Prospective Population-based Study Research Articles

Ambient air pollution, covert cerebrovascular disease and cognition: results from the ISSYS study.

Although air pollution (AP) has been associated with stroke and dementia, data regarding its relationship with covert cerebrovascular disease (cCVD) and cognition over time are sparse. The aim of this study was to explore these relationships. A prospective population-based study of 976 stroke-free and non-demented individuals living in Barcelona, Spain, was conducted during 2010-2016. A land use regression model was used to estimate the exposure of each participant to AP: NOx, NO2, PM2.5, PM10, PMcoarse and PM2.5 absorbance. Cognitive function and cCVD were assessed at baseline (n = 976) and 4 years after (n = 317). Multivariate-adjusted models were developed. At baseline, 99 participants (10.1%) had covert brain infarcts and 91 (9.3%) had extensive periventricular white matter hyperintensities (WMHs). Marked subcortical WMH progression was seen in 19.7%; the incidence of other covert cerebrovascular lessons ranged between 5% and 6% each. PM2.5 was related to higher odds of having a covert brain infarct (odds ratio [OR] 2.21; 95% confidence interval [CI] 1.06-4.60). PM2.5 absorbance was related to higher odds of having extensive subcortical WMHs (OR 1.72; 95% CI 1.13-2.60), whereas NO2 was related to higher odds of having extensive subcortical (OR 1.66; 95% CI 1.17-2.35) or periventricular (OR 1.96; 95% CI 1.10-3.50) WMHs and to higher odds of developing marked subcortical WMH progression (OR 1.40; 95% CI 1.05-1.90). NOx was related to incident cerebral microbleeds (OR 1.36; 95% CI 1.04-1.79). There was no association between AP and cognition. Air pollutant predicts the presence and accumulation of cCVD. Its impact on cognitive impairment remains to be determined.

Serum Branched-Chain Amino Acids and Long-Term Complications of Liver Cirrhosis: Evidence from a Population-Based Prospective Study

Background and Aims: The role of serum branched-chain amino acids (BCAAs) in long-term liver cirrhosis complication events remains unclear. We aimed to evaluate the associations between serum BCAAs and the risk of liver-related events. Methods: We included a total of 64,005 participants without liver cirrhosis complication events at baseline from the UK Biobank. Cox proportional hazards regression models were utilized to estimate multivariable hazard ratios (HRs) and 95% CIs for the incidence of liver cirrhosis complication events, adjusting for potential confounders, including sociodemographic and lifestyle factors. Relationships between serum BCAAs and liver cirrhosis complications were examined using nonparametrically restricted cubic spline regression. Results: During a median follow-up of 12.7 years, 583 participants developed liver cirrhosis complication events. The multivariable Cox regression model suggested that total BCAAs (HR = 0.88, 95% CI 0.82–0.95), serum leucine (HR = 0.88, 95% CI 0.81–0.95), serum isoleucine (HR = 0.88, 95% CI 0.82–0.96), and serum valine (HR = 0.87, 95% CI 0.82–0.96) were all independent protective factors for liver cirrhosis complications after adjustment for sociodemographic and lifestyle factors. Cox models with restricted cubic splines showed U-shaped associations between serum valine and liver cirrhosis complication incidence. Serum total BCAA and isoleucine concentrations might reduce the risk of liver cirrhosis complications by raising the risk of (type 2 diabetes mellitus) T2DM. Conclusion: Lower serum BCAA levels exacerbate the long-term risk of liver cirrhosis complications. Future studies should confirm these findings and identify the biological pathways of these associations.

Depressive symptoms and sex differences in the risk of post-COVID-19 persistent symptoms: a prospective population-based cohort study

Depressive symptoms and sex differences in the risk of post-COVID-19 persistent symptoms: a prospective population-based cohort study

Gestational weight gain as a mediator of the relationship between pre-pregnancy body mass index and the risk of preterm birth: A four-way decomposition analysis.

The aim of the present study was to examine and quantify whether the association between preterm birth (PTB) and pre-pregnancy body mass index (BMI) is mediated by gestational weight gain (GWG). This is a secondary analysis of a large randomized community non-inferiority trial using a cohort design. The data of 26 101 pregnant women in their first trimester who sought prenatal care and met eligibility criteria were included. The four-way decomposition method was applied to screen for all types of association effects of pre-pregnancy BMI on the risk of PTB. These effects include the total, direct, and various indirect effects including pure mediation via GWG, interactive effects with GWG, and mediated interaction with GWG, all adjusted for potential confounders. Among the study participants, 24 461 (93.7%) had term deliveries, while 1640 (6.3%) experienced PTB. The results of the study showed that there was a positive association between pre-pregnancy BMI among those with BMI more than 25 kg/m2 and the risk of PTB and this association was negatively mediated and interacted by GWG, which differed quantitatively between those who had inadequate, adequate, or excessive GWG. The total association effect showed that the risk was lowest for those who had underweight pre-pregnancy BMI and adequate GWG (excess relative risk [RR]: 0.06, 95% CI: 0.01-0.11, P value: 0.022) and was highest for those who had obese pre-pregnancy BMI and excessive GWG (excess RR: 0.67, 95% CI: 0.35-1.00, P value <0.001). The findings of the present prospective population-based study demonstrated that pre-pregnancy BMI >25 kg/m2 is directly and positively associated with the risk of preterm birth. The highest risk of preterm birth was observed among individuals with an obese pre-pregnancy BMI who also experienced excessive GWG.

The Norwegian Watch and Wait study: Norwait for rectal cancer. A report from a failed study-a word of caution.

The paucity of prospective data on the subject of Watch and Wait for rectal cancer prompted the implementation of Norwait, a population-based study including rectal cancer patients after neoadjuvant therapy. The aim of the study was to assess the accuracy of clinical complete response (cCR) and quantify the regrowth rates. Norwait was a prospective population-based observational study with ethical approval (2017/935) registered at clinicaltrials.com (NTC03402477). Residents of Norway with histologically proven rectal cancer located within 15cm from anal verge were eligible following completion of radiotherapy or chemoradiation at seven hospitals. cCR was the disappearance of tumour and of any ulcer with/without the appearance of whitening of prior tumour site and telangiectasia evaluated at 12weeks by digital rectal exam, and endoscopic imaging. The study aimed to include 100 cCR patients with regrowth rates as primary endpoint. The data are presented in crude form. Eighty-two patients were included in seven hospitals from 2018 to 2020 when the study was terminated. Fifty-one patients were included in six hospitals, whereas protocol violations were identified in one hospital, where thirty-one (rather than protocol-estimated 12) patients were enrolled. Amongst the 31 patients, there were only 2 with documented cCR. Of the latter 29, there were 16 with ulcer or persistent tumour, and 13 without any documentation of cCR. Of these, 23 underwent surgery with a delay up to 50weeks. At median 54-month follow-up of 31 patients, there were 77% local regrowths (n = 23), 40% metachronous metastases (n = 12) and 23% deaths (n = 7). At median 54-month follow-up of 51 cCR patients, there were 53% local regrowths (n = 27), 14% metachronous metastases (n = 7) and 4% deaths (n = 2). Norwait admonishes a word of caution reaching beyond the inconclusive results of a population-based study jeopardised by serious violation to protocol and legislation for conducting safe research.

Diagnostic accuracy of dipsticks for urinary tract infections in acutely hospitalised patients: a prospective population-based observational cohort study

ObjectiveTo determine the added diagnostic value of dipsticks for urinary tract infections (UTI) in acutely hospitalised individuals.DesignProspective population-based cohort study.SettingNorth Denmark.ParticipantsAll adults (≥18 years) examined with dipsticks at emergency departments...

Personalized starting age of gastric cancer screening based on individuals' risk profiles: a population-based prospective study.

The current recommended starting age for gastric cancer (GC) lacks unified guideline and individualized criteria. We aimed to determine risk-stratified starting age for GC screening in China based on individuals' risk profiles, and develop an online calculator for clinical application. In this multi-center population-based prospective study, we divided participants enrolled during 2015-2017 (n = 59,771, aged 40-69) into screened and unscreened groups and observed them for primary endpoints-GC occurrence, all-cause and GC-specific deaths. The median follow-up was 6.07 years. To determine the reference starting age, the effectiveness of GC screening was assessed by age-groups after propensity-score-matching. Further, we categorized the calculated individual risk scores (using well-established risk factors) by quantiles. Subsequently, we used age-specific 10-year cumulative risk curves to estimate the risk-stratified starting age-when the individual's risk level matches reference starting age risk threshold. During follow-up, 475 GC cases, 182 GC deaths and 1,860 all-cause deaths occurred. All-cause and GC-specific mortality decreased among screened individuals aged ≥45 and 50-59 years, respectively. Thus, the average population (reference) starting age was set as 50 years. The 10-year cumulative risk of GC in average population aged 50 was 1.147%. We stratified the starting age using eight risk factors, and categorized participants as low-, medium-, and high-risk individuals, whose risk-stratified starting age was 58, 50, and 46, respectively. While high-risk individuals warrant 3-5 years earlier GC screening than average population (age 50), low-risk individuals can tolerate delayed screening. Our online, personalized starting-age calculator will help risk-adapted GC screening (https://web.consultech.com.cn/gastric/#/).

Personalized starting age of gastric cancer screening based on individuals' risk profiles: a population-based prospective study.

The current recommended starting age for gastric cancer (GC) lacks unified guideline and individualized criteria. We aimed to determine risk-stratified starting age for GC screening in China based on individuals' risk profiles, and develop an online calculator for clinical application. In this multi-center population-based prospective study, we divided participants enrolled during 2015-2017 (n = 59,771, aged 40-69) into screened and unscreened groups and observed them for primary endpoints-GC occurrence, all-cause and GC-specific deaths. The median follow-up was 6.07 years. To determine the reference starting age, the effectiveness of GC screening was assessed by age-groups after propensity-score-matching. Further, we categorized the calculated individual risk scores (using well-established risk factors) by quantiles. Subsequently, we used age-specific 10-year cumulative risk curves to estimate the risk-stratified starting age-when the individual's risk level matches reference starting age risk threshold. During follow-up, 475 GC cases, 182 GC deaths and 1,860 all-cause deaths occurred. All-cause and GC-specific mortality decreased among screened individuals aged ≥45 and 50-59 years, respectively. Thus, the average population (reference) starting age was set as 50 years. The 10-year cumulative risk of GC in average population aged 50 was 1.147%. We stratified the starting age using eight risk factors, and categorized participants as low-, medium-, and high-risk individuals, whose risk-stratified starting age was 58, 50, and 46, respectively. While high-risk individuals warrant 3-5 years earlier GC screening than average population (age 50), low-risk individuals can tolerate delayed screening. Our online, personalized starting-age calculator will help risk-adapted GC screening (https://web.consultech.com.cn/gastric/#/).

Association between Parkinson’s disease and cardiovascular disease mortality: a prospective population-based study from NHANES

Background and aimConflicting results have been reported on the association between Parkinson's disease (PD) and cardiovascular disease (CVD) mortality in different populations. Therefore, studying the relationship between PD and CVD mortality is crucial to reduce mortality caused by the former.MethodsIn this cohort investigation, we enrolled 28,242 participants from the National Health and Nutrition Examination Survey spanning from 2003 to 2018. The 380 cases of PD in the cohort were identified by documenting ‘ANTIPARKINSON AGENTS’ in their reported prescription medications. Mortality outcomes were ascertained by cross-referencing the cohort database with the National Death Index, which was last updated on 31 December 2019. Cardiovascular disease mortality was categorised according to the 10th revision of the International Classification of Diseases by using a spectrum of diagnostic codes. Weighted multivariable Cox regression analysis was used to examine the association between PD and the risk of CVD mortality.ResultsA total of 28,242 adults were included in the study [mean age, 60.156 (12.55) years, 13,766 men (48.74%)], and the median follow-up period was 89 months. Individuals with PD had an adjusted HR of 1.82 (95% CI, 1.24–2.69; p = 0.002) for CVD mortality and 1.84 (95% CI, 1.44–2.33; p < 0.001) for all-cause mortality compared with those without PD. The association between PD and CVD mortality was robust in sensitivity analyses, after excluding participants who died within 2 years of follow-up and those with a history of cancer at baseline [HR,1.82 (95% CI, 1.20–2.75; p = 0.005)].ConclusionsPD was associated with a high long-term CVD mortality rate in the US population.

P-772 Assisted reproductive technology and the risk of minor congenital heart defects in the newborn

Abstract Study question Are children conceived through assisted reproductive technology (ART) at higher risk of minor congenital heart defects (CHD) compared with naturally conceived (NC) children? Summary answer Contrary to previous studies children conceived through ART had similar risk of minor CHDs compared with children conceived naturally. What is known already Congenital heart defects (CHD) may precipitate cardiac arrhythmias, lead to thromboembolic events, culminate in heart failure or even sudden cardiac demise. A systematic review and meta-analysis showed an elevated odds ratio (OR) for diagnosis of any CHD among children conceived through in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) compared with NC children. Other studies indicate that ART is associated with an increased arterial blood pressure and vascular dysfunction in the pulmonary and systemic arterial vasculature. This association persists throughout childhood, adolescence, and early adulthood in individuals conceived through ART; this indicates a lasting impact on the cardiovascular circulatory system. Study design, size, duration The present study is a sub-study to the Copenhagen Baby Heart Study (CBHS), a prospective population-based cohort study of &amp;gt; 25 000 children born in the three main maternity wards in Copenhagen, Denmark, in 2016–2018. Transthoracic echocardiography (TTE) was performed on all children within 60 days of delivery and diagnosis of CHD was reviewed by a specialist in paediatric cardiology. Information regarding parental health, pregnancy, delivery, and the newborn was collected through Danish patient registries. Participants/materials, setting, methods This study includes all children conceived by ART in the CBHS (n = 1 784), and a matched group (1:4 by maternal age at birth) of NC children (n = 7 141). Exclusion criteria were genetic or chromosomal syndromes and heart surgery. Minor CHD was defined as an atrial (ASD) or ventricular septum defects (VSD), bicuspid aortic valve, coarctation of the aorta, pulmonary stenosis, or patent ductus arteriosus. We calculated ORs using logistic regression analyses. Main results and the role of chance The mean maternal age at birth was 34.9 (standard deviation [SD] ±4.4) and 35.1 years (SD ± 4.6) and the newborn mean age at TTE was 12.1 (SD ± 9.3) and 12.2 days (SD ± 9.4) in the ART and NC population, respectively. Parental CHD was registered in 40 (2.2 %) children in the ART group and 121 (1.7 %) in the NC group. Overall, 165 (9.2%) children conceived by ART and 611 (8.6%) NC children were diagnosed with a minor CHD. The most prevalent CHDs were VSD and ASD which accounted for 38.8 % and 35.2 % in children with CHD in the ART group, respectively, and 36.8 % and 33.9 % in children with CHD in the NC group. The unadjusted OR for minor CHD was 1.09 (95% CI 0.91–1.30). Adjustments for maternal age and parental CHD did not change the OR. There were no differences in ORs when stratifying by minor CHD type. We stratified by the method of ART: ICSI and IVF and frozen embryo transfer and fresh embryo transfer, and calculated risk of minor CHD comparing the methods and with NC children. We found no difference in any ORs, crude or adjusted. Limitations, reasons for caution Children born preterm, and children with severe minor and major CHDs, were underrepresented in the cohort indicating parents of such children chose not to participate in a research project that would include another hospital visit. Residual confounding is plausible because parental CHD diagnoses were retrieved from patient registries. Wider implications of the findings The number of children conceived through ART is increasing each year and previous research have found an increased risk of CHD in children conceived through ART. Our findings indicate no increased risk of minor CHD, providing comforting and significant information for advising individuals considering or undergoing ART treatment. Trial registration number NCT02753348

A commentary on "Predicting recurrence and survival in patients with non-metastatic renal-cell carcinoma after nephrectomy: a prospective population-based study with multicenter validation".

A commentary on "Predicting recurrence and survival in patients with non-metastatic renal-cell carcinoma after nephrectomy: a prospective population-based study with multicenter validation".

Influence of Oral Contraceptives on Lipid Profile and Trajectories in Healthy Adolescents—Data From the EVA-Tyrol Study

PurposeOral contraception is one of the most popular contraceptive methods both in adults and adolescents. However, the effects of oral contraception on lipids in adolescents are not well studied. MethodsLipid profiles were measured and contraceptive use was assessed in 14- to 19-year-old female participants of the prospective population-based Early Vascular Ageing-Tyrol Study between 2015 and 2018, twice on average 22 months apart. ResultsFor this analysis, data from 828 young women with a median age of 17.0 years were available. Of them, 317 (38%) used oral contraceptives (OCs). OC users had a slightly higher systolic and diastolic blood pressure and larger changes over time and were more likely to use cigarettes than nonusers. Total cholesterol (179.6 vs. 162.4 mg/dL), low-density lipoprotein-cholesterol (106.4 vs. 94.6 mg/dL), and triglycerides (104.0 vs. 67.0 mg/dL) were significantly higher in OC users after multivariable adjustment in linear regression models. No difference in high-density lipoprotein-cholesterol between the two groups was found. In 558 females, follow-up data were available. Those who initiated OC use had on average 15.4 mg/dL higher low-density lipoprotein-cholesterol and 36.2 mg/dL higher triglyceride level changes between baseline and follow-up than never users. Duration of OC use did not show a significant association with lipid levels and changes. DiscussionWe showed an independent association between OC use and blood lipids as well as lipid trajectories over time in a large cohort of healthy adolescents. These changes are especially relevant to consider in adolescents with other risk factors for dyslipidemia or other cardiovascular risk factors.

Derivation and Validation of ICD-10 Codes for Identifying Incident Stroke

Claims data with International Statistical Classification of Diseases, Tenth Revision (ICD-10) codes are routinely used in clinical research. However, the use of ICD-10 codes to define incident stroke has not been validated against expert-adjudicated outcomes in the US population. To develop and validate the accuracy of an ICD-10 code list to detect incident stroke events using Medicare inpatient fee-for-service claims data. This cohort study used data from 2 prospective population-based cohort studies, the Atherosclerosis Risk in Communities (ARIC) study and the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, and included participants aged 65 years or older without prior stroke who had linked Medicare claims data. Stroke events in the ARIC and REGARDS studies were identified via active surveillance and adjudicated by expert review. Medicare-linked ARIC data (2016-2018) were used to develop a list of ICD-10 codes for incident stroke detection. The list was validated using Medicare-linked REGARDS data (2016-2019). Data were analyzed from September 1, 2022, through September 30, 2023. Stroke events detected in Medicare claims vs expert-adjudicated stroke events in the ARIC and REGARDS studies. The main outcomes were sensitivity and specificity of incident stroke detection using ICD-10 codes. In the ARIC study, there were 110 adjudicated incident stroke events among 5194 participants (mean [SD] age, 80.1 [5.3] years) over a median follow-up of 3.0 (range, 0.003-3.0) years. Most ARIC participants were women (3160 [60.8%]); 993 (19.1%) were Black and 4180 (80.5%) were White. Using the primary diagnosis code on a Medicare billing claim, the ICD-10 code list had a sensitivity of 81.8% (95% CI, 73.3%-88.5%) and a specificity of 99.1% (95% CI, 98.8%-99.3%) to detect incident stroke. Using any diagnosis code on a Medicare billing claim, the sensitivity was 94.5% (95% CI, 88.5%-98.0%) and the specificity was 98.4% (95% CI, 98.0%-98.8%). In the REGARDS study, there were 140 adjudicated incident strokes among 6359 participants (mean [SD] age, 75.8 [7.0] years) over a median follow-up of 4.0 (range, 0-4.0) years. More than half of the REGARDS participants were women (3351 [52.7%]); 1774 (27.9%) were Black and 4585 (72.1%) were White. For the primary diagnosis code, the ICD-10 code list had a sensitivity of 70.7% (95% CI, 63.2%-78.3%) and a specificity of 99.1% (95% CI, 98.9%-99.4%). For any diagnosis code, the ICD-10 code list had a sensitivity of 77.9% (95% CI, 71.0%-84.7%) and a specificity of 98.9% (95% CI, 98.6%-99.2%). These findings suggest that ICD-10 codes could be used to identify incident stroke events in Medicare claims with moderate sensitivity and high specificity.

Influence of non-pharmaceutical interventions during the COVID-19 pandemic on respiratory viral infections - a prospective population-based cohort study.

DRKS.de, German Clinical Trials Register (DRKS), Identifier: DRKS00023418, Registered on 28 October 2020.

Assessment of the appropriate cutoff points for anthropometric indices and their relationship with cardio-metabolic indices to predict the risk of metabolic associated fatty liver disease

BackgroundResearch on Metabolic Associated Fatty Liver Disease (MAFLD) is still in its early stages, with few studies available to identify and predict effective indicators of this disease. On the other hand, early diagnosis and intervention are crucial to reduce the burden of MAFLD. Therefore, the aim of this research was to investigate the effectiveness of eleven anthropometric indices and their appropriate cut-off values as a non-invasive method to predict and diagnose MAFLD in the Iranian population.MethodsIn this cross-sectional study, we analyzed baseline data from the Hoveyzeh Cohort Study, a prospective population-based study conducted in Iran that enrolled a total of 7836 subjects aged 35 to 70 years from May 2016 through August 2018.ResultsThe optimal cut-off values of anthropometric indices for predicting MAFLD risk were determined for waist circumference(WC) (102.25 cm for males and 101.45 cm for females), body mass index (BMI) (27.80 kg/m2 for males and 28.75 kg/m2 for females), waist-to-hip ratio (WHR) (0.96 for both males and females), waist-to-height ratio (WHtR) (0.56 for males and 0.63 for females), body adiposity index (BAI) (23.24 for males and 32.97 for females), visceral adiposity index (VAI) (1.64 for males and 1.88 for females), weight-adjusted waist index (WWI) (10.63 for males and 11.71 for females), conicity index (CI) (1.29 for males and 1.36 for females), body roundness index (BRI) (4.52 for males and 6.45 for females), relative fat mass (RFM) (28.18 for males and 44.91 for females) and abdominal volume index (AVI) (18.85 for males and for 21.37 females). VAI in males (sensitivity: 77%, specificity: 60%, Youden’s Index: 0.37) and RFM in females (sensitivity: 76%, specificity: 59%, Youden’s Index: 0.35) were found to have higher sensitivity and specificity compared to other anthropometric indices. Furthermore, anthropometric indices demonstrated statistically significant correlations with various hepatic and cardiometabolic indices. Among these, the strongest positive correlations were observed between WC, BMI, BAI, BRI, and AVI with the Hepatic Steatosis Index (HSI), TyG-BMI, and TyG-WC, as well as between VAI and the Atherogenic Index of Plasma (AIP), Lipid Accumulation Product (LAP), Cardiometabolic Index (CMI), and the Triglyceride and Glucose (TyG) Index.ConclusionAnthropometric indices are effective in predicting MAFLD risk among Iranian adults, with WWI, VAI, and RFM identified as the strongest predictors. The proposed cutoff values could serve as a straightforward and non-invasive methods for the early diagnosis of MAFLD.

Does sex modify the effect of pre-pandemic body mass index on the risk of Long COVID? Evidence from the longitudinal analysis of the Survey of Health, Ageing and Retirement in Europe.

Research on Long COVID risk factors is ongoing. High body mass index (BMI) may increase Long COVID risk, yet no evidence has been established regarding sex differences in the relationship between BMI and the risk of Long COVID. Investigating the nature of this relationship was the main objective of this study. A population-based prospective study involving a sample of respondents aged 50 years and older (n = 4004) from 27 European countries that participated in the 2020 and 2021 Survey of Health, Ageing and Retirement in Europe's (SHARE) Corona Surveys and in Waves 7 and 8 of the main SHARE survey. Logistic regression models were estimated to produce unadjusted and adjusted estimates of the sex differences in the relationship between BMI and Long COVID. Linear relationship for females, with probability of Long COVID increasing with BMI (68% at BMI = 18, 93% at BMI = 45). Non-linear relationship for males, with probability of Long COVID of 27% at BMI = 18, 68% at BMI = 33, and 40% at BMI = 45. Relationships remained significant after adjusting for known Long COVID risk factors (age and COVID-19 hospitalization), presence of chronic diseases, and respondents' place of residence. Sex differences appear to play an important role in the relationship between BMI and risk of Long COVID. Overall, females were more likely to have Long COVID, regardless of their BMI. Males at the higher end of the BMI spectrum had a lower risk of Long COVID as opposed to their female counterparts. Sex-specific research is recommended for better understanding of Long COVID risk factors.

Cardiovascular disease risk factors and infertility: multivariable analyses and one-sample Mendelian randomization analyses in the Trøndelag Health Study.

Are cardiovascular disease (CVD) risk factors causally associated with higher risk of infertility among women and men? We found evidence to support a causal relationship between smoking initiation and history of infertility in women. Several CVD risk factors are associated with history of infertility. Previous studies using Mendelian randomization (MR) further support a causal relationship between BMI and infertility in women. We used data from the Trøndelag Health Study (HUNT) in Norway, a prospective population-based cohort study, including 26811 women and 15598 men participating in three survey collections in 1995-1997 (HUNT2), 2006-2008 (HUNT3), and 2017-2019 (HUNT4). Our outcome was women's self-reported history of infertility, defined as ever having tried to conceive for 12 months or more or having used ART. We assigned the history of infertility reported by women to their male partners; therefore, the measure of infertility was on the couple level. We used both conventional multivariable analyses and one-sample MR analyses to evaluate the association between female and male CVD risk factors (including BMI, blood pressure, lipid profile measurements, and smoking behaviours) and history of infertility in women and men, separately. A total of 4702 women (18%) and 2508 men (16%) were classified with a history of infertility. We found a higher risk of infertility among female smokers compared to non-smokers in both multivariable and MR analyses (odds ratio (OR) in multivariable analysis, 1.20; 95% CI, 1.12-1.28; OR in MR analysis, 1.13; CI, 1.02-1.26), and potentially for higher BMI (OR in multivariable analysis, 1.13; CI, 1.09-1.18; OR in MR analysis, 1.11, CI, 0.92-1.34). In multivariable analysis in women, we also found evidence of associations between triglyceride levels, high-density lipoprotein cholesterol, lifetime smoking index, and smoking intensity with higher risk of infertility. However, these results were not consistent in MR analyses. We found no robust or consistent associations between male CVD risk factors and infertility. Our main limitation was that the CVD risk factors measured might not adequately capture the relevant time periods for when couples were trying to conceive. Additionally, we did not have information on causes of infertility in either women or men. Women with infertility could have a worse CVD risk factor profile and thus public health interventions aimed at reducing the impact of some CVD risk factors, such as smoking and BMI, could reduce the burden of infertility. However, additional MR studies of the relationship between CVD risk factors and infertility with a larger sample size would be of value. The study was supported by a grant from the European Research Council under the European Union's Horizon 2020 research and innovation program (grant agreements no. 947684). This research was also supported by the Research Council of Norway through its Centres of Excellence funding scheme (project no. 262700) and partly funded by the Research Council of Norway, project: Women's fertility-an essential component of health and well-being (project no. 320656). D.A.L. and A.F. work in a unit that is supported by the University of Bristol and the UK Medical Research Council (MC_UU_00011/6). D.A.L.'s contribution to the article is supported by the European Research Council (101021566), the British Heart Foundation (CH/F/20/90003 and AA/18/7/34219). S.B.'s contribution to the article is supported by the Wellcome Trust (225790/Z/22/Z). B.M.B. is funded by The Liaison Committee for education, research and innovation in Central Norway; and the Joint Research Committee between St. Olavs Hospital and the Faculty of Medicine and Health Sciences, NTNU. The genotyping in HUNT was financed by the National Institute of Health (NIH); University of Michigan; The Research Council of Norway; The Liaison Committee for education, research and innovation in Central Norway; and the Joint Research Committee between St. Olavs Hospital and the Faculty of Medicine and Health Sciences, NTNU. None of the funding organizations influenced the study design, reporting, or interpretation of results. The views expressed in the present article are those of the authors and not necessarily any acknowledged funding organization. D.A.L. reports grants from Medtronic Ltd and Roche Diagnostics outside the submitted work. The other authors have no conflicts of interest. N/A.

The Effect of Thiazide Diuretics on Urinary Prostaglandin E2 Excretion and Serum Sodium in the General Population.

Thiazide-induced hyponatremia is one of the most common forms of hyponatremia, but its pathogenesis is incompletely understood. Recent clinical data suggest links with prostaglandin E2 (PGE2) and a single nucleotide polymorphism (SNP) in the prostaglandin transporter gene (SLCO2A1), but it is unknown if these findings also apply to the general population. To study the associations between serum sodium, thiazide diuretics, urinary excretions of PGE2 and its metabolite (PGEM), and the rs34550074 SNP in SLCO2A1 in the general population. Prospective population-based cohort study (Rotterdam Study). General population. 2,178 participants (65% female, age 64 ± 8 years). None. Serum sodium levels. Higher urinary PGE2 excretion was associated with lower serum sodium: difference in serum sodium for each two-fold higher PGE2 -0.19 mmol/l (95%CI -0.31 to -0.06), PGEM -0.29 mmol/l (95%CI -0.41 to -0.17). This association was stronger in thiazide users (per two-fold higher PGE2 -0.73 vs. -0.12 mmol/l and PGEM -0.6 vs. -0.25 mmol/l, p for interaction < 0.05 for both). A propensity score matching analysis of thiazide vs. non-thiazide users yielded similar results. The SNP rs34550074 was not associated with lower serum sodium or higher urinary PGE2 or PGEM excretion in thiazide or non-thiazide users. Serum sodium is lower in people with higher urinary PGE2 and PGEM excretion and this association is stronger in thiazide users. This suggests that PGE2-mediated water reabsorption regulates serum sodium, which is relevant for the pathogenesis of hyponatremia in general and thiazide-induced hyponatremia in specific.

Outdoor walking, genetic predisposition, and the risk of incident osteoporosis among older adults: A prospective large population-based cohort study

SummaryThis large-scale prospective study showed that a significant association between longer duration of daily outdoor walking and reduced osteoporosis risk was found among older adults, particularly among those with a low genetic predisposition to osteoporosis, which highlighted the importance of outdoor walking as a simple, cost-effective adjunct for preventing osteoporosis.PurposeThe available cross-sectional data and small-scale studies indicate that outdoor walking benefits bone metabolism. Nevertheless, there is a scarcity of comprehensive prospective research investigating the enduring correlation between outdoor walking and osteoporosis. This study aims to conduct a prospective analysis of the correlation between outdoor walking and osteoporosis while also examining potential variations influenced by genetic susceptibility to osteoporosis.Methods24,700 older adults without osteoporosis at baseline were enrolled. These individuals were followed up until December 31, 2021, during which data on outdoor walking was gathered. The genetic risk score for osteoporosis was comprised of 14 single-nucleotide polymorphisms.Results4,586 cases of osteoporosis were identified throughout a median follow-up period of 37.3 months. Those who walked outside for > 30 but ≤ 60 min per day had a hazard ratio (HR) of 0.83 (95% confidence interval (CI): 0.72–0.95) for incident osteoporosis, whereas those who walked outside for > 60 min per day had an HR of 0.60 (95% CI: 0.39–0.92). We found that osteoporosis risk exhibited a declining trend in individuals with low genetic risk. Individuals walking outside for > 60 min per day tended to have the lowest overall osteoporosis risk among those with high genetic risk.ConclusionsA significant negative correlation exists between an extended period of daily outdoor walking and osteoporosis incidence risk. This correlation is particularly pronounced among individuals with low genetic risk. The results above underscore the significance of outdoor walking as a simple and economical adjunct to public health programs to prevent osteoporosis.

Women with a history of gestational diabetes mellitus present an accumulation of cardiovascular risk factors at age 46-A birth cohort study.

The incidence of gestational diabetes mellitus (GDM) is globally increasing, and it has been associated with later type 2 diabetes, metabolic syndrome (MetS), and cardiovascular disease (CVD). However, long-term population-based studies investigating common CVD risk factors years after pregnancy are lacking. To evaluate the future mortality and morbidity in cardiovascular and metabolic diseases, we conducted a thorough investigation of midlife risk factors in women with and without previous GDM. A prospective population-based cohort study was conducted of 3173 parous women from the Northern Finland Birth Cohort, 1966. Study participants were obtained from the national register or patient records. Those with a GDM diagnosis formed the GDM cohort (n = 271), and those without a previous GDM diagnosis formed the control cohort (n = 2902). Clinical examinations were performed on participants at the age of 46 and included anthropometric measurements, oral glucose tolerance test (OGTT), biochemical measurements, and cardiovascular assessment. At the age of 46, women in the GDM cohort had a higher body mass index (BMI, 29.0 kg/m2 vs 26.3 kg/m2, p < 0.001) and greater waist circumference (94.1 cm vs 86.5 cm, p < 0.001) than the control cohort. In the GDM cohort, a higher incidence of impaired glucose tolerance (12.6% vs 7.3%, p = 0.002), more previously diagnosed and OGTT-detected type 2 diabetes (23.3% vs 3.9%, p < 0.001), lower high-density lipoprotein (1.53 mmol/L vs 1.67 mmol/L, p = 0.011), higher triglycerides (1.26 mmol/L vs 1.05 mmol/L, p = 0.002) and a higher fatty liver index (6.82 vs 2.47, p < 0.001), were observed even after adjusting for BMI, polycystic ovary syndrome, parity, level of education, physical activity, smoking, and alcohol consumption. The women in the GDM cohort also had more MetS (42.6% vs 21.9%, p < 0.001) and higher risk scores for CVD and fatal events (Framingham 4.95 vs 3.60, p < 0.001; FINRISK 1.71 vs 1.08, p < 0.001). Women with a previous diagnosis of GDM exhibit more risk factors for CVD in midlife and are at a higher risk for cardiovascular events later in life.