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.

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.

OBJECTIVE: 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).
CONCLUSIONS: In MHD patients, PIV is an independent hazard factor for cardiovascular-related mortality and all-cause mortality.

This study aims to evaluate the neutrophil-to-lymphocyte ratio (NLR) as a predictive biomarker for cardiovascular mortality among cancer patients, utilizing data from the National Health and Nutrition Examination Survey (NHANES). From the NHANES dataset (2007-2018), we analyzed 4974 cancer survivors, investigating the prognostic significance of NLR for all-cause, cardiovascular, and cancer-specific mortality. Survival outcomes were analyzed using Cox regression and Kaplan-Meier methods. Optimal NLR cutoffs were identified as 2.61 for differentiating the higher NLR group from lower NLR group. Elevated NLR levels significantly correlated with increased all-cause mortality (HR 1.11, 95% CI 1.07-1.14, P < 0.001) and cardiovascular mortality (HR 1.14, 95% CI 1.08-1.21, P < 0.001) in adjusted models. Subgroup analyses revealed that age, sex, smoking status, and hypertension significantly influence NLR\'s association with cardiovascular mortality. Specific cancers including breast, prostate, non-melanoma skin, colon and melanoma experience increased all-cause and cardiovascular mortality in the higher NLR group compared to lower NLR group. Elevated NLR is a significant predictor of increased mortality in cancer patients, particularly for cardiovascular outcomes. These findings support that NLR acts as a pivotal prognostic tool with significant implications for clinical practice in the realm of cardio-oncology.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: This real-world study suggests that using these sixteen PRCHMDKD provides time-dependent cardiorenal and survival benefits while ensuring safety for DKD patients.

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.

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.

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.
CONCLUSIONS: In pre-dialysis CKD patients, α-Klotho levels are associated with all-cause and cardiovascular mortality and may be considered an early prognostic marker.

Background: During the first months of the COVID-19 outbreak, an increase was observed in atrial fibrillation (AF)-related mortality in the United States (U.S). We aimed to investigate AF-related mortality trends in the U.S. before, during, and after the COVID-19 pandemic peak, stratified by sociodemographic factors. Methods: using the Wide-Ranging Online Data for Epidemiologic Research database of the Centers for Disease Control and Prevention, we compared the AF-related age-adjusted mortality rate (AAMR) among different subgroups in the two years preceding, during, and following the pandemic peak (2018-2019, 2020-2021, 2022-2023). Result: By analyzing a total of 1,267,758 AF-related death cases, a significant increase of 24.8% was observed in AF-related mortality during the pandemic outbreak, followed by a modest significant decrease of 1.4% during the decline phase of the pandemic. The most prominent increase in AF-related mortality was observed among males, among individuals younger than 65 years, and among individuals of African American and Hispanic descent, while males, African American individuals, and multiracial individuals experienced a non-statistically significant decrease in AF-related mortality during the pandemic decline period. Conclusions: Our findings suggest that in future healthcare crises, targeted healthcare policies and interventions to identify AF, given its impact on patients\' outcomes, should be developed while addressing disparities among different patient populations.

N-terminal pro-Brain-type natriuretic peptide (NT-proBNP) has a predictive value of cardiovascular disease (CVD). Pro-inflammatory diet has been proven to be related to CVD. Our study investigated whether the association between NT-proBNP and mortality differed among general U.S. adults with different dietary inflammatory index (DII) scores. This study utilized the National Health and Nutrition Examination Surveys (NHANES) database from 1999 to 2004. Non-pregnant U.S. adults aged ≥ 20 years and without CVD were included. Cox regression model and restricted cubic splines were used to investigate the associations between NT-proBNP, DII, and mortality. A total of 9788 adults were included, and 2386 all-cause deaths with 668 CVD deaths occurred over 17.08 years of follow-up. NT-proBNP was positively associated with DII scores (P < 0.001). Among subjects without CVD, elevated NT-proBNP was positively associated with an increased risk of mortality, with per unit increase in log transformed NT-proBNP, the risk of all-cause and cardiovascular mortality increased by approximately 1.40 times (HR 2.397, 95%CI 1.966-2.922, P < 0.001) and 2.89 times (HR 3.889, 95%CI 2.756-5.490, P < 0.001) after adjusting for cardiovascular risk factors, similar results were observed after adjusting DII scores. Besides, significant interaction was found between lgNT-proBNP and DII on mortality (all P for interaction < 0.05). While as the DII quartiles increased, the association between lgNT-proBNP and mortality partially weakened. Our findings reveal that the association of NT-proBNP with all-cause and cardiovascular mortality differed with different DII scores among U.S. adults without CVD. A pro-inflammatory diet may partially explain the association between NT-proBNP and mortality and warrant further study.