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Cardio-kidney-metabolic (CKM) syndrome is defined by the American Heart Association as the intersection between metabolic, renal and cardiovascular disease. Understanding the contemporary estimates of CKM related mortality and recent trends in the US is essential for developing targeted public interventions. We collected state-level and county-level CKM-associated age-adjusted premature cardiovascular mortality (aaCVM) (2010-2019) rates from the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER). We linked the county-level aaCVM with a multi-component social deprivation metric: the Social Deprivation Index (SDI: range 0-100) and grouped them as follows: I: 0-25, II: 26-50, III: 51-75, and IV: 76-100. We conducted pair-wise comparison of aaCVM between SDI groups with the multiplicity adjusted Wilcoxon test; we compared aaCVM in men versus women, metropolitan versus nonmetropolitan counties, and non-hispanic white versus non-hispanic black residents. In 3101 analyzed counties in the US, the median CKM associated aaCVM was 61 [interquartile range (IQR): 45, 82]/100 000. Mississippi (99/100 000) and Minnesota (33/100 000) had the highest and lowest values respectively. CKM associated aaMR increased across SDI groups [I - 45 (IQR: 36, 55)/100 000, II- 61 (IQR: 49, 77)/100 000, III- 77 (IQR: 61, 94)/100 000, IV- 89 (IQR: 70, 110)/100 000; all pair-wise p-values < 0.001]. Men had higher rates [85 (64, 91)/100 000] than women [41 (28, 58)/100 000](p-value < 0.001), metropolitan counties [54 (40, 72)/100 000] had lower rates than non-metropolitan counties [66 (49, 90)/100 000](p-value < 0.001), and non-Hispanic Black [110 (86, 137)/100 000] had higher aaMR than non-Hispanic White residents [59 (44, 78)/100 000](p-value < 0.001). In the US, CKM mortality remains high and disproportionately occurs in more socially deprived counties and non-metropolitan counties. Our inability to reduce CKM mortality rates over the study period highlights the need for targeted policy interventions to curb the ongoing high burden., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Low muscle mass is a risk factor for mortality in patients with chronic kidney disease (CKD). However, it is not clear to what extent low muscle mass contributes to this risk, either independently or in combination with metabolic abnormalities and frailty. This study used data from the National Health and Nutrition Examination Survey 1999-2006 and 2011-2018. Low muscle mass was defined as Appendicular Skeletal Mass Index < 7 kg/m 2 in men or < 5.5 kg/m 2 in women. The follow-up duration was from the first anthropometric and clinical measurements to death or the last follow-up. This study enrolled 2072 patients with CKD. Low muscle mass was associated with a lower risk of metabolic abnormalities, but was associated with an elevated mortality risk. Conversely, central obesity was associated with a higher likelihood of metabolic abnormalities and frailty, yet showed no significant association with mortality risk. Subsequently conducted mediation analysis indicated that the effect of low muscle mass on mortality was direct, not mediated by frailty and metabolic abnormalities. In spite of the inverse relationship between low muscle mass and metabolic abnormalities, low muscle mass are directly associated with an increased risk of all-cause mortality. Low muscle mass may directly contribute to mortality in patients with CKD, independent of metabolic abnormalities and frailty in these patients., (© 2024. The Author(s).)

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease. Body mass index (BMI) is the most used obesity index but has important limitations. The weight-adjusted waist index (WWI) is a novel obesity metric and accurately reflects body composition. We explored the association of WWI with all-cause and cardiovascular disease (CVD) mortality in MASLD., Methods: Adult participants with MASLD were included from NHANES 1999-2018. WWI was calculated by dividing the waist circumference (WC) by the square root of body weight. MASLD was diagnosed by the presence of hepatic steatosis and at least one cardiometabolic risk factor in the absence of other causes of steatosis. A fatty liver index ≥60 suggested the presence of hepatic steatosis. Mortality data was obtained by prospectively linking to the National Death Index. Multivariate Cox proportional hazards regression analyses were used to explore these associations and multiple adjustment models were constructed including crude, partial, and fully adjusted models., Results: After adjusting for all covariates including BMI, WWI remained positively and linearly associated with all-cause and CVD mortality in MASLD (hazard ratios [HR] 1.247 and 1.218, respectively). Higher WWI was associated with a significantly increased risk of mortality (both p for trend <0.05). There was an "obesity paradox" between BMI and all-cause mortality in MASLD, with significantly lower all-cause mortality in those with overweight/obesity compared to normal BMI (HR 0.625 and 0.596, respectively, p for trend = 0.024), and no association between BMI and CVD mortality. Interaction analyses indicated that these associations were influenced by several demographic variables and disease status. Time-dependent receiver operating characteristic curves indicated that the predictive value of WWI for mortality in MASLD was higher than that of BMI, WC, and waist-to-height ratio across all follow-up durations., Conclusions: WWI was positively and linearly associated with all-cause and CVD mortality in MASLD, whereas BMI did not accurately reflect mortality risk. WWI provided the optimal predictive value for mortality compared to traditional obesity indicators. These findings emphasize the potential use of WWI as a novel obesity indicator for mortality risk assessment, stratification, and prevention in MASLD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Yang, Zhan, Huang, Tian, Tian and Huang.)

Background and Aim: This study estimated the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) according to cardiometabolic risk factors. The long-term impacts of MASLD on all-cause and cardiometabolic-specific mortality were evaluated., Methods: We enrolled 343 816 adults aged ≥30 years who participated in a health screening program from 1997 through 2013. MASLD was identified on the basis of abdominal ultrasonography and metabolic profiles. The participants were further categorized by liver enzyme elevation. Baseline cardiometabolic comorbidities were classified on the basis of self-reported medication use and clinical seromarkers. All-cause and cardiometabolic-specific deaths were determined through computerized data linkage with nationwide death certifications until December 31, 2020., Results: The overall prevalence of MASLD was 36.4%. Among patients with MASLD, 35.9% had abnormal liver enzyme levels. Compared with patients without MASLD, abnormal liver enzymes were positively associated with cardiometabolic comorbidities in patients with MASLD (P for trend  < 0.001). After follow-up, patients with MASLD had a 9%-29% higher risk of all-cause, cardiovascular-related, or diabetes-related mortality. In the groups with MASLD and elevated and normal liver enzyme levels, the multivariate-adjusted hazard ratios for cardiovascular deaths were 1.14 (1.05-1.25) and 1.10 (1.03-1.17), respectively, and those for diabetes deaths were 1.42 (1.05-1.93) and 1.24 (0.98-1.57), respectively, compared with those in the non-MASLD group (P for trend  < 0.001)., Discussion: Individuals with MASLD and elevated liver enzyme levels exhibited significantly higher risks of all-cause and cardiometabolic deaths and should be monitored and given consultation on cardiometabolic modifications., (© 2024 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: Several reports show a significant association between metabolic dysfunction-associated steatotic liver disease (MASLD) and arterial stiffness (estimated pulse wave velocity [ePWV]) as a surrogate marker of vascular age. We investigate whether ePWV as arterial stiffness in MASLD is associated with all-cause/cause-specific mortality., Methods: This cohort study was based on the third National Health and Nutrition Examination Survey (NHANES, 1988-1994) and NHANES 2007-2014 and linked mortality datasets through 2019. Cox regression models assessed the association between ePWV categorized by quartile and all-cause/cause-specific mortality among individuals with MASLD., Results: During the follow-up of a median of 26.3 years (interquartile range: 19.9-27.9), higher levels of ePWV among individuals with MASLD were associated with increased all-cause mortality, which remained significant after adjusting for demographic, lifestyle, clinical, and metabolic risk factors. Furthermore, higher ePWV in MASLD was associated with higher cardiovascular mortality. There was a 44% (hazard ratio: 1.44, 95% confidence interval: 1.32-1.58) increase in all-cause mortality and a 53% (hazard ratio: 1.53, 95% confidence interval: 1.32-1.77) increase in cardiovascular mortality for every 1 m/s increase in ePWV in MASLD. However, there was no significant association between ePWV and cancer-related mortality. Sensitivity analyses using the NHANES 2007-2014 dataset showed results identical to the original analysis., Conclusion: Higher ePWV in MASLD was associated with a higher risk of all-cause and cardiovascular mortality beyond traditional cardiovascular risk factors. Screening for ePWV in individuals with MASLD may be an effective and beneficial approach to reducing all-cause and cardiovascular mortality., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Metabolic diseases contribute significantly to premature mortality worldwide, with increasing burdens observed among the working-age population (WAP). This study assessed global, regional, and national trends in metabolic disorders and associated mortality over three decades in WAP., Methods: Data from the Global Burden of Disease 2019 study were leveraged to assess global metabolism-associated mortality and six key metabolic risk factors in WAP from 1990-2019. An age-period-cohort model was employed to determine the overall percentage change in mortality., Results: The 2019 global metabolic risk-related mortality rate in WAP rose significantly by 50.73%, while the age-standardized mortality rate declined by 21.5%. India, China, Indonesia, the USA, and the Russian Federation were the top contributing countries to mortality in WAP, accounting for 51.01% of the total. High systolic blood pressure (HSBP), high body mass index (HBMI), and high fasting plasma glucose (HFPG) were the top metabolic risk factors for the highest mortality rates. Adverse trends in HBMI-associated mortality were observed, particularly in lower sociodemographic index (SDI) regions. HFPG-related mortality declined globally but increased in older age groups in lower SDI countries., Conclusions: Despite a general decline in metabolic risk-related deaths in WAP, increasing HBMI- and HFPG-related mortality in lower SDI areas poses ongoing public health challenges. Developing nations should prioritize interventions addressing HBMI and HFPG to mitigate mortality risks in WAP., Competing Interests: Declaration of competing interest The authors declare that no conflict of interest exists., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., (© 2024. The Author(s).)

Objectives: The global burden of non-alcoholic fatty liver disease (NAFLD) is rising. An alternative term, metabolic dysfunction-associated fatty liver disease (MAFLD), instead highlights the associated metabolic risks. This cohort study examined patient classifications under NAFLD and MAFLD criteria and their associations with all-cause mortality., Methods: Participants who attended a paid health check-up (2012-2015) were included. Hepatic steatosis (HS) was diagnosed ultrasonographically. NAFLD was defined as HS without secondary causes, while MAFLD involved HS with overweight/obesity, type 2 diabetes mellitus, or ≥2 metabolic dysfunctions. Mortality was tracked via the Taiwan Death Registry until November 30, 2022., Results: Of 118,915 participants, 36.9% had NAFLD, 40.2% had MAFLD, and 32.9% met both definitions. Participants with NAFLD alone had lower mortality, and those with MAFLD alone had higher mortality, than individuals with both conditions. After adjustment for potential confounders, the hazard ratios (HRs) for all-cause mortality were 1.08 (95% confidence interval [CI], 0.78 to 1.48) for NAFLD alone and 1.26 (95% CI, 1.09 to 1.47) for MAFLD alone, relative to both conditions. Advanced fibrosis conferred greater mortality risk, with HRs of 1.93 (95% CI, 1.44 to 2.58) and 2.08 (95% CI, 1.61 to 2.70) for advanced fibrotic NAFLD and MAFLD, respectively. Key mortality risk factors for NAFLD and MAFLD included older age, unmarried status, higher body mass index, smoking, diabetes mellitus, chronic kidney disease, and advanced fibrosis., Conclusions: All-cause mortality in NAFLD and/or MAFLD was linked to cardiometabolic covariates, with risk attenuated after multivariable adjustment. A high fibrosis-4 index score, indicating fibrosis, could identify fatty liver disease cases involving elevated mortality risk.

Introduction: Genetic pleiotropy, in which the same genes affect two or more traits, may partially explain the frequently observed associations between high physical activity (PA) and later reduced morbidity or mortality. This study investigated associations between PA polygenic risk scores (PRS) and cardiometabolic diseases among the Finnish population., Methods: PRS for device-measured overall PA were adapted to a FinnGen study cohort of 218,792 individuals with genomewide genotyping and extensive digital longitudinal health register data. Associations between PA PRS and body mass index, diseases, and mortality were analyzed with linear and logistic regression models., Results: A high PA PRS predicted a lower body mass index (β = -0.025 kg·m-2 per one SD change in PA PRS, SE = 0.013, P = 1.87 × 10-80). The PA PRS also predicted a lower risk for diseases that typically develop later in life or not at all among highly active individuals. A lower disease risk was systematically observed for cardiovascular diseases (odds ratio [OR] per 1 SD change in PA PRS = 0.95, P = 9.5 × 10-19) and, for example, hypertension [OR = 0.93, P = 2.7 × 10-44), type 2 diabetes (OR = 0.91, P = 4.1 × 10-42), and coronary heart disease (OR = 0.95, P = 1.2 × 10-9). Participants with high PA PRS had also lower mortality risk (OR = 0.97, P = 0.0003)., Conclusions: Genetically less active persons are at a higher risk of developing cardiometabolic diseases, which may partly explain the previously observed associations between low PA and higher disease and mortality risk. The same inherited physical fitness and metabolism-related mechanisms may be associated both with PA levels and with cardiometabolic disease risk., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)

Background & Aims: Recently, international experts proposed redefining non-alcoholic fatty liver disease (NAFLD) as metabolic dysfunction-associated fatty liver disease (MAFLD), based on modified criteria. It is suspected that outcomes such as mortality may differ for these clinical entities. We studied the impact of MAFLD and NAFLD on all-cause and cause-specific mortality in US adults., Methods: We analyzed data from 7,761 participants in the Third National Health and Nutrition Examination Survey and their linked mortality through 2015. NAFLD was diagnosed by ultrasonographic evidence of hepatic steatosis without other known liver diseases. MAFLD was defined based on the criteria proposed by an international expert panel. The Cox proportional hazard model was used to study all-cause mortality and cause-specific mortality between MAFLD and NAFLD, with adjustments for known risk factors., Results: During a median follow-up of 23 years, individuals with MAFLD had a 17% higher risk of all-cause mortality (hazard ratio [HR] 1.17; 95% CI 1.04-1.32). Furthermore, MAFLD was associated with a higher risk of cardiovascular mortality. NAFLD per se did not increase the risk of all-cause mortality. Individuals who met both definitions had a higher risk of all-cause mortality (HR 1.13, 95% CI 1.00-1.26), while individuals who met the definition for MAFLD but not NAFLD had a 1.7-fold higher risk of all-cause mortality (HR 1.66, 95% CI 1.19-2.32). Estimates for all-cause mortality were higher for those with advanced fibrosis and MAFLD than for those with advanced fibrosis and NAFLD., Conclusions: In this US population-based study, MAFLD was associated with an increased risk of all-cause mortality, while NAFLD demonstrated no association with all-cause mortality after adjusting for metabolic risk factors., Lay Summary: Our findings provide further support for the idea that non-alcoholic fatty liver disease (NAFLD) is a part of a broader multi-system disease that also includes obesity, diabetes, high blood pressure, and high cholesterol. Therefore, re-defining NAFLD as metabolic dysfunction-associated fatty liver disease (MAFLD) may help improve our understanding of predictors that increase the risk of death., Competing Interests: Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Context: While adrenal adenomas have been linked with cardiovascular morbidity in convenience samples of patients from specialized referral centers, large-scale population-based data are lacking., Objective: To determine the prevalence and incidence of cardiometabolic disease and assess mortality in a population-based cohort of patients with adrenal adenomas., Design: Population-based cohort study., Setting: Olmsted County, Minnesota, USA., Patients: Patients diagnosed with adrenal adenomas without overt hormone excess and age- and sex-matched referent subjects without adrenal adenomas., Main Outcome Measure: Prevalence, incidence of cardiometabolic outcomes, mortality., Results: (Adrenal adenomas were diagnosed in 1004 patients (58% women, median age 63 years) from 1/01/1995 to 12/31/2017. At baseline, patients with adrenal adenomas were more likely to have hypertension [adjusted odds ratio (aOR) 1.96, 95% CI 1.58-2.44], dysglycemia (aOR 1.63, 95% CI 1.33-2.00), peripheral vascular disease (aOR 1.59, 95% CI 1.32-2.06), heart failure (aOR 1.64, 95% CI 1.15-2.33), and myocardial infarction (aOR 1.50, 95% CI 1.02-2.22) compared to referent subjects. During median follow-up of 6.8 years, patients with adrenal adenomas were more likely than referent subjects to develop de novo chronic kidney disease [adjusted hazard ratio (aHR) 1.46, 95% CI 1.14-1.86], cardiac arrhythmia (aHR 1.31, 95% CI 1.08-1.58), peripheral vascular disease (aHR 1.28, 95% CI 1.05-1.55), cardiovascular events (aHR 1.33, 95% CI 1.01-1.73), and venous thromboembolic events (aHR 2.15, 95% CI 1.48-3.13). Adjusted mortality was similar between the 2 groups., Conclusion: Adrenal adenomas are associated with an increased prevalence and incidence of adverse cardiometabolic outcomes in a population-based cohort., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: It remains uncertain if prior use of oral anticoagulants (OACs) in COVID-19 outpatients with multimorbidity impacts prognosis, especially if cardiometabolic diseases are present. Clinical outcomes 30-days after COVID-19 diagnosis were compared between outpatients with cardiometabolic disease receiving vitamin K antagonist (VKA) or direct-acting OAC (DOAC) therapy at time of COVID-19 diagnosis., Methods: A study was conducted using TriNetX, a global federated health research network. Adult outpatients with cardiometabolic disease (i.e. diabetes mellitus and any disease of the circulatory system) treated with VKAs or DOACs at time of COVID-19 diagnosis between 20-Jan-2020 and 15-Feb-2021 were included. Propensity score matching (PSM) was used to balance cohorts receiving VKAs and DOACs. The primary outcomes were all-cause mortality, intensive care unit (ICU) admission/mechanical ventilation (MV) necessity, intracranial haemorrhage (ICH)/gastrointestinal bleeding, and the composite of any arterial or venous thrombotic event(s) at 30-days after COVID-19 diagnosis., Results: 2275 patients were included. After PSM, 1270 patients remained in the study (635 on VKAs; 635 on DOACs). VKA-treated patients had similar risks and 30-day event-free survival than patients on DOACs regarding all-cause mortality, ICU admission/MV necessity, and ICH/gastrointestinal bleeding. The risk of any arterial or venous thrombotic event was 43% higher in the VKA cohort (hazard ratio 1.43, 95% confidence interval 1.03-1.98; Log-Rank test p = 0.029)., Conclusion: In COVID-19 outpatients with cardiometabolic diseases, prior use of DOAC therapy compared to VKA therapy at the time of COVID-19 diagnosis demonstrated lower risk of arterial or venous thrombotic outcomes, without increasing the risk of bleeding., (© 2021. The Author(s).)

Background: The Coronavirus disease 2019 (COVID-19) pandemic has led to a dramatic crisis in health care systems worldwide. These may have significant implications for the management of cardiometabolic diseases. We conducted a systematic review of published evidence to assess the indirect impact of the COVID-19 pandemic on hospitalisations for cardiovascular diseases and their management., Methods: Studies that evaluated volume of hospitalisations for cardiometabolic conditions and their management with comparisons between the COVID-19 and pre-COVID periods were identified from MEDLINE, Embase and the reference list of relevant studies from January 2020 to 25 February 2021., Results: We identified 103 observational studies, with most studies assessing hospitalisations for acute cardiovascular conditions such as acute coronary syndrome, ischemic strokes and heart failure. About 89% of studies reported a decline in hospitalisations during the pandemic compared to pre-pandemic times, with reductions ranging from 20.2 to 73%. Severe presentation, less utilization of cardiovascular procedures, and longer patient- and healthcare-related delays were common during the pandemic. Most studies reported shorter length of hospital stay during the pandemic than before the pandemic (1-8 vs 2-12 days) or no difference in length of stay. Most studies reported no change in in-hospital mortality among hospitalised patients., Conclusion: Clinical care of patients for acute cardiovascular conditions, their management and outcomes have been adversely impacted by the COVID-19 pandemic. Patients should be educated via population-wide approaches on the need for timely medical contact and health systems should put strategies in place to provide timely care to patients at high risk., Systematic Review Registration: PROSPERO 2021: CRD42021236102., (Copyright © 2021 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Background: Cardiovascular disease (CVD) is the leading cause of death among non-communicable diseases in South Africa. Several metabolic risk factors contribute to the development of CVD. Informal workers such as waste pickers could be unhealthy lifestyle naive, and most public health research on CVD does not include this understudied population. This study estimated the 10-year risk of fatal CVD and its association with metabolic risk factors in an understudied study population of waste pickers in Johannesburg, South Africa., Methods: A cross-sectional survey was conducted among waste pickers in two landfill sites in Johannesburg. We used the Systematic Coronary Risk Evaluation (SCORE) risk charts to estimate the 10-year risk of fatal CVD. We then employed ordinary least squares regression to assess the association between the 10-year risk of fatal CVD with metabolic risk factors. Other variables adjusted in the regression model were HIV status, education, income, injuries from work, clinic visits in the previous 12 months, and alcohol consumption., Results: A total of 370 waste pickers were included in this analysis, 265 (73.41%) were males. The mean age of the participants was 34 years. The majority were between the age of 20 and 39 years. More than 55% of the waste pickers did not visit a clinic in the previous 12 months, and 68.57% were smoking. The 10-year survival probability from CVD was more than 99% for both males and females. In the multivariable regression model, elevated blood glucose showed a non-significant increase in the mean percentage of 10-year risk of fatal CVD. Waste pickers who were overweight/obese, and hypertensive had high statistically significant mean percentages of the 10-year risk of fatal CVD compared to those who did not have the metabolic risk factors., Conclusions: Prevention of 10-year risk of fatal CVD in this understudied population of waste pickers should target the control of obesity, hypertension, and diabetes. Health awareness and education for waste pickers will be an important step in reducing the burden of these metabolic risk factors. We further recommend that health systems should recognize waste pickers as a high-risk group and consider extensive CVDs surveillance., (© 2021. The Author(s).)

Previous studies link obesity and components of metabolic health, such as hypertension or inflammation, to increased hospitalizations and mortality of patients with COVID-19. Here, in two overlapping samples of over 1,000 individuals from the UK Biobank we investigate whether metabolic health as measured by waist circumference, dyslipidemia, hypertension, type 2 diabetes, and systemic inflammation is related to increased COVID-19 infection and mortality rate. Using logistic regression and controlling for confounding variables such as socioeconomic status, age, sex or ethnicity, we find that individuals with worse metabolic health (measured on average eleven years prior to 2020) have an increased risk for COVID-19-related death (adjusted odds ratio: 1.75). We also find that specific factors contributing to increased mortality are increased serum glucose levels, systolic blood pressure and waist circumference., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Morys and Dagher.)

The COVID-19 pandemic forced healthcare services organization to adjust to mutating healthcare needs. Not exhaustive data are available on the consequences of this on non-COVID-19 patients. The aim of this study was to assess the impact of the pandemic on non-COVID-19 patients living in a one-million inhabitants' area in Northern Italy (Bologna Metropolitan Area-BMA), analyzing time trends of Emergency Department (ED) visits, hospitalizations and mortality. We conducted a retrospective observational study using data extracted from BMA healthcare informative systems. Weekly trends of ED visits, hospitalizations, in- and out-of-hospital, all-cause and cause-specific mortality between December 1st, 2019 to May 31st, 2020, were compared with those of the same period of the previous year. Non-COVID-19 ED visits and hospitalizations showed a stable trend until the first Italian case of COVID-19 has been recorded, on February 19th, 2020, when they dropped simultaneously. The reduction of ED visits was observed in all age groups and across all severity and diagnosis groups. In the lockdown period a significant increase was found in overall out-of-hospital mortality (43.2%) and cause-specific out-of-hospital mortality related to neoplasms (76.7%), endocrine, nutritional and metabolic (79.5%) as well as cardiovascular (32.7%) diseases. The pandemic caused a sudden drop of ED visits and hospitalizations of non-COVID-19 patients during the lockdown period, and a concurrent increase in out-of-hospital mortality mainly driven by deaths for neoplasms, cardiovascular and endocrine diseases. As recurrencies of the COVID-19 pandemic are underway, the scenario described in this study might be useful to understand both the population reaction and the healthcare system response at the early phases of the pandemic in terms of reduced demand of care and systems capability in intercepting it., Competing Interests: The authors have declared that no competing interests exist.

There is growing interest in the potential health-related effects of moderate alcohol consumption and, specifically, of beer. This review provides an assessment of beer-associated effects on cardiovascular and metabolic risk factors to identify a consumption level that can be considered "moderate". We identified all prospective clinical studies and systematic reviews that evaluated the health effects of beer published between January 2007 and April 2020. Five of six selected studies found a protective effect of moderate alcohol drinking on cardiovascular disease (beer up to 385 g/week) vs. abstainers or occasional drinkers. Four out of five papers showed an association between moderate alcohol consumption (beer intake of 84 g alcohol/week) and decreased mortality risk. We concluded that moderate beer consumption of up to 16 g alcohol/day (1 drink/day) for women and 28 g/day (1-2 drinks/day) for men is associated with decreased incidence of cardiovascular disease and overall mortality, among other metabolic health benefits.

Aging leads to a number of disorders caused by cellular senescence, tissue damage, and organ dysfunction. It has been reported that anti-inflammatory and insulin-sensitizing compounds delay, or reverse, the aging process and prevent metabolic disorders, neurodegenerative disease, and muscle atrophy, improving healthspan and extending lifespan. Here we investigated the effects of PPARγ agonists in preventing aging and increasing longevity, given their known properties in lowering inflammation and decreasing glycemia. Our molecular and physiological studies show that long-term treatment of mice at 14 months of age with low doses of the PPARγ ligand rosiglitazone (Rosi) improved glucose metabolism and mitochondrial functionality. These effects were associated with decreased inflammation and reduced tissue atrophy, improved cognitive function, and diminished anxiety- and depression-like conditions, without any adverse effects on cardiac and skeletal functionality. Furthermore, Rosi treatment of mice started when they were 14 months old was associated with lifespan extension. A retrospective analysis of the effects of the PPARγ agonist pioglitazone (Pio) on longevity showed decreased mortality in patients receiving Pio compared to those receiving a PPARγ-independent insulin secretagogue glimepiride. Taken together, these data suggest the possibility of using PPARγ agonists to promote healthy aging and extend lifespan., (© 2020 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Retrospective analysis of diagnostic findings from 30 marine-foraging river otter (Lontra canadensis) carcasses opportunistically acquired between 2003 and 2013 revealed trauma as the most common cause of mortality (47%). Within this focal population, causes of trauma included vehicular, gunshot, and one case of suspect intraspecific aggression. Other causes of death included idiopathic (20%), infectious (13%), metabolic (10%), nutritional (7%), and neoplasia (3%). One case of neoplasia, a pancreatic islet cell adenoma, was identified in a 12-yr-old female. In six animals, diffuse renal interstitial fibrosis and multifocal glomerulosclerosis of unknown clinical significance were noted., (© Wildlife Disease Association 2020.)

Androgen deprivation therapy (ADT) has been the cornerstone of prostate cancer treatment. ADT delays cancer progression, alleviates cancer-related symptoms, and is associated with survival gains. Despite these established benefits, the extended duration of therapy comes with known side effects. Furthermore, research from the past decade has generated increased awareness for more potentially lethal cardiometabolic consequences of ADT. In this review, we explore the relationship between ADT and cardiometabolic effects. Current literature on this complex relationship remains conflicting, due to a variety of factors, including study design (randomized vs. observational), treatment decision-making, and patient factors. Looking to the future, a combination of well-designed, randomized controlled trials and high-quality, real-world evidence are needed to definitely establish any ADT cardiovascular safety signal and to evaluate the efficacy of potential screening and therapeutic interventions. Furthermore, a collaborative, integrated approach among all health care professionals is critical to accurately delineate patients' potential risk/benefit treatment options.

The impact of acute and chronic graft-versus-host disease (GVHD) on clinical outcomes was retrospectively analyzed in 960 patients with non-malignant diseases (NMD) who underwent a first allogeneic hematopoietic stem cell transplantation (HSCT). Grade III-IV acute GVHD (but not grade I-II) was significantly associated with a lower rate of overall survival (OS), and higher non-relapse mortality (NRM) than that seen in patients without acute GVHD. Extensive (but not limited) GVHD was significantly associated with a lower OS rate and higher NRM than that seen in patients without chronic GVHD. Any grade of acute (but not chronic) GVHD was significantly associated with a lower incidence of relapse and a lower proportion of patients requiring a second HSCT or donor lymphocyte infusion for graft failure or mixed chimerism, but its impact on OS was almost negligible. Acute GVHD was significantly associated with lower OS rates in all disease groups, whereas chronic GVHD was significantly associated with lower OS rates in the primary immunodeficiency and histiocytosis groups. In conclusion, acute and chronic GVHD, even if mild, was associated with reduced OS in patients receiving HSCT for NMD and effective strategies should, therefore, be implemented to minimize GVHD.

Metabolic disorders are highly prevalent in kidney transplant candidates and recipients and can adversely affect post-transplant graft outcomes. Management of diabetes, hyperparathyroidism, and obesity presents distinct opportunities to optimize patients both before and after transplant as well as the ability to track objective data over time to assess a patient's ability to partner effectively with the health care team and adhere to complex treatment regimens. Optimization of these particular disorders can most dramatically decrease the risk of surgical and cardiovascular complications post-transplant. Approximately 60% of nondiabetic patients experience hyperglycemia in the immediate post-transplant phase. Multiple risk factors have been identified related to development of new onset diabetes after transplant, and it is estimated that upward of 7%-30% of patients will develop new onset diabetes within the first year post-transplant. There are a number of medications studied in the kidney transplant population for diabetes management, and recent data and the risks and benefits of each regimen should be optimized. Secondary hyperparathyroidism occurs in most patients with CKD and can persist after kidney transplant in up to 66% of patients, despite an initial decrease in parathyroid hormone levels. Parathyroidectomy and medical management are the options for treatment of secondary hyperparathyroidism, but there is no randomized, controlled trial providing clear recommendations for optimal management, and patient-specific factors should be considered. Obesity is the most common metabolic disorder affecting the transplant population in both the pre- and post-transplant phases of care. Not only does obesity have associations and interactions with comorbid illnesses, such as diabetes, dyslipidemia, and cardiovascular disease, all of which increase morbidity and mortality post-transplant, but it also is intimately inter-related with access to transplantation for patients with kidney failure. We review these metabolic disorders and their management, including data in patients with kidney transplants., (Copyright © 2020 by the American Society of Nephrology.)

Objectives: Diabetes mellitus (DM) is a global health problem with associated high morbidity and mortality. This study was a retrospective review of post-mortem examination findings of hospitalised patients with DM for causes of death., Materials and Methods: A retrospective, cross-sectional autopsy review of all the patients with DM in our hospital between January 2008 and December 2017 was conducted. The causes of death were classified into cardiovascular, cerebrovascular, acute diabetic emergencies, infection, cancers and unnatural deaths. The demographic data and clinicopathological parameters were extracted, and the data were analysed using the SPSS software version 23., Results: A total of 1092 cases of autopsy were done within the study period, of which 91 cases were on patients with diabetes accounting for 8.3%. Infections with sepsis were the major cause of death, accounting for 51.6% followed by cardiovascular diseases (16.5%), cancers (14.3%), acute diabetic emergencies (6.6%) and cerebrovascular accidents (6.6%), with renal complications and road traffic accidents accounting for 2.2% each. Patients' age ranged from 31 to 84 years, with a modal age of 57 years. There was a male predominance with a male-to-female ratio of 1.5:1. Systemic hypertension co-morbidity was statistically significantly more common in patients aged 60 and above (P = 0.035). The most common lesion observed in the kidneys was benign nephrosclerosis (43.2%)., Conclusions: This study suggests that majority of our patients with diabetes mellitus die from infections with attendant sepsis. Older patients appear to have co-morbid systemic hypertension. Patient education on infection prevention and prompt treatment might be life-saving., Competing Interests: None

The gut microbiota is involved in metabolic disorders induced by androgen deficiency after sexual maturation in males (late-onset hypogonadism). However, its role in the energy metabolism of congenital androgen deficiency (e.g., androgen-insensitive syndrome) remains elusive. Here, we examined the link between the gut microbiota and metabolic disease symptoms in androgen receptor knockout (ARKO) mouse by administering high-fat diet (HFD) and/or antibiotics. HFD-fed male, but not standard diet-fed male or HFD-fed female, ARKO mice exhibited increased feed efficiency, obesity with increased visceral adipocyte mass and hypertrophy, hepatic steatosis, glucose intolerance, insulin resistance, and loss of thigh muscle. In contrast, subcutaneous fat mass accumulated in ARKO mice irrespective of the diet and sex. Notably, all HFD-dependent metabolic disorders observed in ARKO males were abolished after antibiotics administration. The ratios of fecal weight-to-food weight and cecum weight-to-body weight were specifically reduced by ARKO in HFD-fed males. 16S rRNA sequencing of fecal microbiota from HFD-fed male mice revealed differences in microbiota composition between control and ARKO mice. Several genera or species (e.g., Turicibacter and Lactobacillus reuteri , respectively) were enriched in ARKO mice, and antibiotics treatment spoiled the changes. Furthermore, the life span of HFD-fed ARKO males was shorter than that of control mice, indicating that androgen deficiency causes metabolic dysfunctions leading to early death. These findings also suggest that AR signaling plays a role in the prevention of metabolic dysfunctions, presumably by influencing the gut microbiome, and improve our understanding of health consequences in subjects with hypogonadism and androgen insensitivity.

Purpose: The detection and quantification of metabolites relevant for the diagnosis of fatal metabolic disorders by proton magnetic resonance spectroscopy (1H-MRS) was recently demonstrated. This prospective study aimed to compare the concentrations of beta-hydroxybutyrate (BHB), glucose (GLC), and lactate (LAC) derived from both biochemical analyses and 1H-MRS for the diagnosis of fatal metabolic disorders., Methods: In total, 20 cases with suspected fatal metabolic disorders were included in the study. For the agreement based on thresholds, the concentrations of BHB and GLC in the vitreous humor (VH) from the right vitreous and in cerebrospinal fluid (CSF) from the right lateral ventricle were derived from 1H-MRS and biochemical analyses. The predefined thresholds for pathological elevations were 2.5 mmol/l for BHB and 10 mmol/l for GLC based on the literature. In addition, concentrations of the same metabolites in white matter (WM) tissue from the corona radiata of the right hemisphere were analyzed experimentally using both methods. To enable the biochemical analysis, a dialysate of WM tissue was produced. For all three regions, the LAC concentration was determined by both methods., Results: The conclusive agreement based on thresholds was almost perfect between both methods with only one disagreement in a total of 70 comparisons due to the interference of a ferromagnetic dental brace. The differences in the concentrations between both methods showed high standard deviations. Confidence intervals of the bias not including 0 were found in CSF-GLC (- 3.1 mmol/l), WM-GLC (1.1 mmol/l), and WM-LAC (- 6.5 mmol/l)., Conclusion: Despite a considerable total error attributable to both methods, MRS derives the same forensic conclusions as conventional biochemical analyses. An adaptation of the protocol to reduce the detected errors and more data are needed for the long-term validation of MRS for the diagnosis of fatal metabolic disorders. The production of WM dialysates cannot be recommended due to high glycolytic loss.

Purpose of Review: We discuss the findings of the most recent metanalyses on the association between nonalcoholic fatty liver disease (NAFLD), cardiometabolic disease and mortality., Recent Findings: Recent metanalyses have shown that NAFLD is associated with incident type 2 diabetes mellitus (T2DM) and incident cardiovascular disease (CVD). Nonalcoholic steatohepatitis, which can be diagnosed by liver biopsy only in tertiary care centers, is often associated with liver fibrosis, which has been shown by metanalyses to increase both cardiovascular and liver-related mortality. Hyperlipidemia, lipotoxicity and impaired insulin secretion are among the possible mechanisms underlying the association of NAFLD with T2DM and CVD. Metanalyses of the association between NAFLD and mortality in the general population, where risk stratification cannot be performed on the basis of liver biopsy, have given contradictory results., Summary: To establish conclusively whether NAFLD adds to known prognostic factors of death in the general population will require a shared operational definition of NAFLD, purposefully designed cohort studies, and the use of clinically relevant measures of effect size.

Background: Fetal environment has a substantial influence on an individual's health throughout their life course. Animal models of hypertensive disease of pregnancy have demonstrated adverse health outcomes among offspring exposed to hypertensive disease of pregnancy in utero. Although there are numerous descriptions of the neonatal, infant, and pediatric outcomes of human offspring affected by hypertensive disease of pregnancy, there are few data in US populations on later life outcomes, including mortality., Objective: To assess risk for early mortality among offspring of pregnancies complicated by hypertensive disease of pregnancy., Study Design: This is a retrospective cohort study of offspring born to women with singleton or twin pregnancies between 1947 and 1967 with birth certificate information in the Utah Population Database. We identified offspring from delivery diagnoses of gestational hypertension, preeclampsia, or eclampsia. Offspring from these pregnancies (exposed) were matched to offspring of pregnancies without hypertensive disease of pregnancy (unexposed) by maternal age at delivery, birth year, sex, and multiple gestation. We also identified unexposed siblings of exposed offspring for a separate sibling analysis. Mortality follow-up of all offspring continued through 2016, at which time they would have been 49-69 years old. Adjusted hazard ratios for cause-specific mortality comparing exposed with unexposed offspring were estimated using Cox proportional hazard models., Results: We compared mortality risks for 4050 exposed offspring and 6989 matched unexposed offspring from the general population and 7496 unexposed siblings. Mortality risks due to metabolic, respiratory, digestive, nervous, and external causes of death did not differ between exposed and unexposed groups. Mortality risks from cardiovascular disease were greater in exposed offspring compared with unexposed offspring (adjusted hazard ratio, 1.57; 95% confidence interval, 1.16-2.12). In sex-specific models among the general population, cardiovascular disease mortality was significantly associated with exposure among male patients (adjusted hazard ratio, 1.92; 95% confidence interval, 1.27-2.88) but not among female patients (adjusted hazard ratio, 0.97; 95% confidence interval, 0.81-1.94). An interaction between hypertensive disease of pregnancy exposure and birth order on cardiovascular disease mortality was significant (P=.047), suggesting that the effect of hypertensive disease of pregnancy on cardiovascular disease mortality increased with higher birth order. Among siblings, the association between hypertensive disease of pregnancy exposure and cardiovascular disease mortality was not significant (adjusted hazard ratio, 1.39; 95% confidence interval, 0.99-1.95), and this was also true for sex-specific analyses of males (adjusted hazard ratio, 1.26; 95% confidence interval, 0.81-1.94) and females (adjusted hazard ratio, 1.71; 95% confidence interval, 0.96-3.04). As in the general population, there was a significant interaction between hypertensive disease of pregnancy exposure and birth order on cardiovascular disease mortality (P=.011)., Conclusion: In a US population, overall mortality risks are greater for offspring of pregnancies complicated by hypertensive disease of pregnancy compared with unexposed offspring. Among siblings, there was not a significant association between hypertensive disease of pregnancy exposure and cardiovascular disease mortality., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Sub-Saharan Africa has the highest natural twinning rate in the world. Unfortunately, due to lack of adequate care during pregnancy, labor and postnatally, twin mortality in Sub-Saharan Africa also remains very high. Thus, it has been estimated that one in five twins dies during the childhood years. In spite of this, surprisingly few twin studies have been conducted in the region, making additional epidemiological data much needed. In 2009, we established one of the first twin registries in Sub-Saharan Africa at the Bandim Health Project in Guinea-Bissau. The registry had two main objectives. First, we wanted to describe the twinning rate and mortality patterns among newborn twins, including mortality risk factors and hospitalization patterns. Such studies can help the local clinicians improve twin health by identifying the most vulnerable children. Second, and in light of the rapidly increasing diabetes rates in Africa, we wanted to use the registry to particularly focus on metabolic disorders. Twins are often born with low birth weight, which according to the 'thrifty phenotype hypothesis' could predispose them to metabolic disorders later in life. Yet, no such 'fetal programming' data have previously been available from African twins despite the fact that nutritional patterns and influences from other factors (e.g., infections) could be markedly different here compared to high-income settings. In this article, we summarize the findings and current status of the Guinea-Bissau twin registry.

Background: Continuous renal replacement therapies (CRRTs) either as continuous venovenous hemofiltration (CVVH) or hemodiafiltration (CVVHD) are used frequently in critically ill children. Many clinical variables and technical issues are known to affect the result. The factors that could be modified to increase the survival of renal replacement are sought. As a contribution, we present the data on 104 patients who underwent CRRT within a 7-year period., Materials and Method: A total of 104 patients admitted between 2009 and 2016 were included in the study. The demographic information, admittance pediatric risk of mortality (PRISM) scores, indication for CRRT, presence of fluid overload, CRRT modality, durations of CRRT, and pediatric intensive care unit (PICU) stay were compared between survivors and nonsurvivors., Results: The overall rate of survival was 51%. Patients with fluid overload had significantly increased rate of death, CRRT duration, and PICU stay. Multiorgan dysfunction syndrome as the indication for CRRT was significantly related to decreased survival when compared to acute renal failure and acute attacks of metabolic diseases. The CRRT modality was not different between survivors and nonsurvivors. Standardized mortality ratio of the group was calculated to be 0.8., Conclusion: The CRRT in critically ill patients is successful in achieving fluid removal and correction of metabolic imbalances caused by organ failures or attacks of inborn errors of metabolism. It has a positive effect on expected mortality in high-risk PICU patients. To affect the outcome, follow-up should be focused on starting therapy in early stages of fluid overload. Prospective studies defining relative importance of risk factors causing mortality can assist in building up guidelines to affect the outcome.

Elucidating the mechanism underlying the transmission of metabolic disease to subsequent generations requires robust preclinical mouse breeding strategies. Western diets rich in fat and carbohydrates are contributing factors in the rise of diabetes and obesity rates worldwide. Therefore, determining the impact of Western diets consumed by parents on offspring and future generations is critical for understanding the perpetuation of these diseases. Specifically, epigenetic regulation and transgenerational inheritance of metabolic disease is an emerging field of study requiring robust murine models. However, a major challenge to transgenerational studies is offspring mortality, exacerbated by maternal stress during pregnancy. Here, we describe a challenge experienced in our metabolic research in Western diet-fed female mice leading to the loss of litters via pup mortality and cannibalism by the mother. Furthermore, our study evaluates various breeding schemes with pregnancy efficiency and refined husbandry techniques to overcome pup mortality and infanticide, to characterize dams' and pups' metabolic characteristics, and to determine the impact on physiology of dams under detailed breeding schemes.

Indications for liver transplantation (LT) in metabolic disease are evolving. We reviewed the US experience with primary LT for metabolic disease in the Scientific Registry for Transplant Recipients (October 1987 to June 2017) to determine the following: temporal changes in indications, longterm outcomes, and factors predicting survival. Patients were grouped by the presence of structural liver disease (SLD) and whether the defect was confined to the liver. There were 5996 patients who underwent LT for metabolic disease, 2354 (39.3%) being children. LT for metabolic disease increased in children but not in adults. Children experienced a 6-fold increase in LT for metabolic disease without SLD. Indications for LT remained stable in adults. Living donor liver transplantation increased between era 1 and era 3 from 5.6% to 7.6% in children and 0% to 4.5% in adults. Patient and graft survival improved with time. The latest 5-year patient survival rates were 94.5% and 81.5% in children and adults, respectively. Outcomes were worse in adults and in those with extrahepatic disease (P < 0.01), whereas SLD did not affect outcomes. Survival improved with younger age at LT until age <2 years. On multivariate analysis, diagnostic category, inpatient status, age at LT, and transplant era significantly predicted outcomes in all ages with male sex predicting survival in childhood only. Children without structural disease were less likely to die awaiting LT and had improved post-LT survival compared with children with chronic liver disease. In conclusion, LT for metabolic disease is increasingly used for phenotypic correction in children; extrahepatic manifestations significantly impact survival at all ages; where indicated, transplantation should not be unnecessarily delayed; and the development of new allocation models may be required., (Copyright © 2019 by the American Association for the Study of Liver Diseases.)

Purpose: It is unclear whether hypomagnesemia is an independent risk factor or innocent bystander for mortality in maintenance hemodialysis (MHD) patients. Thus, we studied associations between hypomagnesemia and all-cause as well as cardiovascular (CV) mortality in MHD patients., Methods: Baseline clinical characteristics and coronary artery calcium score (CACS) of 353 Japanese MHD patients were reviewed. Three-year survival rate and mortality risk factors were assessed., Results: Median (interquartile range) age, dialysis vintage, serum magnesium (Mg), serum albumin and CACS of the subjects were 68 (60-78) years, 75 (32-151) months, 2.4 (2.2-2.7) mg/dl, 3.6 (3.3-3.8) g/dl, and 1181 (278-3190), respectively. During the 3-year period, 91 patients died. Kaplan-Meier overall 3-year survival rates were 59.0% in in patients with Mg < 2.4 mg/dl (n = 136) and 82.3% in patients with Mg ≥ 2.4 mg/dl (n = 217), (P < 0.0001). In Cox regression models not incorporating serum albumin, Mg < 2.4 mg/dl was significantly associated with 3-year all-cause death, independent of age, dialysis vintage, average ultrafiltration, Log (CACS + 1), warfarin use, serum potassium, high-sensitivity C-reactive protein (hsCRP), phosphate, uric acid, and intact parathyroid hormone [Hazard ratio (HR) 95% confidence interval (CI): 2.82 (1.31-6.29), P = 0.0078], and CV death, independent of age, dialysis vintage, Log (CACS + 1), warfarin use, serum hsCRP, and uric acid [HR (95% CI): 4.47 (1.45-16.76), P = 0.0086]. Nevertheless, associations of Mg < 2.4 mg/dl with all-cause and CV mortality were all absent in models that included serum albumin., Conclusions: Hypomagnesemia is not an independent risk factor for mortality but is associated with malnutrition in MHD patients.

Introduction: Introduction: child excess weight has been associated with obesity in adulthood and, as a consequence, increased risk of death due to cardiometabolic factors. Objective: to identify whether BMI reflects changes in the content and distribution of fat/adipose tissue and the cardiometabolic risk in children between six and nine years old. Material and methods: participants were 537 children (59.8% women) randomly selected. BMI, waist circumference (WC), waist-height index (WHI), body composition, nutritional status and cardiometabolic risk were determined. Student's t-test, one-way ANOVA, Pearson's correlation, Chi-square and diagnostic concordance were applied. An alpha ≤ 0.05 was considered. Results: direct and significant correlations between nutritional status and the anthropometric parameters studied are shown, except for the percentage of adiposity. There were significant variations (p < 0.05) in the percentage of fat and adiposity according to nutritional status of the sample. In addition, there was consistency between the variation of the nutritional status with the cardiometabolic risk evaluated trough WC and WHI. Conclusion: BMI identifies the differences in the amount of fat/adipose tissue in the children between six and nine years old when categorized according to nutritional status. In addition, it reflects direct association with cardiometabolic risk.

Despite improvements, mortality after allogeneic hematopoietic cell transplantation (HCT) for nonmalignant diseases remains a significant problem. We evaluated whether pre-HCT conditions defined by the HCT Comorbidity Index (HCT-CI) predict probability of posttransplant survival. Using the Center for International Blood and Marrow Transplant Research database, we identified 4083 patients with nonmalignant diseases transplanted between 2007 and 2014. Primary outcome was overall survival (OS) using the Kaplan-Meier method. Hazard ratios (HRs) were estimated by multivariable Cox regression models. Increasing HCT-CI scores translated to decreased 2-year OS of 82.7%, 80.3%, 74%, and 55.8% for patients with HCT-CI scores of 0, 1 to 2, 3 to 4, and ≥5, respectively, regardless of conditioning intensity. HCT-CI scores of 1 to 2 did not differ relative to scores of 0 (HR, 1.12 [95% CI, 0.93-1.34]), but HCT-CI of 3 to 4 and ≥5 posed significantly greater risks of mortality (HR, 1.33 [95% CI, 1.09-1.63]; and HR, 2.31 [95% CI, 1.79-2.96], respectively). The effect of HCT-CI differed by disease indication. Patients with acquired aplastic anemia, primary immune deficiencies, and congenital bone marrow failure syndromes with scores ≥3 had increased risk of death after HCT. However, higher HCT-CI scores among hemoglobinopathy patients did not increase mortality risk. In conclusion, this is the largest study to date reporting on patients with nonmalignant diseases demonstrating HCT-CI scores ≥3 that had inferior survival after HCT, except for patients with hemoglobinopathies. Our findings suggest that using the HCT-CI score, in addition to disease-specific factors, could be useful when developing treatment plans for nonmalignant diseases., (© 2019 by The American Society of Hematology.)

Acromegaly is a chronic systemic disease with many complications and is associated with increased mortality when not adequately treated. Substantial advances in acromegaly treatment, as well as in the treatment of many of its complications, mainly diabetes mellitus, heart failure, and arterial hypertension, were achieved in the last decades. These developments allowed change in both prevalence and severity of some acromegaly complications and furthermore resulted in a reduction of mortality. Currently, mortality seems to be similar to the general population in adequately treated patients with acromegaly. In this review, we update the knowledge in complications of acromegaly and detail the effects of different acromegaly treatment options on these complications. Incidence of mortality, its correlation with GH (cumulative exposure vs last value), and IGF-I levels and the shift in the main cause of mortality in patients with acromegaly are also addressed.

The predictive value of total 25-hydroxyvitamin D (25(OH)D, a biomarker of vitamin D status) in relation to lifetime risk of cardiometabolic mortality is not known. The purpose of this study was to determine the association between standardized and annualized total 25(OH)D levels and lifetime risk for cardiometabolic mortality in middle- to older-aged adults. In this study, we followed up 7958 participants in the Third National Health and Nutrition Examination Survey from 1988 to 1994 (NHANES III) until the occurrence of cardiometabolic death or attainment of 95 years of age (median follow-up 17.9 years, 1371 cardiometabolic-deaths). Lifetime risks were estimated according to recommended total 25(OH)D cutoffs by national guidelines, and a combination of total 25(OH)D status and traditional risk factor burden. We also explored variation in lifetime risk estimates by levels of body mass index (BMI). The results of this study showed that annualized total 25(OH)D <30 nmol/L was associated with high lifetime risk of cardiometabolic mortality (40%). Lifetime risks of cardiometabolic mortality were similar for annualized levels between 30-< 50 nmol/L, 50-< 75 nmol/L and ≥75 nmol/L (31-33%). Lifetime risk was highest among participants with annualized total 25(OH)D <30 nmol/L and ≥2 major traditional risk factors (45%), whereas lifetime risk was lowest among participants with annualized 25(OH)D ≥30 nmol/L and low-intermediate risk factors (28%). Lifetime risk estimates were similar across BMI categories. In conclusion, a single measurement of vitamin D deficiency (annualized levels <30 nmol/L) in middle- to older-aged adults is a strong predictor of high lifetime risk for cardiometabolic mortality, particularly among those with high burden of traditional risk factors., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Sedentary time was associated with myocardial infarction (MI) and metabolic diseases in previous studies., Purpose: To investigate whether sedentary time measured before disease onset was associated with all-cause mortality among MI survivors and whether the sedentary time-mortality association was mediated by physical activity status and metabolic phenotypes., Methods: In this prospective community-based cohort including 101,510 Chinese adults, we used sedentary time, evaluated at 2006 (baseline), to predict further all-cause mortality among individuals who then developed new onset MI from 2006 to December 2013 ( n = 989). The post-MI mortality was ascertained after the first non-fatal MI until December 2014. We assessed the mediating effects of physical inactivity and metabolic factors on the sedentary time-mortality association., Results: During 7 years follow up, 180 deaths occurred among these participants with incident MI. Prolonged sedentary time was associated with a higher risk of mortality among MI survivors. The adjusted hazard ratio (HR) of mortality for sedentary time 4-8 hours/day versus <4 hours/day, was 1.62 (95% confidence interval (CI) 1.14-2.31). A high amount of sedentary time (>4 hours/day) and inactive physical activity had an increased risk of all-cause mortality (HR: 2.74, 95% CI 1.34-5.60), relative to those with sedentary time ≤4 hours/day and moderate/vigorous physical activity. Physical inactivity and metabolic factors mediated a small proportion (≤9.2 % for all) of the total association between sedentary time and post-MI mortality., Conclusion: High sedentary time was significantly associated with all-cause mortality among MI survivors, independent of physical activity status and metabolic abnormalities.

Objective: To investigate medical complications (MCs) occurring within 6 months postinjury in brain-injured patients with prolonged disorders of consciousness (DoC) and to evaluate impact of MC on mortality and long-term clinical outcomes., Design: Prospective observational cohort study., Setting: Rehabilitation unit for acquired DoC., Participants: Patients (N=194) with DoC (142 in vegetative state [VS], 52 in minimally conscious state; traumatic etiology 43, anoxic 69, vascular 82) consecutively admitted to a neurorehabilitation unit within 1-3 months postonset., Interventions: Not applicable., Main Outcome Measures: Mortality and improvements in clinical diagnosis and functional disability level (assessed by Coma Recovery Scale-Revised [CRS-R] and Disability Rating Scale) at 12, 24, and 36 months postonset., Results: Within 6 months postinjury, 188 of 194 patients (>95%) developed at least 1 MC and 142 of them (73%) showed at least 1 severe MC. Respiratory and musculoskeletal-cutaneous MCs were the most frequent, followed by endocrino-metabolic abnormalities. Follow-up, complete in 189 of 194 patients, showed that male sex and endocrine-metabolic MCs were associated with higher risk of mortality at all timepoints. Old age, anoxic etiology, lower CRS-R total scores, and diagnosis of VS at study entry predicted no clinical and functional improvements at most timepoints; however, epilepsy predicted no improvement in diagnosis at 24 months postonset only., Conclusions: MCs are very frequent in patients with DoC within at least 6 months after brain injury, regardless of clinical diagnosis, etiology, and age. Endocrino-metabolic MCs are independent predictors of mortality at all timepoints; however,epilepsy predicted poor long-term outcome. Occurrence and severity of MCs in patients with DoC call for long-term appropriate levels of care after the postacute phase., (Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

The objective of this study was to assess the association between individual metabolic diseases (MD) and multiple MD (MD+) in the transition period (±3 wk relative to calving) and the culling risk in the first 120 d in milk (DIM) in Holstein-Friesian dairy cows. Health records from a transition management facility in Germany with 1,946 calvings were analyzed in a 1-yr cohort via survival analysis and a decision tree model. The recorded MD were milk fever (MF), retained placenta (RP), metritis (METR), ketosis (KET), displaced abomasum (DA), twinning (TWIN), and clinical mastitis (MAST). The overall culling within 120 DIM was 18%. The 120 DIM culling risk for healthy cows (64.8% of the total) was 13%, whereas it was 25% for MD (24.5%) and 33% for MD+ (10.7%) cows. The 120 DIM culling risk (%) for each MD and MD+, respectively, was 34.6 and 48 for MF and MF+, 15 and 31.5 for RP and RP+, 9.4 and 22.2 for METR and METR+, 30.7 and 37.3 for KET and KET+, 56.1 and 46.8 for DA and DA+, 30.3 and 34 for TWIN and TWIN+, and 36.6 and 27.8 for MAST and MAST+. Moreover, the incidence risk (%) for each MD and MD+, respectively, was 4 and 2.6 for MF and MF+, 1 and 2.8 for RP and RP+, 8.7 and 6 for METR and METR+, 4.5 and 6.1 for KET and KET+, 0.8 and 2.4 for DA and DA+, 1.7 and 2.7 for TWIN and TWIN+, and 3.6 and 1.8 for MAST and MAST+. Setting the healthy cows as the referent, the 120 DIM hazard ratios (HR) for culling were MD 2.1, MD+ 2.9, MF 3.3, MF+ 4.6, RP+ 2.7, METR+ 1.8, KET 2.6, KET+ 3.3, DA 5.5, DA+ 4.5, TWIN 2.8, TWIN+ 3.0, MAST 3.1, and MAST+ 2.3. According to both decision tree and random forest analyses, MF was the most significant disease influencing survival, followed by DA, MAST, METR, and TWIN. In conclusion, the presence of MD or MD+ during the transition period was associated with increased culling risk in the first 120 DIM. The culling hazard was greater when an MD was complicated with another MD. In this study performed in a well-managed large farm, uncomplicated cases of RP (HR = 1.2) and METR (HR = 0.7) did not have an influence on the 120 DIM culling risk. Interestingly, both decision tree and random forest analyses pointed to MF and DA as main culling reasons in the first 120 DIM in the present dairy herd., (Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The role of dietary fat has been long studied as a modifiable variable in the prevention and treatment of noncommunicable cardiometabolic disease. Once heavily promoted to the public, the low-fat diet has been demonstrated to be non-effective in preventing cardiometabolic disease, and an increasing body of literature has focused on the effects of a relatively higher-fat diet. More recent evidence suggests that a diet high in healthy fat, rich in unsaturated fatty acids, such as the Mediterranean dietary pattern, may, in fact, prevent the development of metabolic diseases such as type 2 diabetes mellitus, but also reduce cardiovascular events. This review will specifically focus on clinical trials which collected data on dietary fatty acid intake, and the association of these fatty acids over time with measured cardiometabolic health outcomes, specifically focusing on morbidity and mortality outcomes. We will also describe mechanistic studies investigating the role of dietary fatty acids on cardiovascular risk factors to describe the potential mechanisms of action through which unsaturated fatty acids may exert their beneficial effects. The state of current knowledge on the associations between dietary fatty acids and cardiometabolic morbidity and mortality outcomes will be summarized and directions for future work will be discussed.

Background: Liver transplantation (LT) is an excellent treatment option for patients with biliary atresia (BA) who fail portoenterostomy surgery. LT is also increasingly performed in patients with metabolic liver diseases. This study compared the outcomes in pediatric patients who underwent LT for metabolic liver diseases and BA., Basic Procedures: Data from 237 pediatric patients who underwent primary LT at Seoul National University Hospital from 1988 to 2015, including 33 with metabolic liver diseases and 135 with BA, were retrospectively analyzed., Main Findings: Compared with children with BA, children with metabolic liver diseases were significantly older at the time of LT (121.3 vs. 37.3 months; P < 0.001), and had lower Child-Pugh (7.1 vs. 8.4; P = 0.010) and Pediatric End-stage Liver Disease (6.5 vs. 12.8; P = 0.042) scores. Overall survival rates were similar (87.8% vs. 90.8%; P = 0.402), but hepatic artery (HA) complications were significantly more frequent in children with metabolic liver diseases (12.1% vs. 1.5%; P = 0.014)., Principal Conclusion: Despite similar overall survival, children with metabolic liver diseases had a higher rate of HA complications., Type of Submission: Original article, Case control study, Retrospective., Evidence Level: III., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Promising school policies to improve children's diets include providing fresh fruits and vegetables (F&V) and competitive food restrictions on sugar-sweetened beverages (SSBs), yet the impact of national implementation of these policies in US schools on cardiometabolic disease (CMD) risk factors and outcomes is not known. Our objective was to estimate the impact of national implementation of F&V provision and SSB restriction in US elementary, middle, and high schools on dietary intake and body mass index (BMI) in children and future CMD mortality., Methods: We used comparative risk assessment (CRA) frameworks to model the impacts of these policies with input parameters from nationally representative surveys, randomized-controlled trials, and systematic reviews and meta-analyses. For children ages 5-18 years, this incorporated national data on current dietary intakes and BMI, impacts of these policies on diet, and estimated effects of dietary changes on BMI. In adults ages 25 and older, we further incorporated the sustainability of dietary changes to adulthood, effects of dietary changes on CMD, and national CMD death statistics, modeling effects if these policies had been in place when current US adults were children. Uncertainty across inputs was incorporated using 1000 Monte Carlo simulations., Results: National F&V provision would increase daily fruit intake in children by as much as 25.0% (95% uncertainty interval (UI): 15.4, 37.7%), and would have small effects on vegetable intake. SSB restriction would decrease daily SSB intake by as much as 26.5% (95% UI: 6.4, 46.4%), and reduce BMI by as much as 0.7% (95% UI: 0.2, 1.2%). If F&V provision and SSB restriction were nationally implemented, an estimated 22,383 CMD deaths/year (95% UI: 18735, 25930) would be averted., Conclusion: National school F&V provision and SSB restriction policies implemented in elementary, middle, and high schools could improve diet and BMI in children and reduce CMD mortality later in life., Competing Interests: The authors have declared that no competing interests exist.

Background and Aims: It is expected that older adults with metabolic abnormalities may benefit from weight loss; however, data on this population are limited. Our study was to assess the effect of obesity and weight change on mortality risk in older adults with metabolic abnormalities., Methods and Results: A total of 3649 Chinese older adults aged 60-90 years with metabolic abnormalities were included between 2000 and 2014. Weight change between two health checkup periods was calculated. During a median follow-up period of 37 months, 503 all-cause mortality and 235 cardiovascular disease mortality occurred. Death rate was the lowest in overweight participants and in the participants with weight stability. After adjustment for covariates, hazard ratios (95% confidence intervals) of overweight participants for all-cause mortality and cardiovascular mortality were 0.71 (0.59, 0.86) and 0.72 (0.55, 0.95), respectively, whereas obesity was not significantly associated with mortality risk. Furthermore, relative to weight stability, risks of mortality significantly increased with the increase in weight loss or weight gain, except small weight gain. These associations were unchanged when the participants were stratified by baseline covariates and even when several definitions of weight change were considered., Conclusions: Overweight was associated with less mortality risk, and obesity was not associated with mortality risk in older adults with metabolic abnormalities. Mortality risk increased with the increase in weight loss or weight gain, regardless of body weight levels at the baseline. These findings suggest that maintaining a stable weight may be the best choice in older adults with metabolic abnormalities., (Copyright © 2018 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

To investigate the spectrum of diseases seen in diabetes mellitus in a forensic context, all autopsy reports of diabetic individuals who presented to Forensic Science, South Australia (FSSA), over a 5-year period from 2005 to 2009 were studied. The leading cause of death was cardiovascular disease (55.0%), followed by unnatural deaths (15.4%) and infections (9.4%). In type 1 diabetics, principal causes of death included cardiovascular disease (44.7%), acute metabolic complications (18.7%), unnatural deaths (17.9%), and infections (8.9%). However, frequencies of these diseases differed in type 2 diabetics, with cardiovascular events responsible for 56.6% of cases, followed by unnatural deaths (15.0%) and infections (10.9%). A larger number of male deaths were seen in all disease categories, except respiratory and gastrointestinal where the frequencies were similar to females. Cardiovascular disease was the leading overall cause of death across all ages except in those under the age of 30 where metabolic complications were more common., (© 2017 American Academy of Forensic Sciences.)

Background: This study was to explore the effect of hyperlipidemia on the incidence of cardio-cerebrovascular diseases in patients with type 2 diabetes., Methods: Three hundred ninety five patients with type 2 diabetes in our hospital from January 2012 to January 2016 were followed up with an average of 3.8 years. The incidence of cardio-cerebrovascular diseases between diabetes combined with hyperlipidemia group (195 patients) and diabetes group (200 patients) were made a comparison. Multivariable Cox's proportional hazards regression model was used to analyze the effect of hyperlipidemia on the incidence of cardio-cerebrovascular diseases in patients with type 2 diabetes., Results: Diastolic blood pressure, systolic blood pressure, high-density lipoprotein, low-density lipoprotein, body mass index and hyper-sensitive C-reactive protein were higher in diabetes combined with hyperlipidemia group than in diabetes group (P < 0.05). At the end of the follow-up period, all-cause mortality, cardio-cerebrovascular diseases mortality, and the incidence of myocardial infarction, cerebral infarction, cerebral hemorrhage and total cardiovascular events were significantly higher in diabetes combined with hyperlipidemia group than in diabetes group (P < 0.05). The analysis results of multivariable Cox's proportional hazards regression model showed that the risks of myocardial infarction and total cardiovascular events in diabetes combined with hyperlipidemia group were respectively 1.54 times (95%CI 1.13-2.07) and 1.68 times (95%CI 1.23-2.24) higher than those in diabetes group. Population attributable risk percent of all-cause mortality and total cardiovascular events in patients with type 2 diabetes combined with hyperlipidemia was 9.6% and 26.8%, respectively., Conclusions: Hyperlipidemia may promote vascular endothelial injury, increasing the risk of cardio-cerebrovascular diseases in patients with type 2 diabetes. Medical staffs should pay attention to the control of blood lipids in patients with type 2 diabetes to delay the occurrence of cardio-cerebrovascular diseases.

Background: Previous studies suggested obstructive sleep apnoea syndrome (OSAS) as a major risk factor for incident cardiovascular events. However, the relationship between OSAS severity, the use of continuous positive airway pressure (CPAP) treatment and the development of cardiovascular disease is still matter of debate., Study Objectives: The aim was to test the association between OSAS and cardiovascular events in patients with concomitant cardio-metabolic diseases and the potential impact of CPAP therapy on cardiovascular outcomes., Methods: Prospective observational cohort study of consecutive outpatients with suspected metabolic disorders who had complete clinical and biochemical workup including polysomnography because of heavy snoring and possible OSAS. The primary endpoint was a composite of major adverse cardiovascular and cerebrovascular events (MACCE)., Results: Median follow-up was 81.3 months, including 434 patients (2701.2 person/years); 83 had a primary snoring, 84 had mild, 93 moderate and 174 severe OSAS, respectively. The incidence of MACCE was 0.8% per year (95% confidence interval [CI] 0.2-2.1) in primary snorers and 2.1% per year (95% CI 1.5-2.8) for those with OSAS. A positive association was observed between event-free survival and OSAS severity (log-rank test; P = .041). A multivariable Cox regression analysis showed obesity (HR = 8.011, 95% CI 1.071-59.922, P = .043), moderate OSAS (vs non-OSAS HR = 3.853, 95% CI 1.069-13.879, P = .039) and severe OSAS (vs non-OSAS HR = 3.540, 95% CI 1.026-12.217, P = .045) as predictors of MACCE. No significant association was observed between CPAP treatment and MACCE (log-rank test; P = .227)., Conclusions: Our findings support the role of moderate/severe OSAS as a risk factor for incident MACCE. CPAP treatment was not associated with a lower rate of MACCE., (© 2018 Stichting European Society for Clinical Investigation Journal Foundation.)

Osteoarthritis (OA) is a common musculoskeletal disorder and occur in different patterns. However, its impact on long-term all-cause-mortality is inconclusive., Study Aims: Investigate 20-year all-cause-mortality in patients with hip/knee arthroplasty (recruited 1995/1996, N = 809) from the Ulm Osteoarthritis Study-cohort, in comparison to general population. Furthermore, to enlighten the triangle between baseline life-style and cardio-metabolic risk factors, phenotypic OA-patterns (laterality, generalization, cause) and all-cause-mortality. Mortality was assessed during 20 years follow-up. Standardized mortality ratios (SMR), adjusted odds ratios and hazard ratios (aHR) were calculated. After five years cohort-mortality was reduced compared to the general population, however 20 years later assimilated (SMR = 1.11; 95%-CI 0.73-1.49). OA-patterns were associated with age, cholesterol, and overweight/obesity. In comparison to primary OA decreased mortality was observed for patients with secondary OA (aHR = 0.76; 95%-CI 0.61-0.95) adjusted for age, smoking, overweight/obesity, diabetes, hypertension, cardiac insufficiency, uric acid, and lower cholesterol. There was no increased mortality in patients after 20 years follow-up compared to general population. Significantly decreased mortality in secondary compared to primary OA suggests a subtype-specific involvement of systemic co-factors in determination of all-cause-mortality. Because cardio-metabolic risk factors were associated with increased risk of bilateral OA and lower long-term survival, those risk factors should be consequently targeted in OA-patients.

Objectives: There are limited data on mortality in patients with type 2 diabetes mellitus (T2DM) in Sub-Saharan Africa. We aimed at determining the mortality rate, and the causes and the predictors of death in patients with T2DM followed as outpatients in a reference hospital in Cameroon., Design: Retrospective cohort study., Setting: A reference hospital in Cameroon., Participants: From December 2015 to March 2016, patients with T2DM aged 18 years and older and who consulted between January 2009 and December 2014, were contacted directly or through their next of kin, and included in this study. All participants with less than 75% of desired data in files, those who could not be reached on the phone and those who refused to provide consent were excluded from the study. Of the 940 eligible patients, 628 (352 men and 276 women) were included and completed the study, giving a response rate of 66.8%., Outcome Measures: Death rate, causes of death and predictors of death., Results: Of the 628 patients (mean age: 56.5 years; median diabetes duration: 3.5 years) followed up for a total of 2161 person-years, 54 died, giving a mortality rate of 2.5 per 100 person-years and a cumulative mortality rate of 8.6%. Acute metabolic complications (22.2%), cardiovascular diseases (16.7%), cancers (14.8%), nephropathy (14.8%) and diabetic foot syndrome (13.0%) were the most common causes of death. Advanced age (adjusted HR (aHR) 1.06, 95% CI 1.02 to 1.10; P=0.002), raised glycated haemoglobin (HbA1c) (aHR 1.16, 95% CI 1.00 to 1.35; P=0.051), low blood haemoglobin (aHR 1.06, 95% CI 1.02 to 1.10; P=0.002) and proteinuria (aHR 2.97, 95% CI 1.40 to 6.28; P=0.004) were identified as independent predictors of death., Conclusions: The mortality rate in patients with T2DM is high in our population, with acute metabolic complications as the leading cause. Patients with advanced age, raised HbA1c, anaemia or proteinuria are at higher risk of death and therefore represent the target of interest to prevent mortality in T2DM., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: The effect of cardio-metabolic profile on the relationship of body mass index (BMI) with mortality is unclear. The aim of this study was to explore association between BMI and mortality at all ages, taking account of cardio-metabolic disorders., Methods: We followed 377,929 individuals (≥ 20 years), who registered for health checkups in 1996-2007, until 2008 and found 9490 deaths. From multivariable Cox proportional hazards models we estimated mortality hazard ratios (HR) for those in high blood pressure, hyperglycemia, high waist circumference, dyslipidemia, and different BMIs categories (the underweight [< 18.5 kg/m 2 ], low normal weight [18.5-21.9 kg/m 2 ], normal weight [22-23.9 kg/m 2 , the referent], overweight [24-26.9 kg/m 2 ], obese1 [27-29.9 kg/m 2 ], and obese2 [≥ 30 kg/m 2 ]). Population attributable risk (PAR) provided estimates of the population mortality burden attributable to high blood pressure, hyperglycemia, high waist circumference, dyslipidemia, and deviant BMIs., Results: Higher blood pressure, hyperglycemia, high waist circumference, and dyslipidemia were significantly predictive of higher mortality for nearly all ages. Compared with the referent BMI, underweight (HR = 1.69, 95% confidence interval = 1.51-1.90) and low normal weight (HR = 1.19, 1.11-1.28) were significant mortality risks, while overweight (HR = 0.82, 0.76-0.89) and obese1 (HR = 0.88, 0.79-0.97) were protective against premature death. The mortality impact of obesity was largely attributable to cardio-metabolic profile and attenuated by age. The population mortality burden with high blood pressure (PAR = 7.29%), hyperglycemia (PAR = 5.15%), high waist circumference (PAR = 4.24%), and dyslipidemia (PAR = 5.66%) was similar to that in the underweight (PAR = 5.50%) or low normal weight (PAR = 6.04%) groups. Findings for non-smokers and by gender were similar., Conclusions: The effect of BMI on mortality varies with age and is affected by cardio-metabolic status. Compared to any deviant BMI, abnormal cardio-metabolic status has a similar or even greater health impact at both the individual and population levels.