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.

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.

The prognostic role of heart rate recovery after exercise and metabolic syndrome in IgA nephropathy.

BACKGROUND: Cardiovascular (CV) morbidity and mortality are higher in chronic kidney disease (CKD) than in the general population. Reduced heart rate recovery (HRR) is an independent risk factor for CV disease. The aim of the study was to determine the prognostic role of HRR in a homogenous group of CKD patients. METHODS: One hundred and twenty-five IgA nephropathy patients (82 male, 43 female, age 54.7 ± 13 years) with CKD stage 1-4 were investigated and followed for average 70 months. We performed a graded exercise treadmill stress test. HRR was derived from the difference of the peak heart rate and the heart rate at 1 min after exercise. Patients were divided into two groups by the mean HRR value (22.9 beats/min). The composite (CV and renal) endpoints included all-cause mortality and any CV event such as stroke, myocardial infarction, revascularisation (CV) and end-stage renal disease, renal replacement therapy (renal). RESULTS: Patients with reduced HRR (< 23 bpm) had significantly more end point events (22/62 patients vs. 9/53 patients, p = 0.013) compared to the higher HRR (≥23 bpm). Of the secondary the endpoints (CV or renal separately) rate of the renal endpoint was significantly higher in the lower HRR group (p = 0.029), while there was no significant difference in the CV endpoint between the two HRR groups (p = 0.285). Independent predictors of survival were eGFR and diabetes mellitus by using Cox regression analysis. Kaplan-Meier curves showed significant differences in metabolic syndrome and non-metabolic syndrome when examined at the combined endpoints (cardiovascular and renal) or at each endpoint separately. The primary endpoint rate was increased significantly with the increased number of metabolic syndrome component (Met.sy. comp. 0 vs. Met. sy. comp. 2+, primary endpoints, p = 0.012). CONCLUSION: Our results showed that reduced HRR measured by treadmill exercise test has a predictive value for the prognosis of IgA nephropathy. The presence of metabolic syndrome may worsen the prognosis of IgA nephropathy.

Visit-to-visit variability in the measurements of metabolic syndrome components and the risk of all-cause mortality, cardiovascular disease, and arterial stiffness.

BACKGROUND AND AIMS: The risk of adverse health conditions varied according to the number of metabolic syndrome components. We aimed to evaluate the risk of mortality and incident cardiovascular events according to the number of components with high variability. METHODS AND RESULTS: A total of 43,737 Kailuan Study participants with ≥3 examinations of waist circumference, fasting blood glucose, systolic blood pressure, triglyceride, and high-density lipoprotein during 2006-2013 were included in the present study. Visit-to-visit variability in each parameter was defined by the intraindividual standard deviation across visits. High variability was defined as the highest quartile of variability. Participants were classified numerically according to the number of high-variability components (e.g., a score of 0 indicated no high-variability component). There were 1551 deaths during a median follow-up of 5.9 years, and 950 incident cardiovascular disease (CVD) cases during a median follow-up of 4.9 years. In the multivariable adjusted model, compared with participants with low variability for all components, participants with ≥3 high-variability components had significantly higher risks for all-cause mortality (hazards ratio [HR], 1.61; 95 % confidence interval [CI], 1.35-1.91) and incident CVD event (HR, 1.45; 95 % CI, 1.16-1.82). Additionally, participants with ≥3 high-variability components had increased odds of arterial stiffness, as measured by brachia-ankle pulse wave velocity (odds ratio [OR], 1.39; 95 % CI, 1.19-1.63). CONCLUSIONS: Our findings suggest that participants with at least three metabolic parameters with high variability experienced increased risk of CVD and all-cause mortality.

Prevalence and impact of metabolic syndrome in patients with multivessel coronary artery disease and acute coronary syndrome.

BACKGROUND AND AIMS: Metabolic syndrome (MetS) is associated with increased incidence of diabetes and cardiovascular diseases in patients initially free from these diseases. However, its prognostic value in patients with established coronary artery diseases remains controversial. Therefore, we aimed to illustrate the prevalence and investigate the impact of MetS in patients with multivessel coronary artery disease (MVD) and acute coronary syndrome (ACS). METHODS AND RESULTS: This was a large registry of consecutive patients with ACS referred to primary percutaneous coronary intervention (PCI) and those with MVD were eligible for this analysis. MetS was defined based on modified Adult Treatment Panel III definition. The primary outcome was major adverse cardiovascular events (MACE), a composite of all-cause death, myocardial infarction and stroke. A total of 2532 patients were included in the current analysis and 993 (39.2%) of them had MetS. The prevalence of MetS increased from 2010 to 2016 (p for trend = 0.005). In patients over 60 years old, the prevalence of MetS decreased with aging (p for trend = 0.002). Female subjects had a higher prevalence than their male counterparts (61.5% verse 32.9% and p < 0.001). Over a median follow-up of 2.3 years, MetS was not significantly associated with MACE (adjusted 95% CI from 0.92 to 1.54). CONCLUSION: MetS was frequently observed in patients with MVD and ACS. Patients with MetS were more likely to be young and female. However, it was not an independent predictor for MACE after primary PCI in those patients.

Cholesterol and Egg Intakes with Cardiometabolic and All-Cause Mortality among Chinese and Low-Income Black and White Americans.

We examined the associations of dietary cholesterol and egg intakes with cardiometabolic and all-cause mortality among Chinese and low-income Black and White Americans. Included were 47,789 Blacks, 20,360 Whites, and 134,280 Chinese aged 40-79 years at enrollment. Multivariable Cox models with restricted cubic splines were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality outcomes using intakes of 150 mg cholesterol/day and 1 egg/week as the references. Cholesterol intake showed a nonlinear association with increased all-cause mortality and a linear association with increased cardiometabolic mortality among Black Americans: HRs (95% CIs) associated with 300 and 600 mg/day vs. 150 mg/day were 1.07 (1.03-1.11) and 1.13 (1.05-1.21) for all-cause mortality (P-linearity = 0.04, P-nonlinearity = 0.002, and P-overall < 0.001) and 1.10 (1.03-1.16) and 1.21 (1.08-1.36) for cardiometabolic mortality (P-linearity = 0.007, P-nonlinearity = 0.07, and P-overall = 0.005). Null associations with all-cause or cardiometabolic mortality were noted for White Americans (P-linearity ≥ 0.13, P-nonlinearity ≥ 0.06, and P-overall ≥ 0.05 for both). Nonlinear inverse associations were observed among Chinese: HR (95% CI) for 300 vs. 150 mg/day was 0.94 (0.92-0.97) for all-cause mortality and 0.91 (0.87-0.95) for cardiometabolic mortality, but the inverse associations disappeared with cholesterol intake > 500 mg/day (P-linearity ≥ 0.12; P-nonlinearity ≤ 0.001; P-overall < 0.001 for both). Similarly, we observed a positive association of egg intake with all-cause mortality in Black Americans, but a null association in White Americans and a nonlinear inverse association in Chinese. In conclusion, the associations of cholesterol and egg intakes with cardiometabolic and all-cause mortality may differ across ethnicities who have different dietary patterns and cardiometabolic risk profiles. However, residual confounding remains possible.

Increasing adiposity and the presence of cardiometabolic morbidity is associated with increased Covid-19-related mortality: results from the UK Biobank.

BACKGROUND: Although obesity, defined by body mass index (BMI), has been associated with a higher risk of hospitalisation and more severe course of illness in Covid-19 positive patients amongst the British population, it is unclear if this translates into increased mortality. Furthermore, given that BMI is an insensitive indicator of adiposity, the effect of adipose volume on Covid-19 outcomes is also unknown. METHODS: We used the UK Biobank repository, which contains clinical and anthropometric data and is linked to Public Health England Covid-19 healthcare records, to address our research question. We performed age- and sex- adjusted logistic regression and Chi-squared test to compute the odds for Covid-19-related mortality as a consequence of increasing BMI, and other more sensitive indices of adiposity such as waist:hip ratio (WHR) and percent body fat, as well as concomitant cardiometabolic illness. RESULTS: 13,502 participants were tested for Covid-19 (mean age 70 ± 8 years, 48.9% male). 1582 tested positive (mean age 68 ± 9 years, 52.8% male), of which 305 died (mean age 75 ± 6 years, 65.5% male). Increasing adiposity was associated with higher odds for Covid-19-related mortality. For every unit increase in BMI, WHR and body fat, the odds of death amongst Covid19-positive participants increased by 1.04 (95% CI 1.01-1.07), 10.71 (95% CI 1.57-73.06) and 1.03 (95% CI 1.01-1.05), respectively (all p < 0.05). Referenced to Covid-19 positive participants with a normal weight (BMI 18.5-25 kg/m2), Covid-19 positive participants with BMI > 35 kg/m2 had significantly higher odds of Covid-19-related death (OR 1.70, 95% CI 1.06-2.74, p < 0.05). Covid-19-positive participants with metabolic (diabetes, hypertension, dyslipidaemia) or cardiovascular morbidity (atrial fibrillation, angina) also had higher odds of death. CONCLUSIONS: Anthropometric indices that are more sensitive to adipose volume and its distribution than BMI, as well as concurrent cardiometabolic illness, are associated with higher odds of Covid-19-related mortality amongst the UK Biobank cohort that tested positive for the infection. These results suggest adipose volume may contribute to adverse Covid-19-related outcomes associated with obesity.

Associations between elevated kidney and liver biomarker ratios, metabolic syndrome and all-cause and coronary heart disease (CHD) mortality: analysis of the U.S. National Health and Nutrition Examination Survey (NHANES).

BACKGROUND: We examined the relationship between ratios of select biomarkers of kidney and liver function on all-cause and coronary heart disease (CHD) mortality, both in isolation, and in combination with metabolic syndrome (MetS), among adults (20 + years, n = 10,604). METHODS: Data was derived from the U.S. National Health and Nutrition Examination Survey (1999-2016) including public-use linked mortality follow-up files through December 31, 2015. RESULTS: Select biomarker ratios of kidney (UACR or albuminuria and BUN-CR) and liver (AST-ALT and GGT-ALP) function in isolation and in combination with MetS were associated with all-cause and CHD mortality. Compared to individuals with neither elevated biomarker ratios nor MetS (HR = 1.00, referent), increased risk of all-cause mortality was observed in the following groups: MetS with elevated UACR (HR, 95% CI = 2.57, 1.99-3.33), MetS with elevated AST-ALT (HR = 2.22, 1.61-3.07), elevated UACR without MetS (HR = 2.12, 1.65-2.72), and elevated AST-ALT without MetS (HR = 1.71, 1.35-2.18); no other biomarker ratios were associated with all-cause mortality. For cause-specific deaths, elevated risk of CHD mortality was associated with MetS with elevated UACR (HR = 1.67, 1.05-2.67), MetS with elevated AST-ALT (HR = 2.80, 1.62-4.86), and elevated BUN-CR without MetS (HR = 2.12, 1.12-4.04); no other biomarker ratios were associated with CHD mortality. CONCLUSION: Future longitudinal studies are necessary to examine the utility of these biomarker ratios in risk stratification for chronic disease management.

Chronic Cardio-Metabolic Disease Increases the Risk of Worse Outcomes Among Hospitalized Patients With COVID-19: A Multicenter, Retrospective, and Real-World Study.

Background Although chronic cardio-metabolic disease is a common comorbidity among patients with COVID-19, its effects on the clinical characteristics and outcome are not well known. Methods and Results This study aimed to explore the association between underlying cardio-metabolic disease and mortality with COVID-19 among hospitalized patients. This multicenter, retrospective, and real-world study was conducted from January 22, 2020 to March 25, 2020 in China. Data between patients with and without 5 main cardio-metabolic diseases including hypertension, diabetes mellitus, coronary heart disease, cerebrovascular disease, and hyperlipidemia were compared. A total of 1303 hospitalized patients were included in the final analysis. Of them, 520 patients (39.9%) had cardio-metabolic disease. Compared with patients without cardio-metabolic disease, more patients with cardio-metabolic disease had COVID-related complications including acute respiratory distress syndrome (9.81% versus 3.32%; P<0.001), acute kidney injury (4.23% versus 1.40%; P=0.001), secondary infection (13.9% versus 9.8%; P=0.026), hypoproteinemia (12.1% versus 5.75%; P<0.001), and coagulopathy (19.4% versus 10.3%; P<0.001), had higher incidences of the severe type of COVID-19 (32.9% versus 16.7%; P<0.001), more were admitted to the intensive care unit (11.7% versus 7.92%; P=0.021), and required mechanical ventilation (9.8% versus 4.3%; P<0.001). When the number of the patients' cardio-metabolic diseases was 0, 1, and >2, the mortality was 4.2%, 11.1%, and 19.8%, respectively. The multivariable-adjusted hazard ratio of mortality among patients with cardio-metabolic disease was 1.80 (95% CI, 1.17-2.77). Conclusions Cardio-metabolic disease was a common condition among hospitalized patients with COVID-19, and it was associated with higher risks of in-hospital mortality.

[Evolution of patients infected with SARS-CoV-2 according to previous metabolic status]. / Evolución de la infección por SARS-CoV-2 en función del estado metabólico previo del paciente.

INTRODUCTION: Introduction: coronavirus disease 2019 (COVID-19) encompasses a wide spectrum of symptoms, including respiratory, gastrointestinal, hematological, and dermatological manifestations. The virus interaction with cells located in the respiratory tract causes the release of inflammatory mediators, whose involvement could be exacerbated by co-existing obesity, diabetes, and cardiovascular events. Objectives: the objective of this research was to analyze the clinically metabolic status in patients who have suffered COVID-19 disease in order to predict the outcome. Methods: this research is a retrospective study based on a cohort of 165 consecutively admitted patients with criteria for COVID-19 pneumonia according to WHO guidelines at the Hospital Universitario Puerta de Hierro between March and April 2020. Recorded variables included demographic and epidemiological data plus diagnoses as well as morbid complications during hospitalization. The Biochemistry Unit Laboratory carried out laboratory analyses according to validated operational procedures. The statistical tests included univariate and multivariate models adjusted for baseline characteristics and clinically relevant features. Results: the most frequent comorbidity in our cohort was arterial hypertension (44.0 %), followed by dyslipidemia (32.1 %), obesity (30.9 %), and diabetes mellitus (20.0 %). The association between admission to the intensive care unit (ICU) with body mass index (BMI) in a multivariate model was statistically significant, evidencing that obese subjects (BMI ≥ 30 kg/m2) have a 19 % higher risk of requiring ICU care. The univariate model revealed a statistically significant association between obesity and ICU admission and length of hospital stay (p < 0.05). The relationship between baseline blood glucose and in-hospital mortality was also statistically significant (p = 0.03), as well as with total cholesterol and ICU admission (p = 0.007). Conclusions: obesity is related to a longer time of hospitalization and a higher rate of admissions to the ICU. Low total cholesterol levels and abnormal baseline blood glucose were risk factors for ICU requirement and in-hospital mortality. Patient categorization based on obesity could be valuable in the development of a precision medicine model within the COVID-19 pandemic.

INTRODUCCIÓN: Introducción: la enfermedad por COVID-19 engloba un amplio espectro de síntomas entre los que destacan los trastornos respiratorios, digestivos, hematológicos y dermatológicos. La interacción del virus con las células ubicadas en el tracto respiratorio provoca la liberación de mediadores inflamatorios cuya producción podría estar relacionada con la obesidad, la diabetes y los eventos cardiovasculares. Objetivos: analizar el estado metabólico al ingreso de los pacientes infectados por SARS-CoV-2 y su capacidad para predecir el desenlace clínico. Métodos: este trabajo consiste en un estudio retrospectivo basado en una cohorte de 165 pacientes ingresados consecutivamente en el Hospital Universitario Puerta de Hierro Majadahonda entre marzo y abril de 2020 con criterios de neumonía COVID-19 según las pautas de la OMS. Las variables registradas incluyeron datos socio-demográficos y epidemiológicos, herramientas diagnósticas y complicaciones durante el ingreso hospitalario. El Servicio de Bioquímica del centro realizó los análisis de laboratorio empleando procedimientos validados. El estudio estadístico incluye modelos univariantes y multivariados, ajustados por las características basales clínicamente relevantes de la población. Resultados: la comorbilidad más frecuente en nuestra población fue la hipertensión arterial (44,0 %), seguida por la dislipemia (32,1 %), la obesidad (30,9 %) y la diabetes mellitus (20,0 %). En el análisis multivariante, la asociación del ingreso en la Unidad de Cuidados Intensivos (UCI) con el índice de masa corporal (IMC) resultó estadísticamente significativa, con un 19 % más de riesgo en aquellos pacientes con IMC ≥ 30 kg/m2. El modelo univariante reveló la asociación estadísticamente significativa de la obesidad y el ingreso en la UCI con la duración de la estancia hospitalaria (p < 0,05). La relación entre glucemia basal y mortalidad intrahospitalaria también resultó estadísticamente significativa (p = 0,03). Los niveles bajos de colesterol total se asociaron a una tasa mayor de ingresos en la UCI (p = 0,007). Conclusiones: la obesidad se asocia a una mayor estancia hospitalaria y necesidad de ingreso en la UCI en los pacientes infectados por el SARS-CoV-2. El descenso en las cifras de colesterol total y una glucemia basal alterada son factores de riesgo del ingreso en la UCI y la mortalidad intrahospitalaria. La categorización en función del grado de obesidad de los pacientes podría ser de utilidad en el desarrollo de un modelo de medicina de precisión en el contexto de la COVID-19.

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).

Association Between Metabolic Syndrome and All-Cause Mortality in Patients with Acute Coronary Syndrome: A Meta-Analysis.

The association between metabolic syndrome (MetS) and survival outcome after acute coronary syndrome (ACS) remains controversial. This meta-analysis sought to examine the association of MetS with all-cause mortality among patients with ACS. Two authors independently searched PubMed and Embase databases (from their inception to June 27, 2020) for studies that examined the association of MetS with all-cause mortality among patients with ACS. Outcome measures were in-hospital mortality and all-cause mortality during the follow-up. A total of 10 studies involving 49 896 ACS patients were identified. Meta-analysis indicated that presence of MetS was associated with an increased risk of long-term all-cause mortality [risk ratio (RR) 1.25; 95% CI 1.15-1.36; n=9 studies] and in-hospital mortality (RR 2.35; 95% CI 1.40-3.95; n=2 studies), respectively. Sensitivity and subgroup analysis demonstrated the credibility of the value of MetS in predicting long-term all-cause mortality. MetS is associated with an increased risk of long-term all-cause mortality among patients with ACS. However, additional studies are required to investigate the association of MetS with in-hospital mortality.

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-related dietary pattern and risk of mortality in kidney transplant recipients.

BACKGROUND AND AIMS: Presence of the metabolic syndrome (MetS) importantly contributes to excess mortality in kidney transplant recipients (KTRs). However, it is unclear which dietary factors drive the adverse role of MetS in KTRs. We aimed to define a dietary pattern that maximally explained the variation in MetS components, and to investigate the association between this MetS-related dietary pattern (MetS-DP) and all-cause mortality in KTRs. METHODS AND RESULTS: We included 429 adult KTRs who had a functioning graft ⩾1 year. A MetS-DP was constructed using habitual dietary intake derived from a 177-item food frequency questionnaire. We used reduced rank regression (RRR), and defined the six components of MetS (waist circumference, systolic blood pressure, diastolic blood pressure, serum triglycerides, HbA1c, and HDL cholesterol) as response variables and 48 food groups as predictor variables. We evaluated the association between the MetS-DP and all-cause mortality using multivariable Cox regression analysis. The MetS-DP was characterized by high intakes of processed meat and desserts, and low intakes of vegetables, tea, rice, fruits, milk, and meat substitutes. During a mean follow-up of 5.3 ± 1.2 years, 63 KTRs (14.7%) died. Compared to the lowest tertile of the Mets-DP score, those with the greatest adherence had a more than 3-fold higher risk of all-cause mortality (hazard ratio [HR] = 3.63; 95% confidence interval [CI], 1.70-7.74, P < 0.001), independent of potential confounders. CONCLUSIONS: We identified a MetS-related dietary pattern which was independently associated with all-cause mortality in KTRs. The association between this dietary pattern and all-cause mortality was mediated by MetS. Clinical trial reg. no. NCT02811835.

The importance of including uric acid in the definition of metabolic syndrome when assessing the mortality risk.

INTRODUCTION: Serum uric acid (SUA) has been depicted as a contributory causal factor in metabolic syndrome (MS), which in turn, portends unfavourable prognosis. AIM: We assessed the prognostic role of SUA in patients with and without MS. METHODS: We used data from the multicentre Uric Acid Right for Heart Health study and considered cardiovascular mortality (CVM) as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart failure. RESULTS: A total of 9589 subjects (median age 58.5 years, 45% males) were included in the analysis, and 5100 (53%) patients had a final diagnosis of MS. After a median follow-up of 142 months, we observed 558 events. Using a previously validated cardiovascular SUA cut-off to predict CVM (> 5.1 mg/dL in women and 5.6 mg/dL in men), elevated SUA levels were significantly associated to a worse outcome in patients with and without MS (all p < 0.0001) and provided a significant net reclassification improvement of 7.1% over the diagnosis of MS for CVM (p = 0.004). Cox regression analyses identified an independent association between SUA and CVM (Hazard Ratio: 1.79 [95% CI, 1.15-2.79]; p < 0.0001) after the adjustment for MS, its single components and renal function. Three specific combinations of the MS components were associated with higher CVM when increasing SUA levels were reported, and systemic hypertension was the only individual component ever-present (all p < 0.0001). CONCLUSION: Increasing SUA levels are associated with a higher CVM risk irrespective of the presence of MS: a cardiovascular SUA threshold may improve risk stratification.

Dynamics of detailed components of metabolic syndrome associated with the risk of cardiovascular disease and death.

Few studies quantify a cascade of dynamic transitions on the detailed components of metabolic syndrome (MetS) and subsequent progressions to cardiovascular disease (CVD) and its death. A total of 47,495 subjects repeatedly attending a community-based integrated screening program in Taiwan were recruited. The refined MetS-related classification (RMRC) in relation to five criteria of MetS was defined as free of metabolic disorder (FMD, none of any criteria), mild metabolic disorder (MMD, 1-2 criteria) and MetS. A multistate Markov model was used for modelling such a multistate process. The estimated progression rate from FMD to MMD was 44.82% (95% CI 42.95-46.70%) whereas the regression rate was estimated as 29.11% (95% CI 27.77-30.45%). The progression rate from MMD to MetS was estimated as 6.15% (95% CI 5.89-6.42%). The estimated annual incidence rates of CVD increased with the severity of RMRC, being 1.62% (95% CI 1.46-1.79%) for FMD, 4.74% (95% CI 4.52-4.96%) for MMD, to 20.22% (95% CI 19.52-20.92%) for MetS. The estimated hazard rate of CVD death was 6.1 (95% CI 4.6-7.7) per thousand. Elucidating the dynamics of MetS-related transition and quantifying the incidence and prognosis of CVD provide a new insight into the design and the evaluation of intervention programs for CVD.

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.

Association between the Mediterranean lifestyle, metabolic syndrome and mortality: a whole-country cohort in Spain.

BACKGROUND: Evidence is limited about the joint health effects of the Mediterranean lifestyle on cardiometabolic health and mortality. The aim of this study was to evaluate the association of the Mediterranean lifestyle with the frequency of the metabolic syndrome (MS) and the risk of all-cause and cardiovascular mortality in Spain. METHODS: Data were taken from ENRICA study, a prospective cohort of 11,090 individuals aged 18+ years, representative of the population of Spain, who were free of cardiovascular disease (CVD) and diabetes at 2008-2010 and were followed-up to 2017. The Mediterranean lifestyle was assessed at baseline with the 27-item MEDLIFE index (with higher score representing better adherence). RESULTS: Compared to participants in the lowest quartile of MEDLIFE, those in the highest quartile had a multivariable-adjusted odds ratio 0.73 (95% confidence interval (CI) 0.5, 0.93) for MS, 0.63. (0.51, 0.80) for abdominal obesity, and 0.76 (0.63, 0.90) for low HDL-cholesterol. Similarly, a higher MELDIFE score was associated with lower HOMA-IR and highly-sensitivity C-reactive protein (P-trend < 0.001). During a mean follow-up of 8.7 years, 330 total deaths (74 CVD deaths) were ascertained. When comparing those in highest vs. lowest quartile of MEDLIFE, the multivariable-adjusted hazard ratio (95% CI) was 0.58 (0.37, 0.90) for total mortality and 0.33 (0.11, 1.02) for cardiovascular mortality. CONCLUSIONS: The Mediterranean lifestyle was associated with lower frequency of MS and reduced all-cause mortality in Spain. Future studies should determine if this also applies to other Mediterranean countries, and also improve cardiovascular health outside the Mediterranean basin.

Clinical profile and outcome of patients with chronic inflammatory arthritis and metabolic syndrome.

Systemic chronic inflammation may favor the onset of metabolic syndrome (MetS) which represents a risk factor for CV events. Rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are disorders with high prevalence of MetS. We assessed the factors associated with MetS and its prognostic role in non-selected RA/AS/PsA patients. Between March 2014 and April 2016, 458 patients (228 RA, 134 PsA, 96 AS) selected for a primary prevention program for cardiovascular diseases were analyzed. Primary and co-primary end points were a composite of all-cause death/all-cause hospitalization and CV death/CV hospitalization, respectively. MetS was diagnosed according to the IDF Task Force on Epidemiology and Prevention. Patients were divided into MetS + (73 = 16%) and MetS - (385 = 84%). At multivariate logistic analysis, cancer, moderate/high disease activity, higher LV mass (LVM) and degree of LV diastolic dysfunction were independently associated with MetS. At 36-month follow-up, the event rate for primary/co-primary end point was 52/15% in MetS + vs 23/7% in MetS - (both p < 0.001). At multivariate Cox regression analysis, MetS was related to primary end point (HR 1.52 [CI 1.01-2.47], p = 0.04) together with higher LVM, disease duration and higher prevalence of biologic DMARDs refractoriness, and to co-primary end point (HR 2.05 [CI 1.16-3.60], p = 0.01) together with older age and higher LVM. The RA/AS/PsA phenotype MetS + is a subject with moderate/high disease activity, LV structural and functional abnormalities at increased risk for cancer. MetS + identifies RA/AS/PsA patients at higher risk for CV and non-CV events, independently of traditional CV risk factors analyzed individually and traditional indexes of inflammation.