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.

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 between physical activity and mortality in patients with osteoporosis: a cohort study of NHANES.

We utilized data from the NHANES to investigate the impact of physical activity on mortality in osteoporotic patients. Our study suggests that osteoporotic patients may require higher volumes of physical activity to reduce mortality risk compared to the general population. In osteoporotic patients, the dose-response relationships between physical activity volumes and both all-cause and cardiovascular mortality were linear. In contrast, these relationships were non-linear in participants without osteoporosis. PURPOSE: To determine the impact of physical activity on mortality in osteoporotic patients. METHODS: A total of 5606 participants were included in this study, including 716 osteoporosis patients. Physical activity was assessed using standardized questionnaire. Participants were categorized into four groups: inactive (no physical activity), low active (physical activity volumes < 150 min/week), moderate active (≥ 150 min/week but < 300 min/week), and high active (≥ 300 min/week). Multivariable Cox regression models, using the inactive group as the reference and adjusted for potential confounders, were performed to estimate the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Osteoporotic patients demonstrated higher mortality rates attributed to various causes compared to non-osteoporosis participants. Physical activity was associated with lower mortality regardless of osteoporosis status. However, Multivariable Cox regression analysis indicated that among osteoporosis patients, only those engaging in ≥ 300 min/week physical activity experienced a significant decrease in mortality (all-cause mortality, HR (95% CI) 0.453 (0.268, 0.767) and cardiovascular mortality, HR (95% CI) 0.521 (0.259, 1.049)), surpassing the threshold of 150 min observed in non-osteoporosis patients. In sensitivity analysis, or when the proportion of vigorous physical activity was included as a confounder in the multivariate Cox regression analysis, only the high active group still showed a significant reduction in mortality. No significant interactions were observed when the analysis was stratified according to age, sex, and body mass index (P for interaction > 0.05). Restricted cubic spline analysis revealed a linear relationship between physical activity volume and all-cause mortality (P < 0.01 [overall] and P = 0.470 [non-linearity]) and cardiovascular-specific mortality (P = 0.003 [overall] and P = 0.610 [non-linearity]) in patients with osteoporosis. In contrast, these relationships were non-linear in participants without osteoporosis. CONCLUSION: Patients with osteoporosis need to engage in ≥ 300 min/week physical activity to significantly reduce their mortality risk. And the higher the volume of physical activity, the lower the risk of death.

Hypertensive patients with periodontitis as predictors of cardiovascular and all-cause mortality: a long-term cohort study.

OBJECTIVES: The aim of this study is to examine the potential correlation between periodontitis and the risk of cardiovascular mortality and all-cause mortality in individuals diagnosed with hypertension, despite the established association between periodontitis and hypertension. METHODS: The study utilized data from the National Health and Nutrition Examination Survey (NHANES) conducted in 1999-2014 involving hypertensive individuals. Following the criteria proposed by Eke et al., periodontitis was classified. Survival estimates were calculated using Kaplan Meier analyses and a Kaplan Meier curve was generated. Weighted multivariate cox regression were employed to assess the association between periodontitis and all-cause mortality, as well as cardiovascular mortality. RESULTS: Of the 21,645 individuals, 6,904 individuals were diagnosed with periodontitis. The Kaplan-Meier survival analysis revealed significantly higher rates of all-cause mortality (34.766% vs. 14.739%) and cardiovascular mortality (12.469% vs. 3.736%) in the periodontitis group compared to the non-periodontitis group. Hazard ratios (HRs) for all-cause mortality were 3.19 (95% CI 2.88-3.53) and for cardiovascular mortality were 3.80 (95% CI 3.13-4.61) in individuals with periodontitis compared to those without periodontitis. CONCLUSION: Periodontitis is a risk factor for mortality in patient with hypertension, especially if it is moderate to severe. Improving periodontal health could lead to better outcomes for these patients.

Associations of Circulating ANGPTL3, C-Terminal Domain-Containing ANGPTL4, and ANGPTL3/8 and ANGPTL4/8 Complexes with LPL Activity, Diabetes, Inflammation, and Cardiovascular Mortality.

BACKGROUND: ANGPTL3/4/8 (angiopoietin-like proteins 3, 4, and 8) are important regulators of LPL (lipoprotein lipase). ANGPTL8 forms complexes with ANGPTL3 and ANGPTL4. ANGPTL4/8 complex formation converts ANGPTL4 from a furin substrate to a plasmin substrate, and both cleavages generate similar C-terminal domain-containing (CD)-ANGPTL4 fragments. Whereas several studies have investigated associations of free ANGPTL proteins with cardiovascular risk, there are no data describing associations of the complexes and CD-ANGPTL4 with outcomes or describing the effects of the complexes on LPL bound to GPIHBP1 (glycosylphosphatidylinositol HDL-binding protein 1). METHODS: Recombinant protein assays were used to study ANGPTL protein and complex effects on GPIHBP1-LPL activity. ANGPTL3/8, ANGPTL3, ANGPTL4/8, and CD-ANGPTL4 were measured with dedicated immunoassays in 2394 LURIC (Ludwigshafen Risk and Cardiovascular Health) study participants undergoing coronary angiography and 6188 getABI study (German Epidemiological Trial on Ankle Brachial Index) participants undergoing ankle brachial index measurement. There was a follow-up for cardiovascular death with a median (interquartile range) duration of 9.80 (8.75-10.40) years in the LURIC study and 7.06 (7.00-7.14) years in the getABI study. RESULTS: ANGPTL3/8 potently inhibited GPIHBP1-LPL activity and showed positive associations with LDL-C (low-density lipoprotein cholesterol) and triglycerides (both P<0.001). However, in neither study did ANGPTL3/8 correlate with cardiovascular death. Free ANGPTL3 was positively associated with cardiovascular death in the getABI study but not the LURIC study. ANGPTL4/8 and especially CD-ANGPTL4 were positively associated with the prevalence of diabetes, CRP (C-reactive protein; all P<0.001), and cardiovascular death in both studies. In the LURIC and getABI studies, respective hazard ratios for cardiovascular mortality comparing the third with the first ANGPTL4/8 tertile were 1.47 (1.15-1.88) and 1.68 (1.25-2.27) when adjusted for sex, age, body mass index, and diabetes. For CD-ANGPTL4, these hazard ratios were 2.44 (1.86-3.20) and 2.76 (2.00-3.82). CONCLUSIONS: ANGPTL3/8 potently inhibited GPIHBP1-LPL enzymatic activity, consistent with its positive association with serum lipids. However, ANGPTL3/8, LDL-C, and triglyceride levels were not associated with cardiovascular death in the LURIC and getABI cohorts. In contrast, concentrations of ANGPTL4/8 and particularly CD-ANGPTL4 were positively associated with inflammation, the prevalence of diabetes, and cardiovascular mortality.

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.

Prognostic value of lymphocyte to C-reactive protein ratio for cardiovascular and all-cause mortality in adults with congestive heart failure in the United States: NHANES 1999-2010.

Background: Lymphocyte to C-reactive protein ratio (LCR) is an emerging inflammatory biomarker, but its association with prognosis in individuals with congestive heart failure (CHF) remains unclear. We sought to evaluate the relationship between LCR and cardiovascular (CV) and all-cause mortality in individuals diagnosed with CHF. Methods: We included 718 CHF individuals, using NHANES 1999-2010 data. ROC curves were used to compare the prognostic value of LCR, C-reactive protein, and lymphocyte counts for 3-year, 5-year, and 10-year CV and all-cause mortality risk. The population was divided into 4 groups based on the value of LCR according to the quartile. Prognosis analysis utilized the Kaplan-Meier method and Cox-regression analysis while accounting for NHANES recommended weights. Results: Kaplan-Meier curves demonstrated a significantly worse prognosis in the low LCR group compared to the high LCR group (log-rank test; p < 0.001). For 3-year CV mortality, the multivariable-adjusted hazard ratios [95 % confidence interval] for LCR quartiles (Q 2,3,4 vs Q 1) were 0.43 (0.21-0.87), 0.38 (0.13-1.07), 0.34 (0.13-0.88), (P for trend = 0.033). For 3-year all-cause mortality, aHRs were 0.36 (0.22-0.60), 0.51 (0.29-0.89), 0.35 (0.18-0.64), (P for trend = 0.002). Similar findings were observed for 5- and 10-year CV and all-cause mortality. Conclusions: Elevated LCR emerged as an independent prognostic factor for CV and all-cause mortality in individuals with CHF. Moreover, the implementation of anti-inflammatory therapy exhibits the potential to improve outcomes for decreased LCR patients with CHF.

Association of weight-adjusted-waist index with all-cause and cardiovascular mortality in individuals with diabetes or prediabetes: a cohort study from NHANES 2005-2018.

Weight-adjusted waist index (WWI) is a new marker of central obesity. This study explored the association of WWI with all-cause and cardiovascular disease (CVD) mortality in individuals with diabetes or prediabetes. 6551 participants with diabetes or prediabetes from the National Health and Nutrition Examination Survey (NHANES) records between 2005 and 2018 were included. The association of WWI with all-cause and CVD mortality was assessed using Kaplan-Meier survival analysis, Cox proportional hazards model (Cox regression), and restricted cubic spline (RCS). The predictive value of WWI for mortality was analyzed using time-dependent receiver operating characteristic curves (ROC). There were 1083 all-cause deaths and 360 CVD deaths. Multivariable-adjusted Cox regression analyses showed WWI was positively correlated with the risk of all-cause and CVD mortality in subjects with diabetes or prediabetes. Multivariate-adjusted RCS analyses showed a linear and positive correlation of WWI with all-cause mortality risk, and a nonlinear relationship with CVD mortality, with a threshold of 12.35. The area under the curve (AUC) for 3, 5, and 10-years survival for all-cause mortality was 0.795, 0.792, and 0.812, respectively, and for CVD mortality was 0.815, 0.833, and 0.831, respectively. WWI is a valuable predictor of all-cause mortality risk in patients with diabetes and prediabetes, and a valuable predictor of CVD mortality risk when patients with diabetes and prediabetes are considered as a whole.

Predictive Value of Life's Crucial 9 for Cardiovascular and All-Cause Mortality: A Prospective Cohort Study From the NHANES 2007 to 2018.

BACKGROUND: The predictive value of Life's Crucial 9 (LC9), a recently proposed cardiovascular health risk score combining psychological health and Life's Essential 8 (LE8), remains unclear. METHODS AND RESULTS: In this cohort study, we included 16 290 adults without cardiovascular disease from the 2007 to 2018 cycles of NHANES (National Health and Nutrition Examination Survey). The LC9 was the mean of the LE8 score and the depression score, which represented a dimension of psychological health. The study outcomes were cardiovascular and all-cause mortality. Cox proportional hazard models were fitted to estimate the association of LC9 and LE8 scores with outcomes. The differences in Harrell's concordance index, net reclassification improvement index, and integrated discrimination improvement were calculated to assess the predictive ability of the depression score in addition to the LE8 score. During a median follow-up of 7.08 years, 879 (5.40%) participants died, and 242 (1.49%) died from cardiovascular disease. The adjusted hazard ratio (HR) of per LE8 10-score increase for cardiovascular mortality was 0.80 (95% CI, 0.72-0.88; P<0.001) and the adjusted HR of per LC9 10-score increase was 0.77 (95% CI, 0.69-0.86; P<0.001). Adding the depression score to the LE8 score, the improvement in concordance index for cardiovascular mortality was 0.001 (95% CI, -0.001 to 0.003; P=0.30), the net reclassification improvement index was 10.6% (95% CI, -7.6% to 18.9%; P=0.073), and the IDI was 0.002 (95% CI, 0.000-0.007; P=0.033). The results for all-cause mortality showed similar patterns. CONCLUSIONS: Compared with the LE8, the improvement in the predictive value of LC9 was negligible. It may not be necessary to add a depression score to the current cardiovascular health score.

Sodium-glucose co-transporter 2 inhibitors for all-cause and cardiovascular death in people with different stages of CKD: A systematic review and meta-analysis.

BACKGROUND: Sodium-glucose co-transporter-2 inhibitors (SGLT2is) reduce cardiovascular risk in people with diabetes and established cardiovascular disease, but emerging studies in chronic kidney disease (CKD) have inconsistent results. In this systematic review, we evaluate the effects of SGLT2is on cardiovascular mortality in people with CKD as a whole and across subgroups stratified by baseline kidney function and among people at low, moderate, high and very high risk according to KDIGO- CKD classification system. METHODS: Literature search was conducted in PubMed/MEDLINE, Cochrane/CENTRAL, Scopus and Web of Science up to 30 November 2023. We included randomized controlled trials assessing the effect of SGLT2is on cardiovascular mortality in people with CKD. Secondary outcomes included all-cause mortality and major adverse cardiac events (MACE). RESULTS: Eleven studies (n = 83,203 participants) were included. In people with CKD, treatment with SGLT2is compared to placebo reduced the risk of cardiovascular death by 14% (hazard ratio [HR] .86; 95%CI .79-.94), all-cause death by 15% (HR .85; 95%CI .79-.91) and MACEs by 13% (HR .87; 95%CI .81-.93). A consistent treatment effect was observed across eGFR-subgroups (≥60 mL/min/1.73 m2: HR .82, 95%CI .65-1.02; <60 mL/min/1.73 m2: HR .86, 95%CI .77-.96, p-subgroup difference = .68) and KDIGO risk-categories (low, moderate, high and very high) (p-subgroup difference = .69) for cardiovascular death; reduction in the risk of all-cause death tended to be greater in the highest KDIGO risk categories. A consistent treatment effect on cardiovascular mortality was observed for different SGLT2is agents studied. Sensitivity analysis for cardiovascular mortality endpoint including studies in diabetic people yielded similar results (HR .86; 95%CI .77-.97). CONCLUSIONS: Treatment with SGLT2is led to a significant reduction in the risk of cardiovascular and all-cause mortality in people with different CKD stages. These findings support the use of SGLT2is as an adjunct cardiovascular protective therapy in CKD. PROSPERO REGISTRATION NUMBER: PROSPERO registration number: CRD42022382863.

Abdominal aortic aneurysm repair in Sweden vs. Finland: benefits of population-wide screening.

BACKGROUND AND AIMS: In 2006, screening of 65-year-old men for abdominal aortic aneurysm (AAA) was started in Sweden. Decline in aneurysm-related mortality has been reported since, but aneurysm incidence has been diminishing globally. Neighbouring Finland with similar population structure and health care system has no AAA screening programme. The aim of this study was to compare incidence and results of AAA repair in Sweden and Finland to differentiate the effect of screening from other changes in the epidemiology and treatment of AAA. METHODS: All repairs for intact AAA (iAAA) or ruptured AAA (rAAA) from 1998 to 2017 were identified from national registers, and mortality data for these patients were collected. RESULTS: A total of 15 927 operations for iAAA were performed in Sweden and 6933 in Finland. In Sweden, the yearly operation volume increased after introduction of screening. Both countries showed a decrease in number of rAAA operations, but the decrease was more pronounced in Sweden. Sweden had a higher proportion of all AAA repairs because of rupture in the start of the study but by the end, the proportions were similar in both countries. Long-term survival improved for 65-79-old men in Sweden after start of screening. CONCLUSIONS: This study reveals improvements in results of AAA repair in Sweden. A decrease in rAAA repair and increase in iAAA repair were evident after AAA screening was started in 2006 and resulted in better outcomes. These changes are likely the result of AAA screening as they cannot be seen in neighbouring Finland that is lacking an AAA screening programme.

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.

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.

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.

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.

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.

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.

Free fatty acids and mortality among adults in the United States: a report from US National Health and Nutrition Examination Survey (NHANES).

BACKGROUND: The relationship between free fatty acids (FFAs) and the risk of mortality remains unclear. There is a scarcity of prospective studies examining the associations between specific FFAs, rather than total concentrations, of their effect on long-term health outcomes. OBJECTIVE: To evaluate the correlation between different FFAs and all-cause and cardiovascular mortality in a large, diverse, nationally representative sample of adults in the US, and examine how different FFAs may mediate this association. METHODS: This cohort study included unsaturated fatty acids (USFA) and saturated fatty acids (SFA) groups in the US National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014 and provided blood samples for FFAs levels. Multiple model calibration was performed using Cox regression analysis for known risk factors to explore the associations between FFAs and all-cause and cardiovascular mortality. RESULTS: In the group of USFA, 3719 people were included, median follow-up, 6.7 years (5.8-7.8 years). In the SFA group, we included 3900 people with a median follow-up, 6.9 years (5.9-8 years). In the USFA group, myristoleic acid (14:1 n-5) (hazard ratio (HR) 1.02 [1.006-1.034]; P = 0.004), palmitoleic acid (16:1 n-7) (HR 1.001 [1.001-1.002]; P < 0.001), cis-vaccenic acid (18:1 n-7) (HR 1.006 [1.003-1.009]; P < 0.001), nervonic acid (24:1 n-9) (HR 1.007 [1.002-1.012]; P = 0.003), eicosatrienoic acid (20:3 n-9) (HR 1.027 [1.009-1.046]; P = 0.003), docosatetraenoic acid (22:4 n-6) (HR 1.024 [1.012-1.036]; P < 0.001), and docosapentaenoic acid (22:5 n-6) (HR 1.019 [1.006-1.032]; P = 0.005) were positively associated with the all-cause mortality, while docosahexaenoic acid (22:6 n-3) had a statistically lower risk of all-cause mortality (HR 0.998 [0.996-0.999]; P = 0.007). Among the SFA group, palmitic acid (16:0) demonstrated a higher risk of all-cause mortality (HR 1.00 [1.00-1.00]; P = 0.022), while tricosanoic acid (23:0) (HR 0.975 [0.959-0.991]; P = 0.002) and lignoceric acid (24:0) (HR 0.992 [0.984-0.999]; P = 0.036) were linked to a lower risk of all-cause mortality. Besides 23:0 and 24:0, the other FFAs mentioned above were linearly associated with the risks of all-cause mortality. CONCLUSIONS: In this nationally representative cohort of US adults, some different FFAs exhibited significant associations with risk of all-cause mortality. Achieving optimal concentrations of specific FFAs may lower this risk of all-cause mortality, but this benefit was not observed in regards to cardiovascular mortality.

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.