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.

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.

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

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

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

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

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

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

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

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

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.

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.

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

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

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.

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.

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

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

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.

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

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

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

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

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

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

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.

Sociodemographic disparities in cardiovascular mortality by self-rated physical health: A U.S. nationwide county-level analysis.

OBJECTIVE: We investigated the association between self-rated poor physical health (srPPH), a validated proxy measure of health-related quality of life, and age-adjusted cardiovascular mortality (AACVM) rates across overall U.S. counties and within various demographics. STUDY DESIGN: Nationwide county-level analysis. METHODS: We analyzed county-level data spanning 2010-2019 from the Behavioral Risk Factors Surveillance System (BRFSS) and the Centers for Disease Control and Prevention (CDC). This analysis included data from 2892 counties with complete records on srPPH and AACVM. srPPH was defined as the age-adjusted average number of days respondents reported being in poor physical health over the past 30 days. To estimate the average srPPH per resident in each county, the CDC utilized validated statistical models applied to BRFSS data. To assess the association between srPPH and AACVM, we employed Poisson Generalized Linear Mixed Models, generating incident rate ratios (IRRs). RESULTS: Out of the 307,045,647 residents living in 2892 U S. counties in 2010, 8,157,571 (2.7 %) cardiovascular deaths were recorded during the study period. Counties where residents reported the greatest number of physically unhealthy days-indicative of higher srPPH-experienced the highest AACVM rates, despite significant decreases in overall AACVM rates from 2010 to 2019. Moreover, srPPH was independently associated with higher AACVM rates (IRR: 1.018; 95 % CI: 1.011 to 1.025) across most demographic groups, except Hispanics. This association was particularly strong among middle-aged (45-64 years old) women and elderly (≥65 years old) non-Hispanic Black individuals. CONCLUSION: srPPH may serve as a valuable community health marker that can help identify populations at risk for cardiovascular mortality, independent of other social determinants of health. When used in combination with objective measures of cardiovascular health, this metric can enhance targeted screening and intervention efforts in high-risk populations.

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

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