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.

Synergistic effects of glucose tolerance and BMI on cardiovascular events and all-cause mortality in a healthy population: CA.ME.LI.A study 7 years follow-up.

The CA.ME.LI.A (CArdiovascular risks, MEtabolic syndrome, LIver and Autoimmune disease) epidemiological study was conducted in Abbiategrasso (Milan, Italy) to identify risk factors for metabolic and cardiovascular disease in an apparently healthy population of northern Italy. The population (n = 2,545, 1,251 men, 1,254 women) was stratified according to body mass index [normal body weight (NBW): <25 kg/m2; overweight-obese (OWO): ≥25 kg/m2] and according to fasting blood glucose [normal fasting glucose: <100 mg/dL; impaired fasting glucose (IFG): 100-125 mg/dL; diabetes mellitus (DM): ≥126 mg/dL]. The incidence of cardiovascular (CV) events and overall mortality were studied by the Kaplan-Meier method using the log rank test. Univariate analysis was conducted with time-dependent Cox models. During the 7-yr follow-up period, 80 deaths and 149 CV events occurred. IFG [hazard ratio (HR): 2.81; confidence interval (CI): 1.37-5.77; P = 0.005], DM (HR: 4.88; CI: 1.47-16; P = 0.010), or OWO (HR: 2.78; CI:1.68-4.59; P < 0.001) all produced significant increases in CV events and deaths. In the combination IFG/OWO (HR: 5.51; CI: 3.34-9.08; P < 0.001), there was an apparent additive effect of the two conditions, whereas in the combination DM/OWO (HR: 12.71; CI: 7.48-22; P < 0.001), there was an apparent multiplicative effect on the risk for CV events and deaths. In males, the DM/NBW group had a higher incidence of cardiovascular events and deaths than the IFG/OWO group. In contrast, in females, the IFG/OWO group had a higher incidence of cardiovascular events and deaths than the DM/NBW group. In women, there was a greater incidence of CV events in the IFG/OWO group (HR: 6.23; CI: 2.88-13; P < 0.001) than in men in the same group (HR: 4.27; CI: 2.15-8.47; P < 0.001). Consistent with these data, also all-cause mortality was progressively increased by IFG/DM and OWO, with an apparently exponential effect in the combination DM/OWO (HR: 11.78; CI: 6.11-23; P < 0.001). IFG/DM and OWO, alone or in combination, had major effects in increasing mortality for all causes and CV events. The relative contributions of hyperglycemia and overweight/obesity on cardiovascular events and deaths were apparently, to a certain extent, sex dependent. Females were more affected by overweight/obesity either alone or combined with IFG, as compared with males.NEW & NOTEWORTHY For the first time, the combined effects of glucose tolerance and BMI have been investigated in an apparently healthy large population sample of a city in the north of Italy. We found that there are synergistic effects of glucose levels with BMI to increase not only cardiovascular events and deaths but also cancer-related deaths and all-cause 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.

Adiposity and mortality among intensive care patients with COVID-19 and non-COVID-19 respiratory conditions: a cross-context comparison study in the UK.

BACKGROUND: Adiposity shows opposing associations with mortality within COVID-19 versus non-COVID-19 respiratory conditions. We assessed the likely causality of adiposity for mortality among intensive care patients with COVID-19 versus non-COVID-19 by examining the consistency of associations across temporal and geographical contexts where biases vary. METHODS: We used data from 297 intensive care units (ICUs) in England, Wales, and Northern Ireland (Intensive Care National Audit and Research Centre Case Mix Programme). We examined associations of body mass index (BMI) with 30-day mortality, overall and by date and region of ICU admission, among patients admitted with COVID-19 (N = 34,701; February 2020-August 2021) and non-COVID-19 respiratory conditions (N = 25,205; February 2018-August 2019). RESULTS: Compared with non-COVID-19 patients, COVID-19 patients were younger, less often of a white ethnic group, and more often with extreme obesity. COVID-19 patients had fewer comorbidities but higher mortality. Socio-demographic and comorbidity factors and their associations with BMI and mortality varied more by date than region of ICU admission. Among COVID-19 patients, higher BMI was associated with excess mortality (hazard ratio (HR) per standard deviation (SD) = 1.05; 95% CI = 1.03-1.07). This was evident only for extreme obesity and only during February-April 2020 (HR = 1.52, 95% CI = 1.30-1.77 vs. recommended weight); this weakened thereafter. Among non-COVID-19 patients, higher BMI was associated with lower mortality (HR per SD = 0.83; 95% CI = 0.81-0.86), seen across all overweight/obesity groups and across dates and regions, albeit with a magnitude that varied over time. CONCLUSIONS: Obesity is associated with higher mortality among COVID-19 patients, but lower mortality among non-COVID-19 respiratory patients. These associations appear vulnerable to confounding/selection bias in both patient groups, questioning the existence or stability of causal effects.

Association of weight loss with cardiovascular or all-cause mortality in patients with heart failure: A meta-analysis.

BACKGROUND: A consensus has not been reached on the association between weight loss and survival outcomes in patients with heart failure (HF). This meta-analysis aimed to assess the association of weight loss with cardiovascular or all-cause mortality in patients with HF. METHODS: Two authors independently searched the articles indexed in the PubMed and Embase databases up to May 7, 2023. Post hoc analysis of randomized controlled trials or observational studies that reported the utility of weight loss in predicting cardiovascular or all-cause mortality in patients with HF were included. RESULTS: Thirteen studies reporting on 12 articles involving 26,164 patients with HF were included. A comparison of weight loss with stable weight showed that the pooled adjusted hazard ratio (HR) for all-cause mortality was 1.75 (95% confidence intervals [CI] 1.43-2.14). Subgroup analysis revealed that weight loss was associated with an increased risk of all-cause mortality, irrespective of whether patients were overweight/obese (HR 1.76; 95% CI 1.41-2.20) or not (HR 1.90; 95% CI 1.14-3.14). The pooled adjusted HR of cardiovascular mortality was 1.64 (95% CI 1.18-2.28) for patients with weight loss compared to those without. CONCLUSIONS: Weight loss is associated with an increased risk of cardiovascular and all-cause mortality in patients with HF. Assessing weight changes can provide prognostic information for patients with HF.

Metabolic obesity phenotypes and all-cause mortality among the Chinese oldest-old population: a prospective cohort study.

BACKGROUND: The obesity paradox has been reported among older adults. However, whether the favorable effect of obesity is dependent on metabolic status remains largely unknown. We aimed to explore the association of metabolic obesity phenotypes and their changes with all-cause mortality among the Chinese oldest-old population. METHODS: This prospective cohort study included 1207 Chinese oldest old (mean age: 91.8 years). Metabolic obesity phenotypes were determined by central obesity and metabolic status, and participants were classified into metabolically healthy obesity (MHO), metabolically unhealthy obesity (MUO), metabolically healthy non-obesity (MHN), and metabolically unhealthy non-obesity (MUN). The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated by Cox regression models. RESULTS: During 5.3 years of follow-up, 640 deaths were documented. Compared with non-obesity, obesity was associated with a decreased mortality risk among participants with metabolically healthy (HR, 0.75; 95% CI, 0.63-0.91) while this association was insignificant among metabolically unhealthy. Compared to MHO, MHN (HR, 1.27; 95% CI, 1.06-1.53) and MUN (HR, 1.49; 95% CI, 1.10-2.02) were significantly associated with an increased mortality risk. Compared to those with stable MHO, those transited from MHO to MUO demonstrated a higher mortality risk (HR, 1.81; 95% CI, 1.06-3.11). CONCLUSIONS: MHO predicts better survival among the Chinese oldest-old population. These findings suggest that ensuring optimal management of metabolic health is beneficial and taking caution in weight loss based on the individual body weight for the metabolically healthy oldest-old adults.

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.

Metabolically "extremely unhealthy" obese and non-obese people with diabetes and the risk of cardiovascular adverse events: the Silesia Diabetes - Heart Project.

BACKGROUND: There is a growing burden of non-obese people with diabetes mellitus (DM). However, their cardiovascular risk (CV), especially in the presence of cardiovascular-kidney-metabolic (CKM) comorbidities is poorly characterised. The aim of this study was to analyse the risk of major CV adverse events in people with DM according to the presence of obesity and comorbidities (hypertension, chronic kidney disease, and dyslipidaemia). METHODS: We analysed persons who were enrolled in the prospective Silesia Diabetes Heart Project (NCT05626413). Individuals were divided into 6 categories according to the presence of different clinical risk factors (obesity and CKM comorbidities): (i) Group 1: non-obese with 0 CKM comorbidities; (ii) Group 2: non-obese with 1-2 CKM comorbidities; (iii) Group 3: non-obese with 3 CKM comorbidities (non-obese "extremely unhealthy"); (iv) Group 4: obese with 0 CKM comorbidities; (v) Group 5: obese with 1-2 CKM comorbidities; and (vi) Group 6: obese with 3 CKM comorbidities (obese "extremely unhealthy"). The primary outcome was a composite of CV death, myocardial infarction (MI), new onset of heart failure (HF), and ischemic stroke. RESULTS: 2105 people with DM were included [median age 60 (IQR 45-70), 48.8% females]. Both Group 1 and Group 6 were associated with a higher risk of events of the primary composite outcome (aHR 4.50, 95% CI 1.20-16.88; and aHR 3.78, 95% CI 1.06-13.47, respectively). On interaction analysis, in "extremely unhealthy" persons the impact of CKM comorbidities in determining the risk of adverse events was consistent in obese and non-obese ones (Pint=0.824), but more pronounced in individuals aged < 65 years compared to older adults (Pint= 0.028). CONCLUSION: Both non-obese and obese people with DM and 3 associated CKM comorbidities represent an "extremely unhealthy" phenotype which are at the highest risk of CV adverse events. These results highlight the importance of risk stratification of people with DM for risk factor management utilising an interdisciplinary approach.

The obesity paradox exists for perioperative complications and mortality following lower extremity arterial bypass surgery.

OBJECTIVE: The obesity paradox refers to a phenomenon by which obese individuals experience lower risk of mortality and even protective associations from chronic disease sequelae when compared with the non-obese and underweight population. Prior literature has demonstrated an obesity paradox after cardiac and other surgical procedures. However, the relationship between body mass index (BMI) and perioperative complications for patients undergoing major open lower extremity arterial revascularization is unclear. METHODS: We queried the Vascular Quality Initiative for individuals receiving unilateral infrainguinal bypass between 2003 and 2020. We used multivariable logistic regression to assess the relationship of BMI categories (underweight [<18.5 kg/m2], non-obese [18.5-24.9 kg/m2], overweight [25-29.9 kg/m2], Class 1 obesity [30-34.9 kg/m2], Class 2 obesity [35-39.9 kg/m2], and Class 3 obesity [>40 kg/m2]) with 30-day mortality, surgical site infection, and adverse cardiovascular events. We adjusted the models for key patient demographics, comorbidities, and technical and perioperative characteristics. RESULTS: From 2003 to 2020, 60,588 arterial bypass procedures met inclusion criteria for analysis. Upon multivariable logistic regression with the non-obese category as the reference group, odds of 30-day mortality were significantly decreased among the overweight (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.53-0.78), Class 1 obese (OR, 0.65; 95% CI, 0.52-0.81), Class 2 obese (OR, 0.66; 95% CI, 0.48-0.90), and Class 3 obese (OR, 0.61; 95% CI, 0.39-0.97) patient categories. Conversely, odds of 30-day mortality were increased in the underweight patient group (OR, 1.58; 95% CI, 1.16-2.13). Furthermore, a BMI-dependent positive association was present, with odds of surgical site infections with patients in Class 3 obesity having the highest odds (OR, 2.10; 95% CI, 1.60-2.76). Finally, among the adverse cardiovascular event outcomes assessed, only myocardial infarction (MI) demonstrated decreased odds among overweight (OR, 0.82; 95% CI, 0.71-0.96), Class 1 obese (OR, 0.78; 95% CI, 0.65-0.93), and Class 2 obese (OR, 0.66; 95% CI, 0.51-0.86) patient populations. Odds of MI among the underweight and Class 3 obesity groups were not significant. CONCLUSIONS: The obesity paradox is evident in patients undergoing lower extremity bypass procedures, particularly with odds of 30-day mortality and MI. Our findings suggest that having higher BMI (overweight and Class 1-3 obesity) is not associated with increased mortality and should not be interpreted as a contraindication for lower extremity arterial bypass surgery. However, these patients should be under vigilant surveillance for surgical site infections. Finally, patients that are underweight have a significantly increased odds of 30-day mortality and may be more suitable candidates for endovascular therapy.

Low body mass index and risk of mortality after mitral transcatheter edge-to-edge repair procedure: The "obesity paradox".

BACKGROUND: Most patients undergoing the mitral transcatheter edge-to-edge repair (TEER) technique are elderly comorbid patients. Low body mass index (BMI) < 23 kg/m2 has been identified in other elderly populations as a risk factor, but has not been studied sufficiently in mitral TEER. AIMS: We aimed to study the impact of low BMI (23 kg/m2) on the outcome after mitral TEER. METHODS: Patients undergoing first-time TEER for mitral regurgitation at a single tertiary center were included, with the exclusion of patients with preprocedural hemodynamic instability or missing BMI. The primary endpoint was all-cause mortality. Secondary endpoints were long-term major bleeding or admission with heart failure. RESULTS: A total of 120 patients (mean age 76 ± 10 years, 76% men) were included in the study. Thirty-nine (31%) had low BMI. Patients with low BMI had a similar symptomatic benefit as patients with BMI ≥ 23 kg/m2 at 1 year regarding decrease in diuretics dose and decrease in New York Heart Association (NYHA) class (p > 0.05). In a multivariable Cox regression analysis, BMI as a continuous variable (hazard ratio [HR]: 0.93 [95% confidence interval, CI: 0.87-0.99], p = 0.03) and low BMI (HR: 1.99 [95% CI: 1.12-3.52], p = 0.02) were associated with the primary outcome. Low BMI was not significantly associated with major bleeding (subdistribution hazard ratio [SHR]: 2.39 [95% CI: 0.96-5.97], p = 0.06) or admission with heart failure (SHR: 1.06 [95% CI: 0.61-1.88], p = 0.83) during follow-up with univariable competing risk regression analysis. CONCLUSION: Low BMI is a risk factor for mortality after mitral valve TEER, confirming the presence of an "obesity paradox" in this population and should receive attention in patient selection.

The Mediating Role of Comorbidities on the Relationship Between Serum Vitamin D and Five-Year Mortality Risk in Colon Cancer Patients.

This retrospective cohort study explores the relationship between vitamin D levels and 5-year mortality risk among 1,549 colon cancer patients seen at University of California health centers between 2012 and 2019, with a particular focus on the mediating role of comorbidities. Methods leveraged structural equation modeling to assess both direct and indirect pathways linking vitamin D to mortality risk. This analysis revealed a protective direct effect of higher vitamin D levels against mortality risk. Additionally, this study uncovered an indirect pathway, demonstrating that vitamin D lowers mortality risk by mitigating comorbidity, which subsequently influence mortality risk. Study results indicate that approximately 9.2% of the beneficial effect of vitamin D on mortality risk is attributable to its capacity to reduce comorbidity burden. In disaggregated and confounder-adjusted structural modeling, there were significant indirect effects for 25(OH)D on mortality risk through its effects on depression and obesity but not on anxiety, diabetes, or chronic kidney disease. These results suggest that the protective effects of vitamin D in colon cancer etiology appear to be through direct action on cancer progression, though patients who also suffer from depression and obesity would especially benefit from achieving adequate levels of serum vitamin D.

The impact of overweight and obesity on health outcomes in the United States from 1990 to 2021.

AIM: Elevated body mass index (BMI) presents a significant public health challenge in the United States, contributing to considerable morbidity, mortality and economic burden. This study investigates the health burden of overweight and obesity in the United States from 1990 to 2021, leveraging the Global Burden of Disease data set to analyse trends, disparities and potential determinants of high BMI-related health outcomes. MATERIALS AND METHODS: Our study focused on the United States, analysing trends in disability-adjusted life years (DALY) and deaths attributable to high BMI, defined as a BMI of 25 kg/m2 or higher for adults. Statistical analyses included estimated annual percentage change (EAPC) in age-standardized DALY rates and age-standardized death rates. Pearson correlation was performed between EAPCs and the socio-demographic index (SDI), with significance set at p < 0.05. RESULTS: From 1990 to 2021, age-standardized DALY rates attributable to high BMI increased by 24.9%, whereas the age-standardized death rates increased by 5.2%. Age disparities showed DALYs peaking at 60-64 years for males and 65-69 years for females, with deaths peaking at 65-69 years for males and 90-94 years for females. A strong negative correlation was found between the EAPC in age-standardized DALY and death rates and the SDI. CONCLUSIONS: Overweight and obesity significantly impact public health in the United States, especially among older adults and lower socio-demographic regions. Comprehensive public health strategies integrating behavioural, technological and environmental interventions are crucial. Future research should focus on longitudinal studies, personalized interventions and policy-driven approaches to address the multifaceted influences on high BMI.

The prognostic role of cardiopulmonary exercise testing in obesity.

AIM: Poor cardiorespiratory fitness has been suggested to increase the risk of chronic diseases in obesity. We investigated the ability of key variables from cardiopulmonary exercise testing (CPET) to predict all-cause mortality in an obese cohort. METHODS: The sample included 469 participants of both sexes (mean age 40 ± 13 years) who underwent a CPET for clinical reasons between 1 March 2009 and 1 December 2023. All-cause mortality was the prognostic endpoint. A receiver operating characteristic analysis was performed to establish optimal cut-points for CPET variables. Kaplan-Meier and Cox regression analyses were used to determine the association between CPET variables and all-cause mortality. RESULTS: There were 46 deaths during a mean follow-up period of 69 ± 48 months, resulting in an annual mortality rate of 2%. Despite the sample being made up of mostly women (70%), there were more deaths in men (18 vs. 6%, p < 0.001).The optimal thresholds for discrimination of survival were as follows: (a) peak oxygen uptake (pVO2) ≤16 mL/kg/min; (b) minute ventilation/carbon dioxide production (VE/VCO2) slope ≥31; (c) ventilatory power ≤5.8 mmHg; and (d) circulatory power ≤2980 mmHg/mL O2/min. Kaplan-Meier survival plots revealed a significant positive association between lower pVO2, circulatory power and ventilatory power values and survival (log-rank, p < 0.001) and higher mortality for men than women. Adjusted Cox regression models showed that a pVO2 ≤16 mL/kg/min had a 20-fold higher risk of mortality when compared with >16 mL/kg/min. CONCLUSION: Given the strong association of VO2, ventilatory efficiency, circulatory and ventilatory power with all-cause mortality, our findings support the notion that poorer cardiorespiratory fitness is associated with a poor prognosis in patients with obesity.

The global burden of disease attributable to high body mass index in 204 countries and territories: Findings from 1990 to 2019 and predictions to 2035.

AIM: Our study aims to provide an updated estimate of age- and sex-specific deaths and disability-adjusted life years (DALYs) associated with high body mass index (BMI) from 1990 to 2019 at the global, regional and national levels, and to forecast the global burden of disease attributed to high BMI from 2020 to 2035. METHODS: We used the data for the number of deaths, DALYs, age-standardized rate (per 100 000 population), percentage change and population attributable fraction from the Global Burden of Disease Study 2019 (GBD 2019) to examine the disease burden attributable to high BMI. We further applied an autoregressive integrated moving average (ARIMA) model to predict the disease burden for the period 2020-2035. RESULTS: From 1990 to 2019, the deaths and DALYs attributable to high BMI increased by 148% and 155.86% for men, and by 111.67% and 121.78% for women, respectively. In 2019, high BMI directly accounted for 8.52% [95% uncertainty intervals (UI) 0.05, 0.12] of all-cause deaths and 5.89% (95% UI 0.04, 0.08) of global DALYs. The highest death rates were observed in men aged 65-69 and women aged 75-79. The highest DALY rates were observed in the age group of 60-64 for both sexes. In 2019, the highest age-standardized deaths and DALY rates were observed in the Central Asia region [163.15 (95% UI 107.72, 223.58) per 100 000 people] and the Oceania region [4643.33 (95% UI 2835.66, 6902.6) per 100 000 people], respectively. Fiji [319.08 (95% UI 213.77, 444.96) per 100 000 people] and Kiribati [10 000.58 (95% UI 6266.55, 14159.2) per 100 000 people] had the highest age-standardized deaths and DALY rates, respectively. In 2019, the highest age-standardized rates of high BMI-related deaths and DALYs were observed in the middle-high socio-demographic index quintile and in the middle socio-demographic index quintile. The age-standardized deaths and DALY rates attributable to high BMI are projected to increase in both sexes from 2020 to 2035. The death rates are projected to rise from 62.79 to 64.31 per 100 000 people, while the DALY rates are projected to rise from 1946 to 2099.54 per 100 000 people. CONCLUSIONS: High BMIs significantly contribute to the global disease burden. The projected rise in deaths and DALY rates attributable to high BMI by 2035 highlights the critical need to address the impact of obesity on public health. Our study provides policymakers with up-to-date and comprehensive information.

Bariatric surgery and all-cause mortality: A methodological review of studies using a non-surgical comparator.

AIM: Non-randomized studies on bariatric surgery have reported large reductions in mortality within 6-12 months after surgery compared with non-surgical patients. It is unclear whether these findings are the result of bias. STUDY DESIGN AND SETTING: We searched PubMed to identify all non-randomized studies investigating the effect of bariatric surgery on all-cause mortality compared with non-surgical patients. We assessed these studies for potential confounding and time-related biases. We conducted bias analyses to quantify the effect of these biases. RESULTS: We identified 21 cohort studies that met our inclusion criteria. Among those, 11 were affected by immortal time bias resulting from the misclassification or exclusion of relevant follow-up time. Five studies were subject to potential confounding bias because of a lack of adjustment for body mass index (BMI). All studies used an inadequate comparator group that lacked indications for bariatric surgery. Bias analyses to correct for potential confounding from BMI shifted the effect estimates towards the null [reported hazard ratio (HR): 0.78 vs. bias-adjusted HR: 0.92]. Bias analyses to correct for the presence of immortal time also shifted the effect estimates towards the null (adjustment for 2-year wait time: reported HR: 0.57 vs. bias-adjusted HR: 0.81). CONCLUSION: Several important sources of bias were identified in non-randomized studies of the effectiveness of bariatric surgery versus non-surgical comparators on mortality. Future studies should ensure that confounding by BMI is accounted for, considering the choice of the comparator group, and that the design or analysis avoids immortal time bias from the misclassification or exclusion.

Associations of diabesity with all-cause and cardiovascular disease mortality: Findings from the Mexico City Prospective Study.

AIM: To investigate the joint associations of diabetes and obesity with all-cause and cardiovascular disease (CVD) mortality in the Mexico City Prospective Study. MATERIALS AND METHODS: In total, 154 128 participants (67.2% women) were included in this prospective analysis. Diabetes was self-reported, while body mass index was used to calculate obesity. Using diabetes and obesity classifications, six groups were created: (a) normal (no diabetes and normal weight); (b) normal weight and diabetes; (c) overweight but not diabetes (overweight); (d) overweight and diabetes (prediabesity); (e) obesity but not diabetes (obesity); and (f) obesity and diabetes (diabesity). Associations between these categories and outcomes were investigated using Cox proportional hazard models adjusted for confounder factors. RESULTS: During 18.3 years of follow-up, 27 197 (17.6%) participants died (28.5% because of CV causes). In the maximally adjusted model, participants those with the highest risk {hazard ratio (HR): 2.37 [95% confidence interval (CI): 2.24-2.51]}, followed by those with diabesity [HR: 2.04 (95% CI: 1.94-2.15)]. Similar trends of associations were observed for CVD mortality. The highest CV mortality risk was observed in individuals with diabesity [HR: 1.80 (95% CI: 1.63-1.99)], followed by normal weight and diabetic individuals [HR: 1.78 (95% CI: 1.60-1.98)]. CONCLUSION: This large prospective study identified that diabetes was the main driver of all-cause and CVD mortality in all the categories studied, with diabesity being the riskiest. Given the high prevalence of both conditions in Mexico, our results reinforce the importance of initiating prevention strategies from an early age.

Association of High BMI With Morbidity and Mortality in Common Emergency General Surgery Procedures.

INTRODUCTION: Emergency general surgery (EGS) patients are at increased risk for postoperative morbidity and mortality. Obesity is a risk factor for poor outcomes in this population. Our study aimed to explore the association of body mass index (BMI) with postoperative outcomes in patients requiring common EGS procedures. METHODS: A retrospective review of the 2018-2020 National Surgical Quality Improvement Program database identified patients undergoing four common EGS procedures: large bowel resection, small bowel resection, cholecystectomy, and appendectomy. Patients were classified by BMI: normal weight (18.5-24.9 kg/m2), obesity classes I (30-34.9 kg/m2), II (35-39.9 kg/m2), III (40-49.9 kg/m2), and IV (≥50 kg/m2). Main outcomes of interest were major adverse event (MAE) and mortality. RESULTS: From 2018 to 2020, a total of 82,540 patients underwent one of four common EGS procedures. On unadjusted analysis, obesity class IV had higher mortality rates compared to classes I-III (6.2% vs 3.1%, P < 0.001). Patients in obesity classes I-III had lower odds of MAE and death relative to those of normal weight. Compared to other patients with obesity, those in obesity class IV were at increased risk of MAE (odds ratio 1.27; 95% confidence interval 1.13-1.44) and death (odds ratio 1.69; 95% confidence interval 1.34-2.13). CONCLUSIONS: Patients with varying degrees of obesity have different risk profiles following common EGS procedures. While patients in lower obesity classes had reduced odds of adverse outcomes, those with BMI ≥50 kg/m2 were particularly at greater risk for postoperative morbidity and mortality. This vulnerable population warrants further investigation and increased vigilance to ensure high-quality care.

Cardiovascular Outcomes of Sodium-Glucose Cotransporter 2 Inhibitors Across Body Mass Index Spectrum in Patients With Heart Failure: An Updated Systematic Review and Meta-Analysis.

ABSTRACT: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors have shown efficacy in improving cardiovascular outcomes in patients with chronic heart failure (HF). However, their impact on HF patients with varying body mass index (BMI) levels remains uncertain. To explore potential interactions between baseline BMI and the cardiovascular benefits of SGLT-2 inhibitors, we conducted a systematic review of studies from PubMed, Scopus, and the Cochrane Library database spanning from inception to March 2024. Eligible studies reported cardiovascular outcomes according to baseline BMI in HF patients treated with SGLT-2 inhibitors. Ultimately, our analysis included 4 studies encompassing 20,723 patients. We conducted separate random-effects meta-analyses for the composite outcome of first hospitalization for HF (HHF) or cardiovascular death (CVD), total HHF, CVD, and all-cause mortality. Compared with placebo, SGLT-2 inhibitors significantly reduced the risk of the composite outcome of first HHF or CVD (hazard ratio = 0.78, 95% confidence interval: 0.72-0.83) and total HHF (hazard ratio = 0.73, 95% confidence interval: 0.61-0.83), with consistent effects observed across different BMI categories (test for subgroup differences: P = 0.63 and P = 0.56, respectively). Furthermore, no statistical heterogeneity was found in the effects of SGLT-2 inhibitors on CVD ( P = 0.84, I 2 = 0%) and all-cause mortality ( P = 0.52, I 2 = 0%) across each baseline BMI subgroup in patients with HF. No significant difference in safety was found between the placebo and SGLT-2 inhibitor arms. In conclusion, our findings suggest that the cardiovascular benefits of SGLT-2 inhibitors seem to be independent of baseline BMI in patients with HF.

Comparing DOAC and warfarin outcomes in an obese population using the 'real-world' Michigan Anticoagulation Quality Improvement Initiative (MAQI2) registry.

INTRODUCTION: Direct oral anticoagulants (DOACs) have overtaken warfarin in the treatment of nonvalvular atrial fibrillation (AF) and venous thromboembolism (VTE). Limited data explore the safety of DOACs in obesity. METHODS: This multicenter retrospective study between June 2015 and September 2019 uses the Michigan Anticoagulation Quality Improvement Initiative (MAQI2) registry to compare DOACs and warfarin across weight classes (not obese: body mass index (BMI) ⩾ 18.5 and < 30; obese: BMI ⩾ 30 and < 40; severely obese: BMI ⩾ 40). Primary outcomes include major, clinically relevant nonmajor (CRNM), and minor bleeding events per 100 patient-years. Secondary outcomes include stroke, recurrent VTE, and all-cause mortality. RESULTS: DOACs were prescribed to 49% of the 4089 patients with AF and 46% of the 3162 patients with VTE. Compared to patients treated with warfarin, those treated with DOACs had a higher estimated glomerular filtration rate across BMI categories regardless of indication. In the AF population, severely obese patients treated with DOACs had more major (3.4 vs 1.8, p = 0.004), CRNM (8.6 vs 5.9, p = 0.019), and minor bleeding (11.4 vs 9.9, p = 0.001). There was no difference in stroke or all-cause mortality. In the VTE population, both CRNM (7.5 vs 6.7, p = 0.042) and minor bleeding (19.3 vs 10.5, p < 0.001) events occurred at higher rates in patients treated with DOACs. There was no difference in recurrent pulmonary embolism, stroke, or all-cause mortality. CONCLUSION: There is a higher rate of bleeding in severely obese patients with VTE and AF treated with DOACs compared to warfarin, without a difference in secondary outcomes. Further studies to compare the anticoagulant classes and understand bleeding drivers in this population are needed.

Global burden of atrial fibrillation attributable to high body mass index from 1990 to 2021: findings from the Global Burden of Disease Study 2021.

OBJECTIVES: To assess the global burden of atrial fibrillation (AF) attributable to high body mass index (BMI) from 1990 to 2021 and analyze its spatiotemporal distribution characteristics. STUDY DESIGN: An observational study based on GBD 2021 data. METHODS: Data on AF burden due to high BMI were obtained from the Global Burden of Disease Study (GBD) 2021. Estimated annual percentage change (EAPC) was calculated to evaluate temporal trends in age-standardized rates of deaths and disability-adjusted life years (DALYs) over 30 years. RESULTS: In 2021, high BMI-related AF caused 27,000 deaths and 725,000 DALYs globally, a 376% increase since 1990. Females and the elderly (aged 70+) bore a higher burden. Upper-middle-income regions surpassed high-income regions in AF burden. Australasia had the highest age-standardized rates, while High-income Asia Pacific and South Asia had the lowest. South Asia showed rapid growth in age-standardized death rates. CONCLUSION: The global burden of high BMI-related AF varies across regions and time, threatening global health, especially for females and the elderly. Targeted strategies are needed to reduce AF and obesity.