Associations of age at diagnosis of breast cancer with incident myocardial infarction and heart failure: A prospective cohort study.

Background: The associations of age at diagnosis of breast cancer with incident myocardial infarction (MI) and heart failure (HF) remain unexamined. Addressing this problem could promote understanding of the cardiovascular impact of breast cancer. Methods: Data were obtained from the UK Biobank. Information on the diagnosis of breast cancer, MI, and HF was collected at baseline and follow-ups (median = 12.8 years). The propensity score matching method and Cox proportional hazards models were employed. Results: A total of 251,277 female participants (mean age: 56.8 ± 8.0 years), of whom 16,241 had breast cancer, were included. Among breast cancer participants, younger age at diagnosis (per 10-year decrease) was significantly associated with elevated risks of MI (hazard ratio [HR] = 1.36, 95% confidence interval [CI] 1.19-1.56, p<0.001) and HF (HR = 1.31, 95% CI 1.18-1.46, p<0.001). After propensity score matching, breast cancer patients with younger diagnosis age had significantly higher risks of MI and HF than controls without breast cancer. Conclusions: Younger age at diagnosis of breast cancer was associated with higher risks of incident MI and HF, underscoring the necessity to pay additional attention to the cardiovascular health of breast cancer patients diagnosed at younger age to conduct timely interventions to attenuate the subsequent risks of incident cardiovascular diseases. Funding: This study was supported by grants from the National Natural Science Foundation of China (82373665 and 81974490), the Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences (2021-RC330-001), and the 2022 China Medical Board-open competition research grant (22-466).

Associations of fruit intake with adiposity and cardiometabolic biomarkers in UK Biobank.

BACKGROUND: Fruit consumption has been associated with a lower cardiovascular disease (CVD) risk but the underlying mechanisms are unclear. We investigated the cross-sectional and prospective associations of fruit consumption with markers of adiposity, blood pressure, lipids, low-grade inflammation, glycaemia, and oxidative stress. METHODS: The main analyses included 365 534 middle-aged adults from the UK Biobank at baseline, of whom 11 510, and 38 988 were included in the first and second follow-up respectively, free from CVD and cancer at baseline. Fruit consumption frequency at baseline was assessed using a questionnaire. We assessed the cross-sectional and prospective associations of fruit with adiposity (body mass index, waist circumference and %body fat), systolic and diastolic blood pressure, lipids (low-density and high-density lipoproteins, triglycerides and apolipoprotein B), glycaemia (haemoglobin A1c), low-grade inflammation (C-reactive protein) and oxidative stress (gamma-glutamyl-transferase) using linear regression models adjusted for socioeconomic and lifestyle factors. Analyses were repeated in a subset with two to five complete 24-h dietary assessments (n = 26 596) allowing for adjustment for total energy intake. RESULTS: Fruit consumption at baseline generally showed weak inverse associations with adiposity and biomarkers at baseline. Most of these relationships did not persist through follow-up, except for inverse associations with diastolic blood pressure, C-reactive protein, gamma-glutamyl transferase and adiposity. However, for most mechanisms, mean levels varied by less than 0.1 standard deviations (SD) between high and low fruit consumption (> 3 vs < 1 servings/day) in further adjusted models (while the difference was < 0.2 SD for all of them). For example, waist circumference and diastolic blood pressure were 1 cm and 1 mmHg lower in high compared to low fruit intake at the first follow-up (95% confidence interval: -1.8, -0.1 and -1.8, -0.3, respectively). Analyses in the 24-h dietary assessment subset showed overall similar associations. CONCLUSIONS: We observed very small differences in adiposity and cardiometabolic biomarkers between those who reported high fruit consumption vs low, most of which did not persist over follow-up. Future studies on other mechanisms and detailed assessment of confounding might further elucidate the relevance of fruit to cardiovascular disease.

Association between kidney function and Parkinson's disease risk: a prospective study from the UK Biobank.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative influenced by various clinical factors. The potential relationship between renal function and the risk of PD remains poorly understood. This study aims to explore the association between kidney function and the risk of developing PD. METHODS: A population-based cohort study was conducted using data from 400,571 UK Biobank participants. Renal function was assessed using the estimated glomerular filtration rate (eGFR), calculated from serum creatinine and cystatin C levels. The association between eGFR levels and PD risk was evaluated using univariate and multivariate Cox regression analyses, Restricted Cubic Spline (RCS) analysis, and Kaplan-Meier analysis. Additionally, a clinical prediction model was developed and its diagnostic accuracy was evaluated using ROC analysis. A heatmap was also constructed to examine the relationship between clinical factors and gray matter volume in various brain regions. RESULTS: Over a median observation period of 13.8 years, 2740 PD events were recorded. Cox regression and Kaplan-Meier analyses revealed a significant association between decreased eGFR and increased PD risk, particularly in participants with eGFR < 30 ml/min/1.73 m2. This association was confirmed across three adjusted models. RCS analysis demonstrated a nonlinear relationship between decreasing eGFR and increasing PD risk. Furthermore, changes in eGFR were correlated with alterations in subcortical gray matter volume in regions such as the frontal cortex, striatum, and cerebellum. The clinical prediction model showed high diagnostic accuracy with AUC values of 0.776, 0.780, and 0.824 for 4-, 8-, and 16-year predictions, respectively. CONCLUSION: Renal insufficiency is significantly associated with an increased risk of PD, highlighting the importance of maintaining good kidney function as a potential preventive measure against PD.

Daytime napping and the incidence of Parkinson's disease: a prospective cohort study with Mendelian randomization.

BACKGROUND: The causal relationship between daytime napping and the risk of Parkinson's disease (PD) remains unclear, with prospective studies providing limited evidence. This study investigated the association between daytime napping frequency and duration and PD incidence and explored the causality relationship between this association by conducting Mendelian randomization (MR) analysis. METHODS: This prospective cohort study included 393,302 participants, and accelerometer-measured daytime napping data were available only for 78,141 individuals. Cox proportional hazards regression was used to estimate the association between the daytime napping frequency and duration and the PD risk. The role of the systemic immune-inflammation index (SII) in the association between daytime napping frequency and PD risk was assessed through mediation analyses. Moreover, the causal association between the daytime napping frequency and the PD risk was preliminarily explored by conducting two-sample MR analyses. RESULTS: The median follow-up duration was 12.18 years. The participants who reported napping sometimes or usually exhibited a significantly higher PD risk than those who never/rarely napped during the day [sometimes: hazard ratio (HR), 1.13; 95% confidence interval (CI), 1.03-1.23; usually: HR, 1.33; 95% CI, 1.14-1.55], and SII played a mediating role in this association. However, the MR analyses did not indicate that the daytime napping frequency and PD risk were significantly associated. The participants napping for over 1 h exhibited a significantly elevated PD risk (HR, 1.54; 95% CI, 1.11-2.16). Moreover, no significant interaction was identified between napping frequency or duration and genetic susceptibility to PD (P for interaction > 0.05). CONCLUSIONS: In this study, increased daytime napping frequency and duration were associated with an increased PD risk, but no causal relationship was observed between napping frequency and PD risk in the MR analysis. Larger GWAS-based cohort studies and MR studies are warranted to explore potential causal relationships.

Lipid metabolites are associated with the risk of osteoporotic fractures.

We conducted this cross-sectional study to investigate the independent associations between lipid metabolites and osteoporotic fractures among participants aged 40-69 years from the UK Biobank. Serum lipid, lipoprotein levels and nuclear magnetic resonance (NMR) based metabolic biomarkers were measured at the baseline. We conducted multivariable logistic analyses to investigate potential independent associations between concentrations of lipid metabolites and osteoporotic fractures in both men and women. The odds ratios (ORs) for lipid metabolites were calculated based on their lowest tertile. Over a median follow-up period of 15 years, a total of 978 men and 4515 women were diagnosed with osteoporosis, whereas 138 men and 327 women encountered incident fractures. Statistically significant disparities were identified in NMR-based metabolic biomarkers among men and women with incident fractures compared to those without. Out of the 144 distinct lipid metabolites known, 35 exhibited significant associations with incident fractures in patients diagnosed with osteoporosis. Following the adjustment for confounding factors, degree of unsaturation (p = 0.0066) and docosahexaenoic acids (p = 0.0011) in male patients increased the risk of incident fractures. And high level of different metabolites of HDL (p = 0.0153), 3-Hydroxybutyrate (p = 0.0012) and Sphingomyelins (p = 0.0036) decreased the risk of incident fractures in female patients. This outcome indicates that these identified lipid metabolites may potentially have unique roles in independently contributing to the occurrence of osteoporotic fractures.

Association between dietary magnesium intake and incident chronic kidney disease : A prospective observational cohort study.

BACKGROUND: While serum magnesium deficiency is liked to higher cardiovascular disease risk, its association with chronic kidney disease (CKD) remains unclear. OBJECTIVE: To evaluate the relationship between dietary magnesium intake and CKD development in adults with clinically normal kidney function METHODS: The prospective observational cohort study evaluated 188,510 participants (median age, 57.0 years; female, 54.1%) from the UK Biobank. Dietary magnesium intake was assessed through a 24-hour dietary recall questionnaire compromising a list of 206 foods and 32 beverages, and categorized into quintiles. The primary outcome was incident CKD diagnosed through International Classification of Diseases (ICD)-10 and Office of Population Censuses and Surveys (OPCS)-4 codes. Incident CKD, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, was also assessed in a sub-cohort with creatinine follow-up data. RESULTS: The median magnesium intake amount per person was 323.2 (interquartile range [IQR], 269.4-382.7) mg/day. During 1,826,038.1 person-years of follow-up (median, 9.6 years; IQR, 9.3-10.3 years), CKD developed in 5,878 participants. The incidence of CKD was progressively higher in participants with lower magnesium intake (2.8%, 2.8%, 3.0%, 3.2%, and 3.7% in Q5-1, respectively). Cox regression analysis revealed that the hazard ratios (HRs) for incident CKD increased in a stepwise manner towards lower magnesium intake quintiles (adjusted HR (95% CI); Q4, 0.97 (0.89, 1.06); Q3, 1.05 (0.96, 1.14); Q2, 1.12 (1.03, 1.21); Q1, 1.30 (1.20, 1.41)) relative to Q5 (P for linearity <0.001). Similar results were observed with eGFR-defined CKD outcome (adjusted HR (95% CI); Q4, 1.09 (0.92, 1.28); Q3, 1.15 (0.98, 1.35); Q2, 1.21 (1.03, 1.42); Q1, 1.41 (1.20, 1.65) relative to Q5; P for linearity <0.001). CONCLUSIONS: Lower dietary magnesium intake was associated with a higher risk of incident CKD in adults with clinically normal kidney function. Further controlled studies are required to establish the potential benefit of adequate magnesium intake.

Sex-specific cardiovascular risk factors in the UK Biobank.

The lack of sex-specific cardiovascular disease criteria contributes to the underdiagnosis of women compared to that of men. For more than half a century, the Framingham Risk Score has been the gold standard to estimate an individual's risk of developing cardiovascular disease based on the age, sex, cholesterol levels, blood pressure, diabetes status, and the smoking status. Now, machine learning can offer a much more nuanced insight into predicting the risk of cardiovascular diseases. The UK Biobank is a large database that includes traditional risk factors and tests related to the cardiovascular system: magnetic resonance imaging, pulse wave analysis, electrocardiograms, and carotid ultrasounds. Here, we leverage 20,542 datasets from the UK Biobank to build more accurate cardiovascular risk models than the Framingham Risk Score and quantify the underdiagnosis of women compared to that of men. Strikingly, for a first-degree atrioventricular block and dilated cardiomyopathy, two conditions with non-sex-specific diagnostic criteria, our study shows that women are under-diagnosed 2× and 1.4× more than men. Similarly, our results demonstrate the need for sex-specific criteria in essential primary hypertension and hypertrophic cardiomyopathy. Our feature importance analysis reveals that out of the top 10 features across three sexes and four disease categories, traditional Framingham factors made up between 40% and 50%; electrocardiogram, 30%-33%; pulse wave analysis, 13%-23%; and magnetic resonance imaging and carotid ultrasound, 0%-10%. Improving the Framingham Risk Score by leveraging big data and machine learning allows us to incorporate a wider range of biomedical data and prediction features, enhance personalization and accuracy, and continuously integrate new data and knowledge, with the ultimate goal to improve accurate prediction, early detection, and early intervention in cardiovascular disease management. Our analysis pipeline and trained classifiers are freely available at https://github.com/LivingMatterLab/CardiovascularDiseaseClassification.

PheMIME: an interactive web app and knowledge base for phenome-wide, multi-institutional multimorbidity analysis.

OBJECTIVES: To address the need for interactive visualization tools and databases in characterizing multimorbidity patterns across different populations, we developed the Phenome-wide Multi-Institutional Multimorbidity Explorer (PheMIME). This tool leverages three large-scale EHR systems to facilitate efficient analysis and visualization of disease multimorbidity, aiming to reveal both robust and novel disease associations that are consistent across different systems and to provide insight for enhancing personalized healthcare strategies. MATERIALS AND METHODS: PheMIME integrates summary statistics from phenome-wide analyses of disease multimorbidities, utilizing data from Vanderbilt University Medical Center, Mass General Brigham, and the UK Biobank. It offers interactive and multifaceted visualizations for exploring multimorbidity. Incorporating an enhanced version of associationSubgraphs, PheMIME also enables dynamic analysis and inference of disease clusters, promoting the discovery of complex multimorbidity patterns. A case study on schizophrenia demonstrates its capability for generating interactive visualizations of multimorbidity networks within and across multiple systems. Additionally, PheMIME supports diverse multimorbidity-based discoveries, detailed further in online case studies. RESULTS: The PheMIME is accessible at https://prod.tbilab.org/PheMIME/. A comprehensive tutorial and multiple case studies for demonstration are available at https://prod.tbilab.org/PheMIME_supplementary_materials/. The source code can be downloaded from https://github.com/tbilab/PheMIME. DISCUSSION: PheMIME represents a significant advancement in medical informatics, offering an efficient solution for accessing, analyzing, and interpreting the complex and noisy real-world patient data in electronic health records. CONCLUSION: PheMIME provides an extensive multimorbidity knowledge base that consolidates data from three EHR systems, and it is a novel interactive tool designed to analyze and visualize multimorbidities across multiple EHR datasets. It stands out as the first of its kind to offer extensive multimorbidity knowledge integration with substantial support for efficient online analysis and interactive visualization.

Maternal smoking during pregnancy could accelerate aging in the adulthood: evidence from a perspective study in UK Biobank.

BACKGROUND: Maternal smoking during pregnancy (MSDP) is significantly linked to the short- or long-term health of offspring. However, little research has examined whether MSDP affect the aging rate of offspring. METHODS: This study used questionnaires to determine out whether the participants' mothers smoked when they were pregnant. For evaluating aging rate, we used the following several outcome measures: telomere length, frailty index, cognitive function, homeostatic dysregulation score, KDM-age, age-related hospitalization rate, premature death, and life expectancy. RESULT: After adjusting for covariates, we found that the offspring of the MSDP group had significantly shorter telomere length in adulthood by 0.8 % (ß = -0.008,95%CI:-0.009 to -0.006) compared with non-MSDP group. Compared to the non-MSDP group, participants in MSDP group showed higher levels of homeostatic dysregulation (ß = 0.015,95%CI: 0.007-0.024) and were frailer (ß = 0.008,95%CI:0.007-0.009). The KDM age increased by 0.100 due to MSDP (ß = 0.100,95 % CI:0.018-0.181), and the age acceleration of KDM algorithm also increases significantly (ß = 0.101, 95%CI:0.020-0.183). Additionally, we found that the risk of aging-related hospitalizations was significantly higher than the non-MSDP group by 10.4 %(HR = 1.104,95%CI:1.066-1.144). Moreover, MSDP group had a 12.2 % increased risk of all-cause premature mortality (HR = 1.122,95%CI:1.064-1.182) and a significant risk of lung cancer-specific premature mortality increased by 55.4 %(HR = 1.554,95%CI:1.346-1.793). In addition, participants in the MSDP group had significantly decreased cognitive function and shorter life expectancies than those in non-MSDP group. CONCLUSION: Our findings indicated a significant association between MSPD and accelerated aging, elevated hospitalization rates, increased premature mortality rates, and reduced life expectancies in offspring.

Dietary flavonoid intake and risk of hormone-related cancers: A population-based prospective cohort study.

BACKGROUND: Dietary flavonoids may have potential effects on hormone-related cancers (HRCs) due to their anti-cancer properties via regulating hormones and suppressing inflammation and oxidative stress. We aimed to examine the association of flavonoid intake with risks of HRCs and whether this association was mediated by blood biomarkers involved in biological mechanisms. METHODS: This prospective cohort study from UK Biobank included 187,350 participants free of cancer when the last dietary recall was completed. The dietary intakes of flavonoids and subclasses were assessed using 24-hour dietary recalls. Venous blood was collected at baseline and assayed for biomarkers of inflammation, hormones, and oxidative stress. Hazard ratios (HR) and 95 % confidential intervals (CI) for the associations between flavonoid intake and HRCs risk were estimated by the cause-specific Cox proportional hazards model. The role of blood biomarkers in the flavonoids-HRCs association was investigated through mediation analysis. RESULTS: Over a median follow-up of 9.5 years, 3,392 female breast cancer, 417 ovarian cancer, 516 endometrial cancer, 4,305 prostate cancer, 45 testicular cancer, and 146 thyroid cancer cases were documented. Compared to the lowest quintile, multivariable-adjusted HRs (95 % CIs) in the highest quintile of total flavonoid intake were 0.89 (0.80-0.99) for breast cancer, 0.68 (0.50-0.92) for ovarian cancer, and 0.88 (0.80-0.98) for female-specific cancers. For subclasses, intakes of flavonols and anthocyanidins were inversely associated with the risk of female-specific cancers (Ptrend <0.05). Anthocyanidin intake was positively related to prostate cancer risk, whereas isoflavone intake was inversely linked to thyroid cancer risk (Ptrend <0.05). Additionally, certain biomarkers of inflammation, hormones and oxidative stress jointly mediated the association of flavonoid intake with the risk of female-specific cancers and prostate cancer. CONCLUSIONS: Our findings highlighted the importance of dietary flavonoids for the prevention of HRCs in the general population, providing epidemiological evidence for dietary guidelines.

Sex Differences in 'Life's Essential 8' cardiovascular health and Type 2 Diabetes Mellitus Risk Across Menopause Stages.

AIM: The purpose of this paper is to explore sex-based differences in cardiovascular health (CVH) and the incidence of type 2 diabetes mellitus (T2DM) among women at different menopausal stages and men. METHODS: A prospective cohort study was conducted, involving 126,818 participants without pre-existing T2DM from the UK Biobank. CVH was assessed using the Life's Essential 8. Absolute risks (ARs) and hazard ratios (HRs) were separately employed to assess the association between increased CVH and T2DM risk. The Accelerated Failure Time model assessed the impact of CVH on the time to T2DM onset. RESULTS: Over a mean follow-up of 168 months, 4,315 cases of T2DM were documented. In men, each one-point increase in CVH was associated with a 0.268% decrease in AR and a 6.4% decrease in HR for T2DM. In premenopausal, perimenopausal and postmenopausal women, each unit increase in CVH resulted in a 0.105%, 0.180% and 0.166% decrease in AR and a 7.7%, 5.2% and 6.4% decrease in HR of T2DM. The adjusted median time to T2DM onset was delayed by 12.46, 9.83, 11.5 and 21.43 months in the highest quintile of men, premenopausal, perimenopausal and postmenopausal women, respectively, compared with the lowest CVH quintile. CONCLUSIONS: As CVH improved, the reduction in AR for T2DM was more prominent in men than in women. HR trends for CVH and T2DM were similar in men and postmenopausal women. Increased CVH delayed the onset of T2MD in both men and women, with the most significant delay observed in postmenopausal women.

Association between frailty and main work during the LIFE: A cross-sectional analysis of the UK Biobank.

BACKGROUND: The role of main work during the life course in predicting frailty, a typical geriatric syndrome, is still largely unknown. Therefore, with this research, we aimed to investigate the potential association between the main work done during the life with frailty and pre-frailty among participants 60 years and older of the UK Biobank study. METHODS: Frailty and pre-frailty presence were ascertained using a model including 5 indicators (weakness, slowness, weight loss, low physical activity, and exhaustion); the main employment status was ascertained using self-reported information. The association between frailty and main work was explored using an ordinal logistic regression model and reported as odds ratios (ORs) with their 95 % confidence intervals (CIs). RESULTS: The final sample comprised a total of 50,447 individuals (mean age: 64.2 years, females: 50.2 %). Individuals with higher qualifications had a reduced risk of frailty (OR = 0.881, 95%CI = 0.83-0.95, p-value<0.001 for pre-frail and OR = 0.681, 95%CI = 0.63-0.73, p-value<0.001 for frail) compared to those with lower qualifications. Moreover, active participation in the workforce, compared to being inactive, emerged as a protective factor from frailty (OR = 0.753, 95%CI = 0.70-0.81, p-value<0.001). The categories of Associate Professional and Technical Occupations exhibited protective effects against both pre-frailty and frailty. Similarly, occupations categorized as Professional and Management demonstrated protective effects against pre-frailty and frailty when compared to Elementary Occupations. Additionally, engagement in Trades and Services occupations, as opposed to Elementary Occupations, appeared to be protective against frailty. CONCLUSIONS: In this large cross-sectional investigation based on the data of the UK Biobank we found that work during lifetime could be an important factor in determining frailty later in life.

AI-based derivation of atrial fibrillation phenotypes in the general and critical care populations.

BACKGROUND: Atrial fibrillation (AF) is the most common heart arrhythmia worldwide and is linked to a higher risk of mortality and morbidity. To predict AF and AF-related complications, clinical risk scores are commonly employed, but their predictive accuracy is generally limited, given the inherent complexity and heterogeneity of patients with AF. By classifying different presentations of AF into coherent and manageable clinical phenotypes, the development of tailored prevention and treatment strategies can be facilitated. In this study, we propose an artificial intelligence (AI)-based methodology to derive meaningful clinical phenotypes of AF in the general and critical care populations. METHODS: Our approach employs generative topographic mapping, a probabilistic machine learning method, to identify micro-clusters of patients with similar characteristics. It then identifies macro-cluster regions (clinical phenotypes) in the latent space using Ward's minimum variance method. We applied it to two large cohort databases (UK-Biobank and MIMIC-IV) representing general and critical care populations. FINDINGS: The proposed methodology showed its ability to derive meaningful clinical phenotypes of AF. Because of its probabilistic foundations, it can enhance the robustness of patient stratification. It also produced interpretable visualisation of complex high-dimensional data, enhancing understanding of the derived phenotypes and their key characteristics. Using our methodology, we identified and characterised clinical phenotypes of AF across diverse patient populations. INTERPRETATION: Our methodology is robust to noise, can uncover hidden patterns and subgroups, and can elucidate more specific patient profiles, contributing to more robust patient stratification, which could facilitate the tailoring of prevention and treatment programs specific to each phenotype. It can also be applied to other datasets to derive clinically meaningful phenotypes of other conditions. FUNDING: This study was funded by the DECIPHER project (LJMU QR-PSF) and the EU project TARGET (10113624).

Association of healthy lifestyle factors and genetic liability with bipolar disorder: Findings from the UK Biobank.

BACKGROUND: The interplay between genetic and lifestyle factors in the development of bipolar disorder (BD) remains unclear. METHODS: A cohort study was carried out on 365,517 participants from the UK Biobank. Lifestyle scores, based on smoking, physical activity, diet, alcohol consumption, sedentary behavior, sleep duration, and social contact, were grouped as favorable (scores 6-7), intermediate (scores 4-5), or unfavorable (scores 0-3). The BD polygenic risk score (PRS) was also categorized into high, intermediate, and low-risk groups using PRS tertiles. Cox regression models determined hazard ratios (HRs) and 95 % confidence intervals (CIs) for BD. RESULTS: During the 12.9-year follow-up, 529 individuals developed BD. Comparing those with favorable lifestyles to those with unfavorable participants, the HR of developing BD was 3.28 (95 % CI, 2.76-3.89). Similarly, individuals with a high PRS had a risk of 3.20 (95 % CI, 2.83-3.63) compared to those with a low PRS. Notably, individuals with both a high PRS and an unfavorable lifestyle had a significantly higher risk of BD (HR = 6.31, 95 % CI, 4.14-9.63) compared to those with a low PRS and a favorable lifestyle. Additionally, the interaction between PRS and lifestyle contributed an additional risk, with a relative excess risk of 1.74 (95 % CI, 0.40-3.07) and an attributable proportion due to the interaction of 0.37 (95 % CI, 0.16-0.58). CONCLUSIONS: Our findings suggest that genetic liability for BD, measured as PRS, and lifestyle have an additive effect on the risk of developing BD. A favorable lifestyle was associated with a reduced risk of developing BD.

The role of aspirin in the prevention of pancreatic cancer: A nested case-control study in the UK Biobank.

BACKGROUND: Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) usage has been associated with pancreatic ductal adenocarcinoma (PDAC) prevention, though epidemiological data have not reliably demonstrated this. The aim of this study is to identify if aspirin and other NSAIDs are effective in the primary prevention of PDAC in a large UK prospective cohort. METHODS: A nested case-control study was conducted using the UK Biobank cohort. Incident PDAC cases (n = 1129 of whom 239 (21.2 %) were using aspirin) were age and sex-matched with cancer-free controls (n = 8822 of whom 1752 (19.9 %) were using aspirin). Conditional logistic regression models were used to generate odds ratios (ORs) and 95 % confidence intervals (CI) for risk of PDAC with and without regular use of aspirin, non-aspirin NSAIDs and all NSAIDs respectively. Exploratory analyses were carried out assessing interactions with diabetes mellitus (DM) as a condition with increased pancreatic cancer risk. RESULTS: Regular aspirin use at initial recruitment was independently associated with a decreased risk of PDAC (OR [95 % CI] = 0.80 [0.68-0.95] P = 0.01). Regular non-aspirin NSAID use was not associated with a risk reduction of PDAC (OR [95 % CI] = 1.01 [0.84-1.23] P = 0.88). Exploratory analyses showed that in those with DM; regular aspirin use reduced risk of PDAC (OR [95 % CI] = 0.60 [0.42-0.85] P = 0.004) compared to non-use. DISCUSSION: Regular aspirin use is associated with a reduction in risk of PDAC. The reduced risk is more apparent in participants with DM.

Association of glycaemic control with intraocular pressure in a large general population: Results from the UK Biobank.

AIM: To evaluate the association of glycated haemoglobin (HbA1c) and serum glucose with intraocular pressure (IOP) in a large UK general population. MATERIALS AND METHODS: Participants were selected from the UK Biobank, excluding those with eye conditions that may affect IOP. IOP was measured using an ocular response analyser. Goldmann-correlated IOP (IOPg) and corneal-compensated IOP (IOPcc) were outcomes of interest, and ocular hypertension was defined as left-eye IOPg or IOPcc > 21 mmHg. HbA1c and random (non-fasting) serum glucose were the exposures of interest. Multivariate restricted cubic spline models, as well as linear regression, were applied to explore the associations of interest. RESULTS: Among 68 806 participants (46.5% male), the mean age was 56.7 years. The mean (standard deviation) for IOPg was 15.7 (3.6) mmHg and 15.9 (3.6) mmHg for IOPcc. Occular hypertension was prevalent in 8055 participants (11.7%) and 4178 participants (6.1%) had diabetes. Those with diabetes had higher IOP and a higher prevalence of ocular hypertension. After adjustment for demographic and clinical variables, HbA1c was positively associated with IOP in participants with diabetes, but not in those without diabetes. For every 10-mmol/mol increase in HbA1c, IOPg increased by 0.20 mmHg (95% confidence interval [CI] 0.12, 0.28) and IOPcc by 0.15 mmHg (95% CI 0.07, 0.23); the odds of ocular hypertension was increased by 6% (95% CI 1.00, 1.13) in participants with diabetes. A borderline positive association between serum glucose and IOP was found only in participants without diabetes. CONCLUSIONS: Impaired glycaemic control was associated with elevated IOP and a possible risk of ocular hypertension among participants with diabetes but of normal ocular health.

Constipation is associated with an increased risk of major adverse cardiac events in a UK population.

BACKGROUND: Traditional cardiovascular risk factors, including hypertension, only explain part of major adverse cardiac events (MACE). Understanding what other risk factors contribute to MACE is essential for prevention. Constipation shares common risk factors with hypertension and is associated with an increased risk of several cardiovascular diseases. We hypothesised that constipation is an under-appreciated risk factor for MACE. METHODS: We used the population healthcare and genomic data in the UK Biobank (UKBB) (n=408,354) to study the contribution of constipation (ICD-10 K59.0) to the risk of MACE, defined by any episode of acute coronary syndrome (ACS), ischemic stroke and heart failure (HF). Analyses were controlled for traditional cardiovascular risk factors. We also assessed genetic correlations (rg) between constipation and MACE. RESULTS: Constipation cases (N=23,814) exhibited significantly higher risk of MACE compared to those with normal bowel habits (OR=2.15, P<1.00×10-300). Constipation was also significantly associated with individual MACE subgroups, in order: HF (OR=2.72, P<1.00×10-300), ischemic stroke (OR=2.36, P=2.02×10-230), and ACS (OR=1.62, P=5.82×10-113). In comparison with constipation-free hypertensive patients, hypertensives with constipation showed significantly higher odds of MACE (OR=1.68, P=1.05×10-136) and a 34% increased risk of MACE occurrence (P=2.3×10-50) after adjustment for medications that affect gut motility and other traditional cardiovascular risk factors. Finally, we detected positive genetic correlations between constipation and MACE subgroups ACS (rg=0.27, P=2.12×10-6), ischemic stroke (rg=0.23, P=0.011), and HF (rg=0.21, P=0.0062). CONCLUSION: We identified constipation as a potential risk factor independently associated with higher MACE prevalence. These findings warrant further studies on their causal relationship and identification of pathophysiological mechanisms.

The association of circulating systemic inflammation with premature death and the protective role of the Mediterranean diet: a large prospective cohort study of UK biobank.

BACKGROUND: Although previous studies have identified specific circulating inflammatory markers associated with the risk of mortality, they have often overlooked the broader impact of a comprehensive inflammatory response on health outcomes. This study aims to assess the association between circulating systemic inflammation and age-related hospitalization and premature death, as well as explore the potential mediating effects of various dietary patterns on these associations. METHODS: A total of 448,574 participants enrolled in the UK Biobank study were included. Circulating C-reactive protein(CRP), white blood cell count(WBC), platelet count(Plt), and neutrophil/lymphocyte ratio(NLR) were measured, which were used to establish a weighted systemic inflammatory index of inflammation index(INFLA-Score). Dietary intake information was documented through 24-hour dietary recalls, and dietary pattern scores including Dietary Approaches to Stop Hypertension(DASH), Mediterranean(MED), and Healthy Eating Index-2020(HEI-2020) were calculated. Cox proportional hazards regression models were performed to assess the associations between INFLA-Score and age-related disease hospitalization, cause-specific and all-cause premature death. RESULTS: During a median follow-up of 12.65 years, 23,784 premature deaths were documented. After adjusting for multiple covariates, higher levels of CRP, WBC, NLR, and INFLA-Score were significantly associated with increased risks of age-related disease hospitalization(HRCRP=1.19; 95%:1.17-1.21; HRWBC=1.17; 95%:1.15-1.19; HRNLR=1.18; 95%:1.16-1.20; HRINFLA-Score=1.19; 95%:1.17-1.21) and premature death(HRCRP=1.68; 95%:1.61-1.75; HRWBC=1.23; 95%:1.18-1.27; HRNLR=1.45; 95%:1.40-1.50; HRINFLA-Score=1.58; 95%:1.52-1.64). Compared to the lowest INFLA-Score group, the highest INFLA-Score group was associated with increased values of whole-body and organ-specific biological age, and had a shortened life expectancy of 2.96 (95% CI 2.53-3.41) and 4.14 (95% CI 3.75-4.56) years at the age of 60 years in women and men, respectively. Additionally, we observed no significant association of the INFLA-Score with aging-related hospitalization and premature death among participants who were more adhering to the Mediterranean (MED) dietary pattern(HRAging-related hospitalization=1.07; 95%:0.99-1.16;HRPremature death=1.19; 95%:0.96-1.47). CONCLUSION: A higher INFLA-Score was correlated with an increased risk of age-related hospitalization and premature death. Nevertheless, adherence to a Mediterranean (MED) diet may mitigate these associations.

Cardiovascular Health, Polygenic Risk Score and Cancer Risk: A Prospective Cohort Study.

BACKGROUND: Cancer and cardiovascular disease shared common lifestyle risk factors. However, it remains unclear whether cardiovascular health (CVH) evaluated by Life's Essential 8 can predict cancer risk, and attenuate the influence of genetic susceptibility on cancer. OBJECTIVE: We aimed to evaluate independent and joint associations of CVH and polygenic risk score (PRS) with risks of overall and site-specific cancers. METHODS: We undertook a population-based cohort study based on the UK Biobank. The CVH score was constructed by physical activity, body mass index, nicotine exposure, sleep, diet, blood pressure, lipid profile, and blood glucose. PRSs were assessed individually for 18 cancer types by their independent single-nucleotide polymorphisms previously reported in genome-wide association studies. Multivariable Cox proportional hazards models were applied to explore the independent and joint associations of CVH and PRS with cancer incidence risk. The results were displayed as hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Compared with low CVH, high CVH was associated with decreased risks of overall cancer and the majority of common cancers, including digestive system [HRs (95% CI): 0.33 (0.23, 0.45)-0.66 (0.58, 0.75)], lung [HR (95% CI): 0.25 (0.21, 0.31)], renal [HR (95% CI): 0.42 (0.32, 0.56)], bladder [HR (95% CI): 0.55 (0.44, 0.69)], breast [HR (95% CI): 0.83 (0.74, 0.92)] and endometrial cancers [HR (95% CI): 0.39 (0.30, 0.51)]. For overall cancer in males, there was an interaction between CVH and PRS. Notably, individuals with high CVH across all levels of PRS had lower risks of overall cancer for females and eight site-specific cancers than those with low CVH and high PRS [HRs (95%CIs): 0.18 (0.12, 0.25)-0.79 (0.71, 0.87)]. CONCLUSIONS: High CVH was related to decreased risks of overall cancer and multiple cancers regardless of genetic predispositions. Our findings underscored the value of improving CVH for cancer prevention in the general population.

An Exploration of Shared Risk Factors for Coronary Artery Disease and Cancer from 109 Traits: The Evidence from Two-Sample Mendelian Randomization Studies.

Background: Although observational studies have reported several common biomarkers related to coronary artery disease (CAD) and cancer, there is a shortage of traditional epidemiological data to establish causative linkages. Thus, we conducted a comprehensive two-sample Mendelian randomization (MR) analysis to systematically investigate the causal associations of 109 traits with both CAD and cancer to identify their shared risk and protective factors. Methods: The genetic association datasets pertaining to exposure and outcomes were reviewed using the most recent and public genome-wide association studies (GWAS). Inverse variance weighting (IVW), weighted median (WM), and MR-Egger strategies were implemented for the MR analyses. The heterogeneity and pleiotropy were measured utilizing leave-one-out sensitivity testing, MR-PRESSO outlier detection, and Cochran's Q test. Results: The IVW analyses revealed that genetic-predicted mean sphered cell volume (MSCV) is a protective factor for CAD, and weight is a risk factor. MSCV and weight also show similar effects on cancer. Furthermore, our study also identified a set of risk and protective factors unique to CAD and cancer, such as telomere length. Conclusions: Our Mendelian randomization study sheds light on shared and unique risk and protective factors for CAD and cancer, offering valuable insights that could guide future research and the development of personalized strategies for preventing and treating these two significant health issues.