic risk in early adolescence. Intervention strategies to prevent later obesity and cardiometabolic risk may be more effective if they concurrently target multiple modifiable factors.

Lifestyle and Risk Factor Modification for Reduction of Atrial Fibrillation: A Scientific Statement From the American Heart Association.

Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is associated with substantial morbidity, mortality, and healthcare use. Great strides have been made in stroke prevention and rhythm control strategies, yet reducing the incidence of AF has been slowed by the increasing incidence and prevalence of AF risk factors, including obesity, physical inactivity, sleep apnea, diabetes mellitus, hypertension, and other modifiable lifestyle-related factors. Fortunately, many of these AF drivers are potentially reversible, and emerging evidence supports that addressing these modifiable risks may be effective for primary and secondary AF prevention. A structured, protocol-driven multidisciplinary approach to integrate lifestyle and risk factor management as an integral part of AF management may help in the prevention and treatment of AF. However, this aspect of AF management is currently underrecognized, underused, and understudied. The purpose of this American Heart Association scientific statement is to review the association of modifiable risk factors with AF and the effects of risk factor intervention. Implementation strategies, care pathways, and educational links for achieving impactful weight reduction, increased physical activity, and risk factor modification are included. Implications for clinical practice, gaps in knowledge, and future directions for the research community are highlighted.

Costs Associated With Modifiable Risk Factors in Ventral and Incisional Hernia Repair

Ventral and incisional hernia repair (VIHR) is an extremely common operation, after which complications are also fairly common. A number of preoperative risk factors are known to contribute to increased complications after surgical repair; however, the individual relative association of these risk factors with adverse outcomes and increased spending is unclear. Quantifying the association of individual risk factors may help surgeons implement targeted surgical optimization, improve outcomes, and reduce spending. To identify the attributable association of modifiable risk factors for adverse outcomes after VIHR on outcomes and episode-of-care payments. This cross-sectional study was performed using a population-based sample of adult patients and episode spending data from January 1, 2012, to December 31, 2018, from a statewide multipayer registry. A multilevel mixed-effects logistic regression model was used to examine the contribution of patient-specific risk factors to adverse outcomes. Attributable risk and population attributable risk fraction were calculated to estimate the additional spending attributable to individual risk factors. Data were analyzed from April 2018 to September 2018. Any complications, serious complication, discharge not to home, 30-day emergency department utilization, and 30-day readmission. Episode-of-care spending was calculated for these outcomes. This study included 22 664 patients (median [interquartile range] age, 55 [44-64] years; 10 496 [46.3%] women) undergoing VIHR with identified significant preoperative risk factors. Fourth-quartile body mass index (BMI), calculated as weight in kilograms divided by height in meters squared and defined as a mean (SD) BMI of 43 (6), was associated with increased risk of any complication (odds ratio [OR], 1.64; 95% CI, 1.30-2.06; P < .001) and serious complication (OR, 1.67; 95% CI, 1.22-2.31; P = .002). Insulin-dependent diabetes was associated with increased risk of any complication (OR, 1.34; 95% CI, 1.03-1.73; P = .03), serious complication (OR, 1.51; 95% CI, 1.08-2.12; P = .02), discharge not to home (OR, 1.49; 95% CI, 1.12-1.98; P = .005), and 30-day readmission (OR, 1.68; 95% CI, 1.32-2.14; P < .001). Median (interquartile range) additional episode spending for any complication was $9934 ($9224-$11 851), of which $1304 ($1208-$1552) was attributable to fourth-quartile BMI. Median (interquartile range) additional episode spending for a serious complication was $26 648 ($20 632-$33 166), of which $3638 ($2827-$4544) was attributable to fourth-quartile BMI, $650 ($495-$796) was attributable to insulin-dependent diabetes, and $567 ($433-$696) was attributable to unhealthy alcohol use. In this cross-sectional study, modifiable risk factors, such as obesity, insulin-dependent diabetes, and unhealthy alcohol use, were associated with adverse outcomes after VIHR. These factors were significantly associated with increased health care spending; therefore, preoperative optimization may improve outcomes and decrease episode-of-care costs.

Association of modifiable risk factors and IL-6, CRP, and adiponectin: Findings from the 1993 Birth Cohort, Southern Brazil.

BackgroundThe literature on the relationship between lifestyle behaviors and inflammatory markers is scarce.MethodsA birth cohort was followed since birth up to 22 years in Southern Brazil. Interleukin-6 (IL-6), C-reactive protein (CRP) and adiponectin were measured in nonfasting blood samples drawn at 18 and 22 years of age. Exposures including smoking, alcohol intake, physical inactivity and obesity, were collected at 15, 18 and 22 years. Cross sectional analyses were based on the number of follow-up visits with these exposures and the association with IL-6, CRP and adiponectin at 22 years old. We also carried out a longitudinal Generalized Least Squares (GLS) random-effects analysis with outcomes at 18 and at 22 years old. All analyses were adjusted for several covariates.ResultsThe sample comprised 3,479 cohort members at 22 years. The presence of obesity at ≥ 2 follow-ups showed the highest mean values (SE) for IL-6 [2.45 (1.05)] and CRP [3.74 (1.11)] and the lowest mean value for adiponectin [8.60 (0.37)] (adjusted analyses, females) compared with other exposures; the highest mean of IL-6 [1.65 (1.05)] and CRP [1.78 (1.11)] and the lowest mean of adiponectin [9.98 (0.38)] were for the number of follow-ups with ≥2 exposures compared to those with no exposures at any follow-up (adjusted analyses, females). The longitudinal analysis showed an increase in obesity associated with IL-6 and CRP in both sexes and an inverse association with adiponectin in females; smoking (in males) was associated with IL-6 and CRP, harmful alcohol intake was associated with CRP in males, and increased in physical activity was inversely associated with CRP in men.ConclusionWe concluded that obesity is the main exposure positively associated with IL-6 and CRP and inversely associated with adiponectin (mainly in females). Smoking is also associated with these markers in the longitudinal analysis (in males).