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Introduction and Objectives: Osteoporotic hip fractures in cirrhotic subjects are associated with increased post-fracture mortality. Our aim was to identify unfavorable factors that were associated with increased post-fracture mortality. Patients and Methods: We employed a retrospective evaluation of the short- and long-term prognosis of cirrhotic patients that were admitted with a hip fracture to our institution. Results: A total of 77 cirrhotic and 81 control patients were included. The majority of the patients who died either during the initial three months or during one year of follow-up after the hip fracture were cirrhotic. The patients that did not survive the three-month period suffered from decompensated cirrhosis. The variables that were associated upon multivariate analysis with increased one-year all-cause mortality in both the control and cirrhotic patients were the presence of either cirrhosis, congestive heart failure or low hemoglobin levels upon admission. The variables that were associated upon univariate analysis with increased one-year all-cause mortality only in the cirrhotic patients were the patient's age, the presence of hepatic encephalopathy, as well as the levels of serum albumin, PT (in %) and FIB-4. Our multivariate analysis disclosed that the admission level of PT (in %) was the only parameter that was associated with one-year all-cause mortality among the cirrhotic patients (adjusted OR 0.962, CI: 0.928–0.996, p = 0.029). Conclusions: Patients with decompensated cirrhosis are at an increased risk of dying during the first year after an osteoporotic hip fracture. Cirrhotic patients with osteoporosis who are at risk of hip fractures should be identified and measures to prevent this complication should be implemented. [ABSTRACT FROM AUTHOR]

Background/Objective: We investigated the relationship between daily adequate FV intake and risk of all-cause, cardiovascular disease (CVD), and cancer mortalities among Malaysian adults. Methods: Data from a total of 18,211 Malaysian adults aged 18 years and above whom participated in the National Health and Morbidity Survey 2011 were analyzed. The participants were followed up for approximately 11 years, and mortality data were ascertained through record linkages with the death registry from the Malaysian National Registration Department. Multiple Cox regression was applied to assess the association between daily adequate FV intake and risk of all-cause, CVD, and cancer mortalities, adjusting for sociodemographic, lifestyle, and health conditions. Results: During the follow-up period, we observed a total of 1809 all-cause, 374 CVD, and 216 cancer mortalities. No significant association between daily adequate FV intake with all-cause mortality (adjusted hazard ratio (aHR): 1.01, 95% confidence interval (CI: 0.79–1.31), CVD mortality (aHR: 0.91, 95% CI: 0.57–1.47), and cancer mortality (aHR: 1.27, 95% CI: 0.74–2.17) were observed, even after excluding deaths that occurred in the first two years of observation. Conclusions: Further investigation on the type of FV intake and its preparation method with risk of mortality will provide a holistic insight into the causal relationship between FV intake and mortality. [ABSTRACT FROM AUTHOR]

Mineral bone disease (MBD) is common in dialysis patients. Genetics and the hormonal environment influence the clinical picture and outcomes of women. This study aimed to determine how these factors affect mortality. In 234 female dialysis patients on Continuous Ambulatory (48%) or Automated (29%) Peritoneal Dialysis or Hemodialysis (23%), MBD biochemical variables, as well as bone density and genetic Bsm1 polymorphism of vitamin D receptor (VDR) were performed at baseline. The cohort was followed-up by 17 (IQ range 15–31) months. According to VDR polymorphism, the distribution of patients was bb: 64% and BB+Bb: 36%. Fifty-five patients died from all-cause mortality; the hs-C-reactive protein level was the most significant risk in multivariate Cox analysis. Nineteen died from cardiovascular mortality. None of the variables were significant for cardiovascular mortality. Patients with bb plus inflammation had the highest risk in the analysis; the significance persisted after adjustment for age, diabetes, and parathyroid hormone levels HR 2.33 (95% CI, 1.01–8.33) and after further adjustment for time on dialysis, albumin, and Osteoprotegerin levels HR 3.49 (95% CI, 1.20–10.9). The presence of the bb genotype from VDR and inflammation had the highest risk of death from all-cause mortality in females on CAPD, APD, and HD patient. [ABSTRACT FROM AUTHOR]

Background/Objectives: The effect of glucagon-like peptide-1 receptor (GLP-1R) agonists on calcium homeostasis is poorly understood. This study aimed to investigate the association between GLP-1R agonist use and the risk of hypocalcemia and/or hypercalcemia, as well as other clinical outcomes. Methods: A retrospective cohort study used de-identified patient data from the TriNetX Global Collaborative Network, including 15,655 adult patients prescribed GLP-1R agonists and 15,655 propensity-matched controls. Outcomes included hypocalcemia, hypercalcemia, emergency visits, hospitalizations, cardiovascular events, and all-cause mortality. Results: GLP-1R agonist use was associated with a reduced risk of hypocalcemia (2.7% vs. 5.5%, RR 0.49, 95% CI: 0.44–0.55) but an increased risk of hypercalcemia (2.3% vs. 1.1%, RR 2.02, 95% CI: 1.69–2.42). The effect on hypocalcemia was most pronounced during the first six months of treatment. Among individual agents, tirzepatide showed the most pronounced effect, reducing hypocalcemia risk by 63% while increasing hypercalcemia risk by 85%. Semaglutide demonstrated similar effects, while dulaglutide and liraglutide showed modest effects. Furthermore, GLP-1R agonist use was associated with reduced risks of emergency visits (RR 0.57, 95% CI: 0.54–0.60), hospitalizations (RR 0.40, 95% CI: 0.36–0.44), cardiovascular events, and all-cause mortality (HR 0.27, 95% CI: 0.21–0.36). Conclusions: GLP-1R agonists exhibit a complex influence on calcium homeostasis, reducing hypocalcemia risk while increasing hypercalcemia risk. Beyond calcium regulation, these medications significantly reduce healthcare utilization, improve cardiovascular outcomes, and decrease mortality. Further research is needed to elucidate the mechanisms behind the differential effects of individual GLP-1R agonists, particularly tirzepatide, to optimize personalized treatment approaches and long-term safety. [ABSTRACT FROM AUTHOR]

Adropin—a multifunctional peptide with tissue-protective capacity that regulates energy homeostasis, sensitivity to insulin and inflammatory response—seems to show an inverse association with the presence of cardiovascular and renal diseases, obesity and diabetes mellitus in the general population. The purpose of the study is to elucidate whether adropin may be a plausible predictive biomarker for clinical outcomes in post-ST elevation of myocardial infarction (STEMI) patients with newly diagnosed prediabetes according to the American Diabetes Association criteria. A total of 1214 post-STEMI patients who received percutaneous coronary intervention were identified in a local database of the private hospital "Vita Center" (Zaporozhye, Ukraine). Between November 2020 and June 2024, we prospectively enrolled 498 patients with prediabetes in this open prospective cohort study and followed them for 3 years. The combined clinical endpoint at follow-up was defined as cardiovascular death due to acute myocardial infarction, heart failure, sudden death due to arrhythmia or cardiac surgery, and/or all-cause death. We identified 126 clinical events and found that serum levels of adropin < 2.15 ng/mL (area under the curve = 0.836; 95% confidence interval = 0.745–0.928; sensitivity = 84.9%; specificity = 72.7%; likelihood ratio = 3.11; p = 0.0001) predicted clinical outcomes. Multivariate logistic regression showed that a Gensini score ≥ 32 (Odds ratio [OR] = 1.07; p = 0.001), adropin ≤ 2.15 ng/mL (OR = 1.18; p = 0.001), use of SGLT2i (OR = 0.94; p = 0.010) and GLP-1 receptor agonist (OR = 0.95; p = 0.040) were independent predictors of clinical outcome. Kaplan–Meier plots showed that patients with lower adropin levels (≤2.15 ng/mL) had worse clinical outcomes compared to patients with higher adropin levels (>2.15 ng/mL). In conclusion, low levels of adropin (≤2.15 ng/mL) independently predicted clinical outcomes in post-STEMI patients with newly detected prediabetes and improved the discriminative ability of the Gensini score for 3-year follow-up events. Future clinical studies are needed to clarify whether adropin is a promising molecule to be incorporated into conventional risk scores for the prediction of MACCEs after STEMI. [ABSTRACT FROM AUTHOR]

Background: This study is designed to explore the correlation between multiple healthy lifestyles within the framework of “lifestyle medicine”, and the mortality risk of nonalcoholic fatty liver disease (NAFLD). Methods: The National Health and Nutrition Examination Survey (NHANES) database was employed. The analysis consisted of 5542 participants with baseline NAFLD and 5542 matched non-NAFLD participants from the database. Lifestyle information, including five low risk factors advocated by lifestyle medicine (healthy diet, vigorous physical activity, healthy sleep duration, avoiding smoking, and maintaining a non-depressed psychological status), was collected through a baseline questionnaire. Cox proportional hazards regression models and Kaplan-Meier survival curve were used to evaluate risk of mortality. In addition, subgroups were analyzed according to gender, age, body mass index and waist circumference. Results: In total, 502 deaths (n = 181 deaths from cardiovascular disease (CVD)) were recorded among NAFLD participants after the median follow up duration of 6.5 years. In the multivariate-adjusted model, compared to participants with an unfavorable lifestyle (scoring 0-1), NAFLD participants with a favorable lifestyle (scoring 4-5) experienced a 56% reduction in all-cause mortality and a 66% reduction in CVD mortality. Maintaining an undepressed psychological state and adhering to vigorous exercise significantly reduced CVD mortality risk in NAFLD participants (HR, 0.64 [95% CI, 0.43-0.95]; HR, 0.54 [95% CI, 0.33-0.88]) while maintaining healthy sleep reduced premature mortality due to CVD by 31%. Conclusions: Healthy lifestyle, characterized by maintaining an undepressed mental state and healthy sleep, significantly mitigates the risk of all-cause, CVD, and premature mortality risk among NAFLD patients, with a particularly pronounced effect observed in female and obese subpopulations. [ABSTRACT FROM AUTHOR]

Background: Carotid-femoral pulse wave velocity (cfPWV), acknowledged as a reliable proxy of arterial stiffness, is an independent predictor of cardiovascular (CV) events. Carotid-femoral PWV is considered the gold standard for the estimation of arterial stiffness. cfPWV is a demanding, time consuming and expensive method, and an estimated PWV (ePWV) has been suggested as an alternative method when cfPWV is not available. Our aim was to analyze the predictive role of ePWV for CV and all-cause mortality in the general population. Methods: In a stratified random sample of 1086 subjects from the general Croatian adult population (EH-UH study) (men 42.4%, average age 53 ± 16), subjects were followed for 17 years. ePWV was calculated using the following formula: ePWV = 9.587 − 0.402 × age + 4.560 × 10−3 × age2 − 2.621 × 10−5 × age2 × MBP + 3.176 × 10−3 × age × MBP − 1.832 × 10−2 × MBP. MBP= (DBP) + 0.4(SBP − DBP). Results: At the end of the follow-up period, there were 228 deaths (CV, stroke, cancer, dementia and degenerative diseases, COLD, and others 43.4%, 10.5%, 28.5%, 5.2%, 3.1%, 9.3%, respectively). In the third ePWV tercile, we observed more deaths due to CV disease than to cancer (20.5% vs. 51.04%). In a Cox regression analysis, for each increase in ePWV of 1 m/s, there was a 14% increase risk for CV death. In the subgroup of subjects with higher CV risk, we found ePWV to be a significant predictor of CV deaths (ePWV (m/s) CI 1.108; p < 0.029; HR 3.03, 95% CI 1.118–8.211). Conclusions: In subjects with high CV risk, ePWV was a significant and independent predictor of CV mortality. [ABSTRACT FROM AUTHOR]

We evaluated the long-term risks of overall cancer and all-cause mortality associated with five types of phytopharmaceuticals and the most commonly used estrogen-progestogen medications for the treatment of postmenopausal syndrome in women. Using data from Taiwan's National Health Insurance Research Database (NHIRD) from 1 January 2000 to 31 December 2018, we conducted a 1:2 matched cohort study with 12,087 eligible patients. We compared phytopharmaceuticals -only users (n = 4029, phytopharmaceuticals group) with HRT-only users (n = 8058, HRT group) with a washout period of ≥6 months. The phytopharmaceuticals group had significantly lower risks of overall cancer and all-cause mortality than the HRT group (adjusted hazard ratio [95% confidence interval]: 0.60 [0.40–0.9] and 0.40 [0.16–0.99], respectively) after over 180 days of use. Bupleurum and Peony Formula were associated with lower risks of overall cancer and all-cause mortality (aHR: 0.57 [0.36–0.92] and 0.33 [0.11–1.05], respectively). In conclusion, phytopharmaceuticals may serve as an alternative therapy to HRT for alleviating menopausal symptoms and reducing health risks, leading to more favorable long-term health outcomes. Further randomized control trials are necessary to validate the findings of this study. [ABSTRACT FROM AUTHOR]

Diet is one of the most important ways to intervene and promote the health of older adults and reduce all-cause mortality. This study aimed to investigate the association between dietary patterns and all-cause mortality in the Chinese old. This study involved 11,958 subjects aged 65–116 years in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 2008 to 2018. Dietary patterns were derived from principal component analysis (PCA) with varimax rotation. Four dietary patterns were derived: the 'milk–egg–sugar pattern', 'carnivorous pattern', 'healthy pattern', and 'northeastern pattern'. Cox proportional hazard models were built for males and females separately to estimate the relationship between different dietary patterns and all-cause mortality. After adjusting for all covariates, the milk–egg–sugar pattern played a reverse role in mortality risk in males and females in different quartiles. In the carnivorous pattern, only males in the fourth quartile were observed to have a significantly reduced mortality risk (HR = 0.84 (95% CI: 0.77–0.93)). Both genders benefited from the healthy pattern, which consistently lowered mortality risk across all quartiles (males: HR = 0.87 (95% CI: 0.84–0.89); females: HR = 0.95 (95% CI: 0.92–0.97)). The northeastern pattern also showed an inverse association with all-cause mortality in males (HR = 0.94 (95% CI: 0.92–0.97)) and females (HR = 0.96 (95% CI: 0.93–0.98)). This study showed the association between dietary patterns and all-cause mortality in the Chinese old, which is significant for further quantitative studies. [ABSTRACT FROM AUTHOR]

Background/Objectives: Both hypertension and carotid atherosclerosis are independent risk factors for cardiovascular disease. We aim to investigate the synergistic effects of hypertension and carotid plaques on cardiovascular events and all-cause mortality. Methods: A follow-up study was conducted at the Preventive Cardiology Department of Vilnius University Hospital Santaros Klinikos between 2012 and 2021. The study recruited participants aged 40–65 who did not have overt cardiovascular disease (CVD) and were part of the Lithuanian High Cardiovascular Risk primary preventive program. The study collected demographic and clinical data, including an ultrasound assessment of carotid plaque. Results: The participants were monitored for 4–10 years for CVD events and all-cause mortality. Among 6138 participants, 954 (16%) experienced CVD events. The presence of carotid plaque on both sides was significantly associated with CVD events, myocardial infarction, and all-cause mortality. However, the combination of hypertension and carotid plaque did not significantly increase the risk for CVD events or all-cause mortality. Conclusions: The risk of CVD events or all-cause mortality was not significantly increased by the combination of hypertension and carotid plaque. Cardiovascular events depend on the extent of atherosclerosis in the carotid arteries. [ABSTRACT FROM AUTHOR]

Background: The effect of flavonoid consumption on all-cause and special-cause mortality remains unclear among populations with hypertension. Methods: A total of 6110 people with hypertension from three NHANES survey cycles (2007–2008, 2009–2010, and 2017–2018) were enrolled in this study. Cox proportional hazard models were conducted to estimate the association between the intake of total flavonoids and flavonoid subclasses and all-cause, cancer-related, and cardiovascular disease (CVD)-related mortality. Nonlinear relationships were identified using restricted cubic splines (RCS). Results: During 43,977 person-years of follow-up, 1155 participants died from any cause, 282 participants died from CVD, and 265 participants died from cancer. After adjusting for relevant confounders, including demographic, lifestyle, and dietary intake, a higher intake of total flavonoids was significantly associated with lower all-cause mortality but not CVD-related and cancer-related mortality among the population with hypertension. Compared with extreme quartiles, the hazard ratio (HR) and 95% confidence interval (CI) were 0.74 (0.56–0.97) for all-cause mortality, 0.77 (0.40–1.46) for CVD-related mortality, and 0.62 (0.35–1.08) for cancer-related mortality. In terms of all-cause mortality, this inverse association was optimized at total flavonoid consumption of approximately 375 mg/day. In addition, the negative association between total flavonoid consumption and all-cause mortality was more pronounced in non-obese (BMI < 30 kg/m2) compared to obese (BMI ≥ 30 kg/m2) populations. Higher intakes of anthocyanidin, flavan-3-ol, flavonol, and isoflavone were significantly associated with lower all-cause mortality (HR (95%CI): 0.70 (0.55–0.89); 0.76 (0.59–0.96); 0.66 (0.46–0.94); 0.79 (0.67–0.93), respectively). Higher intakes of anthocyanidin, flavan-3-ol, and flavonol were significantly associated with lower cancer-related mortality (HR (95%CI): 0.55 (0.32–0.93); 0.51 (0.31–0.82); 0.52 (0.28–0.96), respectively). Conclusion: This study suggests that a heightened consumption of total flavonoids and some flavonoid subclasses was linked to lower mortality, which supports the proposal of increasing flavonoid intake as part of healthy diets in patients with hypertension. [ABSTRACT FROM AUTHOR]

Background: Obesity is a risk factor for many diseases, diagnosed by calculating body mass index (BMI). Methods: To find an association between BMI and mortality in adults, we searched PubMed for articles published in the 21st century. Our review included 82 original studies, comprising 2.7 million patients and 23.4 million patient years. Results: The meta-analysis showed a U-shaped relationship between BMI and all-cause mortality risk, with the lowest mortality in the BMI range of 25–30 kg/m2. Subgroup analysis showed a J-shaped relationship, with greater risk in the highest BMI range (>35 kg/m2). Among the elderly, BMI values <20 kg/m2 were associated with the highest risk. Among diabetic patients, a U-shaped relationship was noticed, again with the highest risk in the lowest (<20 kg/m2) and highest BMI range (>35 kg/m2). Among patients with cardiovascular disease, the risk increased with BMI values <25 kg/m2 but did not noticeably change for BMI exceeding that value. Among cancer patients, the relationship was less pronounced than in other subgroups, with a slightly higher risk (>35 kg/m2). Conclusions: Our results show that the lowest mortality is observed among patients with BMI 25–30 kg/m2. Reduction of body mass should not be a universal recommendation in clinical practice, but it should be individualized. [ABSTRACT FROM AUTHOR]

Background: Differences in survival between patients treated with antipsychotic monotherapy vs. polytherapy are debated. This study aimed to examine the association of antipsychotic polytherapy with 2-year all-cause mortality in a population-based cohort. Methods: Data were retrieved from healthcare databases of four local health units of Lombardy, Italy. Subjects aged 18–79 years who received continuous antipsychotic prescriptions in 2018 were identified. Overall survival among patients with antipsychotic monotherapy vs. polytherapy was compared. A multivariate Cox PH model was used to estimate the association between antipsychotic therapy, or antipsychotic use (continuous vs. non-continuous), and all-cause mortality. Adjustments were made for the presence of metabolic disturbances, total antipsychotic dosage amount (olanzapine equivalent doses), age, and sex. Results: A total of 49,875 subjects receiving at least one prescription of antipsychotics during 2018 were identified. Among the 33,221 patients receiving continuative antipsychotic prescriptions, 1958 (5.9%) experienced death from any cause at two years. Patients with continuous antipsychotic use had a 1.13-point increased mortality risk compared with non-continuous users. Patients treated with antipsychotic polytherapy showed an adjusted mortality risk increased by 17% (95% CI: 2%, 33%) compared to monotherapy. Conclusions: The study highlights the potential risks associated with antipsychotic polypharmacy, emphasizing the importance of optimizing drug prescriptions to improve patient safety and reduce mortality rates in individuals receiving antipsychotic therapy. [ABSTRACT FROM AUTHOR]

Background: Our aim was to assess the relationship of the index of microvascular resistance (IMR) in left anterior descending (LAD) artery involved STEMI patients. Methods: Data of 316 STEMI patients who had undergone primary percutaneous coronary intervention (PCI) were collected from three cardiovascular centers from 2005 to 2015. In total, 246 patients with LAD STEMI were enrolled for IMR evaluation. Patients were divided into two groups respective of the cut-off IMR value of 30. All-cause mortality, left ventricular function, improvement of systolic function, and cardiac biomarkers were analyzed and compared. Results: A total of 246 patients were enrolled. The number of patients in the IMR above 30 group was 93 and below 30 was 153. The mean ages for each group were 57.91 ± 11.99 and 54 ± 10.63, respectively. The peak creatinine kinase (CK) (3936.85 ± 2827.32 IU/L vs. 2218.08 ± 2310.41 IU/L, p < 0.001) and CKmb (336.15 ± 195.08 mg/mL vs. 231.53 ± 179.53 mg/mL, p < 0.001) levels were higher for an IMR above the 30 group. The left ventricular ejection fraction (LVEF) (44.57 ± 6.685% vs. 47.35 ± 8.17%, p = 0.006) and improvement of LVEF (2.81 ± 7.135% vs. 5.88 ± 7.65%, p = 0.004) was lower in the IMR above 30 group. All-cause mortality (7.5% vs. 1.3%, p = 0.012) was higher in the IMR above 30 group, and a Cox regression analysis showed that an IMR above 30 was a poor prognostic factor regarding all-cause mortality (HR: 5.151, 95% CI 1.062–24.987, p = 0.042) even after adjusting for classical clinical risk factors. Conclusions: An elevated IMR value represented larger infarct size, more severe LV dysfunction, and higher mortality in LAD STEMI patients after successful PCI. [ABSTRACT FROM AUTHOR]

(1) Background: Systemic inflammation stands as a well-established risk factor for ischemic cardiovascular disease, as well as a contributing factor in the development of cardiac arrhythmias, notably atrial fibrillation. Furthermore, scientific studies have brought to light the pivotal role of localized vascular inflammation in the initiation, progression, and destabilization of coronary atherosclerotic disease. (2) Methods: We comprehensively review recent, yet robust, scientific evidence elucidating the use of perivascular adipose tissue attenuation measurement on computed tomography applied to key anatomical sites. Specifically, the investigation extends to the internal carotid artery, aorta, left atrium, and coronary arteries. (3) Conclusions: The examination of perivascular adipose tissue attenuation emerges as a non-invasive and indirect means of estimating localized perivascular inflammation. This measure is quantified in Hounsfield units, indicative of the inflammatory response elicited by dense adipose tissue near the vessel or the atrium. Particularly noteworthy is its potential utility in assessing inflammatory processes within the coronary arteries, evaluating coronary microvascular dysfunction, appraising conditions within the aorta and carotid arteries, and discerning inflammatory states within the atria, especially in patients with atrial fibrillation. The widespread applicability of perivascular adipose tissue attenuation measurement underscores its significance as a diagnostic tool with considerable potential for enhancing our understanding and management of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

The association between obesity and all-cause mortality in patients undergoing kidney failure with replacement therapy (KFRT) has shown conflicting results. This study aimed to evaluate whether metabolic abnormalities (MA) increase the risk of all-cause mortality in these patients. Between 2009 and 2015, 1141 patients undergoing KFRT were recruited from the Clinical Research Center for End-Stage Renal Disease dataset. Patients were divided into four groups according to the presence of obesity and MA. Multivariate Cox proportional hazard analysis was performed to determine the association between the phenotypes and all-cause mortality. During a mean follow-up of 4.2 years, all-cause mortality was observed in 491 (43.0%) patients. Obesity had a 24% decreased risk of all-cause mortality compared with non-obesity. In contrast, the presence of MA showed a 1.53-fold increased risk of all-cause mortality. There was a significant interaction between obesity and MA (p = 0.006). In Cox proportional hazard analyses after adjustment of confounding factors, the metabolically abnormal non-obesity (MANO) phenotype showed a 1.63-fold increased risk of all-cause mortality compared with the metabolically healthy non-obesity phenotype. In subgroup analysis, the risk of all-cause mortality was higher in the MANO phenotype; this phenotype was significantly associated with a higher all-cause mortality in patients undergoing KFRT. [ABSTRACT FROM AUTHOR]

Background: Dyslipidemia is a known risk factor for cardiac dysfunction, and lipid-lowering therapy with statins reduces symptoms and reduces hospitalization related to left ventricular heart failure. Acute myocardial infarction (AMI) is a cause of morbidity and mortality worldwide. In this study, we aimed to determine the real-world AMI treatment drug combination used in Taiwan by using the NHI database to understand the treatment outcomes of current clinical medications prescribed for hyperlipidemia patients with AMI. Methods: Using the NHI Research Database (NHIRD), we conducted a retrospective cohort study that compared different treatments for AMI in hyperlipidemia patients in the period from 2016 to 2018. We compared the survival outcomes between those treated with and without organic nitrates in this cohort. Results: We determined that most hyperlipidemia patients were aged 61–70 y (29.95–31.46% from 2016 to 2018), and the annual AMI risk in these patients was <1% (0.42–0.68% from 2016 to 2018). The majority of hyperlipidemia patients with AMI were women, and 25.64% were aged 61–70 y. Receiving organic nitrates was associated with lower all-cause mortality rates (HR, 95% CI, p-value = 0.714, 0.674–0.756, p < 0.0001). After multivariate analysis, the overall survival in four groups (beta-blockers, beta-blocker + diuretics, diuretics, and others) receiving an organic nitrate treatment was significantly higher than in the groups that were not treated with organic nitrates (beta-blockers HR = 0.536, beta-blocker + diuretics HR = 0.620, diuretics HR = 0.715, and others HR = 0.690). Conclusions: The survival benefit was significantly greater in patients treated with organic nitrates than in those treated without organic nitrates, especially when combined with diuretics. A combination of organic nitrates could be a better treatment option for hyperlipidemia patients with AMI. [ABSTRACT FROM AUTHOR]

Large epidemiological studies show U-shaped relationships between high-density lipoprotein cholesterol (HDL-C) levels and all-cause mortality in individuals without atherosclerotic cardiovascular diseases (ASCVD). Association in those with ASCVD by sex is unclear. We examined the association between HDL-C levels and 10-year all-cause mortality in subjects (≥40 years of age) with ASCVD using the 2010 National Health Insurance Service and the National Death Registry of Korea. We categorized HDL-C levels into three groups (low: <40 mg/dL for males, <50 mg/dL for females; high: 40–90 mg/dL for males, 50–90 mg/dL for females; extremely high: >90 mg/dL) and 10 mg/dL intervals. We conducted a sex-stratified and adjusted Cox proportional hazards analysis. Out of 1,711,548 individuals (54% female, mean age 61.4 years), 10-year mortality was observed in 218,252 (12.8%). Males had a higher mortality rate than females (16.2% vs. 9.8%; p < 0.001). When adjusting for age, body mass index, LDL-cholesterol, triglycerides, hypertension, diabetes, smoking, and alcohol consumption, the low and extremely high HDL-C groups had significantly higher hazard ratios for 10-year mortality compared to the high HDL-C group in males [1.183 (1.166–1.199), 1.359 (1.288–1.434)] and in females [1.153 (1.138–1.169), 1.095 (1.029–1.167)]. The frequency distribution bars for the 10-year mortality rate showed sex-specific nadirs of 50–59 mg/dL in males and 70–79 mg/dL in females. In this ASCVD cohort, the extremely high HDL-C (>90 mg/dL) group had 35.9% and 9.5% higher 10-year mortality risks than the high HDL-C group for males and females, respectively. There was a slightly U-shaped relationship between baseline HDL-C levels and a 10-year mortality rate, with earlier inflection in males than in females. [ABSTRACT FROM AUTHOR]

Dietary phytochemical intake associations with cardiovascular health and mortality remain unknown. We studied the relations between total dietary phytochemical intake and cardiovascular health outcomes in a middle-aged Swiss population. We analyzed data spanning 2009 to 2021 from a prospective cohort study in Lausanne, Switzerland, including 3721 participants (54.8% women, 57.2 ± 10.3 years) without cardiovascular disease (CVD) history. Dietary intake was assessed using a validated self-reported food frequency questionnaire. The Dietary Phytochemical Index (DPI) and the healthy Dietary Phytochemical Index (hDPI) were calculated as the total energy intake percentage obtained from phytochemical-rich food consumption. The Healthy Plant-Based Diet Index (hPBD) was estimated by scoring healthy plant foods positively and less-healthy plant foods negatively. Indices tertiles and cardiometabolic outcome associations were determined using Cox proportional hazard models. Over 30,217 person-years of follow-up, 262 CVD events, and 178 deaths occurred. Unadjusted analyses found 36%, 33%, and 32% lower CVD risk for the highest hDPI, DPI, and hPBD tertiles, respectively. After adjustment, only the second hDPI tertile showed a 30% lower CVD risk (HR 0.70, 95% CI 0.51–0.95; P for trend 0.362). No other associations emerged. In this middle-aged Swiss cohort, no associations between dietary indices reflecting a phytochemical-rich dietary pattern and incident CVD, all-cause, or CVD mortality were observed. [ABSTRACT FROM AUTHOR]

Since 2020, COVID-19 has caused serious mortality around the world. Given the ambiguity in establishing COVID-19 as the direct cause of death, we first investigate the effects of age and sex on all-cause mortality during 2020 and 2021 in England and Wales. Since infectious agents have their own unique age profile for death, we use a 9-year time series and several different methods to adjust single-year-of-age deaths in England and Wales during 2019 (the pre-COVID-19 base year) to a pathogen-neutral single-year-of-age baseline. This adjusted base year is then used to confirm the widely reported higher deaths in males for most ages above 43 in both 2020 and 2021. During 2020 (+COVID-19 but no vaccination), both male and female population-adjusted deaths significantly increased above age 35. A significant reduction in all-cause mortality among both males and females aged 75+ could be demonstrated in 2021 during the widespread COVID-19 vaccination period; however, deaths below age 75 progressively increased. This finding arises from a mix of vaccination coverage and year-of-age profiles of deaths for the different SARS-CoV-2 variants. In addition, specific effects of age around puberty were demonstrated, where females had higher deaths than males. There is evidence that year-of-birth cohorts may also be involved, indicating that immune priming to specific pathogen outbreaks in the past may have led to lower deaths for some birth cohorts. To specifically identify the age profile for the COVID-19 variants from 2020 to 2023, we employ the proportion of total deaths at each age that are potentially due to or 'with' COVID-19. The original Wuhan strain and the Alpha variant show somewhat limited divergence in the age profile, with the Alpha variant shifting to a moderately higher proportion of deaths below age 84. The Delta variant specifically targeted individuals below age 65. The Omicron variants showed a significantly lower proportion of overall mortality, with a markedly higher relative proportion of deaths above age 65, steeply increasing with age to a maximum around 100 years of age. A similar age profile for the variants can be seen in the age-banded deaths in US states, although they are slightly obscured by using age bands rather than single years of age. However, the US data shows that higher male deaths are greatly dependent on age and the COVID variant. Deaths assessed to be 'due to' COVID-19 (as opposed to 'involving' COVID-19) in England and Wales were especially overestimated in 2021 relative to the change in all-cause mortality. This arose as a by-product of an increase in COVID-19 testing capacity in late 2020. Potential structure–function mechanisms for the age-specificity of SARS-CoV-2 variants are discussed, along with potential roles for small noncoding RNAs (miRNAs). Using data from England, it is possible to show that the unvaccinated do indeed have a unique age profile for death from each variant and that vaccination alters the shape of the age profile in a manner dependent on age, sex, and the variant. The question is posed as to whether vaccines based on different variants carry a specific age profile. [ABSTRACT FROM AUTHOR]

(1) Background: A recent review concluded that there was no strong evidence for beneficial vitamin D effects on cardiovascular disease (CVD) risk, but whether individuals with vitamin D deficiency have a higher risk of CVD should be further studied. (2) Aims: We assessed the association between vitamin D levels and CVD events, CVD mortality, and overall mortality in a prospective population-based study in Lausanne, Switzerland. (3) Methods: A total of 5684 participants (53.6% women, 52.5 ± 10.7 years) were followed for a median of 14.4 years [interquartile range: 10.7–16.6]. Vitamin D blood levels were categorized as normal (≥75 nmol/L or 30 ng/mL), insufficient (50–74 nmol/L or 21–29 ng/mL), and deficient (<50 nmol/L or 20 ng/mL). (4) Results: In total, 568 cardiovascular events, 114 cardiovascular deaths, and 679 deaths occurred during follow-up. After multivariate analysis, vitamin D levels were negatively associated with CVD events: hazard ratio and (95% confidence interval) for a 10 nmol/L increase: 0.96 (0.92–0.99). However, no association was found for CVD [0.93 (0.84–1.04)] and overall mortality [0.98 (0.94–1.02)]. No associations were found between vitamin D categories and CVD events, 0.93 (0.71–1.22) and 1.14 (0.87–1.49); CVD deaths, 0.78 (0.41–1.50) and 1.10 (0.57–2.12); and overall mortality, 1.10 (0.82–1.48); and 1.17 (0.87–1.58) for insufficiency and deficiency, respectively. After excluding participants taking vitamin D supplements, similar results were obtained. (5) Conclusion: In this prospective population-based study, vitamin D levels were inversely associated with CVD events but not with CVD or overall mortality. [ABSTRACT FROM AUTHOR]

Limited data are available on outcomes among COVID-19 patients beyond the acute phase of the disease. All-cause mortality among our COVID-19 patients one year after hospital discharge and factors/conditions associated with death were evaluated. All patients discharged from our COVID center were periodically evaluated by clinical assessment and by digital healthcare registry consultation. All findings acquired on discharge day represented the baseline data and were utilized for statistics. Of the 208 patients admitted, 187 patients were discharged. Among these, 17 patients died within 12 months (non-survivors). Compared to survivors, non-survivor patients were significantly (p < 0.05) older, exhibited significantly greater comorbidities and prevalence of active malignancy, heart failure, and arrhythmias, and showed significantly higher circulating levels of B-type natriuretic peptide, troponin, C-reactive protein, and d-dimer, as well as a longer heart-rate-corrected QT interval and significantly lower values for the glomerular filtration rate. Following multivariate analysis, cancer, arrhythmias, and high C-reactive protein levels were found to be factors independently associated with death. At the one-year follow-up, about 9% of patients discharged from our COVID center had a fatal outcome. Ageing, myocardial injury, impaired renal function, and, in particular, cancer, hyperinflammation, and arrhythmias represented strong predictors of the worst long-term outcome among COVID-19 patients. [ABSTRACT FROM AUTHOR]

Febrile neutropenia (FN) is one of the most important life-threatening complications in haemato-oncology. Our objective was to report all-cause mortality rates in patients ill with a hematological malignancy (HM) hospitalized with a first FN episode and to identify predictors for mortality. We conducted a historical retrospective cohort study of consecutive patients with an HM, >18 years of age, admitted between January 2012 and August 2018 for a first episode of FN. Data on all-cause mortality 12 months after admission for FN were obtained. The Kaplan–Meier curve was used to describe mortality during the follow-up period. Univariate and multivariable analyses identified predictors for 1,3 and 12-month mortality. One hundred and fifty-eight patients (mean age 69.5, 49.4% males) were included. Overall, 54 patients died (15.8%, 25.9%, and 34.1% died after 1, 3, and 12 months, respectively). Lower serum albumin, higher serum gamma-glutamyl transferase (GGT), lower estimated glomerular filtration rate (eGFR), older age, higher temperature, and lower absolute lymphocyte count at admission were independent predictors of all-cause mortality after 12 months. Further studies are needed to confirm our results and identify therapeutic strategies to improve survival. [ABSTRACT FROM AUTHOR]

The role of overall diet on longevity among cancer survivors (CS) needs further elucidation. We performed a systematic review of the literature and a meta-analysis of related cohort studies published up to October 2022 investigating post-diagnosis a priori (diet quality indices) and a posteriori (data-driven) dietary patterns (DPs) in relation to all-cause and cancer-specific mortality. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using random-effects meta-analyses comparing highest versus lowest categories of adherence to DPs. We assessed heterogeneity and risk of bias in the selected studies. A total of 19 cohort studies with 38,846 adult CS, some assessing various DPs, were included in the meta-analyses. Higher adherence to a priori DPs was associated with lower all-cause mortality by 22% (HR = 0.78, 95% CI: 0.73–0.83, I2 = 22.6%) among all CS, by 22% (HR = 0.78, 95% CI: 0.73–0.84, I2 = 0%) among breast CS and by 27% (HR = 0.73, 95% CI: 0.62–0.86, I2 = 41.4%) among colorectal CS. Higher adherence to a "prudent/healthy" DP was associated with lower all-cause mortality (HR = 0.79, 95% CI: 0.64–0.97 I2 = 49.3%), whereas higher adherence to a "western/unhealthy" DP was associated with increased all-cause mortality (HR = 1.48, 95% CI: 1.26–1.74, I2 = 0%) among all CS. Results for cancer-specific mortality were less clear. In conclusion, higher adherence to a "healthy" DP, either a priori or a posteriori, was inversely associated with all-cause mortality among CS. A "healthy" overall diet after cancer diagnosis could protect and promote longevity and well-being. [ABSTRACT FROM AUTHOR]

Despite evidence of SGLT2 inhibitors in improving cardiovascular outcomes of heart failure with preserved ejection fraction (HFpEF), the heterogenous mechanism and characteristic multimorbidity of HFpEF require a phenotypic approach. Metabolic phenotype, one common HFpEF phenotype, has various presentations and prognoses worldwide. We aimed to identify different phenotypes of hypertensive-diabetic HFpEF, their phenotype-related outcomes, and treatment responses. The primary endpoint was time to the first event of all-cause mortality or hospitalization for heart failure (HHF). Among 233 recruited patients, 24.9% experienced primary outcomes within 12 months. A total of 3.9% was lost to follow-up. Three phenotypes were identified. Phenotype 1 (n = 126) consisted of lean, elderly females with chronic kidney disease, anemia, and concentric hypertrophy. Phenotype 2 (n = 62) included younger males with coronary artery disease. Phenotype 3 (n = 45) comprised of obese elderly with atrial fibrillation. Phenotype 1 and 2 reported higher primary outcomes than phenotype 3 (p = 0.002). Regarding treatment responses, SGLT2 inhibitor was associated with fewer primary endpoints in phenotype 1 (p = 0.003) and 2 (p = 0.001). RAAS inhibitor was associated with fewer all-cause mortality in phenotype 1 (p = 0.003). Beta blocker was associated with fewer all-cause mortality in phenotype 1 (p = 0.024) and fewer HHF in phenotype 2 (p = 0.011). Our pioneering study supports the personalized approach to optimize HFpEF management in hypertensive-diabetic patients. [ABSTRACT FROM AUTHOR]

Background: Non-communicable diseases have become a major threat to public health, with cardiovascular diseases (CVDs) and cancer being the top two causes of death each year. Objective: Our objective is to evaluate the balanced association between the effect of red and processed meat intake on the risk of death and the effect of physical activity on the risk of mortality, where the risk of death includes all causes, CVDs, and cancers. Methods: We searched electronic databases, including PubMed, ISI Web of Science, Embase, and the Cochrane Library, for prospective studies reporting risk estimates for the association between the intake of red and processed meat, walking, and muscle-strengthening activity (MSA) and the risk of mortality from all causes, CVDs, and cancer. We extracted fully adjusted effect estimates from original studies and performed a summary analysis using the fixed and random-effect models. Results: A conventional meta-analysis showed that red meat and processed meat were positively associated with the risk of mortality, and daily steps and MSA were negatively associated with the risk of death. Further analysis of the dose–response relationship showed that a risk reduction (20%) from 39.5 min/week of MSA or 4100 steps/d was equivalent to an increased risk of all-cause mortality from a daily intake of 103.4 g/d of red meat or 50 g/d of processed meat. The risk was further decreased as the number of steps per day increased, but the risk reversed when the MSA exceeded the threshold (39.5 min/week). Conclusions: Adherence to physical activity is an effective way to reduce the risk of mortality due to meat intake. However, the total intake of red meat and processed meat should be controlled, especially the latter. Walking is recommended as the main daily physical activity of choice, while MSAs are preferred when time is limited, but it should be noted that longer MSAs do not provide additional benefits. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases are among the leading causes of morbidity and mortality, particularly in individuals with type 2 diabetes. There is a need for new biomarkers to improve the prediction of cardiovascular events and overall mortality. We investigated the association of selected atherosclerosis related biomarkers, specifically osteoprotegerin (OPG), 25-hydroxy-vitamin D (25(OH)D), C-reactive protein (CRP), lipopolysaccharide-binding protein (LBP), and asymmetric dimethylarginine (ADMA), with the occurrence of any cardiovascular event or all-cause mortality (primary outcome) during a 5.6-year follow-up of 190 patients with type 2 diabetes. Data were analyzed using logistic regression to adjust for baseline cardiovascular status and cardiovascular risk factors. The primary outcome occurred in 89 participants (46.8%) during the study. When analyzed individually, 25(OH)D, CRP, and LBP significantly predicted the primary outcome in multivariable models. However, in a model that included all biomarkers, only a decreased level of 25(OH)D remained a significant predictor of the primary outcome. Moreover, the level of 25(OH)D significantly predicted all-cause mortality: a reduction of 10 ng/mL was associated with a two-fold increase in all-cause mortality. Our study thus demonstrates that vitamin D deficiency was the strongest factor associated with the primary outcome and all-cause mortality after a 5.6-year follow-up in patients with type 2 diabetes at high cardiovascular risk. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer is increasingly recognized as two separate diseases: colon cancer and rectal cancer, each with its own causes and outcomes. We included 674 patients with colorectal cancer, with pre-surgery collected blood samples, and patient follow up for an average of 4.4 years. Ninety-three patients (14%) died from various causes including 60 patients with colon cancer and 33 patients with rectal cancer. Higher levels of plasma creatinine increased the risk of death by 39% in patients with rectal but not colon cancer. We further identified a biological pathway (e.g., roadmaps inside our bodies that guide various processes) related to starch and sucrose metabolism, which was linked to worse clinical outcomes in colon cancer but not rectal cancer. There is some evidence, that resistant starch, which resists digestion in the small intestine, may offer protection against colon cancer. Understanding the distinct causes and outcomes of colon and rectal cancer is crucial for tailoring effective treatments. In conclusion, personalized treatment strategies should consider colon cancer and rectal cancer separately and are essential for improving patient outcomes in the future. Colorectal cancer (CRC) is increasingly recognized as a heterogeneous disease. No studies have prospectively examined associations of blood metabolite concentrations with all-cause mortality in patients with colon and rectal cancer separately. Targeted metabolomics (Biocrates AbsoluteIDQ p180) and pathway analyses (MetaboAnalyst 4.0) were performed on pre-surgery collected plasma from 674 patients with non-metastasized (stage I–III) colon (n = 394) or rectal cancer (n = 283). Metabolomics data and covariate information were received from the international cohort consortium MetaboCCC. Cox proportional hazards models were computed to investigate associations of 148 metabolite levels with all-cause mortality adjusted for age, sex, tumor stage, tumor site (whenever applicable), and cohort; the false discovery rate (FDR) was used to account for multiple testing. A total of 93 patients (14%) were deceased after an average follow-up time of 4.4 years (60 patients with colon cancer and 33 patients with rectal cancer). After FDR adjustment, higher plasma creatinine was associated with a 39% increase in all-cause mortality in patients with rectal cancer. HR: 1.39, 95% CI 1.23–1.72, pFDR = 0.03; but not colon cancer: pFDR = 0.96. Creatinine is a breakdown product of creatine phosphate in muscle and may reflect changes in skeletal muscle mass. The starch and sucrose metabolisms were associated with increased all-cause mortality in colon cancer but not in rectal cancer. Genes in the starch and sucrose metabolism pathways were previously linked to worse clinical outcomes in CRC. In summary, our findings support the hypothesis that colon and rectal cancer have different etiological and clinical outcomes that need to be considered for targeted treatments. [ABSTRACT FROM AUTHOR]

Although recent evidence has revealed that a body shape index (ABSI) is correlated with the incidence of death among different ethnicities, there remains a paucity of studies investigating the impact of ABSI on mortality within the Chinese elderly. Our objective was to ascertain the link between ABSI, as well as its alterations over time, and all-cause mortality among Chinese aged 65 y and above. A total of 3789 participants were enrolled from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Cox regressions and restricted cubic splines were employed to assess the association of ABSI and relative changes with all-cause mortality. When nonlinearity was detected, a restricted cubic spline regression was subsequently conducted to compute hazard ratios and 95% confidence intervals. The median survival time was 46 months, and 1342 individuals (35.4%) were reported to have died. ABSI contributed independently to rising death rates among Chinese old populations according to univariate and multivariate Cox regressions. Statistically significant associations were also found stratified by age, sex, and lifestyle. A U-shaped association of ABSI changes with all-cause mortality (p = 0.027) was observed, indicating that old adults with stable ABSI during the follow-up period experienced the lowest risk of mortality. After multivariable adjustment, participants with a 10% reduction in ABSI changes had an increased 9.4% risk of death, while participants with a 10% rise in ABSI changes had an increased 1.9% risk. ABSI and its changes are predictors for all-cause mortality among the elderly Chinese population, which emphasizes the clinical importance of monitoring ABSI and keeping it stable over time. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor-binding protein-1 (IGFBP-1) regulates insulin-like growth factor-I (IGF-I) bioactivity, and is a central player in normal growth, metabolism, and stroke recovery. However, the role of serum IGFBP-1 (s-IGFBP-1) after ischemic stroke is unclear. We determined whether s-IGFBP-1 is predictive of poststroke outcome. The study population comprised patients (n = 470) and controls (n = 471) from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Functional outcome was evaluated after 3 months, 2, and 7 years using the modified Rankin Scale (mRS). Survival was followed for a minimum of 7 years or until death. S-IGFBP-1 was increased after 3 months (p < 0.01), but not in the acute phase after stroke, compared with the controls. Higher acute s-IGFBP-1 was associated with poor functional outcome (mRS score > 2) after 7 years [fully adjusted odds ratio (OR) per log increase 2.9, 95% confidence interval (CI): 1.4-5.9]. Moreover, higher s-IGFBP-1 after 3 months was associated with a risk of poor functional outcome after 2 and 7 years (fully adjusted: OR 3.4, 95% CI: 1.4–8.5 and OR 5.7, 95% CI: 2.5–12.8, respectively) and with increased mortality risk (fully adjusted: HR 2.0, 95% CI: 1.1–3.7). Thus, high acute s-IGFBP-1 was only associated with poor functional outcome after 7 years, whereas s-IGFBP-1 after 3 months was an independent predictor of poor long-term functional outcome and poststroke mortality. [ABSTRACT FROM AUTHOR]

The psychosocial and health consequences of ocular conditions that cause visual impairment (VI) are extensive and include impaired daily activities, social isolation, cognitive impairment, impaired functional status and functional decline, increased reliance on others, increased risk of motor vehicle accidents, falls and fractures, poor self-rated health, and depression. We aimed to determine whether VI increases the likelihood of a poor prognosis, including mental illness, suicide, and mortality over time. In this large, location, population-based, nested, cohort study, we used data from 2000 to 2015 in the Taiwan National Health Insurance Research Database (NHIRD), which includes diagnoses of all the patients with VI. Baseline features, comorbidities, and prognostic variables were evaluated using a 1:4-matched cohort analysis. Furthermore, comparisons were performed using Cox regression and Bonferroni-correction (for multiple comparisons) to study the association between VI and poor prognosis (mental illness, suicide). The study outcome was the cumulative incidence of poor prognosis among the visually impaired and controls. A two-tailed Bonferroni-corrected p < 0.001 was considered statistically significant. Among the 1,949,101 patients enlisted in the NHIRD, 271 had been diagnosed with VI. Risk factors for poor prognosis and the crude hazard ratio was 3.004 (95% confidence interval 2.135–4.121, p < 0.001). Participants with VI had an increased risk of poor prognosis according to the sensitivity analysis, with a poor prognosis within the first year and first five years. VI was associated with suicide and mental health risks. This study revealed that patients with VI have a nearly 3-fold higher risk of psychiatric disorders, including anxiety, depression, bipolar, and sleep disorders, than the general population. Early detection through comprehensive examinations based on increased awareness in the clinical context may help maintain visual function and avoid additional complications. [ABSTRACT FROM AUTHOR]

Background: The impact of vitamin D supplementation on cardiovascular outcomes and mortality risk reduction remains unclear due to conflicting study findings. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs), published between 1983 and 2022, that reported the effect of vitamin D supplementation in adults versus placebo or no treatment on all-cause mortality (ACM), cardiovascular mortality (CVM), non-cardiovascular mortality (non-CVM), and cardiovascular morbidities. Only studies with a follow-up period longer than one year were included. The primary outcomes were ACM and CVM. Secondary outcomes were non-CVM, myocardial infarction, stroke, heart failure, and major or extended adverse cardiovascular events. Subgroup analyses were performed according to low-, fair- and good-quality RCTs. Results: Eighty RCTs were assessed, including 82,210 participants receiving vitamin D supplementation and 80,921 receiving placebo or no treatment. The participants' mean (SD) age was 66.1 (11.2) years, and 68.6% were female. Vitamin D supplementation was associated with a lower risk of ACM (OR: 0.95 [95%CI 0.91–0.99] p = 0.013), was close to statistical significance for a lower risk of non-CVM (OR: 0.94 [95%CI 0.87–1.00] p = 0.055), and was not statistically associated with a lower risk of any cardiovascular morbi-mortality outcome. Meta-analysis of low-quality RCTs showed no association with cardiovascular or non-cardiovascular morbi-mortality outcomes. Conclusions: The emerging results of our meta-analysis present evidence that vitamin D supplementation appears to decrease the risk of ACM (especially convincing in the fair- and good-quality RCTs), while not showing a decrease in the specific cardiovascular morbidity and mortality risk. Thus, we conclude that further research is warranted in this area, with well-planned and executed studies as the basis for more robust recommendations. [ABSTRACT FROM AUTHOR]

Both low and high glycated hemoglobin A1c (HbA1c) levels are well-established causal risk factors for all-cause and cardiovascular mortality in the general population and diabetic patients. However, the relationship between HbA1c with all-cause and cardiovascular mortality among patients with hypertension is unclear. We used NHANES data from 1999 to 2014 as the basis for this population-based cohort study. Based on HbA1c levels (HbA1c > 5, HbA1c > 5.5, HbA1c > 6, HbA1c > 6.5, HbA1c > 7%), hypertensive patients were divided into five groups. An analysis of multivariable Cox proportional hazards was conducted based on hazard ratios (HRs) and respective 95% confidence intervals (CIs). The relationship between HbA1c and mortality was further explored using Kaplan–Meier survival curves, restricted cubic spline curves, and subgroup analyses. In addition, 13,508 patients with hypertension (average age 58.55 ± 15.56 years) were included in the present analysis, with 3760 (27.84%) all-cause deaths during a follow-up of 127.69 ± 57.9 months. A U-shaped relationship was found between HbA1c and all-cause and cardiovascular mortality (all p for likelihood ratio tests were 0.0001). The threshold value of HbA1c related to the lowest risk for all-cause and cardiovascular mortality was 5.3% and 5.7%, respectively. Below the threshold value, increased HbA1c levels reduced the risk of all-cause mortality (HR 0.68, 95% CI 0.51–0.90, p = 0.0078) and cardiovascular mortality (HR 0.77, 95% CI 0.57–1.05, p = 0.0969). Inversely, above the threshold value, increased HbA1c levels accelerated the risk of all-cause mortality (HR 1.14, 95% CI 1.11–1.18, p < 0.0001) and cardiovascular mortality (HR 1.22, 95% CI 1.16–1.29, p < 0.0001). In conclusion, A U-shape relationship was observed between HbA1c and all-cause and cardiovascular mortality among hypertensive patients. [ABSTRACT FROM AUTHOR]

Objective: The present study aimed to evaluate the association between hematocrit (HCT) levels and all-cause mortality in geriatric hip fractures. Methods: Older adult patients with hip fractures were screened between January 2015 and September 2019. The demographic and clinical characteristics of these patients were collected. Linear and nonlinear multivariate Cox regression models were used to identify the association between HCT levels and mortality. Analyses were performed using EmpowerStats and the R software. Results: A total of 2589 patients were included in this study. The mean follow-up period was 38.94 months. Eight hundred and seventy-five (33.8%) patients died due to all-cause mortality. Linear multivariate Cox regression models showed that HCT level was associated with mortality (hazard ratio [HR] = 0.97, 95% confidence interval [CI]: 0.96–0.99, p = 0.0002) after adjusting for confounding factors. However, the linear association was unstable and nonlinearity was identified. A HCT level of 28% was the inflection point for prediction. A HCT level of <28% was associated with mortality (HR = 0.91, 95% CI: 0.87–0.95, p < 0.0001), whereas a HCT level > 28% was not a risk factor for mortality (HR = 0.99, 95% CI: 0.97–1.01, p = 0.3792). We found that the nonlinear association was very stable in the propensity score-matching sensitivity analysis. Conclusions: The HCT level was nonlinearly associated with mortality in geriatric hip fracture patients and could be considered a predictor of mortality in these patients. Registration: ChiCTR2200057323. [ABSTRACT FROM AUTHOR]

Simple Summary: Studies assessing the associations of body composition and mortality have found conflicting results due to small sample sizes and short follow-up periods. Using a nationally representative sample, we assessed the associations between total body fat mass and skeletal muscle index, and all-cause and cancer-specific mortality in cancer survivors. Participants with higher fat mass and sarcopenia were at a higher risk of mortality. Our results have significant clinical and public health implications, since fat and muscle mass are important prognostic factors in cancer patients. The findings also highlight the importance of healthy body composition and the need for more research into the effects of specific interventions, such as physical activities, a healthy diet, and supplemental nutrition aimed at reducing fat mass and preventing muscle loss. Purpose: The importance of body composition on cancer outcomes is of great clinical interest. Measures of body composition that differentiate fat mass from skeletal muscle mass can help redefine our understanding of body composition for cancer survival. We investigated whether the risk of all-cause and cancer-specific mortality differ by levels of total fat mass and sarcopenia status in cancer survivors. Our secondary aim was a subgroup analysis assessing the role of race within these associations. Methods: Participants included 1682 adult cancer survivors who had undergone a dual-energy X-ray absorptiometry (DXA) examination to measure body composition, from the 1999–2006 and 2011–2018 National Health and Nutrition Examination Survey (NHANES). Total fat mass was categorized into tertiles (we assessed high vs. low tertiles), and sarcopenia was considered as having an appendicular skeletal muscle mass index less than 7.26 kg/m2 for males and less than 5.45 kg/m2 for females. Multivariable Cox proportional hazard models estimated the adjusted hazard ratio (aHR) and 95% confidence interval (CI). Results: The mean age of study participants was 61.9 years, and they were followed up for an average of 9.67 years. The prevalence of sarcopenia was 25.0% (N = 304), and 33.4% (N = 561) had a high total fat mass. Participants with a higher fat mass (aHR = 1.30, 95% CI = 1.06–1.61) and with sarcopenia (aHR = 1.51, 95% CI = 1.22–1.88) had a 30% and 51% increased risk of all-cause mortality compared to participants with a low fat mass and with no sarcopenia, respectively. Further, sarcopenia (aHR = 1.74, 95% CI = 1.23–2.29) was associated with a higher risk of cancer-specific mortality in cancer survivors. The association between sarcopenia and all-cause mortality was twice as strong in Black people (aHR = 2.99, 95% CI = 1.39–6.06) compared to White people (aHR = 1.53, 95% CI = 1.19–1.95). Conclusions: Our findings show the opposing relations of fat mass and appendicular skeletal muscle mass index with mortality in a national sample of cancer survivors, and that the relationships may differ by race. These results emphasize the importance of maintaining a healthy body composition among cancer survivors. [ABSTRACT FROM AUTHOR]

In sub-Saharan Africa, idiopathic dilated cardiomyopathy (IDCM) is a common yet poorly investigated cause of heart failure. Cardiovascular magnetic resonance (CMR) imaging is the gold standard for tissue characterisation and volumetric quantification. In this paper, we present CMR findings obtained from a cohort of patients with IDCM in Southern Africa suspected of having a genetic cause of cardiomyopathy. A total of 78 IDCM study participants were referred for CMR imaging. The participants had a median left ventricular ejection fraction of 24% [interquartile range, (IQR): 18–34]. Late gadolinium enhancement (LGE) was visualised in 43 (55.1%) participants and localised in the midwall in 28 (65.0%) participants. At the time of enrolment into the study, non-survivors had a higher median left ventricular end diastolic wall mass index of 89.4 g/m2 (IQR: 74.5–100.6) vs. 73.6 g/m2 (IQR: 51.9–84.7), p = 0.025 and a higher median right ventricular end-systolic volume index of 86 mL/m2 (IQR:74–105) vs. 41 mL/m2 (IQR: 30–71), p < 0.001. After one year, 14 participants (17.9%) died. The hazard ratio for the risk of death in patients with evidence of LGE from CMR imaging was 0.435 (95% CI: 0.259–0.731; p = 0.002). Midwall enhancement was the most common pattern, visualised in 65% of participants. Prospective, adequately powered, and multi-centre studies across sub-Saharan Africa are required to determine the prognostic significance of CMR imaging parameters such as late gadolinium enhancement, extracellular volume fraction, and strain patterns in an African IDCM cohort. [ABSTRACT FROM AUTHOR]

Background and aim: Chronic low-grade inflammation is associated with various health outcomes, including cardiovascular diseases (CVDs) and cancers. Systemic immune inflammation index (SII) and system inflammation response index (SIRI) have lately been explored as novel prognostic markers for all-cause mortality and cardiovascular mortality. However, studies on prediction value in nationwide representative population are scarce, which limit their generalization. To bridge the knowledge gap, this study aims to prospectively assess the association of SII, SIRI with all-cause mortality and cardiovascular mortality in the National Health and Nutrition Examination Survey (NHANES). Methods: From 1999 to 2018, 42,875 adults who were free of pregnancy, CVDs (stroke, acute coronary syndrome), cancers, and had follow-up records and participated in the NHANES were included in this study. SII and SIRI were quantified by calculating the composite inflammation indicators from the blood routine. To explore the characteristics of the population in different SII or SIRI levels, we divided them according to the quartile of SII or SIRI. The associations between SII, SIRI, and all-cause mortality and cardiovascular mortality events were examined using a Cox regression model. To investigate whether there was a reliable relationship between these two indices and mortalities, we performed subgroup analysis based on sex and age. Results: A total of 42,875 eligible individuals were enrolled, with a mean age of 44 ± 18 years old. During the follow-up period of up to 20 years, 4250 deaths occurred, including 998 deaths from CVDs. Cox proportional hazards modeling showed that adults with SII levels of >655.56 had higher all-cause mortality (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.18–1.41) and cardiovascular mortality (HR, 1.33; 95% CI, 1.11–1.59) than those with SII levels of <335.36. Adults with SIRI levels of >1.43 had higher risk of all-cause (HR, 1.39; 95% CI, 1.26–1.52) and cardiovascular death (HR, 1.39; 95% CI, 1.14–1.68) than those with SIRI levels of <0.68. In general population older than 60 years, the elevation of SII or SIRI was associated with the risk of all-cause death. Conclusion: Two novel inflammatory composite indices, SII and SIRI, were closely associated with cardiovascular death and all-cause death, and more attention should be paid to systemic inflammation to provide better preventive strategies. [ABSTRACT FROM AUTHOR]

A noninvasive tool for cardiovascular risk stratification has not yet been established in the clinical routine analysis. Previous studies suggest a prolonged Tpeak-Tend interval (the interval from the peak to the end of the T-wave) to be predictive of death. This meta-analysis was designed to systematically evaluate the association of the Tpeak-Tend interval with mortality outcomes. Medline (via PubMed), Embase and the Cochrane Library were searched from 1 January 2008 to 21 July 2020 for articles reporting the ascertainment of the Tpeak-Tend interval and observation of all-cause-mortality. The search yielded 1920 citations, of which 133 full-texts were retrieved and 29 observational studies involving 23,114 patients met the final criteria. All-cause deaths had longer Tpeak-Tend intervals compared to survivors by a standardized mean difference of 0.41 (95% CI 0.23–0.58) and patients with a long Tpeak-Tend interval had a higher risk of all-cause death compared to patients with a short Tpeak-Tend interval by an overall odds ratio of 2.33 (95% CI 1.57–3.45). Heart rate correction, electrocardiographic (ECG) measurement methods and the selection of ECG leads were major sources of heterogeneity. Subgroup analyses revealed that heart rate correction did not affect the association of the Tpeak-Tend interval with mortality outcomes, whereas this finding was not evident in all measurement methods. The Tpeak-Tend interval was found to be significantly associated with all-cause mortality. Further studies are warranted to confirm the prognostic value of the Tpeak-Tend interval. [ABSTRACT FROM AUTHOR]

Background: For centuries, convalescent plasma (CP) has been recommended to treat a diverse set of viral diseases. Therefore, the present study was undertaken to evaluate the effectiveness of CP in critically ill COVID-19 patients. Methods and Materials: From 23 March 2021 to 29 December 2021, an open-label, prospective cohort, single-centre study was conducted at Chest Disease Hospital, Jammu and Kashmir, Srinagar. Patients with severe manifestation of coronavirus disease 2019 (COVID-19) under BST (best standard treatment) +CP were prospectively observed in order to evaluate effectiveness of CP therapy and historical control under BST were used as the control group Results: A total of 1667 patients were found positive for COVID-19. Of these, 873 (52.4%), 431 (28.8%), and 363 (21.8%) were moderately, severely, and critically ill, respectively. On 35th day post-infusion of CP, all-cause mortality was higher in the BST (best standard treatment) +CP group 12 (37.5%) compared to 127 (35%) in the BST group with an odds ratio (OR) of 1.4 and hazard ratio (HR) (95% CI: 1.08–1.79, p = 0.06). Similarly, 7 (21.9) patients in the BST+CP group and 121 (33.3) patients in the BST group showed the transition from critically ill to moderate disease with subhazard ratio (s-HR 1.37) (95% CI: 1.03–2.9). Conclusions: In the present study, we could not find any significant difference in the CP group and BST +CP in primary outcome of reducing all-cause mortality in critically ill patients with negligible Nabs levels. However, beneficial results were observed with use of CP in a limited number of secondary outcomes which includes days of hospitalization, negative conversion of SARS-CoV-2 on basis of RT-PCR on 7th day and 14th day, need for invasive mechanical ventilation on 14th day post-CP treatment, and resolution of shortness of breath. [ABSTRACT FROM AUTHOR]

Measures of cardiovascular health (CVH) assessed by a combination of behavioral and biological factors has shown protective associations with all-cause mortality. The mechanisms underlying these associations have not been fully elucidated. In this study, we characterized the plasma proteomics profile of CVH and tested whether specific proteins mediated the associations between CVH and all-cause mortality in participants of the InCHIANTI study. Of the 1301 proteins tested, 92 proteins were associated with CVH (22 positively, 70 negatively). Proteins most strongly associated with CVH included leptin (LEP), fatty acid binding protein 3 (FABP3), Angiopoietin-2 (ANGPT2), and growth-differential factor 15 (GDF15). Of the 92 CVH-associated proteins, 33 proteins significantly mediated the associations between CVH and all-cause mortality, with percent mediation ranging from 5 to 30%. The most significant mediating proteins were GDF15 and insulin-like growth factor 2 (IGFBP2). Proteins associated with better CVH were enriched for proteins that reflect the suppression of the complement coagulation and GH/IGF pathways. [ABSTRACT FROM AUTHOR]

Introduction: The therapeutic impact of molnupiravir in the Omicron variant phase is unknown. The goal of the current meta-analysis was to compare the real-world clinical outcomes of molnupiravir for the treatment of mild to moderate COVID-19 during the dominance of the Omicron variant in adult patients to that of a placebo. Methods: To be included, studies had to directly compare the clinical effectiveness of molnupiravir in treating adult COVID-19 patients to that of a placebo. Studies were included based on the following outcomes: all-cause mortality, composite outcome of disease progression, hospitalization rate, and viral load. Results: The current meta-analysis included six studies that indicated that the risk of mortality was reduced by 34%, and the risk of composite outcome of disease progression was reduced by 37% among patients who received molnupiravir. Molnupiravir was associated with faster reduction in viral loads than the placebo. There was no clinical benefit of reducing all-cause mortality in mild to moderate COVID-19 patients with high COVID-19 vaccination coverage. Conclusion: The clinical effectiveness of molnupiravir was associated with COVID-19 vaccination coverage in COVID-19 patients. There is a lack of detailed data on its effectiveness in vaccinated patients, especially those with low COVID-19 vaccination coverage. [ABSTRACT FROM AUTHOR]

In the general population, there is little evidence of a link between blood urea nitrogen (BUN) and long-term mortality. The goal of this study was to explore whether higher BUN concentration is a predictor of cardiovascular disease (CVD) and all-cause mortality. From 1999 to 2006, the National Health and Nutrition Examination Survey (NHANES) included 17,719 adult individuals. Death outcomes were ascertained by linkage to the database records through 31 December 2015. The Cox proportional hazard regression model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD and all-cause mortality in individuals. We also performed stratified analyses based on age, gender, drinking, smoking, history of hypertension and diabetes. During a mean follow-up 11.65 years, a total of 3628 deaths were documented, of which 859 were due to CVD. Participants with higher BUN had a higher risk of CVD and all-cause death compared to those with lower BUN. After multifactor adjustment for demographics, major lifestyle factors, and hypertension and diabetes history, higher BUN levels compared with lower levels were significantly associated with higher risk of CVD (HR: 1.48 [1.08, 2.02], P-trend < 0.001) and all-cause mortality (HR: 1.48 [1.28, 1.72], P-trend < 0.001). In subgroup analyses, we found that the trend in the association of BUN with the risk of death remained strong in female subjects. Greater BUN levels were linked to higher CVD and all-cause mortality in the NHANES of American adults. The importance of BUN in predicting death is supported by our research. [ABSTRACT FROM AUTHOR]

Previous studies have suggested a possible association among dietary zinc and vitamin B6 intake and CVD mortality and all-cause mortality. However, evidence on the association of dietary zinc and vitamin B6 intake and their interactions with CVD mortality and all-cause mortality remains unclear. This prospective study utilized data from the US National Health and Nutrition Examination Survey (NHANES) from 1999 to 2016. After a median follow-up of 10.4 years, 4757 deaths were recorded among 36,081 participants. Higher dietary zinc intake levels (≥9.87 mg/day) were associated with lower CVD mortality (hazard ratio (HR) = 0.85, 95% confidence interval (CI): 0.83–0.87). Vitamin B6 intake levels (≥1.73 mg/day) were associated with lower CVD mortality (HR = 0.91, 95% CI: 0.86–0.96) and all-cause mortality (HR = 0.91, 95% CI: 0.90–0.93). Higher dietary zinc intake and higher vitamin B6 intake were associated with a lower risk of CVD mortality, with an interaction between dietary zinc intake levels and vitamin B intake levels (LZLV group (HR, CI): 1.21,1.12–1.29; LZHV group (HR, CI): 1.42, 1.34–1.50; LZHV group (HR, CI): 1.28, 1.14–1.45; HZHV group (HR, CI): ref). There was also a J-type association (p for nonlinear < 0.001) between the dietary zinc–vitamin B6 ratio and CVD mortality, with a high dietary zinc–vitamin B6 ratio increasing the risk of CVD mortality (HR = 1.27, 95% CI: 1.19–1.35), whereas a moderate dietary zinc–vitamin B6 ratio appeared to be beneficial for CVD mortality. These results suggest that increasing the appropriate proportion of dietary zinc and vitamin B6 intake is associated with a lower risk of CVD mortality. Furthermore, precise and representative studies are needed to verify our findings. [ABSTRACT FROM AUTHOR]

We aimed to investigate the association between dietary zinc intake and total deaths, cancer, and cardiovascular disease death. In this prospective, 10-year, community-based cohort analysis, data from 143,050 adult participants (aged 40 years and older) were analyzed. Dietary zinc intake at baseline was assessed using a food frequency questionnaire. Harrell's C-index was used to determine the optimal cut-off of dietary zinc intake with the log-rank test. Using the Cox proportional hazards regression models, the association between dietary zinc intake and all-cause, cancer, and cardiovascular disease mortality was estimated using hazard ratios and 95% confidence intervals. During the mean 10.1 years of follow-up, 5436 participants expired, of whom 2355 died due to cancer and 985 died due to cardiovascular causes. After adjustment for confounders, dietary zinc intake was inversely associated with all-cause mortality (≤5.60 mg/day vs. >7.98 mg/day; hazard ratio, 1.13; 95% confidence interval, 1.01–1.25) and cardiovascular disease mortality (≤5.12 mg/day vs. >7.28 mg/day; hazard ratio, 1.42; 95% confidence interval, 1.11–1.81) but not with cancer mortality (≤5.60 mg/day vs. >10.08 mg/day; hazard ratio, 1.09; 95% confidence interval, 0.90–1.33). Dietary zinc intake was associated with a lower risk of all-cause mortality and cardiovascular disease mortality but not with cancer mortality. Our findings could suggest that recommending optimal dietary zinc intake is helpful for human health. [ABSTRACT FROM AUTHOR]

This longitudinal cohort study explored the associations of 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), and β-C-terminal telopeptide of type 1 collagen (β-CTX) levels with all-cause mortality in centenarians. The study included 952 centenarians (81.4% female). During a median follow-up of 32 months, 752 (78.9%) centenarians died. The estimated 1-year, 3-year, and 5-year survival rates were 80.0%, 45.7%, and 23.6%, respectively. The association of mortality with 25(OH)D was linear, whereas the associations with PTH and β-CTX were J-shaped, with a lower risk below the median levels. Compared with 25(OH)D of ≥30 ng/mL, 25(OH)D < 30 ng/mL was associated with increased mortality (HR 1.52, 95% CI 1.24–1.86, p < 0.001). Compared with PTH of ≤65 pg/mL, PTH > 65 pg/mL was associated with increased mortality (HR 1.30, 95% CI 1.08–1.56, p = 0.005). Compared with β-CTX of <0.55 ng/mL, β-CTX ≥ 0.55 ng/mL was associated with increased mortality (HR 1.30, 95% CI 1.10–1.54, p = 0.002). A higher β-CTX level (even in the clinical reference range of 0.55–1.01 ng/mL) was associated with increased mortality (HR 1.23, 95% CI 1.04–1.47, p = 0.018). Centenarians with 25(OH)D < 30 ng/mL, PTH > 65 pg/mL, and β-CTX ≥ 0.55 ng/mL had a 2.77-fold (95% CI 1.99–3.85, p < 0.001) increased risk of mortality when compared with those with 25(OH)D of >30 ng/mL, PTH < 65 pg/mL, and β-CTX < 0.55 ng/mL. Lower serum 25(OH)D and higher PTH and β-CTX were independently correlated with increased all-cause mortality in Chinese community-dwelling centenarians. [ABSTRACT FROM AUTHOR]

The association between intakes of riboflavin and mortality has not been examined intensively in general populations. In this study, 10,480 adults in the 2005–2016 National Health and Nutrition Examination Survey (NHANES) were followed-up until 2019 for their vital status. Riboflavin and folate were assessed by two-day 24 h recall. The date and cause of death were obtained from the US Mortality Registry. The risks of all-cause mortality and cardiovascular disease (CVD) mortality were investigated using a Cox regression analysis. During a mean of 8.5 years follow-up, there were 1214 deaths registered (including 373 deaths from CVD and 302 from cancer). Compared to low level (quartile 1, Q1) of riboflavin intake, the hazard ratios (HRs) (95% confidence interval (CI)) for high level (quartile 4, Q4) were 0.53 (0.31–0.90) for CVD mortality and 0.62 (0.48–0.81) for all-cause mortality. The inverse association between riboflavin intake and CVD mortality was only significant among those with a high intake of folate (p for interaction 0.045). Those with a high folate intake (Q4) and low intake of riboflavin (Q1) had the highest risk of CVD mortality (HR 4.38, 95% CI 1.79–10.72), as compared with a high intake of both riboflavin and folate. In conclusion, riboflavin intake was inversely associated with all-cause mortality and CVD mortality, and the association was modified by folate intake. [ABSTRACT FROM AUTHOR]

Introduction: The presence of multiple comorbidities increases the risk of all-cause mortality, but the effects of the comorbidity sequence before the baseline date on mortality remain unexplored. This study investigated the relationship between coronary heart disease (CHD), atrial fibrillation (AF) and heart failure (HF) through their sequence of development and the effect on all-cause mortality risk in type 2 diabetes mellitus. Methods: This study included patients with type 2 diabetes mellitus prescribed antidiabetic/cardiovascular medications in public hospitals of Hong Kong between 1 January 2009 and 31 December 2009, with follow-up until death or 31 December 2019. The Cox regression was used to identify comorbidity sequences predicting all-cause mortality in patients with different medication subgroups. Results: A total of 249,291 patients (age: 66.0 ± 12.4 years, 47.4% male) were included. At baseline, 7564, 10,900 and 25,589 patients had AF, HF and CHD, respectively. Over follow-up (3524 ± 1218 days), 85,870 patients died (mortality rate: 35.7 per 1000 person-years). Sulphonylurea users with CHD developing later and insulin users with CHD developing earlier in the disease course had lower mortality risks. Amongst insulin users with two of the three comorbidities, those with CHD with preceding AF (hazard ratio (HR): 3.06, 95% CI: [2.60–3.61], p < 0.001) or HF (HR: 3.84 [3.47–4.24], p < 0.001) had a higher mortality. In users of lipid-lowering agents with all three comorbidities, those with preceding AF had a higher risk of mortality (AF-CHD-HF: HR: 3.22, [2.24–4.61], p < 0.001; AF-HF-CHD: HR: 3.71, [2.66–5.16], p < 0.001). Conclusions: The sequence of comorbidity development affects the risk of all-cause mortality to varying degrees in diabetic patients on different antidiabetic/cardiovascular medications. [ABSTRACT FROM AUTHOR]

A high ultrafiltration rate (UFR) is associated with increased mortality in hemodialysis patients. However, whether a high UFR itself or heart failure with fluid overload followed by a high UFR causes mortality remains unknown. In this study, 2615 incident hemodialysis patients were categorized according to their initial cardiothoracic ratios (CTRs) to assess whether UFR was associated with mortality in patients with high or low CTRs. In total, 1317 patients (50.4%) were women and 1261 (48.2%) were diabetic. During 2246 (1087–3596) days of follow-up, 1247 (47.7%) cases of all-cause mortality were noted. UFR quintiles 4 and 5 were associated with higher risks of all-cause mortality than UFR quintile 2 in fully adjusted Cox regression analysis. As the UFR increased by 1 mL/kg/h, the risk of all-cause mortality increased 1.6%. Subgroup analysis revealed that in UFR quintile 5, hazard ratios (HRs) for all-cause mortality were 1.91, 1.48, 1.22, and 1.10 for CTRs of >55%, 50–55%, 45–50%, and <45%, respectively. HRs for all-cause mortality were higher in women and patients with high body weight. Thus, high UFRs may be associated with increased all-cause mortality in incident hemodialysis patients with a high CTR, but not in those with a low CTR. [ABSTRACT FROM AUTHOR]

Simple Summary: Concomitant hepatic steatosis is common in patients with chronic hepatitis B (CHB), but data regarding its impact on the natural history of CHB remain sparse and conflicting. Recently, metabolic-associated fatty liver disease (MAFLD) was defined as hepatic steatosis in the presence of metabolic abnormality. The utility of MAFLD and its ability to assess hepatocellular carcinoma (HCC) risk for CHB requires further investigation. In this population-based cohort study of CHB, MAFLD was not associated with an increased risk of HCC. However, it was associated with a higher probability of functional cure for CHB in terms of HBsAg loss, and the MAFLD–HCC association was largely mediated by the development of HBsAg seroclearance driven by hepatic steatosis. On the contrary, the burden of metabolic risk abnormality was robustly associated with an increased risk of HCC in CHB, and this association was observed for participants both with and without hepatic steatosis and for participants both with and without HBsAg seroclearance. The value of metabolic-associated fatty liver disease (MAFLD) and its ability to assess hepatocellular carcinoma (HCC) risk remains uncertain for chronic hepatitis B (CHB). We evaluated the impacts of MAFLD and its coincidental metabolic abnormalities and related genetic predisposition on HCC incidence and mortality outcomes in CHB. We analyzed data from 1453 HBsAg-positive men (median age = 49.2 years at baseline) from a cohort of civil servants recruited from 1989–1992. MAFLD was defined as hepatic steatosis on ultrasound with obesity, diabetes, or metabolic dysfunction at baseline. During follow-up (median = 19.3 years), 105 HCC events occurred. MAFLD was not associated with HCC (adjusted hazard ratio (aHR) = 1.02) but was associated with a higher HBsAg seroclearance rate (aHR = 1.43). In mediation analysis, HBsAg seroclearance driven by hepatic steatosis explained 31.6% of the association between MAFLD and HCC. Antiviral treatment or fatty liver disease-associated genetic variants did not influence the MAFLD–HCC association. In contrast, even after adjustment for MAFLD and the other metabolic abnormalities, diabetes (aHR = 2.28), obesity (aHR = 1.72), and metabolic dysfunction (aHR = 3.30) increased the risk of HCC (all p < 0.030). The risk of HCC increased with the number of metabolic abnormalities (vs 0: aHR = 2.05 and 5.72 for 2 and ≥ 3 metabolic abnormalities, respectively), and the cumulative effect of metabolic abnormalities was found across subgroups categorized by hepatic steatosis as well as in participants both with and without HBsAg seroclearance. In conclusion, MAFLD was not associated with increased HCC incidence in CHB. A more informative assessment of HCC risk can be obtained by taking into account the number of metabolic abnormalities. [ABSTRACT FROM AUTHOR]

Simple Summary: Insufficient physical activity (PA) is a global health issue with significant disease burden. Increasing evidence suggests that higher PA levels have protective effects against chronic diseases. Few prospective cohort studies have explored the association between PA levels and mortality in cancer survivors. Using a large nationally representative survey population of United States adults, this study demonstrated a beneficial association between leisure-time PA and all-cause mortality in cancer survivors. There was a nonlinear relationship between the total PA and the risk of all-cause mortality. Threshold effect analysis demonstrated that cancer survivors should perform PA for at least 1 h per week and performing more PA could provide additional survival benefits for cancer survivors. We designed this study to investigate the associations between physical activity (PA) and the risk of all-cause mortality in cancer survivors using a nationally representative cohort of US adults. This cohort study included 13 cycles of the National Health Interview Surveys, and by matching participants with the National Death Index (2015), survival status was determined. The main outcome was all-cause mortality during follow-up. A total of 20,088 participants aged 62.2 (15.9) years (62.4% women) were analyzed. After an average follow-up of 117.5 months, 7214 (35.9%) participants died. Compared with inactive cancer survivors, we observed a 25% lower all-cause mortality risk among participants performing PA 10 min to 1 h/week (hazard ratio [HR] = 0.75, 95% confidence interval [CI] = 0.67–0.85), a 28% lower risk among those performing PA 1–2.5 h/week (HR = 0.72, 95% CI = 0.67–0.78), a 34% lower risk among those performing PA 2.5–5 h/week (HR = 0.66, 95% CI = 0.60–0.72), a 37% lower risk among those performing PA 5–7.5 h/week (HR = 0.63, 95% CI = 0.56–0.70), a 47% lower risk among those performing PA 7.5–13.3 h/week (HR = 0.53, 95% CI = 0.47–0.61), and a 43% lower risk among those performing PA 13.3–24 h/week (adjusted HR = 0.53, 95% CI = 0.49–0.66). In cancer survivors, leisure-time PA was associated with a lower all-cause mortality. Inactive cancer survivors should be encouraged to perform more PA to reduce the risk of all-cause mortality. [ABSTRACT FROM AUTHOR]