Association of obesity on the outcome of critically ill patients affected by COVID-19 / Asociación de la obesidad en la evolución de los pacientes críticos afectados por COVID-19

Objective To evaluate the impact of obesity on ICU mortality. Design Observational, retrospective, multicentre study. Setting Intensive Care Unit (ICU). Patients Adults patients admitted with COVID-19 and respiratory failure. Interventions None. Primary variables of interest Collected data included demographic and clinical characteristics, comorbidities, laboratory tests and ICU outcomes. Body mass index (BMI) impact on ICU mortality was studied as (1) a continuous variable, (2) a categorical variable obesity/non-obesity, and (3) as categories defined a priori: underweight, normal, overweight, obesity and Class III obesity. The impact of obesity on mortality was assessed by multiple logistic regression and Smooth Restricted cubic (SRC) splines for Cox hazard regression. Results 5,206 patients were included, 20 patients (0.4%) as underweight, 887(17.0%) as normal, 2390(46%) as overweight, 1672(32.1) as obese and 237(4.5%) as class III obesity. The obesity group patients (n = 1909) were younger (61 vs. 65 years, p < 0.001) and with lower severity scores APACHE II (13 [9–17] vs. 13[10−17, p < 0.01) than non-obese. Overall ICU mortality was 28.5% and not different for obese (28.9%) or non-obese (28.3%, p = 0.65). Only Class III obesity (OR = 2.19, 95%CI 1.44–3.34) was associated with ICU mortality in the multivariate and SRC analysis. Conclusions COVID-19 patients with a BMI > 40 are at high risk of poor outcomes in the ICU. An effective vaccination schedule and prolonged social distancing should be recommended. (AU)

Objetivo Evaluar el impacto de la obesidad en la mortalidad de la UCI. Diseño Estudio observacional, retrospectivo y multicéntrico. Ámbito Unidad de Cuidados Intensivos (UCI). Pacientes Pacientes adultos con COVID-19 e insuficiencia respiratoria. Intervenciones Ninguna. Variables de interés principales Características demográficas y clínicas, comorbilidades, pruebas de laboratorio y evolución en la UCI. El impacto del índice de masa corporal (IMC) sobre la mortalidad se estudió como (1) una variable continua, (2) una variable categórica obesidad/no obesidad, y (3) como categorías definidas a priori: bajo peso, normal, sobrepeso, obesidad y obesidad clase III. El impacto de la obesidad se evaluó mediante regresión logística múltiple y splines cúbicos suaves restringidos (SRC) para la regresión de riesgos de Cox. Resultados Se incluyeron 5.206 pacientes, 20 (0,4%) con bajo peso, 887 (17,0%) con peso normal, 2.390 (46%) con sobrepeso, 1.672 (32,1%) con obesidad y 237 (4,5%) con obesidad clase III. Los pacientes obesos (n = 1909) eran más jóvenes (61 vs. 65 años, p < 0,001) y con un nivel más bajo de APACHE II (13 [9–17] frente a 13[10−17, p < 0,01) que los no obesos. La mortalidad global en la UCI fue del 28,5% y no fue diferente entre obesos (28,9%) y no obesos (28,3%,p = 0,65). Sólo la obesidad clase III (OR = 2,19; IC del 95%: 1,44−3,34) se asoció con la mortalidad en la UCI en el análisis multivariante y SRC. Conclusiones Los pacientes con COVID-19 con un IMC > 40 tienen un alto riesgo de mala evolución en la UCI. Debe recomendarse un calendario de vacunación eficaz y un distanciamiento social prolongado. (AU)

Temporal Trends in Obesity-Related Mortality Rates: An Analysis of Gender, Race/Ethnicity, and Geographic Disparities in the United States.

Obesity is a global public health concern linked to premature death and an increased burden of noncommunicable diseases. This study aims to assess obesity-related mortality rates and temporal trends in the United States. We investigate variations by gender, ethnicity, and state-level demographics using data from the Centers for Disease Control and Prevention WONDER database spanning 1999 to 2021. We identified 124,076 obesity-related deaths, with a mean age-adjusted mortality rate (AAMR) of 2.7 per 100,000 population. AAMRs increased over time, with the highest rises observed in non-Hispanic Black/African American and American Indian/Alaska Native populations, and among males. Certain states showed higher AAMRs. These findings underscore racial disparities in obesity-related mortality and the need for further research to address these disparities.

How does obesity affect mortality through blood pressure and blood glucose in Chinese and US citizens? Insights from a causal mediation analysis of two large cohorts.

Background: Obesity, which has reached the scale of a global pandemic, is a leading cause of premature death. It is unclear to what extent its effect on mortality was driven by blood pressure or glucose levels in people of different ethnicities. Methods: We conducted a causal mediation analysis to estimate the mediation effect of blood pressure and glucose between body mass index (BMI) or waist-hip ratio (WHR) on mortality based on data from the China Kadoorie Biobank (CKB) (n = 458 385) and US National Health and Nutrition Examination Survey (NHANES) (1999-2008, n = 20 726). Results: The WHR's effect on mortality was mediated by blood pressure and glucose in the CKB data set by 38.7% (95% confidence interval (CI) = 34.1, 43.2) and 36.4% (95% CI = 31.6, 42.8), whereas in NHANES by 6.0% (95% CI = 2.3, 8.3) and 11.2% (95% CI = 4.7, 22.7), respectively. For associations between BMI and mortality in subjects with overweight or obesity, the mediator proportion of blood glucose and pressure was 49.4% (95% CI = 40.1, 62.5) and 16.9% (95% CI = 13.6, 22.9) in CKB and 9.10% (95% CI = 2.2, 25.9) and 16.7% (95% CI = 7.3, 49.0) in NHANES, respectively. We stratified the patients by their blood glucose, blood pressure level, or both into four groups. The effect of WHR on mortality was comparable across subgroups in either cohort. The associations between BMI and mortality were stronger in patients with higher blood pressure in CKB (P = 0.011) and blood glucose in NHANES (P = 0.035) in patients with overweight and obesity. Conclusions: The relationship between WHR and mortality in the CKB data set was potentially caused by blood pressure and glucose to a much greater extent than in the NHANES one. The effect of BMI influenced by blood pressure was significantly higher among Chinese individuals with overweight and obesity. These results implicate a different intervention strategy is required for blood pressure and blood glucose in China and US to prevent obesity and obesity-related premature death.

Dietary diversity predicts the mortality among older people: Data from the fifth Thai national health examination survey.

OBJECTIVE: To examine the association between dietary diversity (DD) and mortality among Thai older people and to investigate whether age, sex, and nutritional status modify this association. METHODS: The national survey conducted from 2013 to 2015 recruited 5631 people aged >60 years. Dietary diversity score (DDS) was assessed for the consumption of eight food groups using food frequency questionnaires. The Vital Statistics System provided the data on mortality in 2021. The association between DDS and mortality was analyzed by Cox proportional hazard model and adjusted for the complex survey design. Interaction terms between DDS and age, sex, and BMI were also tested. RESULTS: The DDS was inversely associated with mortality (HRadj 0.98, 95%CI: 0.96-1.00). This association was stronger in people aged >70 years (HRadj 0.93, 95%CI: 0.90-0.96 for aged 70-79 years, and HRadj 0.92, 95%CI: 0.88-0.95 for aged >80 years). Inverse association between DDS and mortality was also found in the underweight older population (HRadj 0.95, 95%CI: 0.90-0.99). A positive association was found between DDS and mortality in the overweight/obese group (HRadj 1.03, 95%CI: 1.00-1.05). However, the interaction between the DDS with sex to mortality was not statistically significant. CONCLUSION: Increasing DD reduces mortality among Thai older people, especially in those above 70, and underweight. In contrast, an increase in DD also meant an increase in mortality among the overweight/obese group. Focus should be placed on the nutritional interventions aimed to improve DD for those 70 and over and underweight to reduce mortality.

Association of Bariatric Surgery With Cancer Risk and Mortality in Adults With Obesity.

Importance: Obesity increases the incidence and mortality from some types of cancer, but it remains uncertain whether intentional weight loss can decrease this risk. Objective: To investigate whether bariatric surgery is associated with lower cancer risk and mortality in patients with obesity. Design, Setting, and Participants: In the SPLENDID (Surgical Procedures and Long-term Effectiveness in Neoplastic Disease Incidence and Death) matched cohort study, adult patients with a body mass index of 35 or greater who underwent bariatric surgery at a US health system between 2004 and 2017 were included. Patients who underwent bariatric surgery were matched 1:5 to patients who did not undergo surgery for their obesity, resulting in a total of 30 318 patients. Follow-up ended in February 2021. Exposures: Bariatric surgery (n = 5053), including Roux-en-Y gastric bypass and sleeve gastrectomy, vs nonsurgical care (n = 25 265). Main Outcomes and Measures: Multivariable Cox regression analysis estimated time to incident obesity-associated cancer (a composite of 13 cancer types as the primary end point) and cancer-related mortality. Results: The study included 30 318 patients (median age, 46 years; median body mass index, 45; 77% female; and 73% White) with a median follow-up of 6.1 years (IQR, 3.8-8.9 years). The mean between-group difference in body weight at 10 years was 24.8 kg (95% CI, 24.6-25.1 kg) or a 19.2% (95% CI, 19.1%-19.4%) greater weight loss in the bariatric surgery group. During follow-up, 96 patients in the bariatric surgery group and 780 patients in the nonsurgical control group had an incident obesity-associated cancer (incidence rate of 3.0 events vs 4.6 events, respectively, per 1000 person-years). The cumulative incidence of the primary end point at 10 years was 2.9% (95% CI, 2.2%-3.6%) in the bariatric surgery group and 4.9% (95% CI, 4.5%-5.3%) in the nonsurgical control group (absolute risk difference, 2.0% [95% CI, 1.2%-2.7%]; adjusted hazard ratio, 0.68 [95% CI, 0.53-0.87], P = .002). Cancer-related mortality occurred in 21 patients in the bariatric surgery group and 205 patients in the nonsurgical control group (incidence rate of 0.6 events vs 1.2 events, respectively, per 1000 person-years). The cumulative incidence of cancer-related mortality at 10 years was 0.8% (95% CI, 0.4%-1.2%) in the bariatric surgery group and 1.4% (95% CI, 1.1%-1.6%) in the nonsurgical control group (absolute risk difference, 0.6% [95% CI, 0.1%-1.0%]; adjusted hazard ratio, 0.52 [95% CI, 0.31-0.88], P = .01). Conclusions and Relevance: Among adults with obesity, bariatric surgery compared with no surgery was associated with a significantly lower incidence of obesity-associated cancer and cancer-related mortality.

Obesidad en la mortalidad de pacientes con insuficiencia cardiaca y fracción de eyección reducida / Obesity in the mortality of patients with heart failure and reduced ejection fraction

Introducción: La asociación entre obesidad y menor mortalidad en pacientes con insuficiencia cardiaca y fracción de eyección del ventrículo izquierdo es controversial. Objetivo: Evaluar la asociación entre obesidad y mortalidad en pacientes con insuficiencia cardiaca y fracción de eyección reducida. Métodos: Se realizó un estudio observacional de cohorte prospectivo en pacientes con insuficiencia cardiaca y fracción de eyección reducida en el período comprendido entre enero del 2010 y diciembre de 2020. La muestra quedó conformada por 173 pacientes. Se evaluó la supervivencia mediante el método de Kaplan-Meier, para estimar el efecto del pronóstico de la variable obesidad sobre la mortalidad. Se utilizó el modelo de regresión de Cox. Resultados: Se observó que los pacientes obesos al año de seguimiento tuvieron mejor supervivencia que los que presentaron normopeso (0,6 versus 0,8) a los cinco años presentaron similar supervivencia los tres subgrupos de índice masa corporal (0,6), la mayor mortalidad la presentaron los pacientes bajo peso. La curva de éstos últimos, se distancia del resto de las categorías de IMC, Log Rank p= 0,001. En el modelo de regresión de Cox la obesidad presentó un odd ration OR=´1,159 p=0,648 (intervalo de confianza de 0,615-2,181). Conclusiones: En los pacientes con insuficiencia cardiaca con fracción de eyección reducida no se observó el fenómeno de obesidad paradójica en relación a la mortalidad(AU)

Introduction: The association between obesity and lower mortality in patients with heart failure and left ventricular ejection fraction is controversial. Objective: To evaluate the association between obesity and mortality in patients with heart failure and reduced ejection fraction. Methods: An observational prospective cohort study was carried out, from January 2010 to December 2020, in patients with heart failure and reduced ejection fraction. The sample was made up of 173 patients. Survival was evaluated using Kaplan-Meier method to estimate the prognostic effect of the obesity variable on mortality. Cox regression model was used. Results: It was observed that obese patients at one year of follow-up had better survival than those with normal weight (0.6 versus 0.8). At five years, the three subgroups of body mass index (0.6) showed similar survival and the highest mortality was observed by low weight patients. The curve of the latter differs from the rest of the BMI categories, Log Rank p=0.001. In the Cox regression model, obesity had an odds ratio OR=´1.159 p=0.648 (confidence interval 0.615-2.181). Conclusions: In patients with heart failure with reduced ejection fraction, the phenomenon of paradoxical obesity was not observed in relation to mortality(AU)

Risk of hospitalization and mortality due to COVID-19 in people with obesity: An analysis of data from a Brazilian state.

The aim of this article is to assess the odds ratio of hospitalization and mortality due to COVID-19 in people with obesity using data from residents of Espírito Santo, Brazil. An observational, quantitative, cross-sectional study was carried out from the database available on the official channel of the State Health Secretariat of Espírito Santo. Crude odds ratio estimates (ORs) referring to the association between variables were calculated, as well as adjusted odds ratios (adjusted odds ratios-OR adj.) and their respective 95% confidence intervals (CI 95%). The results indicate that men, non-white, no education or with lower education level and age over 40 years old were more likely to be hospitalized and died of COVID-19. People with obesity are at risk of hospitalization and death due to COVID-19 54% and 113% higher than people who do not have obesity. People with obesity had a higher chance of hospitalization when they were over 40 years old, had breathing difficulty, and the comorbidities diabetes (2.18 higher) and kidney disease (4.10 higher). The odds ratio of death for people with obesity over 60 years old was 12.51 higher, and those who were hospitalized was 17.9 higher compared to those who were not hospitalized.

Cardiorespiratory Fitness, BMI, Mortality, and Cardiovascular Disease in Adults with Overweight/Obesity and Type 2 Diabetes.

INTRODUCTION: We estimated the effects of cardiorespiratory fitness (CRF) and body mass index (BMI) at baseline on mortality and cardiovascular disease events in people with type 2 diabetes who participated in the Look AHEAD randomized clinical trial. METHODS: Look AHEAD compared effects of an intensive lifestyle intervention with diabetes support and education on cardiovascular disease events in 5145 adults age 45-76 yr with overweight/obesity and type 2 diabetes. In 4773 participants, we performed a secondary analysis of the association of baseline CRF during maximal treadmill test (expressed as metabolic equivalents (METs)) on mortality and cardiovascular disease events during a mean follow-up of 9.2 yr. RESULTS: The mean (SD) CRF was 7.2 (2.0) METs. Adjusted for age, sex, race/ethnicity, BMI, intervention group, and ß-blocker use, all-cause mortality rate was 30% lower per SD greater METs (hazard ratio (HR) = 0.70 (95% confidence interval, 0.60 to 0.81); rate difference (RD), -2.71 deaths/1000 person-years (95% confidence interval, -3.79 to -1.63)). Similarly, an SD greater METs predicted lower cardiovascular disease mortality (HR, 0.45; RD, -1.65 cases/1000 person-years) and a composite cardiovascular outcome (HR, 0.72; RD, -6.38). Effects of METs were homogeneous on the HR scale for most baseline variables and outcomes but heterogeneous for many on the RD scale, with greater RD in subgroups at greater risk of the outcomes. For example, all-cause mortality was lower by 7.6 deaths/1000 person-years per SD greater METs in those with a history of cardiovascular disease at baseline but lower by only 1.6 in those without such history. BMI adjusted for CRF had little or no effect on these outcomes. CONCLUSIONS: Greater CRF is associated with reduced risks of mortality and cardiovascular disease events.

A population-based cohort study of obesity, ethnicity and COVID-19 mortality in 12.6 million adults in England.

Obesity and ethnicity are known risk factors for COVID-19 outcomes, but their combination has not been extensively examined. We investigate the association between body mass index (BMI) and COVID-19 mortality across different ethnic groups using linked national Census, electronic health records and mortality data for adults in England from the start of pandemic (January 2020) to December 2020. There were 30,067 (0.27%), 1,208 (0.29%), 1,831 (0.29%), 845 (0.18%) COVID-19 deaths in white, Black, South Asian and other ethnic minority groups, respectively. Here we show that BMI was more strongly associated with COVID-19 mortality in ethnic minority groups, resulting in an ethnic risk of COVID-19 mortality that was dependant on BMI. The estimated risk of COVID-19 mortality at a BMI of 40 kg/m2 in white ethnicities was equivalent to the risk observed at a BMI of 30.1 kg/m2, 27.0 kg/m2, and 32.2 kg/m2 in Black, South Asian and other ethnic minority groups, respectively.

Association between dairy protein and body composition in middle-aged and older women: A community-based, 12-year, prospective cohort study.

BACKGROUND & AIMS: Changes in body composition during aging include decreased muscle mass and increased fat mass. Women with low muscle mass with abdominal obesity (LMAO), in particular, could be at higher risk of morbidities and mortality than those with either sarcopenia or obesity alone. Dairy products, which contain whey protein and all essential amino acids, could have a beneficial role in preserving muscle mass and reducing obesity. We aimed to analyze the association between dairy protein and the development of LMAO in women using a large-scale, community-based prospective cohort. METHODS: Our analysis included 4251 women from the Korean Genome and Epidemiology Study. Participants were categorized into three groups by the tertile of dairy protein intake, which was assessed using a semi-quantitative 103-food item food frequency questionnaire. Appendicular skeletal muscle mass was estimated using the anthropometric equation. Low muscle mass (LM) was defined as a muscle mass of less than 15 kg in women. Abdominal obesity (AO) was defined as a weight to height ratio of 0.58 or greater. LMAO was defined as LM in combination with AO. Multiple Cox hazard regression analysis was conducted to examine associations between dairy protein intake and incident LMAO. RESULTS: During follow-up (mean, 9.6 years), 280 women newly developed LMAO. According to Cox proportional regression models, the hazard ratios (95% confidence interval) for incident LMAO in the middle and highest tertiles were 0.89 (0.74-1.06) and 0.71 (0.59-0.86), compared with lowest tertile, after adjusting for confounding variables. CONCLUSIONS: These findings indicate that high dairy protein intake is inversely related with LMAO development in Korean women. Dairy protein intake could be effective in preventing incident LMAO.

Gene and metabolite expression dependence on body mass index in human myocardium.

We hypothesized that body mass index (BMI) dependent changes in myocardial gene expression and energy-related metabolites underlie the biphasic association between BMI and mortality (the obesity paradox) in cardiac surgery. We performed transcriptome profiling and measured a panel of 144 metabolites in 53 and 55, respectively, myocardial biopsies from a cohort of sixty-six adult patients undergoing coronary artery bypass grafting (registration: NCT02908009). The initial analysis identified 239 transcripts with biphasic BMI dependence. 120 displayed u-shape and 119 n-shape expression patterns. The identified local minima or maxima peaked at BMI 28-29. Based on these results and to best fit the WHO classification, we grouped the patients into three groups: BMI < 25, 25 ≤ BMI ≤ 32, and BMI > 32. The analysis indicated that protein translation-related pathways were downregulated in 25 ≤ BMI ≤ 32 compared with BMI < 25 patients. Muscle contraction transcripts were upregulated in 25 ≤ BMI ≤ 32 patients, and cholesterol synthesis and innate immunity transcripts were upregulated in the BMI > 32 group. Transcripts involved in translation, muscle contraction and lipid metabolism also formed distinct correlation networks with biphasic dependence on BMI. Metabolite analysis identified acylcarnitines and ribose-5-phosphate increasing in the BMI > 32 group and α-ketoglutarate increasing in the BMI < 25 group. Molecular differences in the myocardium mirror the biphasic relationship between BMI and mortality.

Current forecast of COVID-19 in Mexico: A Bayesian and machine learning approaches.

The COVID-19 pandemic has been widely spread and affected millions of people and caused hundreds of deaths worldwide, especially in patients with comorbilities and COVID-19. This manuscript aims to present models to predict, firstly, the number of coronavirus cases and secondly, the hospital care demand and mortality based on COVID-19 patients who have been diagnosed with other diseases. For the first part, I present a projection of the spread of coronavirus in Mexico, which is based on a contact tracing model using Bayesian inference. I investigate the health profile of individuals diagnosed with coronavirus to predict their type of patient care (inpatient or outpatient) and survival. Specifically, I analyze the comorbidity associated with coronavirus using Machine Learning. I have implemented two classifiers: I use the first classifier to predict the type of care procedure that a person diagnosed with coronavirus presenting chronic diseases will obtain (i.e. outpatient or hospitalised), in this way I estimate the hospital care demand; I use the second classifier to predict the survival or mortality of the patient (i.e. survived or deceased). I present two techniques to deal with these kinds of unbalanced datasets related to outpatient/hospitalised and survived/deceased cases (which occur in general for these types of coronavirus datasets) to obtain a better performance for the classification.

Time-varying association between body mass index and all-cause mortality in patients with hypertension.

BACKGROUND: Relationship between BMI and all-cause mortality in patients with hypertension remains controversial. This study aimed to evaluate the time-varying association between BMI in patients with hypertension and all-cause mortality. METHODS: This population-based cohort study included 212,394 Chinese adults with hypertension from 2007 to 2015 and was followed up until death, loss-to-follow-up, or December 31, 2018. According to the World Health Organization criteria for Asians, BMI was categorized into five groups: underweight (BMI < 18.5 kg/m2), normal weight (18.5-22.9 kg/m2), overweight (23-24.9 kg/m2), class I obesity (25-29.9 kg/m2) and class II obesity (BMI ≥ 30 kg/m2). Cox model was used to estimate the time-varying association of BMI on the risk of mortality by including the interaction term between BMI and time using restricted cubic spline. RESULTS: Compared with normal weight, underweight and class II obesity were associated with higher mortality (Hazard ratio [HRs] at 1 and 10 years of follow-up: 1.51 [95% CI: 1.39-1.65], and 1.27 (1.15-1.41) for underweight, respectively; 1.08 (0.96-1.21), and 1.16 (1.03-1.30) for class II obesity, respectively). However, overweight and class I obesity were associated with lower mortality, although the protective effects gradually attenuated over time (HRs at 1 and 10 years of follow-up: 0.85 (0.81-0.90), and 0.96 (0.91-1.02) for overweight, respectively; 0.80 (0.76-0.84), and 1.04 (0.99-1.10) for class I obesity, respectively). CONCLUSIONS: We found increased mortality among hypertensive patients with underweight and class II obesity while decreased mortality with overweight and class I obesity was observed during the first 5 years of follow-up. Management efforts for hypertension may target controlling body weight in a reasonable range for patients, and probably more attention should be given to underweight patients.

Clinical Characteristics and Outcomes of COVID-19 Patients with Overweight and Obesity: Turkish Nationwide Cohort Study (TurCObesity).

PURPOSE: While obesity is related to more severe outcomes of coronavirus disease 2019 (COVID-19), factors leading to poor prognosis still remain unclear. The present study evaluated the outcomes of COVID-19 patients who were overweight or obese and variables associated with severe disease in a large group of consecutive cases. METHODS: A nationwide retrospective cohort study was performed using the Turkish National Healthcare Database. Demographic characteristics, laboratory tests, comorbidities, and medications of patients registered between March 11 and May 30, 2020, were recorded. RESULTS: A total of 14, 625 patients (median age:42, IQR:26 years; female 57.4%) with normal weight (34.7%), overweight (35.6%), and obesity (29.7%) were included. Hospitalization, ICU admission, intubation/mechanical ventilation, pulmonary involvement, and mortality were significantly higher in patients who were overweight or obese. In adjusted analyses, both overweight (OR, 95% CI: 1.82, 1.04-3.21; p=0.037) and obesity (OR, 95% CI: 2.69, 1.02-1.05; p<0.001) were associated with a higher intubation/mechanical ventilation rate but only obesity was associated with increased mortality (OR, 95% CI: 2.56, 1.40-4.67; p=0.002). Old age, male gender, chronic kidney disease, and high C reactive protein levels were independently associated with COVID-19 mortality in overweight or obese patients. CONCLUSIONS: COVID-19 patients who were overweight or obese were more likely to have adverse outcomes but only obesity was a predictor of mortality. Such patients should receive urgent medical attention and active management, especially the elderly, men, and people with chronic kidney disease.

Understanding the Link Between Obesity and Severe COVID-19 Outcomes: Causal Mediation by Systemic Inflammatory Response.

BACKGROUND: Obesity is an established risk factor for severe COVID-19 outcomes. The mechanistic underpinnings of this association are not well-understood. OBJECTIVE: To evaluate the mediating role of systemic inflammation in obesity-associated COVID-19 outcomes. METHODS: This hospital-based, observational study included 3828 SARS-CoV-2-infected patients who were hospitalized February to May 2020 at Massachusetts General Hospital (MGH) or Columbia University Irving Medical Center/New York Presbyterian Hospital (CUIMC/NYP). We use mediation analysis to evaluate whether peak inflammatory biomarkers (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], D-dimer, ferritin, white blood cell count and interleukin-6) are in the causal pathway between obesity (BMI ≥ 30) and mechanical ventilation or death within 28 days of presentation to care. RESULTS: In the MGH cohort (n = 1202), obesity was associated with greater likelihood of ventilation or death (OR = 1.73; 95% CI = [1.25, 2.41]; P = 0.001) and higher peak CRP (P < 0.001) compared with nonobese patients. The estimated proportion of the association between obesity and ventilation or death mediated by CRP was 0.49 (P < 0.001). Evidence of mediation was more pronounced in patients < 65 years (proportion mediated = 0.52 [P < 0.001] vs 0.44 [P = 0.180]). Findings were more moderate but consistent for peak ESR. Mediation by other inflammatory markers was not supported. Results were replicated in CUIMC/NYP cohort (n = 2626). CONCLUSION: Findings support systemic inflammatory pathways in obesity-associated severe COVID-19 disease, particularly in patients < 65 years, captured by CRP and ESR. Contextualized in clinical trial findings, these results reveal therapeutic opportunity to target systemic inflammatory pathways and monitor interventions in high-risk subgroups and particularly obese patients.

The Relationship Between Obesity and Amputation-free Survival in Patients Undergoing Lower-limb Revascularisation for Chronic Limb-threatening Ischaemia: A Retrospective Cohort Study.

BACKGROUND: The obesity paradox is a well-documented phenomenon in cardiovascular disease, however it remains poorly understood. We aimed to investigate the relationship between body mass (as measured by body mass index [BMI]) and 1-year amputation-free survival (AFS) for patients undergoing lower limb revascularisation for chronic limb-threatening ischaemia (CLTI). METHODS: A retrospective analysis was undertaken of all consecutive patients undergoing lower limb revascularisation for CLTI at the Leicester Vascular Institute between February 2018-19. Baseline demographics and outcomes were collected using electronic records. BMI was stratified using the World Health Organization criteria. One-year AFS (composite of major amputation/death) was the primary outcome. Kaplan-Meier survival analysis and adjusted Cox's proportional hazard models were used to compare groups to patients of normal mass. RESULTS: One-hundred and ninety patients were included. Overall, no difference was identified in 1-year AFS across all groups (pooled P = 0.335). Compared to patients with normal BMI (n = 66), obese patients (n = 43) had a significantly lower adjusted combined risk of amputation/death (aHR 0.39, 95% CI 0.16-0.92, P = 0.032), however no significant differences were observed for overweight (aHR 0.89, 95% CI 0.47-1.70, P = 0.741), morbidly obese (aHR 1.15, 95% CI 0.41-3.20, P = 0.797) and underweight individuals (aHR 1.86, 95% CI 0.56-6.20, P = 0.314). CONCLUSIONS: In the context of CLTI, obesity is potentially associated with favourable amputation-free survival at 1 year, compared to normal body mass. The results of this study support the notion of an obesity paradox existing within CLTI and question whether current guidance on weight management requires a more patient-specific approach.

Aggregation and combination of cardiovascular risk factors and their association with 10-year all-cause mortality: the PERU MIGRANT Study.

OBJECTIVE: To estimate the association between the aggregation and pair-wise combination of selected cardiovascular risk factors (CVRF) and 10-year all-cause mortality. METHODS: Secondary data analysis of the PERU MIGRANT study, a prospective population-based cohort. Ten-year all-cause mortality was determined for participants originally enrolled in the PERU MIGRANT Study (baseline in 2007) through the National Registry of Identification and Civil Status. The CVRF included hypertension, type 2 diabetes mellitus, hypercholesterolemia, and overweight/obesity. Exposures were composed of both the aggregation of the selected CVRF (one, two, and three or more CVRF) and pair-wise combinations of CVRF. Cox regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (95% CI). FINDINGS: Of the 989 participants evaluated at baseline, 976 (98.8%) had information about vital status at 10 years of follow-up (9992.63 person-years), and 63 deaths were recorded. In the multivariable model, adjusting for sociodemographic and lifestyle variables, participants with two CVRF (HR: 2.48, 95% CI: 1.03-5.99), and those with three or more CVRF (HR: 3.93, 95% CI: 1.21-12.74) had higher all-cause mortality risk, compared to those without any CVRF. The pair-wise combinations associated with the highest risk of all-cause mortality, compared to those without such comorbidities, were hypertension with type 2 diabetes (HR: 11.67, 95% CI: 3.67-37.10), and hypertension with overweight/obesity (HR: 2.76, 95% CI: 1.18-6.71). CONCLUSIONS: The aggregation of two or more CVRF and the combination of hypertension with type 2 diabetes or overweight/obesity were associated with an increased risk of 10-year all-cause mortality. These risk profiles will inform primary and secondary prevention strategies to delay mortality from cardiovascular risk factors.

Association of Obesity on Outcomes of Hospitalized Patients with Cerebral Palsy.

OBJECTIVE: Among hospitalized adults with cerebral palsy (CP), it is unknown whether obesity is associated with clinical and resource utilization outcomes. We sought to identify the association of obesity on clinical and resource utilization outcomes in this population. METHODS: This retrospective cohort study analyzed years 2016 and 2017 of the Nationwide Inpatient Sample database and examined hospitalized adults with CP. Regression analyses were used to evaluate mortality and resource utilization. RESULTS: In total, 154,219 adults with CP were hospitalized. Among them, 13,475 (8.7%) had a secondary diagnosis for obesity. Patients with obesity were older (mean age ± standard error of the mean: 49.9 ± 0.18 versus 44.7 ± 0.18 years, P < 0.01), a greater proportion were female (60.7% vs 43.2%, P < 0.01), and were more likely to be insured by Medicare (65.2% vs 56.2%, P < 0.01). Patients with obesity had higher comorbidity burdens (Charlson comorbidity score ≥ 3: 22.3% vs 9.8%, P < 0.01). Those with obesity had lower mortality rates (1.6% vs 2.4%; P < 0.01). After adjustment for confounders, mortality for patients with obesity remained lower (adjusted odds ratio 0.5, 95% confidence interval [CI] 0.4-0.7, P < 0.01). Hospital charges (adjusted mean difference $2499, 95% CI $6202-$1202, P = 0.18) and length of stay (adjusted mean difference 0.01 days; 95% CI -0.28 to 0.31, P = 0.93) were not significantly different between the groups. CONCLUSIONS: Obesity was associated with reduced mortality among adult patients in the hospital who had CP. This finding is consistent with the obesity paradox that has been observed repeatedly in patients with other chronic diseases. Further studies investigating hospitalized patients with CP are needed to corroborate these findings.

Lipid-Lowering Drug Use and Cancer Incidence and Mortality in the ARIC Study.

Background: Lipid-lowering drugs, particularly statins, are associated with reduced incidence of certain cancers in some studies. Associations with cancer mortality are not well studied, and whether associations are similar across race is unknown. Methods: We conducted a prospective analysis of 12 997 cancer-free participants in the Atherosclerosis Risk in Communities Study who were never users at visit 1 (1987-1989). Ever use, duration of use, and age at first use were modeled as time-dependent variables using Cox regression to estimate associations with total, obesity- and smoking-associated, bladder, breast, colorectal, lung, and prostate cancer incidence and mortality. Results: We ascertained 3869 cancer cases and 1661 cancer deaths in 237 999 or more person-years. At 6 years of follow-up, 70.8% of lipid-lowering drug use was a statin. Compared with never use, ever use was associated with lower total, obesity- and smoking-associated cancer mortality and with colorectal cancer mortality (hazard ratio [HR] = 0.50, 95% confidence interval [CI] = 0.32 to 0.79) and incidence (HR = 0.69, 95% CI = 0.53 to 0.92). Inverse associations were consistent by sex and race. Shorter-term use was associated with bladder cancer incidence in men (<10 years: HR = 1.67, 95% CI = 1.02 to 2.73). First use at age 60 years or older was inversely associated with: total mortality, obesity- and smoking-associated mortality, and colorectal cancer mortality; and total incidence, obesity- and smoking-associated incidence, and breast, colorectal, and prostate cancer incidence. Conclusions: This study provides additional evidence for inverse associations between lipid-lowering drug use and cancer incidence and mortality but a positive association with bladder cancer incidence in men. Evaluation of the impact of chemoprevention strategies that include lipid-lowering drugs on population-level cancer burden is needed.