Neutrophil-to-lymphocyte ratio as a predictor of all-cause and cardiovascular mortality in coronary heart disease and hypertensive patients: a retrospective cohort study.

Background: To date, no studies have investigated the correlation between the neutrophil-to-lymphocyte ratio (NLR) and the long-term risk of mortality in individuals with both coronary heart disease (CHD) and hypertension. This study aims to evaluate the association between NLR and all-cause and cardiovascular mortality among this patient population. Methods: National Death Index (NDI) and National Health and Nutrition Examination Survey (NHANES 2001-2018) were the data sources. A nonlinear association between the NLR and mortality risk was shown by restricted cubic spline (RCS) analysis. Using a weighted Cox proportional hazards model, we quantitatively evaluated the effect of NLR on mortality risk.The capacity of NLR to forecast survival was assessed by evaluating time-dependent receiver operating characteristic (ROC) curves. A mediating influence analysis was conducted to assess the influence of NLR on mortality through eGFR as a mediator. Results: The study involved a total of 2136 individuals. During the median follow-up interval of 76.0 months, 801 deaths were recorded. The RCS analysis showed NLR and mortality risk to have a nonlinear relationship. Two groups were established based on the participants' NLR levels: a group with high NLR (NLR > 2.65) and a group with low NLR (NLR < 2.65). After adjusting for potential confounding factors, the Cox proportional hazards model revealed that participants with an increased NLR faced a significantly higher risk of cardiovascular mortality. (HR 1.58, 95% CI 1.33-1.82, p < 0.0001) and all-cause mortality (HR 1.46, 95% CI 1.30-1.62, p < 0.0001). An analysis of interactions and data stratification corroborated the validity of our findings. eGFR was identified as a partial mediator in the association between NLR and mortality rates, contributing 12.17% and 9.66% of the variance in all-cause and cardiovascular mortality, respectively. The predictive performance for cardiovascular mortality was quantified using ROC curves, with respective AUC values of 0.67, 0.65, and 0.64 for predictions over 3, 5, and 10 years. The AUC values for all-cause mortality were 0.66, 0.64, and 0.63 for the same time frames. Conclusion: For patients with CHD and hypertension, an elevated NLR serves as an independent prognostic indicator for both all-cause and cardiovascular mortality.

Metastatic disease and major adverse cardiovascular events preceding diagnosis are the main determinants of disease-specific survival of pheochromocytoma/paraganglioma: long-term follow-up of 303 patients.

Purpose: The natural history in unselected cohorts of patients with pheochromocytoma/ paraganglioma (PPGL) followed for a period >10 years remains limited. We aimed to describe baseline characteristics and outcome of a large cohort and to identify predictors of shorter survival. Methods: This retrospective single-center study included 303 patients with newly diagnosed PPGL from 1968 to December 31, 2023, in 199 prospectively supplemented since July 2020. Mean follow-up was 11.4 (range 0.3-50) years, germline genetic analyses were available in 92.1%. The main outcome measures were overall (OAS), disease-specific (DSS), recurrence-free (RFS) survival and predictors of shorter survival evaluated in patients with metastases at first diagnosis (n=12), metastatic (n=24) and nonmetastatic (n=33) recurrences and without evidence of PPGL after first surgery (n=234). Results: Age at study begin was 49.4 ± 16.3 years. There were 72 (23.8%) deaths, 15 (5.0%), 29 (9.6%) and 28 (9.2%) due to PPGL, cardiovascular disease (CVD) and malignant or other diseases, respectively. Median OAS, DSS1 (tumor-related) and DSS2 (DSS1 and death caused by CVD) were 4.8, 5.9 and 5.2 years (patients with metastases at first diagnosis), 21.2, 21.2 and 19.9 years, and 38.0, undefined and 38.0 years (patients with metastatic and with nonmetastatic recurrences, respectively). Major adverse cardiovascular events (MACE) preceded the first diagnosis in 15% (n=44). Shorter DSS2 correlated with older age (P ≤ 0.001), male sex (P ≤ 0.02), MACE (P ≤ 0.01) and primary metastases (P<0.0001, also for DSS1). Conclusion: The clinical course of unselected patients with PPGL is rather benign. Survival rates remain high for decades, unless there are MACE before diagnosis or metastatic disease.

Glycemic status and effect on mortality: Multifactorial prevention programme for cardiovascular disease in Finnish primary care.

AIMS: To compare 13-year mortality rates in normoglycemic, prediabetic and diabetic subjects attending a community-based screening and intervention programme. METHODS: Population survey identified 2569 cardiovascular disease (CVD) white risk subjects aged 45-70 years and without manifested CVD or diabetes. Oral glucose tolerance test was performed, and multifactorial intervention was provided. Effect of glycemic status on mortality was estimated in models adjusted for age, gender, education years, smoking, body mass index, mean arterial pressure, total cholesterol, and physical activity. RESULTS: Of the subjects, 2055 (77 %) were normoglycemic, 380 (14 %) had prediabetes and 224 (9 %) diabetes. Compared to the normoglycemic group, the fully adjusted hazard ratios (HR) for all-cause mortality were 1.34 (95 % CI: 0.98-1.83) in the prediabetes group and 2.31 (95 % CI: 1.62-3.31) in the diabetes group. Standardized mortality rates were 0.63 (95 % CI: 0.54-0.73), 0.91 (95 % CI: 0.69-1.18), and 1.55 (95 % CI: 1.19-2.02) in the normoglycemic, prediabetes, and diabetes groups, respectively. The most common cause of death was cancer (42 % of all deaths), followed by CVD (28 %). CONCLUSIONS/INTERPRETATION: Screen-detected diabetes carries a substantial risk of death even after primary care intervention. The pattern of excess mortality has shifted towards cancer deaths.

The Predictive Value of Time-Varying Noninvasive Scores on Long-Term Prognosis of NAFLD in South Korea.

Background: This study aimed to examine whether repeated measurements on noninvasive fibrosis scores during follow-up improve long-term nonalcoholic fatty liver disease (NAFLD) outcome prediction. Methods: A cohort study of 2,280 NAFLD patients diagnosed at the Seoul National University Hospital from 2001 to 2015 was conducted. Multivariable Cox regression models with baseline and designated time-point measurements of the fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS) were used to assess the association between these scores and overall mortality, liver-related outcomes, and cardiovascular events. Results: Higher baseline NFS (high versus low probability for advanced fibrosis groups) was associated with higher risk of mortality (adjusted hazard ratio (aHR), (95% confidence interval (CI)), 2.80, [1.39-5.63]) and liver-related outcomes (3.70, [1.27-10.78]). Similar findings were observed for the association of baseline FIB-4 with mortality (2.49, [1.46-4.24]) and liver-related outcomes (11.50, [6.17-21.44]). In models considering designated time-point measurements of the scores, stronger associations were noted. For NFS, a higher time-point measurement was associated with a significantly higher risk of mortality (3.01, [1.65-5.49]) and liver-related outcomes (6.69, [2.62-17.06]). For FIB-4, higher time-point measurements were associated with significantly higher mortality (3.01, [1.88-4.82]) and liver-related outcomes (13.26, [6.89-25.53]). An annual increase in FIB-4 (2.70, [1.79-4.05]) or NFS (4.68, [1.52-14.44]) was associated with an increased risk of liver-related outcomes. No association between NFS/FIB-4 and risk of cardiovascular events was observed in both models. Conclusions: Higher aHRs describing the associations of FIB-4/NFS with overall mortality and liver-related outcomes were observed in the models that included designated time-point measurements of the scores. In addition to the baseline measurement, a routine monitoring on these scores may be important in predicting prognosis of NAFLD patients.

Association of resting heart rate and physical activity with cardiovascular mortality: A population-based cohort study of Korean adults.

To examine the independent and combined association of resting heart rate (RHR) and physical activity (PA) with risk of cardiovascular disease (CVD) mortality. RHR was categorized as < 60, 60-69, 70-79, and ≥ 80 bpm. Meeting PA guidelines was defined as ≥ 150 min/week of moderate to vigorous physical activity (MVPA). Cox proportional hazard models were used to calculate hazard ratios (HRs) for CVD mortality associated with RHR and PA. Among 31,697 participants, 311 CVD deaths occurred during 9.2 years of follow-up. Compared to RHR of 60-69 bpm, the risk of CVD mortality was higher in RHR of < 60 bpm (HR, 1.48; 95% CI, 1.05-2.10) and ≥ 80 bpm (HR, 1.42; 95% CI, 1.06-1.91). Participants who met PA guidelines had a lower risk of CVD mortality (HR, 0.59; 95% CI, 0.44-0.78). Among physically inactive adults compared to participants in RHR of 60-69 bpm with meeting PA guidelines, the adjusted HR for CVD mortality was 2.41 (95% CI, 1.42-4.08) for RHR of < 60 bpm, 1.59 (95% CI, 1.01-2.49) for RHR of 60-69 bpm, 1.98 (95% CI, 1.23-3.20) for RHR of 70-79 bpm and 2.41 (95% CI, 1.50-3.89) for RHR of ≥ 80 bpm Exceeding the minimum level of PA guidelines may attenuate the risk of CVD mortality associated with RHR.

Gut microbiota metabolites and risk of major adverse cardiovascular events and death: A systematic review and meta-analysis.

BACKGROUND: Gut microbial metabolites such as trimethylamine N-oxide (TMAO) and its precursors, namely betaine, L-carnitine, and choline, have been implicated as risk factors for cardiovascular events and mortality development. Therefore, we aim to perform a systematic review and meta-analysis to assess the validity of these associations. METHODS: MEDLINE and Scopus were queried from their inception to August 2023 to identify studies that quantified estimates of the associations of TMAO with the development of major adverse cardiovascular events (MACE) or death. A random-effects meta-analysis was conducted to pool unadjusted or multivariable-adjusted hazard ratios (HR) and their 95% confidence intervals. The primary endpoint was the risk of MACE and all-cause death. RESULTS: 30 prospective observational studies (n = 48 968) were included in the analysis. Elevated TMAO levels were associated with a significantly greater risk of MACE and all-cause death compared to low TMAO levels (HR: 1.41, 95% CI 1.2-1.54, P < .00001, I2 = 43%) and (HR: 1.55, 95% CI 1.37-1.75, P < .00001, I2 = 46%), respectively. Furthermore, high levels of either L-carnitine or choline were found to significantly increase the risk of MACE. However, no significant difference was seen in MACE in either high or low levels of betaine. CONCLUSION: Elevated concentrations of TMAO were associated with increased risks of MACE and all-cause mortality. High levels of L-carnitine/choline were also significantly associated with an increased risk of MACE. However, no significant difference was found between high or low levels of betaine for the outcome of MACE.

Replacement of sedentary behavior with various physical activities and the risk of all-cause and cause-specific mortality.

BACKGROUND: Sedentary behavior (SB) has emerged as a significant health concern that deserves attention. This study aimed to examine the associations between prolonged sedentary behavior and the risk of all-cause and cause-specific mortality as well as to explore desirable alternatives to sitting in terms of physical activity (PA). METHODS: Two prospective cohort investigations were conducted using the UK Biobank and NHANES datasets, with a total of 490,659 and 33,534 participants, respectively. Cox proportional hazards regression models were used to estimate the associations between SB and the risk of all-cause and cause-specific mortality due to cancer, cardiovascular disease (CVD), respiratory diseases, and digestive diseases. In addition, we employed isotemporal substitution models to examine the protective effect of replacing sitting with various forms of PA. RESULTS: During the average follow-up times of 13.5 and 6.7 years, 36,109 and 3057 deaths were documented in the UK Biobank and NHANES, respectively. Both cohorts demonstrated that, compared with individuals sitting less than 5 h per day, individuals with longer periods of sitting had higher risks of all-cause and cause-specific mortality due to cancer, CVD, and respiratory diseases but not digestive diseases. Moreover, replacing SB per day with PA, even substituting 30 min of walking for pleasure, reduced the risk of all-cause mortality by 3.5% (hazard ratio [HR] 0.965, 95% confidence interval [CI] 0.954-0.977), whereas cause-specific mortality from cancer, CVD, and respiratory diseases was reduced by 1.6% (HR 0.984, 95% CI 0.968-1.000), 4.4% (HR 0.956, 95% CI 0.930-0.982), and 15.5% (HR 0.845, 95% CI 0.795-0.899), respectively. Furthermore, the protective effects of substitution became more pronounced as the intensity of exercise increased or the alternative duration was extended to 1 h. CONCLUSIONS: SB was significantly correlated with substantially increased risks of all-cause mortality and cause-specific mortality from cancer, CVD, and respiratory diseases. However, substituting sitting with various forms of PA, even for short periods involving relatively light and relaxing physical activity, effectively reduced the risk of both overall and cause-specific mortality.

Trimethylamine-N-oxide and 5-year mortality: the role of gut microbiota-generated metabolite from the CORE-Thailand cohort.

The gut microbiota metabolite trimethylamine-N-oxide (TMAO)-derived from dietary phosphatidylcholine-is mechanistically linked to cardiovascular disease (CVD) and increased cardiovascular risk. This study examined the relationship between fasting plasma TMAO levels and 5-year all-cause mortality in a cohort of patients at high risk of cardiovascular events (CORE-Thailand Registry). Of the 134 patients, 123 (92%) had established cardiovascular disease, and 11 (8%) had multiple risk factors. Fasting plasma TMAO levels were measured using nuclear magnetic resonance spectroscopy. Within this prospective cohort study, the median TMAO was 3.81 µM [interquartile range (IQR) 2.89-5.50 µM], with a mean age of 65 ± 11 years; 61% were men, and 39.6% had type II diabetes. Among 134 patients, 65 (49%) were identified as the high-TMAO group (≥ 3.8 µM), and 69 (51%) were identified as the low-TMAO group (< 3.8 µM). After a median follow-up of 58.8 months, the high-TMAO group was associated with a 2.88-fold increased mortality risk. Following adjustment for traditional risk factors, high-sensitivity cardiac troponin-T, estimated glomerular filtration rate, angiotensin-converting enzyme (ACEI), or angiotensin-receptor blocker (ARB) use, the high-TMAO group remained predictive of 5-year all-cause mortality risk (the high-TMAO vs. the low-TMAO group, adjusted hazard ratio 2.73, 95% CI 1.13-6.54; P = 0.025). Among Thai patients at high risk of cardiovascular events, increased plasma TMAO levels portended greater long-term mortality risk.

All-cause and cause-specific mortality risk among men and women with hepatitis C virus infection.

BACKGROUND: Hepatitis C virus (HCV) infection affects men and women differently, yet few studies have investigated sex differences in long-term mortality risk among the HCV-infected population. We conducted a population-based study to elucidate all-cause and cause-specific mortality among men and women with HCV infection. METHODS: The study population consisted of adult participants from the 1999-2018 National Health and Nutrition Examination Survey, including 945 HCV-infected and 44,637 non-HCV-infected individuals. HCV infection was defined as either HCV seropositivity or detectable HCV RNA. Participants were followed until the date of death or December 31, 2019, to determine survival status. RESULTS: The HCV-infected population, both male and female, tended to be older, more likely to be Black, single, have lower income, lower BMI, higher prevalence of hypertension, and were more likely to be current smokers. During a median follow-up of 125.0 months, a total of 5,309 participants died, including 1,253 deaths from cardiovascular disease (CVD) and 1,319 deaths from cancer. The crude analysis showed that the risk of death from all causes and from cancer, but not from CVD, was higher in the HCV-infected population. After adjusting for potential confounders, we found that both HCV-infected men (HR 1.41, 95% CI 1.10-1.81) and women (HR 2.03, 95% CI 1.36-3.02) were equally at increased risk of all-cause mortality compared to their non-HCV infected counterparts (p for interaction > 0.05). The risk of cancer-related mortality was significantly increased in HCV-infected women (HR 2.14, 95% CI 1.01-4.53), but not in men, compared to non-HCV-infected counterparts. Among HCV-infected population, there was no difference in the risks of all-cause, CVD-related, or cancer-related death between men and women. CONCLUSION: Both men and women with HCV infection had an increased risk of death from all causes compared to their non-HCV infected counterparts, but we did not observe a significant sex difference.

Neutrophil-to-lymphocyte ratio as a predictor of cardiovascular mortality in cancer survivors.

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.

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

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

The association between triglyceride-glucose index and its combination with systemic inflammation indicators and all-cause and cardiovascular mortality in the general US population: NHANES 1999-2018.

BACKGROUND: The correlation between the triglyceride-glucose (TyG) index and mortality in the general population remains controversial, with inconsistent conclusions emerging from different studies. OBJECTIVE: This study aims to investigate whether there is an association between the TyG index and mortality in the general population in the United States, and to explore whether a new index combining the TyG index with systemic inflammation indicators can better predict all-cause and cardiovascular mortality risks in the general population than using the TyG index alone. METHODS: Calculate the systemic inflammation indicators and TyG index for each participant based on their complete blood count, as well as their triglyceride and glucose levels in a fasting state. TyG-inflammation indices were obtained by multiplying the TyG index with systemic inflammation indicators (TyG-NLR, TyG-MLR, TyG-lgPLR, TyG-lgSII, and TyG-SIRI). Based on the weighted Cox proportional hazards model, assess whether the TyG and TyG-Inflammation indices are associated with mortality risk in the general population. Restricted cubic splines (RCS) are used to clarify the dose-response relationship between the TyG and TyG-Inflammation indices and mortality, and to visualize the results. Time-dependent receiver operating characteristic (ROC) curves are used to evaluate the accuracy of the TyG and TyG-Inflammation indices in predicting adverse outcomes. RESULTS: This study included 17,118 participants. Over a median follow-up period of 125 months, 2595 patients died. The TyG index was not found to be related to mortality after adjusting for potentially confounding factors. However, the TyG-inflammation indices in the highest quartile (Q4), except for TyG-lgPLR, were significantly associated with both all-cause and cardiovascular mortality, compared to those in the lowest quartile (Q1). Among them, TyG-MLR and TyG-lgSII showed the strongest correlations with all-cause mortality and cardiovascular mortality. Specifically, compared to their respective lowest quartiles (Q1), participants in the highest quartile (Q4) of TyG-MLR had a 48% increased risk of all-cause mortality (95% CI: 1.23-1.77, P for trend < 0.0001), while participants in the highest quartile (Q4) of TyG-lgSII had a 92% increased risk of cardiovascular mortality (95% CI: 1.31-2.81, P for trend < 0.001). Time-dependent ROC curve analysis showed that the TyG-MLR had the highest accuracy in predicting long-term mortality outcomes. CONCLUSIONS: The TyG-Inflammation indices constructed based on TyG and systemic inflammation indicators are closely related to mortality in the general population and can better predict the risk of adverse outcomes. However, no association between TyG and mortality in the general population was found.

Gender differences in cardiovascular outcomes of kidney transplant recipients: A retrospective cohort study.

The purpose of this study was to investigate gender differences in cardiovascular outcomes of kidney transplant recipients (KTRs). Here, a retrospective cohort study was conducted, and data from the National Health Insurance Research Database in Taiwan were used. In total, 2904 patients who had end-stage renal disease (ERSD) and received kidney transplantation (KT) were identified by propensity score matching (PSM) and were enrolled from 1997 to 2012, with follow-up ending in 2013. Besides, major adverse cardiovascular events (MACEs) were defined as a composite of all-cause mortality, nonfatal myocardial infarction, and nonfatal strokes. Apart from that, hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated by Cox regression, while the Bayesian network model was constructed to assess the importance of risk factors for MACEs. Furthermore, the original cohort was a sensitivity analysis. Women had a lower risk of MACEs compared with men (hazard ratio [HR]: 0.84; 95% CI: 0.72-0.98; P = .024). Beyond that, stratified analysis of age and waiting time for KT showed that the risk of MACEs was significantly lower in women than in men among KTRs aged > 50 years (HR: 0.79; 95% CI: 0.62-1.0; P = .05) or waiting time for KT ≤ 6 years (HR: 0.85; 95% CI: 0.72-0.99; P = .04). Bayesian network indicated that age is an important determinant of cardiovascular outcomes in KTRs, regardless of gender. In Taiwan, women had a lower risk of adverse cardiovascular outcomes than men in KTRs aged > 50 years or with a waiting time for KT ≤ 6 years. Furthermore, age is an important independent determinant for the prognosis of KTRs.

Associations of prognostic nutritional index with risk of all-cause and cardiovascular disease mortalities in persons with gestational diabetes mellitus: A NHANES-based analysis.

OBJECTIVE: To investigate relationships between prognostic nutritional index (PNI) during pregnancy and risk of all-cause mortality (ACM) and cardiovascular disease (CVD) mortality in persons with gestational diabetes mellitus (GDM). METHODS: A cross-sectional study was conducted using NHANES data from 2007 to 2018, and weighted Cox regression models were established. Restricted cubic spline analysis was used to unveil associations of PNI with risk of ACM and CVD mortalities in individuals with GDM. Receiver operating characteristic curve was employed for determination of threshold value for association of PNI with mortality. Sensitivity analysis was performed to verify the stability of the results. RESULTS: 734 GDM individuals and 7987 non-GDM individuals were included in this study. In GDM population, after adjusting for different categorical variables, PNI was significantly negatively correlated with ACM risk. Subgroup analysis showed that among GDM populations with no physical activity, moderate physical activity, parity of 1 or 2, negative correlation between PNI and risk of ACM was stronger than other subgroups. Sensitivity analysis results showed stable negative correlations between PNI and ACM and CVD mortality of total population, and between PNI and ACM of GDM. CONCLUSION: In individuals with GDM, PNI was negatively correlated with ACM risk, especially in populations with no physical activity, moderate physical activity, and parity of 1 or 2. PNI = 50.75 may be an effective threshold affecting ACM risk in GDM, which may help in risk assessment and timely intervention for individuals with GDM.

Occurrence of metabolic syndrome in midlife in relation to cardiovascular morbidity and all-cause mortality-lessons from a population-based matched cohort study with 27 years follow-up.

OBJECTIVES: We examined how asymptomatic metabolic syndrome (MetS) in midlife affects cardiovascular (CV) morbidity and all-cause mortality later in life and studied difference in time to event and from the individual components related to MetS. DESIGN: Population-based matched cohort study including data from a screening programme for identification of CV risk factors. SETTING: Primary care, County of Västmanland, Sweden. PARTICIPANTS: All inhabitants turning 40 or 50 years between 1990 and 1999 were invited to a health screening. Total 34 269 (60.1%) individuals completed the health examination. Participants that met a modified definition of MetS were individually matched to two controls without MetS with regard to age, sex and date of health examination. INTERVENTIONS: None. MAIN OUTCOME MEASURES: CV events and all-cause mortality from the index examination to June 2022. RESULTS: All 5084 participants with MetS were matched to two controls. There were 1645 (32.4%) CV events in the MetS group and 2321 (22.8%) CV events for controls. 1317 (25.9%) MetS and 1904 (18.7%) control subjects died. The adjusted HRs (aHR) for CV event and death were significantly higher when MetS was present (aHR) 1.39*** (95% CI 1.28 to 1.50) and 1.27*** (95% CI 1.16 to 1.40) respectively. The factor analysis identified three dominating factors: blood pressure, cholesterol and blood glucose. Mean time for first CV event and death was 2.6 years and 1.5 years shorter respectively for participants within the highest quartile compared with participants with lower mean arterial blood pressure (MAP). The aHR for each 10 mm Hg increased MAP were 1.19*** (95% CI 1.15 to 1.23) for CV event and 1.16*** (95% CI 1.11 to 1.21) for death. CONCLUSION: The risk of a CV event and premature death is significantly increased when MetS is present. Early detection of metabolic risk factors, especially, high blood pressure, opens a window of opportunity to introduce preventive treatment to reduce CV morbidity and all-cause mortality.

Association of serum uric acid to all-cause and cardiovascular mortality in patients with cardiovascular disease.

Serum uric acid (SUA) has been linked to mortality in heart failure, hypertension, diabetes, hyperlipidemia, obstructive sleep apnea, and metabolic dysfunction-associated fatty liver disease. However, data are lacking on how it affects the mortality risk of patients with cardiovascluar disease (CVD). This study evaluated the data of 4 308 individuals from the National Health and Nutrition Examination Survey 1999-2008 using multivariate Cox proportional hazards regression, trend, restricted cubic splines (RCS), subgroup and inflection point analyses. All-cause and cardiovascular mortality accounted for 42.8% and 17.6% of cases, respectively, over a median 80- month follow-up. Upon control for confounding variables, no linear trend was seen in the Cox proportional hazards regression analysis between SUA and all-cause (P = 0.001) or cardiovascular death (P = 0.007) mortality. On the RCS analysis, SUA showed an L-shaped connection with all-cause (non-linear P < 0.001) and cardiovascular mortality (non-linear P = 0.003) mortality. On the inflection point analysis, patients with CVD and an SUA ≥ 6.127 mg/dL had an all-cause mortality hazard ratio of 1.146 (95% confidence interval, 1.078-1.217; P < 0.001), while those with CVD and an SUA ≥ 5.938 mg/dL had a cardiovascular mortality hazard ratio of 1.123 (95% confidence interval, 1.03-1.225; P = 0.007). In patients with CVD, higher SUA was non-linearly correlated with all-cause and cardiovascular mortality.

A protein risk score for all-cause and respiratory-specific mortality in non-Hispanic white and African American individuals who smoke.

Protein biomarkers are associated with mortality in cardiovascular disease, but their effect on predicting respiratory and all-cause mortality is not clear. We tested whether a protein risk score (protRS) can improve prediction of all-cause mortality over clinical risk factors in smokers. We utilized smoking-enriched (COPDGene, LSC, SPIROMICS) and general population-based (MESA) cohorts with SomaScan proteomic and mortality data. We split COPDGene into training and testing sets (50:50) and developed a protRS based on respiratory mortality effect size and parsimony. We tested multivariable associations of the protRS with all-cause, respiratory, and cardiovascular mortality, and performed meta-analysis, area-under-the-curve (AUC), and network analyses. We included 2232 participants. In COPDGene, a penalized regression-based protRS was most highly associated with respiratory mortality (OR 9.2) and parsimonious (15 proteins). This protRS was associated with all-cause mortality (random effects HR 1.79 [95% CI 1.31-2.43]). Adding the protRS to clinical covariates improved all-cause mortality prediction in COPDGene (AUC 0.87 vs 0.82) and SPIROMICS (0.74 vs 0.6), but not in LSC and MESA. Protein-protein interaction network analyses implicate cytokine signaling, innate immune responses, and extracellular matrix turnover. A blood-based protein risk score predicts all-cause and respiratory mortality, identifies potential drivers of mortality, and demonstrates heterogeneity in effects amongst cohorts.

Interleukin-receptor antagonist and tumour necrosis factor inhibitors for the primary and secondary prevention of atherosclerotic cardiovascular diseases.

BACKGROUND: Atherosclerotic cardiovascular disease (ACVD) is worsened by chronic inflammatory diseases. Interleukin receptor antagonists (IL-RAs) and tumour necrosis factor-alpha (TNF) inhibitors have been studied to see if they can prevent cardiovascular events. OBJECTIVES: The purpose of this study was to assess the clinical benefits and harms of IL-RAs and TNF inhibitors in the primary and secondary prevention of ACVD. SEARCH METHODS: The Cochrane Heart Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (including In-Process & Other Non-Indexed Citations), Ovid Embase, EBSCO CINAHL plus, and clinical trial registries for ongoing and unpublished studies were searched in February 2024. The reference lists of relevant studies, reviews, meta-analyses and health technology reports were searched to identify additional studies. No limitations on language, date of publication or study type were set. SELECTION CRITERIA: RCTs that recruited people with and without pre-existing ACVD, comparing IL-RAs or TNF inhibitors versus placebo or usual care, were selected. The primary outcomes considered were all-cause mortality, myocardial infarction, unstable angina, and adverse events. DATA COLLECTION AND ANALYSIS: Two or more review authors, working independently at each step, selected studies, extracted data, assessed the risk of bias and used GRADE to judge the certainty of evidence. MAIN RESULTS: We included 58 RCTs (22,053 participants; 21,308 analysed), comparing medication efficacy with placebo or usual care. Thirty-four trials focused on primary prevention and 24 on secondary prevention. The interventions included IL-1 RAs (anakinra, canakinumab), IL-6 RA (tocilizumab), TNF-inhibitors (etanercept, infliximab) compared with placebo or usual care. The certainty of evidence was low to very low due to biases and imprecision; all trials had a high risk of bias. Primary prevention: IL-1 RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality(RR 0.33, 95% CI 0.01 to 7.58, 1 trial), myocardial infarction (RR 0.71, 95% CI 0.04 to 12.48, I² = 39%, 2 trials), unstable angina (RR 0.24, 95% CI 0.03 to 2.11, I² = 0%, 2 trials), stroke (RR 2.42, 95% CI 0.12 to 50.15; 1 trial), adverse events (RR 0.85, 95% CI 0.59 to 1.22, I² = 54%, 3 trials), or infection (rate ratio 0.84, 95% 0.55 to 1.29, I² = 0%, 4 trials). Evidence is very uncertain about whether anakinra and cankinumab may reduce heart failure (RR 0.21, 95% CI 0.05 to 0.94, I² = 0%, 3 trials). Peripheral vascular disease (PVD) was not reported as an outcome. IL-6 RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 0.68, 95% CI 0.12 to 3.74, I² = 30%, 3 trials), myocardial infarction (RR 0.27, 95% CI 0.04 to1.68, I² = 0%, 3 trials), heart failure (RR 1.02, 95% CI 0.11 to 9.63, I² = 0%, 2 trials), PVD (RR 2.94, 95% CI 0.12 to 71.47, 1 trial), stroke (RR 0.34, 95% CI 0.01 to 8.14, 1 trial), or any infection (rate ratio 1.10, 95% CI: 0.88 to 1.37, I2 = 18%, 5 trials). Adverse events may increase (RR 1.13, 95% CI 1.04 to 1.23, I² = 33%, 5 trials). No trial assessed unstable angina. TNF inhibitors The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 1.78, 95% CI 0.63 to 4.99, I² = 10%, 3 trials), myocardial infarction (RR 2.61, 95% CI 0.11 to 62.26, 1 trial), stroke (RR 0.46, 95% CI 0.08 to 2.80, I² = 0%; 3 trials), heart failure (RR 0.85, 95% CI 0.06 to 12.76, 1 trial). Adverse events may increase (RR 1.13, 95% CI 1.01 to 1.25, I² = 51%, 13 trials). No trial assessed unstable angina or PVD. Secondary prevention: IL-1 RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 0.94, 95% CI 0.84 to 1.06, I² = 0%, 8 trials), unstable angina (RR 0.88, 95% CI 0.65 to 1.19, I² = 0%, 3 trials), PVD (RR 0.85, 95% CI 0.19 to 3.73, I² = 38%, 3 trials), stroke (RR 0.94, 95% CI 0.74 to 1.2, I² = 0%; 7 trials), heart failure (RR 0.91, 95% 0.5 to 1.65, I² = 0%; 7 trials), or adverse events (RR 0.92, 95% CI 0.78 to 1.09, I² = 3%, 4 trials). There may be little to no difference between the groups in myocardial infarction (RR 0.88, 95% CI 0.0.75 to 1.04, I² = 0%, 6 trials). IL6-RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 1.09, 95% CI 0.61 to 1.96, I² = 0%, 2 trials), myocardial infarction (RR 0.46, 95% CI 0.07 to 3.04, I² = 45%, 3 trials), unstable angina (RR 0.33, 95% CI 0.01 to 8.02, 1 trial), stroke (RR 1.03, 95% CI 0.07 to 16.25, 1 trial), adverse events (RR 0.89, 95% CI 0.76 to 1.05, I² = 0%, 2 trials), or any infection (rate ratio 0.66, 95% CI 0.32 to 1.36, I² = 0%, 4 trials). No trial assessed PVD or heart failure. TNF inhibitors The evidence is very uncertain about the effect of the intervention on all-cause mortality (RR 1.16, 95% CI 0.69 to 1.95, I² = 47%, 5 trials), heart failure (RR 0.92, 95% 0.75 to 1.14, I² = 0%, 4 trials), or adverse events (RR 1.15, 95% CI 0.84 to 1.56, I² = 32%, 2 trials). No trial assessed myocardial infarction, unstable angina, PVD or stroke. Adverse events may be underestimated and benefits inflated due to inadequate reporting. AUTHORS' CONCLUSIONS: This Cochrane review assessed the benefits and harms of using interleukin-receptor antagonists and tumour necrosis factor inhibitors for primary and secondary prevention of atherosclerotic diseases compared with placebo or usual care. However, the evidence for the predetermined outcomes was deemed low or very low certainty, so there is still a need to determine whether these interventions provide clinical benefits or cause harm from this perspective. In summary, the different biases and imprecision in the included studies limit their external validity and represent a limitation to determining the effectiveness of the intervention for both primary and secondary prevention of ACVD.

Association between different stages of cardiovascular-kidney-metabolic syndrome and the risk of all-cause mortality.

BACKGROUND AND AIMS: Poor cardiovascular-kidney-metabolic (CKM) health is a major determinant of all-cause mortality, which poses a significant burden on global public health systems and socio-economics. However, the association between different stages of CKM syndrome and the risk of all-cause mortality remains unclear. This study aimed to evaluate the association between different stages of CKM syndrome and risk of all-cause mortality. METHODS: A total of 97,777 adults from the Kailuan Study were included. Cox proportional hazards regression models were applied to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) of all-cause mortality according to different stages of CKM syndrome. RESULTS: Over a median follow-up of 15.0 (14.7-15.2) years, we identified 14,805 all-cause mortality cases. The stage of CKM syndrome was positively associated with the risk of all-cause mortality (p-trend <0.001). Compared with Stage 0, the multivariable-adjusted HRs (95 % CIs) of all-cause mortality were 1.24 (1.06-1.45) for Stage 1, 1.72 (1.48-2.00) for Stage 2, 2.58 (2.22-3.01) for Stage 3 and 3.73 (3.19-4.37) for Stage 4. Moreover, the observed associations were more pronounced in younger adults (aged <60 years) compared with older adults (p for interaction <0.001). CONCLUSIONS: Our data showed that a higher stage of CKM syndrome was associated with a higher risk of all-cause mortality, with a particularly pronounced association observed in younger adults. The study emphasized the need for targeted public health strategies and clinical management tailored to the stages of CKM syndrome, aiming to alleviate its burden on individuals and healthcare systems.