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.

Glycated Hemoglobin Variability Is Associated With Adverse Outcomes in Patients With Heart Failure Irrespective of Diabetic Status.

BACKGROUND: The effect of glycated hemoglobin (HbA1c) variability on adverse outcomes in patients with heart failure (HF) is unclear. We aim to investigate the predictive value of HbA1c variability on the risks of all-cause death and HF rehospitalization in patients with HF irrespective of their diabetic status. METHODS AND RESULTS: Using a previously validated territory-wide clinical data registry, HbA1c variability was assessed by average successive variability (ASV) or SD of all HbA1c measurements after HF diagnosis. Multivariable Cox proportional hazards models were used to estimate the adjusted hazard ratio (HR) and its corresponding 95% CI. A total of 65 950 patients with HF were included in the study. Over a median follow-up of 6.7 (interquartile range, 4.0-10.6) years, 34 508 patients died and 52 446 required HF rehospitalization. Every unit increment of variability in HbA1c was significantly associated with higher HF rehospitalization (HR ASV, 1.20 [95% CI, 1.18-1.23]) and all-cause death (HR ASV, 1.50 [95% CI, 1.47-1.53]). Diabetes significantly modified the association between HbA1c variability and outcomes (Pinteraction<0.001). HbA1c variability in patients with HF without diabetes conferred a higher risk of rehospitalization (HR ASV, 1.92 [95% CI, 1.70-2.17] versus HR ASV, 1.19 [95% CI, 1.17-1.21]), and all-cause death (HR ASV, 3.90 [95% CI, 3.31-4.61] versus HR ASV, 1.47 [95% CI, 1.43-1.50] compared with patients with diabetes). CONCLUSIONS: HbA1c variability is significantly associated with greater risk of rehospitalization and all-cause death in patients with HF, irrespective of their diabetic status. These observations were more pronounced in patients with HF without diabetes.

Development and validation of a diagnostic nomogram in pulmonary hypertension due to left heart disease.

BACKGROUND: Pulmonary hypertension (pH) due to left heart disease (pH-LHD) is the most common form of pH in clinical practice. OBJECTIVES: The purpose of the study is to develop a diagnostic nomogram predictive model combining conventional noninvasive examination and detection indicators. METHODS: Our study retrospectively included 361 patients with left heart disease (LHD) who underwent right heart catheterization between 2013 and 2020. All patients were randomly divided into a training cohort (253, 70 %) and a validation cohort (108, 30 %). pH was defined as resting mean pulmonary arterial pressure (mPAP) ≥25 mmHg measured by RHC examination. Data dimension reduction and feature selection were used by Lasso regression model. The nomogram was constructed based on multivariable logistic regression. RESULTS: A total of 175 patients with LHD were diagnosed with pH during their hospitalization, representing 48.5 % of the cohort. The mean age of the overall group was 55.6 years, with 76.7 % being male patients. Excessive resting heart rate, elevated New York Heart Association functional class, increased red blood cell distribution width, right ventricular end-diastolic diameter, and pulmonary artery systolic pressure measured by echocardiography were independently associated with the prevalence of pH-LHD. The inclusion of these 5 variables in the nomogram showed good discrimination (AUC = 0.866 [95 % CI, 0.820-0.911]) and optimal calibration (Hosmer-Lemeshow test, P = 0.791) for the validation cohort. CONCLUSIONS: The noninvasive nomogram of pH-LHD developed in this study has excellent diagnostic value and clinical applicability, and can more accurately evaluate the presence risk of pH in patients with LHD.

Correlation of ventricle epicardial fat volume and triglyceride-glucose index in patients with chronic heart failure.

To explore the association of ventricle epicardial fat volume (EFV) calculated by cardiac magnetic resonance (CMR) and the insulin resistance indicator of triglyceride-glucose (TyG) index in patients with chronic HF (CHF), this retrospective cohort study included adult CHF patients with confirmed diagnosis of heart failure from January 2018 to December 2020. All patients underwent 3.0T CMR, and EFV were measured under short-axis cine. Spearman correlation, multivariate linear regression, and restricted cubic spline (RCS) regression were used to analyze their association. There were 516 patients with CHF, of whom 69.8% were male. Median EFV was 57.14mL and mean TyG index was 8.48. Spearman correlation analysis showed that TyG index was significantly correlated with the EFV in CHF patients (r = 0.247, P < 0.001). Further analysis showed that TyG index levels were significantly associated with EFV as both continuous variables (Unstandardized ß = 6.556, P < 0.001) and across the increasing quartiles (ß = 7.50, 95% CI [1.41, 13.59], P < 0.05). RCS demonstrated there were a positive trend and linear association between EFV and TyG index in CHF patients (P for nonliearity = 0.941). In patients with CHF, the TyG index was positively and linearly associated with the EFV, which supports the metabolic roles of epicardial adipose tissue regarding insulin resistance.

Comparison of arterial stiffness indices measured by pulse wave velocity and pulse wave analysis for predicting cardiovascular and all-cause mortality in a Chinese population.

Arterial stiffness measured by pulse wave velocity and pulse wave analysis has been widely studied in different populations in terms of its correlation with cardiovascular events and all-cause mortality. It remains unknown which arterial stiffness index is better for risk stratification in the general population. We included 4129 participants from Gaoyou County, Jiangsu Province, China, with a median follow-up of 11 years. The primary endpoint was cardiovascular mortality, and the secondary endpoint was all-cause mortality. Harrell's C-index, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) based on the Cox proportional hazards regression model were evaluated to assess predictive discrimination and accuracy. The associations between the 4 indices and cardiovascular mortality remained significant after adjusting for the Framingham Risk Score (FRS) and/or associated risk factors. Considering reclassification based on the newly integrated models (FRS model combined with the 4 indices), NRI for cardiovascular mortality showed that haPWV and baPWV had more significant improvement in reclassification compared with C1 and C2 [NRI with 95% CI: haPWV 0.410 (0.293, 0.523); baPWV 0.447 (0.330, 0.553); C1 0.312 (0.182, 0.454); C2 0.328 (0.159, 0.463); all P < 0.05]. This study showed that pulse wave velocity (haPWV and baPWV) provides better discrimination of long-term risk than arterial elasticity indices (C1 and C2) in the general population.

Association of flavonoid intake with coronary artery disease risk in the older population based on the National Health and Nutrition Examination Survey.

We investigated the association between flavonoid intake and coronary artery disease (CAD) risk in older adults. Data were extracted from the National Health and Nutrition Examination Survey (age ≥ 70 years; 2007-2010 and 2017-2018; n = 2 417). The total flavonoid and flavonoid subclass intake was calculated using validated food frequency questionnaires. The association between flavonoid intake and CAD risk was examined using generalized linear models with restricted cubic spline models. After multivariate adjustment, anthocyanin intake was positively associated with CAD risk; no significant associations were observed between other flavonoid subcategories and endpoint outcomes. Anthocyanins exhibited a non-linear association with CAD risk, and threshold effect analysis showed an inflection point of 15.8 mg/day for anthocyanins. Per unit increase in anthocyanins, the odds of CAD on the left of the inflection point decreased by 2%, while the odds on the right increased by 35.8%. Excessive flavonoid intake may increase CAD risk in the older population.

Risk of hyperkalaemia in patients with type 2 diabetes mellitus prescribed with SGLT2 versus DPP-4 inhibitors.

AIMS: To investigate the risk of hyperkalaemia in new users of sodium-glucose cotransporter 2 (SGLT2) inhibitors vs. dipeptidyl peptidase-4 (DPP-4) inhibitors among patients with type 2 diabetes mellitus (T2DM). METHODS AND RESULTS: Patients with T2DM who commenced treatment with an SGLT2 or a DPP-4 inhibitor between 2015 and 2019 were collected. A multivariable Cox proportional hazards analysis was applied to compare the risk of central laboratory-determined severe hyperkalaemia, hyperkalaemia, hypokalaemia (serum potassium ≥6.0, ≥5.5, and <3.5 mmol/L, respectively), and initiation of a potassium binder in patients newly prescribed an SGLT2 or a DPP-4 inhibitor. A total of 28 599 patients (mean age 60 ± 11 years, 60.9% male) were included after 1:2 propensity score matching, of whom 10 586 were new users of SGLT2 inhibitors and 18 013 of DPP-4 inhibitors. During a 2-year follow-up, severe hyperkalaemia developed in 122 SGLT2 inhibitor users and 325 DPP-4 inhibitor users. Use of SGLT2 inhibitors was associated with a 29% reduction in incident severe hyperkalaemia [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.58-0.88] compared with DPP-4 inhibitors. Risk of hyperkalaemia (HR 0.81, 95% CI 0.71-0.92) and prescription of a potassium binder (HR 0.74, 95% CI 0.67-0.82) were likewise decreased with SGLT2 inhibitors compared with DPP-4 inhibitors. Occurrence of incident hypokalaemia was nonetheless similar between those prescribed an SGLT2 inhibitor and those prescribed a DPP-4 inhibitor (HR 0.90, 95% CI 0.81-1.01). CONCLUSION: Our study provides real-world evidence that compared with DPP-4 inhibitors, SGLT2 inhibitors were associated with lower risk of hyperkalaemia and did not increase the incidence of hypokalaemia in patients with T2DM.

Low lean mass with obesity in older adults with hypertension: prevalence and association with mortality rate.

BACKGROUND: The influence of sarcopenic obesity (SO) on overall survival in older adults with hypertension has not been addressed. The aim of this study was to investigate the prevalence and mortality predictive value of various body composition phenotypes, focusing mainly on SO, in older adults with hypertension. METHODS: We included 1105 hypertensive patients aged ≥ 60 years from the National Health and Nutrition Examination Survey 1999-2004. Sarcopenia was broadly defined based on low lean mass (LLM; as measured by dual-energy X-ray absorptiometry), and was defined using appendicular lean mass (ALM) divided by height squared (ALM/height2), weight (ALM/weight), and body mass index (BMI; ALM/BMI), respectively. Obesity was defined as BMI ≥ 30 kg/m2, body fat percentage ≥ 30/42%, or waist circumference ≥ 102/88 cm. The prevalence of LLM with obesity was estimated according to each ALM index (ALMI). Multivariable Cox regression analysis and sensitivity analysis were used to examine the association between various body composition phenotypes and all-cause mortality. RESULTS: In older adults with hypertension, the prevalence of LLM with obesity by the ALM/height2 index (9.8%) was lower relative to the ALM/weight (11.7%) and ALM/BMI indexes (19.6%). After a median follow-up of 15.4 years, 642 deaths occurred. In the fully adjusted models, LLM with obesity was significantly associated with a higher risk of all-cause mortality (hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.14-2.49, P = 0.008; HR 1.48, 95% CI 1.04-2.10, P = 0.028; HR 1.30, 95% CI 1.02-1.66, P = 0.037; respectively) compared with the normal body phenotype, with no statistical differences found in individuals with LLM or obesity alone. Sensitivity analysis confirmed the robustness of the results. CONCLUSIONS: The prevalence of LLM with obesity markedly differed in older adults with hypertension according to the 3 different ALMIs, varying from 9.8%, 11.7%, to 19.6%. Patients with both LLM and obesity had a higher risk of all-cause mortality. Further large, prospective, cohort studies are warranted to validate these findings and uncover underlying mechanisms.

Association of Blood Trace Elements Levels with Cardiovascular Disease in US Adults: a Cross-Sectional Study from the National Health and Nutrition Examination Survey 2011-2016.

We aimed to explore the overall association between trace elements and cardiovascular disease (CVD) and its types in humans. A total of 5101 participants' blood samples from the 2011-2016 National Health and Nutrition Examination Survey were included. Biochemical data were collected from laboratory tests conducted at mobile screening centers. After assessing linearity, weighted logistic regression estimated the association between trace elements and various CVD types. Weighted quantile sum (WQS) regression and quantile-based g-computation (Qgcomp) evaluated the overall relationship between biological trace elements and CVD types. After fully adjusting for confounding factors, the odds ratios of overall CVD morbidity corresponding to the second, third, and fourth quartiles of higher selenium (Se) concentration were 0.711 (95% CI, 0.529-0.956, p = 0.024), 0.734 (95% CI, 0.546-0.987, p = 0.041), and 0.738 (95% CI, 0.554-0.983, p = 0.038), respectively. Moreover, an increase in the concentration of copper (Cu) was associated with an increased risk of stroke (95% CI, 1.012-1.094, p = 0.01), heart failure (95% CI, 1.001-1.095, p = 0.046), and heart attack (95% CI, 1.001-1.083, p = 0.046). As the concentration of trace elements in the body increased, there was a significant positive association between Cu and CVD prevalence. On the other hand, Se and zinc were negatively associated with CVD prevalence. A nonlinear relationship between Se and CVD was found, and an appropriate Se intake may reduce the risk of CVD. Cu levels positively correlated with CVD risk. However, prospective cohort studies are warranted to confirm the causal effects of the micronutrients on CVD and its types.

Associations of urinary di(2-ethylhexyl) phthalate metabolites with lipid profiles among US general adult population.

Background: Di(2-ethylhexyl) phthalate (DEHP) a parent compound that is metabolized into 4 phthalate metabolites, which correlate to adverse cardio-metabolic risk factors. This study aimed to explore the links between urinary DEHP metabolites and serum lipids in the U.S. general adult population. Methods: In this cross-sectional study, data on 11 urinary phthalate metabolites from the 2005-2018 National Health and Nutrition Examination Surveys (NHANES) were analyzed. Multivariate linear regression and restricted cubic spline (RCS) were used to examine the relationship between phthalate metabolites [specific DEHPs: mono-(2-ethyl-5-carboxy-pentyl) phthalate (MECPP), mono-(2-ethyl-5-hydroxy-hexyl) phthalate (MEHHP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-oxo-hexyl) phthalate (MEOHP)] and serum lipids (triglycerides [TG], total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], and high-density lipoprotein cholesterol [HDL-C]). To identify mixed exposure effects of phthalate metabolites, quantile g-computation (QG-C) and weighted quantile sum (WQS) regression were employed for the lipid profiles. Results: A total of 9141 adults were included in the analysis. MECPP, MEHHP, MEHP, and MEOHP in the highest quartile had a negative relationship with HDL-C compared to the lowest quartile (All P for trend <0.05). TG showed a significant positive relation with MECPP, MEHHP, and MEOHP (All P for trend <0.05), but there was no notable association with MEHP. RCS demonstrated a linear relationship of DEHP metabolites with HDL-C, TC, TG, and LDL-C (all P for nonlinearity >0.05). The WQS index of DEHP metabolites showed independent correlations with HDL-C [ß = -0.26, 95%CI (-0.43, -0.09), P = 0.002], TC [ß = 0.55, 95%CI (0.13, 0.98), P = 0.011], and TG [ß = 2.40, 95%CI (0.85, 3.96), P = 0.003]. Conclusion: Our study suggests that environmental DEHP exposure may affect serum HDL-C and TG levels in the general adult population. Further research is warranted to confirm these findings and illuminate the underlying mechanisms of DEHP exposure on lipids.

Integrated Bioinformatic Analyses Reveal Immune Molecular Markers and Regulatory Networks for Cerebral Ischemia-Reperfusion.

BACKGROUND: Cerebral ischemia-reperfusion injury (CIR) following a stroke results in secondary damage and is a leading cause of adult disability. The present study aimed to identify hub genes and networks in CIR to explore potential therapeutic agents for its treatment. METHODS: Differentially expressed genes based on the GSE23163 dataset were identified, and weighted gene co-expression network analysis was performed to explore co-expression modules associated with CIR. Hub genes were identified by intersecting immune gene profiles, differentially expressed genes, and modular genes. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, and transcription factor-microRNA-gene regulatory network analyses were then conducted in selected crucial modules. Subsequently, their expression levels in animal models were verified using real-time quantitative polymerase chain reaction and Western blotting. Finally, potential drug molecules were screened for, and molecular docking simulations were performed to identify potential therapeutic targets. RESULTS: Seven hub genes-namely, Ccl3, Ccl4, Ccl7, Cxcl1, Hspa1a, Cd14, and Socs3-were identified. Furthermore, we established a protein interaction network using the STRING database and found that the core genes selected through the cytohubba plugin remained consistent. Animal experiments showed that at the transcriptional level, all seven genes showed significant differences (p < 0.001, fold change vs sham, 5-200). At the translational level, however, only Ccl3, Ccl4, Ccl7, Hspa1a, and Socs3 showed significant differences, while Cxcl1 and Cd14 did not. Nifedipine, with the highest predicted score, was identified as a therapeutic agent and successfully docked with the protein encoded by the hub genes. CONCLUSIONS: The expression of Ccl3, Ccl4, Ccl7, Hspa1a, and Socs3 was significantly different in CIR tissues compared to normal tissues both at the transcriptional and translational levels. Systems biology approaches indicated that these could be possible CIR marker genes, providing a stepping stone for further experimental studies.

Negative association between triglyceride glucose index and BMI-adjusted skeletal muscle mass index in hypertensive adults.

BACKGROUND: The triglyceride glucose (TyG) index, an indicator of insulin resistance, is often associated with adverse outcomes in various cardiovascular diseases, while hypertension is associated with an increased risk of cardiovascular diseases. As the loss of muscle mass in people with hypertension is poorly understood, the current study aimed to explore the relationship between TyG index and muscle mass in hypertensive population. METHODS: We analyzed data from hypertensive adult participants in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. The TyG index and body mass index (BMI)-adjusted skeletal muscle mass index (SMI) were calculated and the relationship between the two was evaluated using multivariable linear regression and restricted cubic spline (RCS) regression models. RESULTS: A total of 1633 participants in the dataset were included for the final analysis. In the multivariable regression analysis, the adjusted ß of SMI with a 95% confidence interval (CI) for the highest TyG index quartile was - 5.27 (- 9.79 to - 0.75), compared with the lowest quartile. A negative linear relationship between TyG index and SMI was plotted by RCS regression (nonlinear P = 0.128). Stratified models of non-smoking women of different ages also demonstrated that SMI decreased as TyG index increased (all P for trend < 0.05). CONCLUSION: This linear and negative correlation between TyG index and SMI in hypertensive patients suggests that insulin resistance adversely affects muscle mass.

Prognostic value of ventricle epicardial fat volume by cardiovascular magnetic resonance in chronic heart failure.

The purpose of this study is to explore the prognostic values of ventricle epicardial fat volume (EFV) calculated by cardiac magnetic resonance in patients with chronic heart failure (CHF). A total of 516 patients with CHF (left ventricular ejection fraction ≤ 50%) were recruited, and 136 (26.4%) of whom experienced major adverse cardiovascular events (MACE) within median follow-up of 24 months. The target marker-EFV was found to be associated with MACE in both univariate and multivariable analysis adjusted for various clinical variables (p < 0.01), regardless as a continuous variable and categorized by X-tile program. EFV also showed promising predictive ability, with an area under the curve of 0.612, 0.618, and 0.687 for the prediction of 1-year, 2-year, and 3-year MACE, respectively. In conclusion, EFV could be a useful prognostic marker for CHF patients, helping to identify individuals at greater risk of MACE.

Construction of a web-based dynamic nomogram for predicting the prognosis in acute heart failure.

AIMS: The early identification and appropriate management may provide clinically meaningful and substained benefits in patients with acute heart failure (AHF). This study aimed to develop an integrative nomogram with myocardial perfusion imaging (MPI) for predicting the risk of all-cause mortality in AHF patients. METHODS AND RESULTS: Prospective study of 147 patients with AHF who received gated MPI (59.0 [47.5, 68.0] years; 78.2% males) were enrolled and followed for the primary endpoint of all-cause mortality. We analysed the demographic information, laboratory tests, electrocardiogram, and transthoracic echocardiogram by the least absolute shrinkage and selection operator (LASSO) regression for selection of key features. A multivariate stepwise Cox analysis was performed to identify independent risk factors and construct a nomogram. The predictive values of the constructed model were compared by Kaplan-Meier curve, area under the curves (AUCs), calibration plots, continuous net reclassification improvement, integrated discrimination improvement, and decision curve analysis. The 1, 3, and 5 year cumulative rates of death were 10%, 22%, and 29%, respectively. Diastolic blood pressure [hazard ratio (HR) 0.96, 95% confidence interval (CI) 0.93-0.99; P = 0.017], valvular heart disease (HR 3.05, 95% CI 1.36-6.83; P = 0.007), cardiac resynchronization therapy (HR 0.37, 95% CI 0.17-0.82; P = 0.014), N-terminal pro-B-type natriuretic peptide (per 100 pg/mL; HR 1.02, 95% CI 1.01-1.03; P < 0.001), and rest scar burden (HR 1.03, 95% CI 1.01-1.06; P = 0.008) were independent risk factors for patients with AHF. The cross-validated AUCs (95% CI) of nomogram constructed by diastolic blood pressure, valvular heart disease, cardiac resynchronization therapy, N-terminal pro-B-type natriuretic peptide, and rest scar burden were 0.88 (0.73-1.00), 0.83 (0.70-0.97), and 0.79 (0.62-0.95) at 1, 3, and 5 years, respectively. Continuous net reclassification improvement and integrated discrimination improvement were also observed, and the decision curve analysis identified the greater net benefit of the nomogram across a wide range of threshold probabilities (0-100% at 1 and 3 years; 0-61% and 62-100% at 5 years) compared with dismissing the included factors or using either factor alone. CONCLUSIONS: A predictive nomogram for the risk of all-cause mortality in patients with AHF was developed and validated in this study. The nomogram incorporated the rest scar burden by MPI is highly predictive, and may help to better stratify clinical risk and guide treatment decisions in patients with AHF.

Associations of Serum Carotenoids With Risk of All-Cause and Cardiovascular Mortality in Hypertensive Adults.

Background Systemic oxidative stress is involved in the development of hypertension, whereas carotenoids are a group of natural antioxidants. Our study aims to evaluate the relationships between the serum concentrations of major carotenoids and mortality in hypertensive adults. Methods and Results Data on 5 serum carotenoids from the National Health and Nutrition Examination Survey (NHANES) III and NHANES 2001-2006 were included. Outcome measures (all-cause and cardiovascular mortality) were identified from the National Death Index through December 31, 2019. Multiple Cox proportional hazards regression and restricted cubic spline analyses were performed to determine the association between carotenoid levels and outcomes. A total of 8390 hypertensive adults were included in the analysis. At a median follow-up duration of 16.6 years, all-cause and cardiovascular mortality occurred in 4005 (47.74%) and 1205 (14.36%) participants, respectively. Compared with the lowest quartiles, the highest quartiles of 5 major serum carotenoids were associated with lower risk of all-cause mortality, with multivariable-adjusted hazard ratios (HRs) of 0.63 (95% CI, 0.56-0.71) for α-carotene, 0.70 (95% CI, 0.61-0.80); for ß-carotene, 0.67 (95% CI, 0.58-0.76); for ß-cryptoxanthin, 0.74 (95% CI, 0.64-0.86) for lycopene; and 0.72 (95% CI, 0.63-0.83) for lutein/zeaxanthin. For cause-specific mortality, this association with the fourth quartile of serum carotenoids was evident for a reduced rate of cardiovascular mortality, with a 32% reduction for α-carotene (HR, 0.68 [95% CI, 0.55-0.86]), a 29% reduction for ß-cryptoxanthin (HR, 0.71 [95% CI, 0.56-0.89]), and a 26% reduction for lycopene (HR, 0.74 [95% CI, 0.59-0.94]), but not for ß-carotene and lutein/zeaxanthin. In addition, we found that serum α-carotene, ß-carotene, ß-cryptoxanthin, and lutein/zeaxanthin levels were nonlinearly related to all-cause mortality with inflection points of 2.43, 8.49, 5.12, and 14.17 µg/dL, respectively. Serum α-carotene, ß-cryptoxanthin, and lutein/zeaxanthin concentrations showed nonlinear associations with cardiovascular mortality with inflection points of 2.31, 5.26, and 15.40 µg/dL, respectively. Conclusions Findings suggest that higher serum carotenoid concentrations were associated with lower risks of all-cause and cardiovascular mortality in hypertensive adults.

Nonlinear associations of serum cobalamin with risk of all-cause and cardiovascular mortality in hypertensive adults.

Our study aims to evaluate the associations between the serum cobalamin (vitamin B12) and related biomarkers with mortality in hypertensive adults. Data on serum cobalamin from the National Health and Nutrition Examination Survey (NHANES) 1999-2006 and 2011-2014 were included. Mortality status was linked to National Death Index mortality data through 31 December, 2019. Cox regression and restricted cubic spline (RCS) analyses were used to determine the hazard ratios (HRs) and 95% CIs for mortality risk. A total of 9934 hypertensive adults were included in the analysis (mean age, 58.1 ± 17.5 years; 4899 [49.3%] men). At 11.0 years of mean follow-up, 935 cardiovascular deaths and 3096 all-cause deaths were identified. Compared to the third quartiles, the first and fourth quartiles of serum cobalamin were associated with risk of cardiovascular mortality, with multivariable-adjusted HRs of 1.26 (1.05-1.53) and 1.40 (1.17-1.68). Similar results were observed in the relationship between serum cobalamin and all-cause mortality. These results were supported by the RCS analysis. The inflection points for the nonlinear associations of serum cobalamin with cardiovascular and all-cause mortality were 649.9 pg/mL and 577.2 pg/mL, respectively. In addition, compared with the second quartile of circulating methylmalonic acid (MMA, a cobalamin-deficiency marker), this association with the fourth quartile was evident for an increased rate of cardiovascular and all-cause mortality, with 111% (HR = 2.11, 1.71-2.61) and 73% (HR = 1.73, 1.55-1.93) increase. Findings suggest that both lower and higher serum cobalamin concentrations were associated with a higher risk of cardiovascular and all-cause mortality in hypertensive adults. This study was a prospective cohort study that included serum cobalamin data from 9934 hypertensive adults from the NHANES from 1999-2006 and 20011-2014. Findings suggested that both lower and higher serum cobalamin concentrations were associated with a higher risk of cardiovascular and all-cause mortality in hypertensive adults.

Urinary phenols and parabens metabolites associated with cardiovascular disease among adults in the United States.

The field of environmental health has begun to examine the effects of higher-order chemical combinations. The current literature lacks studies exploring associations between multiple organic chemical mixtures and cardiometabolic diseases (CVDs). This study aimed to evaluate associations between urinary phenols, parabens metabolites, and total and individual CVDs among a nationally representative sample of adults in the US. This cross-sectional study analyzed 7 urinary chemicals detected among the general population from the 2005-2016 National Health and Nutrition Examination Survey (NHANES, n=10,428). Multivariate logistic regression and weighted quantile sum (WQS) regression were applied to examine relationships between phenols and parabens metabolites, alone and in combination, and total and individual CVDs prevalence. Compared with the lowest quartile, URBPA (OR: 1.52; 95% CI: 1.20-1.91; P=0.001) levels in the highest quartile were independently associated with increased total CVD. The WQS index of phenols and parabens mixtures were independently correlated with total CVD (adjusted odds ratios [OR]: 1.16; 95% confidence interval [CI]:1.06-1.28; P=0.002), angina (adjusted OR: 1.30; 95% CI: 1.07-1.59; P=0.009), and heart attack (adjusted OR: 1.30; 95% CI: 1.12-1.51, P<0.001). Urinary bisphenol A (URBPA, weight=0.636) was the most heavily weighted component in the total CVD model. Restricted cubic spline regression demonstrated positive correlations and nonlinear associations between URBPA and both total CVD (P for nonlinearity=0.032) and individual CVD (heart attack; P for nonlinearity=0.031). Our findings suggested that high combined levels of phenols, and parabens are associated with an increased CVD risk, with URBPA contributing the highest risk.

Associations of thiocyanate, nitrate, and perchlorate exposure with dyslipidemia: a cross-sectional, population-based analysis.

The aim of this study was to assess the associations of urinary thiocyanate, nitrate, and perchlorate concentrations with dyslipidemia, individually and in combination, which has not previously been studied. Data from the 2001-2002 and 2005-2016 National Health and Nutrition Examination Surveys (NHANES) were analyzed in this cross-sectional study. The dependent variables were continuous serum lipid variables (triglycerides [TG], total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], non-HDL-C, and apolipoprotein B [Apo B]) and binary serum lipid variables, with the latter reflecting dyslipidemia (elevated TG, ≥ 150 mg/dL; elevated TC, ≥ 200 mg/dL; elevated LDL-C, ≥ 130 mg/dL; lowered HDL-C, < 40 mg/dL in men and < 5 0 mg/dL in women; elevated non-HDL-C, ≥ 160 mg/dL; and elevated Apo B, ≥ 130 mg/dL). Multivariate logistic, linear, and weighted quantile sum (WQS) regression analyses were used to explore the associations of thiocyanate, nitrate, and perchlorate with the continuous and binary serum lipid variables. The linearity of the associations with the binary serum lipid variables was assessed using restricted cubic spline (RCS) regression. A total of 15,563 adults were included in the analysis. The multivariate linear and logistic regression analyses showed that thiocyanate was positively associated with multiple continuous (TG, TC, LDL-C, non-HDL-C, and Apo B, but not HDL-C) and binary (elevated TG, TC, LDL-C, and non-HDL-C) serum lipid variables, whereas perchlorate was negatively associated with elevated LDL-C. Multivariate RCS logistic regression revealed a linear dose-response relationship between thiocyanate and elevated TG, TC, LDL-C, non-HDL-C, and Apo B, but a nonlinear relationship with lowered HDL-C (inflection point = 1.622 mg/L). WQS regression showed that a mixture of thiocyanate, nitrate, and perchlorate was positively associated with all binary serum lipid variables except for Apo B. Our findings indicate that urinary thiocyanate, nitrate, and perchlorate concentrations, individually and in combination, were associated with dyslipidemia.

CHA2DS2-VASc score for in-hospital recurrence risk stratification in patients with myocardial infarction.

Background: Using the CHA2DS2-VASc score to recognize the risk of stroke in patients with atrial fibrillation has been well-established. However, few studies have assessed whether the CHA2DS2-VASc score has a similar predictive value in recurrence after myocardial infarction (MI). Methods: We conducted a retrospective observational cohort study of adult inpatients with MI. The CHA2DS2-VASc and modified CHA2DS2-VASc (MCHA2DS2-VASc) scores of all patients were calculated. The associations of both scores with recurrent MI were analyzed. Results: A total of 6,700 patients with MI (60.0 ± 11.1 years, 77.2% men) were enrolled, and 759 (11.3%) presented a definite recurrence during hospitalization. After multivariable adjustment by logistic regression in patients with MI, the CHA2DS2-VASc and MCHA2DS2-VASc scores were independently associated with recurrence. The MCHA2DS2-VASc score showed a better predictive value for risk of recurrence than that of CHA2DS2-VASc in overall [area under the receiver operating characteristic curve (AUC) 0.757 vs. 0.676] or male patients (AUC 0.759 vs. 0.708). MCHA2DS2-VASc was superior to CHA2DS2-VASc for identifying "truly high-risk" patients with MI, regardless of overall patients or sex-specific subgroups. The two scores had a similar focus on the identification of "low-risk" patients in overall or women, but not in men. Conclusion: The CHA2DS2-VASc and MCHA2DS2-VASc scores for predicting recurrence are validated in patients with MI. However, MCHA2DS2-VASc could be more helpful to secondary prevention than CHA2DS2-VASc after MI, especially in men. The superiority of MCHA2DS2-VASc compared with CHA2DS2-VASc in women is just more discriminatory for "truly high-risk" patients.

Associations of Inflammation with Risk of Cardiovascular and All-Cause Mortality in Adults with Hypertension: An Inflammatory Prognostic Scoring System.

Background: Inflammation is one of the major pathways in the progression of hypertension (HTN), and the related inflammatory markers have demonstrated certain predictive values. The current study aimed to integrate these markers to construct an inflammatory prognostic scoring (IPS) system and to assess the prognostic values of IPS in patients with HTN. Methods: A total of 9846 adult participants with HTN from NHANES 1999-2010 were enrolled and followed up. Demographic characteristics and the related laboratory results for the 12 inflammatory markers were collected. LASSO-COX regression, Kaplan-Meier, restricted cubic spline COX regression (RCS), receiver operator characteristic curve (ROC), and random survival forests (RSF) analysis were applied to explore the values of individual and IPS parameters. Results: At the census date of follow-up, 2387 (24.2%) were identified as all-cause deaths and 484 (4.9%) as cardiovascular deaths. All inflammatory markers showed certain prognostic values. Then, based on the LAASO analysis, LDH, ALP, LYM, NLR, MLR, SIRI, and RDW were included in the construction of the IPS system. The higher IPS had significantly worse long-term prognosis in Kaplan-Meier analysis (p log-rank <0.001). Also, IPS remained an independent prognosticator compared to the lowest quartile (All p for trend <0.001), and the ROC showed satisfactory values in the long-term prognosis of both cardiovascular and all-cause mortality. RCS further showed a linear association of IPS with cardiovascular mortality and all-cause mortality (p for non-linearity >0.05). Two different algorithms of RSF, variable importance and minimal depth, to evaluate the prognostic importance showed that IPS was the best in survival prediction. Conclusion: Our results highlight that a higher IPS (system integrating the inflammatory markers) was associated with the increased risk of cardiovascular and all-cause mortality in patients with HTN, suggesting that IPS is a useful method for risk stratification in HTN.