J-shaped Association Research Articles

J-shaped association of serum uric acid with all-cause and cardiovascular mortality in patients with diabetic kidney disease.

The association of serum uric acid (SUA) with mortality remains unclear in patients with diabetic kidney disease (DKD). Thus, this prospective cohort study aimed to explore the association of SUA with all-cause and cardiovascular disease (CVD) mortality among patients with DKD in a large, nationally representative sample. This cohort study included data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 and the National Death Index mortality data until 31 December 2019. The restricted cubic spline and the Cox proportional hazards regression were conducted to describe the association of SUA with all-cause and CVD mortality and evaluate potential nonlinear associations. The analysis included 3470 patients with DKD from NHANES 1999-2018. During the follow-up time of 24,633 person-years, we recorded 1489 all-cause deaths, including 542 CVD deaths. We identified a J-shaped association of SUA with all-cause and CVD mortality. The corresponding inflection points were observed at 5.1 and 5.7mg/dL. When SUA were higher than inflection points, each 1mg/dL increase in SUA was linked to a 13% and 22% higher risk of all-cause (HR: 1.13; 95% CI: 1.07-1.20;P < 0.001) and CVD (HR: 1.22; 95% CI: 1.06-1.41;P = 0.006) mortality, respectively. This study indicated the J-shaped association of SUA with all-cause and CVD mortality in patients with DKD. The corresponding inflection points were 5.1 mg/dL for all causes and 5.7mg/dL for CVD, respectively. More clinical randomized trials are needed to confirm the optimal uric acid-lowering target.

Elevated neutrophil percentage-to-albumin ratio predicts increased all-cause and cardiovascular mortality among individuals with diabetes.

Evidence regarding the neutrophil percentage-to-albumin ratio (NPAR) and mortality risk in diabetes patients is scarce. This study aimed at investigating the prognostic value of NPAR for mortality in patients with diabetes. This retrospective analysis was conducted on 6,962 diabetic patients from the NHANES database. Restricted cubic spline (RCS) was used to visualize the association of the NPAR with mortality risk. Weighted multivariable Cox regression models and subgroup analyses were adopted to assess the association of the NPAR with all-cause and cardiovascular mortality. Time-dependent receiver operating characteristic curve (ROC) analysis was conducted to evaluate the accuracy of the NPAR in predicting survival outcomes. Mediation analysis explored the indirect impact of NPAR on mortality mediated through eGFR. During a median follow-up of 6.7 years, there were 1,804 deaths were recorded, including 602 cardiovascular deaths. The RCS regression showed that NPAR has a J-shaped association with all-cause mortality, and a positive linear association with CVD mortality. Each one-unit increase in NPAR was linked with a 14% and 12% increased risk of all-cause and cardiovascular mortality, respectively. The association was consistent in subgroup analyses based on age, sex, race, BMI, hypertension, CKD, and history of CVD. The time-dependent ROC curve showed the area under the curve of were 0.809 for all-cause mortality, and 0.780 for CVD mortality. In mediation analyses, eGFR partially mediated these relationships. An elevated NPAR is independently associated with increased all-cause and cardiovascular mortality in diabetes patients.

Alcohol and mortality in Mexico: prospective study of 150 000 adults

Alcohol consumption is a leading cause of premature death globally, but there is no large-scale prospective evidence from Mexico. The Mexico City Prospective Study recruited 150 000 adults aged 35 years or older between 1998 and 2004. Participants were followed up until Oct 1, 2022 for cause-specific mortality. Cox regression in those with no self-reported chronic disease at entry (adjusted for age, sex, district, education, physical activity, smoking, and diabetes) was used to relate baseline-reported alcohol consumption (never, former, occasional [less than monthly], and regular [at least monthly, split into <70, ≥70 to <140, ≥140 to <210, and ≥210 g/week]) to mortality at ages 35-74 from all causes, and from a pre-specified alcohol-related set of underlying causes. Heavy episodic drinking (normally consuming >5 [men] or >4 [women] drinks on a single occasion) and type of preferred drink were also examined. Among 138 413 participants aged 35-74 years at recruitment, 21 136 (15%) were regular alcohol drinkers (14 863 [33%] men, 6273 [7%] women), of whom 13 383 (63%) favoured spirits and 6580 (31%) favoured beer. During follow-up, there were 13 889 deaths at ages 35-74 years, including 3067 deaths from the pre-specified alcohol-related causes. Overall, J-shaped associations with mortality were observed. Compared with occasional drinkers, those with baseline-reported consumption ≥210 g/week had 43% higher all-cause mortality (rate ratio [RR] 1·43 [95% CI 1·30-1·56]) and nearly three times the mortality from the pre-specified alcohol-related causes (2·77 [2·39-3·20]). Death from liver disease was strongly related to alcohol consumption; the RR comparing regular drinkers of ≥140 g/week with occasional drinkers was 4·03 (3·36-4·83). Compared with occasional light drinking, occasional heavy episodic drinking was associated with 20% higher alcohol-related mortality (1·20 [1·06-1·35]), and regular heavy episodic drinking was associated with 89% higher alcohol-related mortality (1·89 [1·67-2·15]). Drinks with alcohol percentages higher than spirits were associated with the greatest increased mortality risk, even after accounting for the total alcohol consumed. In this Mexican population, higher alcohol consumption, episodic drinking, and very high percentage alcoholic products were all associated with increased mortality. Wellcome Trust, the Mexican Health Ministry, the National Council of Science and Technology for Mexico, Cancer Research UK, British Heart Foundation, and the UK Medical Research Council. For the Spanish translation of the abstract see Supplementary Materials section.

Metabolic dysfunction-associated steatotic liver disease in patients with type 2 diabetes: risk of heart failure

Background and aimsThe association between metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM) is unclear. This study aimed to investigate the impact of spectrum of SLD on the risk of heart failure and cardiovascular (CV) mortality in patients with T2DM.MethodsIn a nationwide cohort study, 2,745,689 adults with T2DM were followed from 2009 to 2012 until 2018. Participants were categorized into no steatotic liver disease (no SLD) and SLD groups. The SLD group was stratified based on metabolic risk factors, alcohol consumption and viral hepatitis. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for heart failure (HF) and CV mortality risk.ResultsThe prevalence of MASLD, metabolic alcohol-associated liver disease (MetALD), alcohol-associated liver disease with metabolic dysfunction (ALD with MD) and MASLD with viral hepatitis (VH) was 49.6%, 7.2%, 2.3%, and 2.0%. Individuals with MASLD (adjusted HR [aHR], 1.11), MetALD (aHR, 1.14), ALD with MD (aHR, 1.32) and MASLD with VH (aHR, 1.12) had a higher risk of developing HF compared with the no SLD group. The risk of CV mortality was also increased in those with SLD groups compared to those with no SLD. The risk of new-onset HF and CV mortality showed a J-shaped association with alcohol consumption regardless of SLD status.ConclusionSLD is independent risk factor of new-onset HF and CV mortality in persons with T2DM, and alcohol consumption has a J-shaped association with risk of HF and CV mortality, regardless of SLD status.

A nonlinear relationship between dietary inflammatory index and stroke among US adults with metabolic dysfunction-associated steatotic liver disease.

Some studies have found that high dietary inflammatory index (DII) increases stroke risk, but previous studies have mostly been conducted in the general population, and the exact relationship between DII and stroke in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) is not clear. This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (2009-2016) to investigate the association between the DII and stroke. DII was computed according to established methods. Participants were categorized into tertiles of DII (Q1-Q3). Multivariate weighted logistic regression analysis, smooth curve fitting, and subgroup analysis were employed to explore this relationship. Subgroup analyses were conducted based on demographic and clinical variables. A total of 2426 individuals were enrolled in our study. The overall prevalence of stroke in the study population was 4.66%. The smooth curve fitting analysis indicated a J-shaped relationship between DII and stroke among individuals with MASLD. In multivariate weighted logistic regression analysis, the odds ratio (OR) of DII is 1.17 (95% CI: 1.03-1.38) for stroke, with a turning point of 1.89. After the turning point, the OR (95% CI) was 1.22 (1.08-2.56). In subgroup analysis, DII still increased the risk of stroke independently. Our study highlighted a J-shaped association between DII and stroke in adults with MASLD from USA.

Association between intake of whole grain and periodontitis among adults in the United States: a population-based study

The objective was to examine the association between the intakes of whole grains, refined grains, and whole/refined ratio with periodontitis. Data from 7,753 adults participating in NHANES 2009–2014 were used. The intakes of whole grains, refined grains, and whole/refined ratio were collected and calculated. Periodontitis was defined according to the CDC. The relationship between periodontitis and grains intakes were evaluated by using multivariate models. Dose-response relationship was modelled by restricted cubic spline regression. In the fully adjusted model, the whole grains intake (Q4 ORs: 0.70 (0.56,0.89)) and whole/refined grain ratio (Q4 ORs: 0.75 (0.60,0.93)) were negatively associated with periodontitis. The results of restricted cubic spline regression showed an OR of 0.89 (95% CI: 0.84,0.95) for per 28.3 g/d increase in whole grain intake, and the whole/refined grain ratio had a J-shaped association with periodontitis. Increased intake of whole grains was associated with lower prevalence of periodontitis.

Long-term weight change in midlife, cardiac magnetic resonance parameters, risk of atrial fibrillation: a large prospective cohort study

Abstract Background Although obesity is a well-established risk factor for atrial fibrillation (AF), the relationship between weight change and the risk of AF remains controversial. Furthermore, the extent to which obesity-associated AF risk is mediated by cardiac remodeling is unclear. Purpose We aimed to evaluate the impacts of obesity and weight change on the risk of atrial fibrillation, and the role of cardiac remodeling in obesity-AF association. Methods This is a population-based prospective cohort of UK Biobank participants recruited from 2006 to 2010. A total of 490,969 participants and 19,634 participants were included for BMI and BMI change analysis, respectively. Body mass index (BMI) was assessed at baseline and follow-up assessment (2012-2013). Cardiovascular measurements were derived from cardiovascular magnetic resonance. Cox proportional hazard models were used to assess the associations of obesity and change in BMI with AF. The nonlinear associations of BMI and BMI change with AF were tested using a restricted cubic spine (RCS). Mediation analysis was conducted to quantify the role of cardiac remodeling in the association between obesity and AF. Results Among the 490,969 participants included (mean age: 56.4 ± 8.1 years, 54.9% women), 33,297 incident AF cases were observed during a median follow-up of 14.0 years. Overweight (hazard ratio [HR], 1.12, 95% confidence interval [CI] 1.09-1.15, P &amp;lt; 0.001) and obesity (1.73, 1.68-1.78, P &amp;lt; 0.001) significantly increased the risk of AF, particularly in men, those with age &amp;lt; 60 years and low genetic risk. During a median follow-up of 4.43 years, 1,217 (6.2%) participants experienced &amp;gt; 2% BMI loss per year and 1,318 (6.7%) participants experienced &amp;gt; 2% BMI gain per year. Compared to stable BMI, BMI loss was associated with a lower risk of AF (0.75, 0.57-0.99, P = 0.039). In addition, we found that BMI loss from obesity to overweight was associated with a reduced risk of AF (0.74, 0.54-1.02, P = 0.069) compared with maintaining baseline BMI category. Participants with stable obesity had a higher risk of AF (1.81, 1.52-2.16, P &amp;lt; 0.001) than those with stable normal weight. In addition, RCS indicated BMI had a J-shaped association with AF while BMI change had a linear association with AF. Mediation analyses revealed that left ventricular myocardial mass, left atrial maximum volume, and left atrial minimum volume were the three strongest mediating factors between obesity and AF, with a mediated proportion of 85.28%, 64.43%, and 55.89% of the total effect, respectively. Conclusion BMI decrease over 2% per year was associated with a lower risk of AF, especially in those changing from obesity to overweight. Left ventricular myocardial mass plays a central role in mediating obesity-related AF. Our findings support weight management at the population level to mitigate the growing epidemic of AF and ways targeting left ventricular myocardial mass are waiting to be further explored.Associations of BMI, BMI change with AFThe mediating role of cardiac remodeling

The triglyceride-glucose index is a predictor for cardiovascular events and all-cause mortality in young and middle-aged patients with metabolic syndrome

Abstract Aims The association between the triglyceride-glucose (TyG) index and cardiovascular risk in young and middle-aged individuals with Metabolic syndrome (MetS) remains unclear. This study aimed to investigate the relationship between baseline TyG index and cardiovascular events and all-cause mortality in these patients among American adults. Methods This study enrolled 4937 young and middle-aged patients with MetS from the National Health and Nutrition Examination Survey (1999–2018). Mortality outcomes were determined by linking to National Death Index records up to December 31, 2019. Multivariate Cox proportional hazards models were constructed to analyze explore the associations between baseline TyG index and cardiovascular events or all-cause mortality. Non-linear correlations were explored using restricted cubic splines, and a two-piecewise Cox proportional hazards model for both sides of the inflection point was constructed. Results During the up to 9.3 years follow-up period, a total of 463 all-cause deaths and 143 cardiovascular events were recorded. The multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) escalate from the lowest to the highest TyG index quartile. Specifically, for cardiovascular events, the HRs range from 1.00 (reference) to 2.29 (1.22, 4.31) with a significant trend (P = 0.004). For all-cause mortality, the HRs vary from 1.00 (reference) to 1.59 (1.09, 2.32), also showing a significant trend (P = 0.003). The restricted cubic splines revealed a J-shaped association between the baseline TyG index with cardiovascular events and all-cause mortality in MetS patients. Conclusions The high TyG index was identified as an independent predictor of elevated rates of cardiovascular events among young and middle-aged patients with MetS. Additionally, a J-shaped curve pattern was observed in the association between these factors.

Modification of the association between coffee consumption and constipation by alcohol drinking: A cross-sectional analysis of NHANES 2007-2010.

The association between coffee consumption and constipation remains unclear. This study aimed to examine the relationship of coffee consumption with the risk of constipation, while also investigating potential effect modifiers. This cross-sectional study included 7844 participants from the National Health and Nutrition Examination Survey (NHANES) 2007-2010. Coffee consumption was extracted from the 24-hour dietary recall. Constipation was assessed using the Bristol Stool Form Scale. The association between coffee consumption and constipation was assessed using multivariable restricted cubic spline and logistic regression with odds ratio (OR) and 95% confidence interval (CI). There was a J-shaped relationship between total coffee consumption and the risk of constipation in the whole population (p for nonlinearity = 0.049), with 1-2 cups/day of total coffee potentially reducing the risk of constipation by 39% (OR 0.61, 95% CI 0.35-1.06, p = 0.07). As for caffeinated coffee, a J-shaped association between its consumption and the risk of constipation was also observed in the whole population (p for nonlinearity = 0.008), with 1-2 cups/day being significantly associated with a reduced risk (OR 0.57, 95% CI 0.35-0.95, p = 0.03). When restricting to never drinkers of alcohol, the associations between total and caffeinated coffee consumption and constipation shifted to inverse linear trends, where at least 3 cups/day was significantly associated with an 88% reduction in constipation risk (total coffee: OR 0.12, 95% CI 0.02-0.68, p = 0.02; caffeinated coffee: OR 0.12, 95% CI 0.02-0.70, p = 0.02). Decaffeinated coffee showed no association with constipation. Consuming 1-2 cups of caffeinated coffee daily was associated with a reduced risk of constipation in the general population. Among never drinkers of alcohol, a linear protective effect was observed, with a notable 88% reduction in constipation risk for those consuming at least 3 cups per day. Moderate caffeinated coffee intake may therefore be a viable dietary strategy for managing constipation in the general population.

Association of platelet-to-HDL cholesterol ratio with frailty and all-cause mortality

BackgroundFrailty often requires intensive care, and the admission outcomes of frail patients are often poor. However, owing to the lack of reliable diagnostic indicators, quickly identifying frailty is challenging. The present study aimed to explore the associations of the platelet/high-density lipoprotein cholesterol ratio (PHR; a novel inflammatory indicator) with frailty and all-cause mortality.MethodsThe present study analyzed data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. Frailty was assessed on the basis of the 49-item Frailty Index. The associations of the PHR with frailty and long-term survival prognosis were explored through weighted logistic regression, weighted restricted cubic spline (RCS), and weighted Cox regression, with adjustments for demographic factors, lifestyle, blood lipids, medication history, and complications. In addition, subgroup and interaction analyses were conducted. Finally, several sensitivity analyses were performed.ResultsA total of 15,615 adult participants were included, with 7,928 women (53.63%) and an average age of 60.76 years. After fully adjusting for confounding variables, the prevalence of frailty in the highest PHR quartile group of was significantly greater than that in the lowest quartile group (OR: 1.23, 95% CI: 1.04–1.47; P = 0.02). The RCS showed that the inflection point was 166.7. Before and after the inflection point, the PHR was negatively associated (OR: 0.88, 95% CI: 0.80–0.97, P = 0.01) and positively associated (OR: 1.10, 95% CI: 1.02–1.19, P = 0.01) with frailty, respectively. Subgroup analysis suggested that the association between PHR and frailty was stronger in women than in men. A total of 5,544 frail participants were included in the survival analysis. The RCS revealed that the PHR was associated with the all-cause mortality risk of frail participants in a U-shaped manner, with an inflection point of 240.4. Before and after the inflection point, the PHR decreased (HR: 0.89, 95% CI: 0.81–0.97, P = 0.01) and the all-cause mortality risk increased (HR: 1.08, 95% CI: 1.02–1.14, P = 0.01), respectively.ConclusionThe present study suggests that there is a J-shaped association between PHR and frailty in the adult population of the United States and that the association between the PHR and frailty is stronger in women. In addition, the PHR has a U-shaped relationship with the all-cause mortality risk of frail patients.

Associations of body composition measures with circulating insulin-like growth factor-I, testosterone, and sex hormone-binding globulin concentrations in 16,000 men.

Adiposity is positively associated with risk of some cancer sites and other health conditions in men; however, it is unclear if endogenous hormones play a role in these associations. We examined how body composition, measured from magnetic resonance imaging (MRI) and common measures of adiposity (e.g., body mass index (BMI)), are related to hormone concentrations in men from the UK Biobank study. Up to 16,237 men with available body composition data (including visceral, subcutaneous, and liver fat, muscle fat infiltration (MFI), lean tissue, and common adiposity measures) and serum hormone measurements (insulin-like growth factor-I (IGF-I), total testosterone, sex hormone-binding globulin (SHBG), and calculated free testosterone) were included. Multivariable-adjusted linear regression models were used to determine the geometric mean hormone and SHBG concentrations across categories of each exposure. Common measurements of adiposity were highly correlated with MRI measures of central and total adiposity (r = 0.76-0.91), although correlations with ectopic fat (liver fat and MFI) were lower (r = 0.43-0.54). Most adiposity measurements showed an inverse U- or J-shaped association with circulating IGF-I and free testosterone; however, MFI was linearly inversely associated, and lean tissue volume was positively associated with both IGF-I and free testosterone concentrations. All body composition measures were inversely associated with total testosterone and SHBG concentrations (relative geometric mean difference between Q5 vs. Q1: 20-30%). Our results show that common adiposity and most MRI measures of adiposity relate similarly to serum hormone concentrations; however, associations with ectopic fat (particularly MFI) and lean tissue were different.

Ultra-processed foods and the incidence of pre-diabetes and type 2 diabetes among Iranian adults: the Tehran lipid and glucose study

BackgroundNo study has investigated the association between ultra-processed food (UPF) and pre-diabetes development. Furthermore, prior investigations on the association between UPF and the risk of type 2 diabetes (T2D) were primarily conducted in Europe and America, and studies in other regions are lacking. We investigated the association between ultra-processed foods and the risk of pre-diabetes and T2D in a cohort of Iranians.MethodsThis prospective study, with a sample size of 1954 for pre-diabetes and 2457 for T2D, was conducted among adults’ participants (aged ≥ 18 years) from the Tehran Lipid and Glucose Study (TLGS). We defined UPF intake using NOVA calcification as a proportion of total energy, and calculated its average intake during the follow-ups. The hazard ratios (HR) and 95% confidence intervals (95% CI) for pre-diabetes/T2D across tertiles of total UPF and per 10% of its increment were examined using Cox proportional hazards models. We also investigated the possibility of non-linear association using a restricted cubic spline regression.ResultsWe identified 766 and 256 cases of pre-diabetes and T2D, respectively, during a median follow-up of 7 years for pre-diabetes and 8.6 years for T2D. In the multivariable adjusted model, a 10% increase in total UPF intake was associated with a 12% higher risk of pre-diabetes (HR = 1.12; 95% 1.02, 1.23). The incidence of pre-diabetes was also higher in those in tertile 3 than those in tertile 1 (HR = 1.28; 95% CI = 1.07, 1.52). Following additional adjustment for diet quality, the results remained unchanged. Spline regression demonstrated a J-shaped association between UPF and the risk of pre-diabetes; the risk of pre-diabetes did not increase until UPF consumption exceeded about 24% of total energy intake. Of the individual UPF, hydrogenated fat/mayonnaise/ margarine group was related to an increased risk of pre-diabetes. The total UPF and its individual items were not associated with T2D.ConclusionsThis study found a positive, non-linear relationship between total UPF and the risk of pre-diabetes in Iranian adults. Our data could not show any significant association between UPF and T2D risk.

Dose-Response Associations of Internet Use Time and Internet Addiction With Depressive Symptoms Among Chinese Children and Adolescents: Cross-Sectional Study.

Children's lives are increasingly mediated by digital technologies, yet evidence regarding the associations between internet use and depression is far from comprehensive and remains unclear. This study aimed to investigate the dose-response association between internet use, including use time and addiction behaviors, and depressive symptoms among children and adolescents in Zhejiang Province. Data were collected from a school-based health survey China Common Disease and Risk Factor Surveillance Among Students, encompassing 21,336 students in Zhejiang Province. The daily internet use time, internet addiction (IA) behaviors, and depressive symptoms were assessed with questionnaires. Logistic regression models were used to explore the associations of internet use time and IA behaviors with depressive symptoms among children and adolescents. Restricted cubic spline curves were used to determine the dose-response associations. A total of 6225 (29.2%) students had depressive symptoms. Compared to those reporting no internet use, boys using the internet for >2 hours/day (odds ratio [OR] 1.53, 95% CI 1.34-1.74) and girls using internet for 1.1-2 hours/day (OR 1.22, 95% CI 1.06-1.39) and >2 hours/day (OR 1.70, 95% CI 1.50-1.93) were at higher risks of depressive symptoms. A significant J-shaped association was identified between internet use time and depressive symptoms among children and adolescents, especially in boys and primary school students (nonlinear P values were .006, .003, and <.001, respectively). Increased IA behaviors were associated with a higher odd of depressive symptoms (1 IA behavior: OR 2.01, 95% CI 1.83-2.21; 2 IA behaviors: 2.91, 95% CI 2.57-3.29; and ≥3 IA behaviors: 4.72, 95% CI 4.26-5.22). A positive nonlinear association between the number of IA behaviors and depressive symptoms was found in total population, girls, and primary school students (nonlinear P values were .02, .002, .007, respectively). Findings suggested that excessive internet use time and IA behaviors were significantly associated with an increased risk of depressive symptoms, highlighting the importance of interventions to regulate and educate about adequate internet use during childhood and adolescence.

Consumption of milk and other dairy products and incidence of Parkinson's disease: a prospective cohort study in French women.

Previous studies showed positive associations between milk intake and Parkinson's disease (PD) in men but not in women, but few studies were available in women. Due to the long prodromal PD phase, reverse causation represents a major threat to investigations of diet in PD; cohort studies with a long follow-up are needed. We investigated associations between intake of milk and other dairy products with PD incidence in women from the E3N cohort study (1993-2018). PD diagnoses were validated using medical records and drug claim databases. Diet was assessed via a dietary questionnaire. Hazard ratios (HR) were estimated using multivariable Cox regression models. Exposures were lagged by 5y in main analyses and longer lags in sensitivity analyses. We examined the impact of adjustment for premotor symptoms (constipation/depression). During a mean follow-up of 18.8y, 845 of 71,542 women developed PD. Main analyses showed a J-shaped association between total milk intake and PD (P-non linearity = 0.045), with a significant linear positive association among drinkers (HR/1-SD = 1.09, 95% CI = 1.01-1.18, P = 0.024), that was explained in secondary analyses by a different pattern of association for plain milk (alone or with cereals) and milk added to drinks (tea/coffee/chicory). PD incidence increased significantly with plain milk consumption (HR/1-SD = 1.08 [1.02-1.14], P = 0.014). A U-shaped relation was observed for milk added to drinks (P-non linearity = 0.038), with lower PD incidence in women with moderate consumption (HR = 0.77 [0.61-0.97], P = 0.030) and no difference between non-drinkers and those with the highest consumption (HR = 0.98 [0.79-1.21], P = 0.848). Findings were similar in analyses using longer lags and adjusted for constipation/depression. Consumption of other dairy products was not associated with PD. A J-shaped association between total milk intake and PD was explained by a different pattern of association for plain milk intake and milk added to drinks. Reverse causation is unlikely to explain a positive association of plain milk with PD incidence in women. The U-shaped relation for milk added to drinks could be explained by an interaction between milk and coffee/tea/chicory. Further studies are warranted to elucidate the underlying mechanisms.

J-shaped association between apolipoprotein B and CV outcomes in statin-treated patients with chronic coronary syndrome

Introduction and objectivesThe association between apolipoprotein B (apoB) and residual cardiovascular (CV) risk in patients with chronic coronary syndrome (CCS) remains unclear. We aimed to investigate the association between apoB levels and CV outcomes in statin-treated CCS patients. MethodsWe enrolled 8641 statin-treated CCS patients at Fuwai Hospital. The patients were divided into 5 groups based on to apoB quintiles (Q1 to Q5). The primary endpoint was 3-year CV events, including CV death, nonfatal myocardial infarction, and nonfatal stroke. ResultsDuring a median follow-up of 3.17 years, there were 232 (2.7%) CV events. After multivariable adjustment, a restricted cubic spline illustrated a J-shaped relationship between apoB levels and 3-year CV events, with the risk remaining flat until apoB levels exceeded 0.73g/L, after which the risk increased (nonlinear P <.05). Kaplan-Meier curves showed the lowest CV event rate in the Q3 group (0.68-0.78g/L). Compared with the Q3 group, multivariable Cox regression models revealed that both low (Q1, ≤0.57g/L) and high (Q5, >0.93g/L) apoB levels were associated with an increased risk of major adverse cardiac events (all P <.05). Notably, patients with low apoB levels (Q1) had the highest risk of CV death (HR, 2.44; 95%CI, 1.17-5.08). ConclusionsOur analysis indicates that both low and high levels of apoB are associated with elevated CV risk, with the risk being particularly pronounced at higher levels (> 0.73g/L).

Association of haemoglobin glycation index with all-cause and cardiovascular disease mortality in diabetic kidney disease: a cohort study

BackgroundWhile the high haemoglobin glycation index (HGI) has been extensively investigated in diabetic populations, its impact on patients with diabetic kidney disease (DKD) remains unclear.MethodsWe examined data from the National Health and Nutrition Examination Surveys (NHANES) conducted between 1999 and 2018. HGI was determined using the formula recommended by Hempe et al., which calculates the difference between measured and predicted HbA1c. Predicted HbA1c was derived from the equation: 0.024 FPG + 3.1. National death index records up to December 31, 2019, were utilized to assess mortality outcomes. To estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for both all-cause and cardiovascular disease (CVD) mortality, we utilized Cox proportional hazard models. A restricted cubic spline analysis was performed to explore the potential nonlinear relationship between HGI levels and mortality.ResultsOur cohort study comprised data from 1,057 participants with DKD (mean [SE] age, 61.61 [0.57] years; 48.24% female). The mean HGI level was 0.44 (SE 0.04). Over a median follow-up period of 6.67 years, we observed 381 deaths, including 140 due to CVD. Compared with participants in the second tertile of HGI levels (0.03–0.74), those in the lowest tertile of HGI (-5.29–0.02) exhibited an all-cause mortality hazard ratio of 1.39 (95% CI, 1.02–1.88) and a CVD mortality hazard ratio of 1.10 (95% CI, 0.67–1.81). Conversely, participants in the highest tertile (0.75–9.60) demonstrated an all-cause mortality hazard ratio of 1.48 (95% CI, 1.05–2.08) and a CVD mortality hazard ratio of 2.06 (95% CI, 1.13–3.77) after further adjusting for HbA1c and other important variables. Additionally, a restricted cubic spline analysis revealed a U-shaped relationship between HGI and all-cause mortality (P < 0.001 for nonlinearity) and a J-shaped relationship between HGI and CVD mortality (P = 0.044 for nonlinearity).ConclusionsOur cohort study suggests that HGI in DKD populations exhibits a U-shaped association with all-cause mortality and a J-shaped association with CVD mortality, independent of HbA1c levels.

Association between coffee and tea consumption and the risk of dementia in individuals with hypertension: a prospective cohort study

Many studies have shown that drinking coffee and tea may be associated with the risk of hypertension and dementia. Limited research exists on their impact on dementia risk in hypertensive patients. This study aimed to determine the association between coffee and tea consumption and the risk of dementia development in hypertensive population by utilizing Cox proportional risk modeling with 453,913 participants from a UK biobank. Our findings reveal a J-shaped and U-shaped association between the risk of all-cause dementia and the consumption of coffee and tea respectively in hypertensive people. The hypertensive patients who drink 0.5–1 cup of coffee or 4–5 cups of tea per day have the lowest risk of dementia. A U-shaped relationship was observed between daily caffeine consumption and the risk of developing all-cause dementia and vascular dementia in the hypertensive population. Furthermore, the significant association between the amount of coffee and tea consumed and the risk of all-cause and vascular dementia were more likely to be found in hypertensive patients than in the non-hypertensive population.

Association between alcohol consumption and incidence of dementia in current drinkers: linear and non-linear mendelian randomization analysis

Previous conventional epidemiological studies found a J-shape relationship between alcohol consumption and dementia, but this result was subject to confounding biases and reverse causation. Therefore, we aimed to investigate the potential linear or non-linear causal association between alcohol consumption and the incident risk of dementia in current drinkers. This study used data from the UK Biobank to investigate the relationship between alcohol consumption and dementia risk. 313,958 White British current drinkers, who were free of dementia during 2006-2010, were followed up until 2021. Alcohol consumption was self-reported and calculated according to the National Health Service guideline. The primary outcome was all-cause dementia identified through hospital and mortality records. We used multivariable Cox models with restricted cubic splines for conventional analysis and both non-linear and linear Mendelian Randomization (MR) analyses to assess causal relationships, employing a genetic score based on 95 SNPs identified from a meta-genome-wide association study of 941,280 people from Europe. 313,958 current drinkers consumed an average of 13.6 [IQR: 7.1-25.2] units/week alcohol (men averaged 20.2 [11.1-33.9] units/week and women 9.5 [5.3-16.7] units/week). During a mean follow-up of 13.2 years, 5394 (1.7%) developed dementia. Multivariable Cox model with restricted cubic spline functions identified a J-shaped relationship between alcohol consumption and dementia risk, with the lowest risk at 12.2 units/week. The non-linear MR failed to identify a significant non-linear causal relationship (p=0.45). Both individual-level (HR: 2.22 95%CI [1.06-4.66]) and summary-level (1.89 [1.53-2.32]) linear MR analyses indicated that higher genetically predicted alcohol consumption increased dementia risk. This study identified a positive linear causal relationship between alcohol consumption and dementia among current drinkers. The J-shaped association found in conventional epidemiological analysis was not supported by non-linear MR analyses. Our findings suggested that there was no safe level of alcohol consumption for dementia. The Shenzhen Science and Technology Program and the Strategic Priority Research Program of Chinese Academy of Sciences.

Sugar-sweetened beverages, low/no-calorie beverages, fruit juices intake and risks of metabolic syndrome in adults: The SWEET project

Background and aimsMetabolic syndrome (MetS) is an important determinant of cardiometabolic disease development, with excessive sugar intake as one of the key modifiable risk factors. However, evidence on the association between sugar-sweetened beverages (SSB), their replacement by low/no caloric beverages (LNCB), and MetS development is still limited. Methods and resultsData from participants’ of Lifelines (n = 58 220), NQPlus (n = 1094) and Feel4Diabetes (n = 342) were prospectively analysed. Dose-response associations were investigated using restricted cubic spline analyses (Lifelines). Cox proportional hazard regression analysis with robust variance was used to quantify associations between intakes of SSB, fruit juices (FJ) and LNCB and MetS incidence; data were pooled using random-effects models. Associations were adjusted for demographic, lifestyle and other dietary factors. In Lifelines, NQPlus, and Feel4Diabetes, 3853 (7 %), 47 (4 %), and 39 (11 %) participants developed MetS, respectively. Pooled analyses showed that each additional serving of SSB was associated with a 6 % higher risk of MetS (95%CI 1.02–1.10). A J-shaped association was observed for FJ and MetS, with a significant inverse association at moderate intake levels (IPR 0.89, 95 % CI 0.82–0.96). LNCB intake was not associated with MetS (IPR 1.59, 95%CI 0.74–2.43), but findings across studies were inconsistent (I2 94 %, p-value <0.01). Replacing SSB with FJ or LNCB did not show any associations with MetS incidence. ConclusionSSB intake was adversely associated with MetS incidence. A J-shaped association was observed between FJ and MetS. For LNCB, results were inconsistent across studies and therefore findings must be interpreted cautiously.

Abstract P339: Association of Pre-Donation Blood Pressure with Kidney Function in Living Kidney Donors

Background: Although BP is associated with kidney outcomes, its clinical significance in living kidney donors (LKD) is unknown. We aim to examine the association between pre-donation BP and the risk of kidney function decline in LKD. Methods: A retrospective cohort study using OPTN/SRTR including adult LKD, who underwent donation between 6/1972 and 9/2022, was utilized to examine the association of quartile (Q) of pre-donation SBP and DBP with time-to-event of ≥35% decline in post-donation eGFR from pre-donation eGFR by multiple Cox regression. Results: Of 174,311 adult LKD, mean±SD age was 41±12 years and 60% were female. Mean pre-donation SBP and DBP were 122±13 and 74±9 mmHg, respectively. Mean pre-donation SBP in Q 1, 2, 3, and 4 were 106±6, 117±2, 126±3, and 140±9 mmHg, respectively and the corresponding DBP were 62±5, 71±2, 78±2, and 86±5 mmHg, respectively. The median (IQR) of pre-donation eGFR was 91 (75, 111) mL/min/1.73 m 2 . Median(IQR) eGFR at immediate post-donation, 6-, 12-, and 24-months post-donation were 50 (40, 62), 54 (44, 67), 55 (45, 68), and 57 (47, 70) mL/min/1.73 m 2 , respectively. Out of 38,780 LKD with post-donation eGFR data at 6, 12, or 24 months, 31,054 had the event of ≥35% decline in post-donation eGFR from pre-donation eGFR with a median time to follow-up of 6.77 months(IQR 5.93, 12.67). The incidence rate of the event was 0.08 person-months. Compared to patients with SBP in Q 1, those with SBP in Q 2, 3, and 4 had a significantly increased risk for the event(HR SBP Q2,3,4 1.05, 1.08, and 1.15; P &lt;0.001 – 0.003) but only patients with DBP in Q 3 and 4 had a significantly increased risk for the event (HR SBP Q3,4 1.04 and 1.09). After adjusting for age, gender, race/ethnicity, U.S. citizenship, education level, history of pre-donation HTN, diabetes, pre-donation BMI, DBP, and urine protein:creatinine ratio, there was a J-shaped association between pre-donation SBP and post-donation eGFR decline and only patients in the Q 2 became significantly associated with lower the risk for the event (HR 0.87, 95%CI 0.76, 0.99; Fig1). The pre-donation DBP – post-donation eGFR association was similar to the SBP – eGFR association but there was no statistically significant in all Q (Fig2). There was no effect-measured modifier for all covariates. Conclusions: Pre-donation SBP in a normal range(113 - 120 mmHg) is associated with the lowest risk for a post-donation eGFR decline. BP control in the normal range should be achieved for potential LKD.