Association of metabolic syndrome and sarcopenia with all-cause and cardiovascular mortality: a prospective cohort study based on the NHANES.

Background: Metabolic syndrome (MetS) and sarcopenia (SP) have emerged as significant public health concerns in contemporary societies, characterized by shared pathophysiological mechanisms and interrelatedness, leading to profound health implications. In this prospective cohort study conducted within a US population, we aimed to examine the influence of MetS and SP on all-cause and cardiovascular mortality. Methods: This study analyzed data from the National Health and Nutrition Examination Survey (NHANES) III for the years 1999-2006 and 2011-2018, and death outcomes were ascertained by linkage to National Death Index (NDI) records through December 31, 2019. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for all-cause and cardiovascular mortality. In addition, subgroup and sensitivity analyses were conducted to test the robustness of the results. Results: Over a median follow-up period of 13.3 years (95% CI: 12.8-13.8), 1714 deaths were observed. The groups characterized by MetS-/SP+, MetS+/SP-, and MetS+/SP+ exhibited higher all-cause mortality rates in comparison to the MetS-/SP- group, with the MetS+/SP+ group (HR 1.76, 95% CI: 1.37-2.25) displaying the highest all-cause mortality. Increased cardiovascular mortality was observed in the MetS+/SP- (HR 1.84, 95% CI: 1.24-2.72), and MetS+/SP+ groups (HR 2.39, 95% CI: 1.32-4.35) compared to the MetS-/SP- group, whereas it was not statistically significant in the MetS-/SP+ group. However, among males and individuals aged < 60, the presence of both MetS and SP (MetS+/SP+ group) was found to be significantly associated with a higher risk of all-cause and cardiovascular mortality. Conclusion: The coexistence of MetS and SP increased the risk of all-cause and cardiovascular mortality, particularly in males and in nonelderly populations. Individuals with either MetS or SP may require more careful management to prevent the development of other diseases and thereby reduce mortality.

Cardiovascular morbidity and mortality in lean vs. non-lean MASLD: A comprehensive meta-analysis.

BACKGROUND: Lean metabolic dysfunction-associated steatotic liver disease (MASLD), characterized by a BMI < 25 kg/m² (or < 23 kg/m² in Asians), presents a challenging prognosis compared to non-lean MASLD. This study examines cardiovascular outcomes in both lean and non-lean MASLD cohorts. METHODS: In this meta-analysis, pooled odds ratios (ORs) within 95 % confidence intervals (CIs) were calculated for primary outcomes (cardiovascular mortality and major adverse cardiovascular events [MACE]) and secondary outcomes (cardiovascular disease [CVD], all-cause mortality, hypertension, and dyslipidemia). Studies comparing lean and non-lean MASLD within the same cohorts were analyzed, prioritizing those with larger sample sizes or recent publication dates. RESULTS: Twenty-one studies were identified, encompassing lean MASLD patients (n = 7153; mean age 52.9 ± 7.4; 56 % male) and non-lean MASLD patients (n = 23,514; mean age 53.2 ± 6.8; 63 % male). Lean MASLD exhibited a 50 % increase in cardiovascular mortality odds compared to non-lean MASLD (OR: 1.5, 95 % CI 1.2-1.8; p < 0.0001). MACE odds were 10 % lower in lean MASLD (OR: 0.9, 95 % CI 0.7-1.2; p = 0.7), while CVD odds were 40 % lower (p = 0.01). All-cause mortality showed a 40 % higher odds in lean MASLD versus non-lean MASLD (p = 0.06). Lean MASLD had 30 % lower odds for both hypertension (p = 0.01) and dyslipidemia (p = 0.02) compared to non-lean MASLD. CONCLUSION: Despite a favorable cardiometabolic profile and comparable MACE rates, lean individuals with MASLD face elevated cardiovascular mortality risk.

Risk of heavy metal(loid) compositions in fine particulate matter on acute cardiovascular mortality: a poisson analysis in Anyang, China.

Fine particulate matter (PM2.5) is a risk factor of cardiovascular disease. Associations between PM2.5 compositions and cardiovascular disease are a point of special interest but inconsistent. This study aimed to explore the cardiovascular effects of heavy metal(loid) compositions in PM2.5. Data for mortality, air pollutants and meteorological factors in Anyang, China from 2017 to 2021 were collected. Heavy metal(loid) in PM2.5 were monitored and examined monthly. A Case-crossover design was applied to the estimated data set. The interquartile range increase in cadmium (Cd), antimony (Sb) and arsenic (As) at lag 1 was associated with increment of 8.1% (95% CI: 3.3, 13.2), 4.8% (95% CI: 0.2, 9.5) and 3.5% (95% CI: 1.1, 6.0) cardiovascular mortality. Selenium in lag 2 was inversely associated with cerebrovascular mortality (RR = 0.920 95% CI: 0.862, 0.983). Current-day exposure of aluminum was positively associated with mortality from ischemic heart disease (RR = 1.083 95% CI: 1.001, 1.172). Stratified analysis indicated sex, age and season modified the cardiovascular effects of As (P < 0.05). Our study reveals that heavy metal(loid) play key roles in adverse effects of PM2.5. Cd, Sb and As were significant risk factors of cardiovascular mortality. These findings have potential implications for accurate air pollutants control and management to improve public health benefits.

Association of sleep timing with all-cause and cardiovascular mortality: the Sleep Heart Health Study and the Osteoporotic Fractures in Men Study.

STUDY OBJECTIVES: Previous studies have highlighted the importance of sleep patterns for human health. This study aimed to investigate the association of sleep timing with all-cause and cardiovascular disease mortality. METHODS: Participants were screened from two cohort studies: the Sleep Heart Health Study (SHHS; n = 4,824) and the Osteoporotic Fractures in Men Study (n = 2,658). Sleep timing, including bedtime and wake-up time, was obtained from sleep habit questionnaires at baseline. The sleep midpoint was defined as the halfway point between the bedtime and wake-up time. Restricted cubic splines and Cox proportional hazards regression analyses were used to examine the association between sleep timing and mortality. RESULTS: We observed a U-shaped association between bedtime and all-cause mortality in both the SHHS and Osteoporotic Fractures in Men Study groups. Specifically, bedtime at 11:00 pm and waking up at 7:00 am was the nadir for all-cause and cardiovascular disease mortality risks. Individuals with late bedtime (> 12:00 am) had an increased risk of all-cause mortality in SHHS (hazard ratio 1.53, 95% confidence interval 1.28-1.84) and Osteoporotic Fractures in Men Study (hazard ratio 1.27, 95% confidence interval 1.01-1.58). In the SHHS, late wake-up time (> 8:00 am) was associated with increased all-cause mortality (hazard ratio 1.39, 95% confidence interval 1.13-1.72). No significant association was found between wake-up time and cardiovascular disease mortality. Delaying sleep midpoint (> 4:00 am) was also significantly associated with all-cause mortality in the SHHS and Osteoporotic Fractures in Men Study. CONCLUSIONS: Sleep timing is associated with all-cause and cardiovascular disease mortality. Our findings highlight the importance of appropriate sleep timing in reducing mortality risk. CITATION: Ma M, Fan Y, Peng Y, et al. Association of sleep timing with all-cause and cardiovascular mortality: the Sleep Heart Health Study and the Osteoporotic Fractures in Men Study. J Clin Sleep Med. 2024;20(4):545-553.

Insulin resistance potentiates the effect of remnant cholesterol on cardiovascular mortality in individuals without diabetes.

BACKGROUND AND AIMS: Remnant cholesterol (RC) and insulin resistance (IR) have been independently associated with cardiovascular risk. Here, we evaluated the role of IR and RC on cardiovascular disease (CVD) mortality. METHODS: We conducted an analysis of 16,113 individuals ≥20 years without diabetes from the National Health and Nutrition Examination Survey (NHANES-III/IV). RC levels were calculated using total cholesterol, non-HDL-c, and LDL-c; IR was defined as HOMA2-IR≥2.5 and CVD mortality as a composite of cardiovascular and cerebrovascular mortality. Multiple linear regression was used to assess the relationship between HOMA2-IR and RC and Cox regression models to assess their joint role in CVD mortality. Causally ordered mediation models were used to explore the mediating role of IR in RC-associated CVD mortality. RESULTS: We identified an association between higher HOMA2-IR and higher RC levels. The effect of IR on CVD mortality was predominant (HR 1.32, 95%CI 1.18-1.48) and decreased at older ages (HR 0.934, 95%CI 0.918-0.959) compared to RC (HR 0.983, 95%CI 0.952-1.014). Higher risk of CVD mortality was observed in individuals with IR but normal RC (HR 1.37, 95%CI 1.25-1.50) and subjects with IR and high RC (HR 1.24, 95%CI 1.13-1.37), but not in subjects without IR but high RC. In mediation models, HOMA2-IR accounted for 78.2% (95%CI 28.11-98.89) of the effect of RC levels on CVD mortality. CONCLUSIONS: Our findings suggest that RC potentiates the risk of CVD mortality through its effect on whole-body insulin sensitivity, particularly among younger individuals.

Association of Serum AGR With All-Cause and Cause-Specific Mortality Among Individuals With Diabetes.

BACKGROUND: There is insufficient data to support a link between serum AGR and mortality in individuals with diabetes. This prospective study sought to investigate the relationship between serum AGR and all-cause and cause-specific mortality in adult diabetics. METHODS: This study included 8508 adults with diabetes from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Death outcomes were ascertained by linkage to National Death Index records through 31 December 2019. Hazard ratios (HR) and 95% confidence intervals (CIs) for mortality from all causes, cardiovascular disease (CVD), and cancer were estimated using weighted Cox proportional hazards models. RESULTS: 2415 all-cause deaths, including 688 cardiovascular deaths and 413 cancer deaths, were recorded over an average of 9.61 years of follow-up. After multivariate adjustment, there was a significant and linear relationship between higher serum AGR levels and reduced all-cause and cause-specific mortality in a dose-response manner. The multivariate-adjusted HR and 95% CI for all-cause mortality (Ptrend<0.0001), cardiovascular mortality (Ptrend<0.001), and cancer mortality (Ptrend<0.01) were 0.51(0.42,0.60), 0.62(0.46,0.83), and 0.57(0.39,0.85), respectively, for individuals in the highest AGR quartile. There was a 73% decreased risk of all-cause death per one-unit rise in natural log-transformed serum AGR, as well as a 60% and 63% decreased risk of mortality from CVD and cancer, respectively (all P<0.001). Both the stratified analysis and the sensitivity analyses revealed the same relationships. CONCLUSIONS: AGR is a promising biomarker in risk predictions for long-term mortality in diabetic individuals, particularly in those under age 60 and heavy drinker.

The neutrophil-to-lymphocyte ratio is associated with all-cause and cardiovascular mortality among individuals with hypertension.

BACKGROUND: Identifying reliable prognostic markers is crucial for the effective management of hypertension. The neutrophil-to-lymphocyte ratio (NLR) has emerged as a potential inflammatory marker linked to cardiovascular outcomes. This study aims to investigate the association of NLR with all-cause and cardiovascular mortality among patients with hypertension. METHODS: This study analyzed data from 3067 hypertensive adults in the National Health and Nutritional Examination Surveys (NHANES) from 2009 to 2014. Mortality details were obtained from the National Death Index (NDI). Restricted cubic spline (RCS) was deployed to visualize the association of the NLR with mortality risk. Weighted Cox proportional hazards models were employed to assess the independent association of NLR with mortality risk. Time-dependent receiver operating characteristic curve (ROC) analysis was conducted to access the predictive ability of NLR for survival. Mediation analysis was used to explore the indirect impact of NLR on mortality mediated through eGFR. RESULTS: Over a median 92.0-months follow-up, 538 deaths occurred, including 114 cardiovascular deaths. RCS analysis revealed a positive association between NLR and both all-cause and cardiovascular mortality. Participants were stratified into higher (> 3.5) and lower (≤ 3.5) NLR groups. Weighted Cox proportional hazards models demonstrated that individuals with higher NLR had a significantly increased risk of all-cause (HR 1.96, 95% confidence interval (CI) 1.52-2.52, p < 0.0001) and cardiovascular mortality (HR 2.33, 95% CI 1.54-3.51, p < 0.0001). Stratified and interaction analysis confirmed the stability of the core results. Notably, eGFR partially mediated the association between NLR and both all-cause and cardiovascular mortality by a 5.4% and 4.7% proportion, respectively. Additionally, the areas under the curve (AUC) of the 3-, 5- and 10- year survival was 0.68, 0.65 and 0.64 for all-cause mortality and 0.68, 0.70 and 0.69 for cardiovascular mortality, respectively. CONCLUSION: Elevated NLR independently confers an increased risk for both all-cause and cardiovascular mortality in individuals with hypertension.

Relationship of serum total cholesterol and triglyceride with risk of mortality in maintenance hemodialysis patients: a multicenter prospective cohort study.

OBJECTIVE: The relationship between serum total cholesterol (TC) and triglyceride (TG) levels and mortality in maintenance hemodialysis (MHD) patients remains inconsistent. We aimed to explore the individual and combined association of TC and TG levels with the risk of mortality in Chinese MHD patients. METHODS: 1036 MHD patients were enrolled in this multicenter, prospective cohort study. The serum levels of total cholesterol and triglycerides were measured at baseline. The primary outcome was all-cause mortality and secondary outcome was cardiovascular disease (CVD) mortality. RESULTS: During a median follow-up duration of 4.4 years (IQR= 2.0-7.9 years), 549 (53.0%) patients died, and 297 (28.7%) deaths were attributed to CVD. Compared with patients with TC levels in the first three quartiles (<182.5 mg/dL), a significantly higher risk of all-cause mortality was found in participants with TC in the fourth quartile (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.17-1.76). However, a significantly lower risk of all-cause mortality was observed in participants with TG in the fourth quartile (≥193.9 mg/dL) (HR, 0.78; 95%CI: 0.63-0.98), compared with participants with TG in the first three quartiles. Similar trends were observed in CVD mortality. When analyzed jointly, patients with lower TC (<182.5 mg/dL) and higher TG (≥193.9 mg/dL) levels had the lowest risk of all-cause mortality and CVD mortality.Conclusions: In MHD patients in southern China, higher TC levels were associated with higher risk of mortality, while higher TG levels were related to lower risk of mortality. Patients with lower TC and higher TG levels had the best survival prognosis.

The impact of baseline dietary fatty acid intake on the association between lipoprotein(a) and mortality in two US cohorts.

Background: Lipoprotein(a) (Lp(a)) is an established casual risk factor for atherosclerotic cardiovascular disease. It remains unknown whether dietary fat modifies the association of Lp(a) with cardiovascular death. Aim: To understand if dietary fat modifies the association between Lp(a) and cardiovascular death. Methods: We utilized the Atherosclerotic Risk in Communities (ARIC) study and National Health and Nutrition Examination Survey (NHANES) III cohorts and used multivariate cox proportional hazard modeling to test the association between Lp(a), dietary fats, and cardiovascular death. Results: The sample (n = 22,805) had average age 51.3 years and was mostly female (55.4%). Lp(a) ≥ 30 mg/dL was associated with CV death in both ARIC (1.36, p = 0.001) and NHANES (1.31, p = 0.03). In multivariate analysis, no categorical or individual fatty acids modified the association between Lp(a) and CV death. Conclusion: There was no evidence that baseline dietary fat intake modified the association between Lp(a) and CV death.

Risk factors for and risk of all-cause and atherosclerotic cardiovascular disease mortality in people with type 2 diabetes and peripheral artery disease: an observational, register-based cohort study.

BACKGROUND: Type 2 diabetes (T2D) and peripheral artery disease (PAD) are recognized as independent risk factors contributing to excess mortality. Contemporary observational studies exploring the associations of risk factors, and risk of all-cause and atherosclerotic cardiovascular disease mortality in persons with T2D following the onset of incident peripheral artery disease are limited. The objectives of this study were to investigate the associations of risk factors, and assess mortality risks in people with T2D compared with controls without T2D after the onset of PAD. METHODS: All persons with T2D (n = 150,215) registered in the Swedish National Diabetes Register between 2005 and 2009 were included, along with 346,423 controls without T2D matched for sex and age. Data were retrieved from several national registries, capturing information on risk factors, onset of incident peripheral artery disease, other comorbidities, socioeconomic factors, and outcomes. To compare persons with T2D and controls following the onset of peripheral artery disease regarding the risk of all-cause, and atherosclerotic cardiovascular disease mortality, Cox proportional hazard models and Kaplan-Meier curves were employed. A gradient-boosting model was utilized to estimate the relative statistical contribution of risk factors to the modeling of incident mortality risk in people with both T2D and peripheral artery disease. RESULTS: Crude rates of incident all-cause mortality were higher in individuals with T2D compared with controls, following the onset of PAD (600.4 (95% CI, 581.4-619.8) per 10,000 person-years versus 549.1 (95% CI, 532.1-566.5) per 10,000 person-years). Persons with T2D had an adjusted hazard ratio (HR) for all-cause mortality of 1.12 (95% CI, 1.05-1.19, P < 0.01) compared with controls after onset of incident PAD. The comparable adjusted HR for cardiovascular mortality was 1.13 (95% CI, 1.07-1.19, P < 0.01). High age and hyperglycemia at baseline played a significant role in contributing to the predictive models for incident all-cause and cardiovascular mortality among individuals with both T2D and PAD. CONCLUSIONS: The presence of T2D with concomitant PAD is related to an increased risk of both all-cause and cardiovascular mortality compared with individuals with only PAD. This argues for implementing optimized and intensive treatment strategies for individuals with both conditions.

Comparison of Racial and Ethnic Mortality Disparities among Post-9/11 Veterans with and without Traumatic Brain Injury to the Total U.S. Adult Population.

INTRODUCTION: The extent of racial/ethnic disparities and whether they are attenuated in the Veteran population compared to the total US population is not well understood. We aimed to assess racial/ethnic mortality disparities from all-cause, cardiovascular (CVD) and cancer among post-9/11 military Veterans with and without exposure to TBI, compared to the total US population. METHODS: This cohort study included 2,502,101 US military Veterans (18,932,083 person-years) who served after 09/11/2001 with 3 or more years of care in the Military Health System (MHS); or had 3 or more years of care in the MHS and 2 or more years of care in the Veterans Health Administration. Mortality follow-up occurred from 01/01/2002 to 12/31/2020. Mortality rate ratios (MRR) from negative binomial regression models were reported for racial/ethnic groups compared to White non-Hispanic Veterans for all-cause, CVD and cancer mortality. Veteran MRR were compared to the total US population. RESULTS: Mortality rates for Black Non-Hispanic Veterans were higher for all-cause (MRR = 1.21;95%CI: 1.13-1.29; p < 0.001), CVD (MRR = 1.78;95%CI: 1.62-1.96; p < 0.001) and cancer (MRR = 1.17;95%CI: 1.10-1.25; p < 0.001) than in White Non-Hispanic Veterans. Among Veterans with TBI, only Black Non-Hispanics had higher mortality than White Non-Hispanics and only for CVD (MRR = 1.32;95%CI: 1.12-1.54; p < 0.001), while CVD mortality was higher among Veterans without TBI (MRR = 1.77;95%CI: 1.63-1.93;p < 0.001). MRR for Black Non-Hispanics in the total US population, were consistently higher than those in the Veteran population for all-cause (MRR = 1.52;95%CI: 1.46-1.58; p < 0.001), CVD (MRR = 2.03;95%CI: 1.95-2.13; p < 0.001) and cancer (MRR = 1.26;95%CI: 1.22-1.30; p < 0.001). CONCLUSION: This Veteran cohort experienced less racial/ethnic disparity in mortality than the total US population, especially among Veterans with TBI.

Impact of weighting on the association between sociodemographic characteristics, health behaviours and cancer, cardiovascular and all-cause mortality in the Australian 45 and Up Study.

BACKGROUND: Weighting can improve study estimate representativeness. We examined the impact of weighting on associations between participants' characteristics and cancer, cardiovascular and all-cause mortality in the Australian 45 and Up Study cohort. METHODS: Raking weighted cohort data to the 2006 Australian population for seven sociodemographic characteristics. Deaths were ascertained via linkage to routinely collected data. Cox's proportional hazards regression quantified associations between 11 sociodemographic and health characteristics and cancer, cardiovascular and all-cause mortality. The ratios of hazard ratios (RHRs) compared unweighted and weighted estimates. RESULTS: Among 195,052 included participants (median follow-up 11.4 years), there were 7200 cancer, 5912 cardiovascular and 21,840 all-cause deaths. Overall, 102/111 (91.9%) weighted HRs did not differ significantly from unweighted HRs (100%, 86.5% and 89.2% of 37 HRs for cancer, cardiovascular and all-cause mortality, respectively). Significant differences included a somewhat stronger association between single/widowed/divorced (versus married/de-facto) and cardiovascular mortality (unweighted HR=1.25 (95%CI:1.18-1.32), weighted HR=1.33 (95%CI:1.24-1.42), RHR=1.06 (95%CI:1.02-1.11)); and between no school certificate/qualification (versus university degree) and all-cause mortality (unweighted HR=1.21 (95%CI:1.15-1.27), weighted HR=1.28 (95%CI:1.19-1.38), RHR=1.06 (95%CI:1.03-1.10)). CONCLUSION: Our results support the generalisability of most estimates of associations in the 45 and Up Study, particularly in relation to cancer mortality. Slight distortion of a few associations with cardiovascular or all-cause mortality were observed.

Inter-leg systolic blood pressure difference has been associated with all-cause and cardiovascular mortality: analysis of NHANES 1999-2004.

BACKGROUND: Inter-leg systolic blood pressure difference (ILSBPD) has emerged as a novel cardiovascular risk factor. This study aims to investigate the predictive value of ILSBPD on all-cause and cardiovascular mortality in general population. METHODS: We combined three cycles (1999-2004) of the National Health and Nutrition Examination Survey (NHANES) data. Levels of ILSBPD were calculated and divided into four groups based on three cut-off values of 5, 10 and 15mmHg. Time-to-event curves were estimated with the use of the Kaplan-Meier method, and two multivariable Cox proportional hazards regression models were conducted to assess the hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause and cardiovascular mortality associated with ILSBPD. RESULTS: A total of 6 842 subjects were included, with the mean (SD) age of 59.5 (12.8) years. By December 31, 2019, 2 544 and 648 participants were identified all-cause and cardiovascular mortality respectively during a median follow-up of 16.6 years. Time-to-event analyses suggested that higher ILSBPD was associated with increased all-cause and cardiovascular mortality (logrank, p < 0.001). Every 5mmHg increment of ILSBPD brings about 5% and 7% increased risk of all-cause and cardiovascular mortality, and individuals with an ILSBPD ≥ 15mmHg were significantly associated with higher incidence of all-cause mortality (HR 1.43, 95%CI 1.18-1.52, p < 0.001) and cardiovascular mortality (HR 1.73, 95%CI 1.36-2.20, p < 0.001) when multiple confounding factors were adjusted. Subgroup and sensitivity analysis confirmed the relationship. CONCLUSIONS: Our findings suggest that the increment of ILSBPD was significantly associated with higher risk of all-cause and cardiovascular mortality in general population.

Association of secondhand smoke exposure with all-cause mortality and cardiovascular death in patients with hypertension: Insights from NHANES.

BACKGROUND AND AIM: The impact of environmental chemical exposure on blood pressure (BP) is well-established. However, the relationship between secondhand smoke exposure (SHSE) and mortality in hypertensive patients in the general population remains unclear. METHODS AND RESULTS: This cohort study included US adults in the National Health and Nutrition Examination Survey from 2007 to 2018. All-cause mortality and cause-specific mortality outcomes were determined by associating them with the National Death Index records. Cox proportional risk models were used to estimate hazard ratios (HRs) for all-cause mortality and cardiovascular disease (CVD) mortality, and 95% confidence intervals (CIs) for SHSE. The cohort included 10,760 adult participants. The mean serum cotinine level was 0.024 ng/mL. During a mean follow-up period of 76.9 months, there were 1729 deaths, including 469 cardiovascular disease deaths recorded. After adjusting for lifestyle factors, BMI, hypertension duration, medication use, and chronic disease presence, the highest SHSE was significantly associated with higher all-cause and CVD mortality. CONCLUSIONS: This study demonstrates that higher SHSE is significantly associated with higher all-cause mortality and CVD mortality. Further research is necessary to elucidate the underlying mechanisms.

Associations of iron metabolism and inflammation with all-cause and cardiovascular mortality in a large NHANES community sample: Moderating and mediating effects.

BACKGROUND AND AIMS: This study aimed to assess the associations between serum iron concentration, C-reactive protein (CRP) concentration and the risk of all-cause mortality and cardiovascular mortality in the general population and to explore potential mediating and moderating effects. METHODS AND RESULTS: This study analyzed data from the National Health and Nutrition Examination Survey spanning the years 1999-2010, encompassing 23,634 participants. Cox proportional hazards regression models were employed to investigate the independent associations of serum iron and CRP with all-cause and cardiovascular mortality. Moderation and mediation analyses explored the moderating effect of CRP on the association between the serum iron concentration and all-cause and cardiovascular mortality, and the mediating role of the serum iron concentration in the association between the CRP concentration and all-cause and cardiovascular mortality. After multivariate adjustments in the Cox model, serum iron and CRP levels were independently correlated with both all-cause and cardiovascular mortality risk. Moderation analyses revealed a more pronounced correlation between the serum iron concentration and both all-cause and cardiovascular mortality in participants with higher CRP levels. Mediation analysis indicated that the serum iron concentration partly mediated the impact of CRP on the risk of all-cause mortality (13.79%) and cardiovascular mortality (24.12%). CONCLUSION: Serum iron and CRP are independently associated with all-cause and cardiovascular mortality. Moreover, the associations between serum iron concentrations and both all-cause and cardiovascular mortality are more pronounced in individuals with elevated CRP. Serum iron partially mediates the effect of CRP on all-cause and cardiovascular mortality.

Association between triglyceride-glucose related indices with the all-cause and cause-specific mortality among the population with metabolic syndrome.

BACKGROUND: Triglyceride-glucose (TyG) index has been determined to play a role in the onset of metabolic syndrome (MetS). Whether the TyG index and TyG with the combination of obesity indicators are associated with the clinical outcomes of the MetS population remains unknown. METHOD: Participants were extracted from multiple cycles of the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018 years. Three indicators were constructed including TyG index, TyG combining with waist circumference (TyG-WC), and TyG combining with waist-to-height ratio (TyG-WHtR). The MetS was defined according to the National Cholesterol Education Program (NCPE) Adult Treatment Panel III. Kaplan-Meier (KM) curves, restricted cubic splines (RCS), and the Cox proportional hazard model were used to evaluate the associations between TyG-related indices and mortality of the MetS population. The sensitive analyses were performed to check the robustness of the main findings. RESULTS: There were 10,734 participants with MetS included in this study, with 5,570 females and 5,164 males. The median age of the study population was 59 years old. The multivariate Cox regression analyses showed high levels of TyG-related indices were significantly associated with the all-cause mortality of MetS population [TyG index: adjustedhazard ratio (aHR): 1.36, 95%confidence interval (CI): 1.18-1.56, p < 0.001; TyG-WHtR index: aHR = 1.29, 95%CI: 1.13-1.47, p < 0.001]. Meanwhile, the TyG-WC and TyG-WHtR index were associated with cardiovascular mortality of the MetS population (TyG-WC: aHR = 1.45, 95%CI: 1.13-1.85, p = 0.004; TyG-WHtR: aHR = 1.50 95%CI: 1.17-1.92, p = 0.002). Three TyG-related indices showed consistent significant correlations with diabetes mortality (TyG: aHR = 4.06, 95%CI: 2.81-5.87, p < 0.001; TyG-WC: aHR = 2.55, 95%CI: 1.82-3.58, p < 0.001; TyG-WHtR: aHR = 2.53 95%CI: 1.81-3.54, p < 0.001). The RCS curves showed a non-linear trend between TyG and TyG-WC indices with all-cause mortality (p for nonlinearity = 0.004 and 0.001, respectively). The sensitive analyses supported the positive correlations between TyG-related indices with mortality of the MetS population. CONCLUSION: Our study highlights the clinical value of TyG-related indices in predicting the survival of the MetS population. TyG-related indices would be the surrogate biomarkers for the follow-up of the MetS population.

Prediabetes is associated with increased cardiac events in patients with cancer who are prescribed anthracyclines.

BACKGROUND: Prediabetes, which is a precedent of overt diabetes, is a known risk factor for adverse cardiovascular outcomes. Its impact on adverse cardiovascular outcomes in patients with cancer who are prescribed anthracycline-containing chemotherapy (ACT) is uncertain. The objective of this study was to evaluate the association of prediabetes with cardiovascular events in patients with cancer who are prescribed ACT. METHODS: The authors identified patients with cancer who received ACT from 2000 to 2019 from Clinical Data Analysis Reporting System of Hong Kong. Patients were divided into diabetes, prediabetes, and normoglycemia groups based on their baseline glycemic profile. The Primary outcome, a major adverse cardiovascular event (MACE), was the composite event of hospitalization for heart failure and cardiovascular death. RESULTS: Among 12,649 patients at baseline, 3997 had prediabetes, and 5622 had diabetes. Over median follow-up of 8.7 years, the incidence of MACE was 211 (7.0%) in the normoglycemia group, 358 (9.0%) in the prediabetes group, and 728 (12.9%) in the diabetes group. Compared with normoglycemia, prediabetes (adjusted hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.01-1.43) and diabetes (adjusted HR, 1.46; 95% CI, 1.24-1.70) were associated with an increased risk of MACE. In the prediabetes group, 475 patients (18%) progressed to overt diabetes and exhibited a greater risk of MACE (adjusted HR, 1.76; 95% CI, 1.31-2.36) compared with patients who remained prediabetic. CONCLUSIONS: In patients with cancer who received ACT, those who had prediabetes at baseline and those who progressed to diabetes at follow-up had an increased risk of MACE. The optimization of cardiovascular risk factor management, including prediabetes, should be considered in patients with cancer who are treated before and during ACT to reduce cardiovascular risk. PLAIN LANGUAGE SUMMARY: Patients with cancer who have preexisting diabetes have a higher risk of cardiovascular events, and prediabetes is often overlooked. In this study of 12,649 patients with cancer identified in the Clinical Data Analysis Reporting System of Hong Kong who were receiving treatment with anthracycline drugs, prediabetes was correlated with increased deaths from cardiovascular disease and/or hospitalizations for heart failure. Patients who progressed from prediabetes to diabetes within 2 years had an increased risk of combined hospitalization for heart failure and death from cardiovascular disease. These findings indicate the importance of paying greater attention to cardiovascular risk factors, including how prediabetes is managed, in patients who have cancer and are receiving chemotherapy with anthracyclines, emphasizing the need for surveillance, follow-up strategies, and consideration of prediabetes management in cancer care.

Dietary n-3 fatty acids intake and all-cause and cardiovascular mortality in patients with pre-diabetes and diabetes.

BACKGROUND: While the association between n-3 polyunsaturated fatty acids (PUFA) and cardiovascular events has been thoroughly examined, there is still a scarcity of research regarding their impact on the long-term prognosis in diabetic patients. METHOD: Herein, a total of 16,539 eligible individuals were enrolled from the National Health and Nutrition Examination Survey (NHANES) 2003-2018, and categorized into T1, T2, and T3 based on the tertiles of n-3 PUFA. The Cox proportional risk regression models, Kaplan-Meier curve, and subgroup analysis were conducted to evaluate the association between n-3 PUFA and mortality. Restricted cubic spline (RCS) curves graphically demonstrated the dose-response relationship. Additionally, weighted quantile sum (WQS) models were adopted to measure the mixed and individual effects of n-3 PUFA on mortality. RESULTS: Following a median follow-up period of 8.42 years, 3,010 individuals died, with 989 deaths attributed to cardiovascular diseases. Significantly lower risk of all-cause [T2: 0.81 (0.71, 0.92), T3: 0.77 (0.64, 0.94)] and cardiovascular [T2: 0.75 (0.61, 0.93)] mortality was observed after adjusting for multivariable compared to the reference (T1). Meanwhile, the RCS curve revealed a negative non-linear association between the n-3 PUFA and mortality. None of the interactions in any subgroup analysis were statistically significant except for BMI (p for interaction = 0.049). Finally, the WQS analysis demonstrated alpha-linolenic acid (ALA) and docosapentaenoic acid (DPA) as the main contributors to the n-3 PUFA benefits against mortality. CONCLUSIONS: Increased dietary intake of n-3 PUFA, particularly ALA and DPA, was associated with a reduced risk of all-cause and cardiovascular mortality among Americans with prediabetes and diabetes.

Projecting heat-related cardiovascular mortality burden attributable to human-induced climate change in China.

BACKGROUND: Cardiovascular disease (CVD) has been found to be particularly vulnerable to climate change and temperature variability. This study aimed to assess the extent to which human-induced climate change contributes to future heat-related CVD burdens. METHODS: Daily data on CVD mortality and temperature were collected in 161 Chinese communities from 2007 to 2013. The association between heat and CVD mortality was established using a two-stage time-series design. Under the natural forcing, human-induced, and combined scenarios, we then separately projected excess cause-/age-/region-/education-specific mortality from future high temperature in 2010-2100, assuming no adaptation and population changes. FINDINGS: Under shared socioeconomic pathway with natural forcing scenario (SSP2-4.5-nat), heat-related attributable fraction of CVD deaths decreased slightly from 3.3% [95% empirical confidence interval (eCI): 0.3, 5.8] in the 2010s to 2.8% (95% eCI: 0.1, 5.2) in the 2090s, with relative change of -0.4% (95% eCI: -0.8, 0.0). However, for combined natural and human-induced forcings, this estimate would surge to 8.9% (95% eCI: 1.5, 15.7), 14.4% (95% eCI: 1.5, 25.3), 21.3% (95% eCI: -0.6, 39.4), and 28.7% (95% eCI: -3.3, 48.0) in the 2090s under SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5 scenarios, respectively. When excluding the natural forcing, the number of human-induced heat-related CVD deaths would increase from approximately eight thousand (accounting for 31% of total heat-related CVD deaths) in the 2010s to 33,052 (68%), 63,283 (80%), 101,091 (87%), and 141,948 (90%) in the 2090s under SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5 scenarios, respectively. Individuals with stroke, females, the elderly, people living in rural areas, and those with lower education level would exhibit heightened susceptibility to future high temperature. In addition, Southern and Eastern regions of China were expected to experience a faster increase in heat-related attributable fraction of CVD deaths. INTERPRETATION: Human activities would significantly amplify the future burden of heat-related CVD. Our study findings suggested that active adaptation and mitigation measures towards future warming could yield substantial health benefits for the patients with CVD. FUNDING: National Natural Science Foundation of China.

Evaluating the predictive value of late gadolinium enhancement assessed by cardiac magnetic resonance on sudden cardiac death in patients selected for implantable cardioverter defibrillator and cardiac resynchronization therapy implantation: a systematic review and meta-analysis.

AIMS: Late gadolinium enhancement (LGE) assessed by cardiovascular magnetic resonance (CMR) can evaluate myocardial scar associated with a higher risk of sudden cardiac death (SCD), which can guide the selection between cardiac resynchronization therapy with or without a defibrillator (CRT-P/CRT-D). Our aim was to investigate the association between LGE and SCD risk in patients with CRT using the LGE-CMR technique. METHODS AND RESULTS: We performed a systematic literature search using four databases. The target population was CRT candidates. The primary endpoint was SCD. The risk of bias was assessed using the QUIPS tool. Fifteen eligible articles were included with a total of 2494 patients, of whom 27%, 56%, and 19% had an implantable cardioverter defibrillator (ICD), CRT-D, and CRT-P, respectively. Altogether, 54.71% of the cohort was LGE positive, who had a 72% higher risk for SCD (HR 1.72; 95% CI 1.18-2.50) compared to LGE negatives. In non-ischemic patients, the proportion of LGE positivity was 46.6%, with a significantly higher risk for SCD as compared to LGE negatives (HR 2.42; 95% CI 1.99-2.94). The subgroup of CRT-only patients showed no difference between the LGE-positive vs. negative candidates (HR 1.17; 95% CI 0.82-1.68). Comparable SCD risk was observed between articles with short- (OR 7.47; 95% CI 0.54-103.12) vs. long-term (OR 6.15; 95% CI 0.96-39.45) follow-up time. CONCLUSION: LGE-CMR positivity was associated with an increased SCD risk; however, in CRT candidates, the difference in risk reduction between LGE positive vs. negative patients was statistically not significant, suggesting a role of reverse remodeling. LGE-CMR before device implantation could be crucial in identifying high-risk patients even in non-ischemic etiology.