Life's essential 8, genetic susceptibility, and risk of inflammatory bowel diseases: a population-based cohort study.

BACKGROUND: Evidence has shown that the individual metrics in Life's Essential 8 (LE8), an updated cardiovascular health (CVH) concept proposed by the American Heart Association, play a role in the development of inflammatory bowel disease (IBD). However, epidemiological evidence on the overall LE8 on IBD risk remains limited. We aimed to assess the longitudinal associations of LE8-defined CVH and the risks of IBD and its subtypes, ulcerative colitis (UC) and Crohn's disease (CD). We also tested whether genetic susceptibility could modify these associations. METHODS: A total of 260,836 participants from the UK Biobank were included. LE8 scores were determined by 8 metrics (physical activity, diet, nicotine exposure, sleep, body mass index, blood pressure, blood glucose, and blood lipids), and were divided into three levels: low CVH (0-49), moderate CVH (50-79), and high CVH (80-100). Cox proportional hazards models were used to calculate the hazard ratios (HRs) and confidence intervals (CIs) of the risk of IBD in relation to CVH status. RESULTS: Over a median follow-up 12.3 years, we documented 1,500 IBD cases (including 1,070 UC and 502 CD). Compared to participants with low CVH, the HRs (95% CIs) of those with high CVH for IBD, UC, and CD were 0.67 (0.52, 0.83), 0.70 (0.52, 0.93), and 0.55 (0.38, 0.80), respectively. These associations were not modified by genetic susceptibility (all P for interactions > 0.05). The lowest HR (UC: 0.30, 95% CI: 0.20-0.45; CD: 0.33, 95% CI: 0.20-0.57) was observed in participants with both high CVH and low genetic risk. CONCLUSIONS: Better CVH, defined by LE8, was associated with significantly lower risks of IBD, UC, and CD, irrespective of genetic predisposition. Our results underscore the importance of adherence to LE8 guidelines for maintaining CVH as a potential strategy in the prevention of IBD.

Life's Essential 8, genetic susceptibility, and the risk of psoriatic disease: a prospective cohort study.

BACKGROUND: Psoriatic disease (PsD) is closely associated with cardiovascular diseases. The Life's Essential 8 (LE8) score is a new metric for assessing cardiovascular health (CVH), where a higher score indicates better CVH. However, the longitudinal association between LE8 score and the risk of PsD remains uncertain. The main aim of the present study was to explore the association between LE8 scores and the risk of PsD. OBJECTIVE: To investigate the associations between LE8 score, genetic susceptibility, and the risk of PsD within a cohort design. METHODS: This cohort study included 261,642 participants from the UK Biobank without PsD at baseline. LE8 comprises eight indicators: diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipids, blood glucose, and blood pressure. Cox proportional hazard models were employed to examine the association between the participants' LE8 scores, PsD genetic risk, and the risk of PsD. Hazard ratios (HRs) and 95% confidential intervals (CIs) were calculated. RESULTS: During an average follow-up of 12.32 years, 1,501 participants developed PsD. Compared to participants with low LE8 scores, the HRs (95% CIs) of developing PsD for those with moderate and high LE8 scores were 0.51 (0.43, 0.59) and 0.34 (0.27, 0.42) after adjustments, respectively. Dose-response analysis revealed a linear negative association between continuous LE8 score and the risk of developing PsD (P < 0.001), with no evidence of non-linear association detected. The genetic susceptibility to PsD did not modify this association (P for interaction = 0.63). Subgroup analyses revealed that women demonstrated a more pronounced beneficial association between LE8 scores and PsD risk (P for interaction = 0.02). CONCLUSIONS: Our study suggests that a higher LE8 score, regardless of genetic risk, was associated with a lower risk of PsD, particularly among women. Consequently, maintaining a high CVH status is recommended to prevent PsD and assess associated risks.

Life's Essential 8 and risks of cardiovascular morbidity and mortality among individuals with type 2 diabetes: A cohort study.

BACKGROUND: The association of cardiovascular health levels, as measured by the Life's Essential 8 score, with cardiovascular disease (CVD) incidence and mortality among individuals with type 2 diabetes (T2D) has not been fully elucidated. METHODS: This cohort study included 15,118 participants with T2D from the UK Biobank who were free of CVD and cancer at baseline. The cardiovascular health of participants was evaluated using the Life's Essential 8 score, categorizing their health levels into low, moderate, and high based on this assessment. RESULTS: During a median follow-up period of 13.0 years, we observed a total of 4421 cases of CVD, comprising 3467 cases of coronary heart disease (CHD), 811 cases of stroke, 1465 cases of heart failure (HF), and 523 cases of CVD mortality. Compared to participants with low cardiovascular health, those with high cardiovascular health had a 52 %, 50 %, 47 %, 67 %, and 51 % lower risk of CVD, CHD, stroke, HF, and CVD mortality, respectively. Among the components of the Life's Essential 8 score, body mass index showed the highest population attributable risk of 12.1 %. Similar findings were observed in joint analyses of cardiovascular health and diabetes severity status. CONCLUSIONS: This study emphasizes the importance of maintaining good cardiovascular health among individuals with T2D to reduce their risk of CVD incidence and mortality.

Associations between frailty, genetic predisposition, and chronic kidney disease risk in middle-aged and older adults: A prospective cohort study.

OBJECTIVES: Cross-sectional evidence has shown that frailty is highly prevalent in patients with chronic kidney disease (CKD). However, there is limited evidence of the longitudinal associations between frailty, genetic predisposition to CKD, and the risk of CKD in the general population. Therefore, this study aimed to examine such associations among participants in the UK Biobank. STUDY DESIGN: This is a prospective cohort study included 370,965 middle-aged and older adults from the UK Biobank. Physical frailty was assessed using a modified version of the Fried phenotype classification. A weighted genetic risk score was built using 263 variants associated with estimated glomerular filtration rate. MAIN OUTCOME MEASURES: Incident CKD was identified from hospital inpatient records. RESULTS: Over a median follow-up of 12.3 years, we documented a total of 11,121 incident CKD cases. Time-dependent Cox proportional hazards regression models indicated that individuals with frailty (hazard ratio [HR]: 1.94, 95 % confidence interval [CI]: 1.81-2.08) and pre-frailty (HR: 1.27, 95 % CI: 1.22-1.33) had an increased risk of developing CKD, compared with non-frail individuals. No significant interaction between frailty and genetic risk score was observed (P for interaction = 0.41). The highest risk was observed among the individuals with high genetic risk and frailty (HR: 2.31, 95 % CI: 2.00-2.68). CONCLUSION: Our results demonstrated that frailty and pre-frailty were associated with increased risk of incident CKD in middle-age and older adults, regardless of genetic risk of CKD. Our study underscores the importance of frailty screening and intervention as a potential strategy to prevent CKD. Future clinical trials are needed to validate our findings.

Physical frailty, genetic predisposition, and the risks of severe non-alcoholic fatty liver disease and cirrhosis: a cohort study.

BACKGROUND: Frailty, defined as a phenotype of decreased physiological reserves and diminished ability to respond to stressors, has been linked to the development of chronic diseases. Epidemiological evidence connecting frailty to non-alcoholic fatty liver disease (NAFLD) and cirrhosis risks remain sparse. We aimed to assess the longitudinal associations of frailty with the risks of severe NAFLD and cirrhosis in middle-aged to older adults and further explore the modification role of genetic risk on these associations. METHODS: This study included a total of 398 386 participants from the UK Biobank. Incident cases of severe NAFLD and cirrhosis were ascertained through linked hospital records and death registries. Frailty status was assessed by a modified version of the frailty phenotype, encompassing five key components: weight loss, tiredness, physical activity, gait speed, and grip strength. Participants were classified as pre-frailty if they met one or two of these criteria, and as frailty if they met three or more. Genetic predisposition to NAFLD and cirrhosis was estimated by genetic risk score (GRS) and further categorized into high, intermediate, and low genetic risk levels according to tertiles of GRSs. Cox proportional hazards regression model was employed to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for their associations. RESULTS: The mean (standard deviation) age of the study population was 56.6 (8.03) years. 214 408 (53.8%) of the participants was female; 14 924 (3.75%) of participants met the criteria for frailty, 170 498 (42.8%) for pre-frailty, and 212 964 (53.5%) for non-frailty. Over a median follow-up of 12.0 years, we documented 4439 incident severe NAFLD and 3323 incident cirrhosis cases, respectively. Compared with non-frailty, both pre-frailty (HR: 1.50; 95% CI: 1.40-1.60) and frailty (HR: 1.98; 95% CI: 1.77-2.21) were associated with increased risk of NAFLD. Similar associations were observed for cirrhosis, the corresponding HRs (95% CIs) for non-frailty, pre-frailty, and frailty were 1.00 (reference), 1.29 (1.20, 1.38), and 1.90 (1.66, 2.18). Such associations were consistent across all genetic risk levels, with no observed interactions between frailty and GRSs (all P for interactions ≥0.10). Compared with participants with frailty and a low level of genetic risk, the greatest risk increasement in developing severe NAFLD (HR: 3.36; 95% CI: 2.83-3.99) and cirrhosis (HR: 2.81; 95% CI: 2.29-3.44) was both observed in those with frailty and a high level of genetic risk. CONCLUSIONS: Our findings indicate that frailty is a significant predictor of severe NAFLD and cirrhosis, irrespective of genetic predisposition.

Physical frailty, genetic predisposition, and incident arrhythmias.

BACKGROUND: Cross-sectional evidence suggests a possible link between frailty and atrial fibrillation (AF). It remains unclear whether frailty and incident arrhythmias are longitudinally associated. This study aimed to determine whether the frailty phenotype is longitudinally associated with incident arrhythmias, especially AF. METHODS: In this prospective cohort of UK Biobank, individuals with arrhythmias at baseline, those without data for frailty phenotype, and no genetic data were excluded. Five domains of physical frailty, including weight loss, exhaustion, low physical activity, low grip strength, and slow gait speed, were assessed. A total of 142 single-nucleotide polymorphisms was used to calculate the polygenic risk score (PRS) for AF. Hospital inpatient records and death records were used to identify incident arrhythmias. RESULTS: This study included 464 154 middle-aged and older adults (mean age 56.4 ± 8.1 years, 54.7% female) without arrhythmia at baseline. During a median follow-up of 13.4 years (over 5.9 million person-years), 46 454 new-onset arrhythmias cases were recorded. In comparison with non-frailty, the multivariable-adjusted hazard ratios (HRs) of AF were 1.12 (95% CI: 1.09, 1.15, P < 0.0001) and 1.44 (95% CI: 1.36, 1.51, P < 0.0001) for participants with pre-frailty and frailty, respectively. Similar associations were observed for other arrhythmias. We found that slow gait speed presented the strongest risk factor in predicting all arrhythmias, including AF (HR 1.34, 95% CI: 1.30, 1.39), bradyarrhythmias (HR 1.30, 95% CI: 1.22, 1.37), conduction system diseases (HR 1.29, 95% CI: 1.22, 1.36), supraventricular arrhythmias (HR 1.32, 95% CI: 1.19, 1.47), and ventricular arrhythmias (HR 1.37, 95% CI: 1.25, 1.51), with all P values <0.0001. In addition to slow gait speed, weight loss (HR 1.13, 95% CI: 1.09, 1.16, P < 0.0001) and exhaustion (HR 1.11, 95% CI: 1.07, 1.14, P < 0.0001) were significantly associated with incident AF, whereas insignificant associations were observed for physical activity (HR 1.03, 95% CI: 0.996, 1.08, P = 0.099) and low grip strength (HR 1.00, 95% CI: 0.97, 1.03, P = 0.89). We observed a significant interaction between genetic predisposition and frailty on incident AF (P for interaction <0.0001), where those with frailty and the highest tertile of PRS had the highest risk of AF (HR 3.34, 95% CI: 3.08, 3.61, P < 0.0001) compared with those with non-frailty and the lowest tertile of PRS. CONCLUSIONS: Physical pre-frailty and frailty were significantly and independently associated with incident arrhythmias. Although direct causal inference still needs to be further validated, these results suggested the importance of assessing and managing frailty for arrhythmia prevention.

Association of the serum levels of saturated fatty acids and mild cognitive impairment: a cross-sectional study.

OBJECTIVES: To investigate the association of serum saturated fatty acids (SFAs) and prevalent mild cognitive impairment (MCI) among middle-aged and elderly Chinese. METHODS: A total of 607 Chinese adults aged at least 45 years were included in the baseline survey of The Lifestyle and Healthy Aging of Chinese Square Dancer Study. Serum concentrations of individual SFAs including 6 even-chain SFAs (C14:0, C16:0, C18:0, C20:0, C22:0, and C24:0) and 4 odd-chain SFAs (C15:0, C17:0, C21:0, and C23:0), were quantified by Gas chromatography system with a mass spectrometer. According to Petersen's criteria, prevalent MCI was diagnosed by neurologists through uniformed neuropsychological tests, including trail-making test-part B (TMT-B), auditory verbal learning test (AVLT), digit symbol substitution test (DSST), and verbal fluency test (VFT). RESULTS: The median age was 62 years with an interquartile range of 57.0 to 67.0 years, and 86 (14.17%) participants were living with MCI. Higher levels of either even-chain or odd-chain individual SFAs were associated with the higher odds of MCI, and their odds ratios (ORs) and 95% confidence intervals (95%CIs) were 2.054 (1.012 to 4.171) for C14:0, 2.246 (1.061 to 4.755) for C16:0, 2.789 (1.321 to 5.886) for C18:0, and 2.329 (1.136 to 4.778) for C15:0, and 2.761 (1.310 to 5.820) for C17:0, respectively. CONCLUSIONS: The serum concentration of SFAs was positively related to the odds of MCI in middle-aged and elderly adults. Determining the link between SFAs profiles and MCI may inform a better understanding of the potential role of saturated fat intake on cognitive function.

Pulmonary function, genetic predisposition, and the risk of cirrhosis: A prospective cohort study.

OBJECTIVE: Pulmonary function is associated with the development of chronic liver disease. However, evidence of the association between pulmonary function and cirrhosis risk is still lacking. This study aimed to investigate the longitudinal associations of pulmonary function with the development of cirrhosis, and to explore whether genetic predisposition to cirrhosis could modify these associations. METHODS: Of 294,835 participants free of cirrhosis and had undergone spirometry at baseline from the UK Biobank were included. Cirrhosis diagnoses were ascertained through linked hospital records and death registries. Cox proportional hazard models were employed to investigate the longitudinal associations between pulmonary function, genetic predisposition, and cirrhosis risk. RESULTS: During a median follow-up of 12.0 years, 2598 incident cirrhosis cases were documented. Compared to individuals with normal spirometry findings, those with preserved ratio impaired spirometry (PRISm) findings (hazard ratio [HR] and 95% confidence interval [CI]: 1.32 [1.18, 1.48]) and airflow obstruction (HR [95%CI]: 1.19 [1.07, 1.31]) had a higher risk of developing cirrhosis after adjustments. These associations were consistent across all categories of genetic predisposition, with no observed modifying effect of genetic predisposition. In joint exposure analyses, the highest risk was observed in individuals with both a high genetic predisposition for cirrhosis and PRISm findings (HR [95% CI]: 1.74 [1.45, 2.08]). CONCLUSIONS: Our findings indicate that worse pulmonary function is a significant risk factor of cirrhosis, irrespective of genetic predisposition. Early identification and appropriate intervention for pulmonary function may lead to more effective healthcare resource utilization and reduce the burden associated with cirrhosis.

Intensity-Specific Physical Activity Measured by Accelerometer, Genetic Susceptibility, and the Risk of Kidney Stone Disease: Results From the UK Biobank.

RATIONALE & OBJECTIVE: Kidney stone disease (KSD), a significant healthcare problem within both developed and developing countries, has been associated with genetic risk factors. As well, an association between physical activity and KSD risk has been hypothesized but studies have yielded inconsistent findings. This study aimed to investigate the association between the intensity of physical activity and the incidence of KSD accounting for genetic risk. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: A total of 80,473 participants from the UK Biobank Study. EXPOSURES: Physical activity levels, including total physical activity (TPA), moderate-to-vigorous intensity physical activity (MVPA), and light-intensity physical activity (LPA), were measured using accelerometers and quantified using a machine learning model. A polygenic risk score (PRS) for KSD was also constructed. OUTCOMES: Individuals with KSD were identified using the International Classification of Diseases 10th Edition, and procedure codes for KSD surgery. ANALYTICAL APPROACH: A Fine and Gray survival model was used to estimate the associations of incident KSD with TPA, MVPA, LPA, and PRS (as categorical variables). Restricted cubic splines were used to examine potential non-linear associations within the fully adjusted models. RESULTS: During an average follow-up of 6.19 years, 421 participants developed KSD. Participants in the highest quartiles of TPA, MVPA, and LPA had lower adjusted rates of KSD compared to those in the lowest quartiles: HRs (95% confidence interval) of 0.50 (0.44, 0.56), 0.57 (0.51, 0.64), and 0.66 (0.59, 0.74), respectively. TPA, MVPA, and LPA were associated with lower risk of KSD in participants with low and high genetic predisposition for KSD. LIMITATIONS: Selection bias as participants who provided accelerometry data may have been more adherent to health care. CONCLUSION: Physical activity was negatively associated with the risk of KSD, regardless of the genetic risk. Future large studies are warranted to confirm and explain the mechanisms underlying these associations.

Intensity-specific physical activity measured by accelerometer and the risk of mortality among individuals with cardiometabolic diseases: A prospective study from the UK Biobank.

BACKGROUND: While the health benefits of physical activity for general population are well-recognized, the prospective associations of physical activity volume and intensity with mortality among cardiometabolic disease individuals remain unclear. OBJECTIVE: The objective of this study was to investigate the associations of accelerometer-measured intensity-specific physical activity with mortality risk among population with cardiometabolic disease. DESIGN: Prospective cohort study. SETTING: Participants were recruited from the United Kingdom (UK) across 22 assessment centers from 2006 to 2010. PARTICIPANTS: A total of 9524 participants from the UK Biobank (median: 67.00 years, interquartile range: 61.00-70.00 years) were included in final study. METHODS: Accelerometer-measured total volume, moderate-to-vigorous and light intensity physical activity collecting from 2013 to 2015 were quantified using a machine learning model. Multivariable restricted cubic splines and Cox proportional hazard models with hazard ratios (HRs) and 95 % confidence intervals (CIs) were employed to examine the associations of interests. RESULTS: During the follow-up period (median: 6.87 years; interquartile range: 6.32-7.39 years), there were 659 (6.92 %) death events with 218 (2.29 %) cardiovascular disease-related deaths and 441 (4.63 %) non-cardiovascular disease-related deaths separately. In the fully adjusted models, compared with participants in the lowest quartiles of total volume, moderate-to-vigorous and light physical activities, the adjusted HRs (95 % CIs) of all-cause mortality for those in the highest quartiles were 0.40 (0.31, 0.52), 0.48 (0.37, 0.61), and 0.56 (0.44, 0.71) while those for cardiovascular diseases-related mortality were 0.35 (0.22, 0.55), 0.52 (0.35, 0.78) and 0.59 (0.39, 0.88), and for non-cardiovascular diseases-related mortality, they were 0.42 (0.30, 0.59), 0.40 (0.29, 0.54) and 0.54 (0.40, 0.73), separately. The optimal moderate-to-vigorous-intensity physical activity level for cardiovascular diseases-related mortality reduction was found to be in the third quartile (17.75-35.33 min/day). Furthermore, the observed inverse associations were mainly non-linear. CONCLUSIONS: Promoting physical activity, regardless of intensity, is essential for individuals with cardiometabolic disease to reduce mortality risk. For both all-cause and cardiovascular disease-related and non-cardiovascular disease-related mortality, the observed decrease in risk seems to level off at a moderate level. The current findings deriving from precise device-based physical activity data provide inference for secondary prevention of cardiometabolic disease.

Serum urate levels and neurodegenerative outcomes: a prospective cohort study and mendelian randomization analysis of the UK Biobank.

BACKGROUND: Previous studies on the associations between serum urate levels and neurodegenerative outcomes have yielded inconclusive results, and the causality remains unclear. This study aimed to investigate whether urate levels are associated with the risks of Alzheimer's disease and related dementias (ADRD), Parkinson's disease (PD), and neurodegenerative deaths. METHODS: This prospective study included 382,182 participants (45.7% men) from the UK Biobank cohort. Cox proportional hazards models were used to assess the associations between urate levels and risk of neurodegenerative outcomes. In the Mendelian randomization (MR) analysis, urate-related single-nucleotide polymorphisms were identified through a genome-wide association study. Both linear and non-linear MR approaches were utilized to investigate the potential causal associations. RESULTS: During a median follow-up period of 12 years, we documented 5,400 ADRD cases, 2,553 PD cases, and 1,531 neurodegenerative deaths. Observational data revealed that a higher urate level was associated with a decreased risk of ADRD (hazard ratio [HR]: 0.93, 95% confidence interval [CI]: 0.90, 0.96), PD (HR: 0.87, 95% CI: 0.82, 0.91), and neurodegenerative death (HR: 0.88, 95% CI: 0.83, 0.94). Negative linear associations between urate levels and neurodegenerative events were observed (all P-values for overall < 0.001 and all P-values for non-linearity > 0.05). However, MR analyses yielded no evidence of either linear or non-linear associations between genetically predicted urate levels and the risk of the aforementioned neurodegenerative events. CONCLUSION: Although the prospective cohort study demonstrated that elevated urate levels were associated with a reduced risk of neurodegenerative outcomes, MR analyses found no evidence of causality.

The Inverted U-Shaped Association between Serum Vitamin D and Serum Uric Acid Status in Children and Adolescents: A Large Cross-Sectional and Longitudinal Analysis.

BACKGROUND: Serum vitamin D is associated with hyperuricemia. However, previous studies have been controversial, with limited focus on children and adolescents. OBJECTIVE: This study aimed to examine the cross-sectional and longitudinal associations between serum vitamin D and serum uric acid (SUA) levels in children and adolescents. METHODS: The cross-sectional survey comprised 4777 participants aged 6 to 18 years, while the longitudinal survey involved 1641 participants aged 6 to 12 years, all derived from an ongoing cohort study in Shenzhen, China. Restricted cubic splines were used to visualize the dose-response relationship between vitamin D and SUA and the risk of higher SUA status. Two-segment generalized linear models (GLM) and logistic models were used to assess the association between vitamin D and SUA and higher SUA status, respectively. The longitudinal analysis used GLM. RESULTS: We observed an inverted U-shaped relationship between vitamin D and SUA (p-overall < 0.0001, p-nonlinear = 0.0002), as well as the risk of higher SUA status (p-overall = 0.0054, p-nonlinear = 0.0015), with the vitamin D inflection point at 24.31 and 21.29 ng/mL, respectively. A 10 ng/mL increment in 25(OH)D3 levels, when below 20.92 ng/mL, was associated with a 68% rise in the risk of higher SUA status (OR: 1.68, 95%CI: 1.07-2.66). Conversely, when 25(OH)D3 levels were above or equal to 20.92 ng/mL, a 10 ng/mL increment was associated with a 45% reduction risk of higher SUA status (OR: 0.55, 95%CI: 0.36-0.84). Longitudinal analysis indicated that the annual change of SUA was from -4.80 (ß, 95%CI: -10.74, 1.13) to -9.00 (ß, 95%CI: -15.03, -2.99) and then to -6.77 (ß, 95%CI: -12.83, -0.71, p for trend = 0.0212) µmol/L when increasing the quartile of vitamin D3. CONCLUSIONS: An inverse U-shaped relationship was observed between vitamin D and SUA as well as the risk of higher SUA status. Sufficient vitamin D levels appear to play a preventative role against the age-related increase in SUA. Ensuring adequate vitamin D levels may be beneficial in improving uric acid metabolism.

Ultra-processed food consumption, genetic susceptibility, and the risk of hip/knee osteoarthritis.

BACKGROUND: The associations between ultra-processed food (UPF) consumption, genetic susceptibility, and the risk of osteoarthritis (OA) remain unknown. This study was to examine the effect of UPF consumption, genetic susceptibility, and their interactions on hip/knee OA. METHODS: Cohort analyses included 163,987 participants from the UK Biobank. Participants' UPF consumption was derived from their 24-h dietary recall using a questionnaire. Genetic risk scores (GRSs) of 70 and 83 single nucleotide polymorphisms (SNPs) for hip and knee OA were constructed. FINDINGS: After 1,461,447 person-years of follow-up, 11,540 patients developed OA. After adjustments, compared to participants in the low quartile of UPF consumption, those in the high quartile had a 10 % (hazard ratio [HR], 1.10; 95% confidence interval [CI], 1.03-1.18) increased risk of knee OA. No significant association was found between UPF consumption and hip OA. Replacing 20% of UPF diet weight with an equivalent proportion of unprocessed or minimally processed food caused a 6% (HR, 0.94; 95% CI, 0.89-0.98) decreased risk of knee OA, respectively. A significant interaction was found between UPF consumption, genetic predisposition, and the risk of knee OA (P = 0.01). Participants with lower OA-GRS scores experienced higher knee OA risks due to UPF consumption. INTERPRETATION: UPF consumption was associated with a higher risk of knee OA but not hip OA, particularly in those with lower genetic susceptibility. These results highlight the importance of reducing UPF consumption to prevent knee OA.

Joint association of serum urate and healthy diet with chronic obstructive pulmonary disease incidence: results from the UK Biobank study.

Background: The role of serum urate (SU) levels in the development of chronic obstructive pulmonary disease (COPD) remains a topic of debate, and it is unclear whether a healthy diet can mitigate the impact of SU on COPD risk. The objective of this study is to examine whether and to what extent a healthy diet can reduce the risk of COPD in relation to SU levels. Methods: The cohort analysis included 155 403 participants from the UK Biobank. SU levels were measured at the time of recruitment. A healthy diet score was calculated based on the consumption of vegetables, fruits, fish, processed meats, unprocessed red meat, whole grains, and refined grains. The Cox proportional hazards model was used to analyze the associations between SU levels, a healthy diet score, and the risk of COPD. Results: During a follow-up period of 1 409 969 person-years, 2918 incident cases of COPD were identified. Compared with the lowest SU level group, the hazard ratio (HR) and 95% confidence interval (CI) for COPD were 1.17 (1.03, 1.34) for participants with the highest SU level (hyperuricemia), indicating a positive association. Additionally, a dose-response relationship was observed between SU levels and the incidence of COPD (P-value for overall <0.0001). In the combined effect analysis, compared to individuals with high SU (hyperuricemia) + a low diet score (diet score <4), those with normal SU + a high diet score (diet score ≥4) had a HR (95% CI) of 0.75 (0.65, 0.87) for COPD. Conclusions: In summary, there is a positive association between SU levels and the risk of COPD. Furthermore, a healthier diet can mitigate the risk of COPD associated with high SU levels.

Sugar types, genetic predictors of the gut microbiome, and the risk of chronic kidney disease: a prospective cohort study.

Background: Emerging studies suggest that focusing on the intake of specific types or sources of sugars may yield greater benefits in preventing chronic kidney disease (CKD). Objective: We aimed to investigate the associations between free and non-free sugar intakes and CKD risk as well as the potential sugar type-gut microbiome interactions. Methods: A total of 138 064 participants from the UK Biobank were included in this prospective study. The free and non-free sugar intakes were assessed using repeated web-based 24-hour dietary recalls. A cause-specific competing risk model was used to estimate hazard ratios (HRs) and the corresponding confidence intervals (CIs) of incident CKD, treating deaths before incident CKD as competing events. Results: During a median follow-up of 10.5 years, 2,923 participants (2.1%) developed CKD. The free sugar intake was positively associated with the risk of CKD (HRquartile 4 vs. quartile 1 = 1.32, 95% CI = 1.18, 1.47), with a nonlinear relationship (P for nonlinearity = 0.01, the risk increased rapidly after free sugars made up 10% of the total energy). The non-free sugar intake was inversely associated with CKD risk (HRquartile 4 vs. quartile 1 = 0.68, 95% CI = 0.60, 0.77), with an L-shaped nonlinear curve (p for nonlinearity = 0.01, the turning point was at 13.5% of the total energy). We found that the associations between free sugar and non-free sugar intakes and CKD risk were more pronounced in participants with high genetically predicted gut microbial abundance. Furthermore, a significant interaction was observed between the genetically predicted gut microbial abundance and non-free sugar intake (P for interaction = 0.04). Conclusion: A higher intake of free sugars was associated with an elevated risk of CKD, whereas a higher intake of non-free sugars was associated with a reduced risk of CKD. The impact of free sugar intake and non-free sugar intake may be modified by the gut microbial abundance.

[Association of polymorphisms in SEC16B, DNAJC27, FTO and MC4R genes with overweight and obesity in Han preschool children].

OBJECTIVE: To investigate the association of polymorphisms in SEC16B rs633715, DNAJC27 rs713586, FTO rs11642015 and MC4R rs6567160 with overweight and obesity in Han Chinese preschool children. METHODS: A total of 749 Han Chinese preschool children from Henan and Guizhou Province of Long-term Health Effects Assessment Project of Infants and Toddlers Nutritional Pack were selected for the study and divided into an overweight and obese group and a normal control group in 2022. rs633715, rs713586, rs11642015 and rs6567160 were genotyped using Kompetitive allele-specific PCR(KASP) technology. The distribution of genotypic polymorphisms was compared using the χ~2 test. The association between the four loci and overweight and obesity in preschool children was analyzed using a multifactorial logistic regression model. RESULTS: The statistical analysis revealed a significant disparity(P<0.05) in the distribution of genotypic polymorphisms of rs633715 and rs6567160 among preschoolers in Henan and Guizhou Province. CC heterozygous mutant and recessive models at rs633715 locus were associated with susceptibility to overweight and obesity in preschool children [OR and 95% CI 2.915(1.163-7.305), and 2.997(1.226-7.323), respectively, both P<0.05]. TC heterozygous mutant and dominant models at rs713586 locus were also associated susceptibility to overweight and obesity in preschool children(OR and 95% CI were 2.362(1.054-5.289)and 2.362(1.054-5.289), respectively, both P<0.05). rs11642015 and rs6567160 loci were not associated with susceptibility to overweight and obesity in preschool children(P>0.05). The result of the analysis of the cumulative effect of rs633715 and rs713586 showed that the number of genotypes carrying the risk genotype was positively associated with the risk of overweight and obesity in preschool children(P_(trend)<0.01). CONCLUSION: Among Han Chinese preschool children, SEC16B rs633715 and DNAJC27 rs713586 were associated with susceptibility to overweight and obesity in preschool children. Moreover, rs633715 and rs713586 had a cumulative effect on susceptibility to overweight and obesity in preschool children, the number of risk genotypes carried was positively associated with childhood overweight and obesity risk.

Intake of the different types of dairy products, genetic predisposition, and the risks of nonalcoholic fatty liver disease and cirrhosis: a prospective cohort study.

Background: The association of dairy product consumption with nonalcoholic fatty liver disease (NAFLD) and cirrhosis remains controversial. This study aimed to prospectively investigate the associations between the consumption of the different types of dairy products, genetic predisposition, and the risks of NAFLD and cirrhosis. Methods: This cohort study included 190 145 participants from the UK Biobank Study. The consumption of the different types of dairy products was assessed based on the Oxford WebQ at baseline and defined as the sum of milk, yogurt, and cheese. NAFLD and cirrhosis were evaluated using hospital inpatient records and death data in the UK Biobank. The weighted genetic risk score (GRS) for NAFLD and cirrhosis was constructed using 5 and 6 single-nucleotide variants (SNVs), respectively. Cox proportional hazards regression models were utilized to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between genetic factors and different types of dairy products with the incidence of NAFLD and cirrhosis. Results: During a median follow-up of 11.6 years, 1512 NAFLD and 556 cirrhosis cases were ascertained. After adjusting for several potential confounders, the HRs (95% CIs) (Q4 vs. Q1) of NAFLD were 0.86 (0.74, 0.995) for total dairy products, 0.96 (0.84, 1.09) for high-fat dairy products, 0.78 (0.67, 0.92) for low-fat dairy products, 0.86 (0.74, 0.99) for unfermented dairy products, and 0.79 (0.68, 0.91) for fermented dairy products. The multivariable-adjusted HRs (95% CIs) (Q4 vs. Q1) of cirrhosis were 0.75 (0.59, 0.96) for total dairy products, 0.97 (0.78, 1.19) for high-fat dairy products, 0.67 (0.51, 0.89) for low-fat dairy products, 0.75 (0.59, 0.96) for unfermented dairy products, and 0.71 (0.56, 0.90) for fermented dairy products. The associations of high-fat dairy products and fermented dairy products with NAFLD and cirrhosis were found to be nonlinear (P for nonlinear <0.05). No interaction was observed between dairy product consumption and NAFLD or cirrhosis genetic susceptibility. Conclusions: Higher consumption of dairy products, except for high-fat dairy, was correlated with lower risks of NAFLD and cirrhosis, regardless of their differences in genetic susceptibility.

Diabetes status, genetic susceptibility, and incident arrhythmias: A prospective cohort study of 457,151 participants.

AIMS: The association of diabetes onset age and duration with incident arrhythmias remains unclear. This study evaluates the association of diabetes onset age and duration with incident arrhythmias and assesses modifications by the genetic predisposition to atrial fibrillation (AF). METHODS: We included 457,151 participants from the UK Biobank study. Multivariable Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) were used for the association between diabetes status, genetic predisposition, and risk of incident arrhythmias. The polygenic risk score (PRS) for AF comprised 142 single-nucleotide variants. RESULTS: Over 12 years of follow-up, we documented 23,518 AF, 9079 bradyarrhythmia, 9280 conduction system diseases, 3358 supraventricular arrhythmias, and 3095 ventricular arrhythmias. Compared with non-diabetes, the risks of AF increased by 19%, 25%, and 36% for those with diabetes durations <5, 5-9, and ≥10 years, respectively. After multivariate adjustment, with the increase in diabetes onset age, the HRs of outcomes were gradually attenuated. The multivariable-adjusted HRs (95% CI) of diabetes for AF were 1.46 (1.24-1.71) in early middle age (<55 years), 1.21 (1.12-1.30) in late middle age (55-64 years), and 1.15 (1.06-1.24) in the elderly population (≥65 years). A significant interaction between diabetes status and AF-PRS for incident AF was observed (P for interaction <0.001). The same trends were observed for the other arrhythmias. CONCLUSIONS: Diabetes was associated with higher risks of incident arrhythmias, and younger age at onset of diabetes was significantly associated with higher risk of subsequent arrhythmias.

Global epidemiology of type 2 diabetes in patients with NAFLD or MAFLD: a systematic review and meta-analysis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD) shares common pathophysiological mechanisms with type 2 diabetes, making them significant risk factors for type 2 diabetes. The present study aimed to assess the epidemiological feature of type 2 diabetes in patients with NAFLD or MAFLD at global levels. METHODS: Published studies were searched for terms that included type 2 diabetes, and NAFLD or MAFLD using PubMed, EMBASE, MEDLINE, and Web of Science databases from their inception to December 2022. The pooled global and regional prevalence and incidence density of type 2 diabetes in patients with NAFLD or MAFLD were evaluated using random-effects meta-analysis. Potential sources of heterogeneity were investigated using stratified meta-analysis and meta-regression. RESULTS: A total of 395 studies (6,878,568 participants with NAFLD; 1,172,637 participants with MAFLD) from 40 countries or areas were included in the meta-analysis. The pooled prevalence of type 2 diabetes among NAFLD or MAFLD patients was 28.3% (95% confidence interval 25.2-31.6%) and 26.2% (23.9-28.6%) globally. The incidence density of type 2 diabetes in NAFLD or MAFLD patients was 24.6 per 1000-person year (20.7 to 29.2) and 26.9 per 1000-person year (7.3 to 44.4), respectively. CONCLUSIONS: The present study describes the global prevalence and incidence of type 2 diabetes in patients with NAFLD or MAFLD. The study findings serve as a valuable resource to assess the global clinical and economic impact of type 2 diabetes in patients with NAFLD or MAFLD.

Dietary Macronutrient Intake and Cardiovascular Disease Risk and Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies.

Many epidemiological studies have evaluated the intake of macronutrients and the risk of mortality and cardiovascular disease (CVD). However, current evidence is conflicting and warrants further investigation. Therefore, we carried out an umbrella review to examine and quantify the potential dose-response association of dietary macronutrient intake with CVD morbidity and mortality. Prospective cohort studies from PubMed, Embase, and CENTRAL were reviewed, which reported associations of macronutrients (protein, fat, and carbohydrate) with all-cause, CVD, cancer mortality, or CVD events. Multivariable relative risks (RR) were pooled, and heterogeneity was assessed. The results of 124 prospective cohort studies were included in the systematic review and 101 in the meta-analysis. During the follow-up period from 2.2 to 30 years, 506,086 deaths and 79,585 CVD events occurred among 5,107,821 participants. High total protein intake was associated with low CVD morbidity (RR 0.88, 95% confidence interval 0.82-0.94), while high total carbohydrate intake was associated with high CVD morbidity (1.08, 1.02-1.13). For fats, a high intake of total fat was associated with a decreased all-cause mortality risk (0.92, 0.85-0.99). Saturated fatty acid intake was only associated with cancer mortality (1.10, 1.06-1.14); Both monounsaturated fatty acid (MUFA) and polyunsaturated fatty acids (PUFA) intake was associated with all-cause mortality (MUFA: 0.92, 0.86-0.98; PUFA: 0.91, 0.86-0.96). This meta-analysis supports that protein intake is associated with a decreased risk of CVD morbidity, while carbohydrate intake is associated with an increased risk of CVD morbidity. High total fat intake is associated with a low risk of all-cause mortality, and this effect was different in an analysis stratified by the type of fat.