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.

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.

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.

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.

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.

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 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.

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.

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.

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.

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.

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.

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.

Monocyte/lymphocyte ratio as a risk factor of cardiovascular and all-cause mortality in coronary artery disease with low-density lipoprotein cholesterol levels below 1.4 mmol/L: A large longitudinal multicenter study.

BACKGROUND AND AIMS: The monocyte/lymphocyte ratio (MLR), an inflammatory marker, has an unclear relationship with the risk of residual inflammation in patients with coronary artery disease (CAD) and low-density lipoprotein cholesterol (LDL-C) below 1.4 mmol/L. This study aimed to assess the association between the MLR and cardiovascular and all-cause mortalities in these patients. METHODS: A total of 2747 patients diagnosed with CAD via coronary angiography (CAG) and presenting with LDL-C levels < 1.4 mmol/L were enrolled in this observational study conducted from January 2007 to December 2020. Patients were categorized into four groups based on the MLR quartiles. We used Kaplan-Meier analysis and Cox regression models to evaluate the relationship between baseline MLR and cardiovascular and all-cause mortalities. RESULTS: Among the 2747 participants followed up for a median duration of 6 years, there were 184 cardiovascular and 462 all-cause deaths. Elevated MLR levels were found to be associated with an increased risk of both cardiovascular and all-cause mortalities according to the Kaplan-Meier analysis. Multivariate Cox regression analysis demonstrated a significant association between higher MLR and an elevated risk of cardiovascular and all-cause mortality. Compared to the older group, with an increase in MLR levels, the younger group showed a higher hazard ratio for cardiovascular death. Similar results were obtained in the single-vessel disease group. CONCLUSIONS: In patients with CAD and LDL-C levels < 1.4 mmol/L, MLR can serve as a risk factor for both cardiovascular and all-cause mortalities owing to the risk of residual inflammation.

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.

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.

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.

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.

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.

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.