Associations of metabolic changes and polygenic risk scores with cardiovascular outcomes and all-cause mortality across BMI categories: a prospective cohort study.

BACKGROUND: Associations between metabolic status and metabolic changes with the risk of cardiovascular outcomes have been reported. However, the role of genetic susceptibility underlying these associations remains unexplored. We aimed to examine how metabolic status, metabolic transitions, and genetic susceptibility collectively impact cardiovascular outcomes and all-cause mortality across diverse body mass index (BMI) categories. METHODS: In our analysis of the UK Biobank, we included a total of 481,576 participants (mean age: 56.55; male: 45.9%) at baseline. Metabolically healthy (MH) status was defined by the presence of < 3 abnormal components (waist circumstance, blood pressure, blood glucose, triglycerides, and high-density lipoprotein cholesterol). Normal weight, overweight, and obesity were defined as 18.5 ≤ BMI < 25 kg/m2, 25 ≤ BMI < 30 kg/m2, and BMI ≥ 30 kg/m2, respectively. Genetic predisposition was estimated using the polygenic risk score (PRS). Cox regressions were performed to evaluate the associations of metabolic status, metabolic transitions, and PRS with cardiovascular outcomes and all-cause mortality across BMI categories. RESULTS: During a median follow-up of 14.38 years, 31,883 (7.3%) all-cause deaths, 8133 (1.8%) cardiovascular disease (CVD) deaths, and 67,260 (14.8%) CVD cases were documented. Among those with a high PRS, individuals classified as metabolically healthy overweight had the lowest risk of all-cause mortality (hazard ratios [HR] 0.70; 95% confidence interval [CI] 0.65, 0.76) and CVD mortality (HR 0.57; 95% CI 0.50, 0.64) compared to those who were metabolically unhealthy obesity, with the beneficial associations appearing to be greater in the moderate and low PRS groups. Individuals who were metabolically healthy normal weight had the lowest risk of CVD morbidity (HR 0.54; 95% CI 0.51, 0.57). Furthermore, the inverse associations of metabolic status and PRS with cardiovascular outcomes and all-cause mortality across BMI categories were more pronounced among individuals younger than 65 years (Pinteraction < 0.05). Additionally, the combined protective effects of metabolic transitions and PRS on these outcomes among BMI categories were observed. CONCLUSIONS: MH status and a low PRS are associated with a lower risk of adverse cardiovascular outcomes and all-cause mortality across all BMI categories. This protective effect is particularly pronounced in individuals younger than 65 years. Further research is required to confirm these findings in diverse populations and to investigate the underlying mechanisms involved.

Associations between body mass index, biological age and frailty in the critically ill.

BACKGROUND: The relationship between body mass index (BMI) and outcomes in the acute care setting is controversial, with evidence suggesting that obesity is either protective - which is also called obesity paradox - or associated with worse outcomes. The purpose of this study was to assess whether BMI was related to frailty and biological age, and whether BMI remained predictive of mortality after adjusting for frailty and biological age. SUBJECTS: Of the 2950 patients who had a biological age estimated on admission to the intensive care unit, 877 (30 %) also had BMI and frailty data available for further analysis in this retrospective cohort study. METHODS: Biological age of each patient was estimated using the Levine PhenoAge model based on results of nine blood tests that were reflective of DNA methylation. Biological age in excess of chronological age was then indexed to the local study context by a linear regression to generate the residuals. The associations between BMI, clinical frailty scale, and the residuals were first analyzed using univariable analyses. Their associations with mortality were then assessed by multivariable analysis, including the use of a 3-knot restricted cubic spline function to allow non-linearity. RESULTS: Both frailty (p = 0.003) and the residuals of the biological age (p = 0.001) were related to BMI in a U-shaped fashion. BMI was not related to hospital mortality, but both frailty (p = 0.015) and the residuals of biological age (OR per decade older than chronological age 1.50, 95 % confidence interval [CI] 1.04-2.18; p = 0.031) were predictive of mortality after adjusting for chronological age, diabetes mellitus and severity of acute illness. CONCLUSIONS: BMI was significantly associated with both frailty and biological age in a U-shaped fashion but only the latter two were related to mortality. These results may, in part, explain why obesity paradox could be observed in some studies.

Body Roundness Index and All-Cause Mortality Among US Adults.

Importance: Obesity, especially visceral obesity, is an established risk factor associated with all-cause mortality. However, the inadequacy of conventional anthropometric measures in assessing fat distribution necessitates a more comprehensive indicator, body roundness index (BRI), to decipher its population-based characteristics and potential association with mortality risk. Objective: To evaluate the temporal trends of BRI among US noninstitutionalized civilian residents and explore its association with all-cause mortality. Design, Setting, and Participants: For this cohort study, information on a nationally representative cohort of 32 995 US adults (age ≥20 years) was extracted from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018 and NHANES Linked Mortality File, with mortality ascertained through December 31, 2019. Data were analyzed between April 1 and September 30, 2023. Exposures: Biennial weighted percentage changes in BRI were calculated. Restricted cubic spline curve was used to determine optimal cutoff points for BRI. Main Outcome and Measures: The survival outcome was all-cause mortality. Mortality data were obtained from the Centers for Disease Control and Prevention website and linked to the NHANES database using the unique subject identifier. Weibull regression model was adopted to quantify the association between BRI and all-cause mortality. Results: Among 32 995 US adults, the mean (SD) age was 46.74 (16.92) years, and 16 529 (50.10%) were women. Mean BRI increased gradually from 4.80 (95% CI, 4.62-4.97) to 5.62 (95% CI, 5.37-5.86) from 1999 through 2018, with a biennial change of 0.95% (95% CI, 0.80%-1.09%; P < .001), and this increasing trend was more obvious among women, elderly individuals, and individuals who identified as Mexican American. After a median (IQR) follow-up of 9.98 (5.33-14.33) years, 3452 deaths (10.46% of participants) from all causes occurred. There was a U-shaped association between BRI and all-cause mortality, with the risk increased by 25% (hazard ratio, 1.25; 95% CI, 1.05-1.47) for adults with BRI less than 3.4 and by 49% (hazard ratio, 1.49; 95% CI, 1.31-1.70) for those with BRI of 6.9 or greater compared with the middle quintile of BRI of 4.5 to 5.5 after full adjustment. Conclusions and Relevance: This national cohort study found an increasing trend of BRI during nearly 20-year period among US adults, and importantly, a U-shaped association between BRI and all-cause mortality. These findings provide evidence for proposing BRI as a noninvasive screening tool for mortality risk estimation, an innovative concept that could be incorporated into public health practice pending consistent validation in other independent cohorts.

Impact of metabolic phenotype and alcohol consumption on mortality risk in metabolic dysfunction-associated fatty liver disease: a population-based cohort study.

Patients with metabolic dysfunction-associated fatty liver disease (MAFLD) often present with concomitant metabolic dysregulation and alcohol consumption, potentially leading to distinct clinical outcomes. We analyzed data from 8043 participants with MAFLD in the Thai National Health Examination Survey with linked mortality records. According to the MAFLD criteria, 1432 individuals (17.2%) were categorized as having the diabetes phenotype, 5894 (71.0%) as the overweight/obesity phenotype, and 978 (11.8%) as the lean metabolic phenotype. Over 71,145 person-years, 916 participants died. Using Cox proportional hazard models adjusting for physiological, lifestyle, and comorbid factors, both diabetes (adjusted hazards ratio [aHR] 1.59, 95% CI 1.18-2.13) and lean metabolic phenotypes (aHR 1.28, 95% CI 1.01-1.64) exhibited significantly higher mortality risk compared to the overweight/obesity phenotype. A J-shaped relationship was observed between daily alcohol consumption and the risk of all-cause mortality. Daily alcohol intake exceeding 50 g for women and 60 g for men increased the all-cause mortality risk among MAFLD individuals with the lean metabolic phenotype (aHR 3.39, 95% CI 1.02-11.29). Our study found that metabolic phenotype and alcohol consumption have interactive effects on the risk of all-cause mortality in patients with MAFLD, indicating that evaluating both factors is crucial for determining prognostic outcomes and management strategies.

Deciphering the link between healthcare expenditure, corruption, and COVID-19 mortality.

This paper analyzes the determinants of COVID-19 mortality across over 140 countries in 2020, with a focus on healthcare expenditure and corruption. It finds a positive association between COVID-19 deaths and aging populations, obesity rates, and healthcare expenditure while noting a negative association with rural residency and corruption perception. The study further reveals that mortality is positively associated with aging populations in high-income countries and positively associated with obesity in upper-middle to high-income countries. Mortality is positively associated with healthcare expenditure, which likely reflects a country's preparedness and ability to better track, document, and report COVID-19 deaths. On the other hand, mortality is negatively associated with corruption perception in upper-middle-income countries. Further analyses based on 2021 data reveal COVID-19 deaths are positively associated with the proportion of the population aged 65 and older in low to lower-middle-income countries, with obesity in high-income countries, and with tobacco use across most countries. Interestingly, there is no evidence linking COVID-19 deaths to healthcare expenditure and corruption perception, suggesting a post-2020 convergence in preparedness likely due to proactive pandemic responses, which might have also mitigated corruption's impact. Policy recommendations are proposed to aid the elderly, address obesity, and combat tobacco use.

Association of weight-adjusted waist index with all-cause mortality among non-Asian individuals: a national population-based cohort study.

INTRODUCTION: The Weight-Adjusted Waist Index (WWI) is a new indicator of obesity that is associated with all-cause mortality in Asian populations. Our study aimed to investigate the linear and non-linear associations between WWI and all-cause mortality in non-Asian populations in the United States, and whether WWI was superior to traditional obesity indicators as a predictor of all-cause mortality. METHODS: We conducted a cohort study using data from the 2011-2018 National Health and Nutrition Examination Survey (NHANES), involving 18,592 participants. We utilized Cox proportional hazard models to assess the association between WWI, BMI, WC, and the risk of all-cause mortality, and performed subgroup analyses and interaction tests. We also employed a receiver operating characteristics (ROC) curve study to evaluate the effectiveness of WWI, BMI, and WC in predicting all-cause mortality. RESULTS: After adjusting for confounders, WWI, BMI, and WC were positively associated with all-cause mortality. The performance of WWI, BMI, and WC in predicting all-cause mortality yielded AUCs of 0.697, 0.524, and 0.562, respectively. The data also revealed a U-shaped relationship between WWI and all-cause mortality. Race and cancer modified the relationship between WWI and all-cause mortality, with the relationship being negatively correlated in African Americans and cancer patients. CONCLUSIONS: In non-Asian populations in the United States, there is a U-shaped relationship between WWI and all-cause mortality, and WWI outperforms BMI and WC as a predictor of all-cause mortality. These findings may contribute to a better understanding and prediction of the relationship between obesity and mortality, and provide support for effective obesity management strategies.

Association between class III obesity and overall survival in previously untreated younger patients with acute myeloid leukemia enrolled on SWOG S1203.

There has been ongoing debate on the association between obesity and outcomes in acute myeloid leukemia (AML). Currently few studies have stratified outcomes by class I obesity, class II obesity, and class III obesity, and a more nuanced understanding is becoming increasingly important with the rising prevalence of obesity. We examined the association between body mass index (BMI) and outcomes in previously untreated AML in younger patients (age ≤60) enrolled in SWOG S1203 (n = 729). Class III obesity was associated with an increased rate of early death (p = 0.004) and worse overall survival (OS) in multivariate analysis (hazard ratio (HR) 2.48, 95% confidence interval (CI) 1.62-3.80 versus normal weight). Class III obesity was also associated with worse OS after allogeneic hematopoietic cell transplant (HR 2.37, 95% CI 1.24-4.54 versus normal weight). These findings highlight the unique risk of class III obesity in AML, and the importance of further investigation to better characterize this patient population.

Obesity paradox of cardiovascular mortality in older adults in the United States: A cohort study using 1997-2018 National Health Interview Survey data linked with the National Death Index.

BACKGROUND: Large-scale, population-based investigations primarily investigating the association between body mass index (BMI) and cardiovascular disease (CVD) mortality among older and younger adults in the United States (U.S.) are lacking. OBJECTIVE: To evaluate the relationship between BMI and CVD mortality in older (≥65 years) and younger (<65 years) adults and to identify the nadir for CVD mortality. DESIGN: This cohort study used serial cross-sectional data from the 1997 to 2018 National Health Interview Survey (NHIS) linked with the National Death Index. NHIS is an annual nationally representative household interview survey of the civilian noninstitutionalized U.S. SETTING: Residential units of the civilian noninstitutionalized population in the U.S. PARTICIPANTS: The target population for the NHIS is the civilian noninstitutionalized U.S. population at the time of the interview. We included all adults who had BMI data collected at 18 years and older and with mortality data being available. To minimize the risk of reverse causality, we excluded adults whose survival time was ≤2 years of follow-up after their initial BMI was recorded and those with prevalent cancer and/or CVD at baseline. METHODS: We used the BMI record obtained in the year of the NHIS survey. Total CVD mortality used the NHIS data linked to the latest National Death Index data from the survey inception to December 31, 2019. We performed multivariable Cox proportional hazards regression models to estimate adjusted hazard ratios (aHRs) and 95 % confidence intervals (CIs). RESULTS: The study included 425,394 adults; the mean (SD) age was 44 (16.7) years. During a median follow-up period of 11 years, 12,089 CVD-related deaths occurred. In older adults, having overweight was associated with a lower risk of CVD mortality (aHR 0.92 [95 % CI, 0.87-0.97]); having class I obesity (1.04 [0.97-1.12]) and class II obesity (1.12 [1.00-1.26]) was not significantly associated with an increased CVD mortality; and having class III obesity was associated with an increased risk of CVD mortality (1.63 [1.35-1.98]), in comparison with adults who had a normal BMI. Yet, in younger adults, having overweight, class I, II, and III obesity was associated with a progressively higher risk of CVD mortality. The nadir for CVD mortality is 28.2 kg/m2 in older adults and 23.6 kg/m2 in younger adults. CONCLUSION: This U.S. population-based cohort study highlights the significance of considering age as a crucial factor when providing recommendations and delivering self-care educational initiatives for weight loss to reduce CVD mortality.

Toward evidence-based communication on overweight body mass index and mortality.

BACKGROUND: Reducing overweight and obesity has been a longstanding focus of public health messaging and physician-patient interactions. Clinical guidelines by major public health organizations describe both overweight and obesity as risk factors for mortality and other health conditions. Accordingly, a majority of primary care physicians believe that overweight BMI (even without obesity) strongly increases mortality risk. MAIN POINTS: The current evidence base suggests that although both obese BMI and underweight BMI are consistently associated with increased all-cause mortality, overweight BMI (without obesity) is not meaningfully associated with increased mortality. In fact, a number of studies suggest modest protective, rather than detrimental, associations of overweight BMI with all-cause mortality. Given this current evidence base, clinical guidelines and physician perceptions substantially overstate all-cause mortality risks associated with the range of BMIs classified as "overweight" but not "obese." Discrepancies between evidence and communication regarding mortality raise the question of whether similar discrepancies exist for other health outcomes. CONCLUSIONS: Health communication that inaccurately conveys current evidence may do more harm than good; this applies to communication from health authorities to health practitioners as well as to communication from health practitioners to individual patients. We give three recommendations to better align health communication with the current evidence. First, recommendations to the public and health practitioners should distinguish overweight from obese BMI and at this time should not describe overweight BMI as a risk factor for all-cause mortality. Second, primary care physicians' widespread misconceptions about overweight BMI should be rectified. Third, the evidence basis for other potential risks or benefits of overweight BMI should be rigorously examined and incorporated appropriately into health communication.

Risk factors associated with COVID-19 mortality in Mexico.

BACKGROUND: On December 31, 2019, one of the most serious pandemics in recent times made its appearance. Certain health conditions, such as obesity and diabetes mellitus, have been described to be related to COVID-19 unfavorable outcomes. OBJECTIVE: To identify factors associated with mortality in patients with COVID-19. MATERIAL AND METHODS: Retrospective cohort of 998,639 patients. Patient sociodemographic and clinical characteristics were analyzed, with survivors being compared with the deceased individuals. Cox proportional hazards model was used to identify variables predictive of COVID-19-associated mortality. RESULTS: Among the deceased patients, men accounted for 64.3%, and women, for 35.7%, with the difference being statistically significant. Subjects older than 80 years had a 13-fold higher risk of dying from COVID-19 (95% CI = 12,469, 13,586), while chronic kidney disease entailed a risk 1.5 times higher (95% CI = 1,341, 1,798), and diabetes mellitus involved a risk 1.25 times higher (95% CI = 1.238,1.276). CONCLUSIONS: Age, sex, diabetes mellitus and obesity were found to be predictors of COVID-19 mortality. Further research related to chronic obstructive pulmonary disease, cardiovascular diseases, smoking and pregnancy is suggested.

ANTECEDENTES: El 31 de diciembre de 2019, se inició una de las pandemias más graves de los últimos tiempos. Se ha descrito que ciertas condiciones de salud, como la obesidad y la diabetes mellitus, están relacionadas con desenlaces desfavorables por COVID-19. OBJETIVO: Identificar factores asociados a mortalidad en pacientes con COVID-19. MATERIAL Y MÉTODOS: Cohorte retrospectiva de 998 639 pacientes. Se analizaron las características sociodemográficas y clínicas de los pacientes, y se compararon supervivientes con fallecidos. Se utilizó el modelo de riesgos proporcionales de Cox para la identificación de variables predictivas de defunción por COVID-19. RESULTADOS: Entre los fallecidos, los hombres representaron 64.3 % y las mujeres 35.7 %, diferencia que resultó estadísticamente significativa. Las personas con más de 80 años presentaron un riesgo 13 veces mayor de morir por COVID-19 (IC 95 % = 12.469,13.586) y la enfermedad renal crónica, un riesgo de 1.5 (IC 95 % = 1.341, 1.798); la diabetes mellitus tuvo un riesgo de 1.25 (IC 95 % = 1.238,1.276). CONCLUSIONES: La edad, el sexo, la diabetes mellitus y la obesidad resultaron ser entidades predictivas de muerte por COVID-19. Se sugiere más investigación relacionada con enfermedad pulmonar obstructiva crónica, enfermedades cardiovasculares, tabaquismo y embarazo.

Physical activity and mortality in patients with dementia: 2009-2015 National Health Insurance Sharing Service data.

The study aimed to investigate the survival rate of patients with dementia according to their level of physical activity and body mass index (BMI). A total of 5,789 patients with dementia were retrieved from the 2009-2015 National Health Insurance Sharing Service databases. Survival analysis was used to calculate the hazard ratio (HR) for physical activity and BMI. The study sample primarily comprised older adults (65-84 years old, 83.81%) and female (n = 3,865, 66.76%). Participants who engaged in physical activity had a lower mortality risk (HR = 0.91, p = 0.02). Compared to the underweight group, patients with dementia who had normal weight (HR = 0.86, p = 0.01), obesity (HR = 0.85, p = 0.03) and more than severe obesity (HR = 0.72, p = 0.02) demonstrated a lower mortality risk. This study emphasizes the significance of avoiding underweight and engaging in physical activity to reducing mortality risk in patients with dementia, highlighting the necessity for effective interventions.

Associations of obesity with chronic inflammatory airway diseases and mortality in adults: a population-based investigation.

BACKGROUND: The association between obesity and respiratory diseases has been confirmed. However, few studies have reported the relationship between obesity and the risk and mortality of chronic inflammatory airway disease (CIAD). The aim of this study was to reveal the association between obesity and the risk of CIAD, and mortality in patients with CIAD. METHODS: The study was conducted using data from the National Health and Nutrition Examination Survey (NHANES) 2013 to 2018 among adults aged 20 years and above. All participants were grouped according to body mass index (BMI) and waist circumference (WC) levels to study the relationship between obesity and CIAD. Multivariate logistic regression analysis was utilized to examine the connection between CIAD and obesity in a cross-sectional study. The association between obesity and all-cause mortality in individuals with CIAD was examined using multiple cox regression models and smooth curve fitting in a prospective cohort study. RESULTS: When stratified based on BMI in comparison to the normal weight group, the ORs with 95%CIs of CIAD for underweight and obesity were 1.39 (1.01-1.93) and 1.42 (1.27-1.58), respectively. The OR with 95%CI of CIAD for obesity was 1.20 (1.09-1.31) when stratified according to WC. Additionally, underweight was associated with a higher mortality (HR = 2.44, 95% CI = 1.31-4.55), whereas overweight (HR = 0.58,95% CI = 0.39-0.87) and obesity (HR = 0.59,95% CI = 0.4-0.87) were associated with a lower mortality (P for trend < 0.05). There was a non-linear association between BMI and all-cause mortality (P for non-linear = 0.001). An analysis of a segmentation regression model between BMI and all-cause mortality revealed a BMI turning point value of 32.4 kg/m2. The mortality of CIAD patients was lowest when BMI was 32.4 kg/m2. When BMI ≤ 32.4 kg/m2, BMI was inversely associated with all-cause mortality in patients with CIAD (HR: 0.92, 95%CI:0.88-0.97). However, when BMI > 32.4 kg/m2, there was no association between BMI and all-cause mortality (HR:1.02, 95%CI:0.97-1.06). CONCLUSION: Compared to normal weight, underweight and obesity were associated with the increased risk of CIAD. Underweight was associated with increased all-cause mortality, while overweight was associated with reduced all-cause mortality. There was a non-linear association between BMI and all-cause mortality in patients with CIAD. The all-cause mortality was lowest when BMI was 32.4 kg/m2.

Mortality outcomes in diabetic metabolic dysfunction-associated fatty liver disease: non-obese versus obese individuals.

The difference in the survival of obese patients and normal-weight/lean patients with diabetic MAFLD remains unclear. Therefore, we aimed to describe the long-term survival of individuals with diabetic MAFLD and overweight/obesity (OT2M), diabetic MAFLD with lean/normal weight (LT2M), MAFLD with overweight/obesity and without T2DM (OM), and MAFLD with lean/normal weight and without T2DM (LM). Using the NHANESIII database, participants with MAFLD were divided into four groups. Hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause, cardiovascular disease (CVD)-related, and cancer-related mortalities for different MAFLD subtypes were evaluated using Cox proportional hazards models. Of the 3539 participants, 1618 participants (42.61%) died during a mean follow-up period of 274.41 ± 2.35 months. LT2M and OT2M had higher risks of all-cause mortality (adjusted HR, 2.14; 95% CI 1.82-2.51; p < 0.0001; adjusted HR, 2.24; 95% CI 1.32-3.81; p = 0.003) and CVD-related mortality (adjusted HR, 3.25; 95% CI 1.72-6.14; p < 0.0001; adjusted HR, 3.36; 95% CI 2.52-4.47; p < 0.0001) than did OM. All-cause and CVD mortality rates in LT2M and OT2M patients were higher than those in OM patients. Patients with concurrent T2DM and MAFLD should be screened, regardless of the presence of obesity.

CVD incidence and mortality among people with diabetes and/or hypertension: Results from the English longitudinal study of ageing.

BACKGROUND AND AIMS: Diabetes and/or hypertension are the most common conditions in older people, and also related to higher cardiovascular disease (CVD) incidence and mortality. This study aims to explore the risk of CVD incidence and mortality among older people with diabetes and/or hypertension over a 16 years follow-up period and investigates the role of depression and obesity in these relationships. METHODS: 6,855 participants aged 50+ from the English Longitudinal Study of Ageing (ELSA). The main exposure is having diabetes and/or hypertension at baseline (2002/2003) compared to not having, but excluded those with coronary heart disease (CHD) and/or stroke (CVD). Survival models are used for CVD incidence and mortality up to 2018, adjusted for socio-demographic, health, health behaviours, cognitive function, and physical function characteristics. RESULTS: 39.3% of people at baseline had diabetes and/or hypertension. The risk of CVD incidence was 1.7 (95%CI: 1.5; 1.9) higher among people with diabetes and/or hypertension compared to those without and was independent of covariates adjustment. People with diabetes and/or hypertension were also 1.3 (95%CI: 1.1; 1.8) times more likely to die from CVD than those without. We did not find evidence for an elevated risk of CVD incidence and mortality among people with obesity nor among those with depression. CONCLUSIONS: In order to effectively reduce the risk of CVD incidence and mortality among older people, treatment as well as management of hypertension and diabetes should be routinely considered for older people with diabetes and/or hypertension.

Association of body mass index and waist circumference with long-term mortality risk in 10,370 coronary patients and potential modification by lifestyle and health determinants.

BACKGROUND AND AIMS: Body adiposity is known to affect mortality risk in patients with coronary artery disease (CAD). We examined associations of body mass index (BMI) and waist circumference (WC) with long term mortality in Dutch CAD patients, and potential and effect modification of these associations by lifestyle and health determinants. METHODS: 10,370 CAD patients (mean age ∼65 y; 20% female; >80% on cardiovascular drugs) from the prospective Alpha Omega Cohort and Utrecht Cardiovascular Cohort-Secondary Manifestations of ARTerial disease study were included. Cox models were used to estimate categorical and continuous associations (using restricted cubic splines) of measured BMI and WC with all-cause and cardiovascular mortality risk, adjusting for age, sex, smoking, alcohol, physical activity and educational level. Analyses were repeated in subgroups of lifestyle factors (smoking, physical activity, diet quality), education and health determinants (diabetes, self-rated health). RESULTS: During ∼10 years of follow-up (91,947 person-years), 3,553 deaths occurred, including 1,620 from cardiovascular disease. U-shaped relationships were found for BMI and mortality risk, with the lowest risk for overweight patients (BMI ∼27 kg/m2). For obesity (BMI ≥30), the HR for all-cause mortality was 1.31 (95% CI: 1.11, 1.41) in male patients and 1.10 (95% CI: 0.92, 1.30) in female patients, compared to BMI 25-30 kg/m2. WC was also non-linearly associated with mortality, and HRs were 1.18 (95%CI:1.06, 1.30) in males and 1.31 (95%CI:1.05, 1.64) in females for the highest vs. middle category of WC. Results for cardiovascular mortality were mostly in line with the results for all-cause mortality. U-shaped associations were found in most subgroups, associations were moderately modified by physical activity, smoking and educational level. CONCLUSIONS: CAD patients with obesity and a large WC were at increased risk of long-term CVD and all-cause mortality, while mildly overweight patients had the lowest risk. These associations were consistent across subgroups of patients with different lifestyles and health status.

Body mass index, waist circumference, and mortality in subjects older than 80 years: a Mendelian randomization study.

BACKGROUND AND AIMS: Emerging evidence has raised an obesity paradox in observational studies of body mass index (BMI) and health among the oldest-old (aged ≥80 years), as an inverse relationship of BMI with mortality was reported. This study was to investigate the causal associations of BMI, waist circumference (WC), or both with mortality in the oldest-old people in China. METHODS: A total of 5306 community-based oldest-old (mean age 90.6 years) were enrolled in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) between 1998 and 2018. Genetic risk scores were constructed from 58 single-nucleotide polymorphisms (SNPs) associated with BMI and 49 SNPs associated with WC to subsequently derive causal estimates for Mendelian randomization (MR) models. One-sample linear MR along with non-linear MR analyses were performed to explore the associations of genetically predicted BMI, WC, and their joint effect with all-cause mortality, cardiovascular disease (CVD) mortality, and non-CVD mortality. RESULTS: During 24 337 person-years of follow-up, 3766 deaths were documented. In observational analyses, higher BMI and WC were both associated with decreased mortality risk [hazard ratio (HR) 0.963, 95% confidence interval (CI) 0.955-0.971 for a 1-kg/m2 increment of BMI and HR 0.971 (95% CI 0.950-0.993) for each 5 cm increase of WC]. Linear MR models indicated that each 1 kg/m2 increase in genetically predicted BMI was monotonically associated with a 4.5% decrease in all-cause mortality risk [HR 0.955 (95% CI 0.928-0.983)]. Non-linear curves showed the lowest mortality risk at the BMI of around 28.0 kg/m2, suggesting that optimal BMI for the oldest-old may be around overweight or mild obesity. Positive monotonic causal associations were observed between WC and all-cause mortality [HR 1.108 (95% CI 1.036-1.185) per 5 cm increase], CVD mortality [HR 1.193 (95% CI 1.064-1.337)], and non-CVD mortality [HR 1.110 (95% CI 1.016-1.212)]. The joint effect analyses indicated that the lowest risk was observed among those with higher BMI and lower WC. CONCLUSIONS: Among the oldest-old, opposite causal associations of BMI and WC with mortality were observed, and a body figure with higher BMI and lower WC could substantially decrease the mortality risk. Guidelines for the weight management should be cautiously designed and implemented among the oldest-old people, considering distinct roles of BMI and WC.

Fat tissue quantity, waist circumference or waist-to-hip ratio in patients with chronic kidney disease: A systematic review and meta-analysis.

The BMI predicts mortality and cardiovascular disease (CVD) in the general population, while in patients with end-stage chronic kidney disease (CKD) a high BMI is associated with improved survival, a phenomenon referred to as the "obesity paradox". While BMI is easy to determine and helps to categorize patients, it does not differentiate between fat tissue, lean tissue and bone mass. As the BMI may be altered in CKD, e.g. by muscle wasting, we determined in this meta-analysis (i) the association of mortality with fat tissue quantity in CKD and (ii) the association of mortality with abdominal obesity (as measured by waist circumference (WC) or waist-to-hip ratio (WHR)) in CKD. We systematically reviewed databases for prospective or retrospective cohort studies. In eleven studies with 23,523 patients the association between mortality and high fat tissue quantity in CKD was calculated. The pooled hazard ratio (HR) for this association in the CKD group in the dialysis group 0.91 (CI 0.84- 0.98, p = 0.01) which is comparable to the HR for the association with BMI. The HR in patients without dialysis was 0.7 (95% CI 0.53- 0.93, p = 0.01), suggesting a better risk prediction of high fat tissue content with mortality as compared to higher BMI with mortality in patients with CKD without dialysis. Importantly, both BMI and fat tissue quantity in CKD are described by the "obesity paradox": the higher the fat tissue content or BMI, the lower the mortality risk. In thirteen studies with 55,175 patients the association between mortality and high WC or WHR in CKD (with or without dialysis) was calculated. We observed, that the HR in the WHR group was 1.31 (CI 1.08-1.58, p = 0.007), whereas the overall hazard ratio of both groups was 1.09 (CI 1.01-1.18, p = 0.03), indicating that a higher abdominal obesity as measured by WHR is associated with higher mortality in CKD. Our analysis suggests gender-specific differences, which need larger study numbers for validation. This meta-analysis confirms the obesity paradox in CKD using fat tissue quantity as measure and further shows that using abdominal obesity measurements in the routine in obese CKD patients might allow better risk assessment than using BMI or fat tissue quantity. Comparable to the overall population, here, the higher the WHR, the higher the mortality risk.

Prognosis of patients with coexisting obesity and malnutrition after ischemic stroke: A cohort study.

BACKGROUND: The double burden of malnutrition, defined as the coexistence of obesity and malnutrition, is an increasing global health concern and is unclear in patients after ischemic stroke. The current study explored the combined impacts of obesity and malnutrition on patients with ischemic stroke. METHODS: We conducted a single-center prospective cohort study with patients with ischemic stroke enrolled in Minhang Hospital in China between January 2018 and December 2022. Patients were stratified into four categories based on their obesity (defined by body mass index) and nutritional status (classified according to the Controlling Nutritional Status score): (1) nourished nonobese, (2) malnourished nonobese, (3) nourished obese, and (4) malnourished obese. The primary end points were poor outcomes and all-cause mortality at 3 months. RESULTS: A total of 3160 participants with ischemic stroke were included in our study, of which 64.7% were male and the mean age was 69 years. Over 50% of patients were malnourished. At 3-month follow-up, the malnourished nonobese had the worst outcomes (34.4%), followed by the malnourished obese (33.2%), nourished nonobese (25.1%), and nourished obese (21.8%; P < 0.001). In multivariable analyses, with nourished nonobese group as the reference, the malnourished nonobese group displayed poorer outcomes (odds ratio [OR], 1.395 [95% CI, 1.169-1.664], P < 0.001) and higher all-cause mortality (OR, 1.541 [95% CI, 1.054-2.253], P = 0.026), but only a nonsignificant increase in poor prognosis rate (33.2% vs. 25.1%, P = 0.102) and mortality (4.2% vs. 3.6%, P = 0.902) were observed in the malnourished obese group. CONCLUSION: A high prevalence of malnutrition is observed in the large population suffering from ischemic attack, even in the obese. Malnourished patients have the worst prognosis particularly in those with severe nutritional status regardless of obesity, while the best functional outcomes and the lowest mortality are demonstrated in nourished obese participants.

The association between lymphocyte-to-monocyte ratio and all-cause mortality in obese hypertensive patients with diabetes and without diabetes: results from the cohort study of NHANES 2001-2018.

Objective: Obesity, hypertension and diabetes are high prevalent that are often associated with poor outcomes. They have become major global health concern. Little research has been done on the impact of lymphocyte-to-monocyte ratio (LMR) on outcomes in these patients. Thus, we aimed to explore the association between LMR and all-cause mortality in obese hypertensive patients with diabetes and without diabetes. Methods: The researchers analyzed data from the National Health and Nutrition Examination Survey (2001-2018), which included 4,706 participants. Kaplan-Meier analysis was employed to compare survival rate between different groups. Multivariate Cox proportional hazards regression models with trend tests and restricted cubic splines (RCS) analysis and were used to investigate the relationship between the LMR and all-cause mortality. Subgroup analysis was performed to assess whether there was an interaction between the variables. Results: The study included a total of 4706 participants with obese hypertension (48.78% male), of whom 960 cases (20.40%) died during follow-up (median follow-up of 90 months). Kaplan-Meier curves suggested a remarkable decrease in all-cause mortality with increasing LMR value in patients with diabetes and non-diabetes (P for log-rank test < 0.001). Moreover, multivariable Cox models demonstrated that the risk of mortality was considerably higher in the lowest quartile of the LMR and no linear trend was observed (P > 0.05). Furthermore, the RCS analysis indicated a non-linear decline in the risk of death as LMR values increased (P for nonlinearity < 0.001). Conclusions: Increased LMR is independently related with reduced all-cause mortality in patients with obese hypertension, regardless of whether they have combined diabetes.

Association of Baseline Pre-Diagnosis and Post-Diagnosis Obesity and Weight Change with Cardiovascular Risk and Survival Among Nonmetastatic Prostate Cancer Survivors.

INTRODUCTION: Obesity in prostate cancer survivors may increase mortality. Better characterization of this effect may allow better counseling on obesity as a targetable lifestyle factor to reduce mortality in prostate cancer survivors. The purpose of this study was to determine whether pre- and post-diagnostic obesity and weight change affect all-cause mortality, cardiovascular disease specific mortality, and prostate cancer specific mortality in patients with nonmetastatic prostate cancer. PATIENTS AND METHODS: We performed a retrospective cohort analysis of 5,077 patients diagnosed with localized prostate cancer from 1997 to 2017 with median follow-up of 15.5 years. The Utah Population Database linked to the Utah Cancer Registry was used to identify patients at a variety of treatment centers. RESULTS: Pre-diagnosis obesity was associated with a 62% increased risk of cardiovascular disease specific mortality and a 34% increased risk of all-cause mortality (HR 1.62, 95% CI 1.05-2.50; HR 1.34, 95% CI 1.07-1.67, respectively). Post-diagnosis obesity increased the risk of cardiovascular disease specific mortality (HR 1.83, 95% CI 1.31-2.56) and all-cause mortality (HR 1.37, 95% CI 1.16-1.64) relative to non-obese men. We found no association between pre-diagnostic obesity or post-diagnostic weight gain and prostate cancer specific mortality. CONCLUSION: Our study strengthens the conclusion that pre-, post-diagnostic obesity and weight gain increase cardiovascular disease and all-cause mortality but not prostate cancer specific mortality compared to healthy weight men. An increased emphasis on weight management may improve mortality for prostate cancer survivors who are obese.