Exploring the Association between Daily Distributional Patterns of Physical Activity and Cardiovascular Mortality Risk among Older Adults in NHANES 2003-2006.

PURPOSE: Cardiovascular disease (CVD) is one of the leading causes of death worldwide. Physical activity (PA) has previously been shown to be a prominent risk factor for CVD mortality. Traditionally, measurements of PA have been self-reported and based on various summary metrics. However, recent advances in wearable technology provide continuously monitored and objectively measured physical activity data. This facilitates a more comprehensive interpretation of the implications of PA in the context of CVD mortality by considering its daily patterns and compositions. METHODS: This study utilized accelerometer data from the 2003-2006 National Health and Nutrition Examination Survey (NHANES) on 2,816 older adults aged 50-85 and mortality data from the National Death Index (NDI) in December 2019. A novel partially functional distributional analysis method was used to quantify and understand the association between daily distributional patterns of physical activity and cardiovascular mortality risk through a multivariable functional Cox model. RESULTS: A higher mean intensity of daily PA during the day was associated with a reduced hazard of CVD mortality after adjusting for other higher order distributional summaries of PA and age, gender, race, body mass index (BMI), smoking and coronary heart disease (CHD). A higher daily variability of PA during afternoon was associated with a reduced hazard of CVD mortality, after adjusting for the other predictors, particularly on weekdays. The subjects with a lower variability of PA, despite having same mean PA throughout the day, could have a lower reserve of PA and hence could be at increased risk for CVD mortality. CONCLUSIONS: Our results demonstrate that not only the mean intensity of daily PA during daytime, but also the variability of PA during afternoon could be an important protective factor against the risk of CVD-mortality. Considering circadian rhythm of PA as well as its daily compositions can be useful for designing time-of-day and intensity-specific PA interventions to protect against the risk of CVD mortality.

Understanding disparities in cardiovascular death rates among older adults with sick sinus syndrome in the US.

Background: Sick sinus syndrome (SSS) increases with age, and approximately one in 600 patients above 65 develop this condition. In this study, the authors assessed trends in mortality related to SSS among older adults ≥65 years of age in the United States from 1999 to 2019. Methods: Trends in cardiovascular mortality related to SSS were identified by analyzing the data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database, where cardiovascular deaths were listed as the underlying cause of death and SSS was listed as the contributing cause of death between 1999 and 2019. Age-adjusted mortality rates (AAMR) per 1,000,000 population were determined. Results: Between 1999 and 2019, a total of 41,615 SSS-related deaths occurred in older adults. Of these, 17,466 (41.9%) were men and 24,149 (58.1%) were women. Although a decline in cardiovascular mortality related to SSS was apparent from 1999 to 2014, a steep rise was noted from 2014 to 2019 [Annual Percentage Change (APC): 2.9%; 95% CI, 1.5-5.7]. Overall AAMRs were highest among White men (AAMR: 55.8; 95% CI, 54.9-56.6), followed by Black men (AAMR: 44.8; 95% CI, 42-47.6), White women (AAMR: 43.3; 95% CI, 42.8-43.9), and Black women (AAMR: 39.4; 95% CI, 37.6-41.2). Rural dwellers had higher AAMRs compared to urban dwellers. Notably, rural dwellers had a period of stability between 2014 and 2019, while an increase in mortality was apparent among urban dwellers during this period. Lastly, states in the 90th percentile displayed approximately two fold higher AAMR compared to those in the bottom 10th percentile. Conclusion: Sick sinus syndrome-related mortality trends have shown a steady rise from 2014 to 2019. Moreover, NH White adults, rural dwellers, and individuals residing in the states among the 90th percentile demonstrated significantly higher AAMRs. Thus, further investigations and actions are required to reverse these rising trends.

Association of metabolic score for visceral fat with all-cause mortality, cardiovascular mortality, and cancer mortality: A prospective cohort study.

AIM: Our study aimed to evaluate the association between the metabolic score for visceral fat (METS-VF) and mortality. METHODS: We conducted a cohort study comprising 11,120 participants. We employed weighted multivariable Cox regression analysis to assess the relationship between METS-VF and mortality. Restricted cubic spline analyses were used to investigate potential non-linear associations. Receiver operating characteristic curves were used to evaluate the predictive value of METS-VF and other obesity-related indicators for mortality. Subgroup analysis and sensitivity analysis were performed to confirm the robustness of the results. Mendelian randomization analysis was utilized to assess potential causality. RESULTS: Over a median follow-up duration of 83 months, a total of 1014 all-cause deaths, 301 cardiovascular deaths, and 262 cancer deaths occurred. For every 0.2-unit increase in METS-VF, the hazard ratios(HRs) of all-cause mortality, cardiovascular mortality, and cancer mortality were 1.13 [95% confidence interval (CI): 1.06, 1.20], 1.18 (95% CI: 1.06, 1.31), and 1.13 (95% CI: 1.03, 1.25), respectively. In addition, restricted cubic spline analyses revealed no significant non-linear associations between METS-VF and all-cause mortality, cardiovascular mortality, and cancer mortality. In multivariate Cox regression models, hazard ratios of all-cause mortality, cardiovascular mortality and cancer mortality were higher in the highest METS-VF group compared to the reference group. Subgroup and sensitivity analyses confirmed that our results were robust. Receiver operating characteristic curves indicated that METS-VF predicted mortality better than other obesity-related indicators. Mendelian randomization analysis confirmed significant causal relationships. CONCLUSIONS: METS-VF was positively associated with all-cause mortality, cardiovascular mortality, and cancer mortality. These findings suggest that METS-VF could serve as a straightforward, reliable, and cost-effective marker for identifying individuals at high risk of mortality.

Addressing the alarming link between nonalcoholic fatty liver disease and cardiovascular mortality in men.

This editorial discusses the key findings presented in Batta and Hatwal's recent paper titled "Excess cardiovascular mortality in men with non-alcoholic fatty liver disease: A cause for concern!", which was published in the World Journal of Cardiology. Their original article highlights a notable correlation between nonalcoholic fatty liver disease (NAFLD) and increased cardiovascular mortality risk in men. The present commentary explores the implications of their findings, discussing potential mechanisms, risk factors, and the urgent need for integrated clinical approaches to mitigate the dual burden of these diseases. Emphasis should be placed on the importance of early detection, lifestyle modifications, and interdisciplinary collaboration for improving patient outcomes. This editorial aims to highlight the broad implications of NAFLD for cardiovascular health and to advocate for increased awareness and proactive management strategies within the medical community.

Association of plasma proteomics with mortality in individuals with and without type 2 diabetes: Results from two population-based KORA cohort studies.

BACKGROUND: Protein biomarkers may contribute to the identification of vulnerable subgroups for premature mortality. This study aimed to investigate the association of plasma proteins with all-cause and cause-specific mortality among individuals with and without baseline type 2 diabetes (T2D) and evaluate their impact on the prediction of all-cause mortality in two prospective Cooperative Health Research in the Region of Augsburg (KORA) studies. METHODS: The discovery cohort comprised 1545 participants (median follow-up 15.6 years; 244 with T2D: 116 total, 62 cardiovascular, 31 cancer-related and 23 other-cause deaths; 1301 without T2D: 321 total, 114 cardiovascular, 120 cancer-related and 87 other-cause deaths). The validation cohort comprised 1031 participants (median follow-up 6.9 years; 203 with T2D: 76 total, 45 cardiovascular, 19 cancer-related and 12 other-cause deaths; 828 without T2D: 169 total, 74 cardiovascular, 39 cancer-related and 56 other-cause deaths). We used Cox regression to examine associations of 233 plasma proteins with all-cause and cause-specific mortality and Lasso regression to construct prediction models for all-cause mortality stratifying by baseline T2D. C-index, category-free net reclassification index (cfNRI), and integrated discrimination improvement (IDI) were conducted to evaluate the predictive performance of built prediction models. RESULTS: Thirty-five and 62 proteins, with 29 overlapping, were positively associated with all-cause mortality in the group with and without T2D, respectively. Out of these, in the group with T2D, 35, eight, and 26 were positively associated with cardiovascular, cancer-related, and other-cause mortality, while in the group without T2D, 55, 41, and 47 were positively associated with respective cause-specific outcomes in the pooled analysis of both cohorts. Regulation of insulin-like growth factor (IGF) transport and uptake by IGF-binding proteins emerged as a unique pathway enriched for all-cause and cardiovascular mortality in individuals with T2D. The combined model containing the selected proteins (five and 12 proteins, with four overlapping, in the group with and without T2D, respectively) and clinical risk factors improved the prediction of all-cause mortality by C-index, cfNRI, and IDI. CONCLUSIONS: This study uncovered shared and unique mortality-related proteins in persons with and without T2D and emphasized the role of proteins in improving the prediction of mortality in different T2D subgroups.

Interactions of Obstructive Sleep Apnea With the Pathophysiology of Cardiovascular Disease, Part 1: JACC State-of-the-Art Review.

The American Heart Association considers sleep health an essential component of cardiovascular health, and sleep is generally a time of cardiovascular quiescence, such that any deviation from normal sleep may be associated with adverse cardiovascular consequences. Many studies have shown that both impaired quantity and quality of sleep, particularly with obstructive sleep apnea (OSA) and comorbid sleep disorders, are associated with incident cardiometabolic consequences. OSA is associated with repetitive episodes of altered blood gases, arousals, large negative swings in intrathoracic pressures, and increased sympathetic activity. Recent studies show that OSA is also associated with altered gut microbiota, which could contribute to increased risk of cardiovascular disease. OSA has been associated with hypertension, atrial fibrillation, heart failure, coronary artery disease, stroke, and excess cardiovascular mortality. Association of OSA with chronic obstructive lung disease (overlap syndrome) and morbid obesity (obesity hypoventilation syndrome) increases the odds of mortality.

α-Klotho is associated with cardiovascular and all-cause mortality in patients with stage 3b and 4 chronic kidney disease (CKD): a long-term prospective cohort study.

BACKGROUND: α-Klotho deficiency may increase cardiovascular risks and worsen survival. We evaluated the association of α-Klotho with cardiovascular and all-cause mortality in pre-dialysis chronic kidney disease (CKD) patients. METHODS: In this prospective study, 75 non-diabetic CKD stage 3b-4 patients were followed-up for a median of 8 years. Primary and secondary outcomes were all-cause and cardiovascular mortality, respectively. Human soluble α-Klotho ELISA Assay (IBL-Takara 27,998-96Well), Human Fibroblast Growth Factor-23 ELISA Assay (intact FGF23, Merck Millipore MILLENZ FGF23-32 K), and Human Sclerostin ELISA kits (Biomedica, Vienna, BI-20492) were used to measure serum α-Klotho, FGF23 and sclerostin levels in the certified laboratory at the Sechenov University according to the manufacturers' protocols. All patients underwent echocardiography to evaluate left ventricular mass index (LVMI), left ventricular ejection fraction by Simpson method, and cardiac (valve) calcification score by a semi-quantitative point scale. Lateral abdominal radiography by Kauppila method was used to estimate calcification of the abdominal aorta. Cox multivariate regression and receiver-operating characteristic curve (ROC)-analysis were used to evaluate risk factors for death and their cut-off values. RESULTS: Primary and secondary endpoints were reached in 15 (20%) and 9 (12%) patients, respectively. Median α-Klotho levels in deceased and surviving patients were 344 and 484 pg/ml, respectively (p = 0.002). In a multivariate Cox regression model, baseline α-Klotho levels (HR 0.99, 95% CI 0.98-1.00, p = 0.023), aortic calcification (HR 1.18, 95% CI 1.02-1.36, p = 0.029) and left ventricular mass index (LVMI) (HR 1.04, 95% CI 1.00-1.08, p = 0.033) were associated with the primary endpoint, whereas α-Klotho (HR 0.99, 95% CI 0.98-1.00, p = 0.029), aortic calcification (HR 1.23, 95% CI 1.07-1.42, p = 0.003) and LVMI (HR 1.04, 95% CI 1.00-1.08, p = 0.021) were associated with the secondary endpoint. α-Klotho levels had the highest area under the curve (AUC) by ROC analysis, that is, 0.766 (95% CI 0.70-0.82) for the primary endpoint and 0.842 (95% CI 0.79-0.90) for the secondary endpoint with cut-off values of 412 pg/ml (HR 3.06, 95% CI 1.36-6.89, p = 0.007) and 368 pg/ml (HR 4.84, 95% CI 1.59-14.73, p = 0.005), respectively. CONCLUSION: In pre-dialysis CKD patients, α-Klotho levels are associated with all-cause and cardiovascular mortality and may be considered an early prognostic marker.

Association of the panimmune-inflammatory value (PIV) with all-cause and cardiovascular mortality in maintenance hemodialysis patients: a propensity score matching retrospective study.

PURPOSE: The panimmune-inflammatory value (PIV) is a novel inflammatory indicator. However, its role in maintenance hemodialysis (MHD) remains unclear. Our goal was to explore the predictive value of PIV for cardiovascular and all-cause mortality in MHD patients. METHODS: In this retrospective cohort study, 507 patients receiving MHD between November 2017 and December 2022 were enrolled. The PIV value was calculated as follows: neutrophil count × monocyte count × platelet count/lymphocyte count. Patients were divided into two groups on the basis of the median PIV. Propensity score matching (PSM) was used to adjust for imbalances in baseline information between groups. Kaplan‒Meier curves, Cox regression, the Fine‒Gray competing risk model, and restricted cubic spline (RCS) curves were used to analyze the relationship between PIV and mortality. RESULTS: By the end of follow-up, 126 deaths had occurred, 91 of which were due to cardiovascular disease. The Kaplan‒Meier curves demonstrated that MHD patients with higher PIV levels had a poorer prognosis for all-cause death (p = 0.019). PIV levels were linked to all-cause death in multivariate Cox proportional risk regression (HR = 1.76; 95% CI 1.14, 2.72; p = 0.011). The Fine‒Gray model revealed a greater cumulative incidence of cardiovascular death in the higher PIV group (p = 0.035). PIV levels were linked to cardiovascular mortality in the Fine‒Gray competing risk model (HR = 2.06; 95% CI 1.25, 3.42; p = 0.005). The RCS revealed a nonlinear relationship between PIV and mortality risk (p < 0.05). Using 63 years of age as the threshold, we observed a multiplicative interaction effect between age and PIV for all-cause mortality (p = 0.006). CONCLUSION: In MHD patients, PIV is an independent hazard factor for cardiovascular-related mortality and all-cause mortality.

The association between joint Serum Neurofilament Light Chain and type 2 diabetes with all-cause and cardiovascular mortality in US adults: a longitudinal study of NHANES.

BACKGROUND: In the past, there has been a clear conclusion regarding the sole impact of serum neurofilament light chain (sNfL) levels or type 2 diabetes mellitus (DM) on the risk of death. However, the combined effect of sNfL levels and type 2 DM on all-cause and cardiovascular mortality is still uncertain. METHODS: This study was a prospective cohort study based on data from the National Health and Nutrition Examination Survey (NHANES). The sNfL levels were measured through immunological methods using blood samples collected during the survey. The diagnosis of diabetes was based on rigorous criteria, and participants' mortality data were followed up until December 31, 2019. Firstly, we separately examined the effects of sNfL and type 2 DM on all-cause and cardiovascular mortality, and finally studied the comprehensive impact of the combination of sNfL and type 2 DM on the risk of mortality. Cumulative Kaplan-Meier curves, multivariate logistic regression and sensitivity analysis were incorporated throughout the entire study. RESULTS: Participants in the highest quartile of sNfL were observed. Multivariable COX regression model showed that increased sNfL levels and type 2 DM were respectively associated with an increased risk of all-cause and cardiovascular mortality. Furthermore, elevated sNfL levels were significantly associated with an increased risk of all-cause mortality and cardiovascular mortality after adjustment for confounding factors. When considering both elevated sNfL levels and type 2 DM, individuals had a significantly increased risk of mortality. Sensitivity analysis confirmed the robustness of the findings. CONCLUSIONS: These results suggest that elevated levels of sNfL and type 2 DM are associated with an increased risk of all-cause and cardiovascular mortality, and that participants with increased sNfL levels associated with type 2 DM have higher all-cause mortality and cardiovascular mortality.

The association between klotho and kidney and cardiovascular outcomes: a comprehensive systematic review and meta-analysis.

Background: Chronic kidney disease (CKD) and end-stage renal disease (ESKD) are significant global health challenges associated with progressive kidney dysfunction and numerous complications, including cardiovascular disease and mortality. This study aims to explore the potential association between plasma klotho levels and various prognostic outcomes in CKD and ESKD, including all-cause mortality, cardiovascular events, metabolic syndrome development and adverse renal events necessitating renal replacement therapies. Methods: A literature search was conducted through 3 June 2024 using the electronic databases Cochrane Library, Ovid MEDLINE, CINAHL, Web of Science, SCOPUS and PubMed. This systematic review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: Fourteen studies were included. For all-cause mortality, comparing CKD patients with low versus high klotho levels showed a significant association {odds ratio [OR] 1.81 [95% confidence interval (CI) 1.34-2.44], P = .0001}, with substantial heterogeneity (I 2 = 69%). Excluding one study reduced heterogeneity (I 2 = 43%) while maintaining significance [OR 1.97 (95% CI 1.45-2.66), P < .0001]. Cardiovascular mortality was higher in patients with low klotho levels [OR 2.11 (95% CI 1.61-2.76), P < .00001], with low heterogeneity (I 2 = 25%). Excluding one study eliminated heterogeneity (I 2 = 0%) while maintaining significance [OR 2.39 (95% CI 1.83-3.12), P < .00001]. Composite cardiovascular events did not differ significantly between low and high klotho groups [OR 1.51 (95% CI 0.82-2.77), P = .18], but with high heterogeneity (I 2 = 72%). Patients with low klotho levels had a higher risk of adverse renal events [OR 2.36 (95% CI 1.37-4.08), P = .002], with moderate heterogeneity (I 2 = 61%). Sensitivity analysis reduced heterogeneity (I 2 = 0%) while maintaining significance [OR 3.08 (95% CI 1.96-4.85), P < .00001]. Specifically, for ESKD or kidney replacement therapy risk, low klotho levels were associated with an increased risk [OR 2.30 (95% CI 1.26-4.21), P = .007]. Similarly, CKD progression risk was higher in patients with lower klotho levels [OR 2.48 (95% CI 1.45-4.23), P = .0009]. Conclusion: Lower serum klotho levels serve as a significant predictor of adverse outcomes, including increased risks of all-cause mortality, cardiovascular mortality and progression to end-stage kidney disease among CKD patients.

The impact of cardiovascular health on mortality in US adults with cardiometabolic disease: A prospective nationwide cohort study.

BACKGROUND AND AIMS: Individuals with cardiometabolic disease (CMD) face high risks of adverse outcomes. However, there is little evidence of the effectiveness of comprehensive risk assessment using the Life's Essential 8 (LE8) score in CMD. This study aimed to examine the associations between LE8 and all-cause and cardiovascular mortality rates in individuals with CMD. METHODS AND RESULTS: This study included 11,198 NHANES participants, categorized into low, moderate, and high CVH groups according to LE8 scores. The LE8 score consists of eight components: diet, physical activity, nicotine exposure, sleep health, BMI, blood lipids, blood glucose, and blood pressure. A higher LE8 score indicates better cardiovascular health. Multivariable Cox proportional hazard regression and restricted cubic splines were employed to estimate the associations. Subgroup analyses considered age, sex, race and ethnicity, income, marital status, and education. During a median follow-up of 91 months, 1079 deaths were recorded, 325 of which were cardiovascular. The multivariable adjusted hazard ratio (HR) per 10-point increase in LE8 was 0.79 (95% confidence interval (CI), 0.75-0.84) for all-cause mortality and 0.71 (95% CI, 0.64-0.79) for cardiovascular mortality. Participants with moderate and high LE8 levels showed similar inverse associations. Those under 60 exhibited more pronounced associations (P for interaction <0.05). After adjusting for multiple variables, a linear relationship was observed between LE8 and all-cause and cardiovascular mortality in the CMD population. CONCLUSIONS: The newly introduced LE8 showed a significant negative association with all-cause and cardiovascular mortality risk among CMD individuals, highlighting its potential for CMD tertiary prevention.

Self-reported physical activity properties and 20-year all-cause and cardiovascular mortality among community-dwelling older adults.

PURPOSE: Physical activity was previously associated with decreased mortality. Current guidelines recommend >150 min/week or >75 min/week of moderate or high-intensity exercise to maintain a healthy lifestyle; however, exercise properties most strongly associated with low mortality among the elderly may still be explored. METHODS: A total of 1210 community-dwelling older adults, from the third phase (1999-2004) of the Israel Study on Glucose Intolerance, Obesity, and Hypertension, were followed until 2016 and 2019 for cardiovascular and all-cause mortality, respectively. Physical activity properties were recorded and evaluated against all-cause and cardiovascular mortality. RESULTS: Mean age at baseline was 73 ± 7 years, with 638 (53%) females, and 585 (48%) reported habitual exercise. When compared to sedentary individuals, multivariable Cox regressions showed a significantly lower risk for all-cause mortality among currently active individuals [hazard ratio (HR) = 0.72, 95% confidence interval (CI): 0.59-0.88, P = .002], those engaging in light-moderate activity (HR = 0.72, 95% CI: 0.57-0.89, P = .003), those with diverse exercise types (HR = 0.59, 95% CI: 0.44-0.80, P = .001), more sessions/week (HR = 0.94, 95% CI: 0.92-0.97, P < .001), those meeting current exercise recommendations (HR = 0.79, 95% CI: 0.58-0.89, P = .03), those who engaged in walking (HR = 0.58, 95% CI: 0.45-0.76, P < .001), and swimming (HR = 0.66, 95% CI: 0.45-0.96, P = .03). Similar HRs were found for cardiovascular mortality, although a somewhat stronger protective association was observed for swimming (HR = 0.48, 95% CI: 0.24-0.95, P = .04) compared to a sedentary lifestyle. CONCLUSION: The study further supports current exercise guidelines among the elderly. It also underscores the importance of physical activity in older individuals while prioritizing a greater number of sessions/week in addition to the total duration, and highlights specific activity features associated with lower long-term mortality among older adults. Key message • What is already known on this topic - Physical activity was associated with a lower risk for mortality, although the specific properties and the preferred type of exercise among older adults are still debatable. • What this study adds - The study suggests the optimal activity characteristics in older adults while prioritizing activity sessions over time, light-moderate exercise over strenuous activity, diverse activity, and walking and swimming over other activities. • How this study might affect research, practice or policy - Future exercise guidelines should focus on increasing activity sessions throughout the week and not on the cumulative time to maximize the effect on mortality.

Sixteen prescribed Chinese herbal medicines provide time-dependent cardiorenal and survival benefits in patients with overall and advanced diabetic kidney disease: a real-world study in Taiwan.

Background: A causal connection between oxidative stress and inflammation in diabetes, along with its associated renal and cardiovascular complications, has been established. Sixteen prescribed potentially renoprotective Chinese herbal medicines for diabetic kidney disease (PRCHMDKD), which are scientific Chinese medicine (botanical drug) and categorized into five classes (clearing heat, nourishing yin, dampness dispelling, tonifying qi, and harmonizing formulas), exhibit shared antioxidative properties and target multiple oxidative stress pathways. However, the time-response, cumulative effects, and safety (hyperkalemia risk) of these sixteen PRCHMDKD on cardiorenal and survival outcomes in patients with overall and advanced DKD remain unresolved. Methods: This retrospective cohort study analyzed national health insurance claims data in 2000-2017. Four statistical methods, including Cox proportional hazards models, complementary restricted mean survival time (RMST), propensity score matching, and competing risk analysis for end-stage renal disease (ESRD), were employed to investigate this relationship. The study included 43,480 PRCHMDKD users and an equal number of matched nonusers within the overall DKD patient population. For advanced DKD patients, the cohort comprised 1,422 PRCHMDKD users and an equivalent number of matched nonusers. Results: PRCHMDKD use in overall and advanced, respectively, DKD patients was associated with time-dependent reductions in adjusted hazard ratios for ESRD (0.66; 95% CI, 0.61-0.70 vs. 0.81; 0.65-0.99), all-cause mortality (0.48; 0.47-0.49 vs. 0.59; 0.50-0.70), and cardiovascular mortality (0.50; 0.48-0.53 vs. 0.61; 0.45-0.82). Significant differences in RMST were observed in overall and advanced, respectively, DKD patients, favoring PRCHMDKD use: 0.31 years (95% CI, 0.24-0.38) vs. 0.61 years (0.13-1.10) for ESRD, 2.71 years (2.60-2.82) vs. 1.50 years (1.03-1.98) for all-cause mortality, and 1.18 years (1.09-1.28) vs. 0.59 years (0.22-0.95) for cardiovascular mortality. Additionally, hyperkalemia risk did not increase. These findings remained consistent despite multiple sensitivity analyses. Notably, the cumulative effects of utilizing at least four or five classes and multiple botanical drugs from the sixteen PRCHMDKD provided enhanced renoprotection for patients with both overall and advanced DKD. This suggests that there is involvement of multiple targets within the oxidative stress pathways associated with DKD. Conclusion: This real-world study suggests that using these sixteen PRCHMDKD provides time-dependent cardiorenal and survival benefits while ensuring safety for DKD patients.

Association of triglyceride-glucose-body mass index with all-cause and cardiovascular mortality among individuals with chronic kidney disease.

There is still a paucity of research on the relationship between triglyceride-glucose-body mass index (TyG-BMI) and long-term all-cause and cardiovascular disease (CVD) mortality in patients with chronic kidney disease (CKD). The objective of this study was to explore the relationship between the TyG-BMI index and mortality rate and to determine valuable predictive factors for the survival status of this population. Data were obtained from the National Health and Nutrition Examination Survey (NHANES 2001-2018) and the National Death Index (NDI). We used multivariate Cox regression and restricted cubic spline (RCS) to analyze the link between the TyG-BMI index and all-cause and CVD mortality. Subgroup analysis was conducted according to age, gender, race, education and poverty. In addition, receiver operating characteristic (ROC) curves were utilized to assess the differentiation of the TyG-BMI index in predicting mortality. A total of 3089 individuals were enrolled. Over a median follow-up period of 81 months, 1097 individuals passed away. The RCS analysis revealed a U-shaped link between the TyG-BMI index and all-cause and CVD mortality. The ROC curve indicated that the TyG-BMI index has a stronger diagnostic effect than the TyG index. Subgroup analysis results demonstrated that the TyG-BMI index was more significantly correlated with all-cause and CVD mortality rates in elderly patients. In the American population, a U-shaped association was discovered between the baseline TyG-BMI index and all-cause and cardiovascular mortality rates in CKD patients. The thresholds for all-cause and CVD mortality were found to be 299.31 and 294.85, respectively.

Relationships between ankle blood pressure indices and major adverse cardiovascular events in people with and without type 2 diabetes.

BACKGROUND: The relationship between ankle blood pressure (BP) and cardiovascular disease remains unclear. We examined the relationships between known and new ankle BP indices and major cardiovascular outcomes in people with and without type 2 diabetes. METHODS: We used data from 3 large trials with measurements of ankle systolic BP (SBP), ankle-brachial index (ABI, ankle SBP divided by arm SBP), and ankle-pulse pressure difference (APPD, ankle SBP minus arm pulse pressure). The primary outcome was a composite of cardiovascular mortality, myocardial infarction, hospitalization for heart failure, or stroke. Secondary outcomes included death from cardiovascular causes, total (fatal and non-fatal) myocardial infarction, hospitalization for heart failure, and total stroke. RESULTS: Among 42,929 participants (age 65.6 years, females 31.3%, type 2 diabetes 50.1%, 53 countries), the primary outcome occurred in 7230 (16.8%) participants during 5 years of follow-up (19.4% in people with diabetes, 14.3% in those without diabetes). The incidence of the outcome increased with lower ankle BP indices. Compared with people whose ankle BP indices were in the highest fourth, multivariable-adjusted hazard ratios (HRs, 95% CI) of the outcome for each lower fourth were 1.05 (0.98-1.12), 1.17 (1.08-1.25), and 1.54 (1.54-1.65) for ankle SBP; HR 1.06 (0.99-1.14), 1.26 (1.17-1.35), and 1.48 (1.38-1.58) for ABI; and HR 1.02 (0.95-1.10), 1.15 (1.07-1.23), and 1.48 (1.38-1.58) for APPD. The largest effect size was noted for ankle SBP (HRs 1.05 [0.90-1.21], 1.21 [1.05-1.40], and 1.93 [1.68-2.22]), and APPD (HRs 1.08 [0.93-1.26], 1.30 [1.12-1.50], and 1.97 [1.72-2.25]) with respect to hospitalization for heart failure, while only a marginal association was observed for stroke. The relationships were similar in people with and without diabetes (all p for interaction > 0.05). CONCLUSIONS: Inverse and independent associations were observed between ankle BP and cardiovascular events, similarly in people with and without type 2 diabetes. The largest associations were observed for heart failure and the smallest for stroke. Including ankle BP indices in routine clinical assessments may help to identify people at highest risk of cardiovascular outcomes.

Associations between peripheral thyroid sensitivity and all-cause and cardiovascular mortality in the US adults with metabolic syndrome.

Background: The relationship between peripheral sensitivity to thyroid hormones, as indicated by the ratio of free triiodothyronine (fT3) to free thyroxine (fT4) (fT3/fT4), and the prognosis of metabolic syndrome (MetS) remains unclear. Methods: This study utilized data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2012. MetS was defined based on the criteria established by the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III). Kaplan-Meier survival curves, restricted cubic spline (RCS) analysis, and Cox proportional hazards models were employed to investigate the association between peripheral thyroid sensitivity and mortality outcomes among adults with MetS. Results: A total of 3,101 adult participants (1,594 males and 1,507 females; median age: 52.00 years) with MetS were included in the analysis. Multivariate Cox regression analysis revealed that elevated levels of fT4 were positively associated with increased risks of both all-cause and cardiovascular mortality in the MetS population [adjustedhazard ratio (aHR): 2.74, 95% confidence interval (CI): 1.94-3.87, p < 0.001 for all-cause mortality; aHR: 3.93, 95% CI: 2.07-7.45, p < 0.001 for cardiovascular mortality]. Conversely, higher levels of fT3 and the fT3/fT4 ratio were found to be protective factors, reducing the mortality risk in the MetS population (fT3: aHR: 0.76, 95% CI: 0.57-0.99, p = 0.046 for all-cause mortality; fT3/fT4 ratio: aHR: 0.75, 95% CI: 0.67-0.85, p < 0.001 for all-cause mortality; aHR: 0.66, 95% CI: 0.52-0.83, p < 0.001 for cardiovascular mortality). The fT3/fT4 ratio exhibited a nonlinear association with all-cause mortality, but a linear and inverse association with cardiovascular mortality. Conclusion: The findings of this study suggest that higher peripheral thyroid sensitivity, as indicated by the fT3/fT4 ratio, may be associated with reduced mortality risks among adults with MetS. Further research is warranted to validate these associations.

Inflammation and Vitamin D Receptor Polymorphism: Impact on All-Cause and Cardiovascular Mortality in Mexican Women on Dialysis.

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.

Phenotypic age mediates effects of Life's Essential 8 on reduced mortality risk in US adults.

Objective: This study aimed to find out whether phenotypic age could mediate the protective effects of a healthy lifestyle on mortality. Methods: We included adult participants with available data for individual phenotypic age (PhenoAge) and Life's Essential 8 (LE8) scores from the National Health and Nutrition Examination Survey 2005-2010 (three cycles) and linked mortality records until 31 December 2019. Adjusted hazard ratios (HR) were estimated to evaluate the associations of PhenoAge and LE8 scores with all-cause and cardiovascular mortality risk. Mediation analyses were performed to estimate the proportional contribution of PhenoAge to the effect of LE8 on mortality risks. Results: A 1-year increment in PhenoAge was associated with a higher risk of all-cause (HR = 1.04 [95% confidence interval, 1.04-1.05]) and cardiovascular (HR = 1.04 [95% confidence interval, 1.04-1.05]) mortality, independent of chronological age, demographic characteristics, and disease history. High level of LE8 (score: 80-100) was associated with a 3.30-year younger PhenoAge. PhenoAge was estimated to mediate 36 and 22% of the effect of LE8 on all-cause and cardiovascular mortality, respectively (all P < 0.001). As for single-metric scores of LE8, PhenoAge mediated 30%, 11%, 9%, and 7% of the effects of the healthy diet, smoking status, blood pressure, and physical activity on all-cause mortality risk, respectively (all P < 0.05). Conclusion: Adherence to LE8 recommendations slows phenotypic aging. PhenoAge could mediate the effect of LE8 on mortality risk.

Associations of urinary phytoestrogens with all-cause and cardiovascular mortality in adults: a population-based cohort study.

Background: The overall understanding of the correlations between mortality risk and phytoestrogens in general population remains limited. We examined the association between urinary phytoestrogen levels and all-cause and cardiovascular mortality based on the National Health and Nutrition Examination Survey (NHANES). Methods: Weighted Cox proportional hazard regression models were employed to calculate adjusted hazard ratios (HRs) and their 95% confidence intervals (CIs). Nonlinear relationships were assessed using multivariable-adjusted restricted cubic splines (RCS). Results: In the fully adjusted model, the highest quartiles of urinary genistein levels were correlated with significantly elevated all-cause (HR = 1.36, 95%CI: 1.16-1.59) and cardiovascular (HR = 1.58, 95%CI: 1.20-2.09) mortality. Urinary enterolactone levels in the third quartile were associated with reduced all-cause (HR = 0.77, 95%CI: 0.65-0.90) and cardiovascular (HR = 0.74, 95%CI: 0.55-0.99) mortality. In the highest quartiles of urinary daidzein levels, the cardiovascular mortality was significantly increased (HR = 1.44, 95%CI: 1.09-1.90). RCS showed an non-linear relationship between urinary daidzein levels and all-cause mortality (P = 0.04). Conclusion: In the context of a nationally representative sample, genistein exhibited associations with elevated all-cause and cardiovascular mortality, whereas enterolactone showed an association with reduced mortality. The dose-response relationship between urinary daidzein levels and all-cause mortality as well as sex-specific disparities in the impact of phytoestrogen levels should be considered.

Association between estimated glucose disposal rate and cardiovascular mortality across the spectrum of glucose tolerance in the US population.

AIMS: To determine if estimated glucose disposal rate (eGDR) can predict cardiovascular disease mortality risk at different levels of glycaemic tolerance. MATERIALS AND METHODS: The eGDR levels of 11 656 individuals aged 45-79 years from the National Health and Nutrition Examination Survey cycles 1999 to 2010 were analysed. Associations between eGDR levels and all-cause and cardiovascular mortality were examined using Cox proportional hazards and Fine and Gray models, respectively. RESULTS: After a median follow-up of 12.8 years, a total of 2852 participants died, with 777 of those deaths attributed to cardiovascular causes. When comparing participants with eGDR values of ≤4 mg/kg/min to those with eGDR values falling within the ranges of 4-6, 6-8 and >8 mg/kg/min, it was found that the latter groups exhibited lower hazard ratios for both all-cause mortality (0.61 [0.52-0.72], 0.61 [0.52-0.72] and 0.46 [0.39-0.55]) and cardiovascular mortality (0.44 [0.33-0.57], 0.45 [0.34-0.59] and 0.30 [0.23-0.40]). A U-shaped relationship between eGDR and all-cause mortality was observed, with an inflection point at an eGDR of 9.54 mg/kg/min. CONCLUSIONS: In the general population, the association between reduced eGDR and all-cause and cardiovascular mortality was independently significant, contributing to the identification of individuals at high risk for different levels of glucose tolerances.