Strong Association Research Articles

Clinical and Radiographic Features of Peri-Implant Medication-Related Osteonecrosis of the Jaw: ARetrospective Study.

This study aimed to analyze the factors affecting the occurrence of peri-implant medication-related osteonecrosis of the jaw (PI-MRONJ) in patients using anti-resorptive drugs (ARDs) on different implant position, inclinations, and types of prosthesis. The data of 75 patients with bone necrosis that progressed around the implant between 2018 and 2022 were retrospectively examined to identify the factors influencing PI-MRONJ. Data, including patient demographics (age, sex, smoking status, concomitant disease, time of ARD therapy, dose of ARDs, and parafunctional habits) and implant-specific information (type of prosthesis, angle of insertion), were extracted from medical and dental records. Tilted implants with an angle ≥ 5.1° relative to the occlusal plane of the prosthesis had a stronger association with PI-MRONJ in comparison to non-tilted implants (inclination was < 5°). Additionally, the boundary of the area of osteonecrosis around the fixture was larger for the splinted implant-supported crowns than for the single implant supported crowns). In patients taking anti-resorptive medications the inclination of the implant was associated with the occurrence of PI-MRONJ. Further studies are required to confirm the clinical findings.

Impact of Heat on Respiratory Hospitalizations among Older Adults in 120 Large US Urban Areas.

Extreme heat exposure is a well-known cause of mortality among older adults. However, the impacts of exposure on respiratory morbidity across US cities and population subgroups is not well understood. A nationwide study to determine the impact of high heat on respiratory disease hospitalizations among older adults (65+) living in the 120 largest US cities between 2000-2017. Daily rates of inpatient respiratory hospitalizations were examined with respect to variations in ZIP-code-level daily mean temperature and heat index. For each city, we estimated cumulative associations (lag-days 0-6) between warm-season heat (June-September) and cause-specific respiratory hospitalizations using time-stratified conditional quasi-Poisson regression with distributed lag non-linear models. We estimated nationwide associations using multivariate meta-regression and updated city-specific associations via best linear unbiased prediction. With stratified models, we explored effect modification by age, sex, and race (Black/white). Results were reported as percent change in hospitalizations at high temperatures (95th percentile) compared to median temperatures for each outcome, demographic group, and metropolitan area. We identified 3,275,033 respiratory hospitalizations among Medicare beneficiaries across 120 large US cites between 2000 and 2017. Nationwide, 7-day cumulative associations at high temperatures, resulted in a 1.2% (0.4%, 2.0%) increase in hospitalizations for primary diagnoses of all-cause respiratory disease, primarily driven by increases in respiratory tract infections [1.8% (0.6%, 3.0%)], and chronic respiratory diseases/respiratory failure [1.2% (0.0%, 2.4%)]. Stronger associations were observed when exposure was defined using the heat index instead of temperature. Across the 120 cities, we observed considerable geographic variation in the relative risk of heat-related respiratory hospitalizations, and we observed disproportionate burdens of heat-related respiratory hospitalizations among the oldest beneficiaries (85+ years), and among Black beneficiaries living in South Atlantic cities. During the 18-year study period, there were an estimated 11,710 excess respiratory hospitalizations due to heat exposure. Results suggest that high temperature and humidity contribute to exacerbation of respiratory tract infections and chronic lung diseases among older adults. Geographic variation in heat-related hospitalization rates suggests that contextual factors largely account for disproportionate burdens, and area-level influences should be further investigated in multi-city studies.

Triglyceride-glucose index is associated with heart failure with preserved ejection fraction in different metabolic states in patients with coronary heart disease

BackgroundThe triglyceride-glucose (TyG) index is a surrogate indicator of insulin resistance. Therefore, we aimed to determine the association between TyG index and heart failure (HF) with preserved ejection fraction (HFpEF) in patients with coronary heart disease (CHD) and to explore whether such associations would be modified by different metabolic states.MethodsAmong 107,301 CHD patients, 62,794 were included to analyze the relationship between the TyG index and HF. Among them, 8,606 patients who had undergone echocardiography were included to identify different types of HF, including HF with reduced ejection fraction (HFrEF), HF with intermediate-range ejection fraction (HFmrEF), and HFpEF. Among them, 1896 patients were diagnosed with HFpEF. Logistic regression was used to analyze the relationship between the TyG index and HFpEF in CHD patients. In addition, the association between TyG index and HFpEF according to sex, age, blood lipids, and blood pressure was assessed.ResultsA baseline analysis of CHD patients divided into four groups according to the tertile level of the TyG index showed significant differences in the related parameters between the groups. In the multi-adjusted models, the TyG index was significantly associated with the risk of HFpEF (odds ratio [OR]: 1.17; 95% confidence interval [CI]: 1.09–1.25). After adjustment for multivariates, TyG index levels for T2 (OR: 1.33; 95% CI: 1.16–1.52) and T3 (OR: 1.52; 95% CI: 1.32–1.74) were associated with increased OR in HFpEF. In addition, the TyG index of CHD patients was significantly associated with HFpEF in older adults aged &amp;gt; 60 years (OR: 1.20; 95% CI: 1.11–1.29), hypertension (OR: 1.27; 95% CI: 1.17–1.37), and dyslipidemia (OR: 1.15; 95% CI: 1.08–1.24). Moreover, the OR (OR: 1.23; 95% CI: 1.11–1.36) in women is higher than in men (OR: 1.17; 95% CI: 1.02–1.22, indicating a stronger association between TyG index and HFpEF in women.ConclusionsOur findings demonstrated a significant association between TyG index and HFpEF in CHD patients. Furthermore, TyG index was independently associated with HFpEF in hypertension, dyslipidemia, and older patients (aged &amp;gt; 60 years). In addition, the association between the TyG index and HFpEF in CHD patients differed according to sex.

Economic inequalities in adolescents’ internalising symptoms: longitudinal evidence from eight countries

Research, mainly conducted in Europe and North America, has shown an inequitable burden of internalising mental health problems among adolescents from poorer households. We investigated whether these mental health inequalities differ across a diverse range of countries and multiple measures of economic circumstances. In this longitudinal observational cohort study, we analysed data from studies conducted in eight countries (Australia, Ethiopia, India, Mexico, Peru, South Africa, the UK, and Viet Nam) across five global regions. All studies had self-reported measures of internalising symptoms using a validated scale at two timepoints in adolescence; a measure of household income, household consumption expenditure, or subjective wealth; and data collected between 2000 and 2019. Household income (measured in four countries), consumption expenditure (six countries), and adolescents' subjective assessment of household wealth (five countries) were measured in mid-adolescence (14-17 years). The primary outcome (internalising symptoms, characterised by negative mood, affect, and anxiety) was measured later in adolescence between age 17 and 19 years. Analyses were linear regression models with adjustment. Effect estimates were added to random-effects meta-analyses to aid understanding of cross-country differences. The overall pooled sample of eight studies featured 18 910 adolescents (9568 [50·6%] female and 9342 [49·4%] male). Household income had a small or null association with adolescents' internalising symptoms. Heterogeneity (I2 statistic) was 71·04%, falling to 39·71% after adjusting for baseline symptoms. Household consumption expenditure had a stronger association with internalising symptoms (decreases of 0·075 SD in Peru [95% CI -0·136 to -0·013], 0·034 SD in South Africa [-0·061 to -0·006], and 0·141 SD in Viet Nam [-0·202 to -0·081] as household consumption expenditure doubled). The I2 statistic was 74·24%, remaining similar at 74·83% after adjusting for baseline symptoms. Adolescents' subjective wealth was associated with internalising symptoms in four of the five countries where it was measured. The I2 statistic was 57·09% and remained similar after adjusting for baseline symptoms (53·25%). We found evidence for cross-country differences in economic inequalities in adolescents' internalising symptoms, most prominently for inequalities according to household consumption expenditure. Subjective wealth explained greater variance in symptoms compared with the objective measures. Our study suggests that economic inequalities in adolescents' mental health are prevalent in many but not all countries and vary by the economic measure considered. Variation in the magnitude of inequalities suggests that the wider context within countries plays an important role in the development of these inequalities. Wellcome Trust.

Modifiable lifestyle factors in the primordial prevention of hypertension in three US cohorts

Background: Evidence is lacking on the relative contributions of specific lifestyle factors and their overall contribution to prevention of hypertension, in particular early-onset hypertension. Methods: This prospective cohort study included participants of the Nurses’ Health Study (NHS, N=52,780 women, aged 40–67 in 1986), the NHS II (N=83,871 women, aged 27–46 in 1991), and the Health Professionals Follow-up Study (HPFS, N =31,269 men, aged 40–75 in 1986), who were free from hypertension, cardiovascular disease and cancer at baseline. Four modifiable lifestyles were evaluated based on hypertension guidelines: BMI, moderate-to-vigorous physical activity, Dietary Approaches to Stop Hypertension (DASH) score, and alcohol intake. Primary outcome was incident self-reported diagnosis of hypertension with 27-31 years of follow-up. Results: Each lifestyle factor was associated with incident hypertension in dose-dependent manners across the cohorts, with BMI having the strongest associations. On average, adhering to BMI <25 kg/m2 was associated with 20.3 [18.5, 22.0], 25.0 [23.2, 26.8], and 18.6 [16.7, 20.7] months longer periods free from hypertension during 25-year follow-up in each cohort respectively. BMI accounted for approximately 20% of incident hypertension in NHS and HPFS, and 35% of early-onset hypertension (age < 55y). Moderate-to-vigorous physical activity and diet accounted for 10-15% of incident hypertension in women, and the contributions were greater for early-onset hypertension. Conclusion: Healthy weight during adulthood was most substantially associated with incident hypertension among lifestyle factors, but diet, physical activity, and alcohol intake were also related to the risk across all ages, and hypertension-free periods, with stronger associations in early-onset hypertension.

The relative contributions of genetic and non‐genetic factors to the risk of neuroblastoma

ABSTRACTPrevious literature has well‐established genetic factors as being associated with neuroblastoma (NB). About 1%–2% of NB cases are familial, with 85% of these cases predisposed to mutations in the PHOX2B and ALK genes. The genetic basis of sporadic NB has been studied through genome‐wide association studies and next‐generation sequencing approaches. Particularly, germline variants, as well as copy number variations, confer increased risks of NB, often with effect estimates ≥1.5, underscoring the strong genetic contributions to NB. However, the strength of the association varied in non‐genetic factors. Some risk factors, such as birth defects, maternal illicit drug use, and early infections, had relatively stronger associations (effect estimates ≥1.5 or ≤0.67), while some other factors remain inconclusive. This suggests that certain non‐genetic factors may play a more prominent role in NB risk, while further research is needed to clarify the impact of others. We synthesized and critically evaluated existing literature on the risk factors of NB to provide an overview, analyze the current state of knowledge, and outline a research path to address the relative contributions of genetic and non‐genetic factors in NB. Future epidemiologic studies should incorporate novel methods for measuring genetic and non‐genetic factors to comprehensively assess the full extent of factors contributing to NB. Furthermore, the utilization of dried blood spots holds promise to overcome technical and recruitment challenges for future studies. These strategies will contribute to a more holistic understanding of NB etiology and potentially lead to improved prevention strategies.

Air pollution and under-5 child mortality: linking satellite and IPUMS-DHS data across 41 countries in South Asia and Sub-Saharan Africa

BackgroundDespite progress, under-five mortality remains high, especially in Sub-Saharan Africa and South Asia, where around 13,400 children die daily. Environmental pollutants, including PM2.5 from outdoor air and household air pollution, significantly contribute to these preventable deaths.MethodsThis cross-country study combined satellite data with 113 surveys from the IPUMS-DHS dataset (1998–2019) to examine under-five child mortality in 41 developing countries. The integration of Global Annual Particulate Matter with a diameter of 2.5 micrometres or less (PM2.5) Grids from Socioeconomic Data and Applications Center (SEDAC) and geospatial data from the DHS Program enabled a focused analysis of the association between indoor and outdoor air pollution, particularly PM2.5, and child mortality rates using both logistic and multilevel logistic regression models, as well as estimating Population Attributable Fractions (PAF) to quantify the mortality burden attributable to these pollutants.ResultsOutdoor air pollution, measured by a one standard deviation increase in PM2.5, significantly increased the risk of child mortality (Odds Ratio [OR]: 1.14; 95% Confidence Interval [CI]: 1.10–1.18; p < 0.001). Moderate and high household air pollution exposure also heightened this risk, with increases of 37% (OR: 1.37; 95% CI: 1.24–1.53; p < 0.001) and 40% (OR: 1.40; 95% CI: 1.26–1.56; p < 0.001), respectively, compared to no exposure. Multilevel models (Models 5a and 10a) produced similar estimates to standard logistic regression, indicating robust associations. Additionally, Population Attributable Fraction analysis revealed that approximately 11.9% of under-five mortality could be prevented by reducing ambient PM2.5 exposure and 12.0% by mitigating household air pollution. The interaction between indoor and outdoor pollution revealed complex dynamics, with moderate and high household exposure associated with a reduction in mortality risk when combined with PM2.5. Geographical disparities were observed, with stronger correlations between outdoor air pollution and child mortality in Africa compared to Asia, and more pronounced impacts in low-income countries. However, household air pollution had stronger association with child mortality in Africa and lower- and middle-income countries.ConclusionsOur findings could serve as a guide for policy development aimed at reducing under-five mortality, ultimately contributing to the attainment of the Sustainable Development Goal (SDGs).

Early life social predictors of longitudinal relations between childhood BMI and overeating

Abstract Introduction The progression of obesity is a continuous process involving a complex system of genetic, environmental, and behavioural factors. Socioeconomic disadvantage as well as psychological distress may lead to overeating, subsequently associated with increased energy intake and weight gain. Recent evidence indicated that the association between childhood obesity and overeating might be bidirectional. Therefore, this study aimed to longitudinally investigate the directionality of the association between childhood BMI and overeating and to identify antecedent early childhood predictors. Methods The study sample included 5,777 children from the European Longitudinal Study of Parents and Children (ELSPAC), collected between 18 months and 11 years of child age. The outcomes were child BMI and overeating. Predictors included maternal BMI, maternal education, single-parent households, financial difficulties, and adverse childhood experiences (ACEs). The random intercept cross-lagged panel model (RI-CLPM) was applied. Results The results showed temporal stability in the development of overeating and BMI, with a bidirectional relationship that strengthened over time. The child’s BMI was predicted by maternal BMI (β = 0.37, p &amp;lt; 0.001). The child’s overeating was predicted by maternal BMI (β = 0.13, p &amp;lt; 0.001), but a stronger effect was found for ACEs (β = 0.24, p &amp;lt; 0.001). ACEs mediated the impact of maternal education, financial difficulties, and single parenthood on overeating with indirect effects of β = -0.01 (p = 0.005), β = 0.04, (p &amp;lt; 0.001), and β = 0.07 (p &amp;lt; 0.001), respectively. Conclusions We observed stable bidirectional longitudinal effects, with a stronger association from BMI to overeating. The results suggested two main pathways: one linked to maternal BMI and early childhood BMI increase followed by overeating, and the other associated with ACEs mediating the effect of early childhood socioeconomic factors on overeating, leading to gradual BMI gain. #NGEU Key messages • The study revealed a stable bidirectional association between childhood BMI and overeating, with a stronger association from BMI to overeating. • There are two potential pathways in childhood obesity development, one involving maternal BMI, and the second associated with social disadvantage and ACEs.

Protein signatures associated with methylation patterns of heart failure phenotypes

Abstract Introduction The heart failure (HF) syndrome is highly susceptible to the exposome. The interplay between DNA methylation (DNAm), surrogate for exposomal influences, and the plasma proteome in the progression and development of phenotypes of heart failure is unclear. We investigated the relation between methylation patterns of HF phenotypes and proteins signatures. Methods Individuals with symptomatic HF (stage C/D with HFpEF, HFmrEF and HFrEF) of the MyoVasc cohort (N=3,289) were investigated. EDTA-Plasma and DNA were extracted from peripheral blood and stored in -80°C. DNAm was measured using the Infinium MethylationEPIC v2.0 methylation array. Concentrations for 538 proteins were measured using an immuno-qPCR assay in EDTA plasma. Multivariable regression models adjusted for age and sex were used to assess the relationship between DNAm signatures and individual proteins in each phenotype. Ridge-regularized linear regression was used to generate a phenotype-specific protein-signature in relation to each methylation signature, linear regression to estimate links between protein signatures and cardiovascular traits and Cox regression relate protein signatures to clinical outcome. Results Data from 1,317 individuals with symptomatic HF were analyzed. After FDR adjustment, 310 proteins were significantly related to HFpEF methylation signature, 314 to HFmrEF and 266 to HFrEF. Of associated proteins, 49.9% (198) were found in all phenotypes, 8.82% (35) only in HFpEF, 12.1% (48) in HFmrEF and 4.79% (19) in HFrEF. Tumor necrosis, arterial hypertension and T-cell regulation pathways were enriched in all three phenotypes. NT-proBNP had the strongest association with HFrEF (β=0.95 [0.82-1.08], p&amp;lt;0.0001) followed by presence of plaques in carotid artery and C-reactive protein, while left ventricular mass (LVM) had stronger association with HFpEF (β=0.22 [0.11-0.33], p=0.0001). All three signatures were associated with worsening of HF (HFpEF: HR=1.93 [1.61-2.30], p&amp;lt;0.0001; HFmrEF: HR=1.63 [1.29-2.04], p&amp;lt;0.0001; HFrEF: HR=1.64 [1.38-1.95], p&amp;lt;0.0001) and all-cause death in HF (HFpEF: HR=1.93 [1.65-2.26], p&amp;lt;0.0001; HFmrEF: HR=1.95 [1.58-2.42], p&amp;lt;0.0001; HFrEF: HR=2.24 [1.86-2.69], p&amp;lt;0.0001). Methylation-associated protein signatures had stronger associations with clinical outcome than the methylation signatures themselves (p &amp;lt; 0.01). Conclusion This study revealed protein signatures associated with methylation patterns of HF phenotypes that shared common and unique features for HF phenotypes. Important common pathways were enriched in tumour necrosis, arterial hypertension and regulation of T cells. However, important differences between phenotypes were also revealed, e.g. NT-proBNP was strongly associated with the HFrEF protein signature and LVM with the HFpEF signature. The methylation-associated protein signatures emphasise the possible exposomal influence on HF syndrome.

Interleukin-6 and suPAR improves prediction of all-cause mortality in type 1 diabetes - the Thousand &amp; 1 Study

Abstract Background Cardiovascular diseases (CVD) are the leading cause of mortality in type 1 diabetes (T1D). Inflammation frequently accompanies T1D and is suggested as an important contributor to the pathogenesis and progression of CVD. However, current risk prediction models for T1D lack biomarkers of inflammation. Methods A prospective study of individuals with T1D without overt heart disease was evaluated. Interleukin-6 (IL-6), soluble urokinase-type plasminogen activator receptor (suPAR) and high-sensitivity C-reactive protein (hsCRP) were analysed. In Cox proportional hazards model, adjustments were made for variables in the Steno T1 Risk Engine: age, sex, duration of diabetes, HbA1c, systolic blood pressure, glomerular filtration rate, albuminuria status, use of statins, tobacco use and physical activity. The model included the biomarkers as continuous variables, and a "combination" category was defined as simultaneously elevated suPAR &amp;gt; 4 ng/mL and IL-6 &amp;gt; 3 pg/mL. The net reclassification improvement (NRI) and C-statistics were calculated. Results For included individuals (n=1,014, 52% male, mean age 50±15), follow-up was 100% after median of 12.2 years (interquartile range: 11.8 to 12.9).In the fully adjusted model, IL-6 and suPAR were both associated with all-cause mortality (IL-6 hazard ratio (HR): 1.6 (95% confidence interval: 1.04 to 2.4), suPAR HR: 1.9 (1.2 to 2.9). HsCRP was not associated with the outcome. The combination category showed even stronger association: HR 2.7 (1.4 to 5.1). When added to the Steno T1 Risk Engine, IL-6, suPAR, and their combination all added discriminatory power in predicting all-cause mortality assessed by NRI; IL-6: 38% (19 to 58), suPAR: 45% (25 to 65), combination 56% (36 to 76). C-statistics showed similar results for only suPAR. Area under the curve for suPAR: from 0.84 to 0.86 (P=0.049), IL-6: 0.84 to 0.85 (P=0.338), combination: 0.84 to 0.86 (P=0.066). Conclusions IL-6 and suPAR are independently associated with all-cause mortality in T1D without known heart disease. Assessment of IL-6 and suPAR in T1D may enhance risk prediction.Figure 1Figure 2

Parity Moderates the Socioeconomic Predictors of Birth Setting Choice.

The increase in the number of people choosing community birth has raised interest in understanding the factors that influence birth setting choices. This study investigates how parity influences the association between maternal socioeconomic factors and choice of community versus hospital birth. We used 2009-2021 US birth certificate data to identify community births (planned home or birth center births), parity, and maternal characteristics, including Women, Infants, and Children (WIC) program participation, race, ethnicity, educational attainment, marital status, body mass index (BMI), and age. Parity was interacted with each covariate in a multivariable logistic regression model of birth setting. Among 26,526,010 eligible births, 58% were to multiparous mothers, with 1.9% occurring in a birth center or at home. For most maternal characteristics, associations with community birth were stronger in the multiparous group compared to the nulliparous group. For example, being married was associated with greater odds of community birth in both groups, but the strength of this association was greater within the multiparous group (odds ratio 4.00 vs. 1.94, interaction p < 0.001). The same pattern (stronger association with community birth in the multiparous group than in the primiparous group) was observed for race/ethnicity, educational attainment, and WIC participation, all of which were associated with lower odds of community birth. This study shows that parity significantly moderates associations between maternal socioeconomic characteristics and birth setting, implying studies of decision-making in this context should purposively stratify samples and analyses by parity.

Association between lipoprotein particle concentration and size and progression of coronary plaque: the MACS Longitudinal Coronary CT angiography study

Abstract Background People living with HIV have greater risk of cardiovascular diseases (CVD) than people without HIV and tend to have different risk profiles, including higher serum triglycerides and lower LDL cholesterol levels. Nuclear magnetic resonance (NMR) provides a detailed phenotype of lipoproteins. Purpose To examine the associations between lipoprotein particle concentrations and size and progression of coronary artery plaque among people living with and without HIV, and whether these associations differ by HIV serostatus. Methods Men with no clinical CVD in the Multicenter AIDS Cohort Study (MACS) who underwent a coronary CT angiography at baseline (2010-13) and follow-up (2015-17) were included. NMR spectroscopy was completed on fasting serum samples at baseline. Logistic regression models for the change in total coronary plaque volume (in tertiles) were estimated with NMR-derived lipoproteins as predictors. Levels were log-transformed and standardized to make results comparable. Models were adjusted for demographics, statin use and HIV serostatus (model 1) with addition of CVD risk factors (model 2). Interactions by HIV serostatus were also tested. Results A total of 549 men (314 with HIV; 235 without HIV) were included. Mean age was 53 ±7 years; 58% were White, 30% Black, and 12% Hispanic. Coronary plaque was present in 70% and plaque volume progressed in 79% of the cohort. Among men with HIV, 81% had undetectable HIV RNA and 12% had a diagnosis of AIDS at baseline. Men with HIV had significantly higher levels of small LDL-P, and total, medium and large VLDL-P levels compared to men without HIV, and lower levels of total, small and large HDL-P (Table 1). Men with HIV had significantly greater progression of plaque volume (37 mm3) compared to men without HIV (31 mm3, p&amp;lt;0.05). Levels of total and small LDL-P concentrations were directly associated with plaque progression, whereas large HDL-P was inversely associated with plaque progression in the combined sample (Model 2). Associations between total and small LDL-P with plaque progression were stronger in men with HIV than in men without HIV in models 1 and 2 (interaction p&amp;lt;0.01). While associations in fully adjusted models for total VLDL-P and small VLDL-P were significant in men without HIV, there were no significant associations between these particle concentrations with coronary plaque progression among men without HIV (interaction p&amp;lt; 0.01) (Model 2, Table 2). Conclusion Associations between lipid particle concentrations and coronary plaque progression differed between men with and without HIV, with stronger associations seen in men without HIV for total and small LDL-P. Despite having higher VLDL and lower HDL particle concentrations at baseline, these particle concentrations were only associated with plaque progression in men without HIV. Further research is needed to elucidate HIV specific factors for plaque progression to tailor risk reduction strategies.

Low ambient temperature and incident myocardial infarction with or without obstructive coronary arteries: a Chinese nationwide study.

Although non-optimum ambient temperature is a major non-traditional risk factor for acute myocardial infarction, there is no prior knowledge on whether non-optimum ambient temperature could differentially affect myocardial infarction with obstructive coronary artery disease (MI-CAD) and myocardial infarction with non-obstructive coronary arteries (MINOCA). Using the Chinese Cardiovascular Association database-Chest Pain Center Registry, a nationwide, time-stratified, case-crossover investigation was conducted from 2015 to 2021. Meteorological data were obtained from an established satellite-based model, and daily exposures were assigned according to the onset of myocardial infarction in each patient. A conditional logistic regression model combined with distributed lag non-linear models (10 days) was used to estimate the exposure-response relationships. A total of 83 784 MINOCA patients and 918 730 MI-CAD patients were included. The risk of MINOCA and MI-CAD associated with low temperature occurred at lag 2 day and lasted to 1 week. Extremely low temperature was associated with a substantially greater odds ratio (OR) of MINOCA [OR 1.58, 95% confidence interval (CI) 1.31-1.90] than MI-CAD (unmatched: OR 1.32, 95% CI 1.23-1.43; equally matched by age and sex: OR 1.25, 95% CI 1.04-1.50), compared with the corresponding reference temperatures (30°C, 35°C, and 30°C). Stronger associations were observed for patients who were aged ≥65 years, female, or resided in the south. There was no significant difference for the impacts of high temperature on MINOCA and MI-CAD. This nationwide study highlights the particular susceptibility of MINOCA patients to ambient low temperature compared with that of MI-CAD patients.

Sex differences in cardiovascular disease in relation to socioeconomic position in the NAKO study

Abstract Background Low socioeconomic position (SEP) is associated with cardiovascular disease (CVD) risk; yet, the underlying pathways are not fully clear and may affect sexes differently. We investigated sex differences in the relationship of SEP with prevalent CVD, cardiovascular risk factors (CRF) and estimated cardiovascular risk in a contemporaneous German population. Methods Data derived from the baseline examination of 204,780 participants in population-based German National Cohort (NAKO). Logistic, multinomial, and linear regression models were used to estimate sex-specific odds ratios (OR) and beta-coefficients with 95% confidence intervals (CI) of CVD, CRF and very high-risk score (SCORE2 ≥7.5% (age 40-49 years) or ≥ 10% (age 50-69 years)) associated with educational attainment and relative income. Women-to-men ratios of ORs (RORs) with 95%-CI were estimated. Results In women compared to men, low vs. high SEP was more strongly associated with obesity, overweight, self-reported myocardial infarction and hypertension, elevated blood pressure values, antihypertensive medication, and alcohol consumption, but less strongly related to smoking. In women with the lowest vs. highest educational level, the OR for a very high 10-year CVD risk was 3.61 (95%-CI 2.88; 4.53), compared to 1.72 (95%-CI 1.51; 1.96) in men. The women-to-men-ROR was 2.33 (95%-CI 1.78; 3.05), attenuated after age-adjustments. For the comparison of low vs. high relative income, the odds of having a very high 10-year CVD risk was 2.55 (95%-CI 2.04; 3.18) in women, and 2.25 (95%-CI 2.08; 2.42) in men (women-to-men ROR, 1.31 (95%-CI 1.05; 1.63). Conclusions In both sexes, there was an inverse graded relationship between SEP and the likelihood of prevalent CVD and CRF, with stronger associations in women than in men. Although women had a lower estimated 10-year CVD risk compared to men, the likelihood of having a very high CVD risk conferred by low SEP vs. a high one was higher in women than in men.

Proteinuria and the risk of incident atrial fibrillation according to diabetes stage in patients with diabetes: a nationwide population-based cohort study

Abstract Background Proteinuria and diabetes mellitus (DM) are established cardiovascular risk factors, both independently associated with an increased risk of atrial fibrillation (AF). Despite previous findings correlating proteinuria amount with incident AF, regardless of DM diagnosis, the nuanced association at different stages of DM warrants further investigation. Purpose This study aimed to delve into and compare the relationship between proteinuria amount and the risk of incident AF in patients across various stages of DM. Methods A cohort of 3,866,428 individuals without prior AF and type 1 DM, who underwent the 2009 health checkup provided by the National Health Insurance Service in Korea, were categorized into five DM stages: normal, prediabetes, new-onset DM, early DM (diagnosed &amp;lt; 5 years), and late DM (diagnosed ≥ 5 years). Proteinuria was graded using the urine dipstick test, ranging from negative to 3+ or more. AF incidence was tracked until December 31, 2020. Results The cohort, with an average age of 47.0 ± 13.9 years and 45.4% females, demonstrated escalating annual AF incidence rates from 1.90 to 6.45 per 1000 person-years across DM stages (p&amp;lt;0.001) (Figure). Similarly, the rates increased from 2.28 to 7.28 per 1000 person-years by proteinuria levels (p&amp;lt;0.001) (Figure). Adjusted Cox regression models revealed a heightened risk of incident AF associated with higher proteinuria amounts in all DM stages (adjusted hazard ratios for urine dipstick 3+ or more: 1.57, 1.76, 1.44, 2.32, and 2.23, respectively). Notably, the association between proteinuria and incident AF was more pronounced in individuals with early and late DM compared to those with prediabetes and new-onset DM (Figure). Conclusions At each DM stage, from prediabetes to late DM, a higher level of proteinuria corresponds to an increased risk of AF development. Furthermore, a stronger association was observed in patients with longer DM duration compared to those with prediabetes or new-onset DM. These findings underscore the significance of monitoring proteinuria levels across DM stages to assess AF risk comprehensively.

Anxiety or depression in heart failure across the ejection fraction spectrum

Abstract Background Anxiety or depression are commonly described in patients with heart failure (HF) but few data exist on characteristics and clinical outcomes associated with anxiety or depression across the different HF phenotypes. Purpose To assess the prevalence of patient characteristics and clinical outcomes associated with anxiety or depression in patients with HF with preserved, mildly reduced and reduced ejection fraction (HFpEF, HFmrEF, and HFrEF). Methods Patients enrolled in the Swedish Heart Failure Registry between 2000-2021 were included. Self-reported anxiety or depression was collected using EuroQoL 5-dimensional questionnaire (EQ-5D) at baseline and follow-up visits. Anxiety or depression was categorized as "not anxious or depressed", "moderately anxious or depressed" or "severe anxious or depressed". The independent associations between baseline characteristics and presence of anxiety or depression were assessed by a multivariable multinominal regression analysis. Cox proportional hazards regressions were performed to model the time to first event according to levels of anxiety or depression. Outcomes included all-cause death and all-cause hospitalizations. Results A total of 45,247 patients were included among whom 58% reported none, 38% moderate and 5% severe anxious or depressed with similar distribution across the HF phenotypes (Figure). Several characteristics were associated with anxiety or depression with the strongest ones for severe versus none being higher NYHA class (OR 3.10 (2.77-3.47)), liver disease (OR 1.99 (1.56-2.55)), in-patient setting (OR 1.62 (1.43-1.84)), smoking (OR 1.75 (1.52-2.00)) while others were inversely related including male sex (OR 0.51 (0.46-0.56)), higher age (OR 0.60 (0.53-0.67)), referral to HF nurse clinic (OR 0.82 (0.72-0.94)) and higher income level (OR 0.68 (0.62-0.76)). The risk of all-cause death and all-cause hospitalizations increased with increasing levels of anxiety or depression across all HF phenotypes during 12 months of follow up. Severe anxiety or depression had a stronger association with all-cause death in hospitalized patients and all-cause hospitalizations in out-patients. Conclusion In this large contemporary cohort of patients with HF in a real-world setting, anxiety or depression was frequently and similarly distributed across all HF phenotypes. Higher NYHA class, liver disease and in-patient setting were strongly associated with the anxiety or depression while male sex, higher age, and higher income were inversely related with anxiety or depression. Anxiety or depression was significantly associated with worse outcomes at 12 months follow up.Proportion anxiety or depression

Autoimmune diseases and the risk and prognosis of latent autoimmune diabetes in adults.

The aim of this study was to clarify the impact of autoimmune disease (AD) comorbidity on the risk and prognosis of latent autoimmune diabetes in adults (LADA). We used data from a Swedish study comprising newly diagnosed cases of LADA (n=586, stratified into LADAlow and LADAhigh by autoantibody levels), type 2 diabetes (n=2003) and matched control participants (n=2355). Information on 33 ADs and diabetic retinopathy was obtained by linkage to regional and national registers. We estimated the ORs for LADA and type 2 diabetes in relation to ADs before diabetes diagnosis, and the HRs for diabetic retinopathy after diabetes diagnosis. We performed functional pathway analyses to explore biological mechanisms driving the associations. Individuals with ADs exhibit an increased susceptibility to LADA (OR 1.70; 95% CI 1.36, 2.13), particularly those with thyroid dysfunction (OR 1.88; 95% CI 1.38, 2.56), inflammatory bowel disease (OR 1.78; 95% CI 1.00, 3.16) or vitiligo (OR 3.91; 95% CI 1.93, 7.94), with stronger associations being observed for the LADAhigh phenotype. Only psoriasis was linked to type 2 diabetes (OR 1.47; 95% CI 1.08, 1.99). The biological pathways shared by LADA and ADs revolved around immune responses, including innate and adaptive immune pathways. The HRs for diabetic retinopathy in LADA patients with and without AD vs those with type 2 diabetes were 2.11 (95% CI 1.34, 3.32) and 1.68 (95% CI 1.15, 2.45), respectively. We confirm that several common ADs confer an excess risk of LADA, especially LADA with higher GADA levels, but having such a comorbidity does not appear to affect the risk of diabetic retinopathy.

Comparison of the predicting value for incident cardiovascular events by vascular age based on brachial-ankle pulse wave velocity or carotid-femoral pulse wave velocity

Abstract Background There is a good correlation between brachial-ankle pulse wave velocity（baPWV）and carotid-femoral pulse wave velocity (cfPWV). Whether baPWV has the same predictability for cardiovascular risk as cfPWV in calculating vascular age remains to be clarified. Purpose This study examines which vascular age calculated by baPWV or cfPWV has a stronger association with the risk of cardiovascular events. Methods This prospective cohort study included 5725 participants from a community atherosclerosis cohort in Beijing, China. Vascular age was the predicted age in a multivariable regression model, including classical cardiovascular risk factors (sex, systolic and diastolic blood pressure, glycemia, triglyceride, low density lipoprotein cholesterol, waist, body mass index, heart rate, smoking) and treatment (anti-hypertensive agents, hypoglycemic agents, lipid-lowering agents) and pulse wave velocity. Residuals between chronological age and vascular age were defined as ∆-age, and the 10th and 90th percentiles of ∆-age were used as cutoffs to define supernormal vascular aging, normal vascular aging, and early vascular aging, respectively. The major adverse cardiovascular event was a composite of myocardial infarction, stroke, and cardiovascular death. The study used Cox proportional hazards regression to examine the association between vascular age and major adverse cardiovascular events. Results During the median 3-year follow-up period, 172 endpoint events were observed. After adjusting for age and sex, ∆-age as a continuous variable calculated by baPWV was significantly and increasingly associated with cardiovascular events (every 1-year increase led to a rise of 1.04% [95% confidence interval [CI]: 1.00%-1.08%; p=0.03] in cardiovascular events risk). After adjusting for age, sex, smoking, body mass index, hypertension, diabetes, dyslipidemia, anti-hypertensive agents, lipid-lowering agents, hypoglycemic agents, family history of atherosclerotic cardiovascular disease, and estimated glomerular filtration rate, early vascular aging group calculated by baPWV had an increased risk of cardiovascular events (hazard ratio: 1.76; 95% CI: 1.19-2.62 p=0.005), compared with the normal vascular aging group. In contrast, no significant results were observed in vascular age calculated by cfPWV. Conclusion(s) Vascular age calculated by baPWV has a stronger predictive ability for cardiovascular events than that calculated by cfPWV in the Chinese population. Considering baPWV is a simple and convenient method, it is recommended for vascular age calculation.

An equation for estimating low-density lipoprotein-triglyceride content and its use for cardiovascular disease risk stratification

BackgroundThe triglyceride (TG) content of low-density lipoprotein (LDL-TG) has been shown to be more predictive of atherosclerotic cardiovascular disease (ASCVD) events than the cholesterol content of LDL (LDL-C). The goal of our study was to develop an equation for estimating LDL-TG (eLDL-TG) based on the standard lipid panel and to compare it to estimated LDL-C as an ASCVD risk biomarker.MethodsUsing least-square regression analysis, the following eLDL-TG equation was developed: eLDL-TG=TG38.5+NonHDL-C5.75+9.75TGNonHDL-C+244HDL-C−2.95. LDL-TG was measured by the β-quantification (BQ) reference method (N = 40,202). LDL-C was calculated by the Sampson-NIH equation. The association of LDL-C and eLDL-TG with ASCVD risk markers was performed in the National Heart and Nutrition Examination Survey (NHANES) (N = 37,053) and with ASCVD events in a primary prevention cohort from the UK Biobank (UKB) (N = 429,367) and the Atherosclerosis Risk in Communities (ARIC) study (N = 14,632).ResultseLDL-TG showed better ASCVD risk stratification of UKB participants than LDL-C (Wilcoxon Chi-Square: 2,099.6 vs. 418.7, respectively). Receiving-operating characteristics analysis revealed that eLDL-TG had a stronger association with ASCVD events than LDL-C (AUC: 0.596 vs. 0.542, respectively) and other conventional lipid markers. Similar findings were found in ARIC. Discordance analysis in UKB showed that the group with low LDL-C/high eLDL-TG had a similar risk as the high LDL-C/high eLDL-TG group. Furthermore, these same two groups with the highest eLDL-TG levels and the highest ASCVD event rate also had higher mean levels of systolic blood pressure, Body Mass Index, hemoglobin A1C, and C-reactive protein than the two lower eLDL-TG groups. Using eLDL-TG &amp;gt; 44.6 mg/dl (80th percentile) as a cut-point leads to a hazard ratio of 1.32 (95% CI, 1.29–1.36) for ASCVD events, which remained significant after adjustment for LDL-C and apoB. Furthemore, using eLDL-TG as a risk-enhancer test leads to reclassification of 50% more high-risk individuals than current lipid-enhancer test rules.ConclusionsLike LDL-C, LDL-TG can also be calculated from the results of the standard lipid panel. Compared to estimated LDL-C, eLDL-TG was a better risk marker for primary prevention and hence could improve initial ASCVD risk stratification.

Wildfire-sourced fine particulate matter and preterm birth risks in Brazil: A nationwide population-based cohort study

Wildfire-specific particulate matter with diameters ≤ 2.5 µm (PM2.5) is the key component of wildfire smoke, with potentially higher toxicity than PM2.5 from other sources. In this nationwide population-based cohort study, we included 22,163,195 births from Brazil during 20102019. Daily wildfire-specific PM2.5 was estimated through the chemical transport model. Time-varying Cox proportional hazards models were used to characterize the exposure-time-response (E-T-R) relationship between weekly wildfire-specific PM2.5 exposure and preterm birth (PTB) risks, followed by subgroup analyses. A 10 µg/m3 increment in wildfire-specific PM2.5 was associated with a hazard ratio of 1.047 (95 % confidence interval [CI]: 1.032–1.063) for PTB. Stronger associations between wildfire-specific PM2.5 and PTB were observed during earlier pregnancy, among female infants, and pregnant women < 18 years old, in ethnic minorities, with a length of education ≥ 11 years, from low-income or high-temperature municipalities, and residing in North/Northeast regions. An estimated 1.47 % (95 % CI: 1.01 %1.94 %) of PTBs were attributable to wildfire-specific PM2.5 in Brazil, increasing from 2010 to 2019. The PTBs attributable to wildfire-specific PM2.5 surpassed those attributed to non-wildfire PM2.5 (0.31 %, 95% CI: 0.09 %0.57 %). Wildfire emerged as a critical source contributing to the PM2.5-linked PTBs. Prioritized fire management and emission control strategies are warranted for PTB prevention.