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

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

Breast cancer incidence and mortality by metabolic syndrome and obesity: The Women's Health Initiative.

BACKGROUND: In the Women's Health Initiative (WHI) randomized trial, dietary intervention significantly reduced breast cancer mortality, especially in women with more metabolic syndrome (MetS) components. Therefore, this study investigated the associations of MetS and obesity with postmenopausal breast cancer after long-term follow-up in the WHI clinical trials. METHODS: A total of 68,132 postmenopausal women, without prior breast cancer and with normal mammogram, were entered into WHI randomized clinical trials; 63,330 women with an entry MetS score comprised the study population. At entry, body mass index (BMI) was determined; MetS score (0, 1-2, and 3-4) included the following: (1) high waist circumference (≥88 cm), (2) high blood pressure (systolic ≥130 mm Hg and/or diastolic ≥85 mm Hg, or hypertension history), (3) high-cholesterol history, and (4) diabetes history. Study outcomes included breast cancer incidence, breast cancer mortality, deaths after breast cancer, and results by hormone receptor status. RESULTS: After a >20-year mortality follow-up, a higher MetS score (3-4), adjusted for BMI, was significantly associated with more poor prognosis, estrogen receptor (ER)-positive, progesterone receptor (PR)-negative cancers (p = .03), 53% more deaths after breast cancer (p < .001), and 44% higher breast cancer mortality (p = .03). Obesity status, adjusted for MetS score, was significantly associated with more good prognosis, ER-positive, PR-positive cancers (p < .001), more total breast cancers (p < .001), and more deaths after breast cancer (p < .001), with higher breast cancer mortality only in women with severe obesity (BMI, ≥35 kg/m2; p < .001). CONCLUSIONS: MetS and obesity status have independent, but differential, adverse associations with breast cancer receptor subtypes and breast cancer mortality risk. Both represent separate targets for breast cancer prediction and prevention strategies.

Hepatic steatosis, metabolic dysfunction and risk of mortality: findings from a multinational prospective cohort study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) are implicated in the aetiology of non-communicable diseases. Our study aimed to evaluate associations between NAFLD and MetS with overall and cause-specific mortality. METHODS: We used dietary, lifestyle, anthropometric and metabolic biomarker data from a random subsample of 15,784 EPIC cohort participants. NAFLD was assessed using the fatty liver index (FLI) and MetS using the revised definition. Indices for metabolic dysfunction-associated fatty liver disease (MAFLD) were calculated. The individual associations of these indices with overall and cause-specific mortality were assessed using multivariable Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (95%CIs). As a subobjective, risk associations with adaptations of new classifications of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic and alcohol-related liver disease (MetALD) were also assessed. RESULTS: Among the 15,784 sub-cohort participants, a total of 1997 deaths occurred (835 due to cancer, 520 to CVD, 642 to other causes) over a median 15.6 (IQR, 12.3-17.1) years of follow-up. Compared to an FLI < 30, FLI ≥ 60 was associated with increased risks of overall mortality (HR = 1.44, 95%CI = 1.27-1.63), and deaths from cancer (HR = 1.32, 95%CI = 1.09-1.60), CVD (HR = 2.06, 95% CI = 1.61-2.63) or other causes (HR = 1.21, 95%CI = 0.97-1.51). Mortality risk associations were also elevated for individuals with MAFLD compared to those without. Individuals with MetS were at increased risk of all mortality endpoints, except cancer-specific mortality. MASLD and MetALD were associated with higher risk of overall mortality. CONCLUSIONS: Our findings based on a prospective cohort suggest that individuals with hepatic steatosis or metabolic dysfunction have a higher overall and cause-specific mortality risk.

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

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

Association between triglyceride-glucose related indices with the all-cause and cause-specific mortality among the population with metabolic syndrome.

BACKGROUND: Triglyceride-glucose (TyG) index has been determined to play a role in the onset of metabolic syndrome (MetS). Whether the TyG index and TyG with the combination of obesity indicators are associated with the clinical outcomes of the MetS population remains unknown. METHOD: Participants were extracted from multiple cycles of the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018 years. Three indicators were constructed including TyG index, TyG combining with waist circumference (TyG-WC), and TyG combining with waist-to-height ratio (TyG-WHtR). The MetS was defined according to the National Cholesterol Education Program (NCPE) Adult Treatment Panel III. Kaplan-Meier (KM) curves, restricted cubic splines (RCS), and the Cox proportional hazard model were used to evaluate the associations between TyG-related indices and mortality of the MetS population. The sensitive analyses were performed to check the robustness of the main findings. RESULTS: There were 10,734 participants with MetS included in this study, with 5,570 females and 5,164 males. The median age of the study population was 59 years old. The multivariate Cox regression analyses showed high levels of TyG-related indices were significantly associated with the all-cause mortality of MetS population [TyG index: adjustedhazard ratio (aHR): 1.36, 95%confidence interval (CI): 1.18-1.56, p < 0.001; TyG-WHtR index: aHR = 1.29, 95%CI: 1.13-1.47, p < 0.001]. Meanwhile, the TyG-WC and TyG-WHtR index were associated with cardiovascular mortality of the MetS population (TyG-WC: aHR = 1.45, 95%CI: 1.13-1.85, p = 0.004; TyG-WHtR: aHR = 1.50 95%CI: 1.17-1.92, p = 0.002). Three TyG-related indices showed consistent significant correlations with diabetes mortality (TyG: aHR = 4.06, 95%CI: 2.81-5.87, p < 0.001; TyG-WC: aHR = 2.55, 95%CI: 1.82-3.58, p < 0.001; TyG-WHtR: aHR = 2.53 95%CI: 1.81-3.54, p < 0.001). The RCS curves showed a non-linear trend between TyG and TyG-WC indices with all-cause mortality (p for nonlinearity = 0.004 and 0.001, respectively). The sensitive analyses supported the positive correlations between TyG-related indices with mortality of the MetS population. CONCLUSION: Our study highlights the clinical value of TyG-related indices in predicting the survival of the MetS population. TyG-related indices would be the surrogate biomarkers for the follow-up of the MetS population.

Longitudinal economic burden of incident complications among metabolic syndrome populations.

BACKGROUND: This study quantifies the longitudinal economic burden for a wide spectrum of incident complications, metabolic syndrome (MS)-related risk factors, and comorbidities in patients with MS. METHODS: This retrospective study utilized linked data from the 2013 National Health Interview Survey and the 2012-2021 National Health Insurance Research Database to identify MS individuals and their characteristics. The incidence rate of each complication was calculated as the number of complication events in the study period divided by the total person-years during follow-up. The healthcare costs of complications were analyzed using a generalized estimating equation model to determine the cost impact of complications after adjustment for patients' characteristics. Sensitivity analyses on variables with high missing rates (i.e., cause of death, body mass index) were performed. RESULTS: Among 837 identified MS individuals over 8.28 (± 1.35) years of follow-up, the most frequent complications were microvascular diseases (incidence rate for nephropathy/retinopathy/neuropathy: 6.49/2.64/2.08 events per 100 person-years), followed by cardiovascular diseases (2.47), peripheral vascular diseases (2.01), and cancers (1.53). Death was the costliest event (event-year cost per person: USD 16,429) and cancers were the most expensive complications (USD 9,127-11,083 for non-MS- and MS-related cancers). Developing non-MS/MS-related cancers, cardiovascular diseases, and obesity-related medical conditions increased annual costs by 273% (95% CI: 181-397%)/175% (105-269%), 159% (118-207%), and 140% (84-214%), respectively. Microvascular diseases had the lowest cost impact on annual costs (i.e., 27% [17-39%]/27% [11-46%]/24% [11-37%] increases for nephropathy/neuropathy/retinopathy, respectively). Having existing comorbidities increased annual costs by 20% (osteoarthritis) to 108% (depression). Having morbid obesity (i.e., body mass index ≥ 35 kg/m2) increased annual costs by 58% (30-91%). CONCLUSIONS: The economic burden from costly incident complications (i.e., cardiovascular diseases, peripheral vascular diseases, cancers), MS-related risk factors (i.e., morbid obesity), and comorbidities (i.e., depression) highlight the urgent need for early intervention to prevent MS and its progression. The comprehensive cost estimates reported in this study can facilitate the parameterization of economic analyses to identify cost-effective interventions for these patients.

Metabolic score for insulin resistance (METS-IR) predicts all-cause and cardiovascular mortality in the general population: evidence from NHANES 2001-2018.

BACKGROUND: The prevalence of obesity-associated insulin resistance (IR) is increasing along with the increase in obesity rates. In this study, we compared the predictive utility of four alternative indexes of IR [triglyceride glucose index (TyG index), metabolic score for insulin resistance (METS-IR), the triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio and homeostatic model assessment of insulin resistance (HOMA-IR)] for all-cause mortality and cardiovascular mortality in the general population based on key variables screened by the Boruta algorithm. The aim was to find the best replacement index of IR. METHODS: In this study, 14,653 participants were screened from the National Health and Nutrition Examination Survey (2001-2018). And TyG index, METS-IR, TG/HDL-C and HOMA-IR were calculated separately for each participant according to the given formula. The predictive values of IR replacement indexes for all-cause mortality and cardiovascular mortality in the general population were assessed. RESULTS: Over a median follow-up period of 116 months, a total of 2085 (10.23%) all-cause deaths and 549 (2.61%) cardiovascular disease (CVD) related deaths were recorded. Multivariate Cox regression and restricted cubic splines analysis showed that among the four indexes, only METS-IR was significantly associated with both all-cause and CVD mortality, and both showed non-linear associations with an approximate "U-shape". Specifically, baseline METS-IR lower than the inflection point (41.33) was negatively associated with mortality [hazard ratio (HR) 0.972, 95% CI 0.950-0.997 for all-cause mortality]. In contrast, baseline METS-IR higher than the inflection point (41.33) was positively associated with mortality (HR 1.019, 95% CI 1.011-1.026 for all-cause mortality and HR 1.028, 95% CI 1.014-1.043 for CVD mortality). We further stratified the METS-IR and showed that significant associations between METS-IR levels and all-cause and cardiovascular mortality were predominantly present in the nonelderly population aged < 65 years. CONCLUSIONS: In conjunction with the results of the Boruta algorithm, METS-IR demonstrated a more significant association with all-cause and cardiovascular mortality in the U.S. population compared to the other three alternative IR indexes (TyG index, TG/HDL-C and HOMA-IR), particularly evident in individuals under 65 years old.

Exploring the Association of Metabolic Syndrome with In-Hospital Survival of Older Patients Hospitalized with COVID-19: Beyond Chronological Age.

BACKGROUND: Despite the variability and complexity of geriatric conditions, few COVID-19 reports of clinical characteristic prognostication provide data specific to oldest-old adults (over age 85), and instead generally report broadly as 65 and older. OBJECTIVE: To examine metabolic syndrome criteria in adults across 25 hospitals with variation in chronological age. DESIGN AND PARTICIPANTS: This cohort study examined 39,564 hospitalizations of patients aged 18 or older with COVID-19 who received inpatient care between March 13, 2020, and February 28, 2022. EXPOSURE: ICU admission and/or in-hospital mortality. MAIN MEASURES: Metabolic syndrome criteria and patient demographics were examined as risk factors. The main outcomes were admission to ICU and hospital mortality. KEY RESULTS: Oldest old patients (≥ 85 years) hospitalized with COVID-19 accounted for 7.0% (2758/39,564) of all adult hospitalizations. They had shorter ICU length of stay, similar overall hospitalization duration, and higher rates of discharge destinations providing healthcare services (i.e., home health, skilled nursing facility) compared to independent care. Chronic conditions varied by age group, with lower proportions of diabetes and uncontrolled diabetes in the oldest-old cohort compared with young-old (65-74 years) and middle-old (75-84 years) groups. Evaluations of the effect of metabolic syndrome and patient demographics (i.e., age, sex, race) on ICU admission demonstrate minimal change in the magnitude of effect for metabolic syndrome on ICU admission across the different models. CONCLUSIONS: Metabolic syndrome measures are important individual predictors of COVID-19 outcomes. Building on prior examinations that metabolic syndrome is associated with death and ARDS across all ages, this analysis supports that metabolic syndrome criteria may be more relevant than chronological age as risk factors for poor outcomes attributed to COVID-19.

Biological aging mediates the associations of metabolic score for insulin resistance with all-cause and cardiovascular disease mortality among US adults: A nationwide cohort study.

AIM: To investigate the associations of metabolic score for insulin resistance (METS-IR) with all-cause and cardiovascular disease (CVD)-specific mortality and the potential mediating role of biological ageing. METHODS: A cohort of 19 204 participants from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 was recruited for this study. Cox regression models, restricted cubic splines, and Kaplan-Meier survival curves were used to determine the relationships of METS-IR with all-cause and CVD-specific mortality. Mediation analyses were performed to explore the possible intermediary role of biological ageing markers, including phenotypic age (PhenoAge) and biological age (BioAge). RESULTS: During a median follow-up of 9.17 years, we observed 2818 deaths, of which 875 were CVD-specific. Multivariable Cox regression showed that the highest METS-IR level (Q4) was associated with increased all-cause (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.14-1.67) and CVD mortality (HR 1.52, 95% CI 1.10-2.12) compared with the Q1 level. Restricted cubic splines showed a nonlinear relationship between METS-IR and all-cause mortality. Only METS-IR above the threshold (41.02 µg/L) was positively correlated with all-cause death. METS-IR had a linear positive relationship with CVD mortality. In mediation analyses, we found that PhenoAge mediated 51.32% (p < 0.001) and 41.77% (p < 0.001) of the association between METS-IR and all-cause and CVD-specific mortality, respectively. For BioAge, the mediating proportions of PhenoAge were 21.33% (p < 0.001) and 15.88% (p < 0.001), respectively. CONCLUSIONS: This study highlights the detrimental effects of insulin resistance, as measured by METS-IR, on all-cause and CVD mortality. Moreover, it underscores the role of biological ageing in mediating these associations, emphasizing the need for interventions targeting both insulin resistance and ageing processes to mitigate mortality risks in metabolic disorders.

The association of neutrophil-to-lymphocyte ratio with cardiovascular and all-cause mortality among the metabolic syndrome population.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) has emerged as a novel inflammatory marker related to disease prognosis, this study aimed to evaluate the association between NLR and mortality in metabolic syndrome (MetS) patients. METHODS: This study used data from 13,156 participants with MetS, derived from the National Health and Nutrition Examination Survey from 1999 to 2020. The NLR was calculated, and its associations with cardiovascular disease (CVD) mortality and all-cause mortality were assessed by multivariate Cox regression, restricted cubic spline and Kaplan-Meier curves. The study performed subgroup analyses to validate the robustness of the findings in different populations. The predictive ability of NLR was evaluated using time-dependent receiver operating characteristic curve. The indirect impact of eGFR was explored by mediation analysis. RESULTS: As NLR values increased, there was an obvious rise in the risk of mortality in MetS. The fully adjusted continuous model revealed a 16.0%, 14.4% elevated risk of CVD mortality (HR = 1.160; 95% CI: 1. 090-1.234, p < 0.0001) and all-cause mortality (HR = 1.144; 95% CI: 1. 086-1.206, p < 0.0001), respectively, with each one-unit increment in NLR. Comparing the highest to the lowest quartile of NLR, the top quartile exhibited a significantly increased risk of CVD mortality (HR = 2. 447; 95% CI: 1. 561-3. 836, p < 0.0001), and all-cause mortality (HR = 1. 53; 95% CI: 1. 188-1. 972, p = 0.001) among individuals with MetS. Subgroup analyses substantiated the stability of these associations in most populations. The curve under area for the 3, 5, and 10 years were 0.650, 0.716, and 0.645 for CVD mortality, and 0.746, 0.688, and 0.635 for all-cause mortality. Significantly, the eGFR acted as an intermediary in the relationship of NLR with CVD mortality and all-cause mortality, accounting for 9.85% and 9.86% of the effect, respectively. CONCLUSION: The NLR served as a significant indicator for assessing the risk of mortality in the MetS population. Consequently, we recommended the regular assessment of NLR in MetS populations as a potentially advantageous method for evaluating their risk of mortality.

Impacts of cardiometabolic risk factors and alcohol consumption on all-cause mortality among MASLD and its subgroups.

BACKGROUND AND AIMS: Recently, metabolic dysfunction-associated steatotic liver disease (MASLD) has been introduced. However, research on this new nomenclature and definition remains limited. This study aims to assess the impact of cardiometabolic risk factors and alcohol consumption on all-cause mortality in MASLD and its subgroups. METHODS AND RESULTS: We included 2408 participants with MASLD in NHANES III and their linked mortality through 2019. MASLD patients were divided into two groups based on alcohol consumption: Pure MASLD and MetALD. The Cox proportional hazard model was used to assess the association between factors and all-cause mortality. During the median 26.0-year follow-up, there were 1040 deaths. The multivariable Cox regression analysis revealed a significant increase of over two-fold in the all-cause mortality rate among patients with four or more cardiometabolic risk factors compared to those with only one. When focusing on each component of cardiometabolic risk factors individually, only diabetes and hypertension were significantly associated with all-cause mortality (p < 0.05). In a subgroup analysis, each additional cardiometabolic factor was linked to an increase in all-cause mortality in both pure MASLD (hazard ratio 1.16; 95% CI 1.06-1.28; p = 0.002) and MetALD (HR 1.77; 95% CI 1.26-2.49; p = 0.001). Notably, an elevation in alcohol consumption was significantly associated with an increase in all-cause mortality rate only in the MetALD (p < 0.001). CONCLUSIONS: This study found that the presence of diabetes or hypertension was significantly associated with all-cause mortality. We also explored the different impacts of these factors and alcohol consumption within MASLD subgroups.

Cardiovascular-Kidney-Metabolic Syndrome: Association with Adverse Events After Major Noncardiac Surgery.

BACKGROUND: The American Heart Association (AHA) recently defined the cardiovascular-kidney-metabolic syndrome (CKM) as a new entity to address the complex interactions between heart, kidneys, and metabolism. The aim of this study was to assess the outcome impact of CKM syndrome in patients undergoing noncardiac surgery. METHODS: This is a secondary analysis of a prospective international cohort study including patients aged ≥45 years with increased cardiovascular risk undergoing noncardiac surgery. Main exposure was CKM syndrome according to the AHA definition. The primary end point was a composite of major adverse cardiovascular events (MACE) 30 days after surgery. Secondary end points included all-cause mortality and non-MACE complications (Clavien-Dindo class ≥3). RESULTS: This analysis included 14,634 patients (60.8% male, mean age = 72±8 years). MACE occurred in 308 patients (2.1%), and 335 patients (2.3%) died. MACE incidence by CKM stage was as follows: CKM 0: 5/367 = 1.4% (95% confidence interval [CI], 0.4%-3.2%); CKM 1: 3/367 = 0.8% (95% CI, 0.2%-2.4%); CKM 2: 102/7440 = 1.4% (95% CI, 1.1%-1.7%); CKM 3: 27/953 = 2.8% (95% CI, 1.9%-4.1%); CKM 4a: 164/5357 = 3.1% (95% CI, 2.6%-3.6%); CKM 4b: 7/150 = 4.7% (95% CI, 1.9%-9.4%). In multivariate logistic regression, CKM stage ≥3 was independently associated with MACE, mortality, and non-MACE complications, respectively (MACE: OR 2.26 [95% CI, 1.78-2.87]; mortality: OR 1.42 [95% CI: 1.13 -1.78]; non-MACE complications: OR 1.11 [95% CI: 1.03-1.20]). CONCLUSION: The newly defined CKM syndrome is associated with increased morbidity and mortality after non-cardiac surgery. Thus, cardiovascular, renal, and metabolic disorders should be regarded in mutual context in this setting.

Dietary niacin Intake and its association with all-cause and cardiovascular mortality rates in individuals with metabolic syndrome.

BACKGROUND: Individuals with metabolic syndrome face elevated cardiovascular and mortality risks, and there is ongoing debate regarding the cardiovascular effects of niacin and its impact on the prognosis of metabolic syndrome. EXPOSURE: Levels of dietary niacin intake based on 24-hour dietary recall. METHODS: Kaplan-Meier survival curves were used to compare survival status among quartiles of dietary niacin intake. Weighted Cox proportional hazards models and restricted cubic splines were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of all-cause and CVD mortality associated with the exposure. RESULTS: This cohort study included 8,744 participants, and during a median follow-up period of 106 months, 1,552 (17.7%) deaths were recorded, with 511 attributed to cardiovascular disease. Kaplan-Meier curves comparing quartiles of dietary niacin intake showed significant differences in both all-cause and cardiovascular mortality rates (log-rank p < 0.001). In the fully adjusted model, the highest quartile of dietary niacin intake was associated with HRs of 0.68 (95% CI: 0.54, 0.87, P = 0.002) for all-cause mortality and 0.63 (95% CI: 0.39, 0.78, P < 0.001) for cardiovascular mortality. CONCLUSION: The results of this cohort study suggest that higher dietary niacin intake is associated with reduced cardiovascular and all-cause mortality risks in the metabolic syndrome population. Furthermore, there appears to be a dose-response relationship between dietary niacin intake and the risks of all-cause and cardiovascular mortality.

Associations between body fat anthropometric indices and mortality among individuals with metabolic syndrome.

BACKGROUND: The distribution of body fat and metabolic health may contribute to the onset of metabolic syndrome (MetS), but the associations between body fat anthropometric indices (AIs) and mortality in individuals with MetS remain unclear. METHODS: Participants aged 18 years or older with MetS were recruited from the NHANES 1999-2018. The body fat anthropometric indices included the a body shape index (ABSI), body roundness index (BRI), cardiometabolic index (CMI), visceral adiposity index (VAI), waist triglyceride index (WTI), lipid accumulation product (LAP), atherogenic index of plasma (AIP), and triglyceride‒glucose (TyG) index. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII) criteria. Mortality data were obtained from the National Death Index through December 31, 2019. RESULTS: Data were collected from 8,379 individuals with MetS, with a median follow-up of 8.5 years, of whom 1,698 died from all causes and 568 from the CCD. The random survival forest (RSF) analysis indicated that the ABSI had the strongest predictive power for both all-cause mortality and CCD mortality among the eight body fat AIs. After adjusting for multiple variables, the ABSI was found to be linearly and positively associated with all-cause and CCD mortality in individuals with MetS. Participants in the highest quartile of ABSI had an increased risk of all-cause (HR = 1.773 [1.419-2.215]) and CCD (HR = 1.735 [1.267-2.375]) mortality compared with those in the lowest quartile. Furthermore, the ABSI predicted areas under the curve (AUCs) of 0.735, 0.723, 0.718, and 0.725 for all-cause mortality at 3, 5, 10, and 15 years, respectively, and 0.774, 0.758, 0.725, and 0.715 for CCD mortality, respectively. CONCLUSION: Among eight body fat AIs, the ABSI exhibited the strongest predictive power for mortality in individuals with MetS. Higher ABSI values significantly increased all-cause mortality and CCD mortality in participants with MetS.

Interrelationships among abnormal P-wave axis, metabolic syndrome and its components, and mortality in US adults.

BACKGROUND: Metabolic syndrome (MetS) is associated with increased rates of cardiovascular disease and mortality and is linked to abnormal electrocardiogram (ECG) parameters. We aimed to explore the relationships and interactions among MetS and its components, abnormal P-wave axis (aPWA), and mortality rates. METHODS: We analyzed data from 7526 adult participants with sinus rhythm recruited from the National Health and Nutrition Examination Survey III. MetS was classified based on the NCEP ATP III-2005 definition. aPWA included all P-wave axis outside 0-75°. The National Death Index was utilized to identify survival status. Hazard ratios (HRs) and 95% confidence intervals (CIs) categorized by aPWA, MetS, and their components were analyzed using Cox proportional hazards models to investigate all-cause and cardiovascular mortalities. RESULTS: Within a median follow-up period of 20.76 years, 4686 deaths were recorded, of which 1414 were attributable to cardiovascular disease. Participants with both MetS and aPWA had higher all-cause (HR: 1.45, 95% CI: 1.29-1.64, interaction P = 0.043) and cardiovascular (HR: 1.36, 95% CI: 1.02-1.79, interaction P-value = 0.058) mortality rates than participants without MetS and with a normal P-wave axis. Participants with the greatest number of MetS components and aPWA had a higher risk of all-cause mortality (HR: 1.70, 95% CI: 1.13-2.55, P = 0.011). CONCLUSIONS: Individuals with both aPWA and MetS have a higher risk of mortality, and those with a greater number of MetS components and aPWA have a higher risk of all-cause mortality. These findings highlight the significance of integrating ECG characteristics with metabolic health status in clinical assessment.

Association between metabolic syndrome and outcomes of large-artery atherosclerosis stroke treated with reperfusion therapy.

AIM: We aimed to investigate the impact of metabolic syndrome (MetS) on the outcomes of stroke patients with large-artery atherosclerosis who underwent reperfusion therapy. METHODS: A retrospective analysis was carried out on patients receiving reperfusion therapy for atherothrombotic stroke between January 2019 and May 2021. MetS was diagnosed according to the AHA/NHLBI criteria. The primary outcome was the composite outcome of disability (modified Rankin Scale [mRS] score 3-5), death or stroke recurrence within 3 months of stroke onset. Secondary outcomes included disability and death within 3 months as well as hemorrhagic transformation (HT) and symptomatic intracranial hemorrhage (sICH) within 24 hours after reperfusion treatment. The independent association of MetS with the above outcomes and the highly correlated components of MetS was examined using binary logistic regression analysis. RESULTS: A total of 174 patients were enrolled. MetS patients had a higher proportion of the composite outcome (p = 0.012), disability (p = 0.029) and HT (p = 0.049) than those without MetS, except for death (p = 0.375) and sICH (p = 0.306). Following adjustments, MetS remained independently associated with the composite outcome (adjusted OR, 3.011 [95 %CI 1.372-6.604]; p = 0.006) and disability (adjusted OR, 2.727 [95 %CI 1.220-6.098]; p = 0.015), but not HT (adjusted OR, 1.872 [95 %CI 0.854-4.104]; p = 0.117). Hypertriglyceridemia was remarkedly associated with the composite outcome (adjusted OR, 9.746 [95 % CI 2.402-39.536]; p = 0.001) and disability (adjusted OR, 6.966 [95 % CI 1.889-25.692]; p = 0.004). CONCLUSION: MetS is independently associated with an increased risk of composite outcome and disability in patients with large-artery atherosclerosis stroke receiving reperfusion therapy, and hypertriglyceridemia is the main component that drives the effect of MetS on outcomes.

Low calf circumference can predict nutritional risk and mortality in adults with metabolic syndrome aged over 80 years.

BACKGROUND: Metabolic disorders and malnutrition are a double burden worldwide. The aim was to determine whether low calf circumference (CC) could predict nutritional risk and the cut-off values of CC for predicting nutritional risk in metabolic syndrome (MetS) patients aged over 80 years. We aimed to evaluate the risk factors for predicting mortality in MetS. METHODS: A total of 514 patients aged over 80 years with MetS were enrolled and followed for 2.5 years. On admission, demographic data, CC, and laboratory parameters were obtained. Patients with a Nutritional Risk Screening 2002 (NRS 2002) total score ≥ 3 were considered to have nutritional risk. RESULTS: The CC level was significantly lower in the nutritional risk group than in the non-nutritional risk with MetS group (27.1 ± 4.0 cm vs. 30.8 ± 3.9 cm). Logistic regression analysis of nutritional risk revealed that increasing CC (adjusted OR, 0.81; 95% CI, 0.74-0.88) was an independent protective factor against nutrition risk. The best CC cut-off value for predicting nutritional risk according to the NRS 2002 was 28.8 cm. Cox regression multivariate models showed nutritional risk (HR, 2.48; 95% CI, 1.22-5.04) and decreased CC (HR, 2.78; 95% CI, 1.27-5.98) remained independent risk factors for mortality. CONCLUSION: Decreased CC could predict not only nutritional risk but also mortality in MetS patients aged over 80 years. The elderly who had MetS with nutritional risk should be discovered early, early intervention and early treatment. CC may be a valuable index to screen out this population.

Association of serum HDL-cholesterol and apolipoprotein A1 levels with risk of severe SARS-CoV-2 infection.

Individuals with features of metabolic syndrome are particularly susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus associated with the severe respiratory disease, coronavirus disease 2019 (COVID-19). Despite considerable attention dedicated to COVID-19, the link between metabolic syndrome and SARS-CoV-2 infection remains unclear. Using data from the UK Biobank, we investigated the relationship between severity of COVID-19 and metabolic syndrome-related serum biomarkers measured prior to SARS-CoV-2 infection. Logistic regression analyses were used to test biomarker levels and biomarker-associated genetic variants with SARS-CoV-2-related outcomes. Among SARS-CoV-2-positive cases and negative controls, a 10 mg/dl increase in serum HDL-cholesterol or apolipoprotein A1 levels was associated with ∼10% reduced risk of SARS-CoV-2 infection, after adjustment for age, sex, obesity, hypertension, type 2 diabetes, and coronary artery disease. Evaluation of known genetic variants for HDL-cholesterol revealed that individuals homozygous for apolipoprotein E4 alleles had ∼2- to 3-fold higher risk of SARS-CoV-2 infection or mortality from COVID-19 compared with apolipoprotein E3 homozygotes, even after adjustment for HDL-cholesterol levels. However, cumulative effects of all evaluated HDL-cholesterol-raising alleles and Mendelian randomization analyses did not reveal association of genetically higher HDL-cholesterol levels with decreased risk of SARS-CoV-2 infection. These results implicate serum HDL-cholesterol and apolipoprotein A1 levels measured prior to SAR-CoV-2 exposure as clinical risk factors for severe COVID-19 infection but do not provide evidence that genetically elevated HDL-cholesterol levels are associated with SAR-CoV-2 infection.

Metabolic syndrome risk components and mortality after triple-negative breast cancer diagnosis in postmenopausal women in the Women's Health Initiative.

BACKGROUND: Triple-negative breast cancer (TNBC) has a high recurrence risk and poor clinical outcomes. Associations between metabolic syndrome (MetS) risk components and mortality in postmenopausal women with TNBC were examined in the Women's Health Initiative. METHODS: Five hundred forty-four postmenopausal women were diagnosed with nonmetastatic TNBC. Baseline risk components included a high waist circumference (≥88 cm), high blood pressure, hypercholesterolemia, and diabetes. Groups were categorized by the number of MetS risk components: none, 1 or 2, or 3 or 4. Hazard ratios (HRs) and 95% confidence intervals (CIs) across groups were computed with multivariable adjusted Cox models. Outcomes included breast cancer-specific mortality and breast cancer overall mortality (breast cancer followed by death from any cause). Variables in the multivariable model included age at TNBC diagnosis; race/ethnicity; income; education; clinical/observational trial status; history of oral contraceptive, hormone, and/or statin use; cancer stage; and chemotherapy and/or radiation treatment status. RESULTS: Of the 544 participants with TNBC, 33% had no MetS risk components (n = 178), 59% had 1 or 2 risk components (n = 323), and 8% had 3 or 4 risk components (n = 43). After a median follow-up from diagnosis of 8.3 years, multivariable results showed that women with 3 or 4 risk components had a nonsignificantly higher risk of breast cancer mortality (HR, 2.05; 95% CI, 0.94-4.47 trend P = .114) and a significantly higher risk of overall mortality (HR, 2.13; 95% CI, 1.22-3.71; trend P = .006) versus women with 0 risk components. CONCLUSIONS: Postmenopausal women with TNBC and 3 or 4 MetS risk components have a nonsignificantly higher breast cancer mortality risk and a significantly higher overall mortality risk, likely because of negative influences of metabolic risk factors on several causes of death.

Low-fat dietary pattern and breast cancer mortality by metabolic syndrome components: a secondary analysis of the Women's Health Initiative (WHI) randomised trial.

BACKGROUND: In the Women's Health Initiative (WHI) dietary modification (DM) randomised trial, the low-fat dietary intervention reduced deaths from breast cancer (P = 0.02). Extending these findings, secondary analysis examined dietary intervention influence on breast cancer mortality by metabolic syndrome (MS) components. METHODS: In total, 48,835 postmenopausal women with no prior breast cancer were randomised to a low-fat dietary intervention or comparison groups. Four MS components were determined at entry in 45,833 participants: (1) high waist circumference, (2) high blood pressure, (3) high cholesterol and (4) diabetes history. Forest plots of hazard ratios (HRs) were generated with P-values for interaction between randomisation groups and MS component score. Primary outcome was death from breast cancer by metabolic syndrome score. RESULTS: HRs and 95% confidence intervals (CI) for dietary intervention influence on death from breast cancer were with no MS components (n = 10,639), HR 1.09, 95% CI 0.63-1.87; with 1-2 MS components (n = 30,948), HR 0.80, 95% CI 0.62-1.02; with 3-4 MS components (n = 4,246), HR 0.31, 95% CI 0.14-0.69 (interaction P = 0.01). CONCLUSIONS: While postmenopausal women with 3-4 MS components were at higher risk of death from breast cancer, those randomised to a low-fat dietary intervention more likely had reduction in this risk. REGISTRY: ClinicalTrials.gov (NCT00000611).