Comorbidity burden on mortality in patients with systemic sclerosis.

INTRODUCTION: Systemic sclerosis (SSc) is a serious life-threatening tissue disease. A significant aspect of its mortality arises from comorbid conditions. Our study aimed at mapping out the prevalence of these comorbidities and their relation to mortality, thus creating a 'comorbidome'. METHODS: In our retrospective, single-centre observational study, we recorded each patient's data, including demographic informations, vital stats and SSc-related organ involvement, along with the presence or absence of 14 predefined comorbidities. We also documented the dates of their initial and most recent visits. To construct survival curves, we used the Kaplan-Meier method, followed by a Cox regression model for multivariate analysis. RESULTS: Our study involved 400 participants, 74 of whom unfortunately passed away. It is important to note that three specific comorbidities showed significant correlation to mortality: neoplasia, cardiovascular diseases and polypharmacy, as well as two SSc-specific organ involvements (lung and cardiac). CONCLUSION: Our research led to the successful creation of the SSc comorbidome. Comorbidities are a major concern for patients suffering from SSc, particularly cardiovascular diseases and neoplasms. Our study highlights the effects of polypharmacy. The resultant comorbidome offers a comprehensive and analytical perspective on this complex issue and underscores the inter-relatedness of the data. Our study, however, was limited by a small sample size. Therefore, to confirm our findings, validation on a larger scale is necessary. This could potentially contribute to the creation of a future mortality scoring tool.

Association between periodontitis with the all-cause and cause specific mortality among the population with hyperlipidemia.

BACKGROUND: To explore the association between periodontitis and all-cause as well as cause-specific mortality rates in U.S. adults with hyperlipidemia. METHODS: Participants were extracted from NHANES during 1988-1994, 1999-2004 and 2009-2014 periods. To assess the association between moderate-to-severe periodontitis and mortality rates for both all-cause and cause-specific mortality, hazard ratios (HRs), time ratios (TRs), and their respective 95% confidence intervals (CIs) were calculated using Cox proportional hazards and Weibull accelerated failure time (AFT) models. RESULTS: Over a median follow-up duration of 11.83 years, 4,623 deaths of 16,848 participants were recorded. Multivariate Cox regression and AFT analyses showed moderate-to-severe periodontitis were associated with an increased risk of all-cause (HR: 1.31, 95% CI: 1.20-1.44, P < 0.001; TR: 0.85, 95% CI: 0.80-0.90, P < 0.001), cardiovascular disease (CVD)-related (HR: 1.36, 95% CI: 1.14-1.63, P = 0.001; TR: 0.83, 95% CI: 0.75-0.92, P < 0.001) and cancer-related mortality ( HR: 1.35, 95% CI: 1.12-1.63, P = 0.002; TR: 0.82, 95% CI: 0.72-0.93, P = 0.002). Meanwhile, there was a significant upward trend in the risk of mortality with increasing severity of periodontitis (P for trend < 0.001). CONCLUSIONS: Our study highlights the moderate-to-severe periodontitis is associated with an increased risk of all-cause, CVD-related and cancer-related mortality among U.S. adults with hyperlipidemia. And the mortality risk increasing alongside the severity of periodontitis.

Kaposi's sarcoma-associated herpesvirus infection and its association with all-cause and cardiovascular mortality in the general adults: A prospective cohort study.

To investigate the association between Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 (HHV8) infection and both all-cause and cardiovascular mortality in a representative cohort of US adults, data from the National Health and Nutrition Examination Survey III (NHANES III; 1988‒1994) were analyzed, including 13,993 participants aged 18‒90 years who underwent KSHV serology evaluations. Mortality outcomes were ascertained through December 2019 using the National Death Index. Cox proportional hazards models were employed to examine the association between KSHV seropositivity and mortality, adjusting for potential confounders such as age, sex, ethnicity, body mass index, and serum TG. Over a median follow-up period of 26.5 years, 5503 deaths were recorded. KSHV seropositivity was associated with an increased hazard of all-cause mortality (Hazard Ratio [HR]: 1.32, 95% Confidence Interval [CI]: 1.03‒1.69) and cardiovascular mortality (HR: 1.58, 95% CI: 1.00‒2.50) after adjusting for age, sex, ethnicity, and body mass index. Notably, the association between KSHV infection and all-cause mortality persisted among women (HR: 1.32, 95% CI: 1.02‒1.72) after adjusting for all confounders, whereas the association with cardiovascular mortality was only statistically significant for men (HR: 1.90, 95% CI: 1.02, 3.53).KSHV infection may represent an independent risk factor for all-cause and cardiovascular mortality among US adults. These findings highlight the need for further research to validate these associations in independent populations and to elucidate the biological mechanisms underlying the observed increased mortality associated with KSHV infection.

Glucagon-like peptide-1 receptor agonists may benefit cardiopulmonary outcomes in patients with COPD.

BACKGROUND: Clinical studies have shown that glucagon-like peptide-1 receptor agonists (GLP-1 RA) can have beneficial effects on cardiopulmonary function. We conducted this longitudinal cohort study to compare the risk of cardiopulmonary outcomes and mortality between GLP-1 RA use and no use in patients with type 2 diabetes (T2D) and chronic obstructive pulmonary disease (COPD). METHODS: The study identified 8060 matched GLP-1 RA users and non-users from Taiwan's National Health Insurance Research Database from 1 January 2008 to 31 December 2019. Cox proportional hazards models were used to determine the risk of cardiopulmonary outcomes between GLP-1 RA users and non-users. RESULTS: The mean follow-up time was 2.51 and 2.46 years for GLP-1 RA users and non-users, respectively. In the matched cohorts, GLP-1 RA users had a significantly lower risk of mortality (adjusted HR (aHR) 0.46, 95% CI 0.38 to 0.56), cardiovascular events (aHR 0.73, 95% CI 0.65 to 0.82), non-invasive positive pressure ventilation (aHR 0.66, 95% CI 0.47 to 0.93), invasive mechanical ventilation (aHR 0.64, 95% CI 0.51 to 0.8) and bacterial pneumonia (aHR 0.76, 95% CI 0.65 to 0.88) than GLP-1 RA non-users. The subsequent analyses for various subgroup and medication duration also showed that GLP-1 RA was associated with a significantly lower risk of mortality, cardiovascular events, ventilation support and bacterial pneumonia than non-GLP-1 RA. CONCLUSION: This nationwide cohort study showed that GLP-1 RA had a lower risk of cardiopulmonary outcomes and all-cause mortality than non-GLP-1 RA in patients with T2D and COPD. GLP-1 RA may help manage diabetes in people with COPD.

Association of hyperandrogenaemia with hypertension and cardiovascular events in pre-menopausal women: a prospective population-based cohort study.

OBJECTIVE: The present study aimed to clarify the conflicting association of premenopausal hyperandrogenaemia (HA) with the development of hypertension and cardiovascular disease (CVDs) in women. DESIGN: A population-based cohort study including 5889 women. METHODS: The association of serum testosterone (T), sex hormone-binding globulin (SHBG), and free androgen index (FAI) at age 31 with blood pressure (BP) and hypertension (BP ≥ 140/90 mmHg and/or use of antihypertensive medication) at ages 31 and 46 and with CVDs (angina pectoris [AP] and/or acute myocardial infarction [AMI] n = 74, transitory cerebral ischaemia and/or stroke n = 150) and combined CVD events (AP, AMI, stroke, heart failure, or CVD mortality n = 160) by age 53 was investigated. RESULTS: T and FAI were positively associated with systolic and diastolic BP at ages 31 and 46 in the multivariable model. Compared to their lowest quartile, the highest quartiles of T and FAI were positively associated with hypertension at age 31 in the multivariable model. During the 22-year follow-up, FAI was positively associated with increased risk of AP/AMI (hazard ratio [HR]: 2.02, 95% CI: 1.06-3.85) and overall CVD events or mortality (HR: 1.54, 95% CI: 1.02-2.33) in the unadjusted models. However, the significance disappeared after adjusting for body mass index (BMI). CONCLUSIONS: Women with HA at premenopausal age had an elevated risk of hypertension, and together with BMI, increased risk of CVD events and CVD mortality during the 22-year follow-up. However, because of several study limitations regarding ethnicity and BMI characteristics, a longer follow-up of this cohort and future studies in ethnically diverse populations are needed to verify the results.

Saturation association between serum 25-hydroxyvitamin D levels and mortality in elderly people with hyperlipidemia: a population-based study from the NHANES (2001-2016).

Background: 25-hydroxyvitamin D is the body's main storage form of vitamin D and is internationally recognized as the best indicator of vitamin D status in the human body. There is a scarcity of research investigating the interrelationship between serum 25-hydroxyvitamin D (25(OH)D) levels and mortality among elderly individuals with hyperlipidemia. To address this knowledge gap, we examined the association between serum 25(OH)D levels and mortality in an older hyperlipidemic population from NHANES, while controlling for other influential factors. The study sought to elucidate the correlation between serum 25(OH)D levels and mortality about all-cause mortality, cardiovascular disease (CVD), malignant neoplasms, and mortality from other causes. Methods: The data from NHANES 2001-2016, including 9,271 participants were analyzed to examine the association between serum 25(OH)D levels and mortality. The interrelationship was illustrated using Kaplan-Meier curves and restricted cubic splines, while the Cox proportional hazards model was utilized to estimate the multifactor adjusted hazard ratio (HR). Results: This study included 9,271 participants (43.28% male) with an average age of 69.58 years, and the average duration of participant follow-up was 88.37 months. Kaplan-Meier curves demonstrated that lower serum 25(OH)D levels were associated with increased risks of all-cause mortality, cardiovascular mortality, malignant neoplasm mortality, and mortality from other causes. This negative association was further confirmed by the Cox proportional hazards models. Additionally, restricted cubic splines not only revealed this negative association but also highlighted the saturated serum 25(OH)D levels. Moreover, subgroup analyses indicated that the inverse correlation between serum 25(OH)D levels and all-cause mortality was more pronounced in the non-obese and smoking population. And the inverse correlation with mortality from other causes was even stronger in the non-obese population. Conclusions: In the elderly population with hyperlipidemia, 25(OH)D serum levels were negatively correlated with both cause-specific mortality and all-cause mortality. Moreover, there was a threshold effect in this negative association.

Long-term exposure to PM2.5 and mortality: a national health insurance cohort study.

BACKGROUND: Previous studies with large data have been widely reported that exposure to fine particulate matter (PM2.5) is associated with all-cause mortality; however, most of these studies adopted ecological time-series designs or have included limited study areas or individuals residing in well-monitored urban areas. However, nationwide cohort studies including cause-specific mortalities with different age groups were sparse. Therefore, this study examined the association between PM2.5 and cause-specific mortality in South Korea using the nationwide cohort. METHODS: A longitudinal cohort with 187 917 National Health Insurance Service-National Sample Cohort participants aged 50-79 years in enrolment between 2002 and 2019 was used. Annual average PM2.5 was collected from a machine learning-based ensemble model (a test R2 = 0.87) as an exposure. We performed a time-varying Cox regression model to examine the association between long-term PM2.5 exposure and mortality. To reduce the potential estimation bias, we adopted generalized propensity score weighting method. RESULTS: The association with long-term PM2.5 (2-year moving average) was prominent in mortalities related to diabetes mellitus [hazard ratio (HR): 1.03 (95% CI: 1.01, 1.06)], circulatory diseases [HR: 1.02 (95% CI: 1.00, 1.03)] and cancer [HR: 1.01 (95% CI: 1.00, 1.02)]. Meanwhile, circulatory-related mortalities were associated with a longer PM2.5 exposure period (1 or 2-year lags), whereas respiratory-related mortalities were associated with current-year PM2.5 exposure. In addition, the association with PM2.5 was more evident in people aged 50-64 years than in people aged 65-79 years, especially in heart failure-related deaths. CONCLUSIONS: This study identified the hypothesis that long-term exposure to PM2.5 is associated with mortality, and the association might be different by causes of death. Our result highlights a novel vulnerable population: the middle-aged population with risk factors related to heart failure.

Application of a deep-learning marker for morbidity and mortality prediction derived from retinal photographs: a cohort development and validation study.

BACKGROUND: Biological ageing markers are useful to risk stratify morbidity and mortality more precisely than chronological age. In this study, we aimed to develop a novel deep-learning-based biological ageing marker (referred to as RetiPhenoAge hereafter) using retinal images and PhenoAge, a composite biomarker of phenotypic age. METHODS: We used retinal photographs from the UK Biobank dataset to train a deep-learning algorithm to predict the composite score of PhenoAge. We used a deep convolutional neural network architecture with multiple layers to develop our deep-learning-based biological ageing marker, as RetiPhenoAge, with the aim of identifying patterns and features in the retina associated with variations of blood biomarkers related to renal, immune, liver functions, inflammation, and energy metabolism, and chronological age. We determined the performance of this biological ageing marker for the prediction of morbidity (cardiovascular disease and cancer events) and mortality (all-cause, cardiovascular disease, and cancer) in three independent cohorts (UK Biobank, the Singapore Epidemiology of Eye Diseases [SEED], and the Age-Related Eye Disease Study [AREDS] from the USA). We also compared the performance of RetiPhenoAge with two other known ageing biomarkers (hand grip strength and adjusted leukocyte telomere length) and one lifestyle factor (physical activity) for risk stratification of mortality and morbidity. We explored the underlying biology of RetiPhenoAge by assessing its associations with different systemic characteristics (eg, diabetes or hypertension) and blood metabolite levels. We also did a genome-wide association study to identify genetic variants associated with RetiPhenoAge, followed by expression quantitative trait loci mapping, a gene-based analysis, and a gene-set analysis. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and corresponding 95% CIs for the associations between RetiPhenoAge and the different morbidity and mortality outcomes. FINDINGS: Retinal photographs for 34 061 UK Biobank participants were used to train the model, and data for 9429 participants from the SEED cohort and for 3986 participants from the AREDS cohort were included in the study. RetiPhenoAge was associated with all-cause mortality (HR 1·92 [95% CI 1·42-2·61]), cardiovascular disease mortality (1·97 [1·02-3·82]), cancer mortality (2·07 [1·29-3·33]), and cardiovascular disease events (1·70 [1·17-2·47]), independent of PhenoAge and other possible confounders. Similar findings were found in the two independent cohorts (HR 1·67 [1·21-2·31] for cardiovascular disease mortality in SEED and 2·07 [1·10-3·92] in AREDS). RetiPhenoAge had stronger associations with mortality and morbidity than did hand grip strength, telomere length, and physical activity. We identified two genetic variants that were significantly associated with RetiPhenoAge (single nucleotide polymorphisms rs3791224 and rs8001273), and were linked to expression quantitative trait locis in various tissues, including the heart, kidneys, and the brain. INTERPRETATION: Our new deep-learning-derived biological ageing marker is a robust predictor of mortality and morbidity outcomes and could be used as a novel non-invasive method to measure ageing. FUNDING: Singapore National Medical Research Council and Agency for Science, Technology and Research, Singapore.

The correlation between Life's essential 8 and cardiovascular disease and mortality in individuals with nonalcoholic fatty liver disease: a cross-sectional study.

It is currently unclear whether there is a connection between Life's Essential 8 (LE8) and cardiovascular disease (CVD), as well as mortality in people with nonalcoholic fatty liver disease (NAFLD). Our goal was to explore these relationships by examining data collected in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. We identified eligible participants with NAFLD based on NHANES 2005-2018 data. CVD status was acquired through self-reported information, and using the National Death Index, mortality data were prospectively matched. The diagnosis of NAFLD relied on noninvasive biomarkers. The research involved 9094 individuals who were identified as having NAFLD, with a mean age of 52.05 years. Each incremental LE8 score exhibited a significant association, leading to a 3%, 3%, 4%, 3%, 3%, 4%, and 4% reduction in the odds of experiencing CVD, ischemic heart disease, congestive heart failure, coronary heart disease, heart attack, angina, and stroke in individuals with NAFLD. A strong correlation was found between maintaining a superior level of Cardiovascular Health (CVH), as shown by a LE8 score ranging from 80 to 100, and a reduced occurrence of CVD and its various forms in NAFLD (all p for trend < 0.0001). Likewise, LE8 demonstrated protective benefits on mortality in NAFLD, showing that following a high CVH (in contrast to low CVH) was linked to reductions of 64%, 71%, and 74% in all-cause, CVD, and cancer mortality, respectively. Restricted cubic spline analyses suggested noteworthy dose-response relationships between LE8 and CVD, specifically its types in NAFLD, and a nonlinear correlation with CVD mortality. Interaction analyses highlighted age and race as significant effect modifiers. CVH, as evaluated by LE8, demonstrated an independent association with decreased odds of CVD and mortality risk in individuals with NAFLD. Our findings substantiate that adhering to LE8 may alleviate the excessive burden of CVD and mortality in the context of NAFLD.

Association between urinary incontinence and mortality risk among US adults: a prospective cohort study.

BACKGROUND: Urinary incontinence is frequent in the general population and affects men and women of all ages. UI carries an unsuspected load on the healthcare system. To investigate whether urinary incontinence is associated with all-cause, cardiovascular disease (CVD) and cancer mortality among US adults. METHODS: The analyzed data was collected from the 2007-2016 National Health and Nutrition Examination Survey (NHANES) data. A total of 25,182 US participants with complete information about follow-up information and urinary incontinence (UI) were included in this cohort study. Univariate Cox regression analyses, the UpSet plot, multivariate Cox regression analysis, subgroup analysis of all-cause mortality, and Kaplan-Meier survival curve were employed to support the research objectives. RESULTS: A total of 25,182 participants had a mean age of 49.8 ± 17.8 years, with 49.3% of them being male and 50.7% of them being female. In the unadjusted model, we found that the risk of all-cause mortality increased by 12% (95% CI 1.03-1.22, P = 0.008), the risk of CVD mortality increased by 21% (95% CI 1.07-1.36, P = 0.002), and the risk of Cancer mortality increased by 8% (95% CI 0.95-1.22, P = 0.243) among individuals with urinary incontinence. After adjusting for multiple variables, we found that the risk of all-cause mortality in patients with urinary incontinence decreased by 1% (95% CI 0.9-1.09), but this decrease was statistically insignificant (P = 0.868), and the risk of Cancer mortality decreased by 3% (95% CI 0.84-1.12, P = 0.686). The association between urinary incontinence and mortality risk were stable in stratified analyses. CONCLUSIONS: In our study, we found that urinary incontinence itself is an independent risk factor for death. The association between urinary incontinence and mortality became less significant after adjusting for covariates, this is a common occurrence in statistical analysis. Future research, with larger sample sizes and more robust study designs, is needed to further elucidate the complex relationship between urinary incontinence and mortality risk.

Prognostic factors for premature cardiovascular disease mortality in Malaysia: a modelling approach using semi-parametric and parametric survival analysis with national health and morbidity survey linked mortality data.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of premature mortality worldwide. Despite existing research on CVD risk factors, the study of premature CVD mortality in Malaysia remains limited. This study employs survival analysis to model modifiable risk factors associated with premature CVD mortality among Malaysian adults. METHOD: We utilised data from Malaysia's National Health and Morbidity Survey (NHMS) conducted in 2006, 2011, and 2015, linked with mortality records. The cohort comprised individuals aged 18 to 70 during the NHMS interview. Follow-up extended to 2021, focusing on CVD-related premature mortality between ages 30 and 70. We employed six survival models: a semi-parametric Cox proportional hazard (PH) and five parametric survival models, which were Exponential, Weibull, Gompertz, log-normal and log-logistic distributions using R software. The age standardized incidence rate (ASIR) of premature CVD mortality was calculated per 1000 person-years. RESULTS: Among 63,722 participants, 886 (1.4%) experienced premature CVD mortality, with an ASIR of 1.80 per 1000 person-years. The best-fit models (based on AIC value) were the stratified Cox model by age (semi-parametric) and the log-normal accelerated failure time (AFT) model (parametric). Males had higher risk (Hazard Ratio, HR = 2.68) and experienced 49% shorter survival time (Event Time Ratio, ETR = 0.51) compared to females. Compared to Chinese ethnicity, Indians, Malays, and other Bumiputera had higher HR and lower survival times. Rural residents and those with lower education also faced increased HRs and reduced survival times. Diabetes (diagnosed: HR = 3.26, ETR = 0.37; undiagnosed: HR = 1.63, ETR = 0.63), hypertension (diagnosed: HR = 1.84, ETR = 0.53; undiagnosed: HR = 1.46, ETR = 0.68), and undiagnosed hypercholesterolemia (HR = 1.31, ETR = 0.80) increased risk and decreased survival times. Additionally, current smoking and abdominal obesity elevated risk (HR = 1.38, 1.60) and shortened survival (ETR = 0.81, 0.71). CONCLUSION: The semi-parametric and parametric survival models both highlight the considerable impact of socioeconomic status and modifiable risk factors on premature CVD mortality, underscoring the imperative for targeted interventions to effectively mitigate these effects.

Association of weight change with all-cause and cause-specific mortality: an age-stratified analysis.

BACKGROUND: The associations of weight change with all-cause and cause-specific mortality stratified by age remains unclear. We evaluated the age-stratified (< 65 vs ≥ 65 years) associations of weight change with all-cause and cause-specific mortality in a large sample of Chinese adults. METHODS: Our cohort study included 746,991 adults aged at least 45 years from the Shenzhen Healthcare Big Data Cohort in China. BMI change were categorized as change within 5% (stable), decrease by 5% to 10%, decrease by > 10%, increase by 5% to 10%, and increase by > 10%. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause, non-communicable disease, cardiovascular disease (CVD), and cancer mortality according to BMI change, with adjustment for potential confounders. RESULTS: During a median follow-up of 2.2 years (2,330,180 person-years), there were 10,197 deaths. A notable interaction emerged between weight change and age. For participants ≥ 65 years, compared with stable BMI, more than a 10% decrease in BMI was associated with higher risk of all-cause mortality (HR: 1.69, 95% CI: 1.54-1.86), non-communicable disease mortality (HR: 1.67, 95% CI: 1.52-1.84), CVD mortality (HR: 1.55, 95% CI: 1.34-1.80), and cancer mortality (HR: 1.59, 95% CI: 1.33-1.92). Similar patterns of results for 5% to 10% decrease in BMI were observed. More than a 10% increase in BMI was associated with increased risk of all-cause mortality (HR: 1.13, 95% CI: 1.04-1.24), non-communicable disease mortality (HR: 1.14, 95% CI: 1.04-1.25), and CVD mortality (HR: 1.27, 95% CI: 1.12-1.44). For participants < 65 years, only more than a 10% decrease in BMI was associated with higher risk of all-cause mortality (HR: 1.41, 95% CI: 1.12-1.77), non-communicable disease mortality (HR: 1.43, 95% CI: 1.13-1.81), and cancer mortality (HR: 1.79, 95% CI: 1.29-2.47). CONCLUSIONS: Weight loss and excessive weight gain were associated with increased risks of mortality among older adults, while only excessive weight loss was associated with increased risks of mortality among middle-aged adults.

How likely are Eastern European and central Asian countries to achieve global NCD targets: multi-country analysis.

BACKGROUND: In Europe, mortality rates from noncommunicable diseases (NCDs) among persons 30-69 years of age ("NCD premature mortality rates") have declined significantly, except in twelve countries of Eastern Europe and Central Asia, namely Armenia, Azerbaijan, Belarus, Georgia, Kazakhstan, Kyrgyzstan, Moldova, Russia, Tajikistan, Turkmenistan, Ukraine and Uzbekistan. Data on long-term trends in NCD mortality in these countries are limited. We analyzed NCD premature mortality rates, identified change points in NCD mortality trends and forecasted how likely countries are to achieve the global NCD targets, stratified by gender and NCD type. METHODS: We used the 1990-2019 Global Burden of Disease database to analyze NCD trends and identified country-specific change points by using piecewise linear regression. We assessed the likelihood of achieving the global targets for reducing NCD premature mortality rates among persons 30-69 years of age from four NCDs: cancers, diabetes, cardiovascular and chronic respiratory diseases. The global NCD targets are 25% reduction in mortality from 2010 to 2025 (WHO 25X25 target) and 33%-from 2015 to 2030 (SDG 3.4.1). We applied the analysis to both genders and four NCDs. RESULTS: Only Kazakhstan and Russia are likely to achieve the global NCD targets. For Kazakhstan, WHO 25X25 and SDG 3.4.1 global targets for mortality rates were 494.3 and 374.8 per 100,000 population respectively; the corresponding predicted values (PVs) were 360.6 [CI 260.1-461.1] and 245.1 [CI 113.4-376.8]. For Russia, WHO 25X25 and SDG 3.4.1 global targets were 560.5 and 442.8 per 100,000 population respectively; the corresponding PVs were 427.7 [CI 270.3-585.1] and 311.0 [CI 102.8-519.1]. Achieving NCD global targets is less likely for Kyrgyzstan, while it is unlikely for the rest of countries. Most countries had higher mortality rates and slower progress among men compared with women. The likelihood of achieving overall global NCD targets was mainly explained by reduction in cardiovascular mortality. CONCLUSIONS: In most Eastern Europe and Central Asia countries, progress towards achieving NCD global targets is slow, or there's a reverse trend. Further quantitative and qualitative research is needed to understand the underlying reasons. Separate indicators are needed to monitor trends for cancers, diabetes and chronic respiratory diseases.

Analysis of angiotensin II type 1 receptor and osteoprotegerin gene polymorphism on the risk of cardiovascular mortality risk and progressivity of chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is a significant global public health issue with increased risk of atherosclerotic cardiovascular disease (ASCVD) and cardiovascular mortality. Single nucleotide polymorphisms (SNPs) on angiotensin II type 1 receptor (AT1R) A1166C and osteoprotegerin (OPG) C950T gene have received significant attention as a genetic risk factor for cardiovascular disease and CKD. METHODS: This was a cross-sectional study involving 75 adults with CKD recruited from Nephrology Outpatient Clinics of Universitas Airlangga Hospital, Surabaya, Indonesia. Demographic data was obtained from interviews and medical records. The "CKD Patch" application was used to asses ASCVD and cardiovascular mortality risk scores. Statistical analysis was performed by using SPSS version 26. RESULTS: We detected four different AT1R gene polymorphisms (A1166C, A1160C, G1170T, and G1181C) and two OPG gene polymorphisms (T950C and G1181C) in Indonesian CKD patients. A1160C and G1181C polymorphisms were novel SNPs, newly discovered in this research. No significant association was found between AT1R SNPs and kidney prognostic markers or ASCVD risk/mortality risk scores. However, for OPG C950T we found that TT genotype had a significantly higher ACR than TC or CC genotype (P=0.032). As for OPG G1181C, we found that GG genotype had a higher serum creatinine and albumin to creatinine ratio compared to GC and CC genotypes (P=0.004 and 0.029, respectively). Genotype GC for OPG G1181C was also shown to be protective for having better kidney markers and lowest cardiovascular mortality risk compared to GG and CC genotypes (P=0.018 and 0.032, respectively). CONCLUSIONS: Increased ASCVD risk and mortality risk score was not found on individuals with AT1R gene SNPs. However, for OPG gene polymorphism, C950T and G1181C were associated with kidney progression and cardiovascular mortality.

Fatty liver index as an independent predictor of all-cause and disease-specific mortality.

PURPOSE: This study aims to assess the prognostic value of the fatty liver index (FLI), a noninvasive tool for hepatic steatosis assessment, in predicting all-cause and disease-specific mortality. METHODS: We linked data from the National Health and Nutrition Examination Survey III (1988-1994) with Public-Use Mortality Files, forming a cohort of 11 297 participants with a median follow-up period of 26.25 years. Cox proportional hazards models were used to evaluate the association between FLI and all-cause mortality, while Fine and Gray's models assessed the relationship between FLI and disease-specific mortality. RESULTS: The FLI ≥ 60 was independently associated with an increased risk of all-cause mortality (hazard ratio = 1.24, P  < 0.001), as well as mortality from malignant neoplasms (hazard ratio = 1.18, P  = 0.048), diabetes (hazard ratio = 2.62, P  = 0.001), and cardiovascular diseases (CVDs) (hazard ratio = 1.18, P  = 0.018), compared to FLI < 30. No significant associations were found with Alzheimer's disease, influenza and pneumonia, chronic lower respiratory diseases, or renal disorders. Subgroup analyses indicated that individuals who were females aged 40-60 (hazard ratio = 1.67, P  = 0.003), non-overweight (hazard ratio = 1.75, P  = 0.007), or without abdominal obesity (hazard ratio = 1.75, P  = 0.007) exhibited a stronger association between FLI ≥ 60 and all-cause mortality. CONCLUSION: These findings support the prognostic value of the FLI for predicting mortality from all causes, malignant neoplasms, diabetes, and CVDs. Targeted attention is needed in postmenopausal women, non-overweight, and non-abdominally obese populations.

Association of prophylactic low-dose aspirin use with all-cause and cause-specific mortality in cancer patients.

The long-term use of aspirin for preventing cardiovascular disease has been recommended for decades. However, there is currently uncertainty regarding the long-term effects of aspirin use on the risk of all-cause, cardiovascular, and cancer mortality in cancer patients. The aim of this work was to analyze the connection between the prophylactic use of low-dose aspirin and the risk of all-cause death, cardiovascular death, and carcinoma death in carcinoma patients in the United States. A cohort study was conducted using National Health and Nutrition Examination Survey (NHANES) data (2011-2012, 2013-2014, 2015-2016, and 2017-2018) and associated mortality data. The 95% confidence intervals (CIs) and hazard ratios (HRs) between non-aspirin use and prophylactic low-dose aspirin use and the risk of death were measured via Cox proportional hazard regression models. A total of 1819 participants were included in the present research, of whom 945 were nonaspirin users and 874 were prophylactic aspirin users. Compared with non-aspirin users, prophylactic low-dose aspirin users had a decreased risk of all-cause death (HR = 0.647, 95% CI = 0.489-0.857). There was no statistically significant difference in the risk of cardiovascular death (HR = 0.623, 95% CI = 0.362-1.074) or cancer death (HR = 0.709, 95% CI = 0.410-1.226). Prophylactic use of low-dose aspirin may lower all-cause mortality in individuals with cancer but does not have a substantial effect on cardiovascular risk or cancer-specific mortality in this patient population.

Prognostic impact of switching to the 2021 chronic kidney disease epidemiology collaboration creatinine-based equation in Caucasian patients with type 2 diabetes: the Renal Insufficiency and Cardiovascular events (RIACE) Italian Multicenter Study.

BACKGROUND: A Chronic Kidney Disease (CKD) Epidemiology Collaboration (EPI) formula not including a Black race coefficient has been recently developed and is now recommended in the US. The new (2021) equation was shown to yield higher estimated glomerular filtration rate (eGFR) values than the old (2009) one in a non-Black general population sample, thus reclassifying a significant number of individuals to a better eGFR category. However, reclassified individuals were previously shown to have a lower risk of progression to end-stage kidney disease, but higher adjusted risks for all-cause death and morbidity and mortality from cardiovascular disease than those not reclassified. This study evaluated the prognostic impact of switching from the 2009 to the 2021 CKD-EPI equation in non-Black individuals with type 2 diabetes. METHODS: The Renal Insufficiency And Cardiovascular Events (RIACE) was a prospective cohort study enrolling 15,773 Caucasian patients in 19 Italian centers in 2006-2008. Cardiometabolic risk profile, treatments, complications, and comorbidities were assessed at baseline and eGFR was calculated with the two equations. Vital status was retrieved on 31 October 2015 for 15,656 participants (99.3%). RESULTS: With the 2021 equation, the eGFR value increased in all patients, except for 293 individuals with a 2009 eGFR ≥ 105 ml·min- 1·1.73 m- 2. The median difference was 4.10 ml·min- 1·1.73 m- 2 and was higher in males, older individuals and those in the G2 category. Reclassification decreased the percentage of patients with reduced eGFR from 17.28 to 13.96% and with any CKD from 36.23 to 34.03%. Reclassified individuals had better cardiometabolic risk profile and lower prevalence of complications and use of medications than non-reclassified individuals. Risk of death versus the 2009 G1 category was lower for reclassified than non-reclassified participants in all eGFR categories and, particularly, in each 2009 eGFR category, though difference was significant only in the G4-G5 category. The Receiver Operator Characteristic curves were statistically, but not clinically different with the two equations. CONCLUSION: Changing from the 2009 to the 2021 CKD-EPI equation results in higher eGFR and lower CKD prevalence, with a lower risk of death in reclassified patients with an eGFR < 30 ml·min- 1·1.73 m- 2, but virtually no impact on mortality prediction. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00715481, retrospectively registered 15 July, 2008.

Excessive occupational sitting increases risk of cardiovascular events among working individuals with type 1 diabetes in the prospective Finnish Diabetic Nephropathy Study.

BACKGROUND: Sedentary behavior, such as excessive sitting, increases risk of cardiovascular disease and premature mortality in the general population, but this has not been assessed in type 1 diabetes. Occupational sitting is increasingly ubiquitous and often constitutes the largest portion of daily sitting time. Our aim was to identify clinical factors associated with excessive occupational sitting in type 1 diabetes and, in a prospective setting, to explore its association with cardiovascular events and all-cause mortality, independent of leisure-time physical activity. METHODS: An observational follow-up study of 1,704 individuals (mean age 38.9 ± 10.1 years) from the Finnish Diabetic Nephropathy Study. Excessive occupational sitting, defined as ≥ 6 h of daily workplace sitting, was assessed using a validated self-report questionnaire. Data on cardiovascular events and mortality were retrieved from national registries. Multivariable logistic regression identified independently associated factors, while Kaplan-Meier curves and Cox proportional hazard models were used for prospective analyses. RESULTS: Factors independently and positively associated with excessive occupational sitting included a high occupational category [OR 6.53, 95% CI (4.09‒10.40)] and older age [1.02 (1.00‒1.03)], whereas negatively associated factors included current smoking [0.68 (0.50‒0.92)], moderate albuminuria [0.55 (0.38‒0.80)], and high leisure-time physical activity [0.52 (0.36‒0.74)]. During a median follow-up of 12.5 (6.5-16.4) years, 163 individuals (9.6%) suffered cardiovascular events, and during a median follow-up of 13.7 (9.4-16.6) years, 108 (6.3%) deaths occurred. Excessive occupational sitting increased cardiovascular event risk (hazard ratio [HR] 1.55 [95% CI 1.10‒2.18]) after adjustment for confounders and other covariates. Furthermore, in a stratified multivariable analysis among current smokers, excessive occupational sitting increased the risk of all-cause mortality (2.06 [1.02‒4.20]). CONCLUSIONS: Excessive occupational sitting is associated with a higher risk of cardiovascular events and all-cause mortality in individuals with type 1 diabetes. This association persists regardless of leisure-time physical activity, after adjusting for independently associated variables identified in our cross-sectional analyses. These findings underscore the need to update physical activity guidelines to better address sedentary behavior and improve outcomes for individuals with type 1 diabetes. Targeting occupational sitting should be considered a key focus for interventions aimed at reducing overall sedentary time.

Joint effects of depression and social determinants of health on mortality risk among U.S. adults: a cohort study.

BACKGROUND: Unfavorable social determinants of health (SDoH) are associated with depression. Both depression and SDoH are associated with increased risks of mortality, but their joint impacts on mortality risks remain unclear. This study aims to investigate the joint effects of depression and SDoH on mortality risk. METHODS: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2007-2018, 24,727 adults aged ≥ 20 were included. SDoH was assessed based on the 5 domains outlined in the U.S. Healthy People 2030 initiative. The cumulative number of unfavorable SDoH was calculated and categorized into low and high burden levels. The definition of depression was based on the Patient Health Questionnaire-9 (PHQ-9) scores ≥ 10. The joint associations of depression and SDoH with all-cause, cardiovascular disease (CVD), and cancer mortality were examined using Cox proportional hazard models. RESULTS: We identified 2,377 (6.84%) all-cause deaths (CVD, 717; cancer, 606) during a median follow-up of 7.0 years. Depression was associated with increased mortality risks, and SDoH could explain 32.4% and 28.3% of the associations between depression and all-cause and CVD mortality, respectively. No significant interactions were observed between depression and SDoH on mortality. However, a low burden of unfavorable SDoH reduced the risk of all-cause mortality in depressed patients (hazard ratio [HR], 0.58; 95% confidence interval [CI]: 0.36-0.92). In the joint analysis, individuals with both depression and a high burden of unfavorable SDoH had the highest risks of all-cause and CVD mortality. Specifically, compared with individuals with no depression and a low burden of unfavorable SDoH, those with depression and a high burden of unfavorable SDoH had higher risks of all-cause (HR, 2.52; 95% CI: 2.01-3.18) and CVD mortality (HR, 2.79; 95% CI: 1.95-3.99). CONCLUSION: Adults with both depression and a high burden of unfavorable SDoH had the highest risks of all-cause mortality and CVD mortality. The result suggests considering depression and SDoH jointly in developing targeted intervention strategies to improve survival outcomes and calls for larger cohort studies and clinical trials to validate our findings.

Population-Level Distribution, Risk Factors, and Burden of Mortality and Disability-Adjusted Life Years Attributable to Major Noncommunicable Diseases in Western Europe (1990-2021): Ecological Analysis.

Background: Cardiovascular diseases (CVDs) and neoplasms are leading causes of mortality worldwide. Objective: This study aims to provide a comprehensive analysis of the mortality burden and disability-adjusted life years (DALYs) attributable to CVDs and neoplasms in Western Europe, investigate associated risk factors, and identify regional disparities. Additionally, the study evaluates the effectiveness of the Action Plan for the Prevention and Control of Non-Communicable Diseases (NCDs) in promoting healthier lives in the region. Methods: The study collected data on mortality and DALYs due to CVDs and cancers from 24 Western European countries using the Global Burden of Disease Study 2021. The analysis explored age, sex, and country-specific patterns, as well as risk factors contributing to these deaths. Additionally, the study examined time trends by calculating the annual percent change in mortality rates from 1990 to 2021 by region and cause. Results: In 2021, CVDs and neoplasms accounted for 27.8% and 27.1% of total deaths in Western Europe, with age-standardized death rates of 106.8 and 125.8 per 100,000, respectively. The top two CVDs in this region were ischemic heart disease and stroke, with age-standardized death rates of 47.27 (95% uncertainty interval [UI] 50.42-41.45) and 27.06 (95% UI 29.17-23.00), respectively. Similarly, the top two neoplasms were lung cancer and colorectal cancer, with age-standardized death rates of 26.4 (95% UI 27.69-24.47) and 15.1 (95% UI 16.25-13.53), respectively. Between 1990 and 2021, CVD mortality rates decreased by 61.9%, while cancer rates decreased by 28.27%. Finland had the highest CVD burden (39.5%), and Monaco had the highest rate of cancer-related deaths (34.8%). Gender differences were observed, with males experiencing a higher burden of both CVDs and cancer. Older individuals were also more at risk. Smoking had a stronger impact on CVD mortality and DALYs in males, while a higher Human Development Index was associated with increased cancer deaths and DALYs in females. Conclusions: The study findings highlight the substantial burden of NCDs, particularly CVDs and cancer, in Western Europe. This underscores the critical need for targeted interventions and effective implementation of the Action Plan for the Prevention and Control of NCDs to achieve the goal of ensuring healthy lives for all.