Association between glucose levels and all-cause mortality in cancer survivors: findings from NHANES 1999-2018.

BACKGROUND: Hyperglycemia is a rapidly increasing risk factor for cancer mortality worldwide. However, the dose‒response relationship between glucose levels and all-cause mortality in cancer survivors is still uncertain. METHODS: We enrolled 4,491 cancer survivors (weighted population 19,465,739) from the 1999-2019 National Health and Nutrition Examination Survey (NHANES). Cancer survivors were defined based on the question of whether they had ever been diagnosed with cancer by a doctor or a health professional. Hemoglobin A1c (HbA1c) was selected in this study as a stable marker of glucose level. Mortality was ascertained by linkage to National Death Index records until December 31, 2019. Cox proportional hazard, Kaplan‒Meier survival curves and Restricted cubic spline regression models were used to evaluate the associations between HbA1c and all-cause mortality risk in cancer survivors. RESULTS: In NHANES, after adjusting for confounders, HbA1c had an independent nonlinear association with increased all-cause mortality in cancer survivors (nonlinear P value < 0.05). The threshold value for HbA1c was 5.4%, and the HRs (95% CI) below and above the threshold value were 0.917 (0.856,0.983) and 1.026 (1.010,1.043), respectively. Similar associations were found between fasting glucose and all-cause mortality in cancer survivors, and the threshold value was 5.7 mmol/L. CONCLUSIONS: HbA1c was nonlinearly associated with all-cause mortality in cancer survivors, and the critical value of HbA1c in decreased mortality was 5.4%, suggesting optimal glucose management in cancer survivors may be a key to preventing premature death in cancer survivors.

STING1-accelerated vascular smooth muscle cell senescence-associated vascular calcification in diabetes is ameliorated by oleoylethanolamide via improved mitochondrial DNA oxidative damage.

Vascular calcification is a prevalent hallmark of cardiovascular risk in elderly and diabetic individuals. Senescent vascular smooth muscle cells (VSMCs) participate in calcification; however, the associated underlying mechanisms remain unknown. Aberrant activation of the cytosolic DNA sensing adaptor stimulator of interferon gene 1 (STING1) caused by cytosolic DNA, particularly that leaked from damaged mitochondria, is a catalyst for aging-related diseases. Although oleoylethanolamide (OEA) is an endogenous bioactive lipid mediator with lipid overload-associated vasoprotective effects, its benefit in diabetic vascular calcification remains uncharacterized. This study focused on the role of STING1 in mitochondrial dysfunction-mediated calcification and premature VMSC senescence in diabetes and the effects of OEA on these pathological processes. In diabetic in vivo rat/mouse aorta calcification models and an in vitro VSMC calcification model induced by Nε-carboxymethyl-lysine (CML), senescence levels, STING1 signaling activation, and mitochondrial damage markers were significantly augmented; however, these alterations were markedly alleviated by OEA, partially in a nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent manner, and similar anti-calcification and senescence effects were observed in STING1-knockout mice and STING1-knockdown VSMCs. Mechanistically, mitochondrial DNA (mtDNA) damage was aggravated by CML in a reactive oxygen species-dependent manner, followed by mtDNA leakage into the cytosol, contributing to VSMC senescence-associated calcification via STING1 pathway activation. OEA treatment significantly attenuated the aforementioned cytotoxic effects of CML by enhancing cellular antioxidant capacity through the maintenance of Nrf2 translocation to the nucleus. Collectively, targeting STING1, a newly defined VSMC senescence regulator, contributes to anti-vascular calcification effects.

Synergistic effect of lipoprotein(a) and high-sensitivity C-reactive protein on the risk of all-cause and cardiovascular death in patients with acute myocardial infarction: a large prospective cohort study.

Objective: Although lipoprotein(a) [Lp(a)] and high-sensitivity C-reactive protein (Hs-CRP) are closely associated with the mortality of acute myocardial infarction (AMI), their synergistic effect on the risk of death remains unknown. Therefore, this study aimed to explore the combined effect of Lp(a) and Hs-CRP on the incidence of all-cause and cardiovascular death in AMI patients. Methods: A comprehensive cohort study enrolled 912 AMI patients, categorizing them into four groups based on Lp(a) and Hs-CRP levels: Group 1 [Lp(a) < 30 mg/dL & Hs-CRP < 2 mg/L], Group 2 [Lp(a) < 30 mg/dL & Hs-CRP ≥ 2 mg/L], Group 3 [Lp(a) ≥ 30 mg/dL & Hs-CRP < 2 mg/L], and Group 4 [Lp(a) ≥ 30 mg/dL & Hs-CRP ≥ 2 mg/L]. Cox regression analysis, Kaplan-Meier survival analysis and sensitivity analysis were employed to determine the combined effects of Lp(a) and Hs-CRP on the risk of all-cause and cardiovascular death. Results: Over a median observation period of 38.98 months, 217 patients passed away, with 137 deaths attributed to cardiovascular causes. The multivariate Cox regression analysis revealed that in the comprehensively adjusted Model 3, only Lp(a) and the combination of Lp(a) and Hs-CRP exhibited a strong association with cardiovascular death risk. Specifically, for Lp(a) levels ≥ 30 mg/dL compared to < 30 mg/dL, the hazard ratio (HR) was 2.434 with a 95% confidence interval (CI) of 1.653-3.583 (P < 0.001); for log10(Lp(a)), the HR was 2.630 with a 95% CI of 1.530-4.523 (P < 0.001); for Group 4 versus Group 1, the HR was 2.346 with a 95% CI of 1.054-5.220 (P = 0.037); and for Group 4 versus Groups 1 + 2 + 3, the HR was 1.878 with a 95% CI of 1.284-2.748 (P = 0.001). Sensitivity analysis indicated that the synergy between Lp(a) and Hs-CRP continued to be independently associated with the risk of cardiovascular death. For Group 3 versus Group 1, the HR was 3.353 with a 95% CI of 1.133-9.917 (P = 0.029); for Group 4 versus Group 1, the HR was 3.710 with a 95% CI of 1.466-9.392 (P = 0.006); and for Group 4 versus Groups 1 + 2 + 3, the HR was 2.433 with a 95% CI of 1.620-3.656 (P < 0.001). Conclusions: Compared to elevated levels of either Lp(a) or Hs-CRP alone, the concurrent high levels of both significantly increased the risk of cardiovascular death in patients with AMI, underscoring the importance of considering their combined effects in the prognostic management of AMI patients.

Association of serum five heavy metals level with all-cause and cause-specific mortality: a large population-based cohort study.

The study aimed to explore the association between five heavy metals exposure (Cadmium, Lead, Mercury, Manganese, and Selenium) and mortality [all-cause, cardiovascular disease (CVD), and cancer-related]. We integrated the data into the National Health and Nutrition Examination Survey from 2011 to 2018 years. A total of 16,092 participants were recruited. The link between heavy metals exposure and mortality was analyzed by constructing a restricted cubic spline (RCS) curve, Cox proportional hazard regression model, and subgroup analysis. The RCS curve was used to show a positive linear relationship between Cadmium, Lead, and all-cause mortality. In contrast, there was a negative linear correlation between Mercury and all-cause mortality. Additionally, Manganese and Selenium also had a J-shaped and L-shaped link with all-cause mortality. The positive linear, positive linear, negative liner, J-shaped, and L-shaped relationships were observed for Cadmium, Lead, Mercury, Manganese, and Selenium and CVD mortality, respectively. Cadmium, Lead, Mercury, and Selenium were observed to exhibit positive linear, U-shaped, negative linear, and L-shaped relationships with cancer-related mortality, respectively. There was an increase and then a decrease in the link between Manganese and cancer-related morality. This study revealed the correlation between the content of different elements and different types of mortality in the U.S. general population.

How safe are proprotein convertase subtilisinekexin type 9 inhibitors in diabetes?

PURPOSE OF REVIEW: To examine the safety of proprotein convertase subtilisinekexin type 9 (PCSK9) inhibitors in patients with diabetes, specifically focusing on their impact on glucose metabolism. RECENT FINDINGS: Patients with diabetes often require intensified lipid-lowering therapy. PCSK9 inhibitors can reduce low-density lipoprotein cholesterol (LDL-C) concentrations by approximately 60%, and significantly reduce cardiovascular risk when added to statin therapy. Some studies have suggested an association between low LDL-C levels and an increased risk of new-onset diabetes, and genetics has almost consistently shown an increased glucose concentration and risk of diabetes. Most clinical trials have not demonstrated a deterioration in glycaemic control in patients with diabetes after the use of PCSK9 inhibitors, and they do not lead to other significant treatment-emergent adverse events. SUMMARY: Although the majority of patients with diabetes are undergoing background statin therapy, which may mask potential adverse effects of PCSK9 inhibitors on glycaemic control, current data suggest that the benefits outweigh the risks for diabetic patients using PCSK9 inhibitors. Considering the different nature of genetic studies and of clinical trials, close monitoring of glucose parameters is necessary, especially in individuals with prediabetes.

The supplementation of Rothia as a potential preventive approach for bone loss in mice with ovariectomy-induced osteoporosis.

There is an inseparable link between bone metabolism and gut microbiota, and the supplementation of probiotics exhibits a significant role in maintaining the homeostasis of gut microbiota and inhibiting bone loss. This study aims to explore the preventive and therapeutic potentials and the specific mechanisms of Rothia on osteoporosis. The mice models of osteoporosis induced by ovariectomy (OVX) were built, and the regular (once a day) and quantitative (200 µL/d) gavage of Rothia was performed for 8 weeks starting from 1 week after OVX. Microcomputed tomography was used to analyze the bone mass and bone microstructure of mice in each group after sacrifice. Histological staining and immunohistochemistry were then applied to identify the expression of pro-inflammatory cytokines, intestinal permeability, and osteogenic and osteoclastic activities of mice. The collected feces of mice in each group were used for 16S rRNA high-throughput sequencing to detect the alterations in composition, abundance, and diversity of gut microbiota. This study demonstrated that the gavage of Rothia alleviated bone loss in mice with OVX-induced osteoporosis, improved OVX-induced intestinal mucosal barrier injury, optimized intestinal permeability (zonula occludens protein 1 and occludin), reduced intestinal inflammation (tumor necrosis factor-α and interleukin-1ß), and regulated imbalance of gut microbiota. Based on "gut-bone" axis, this study revealed that regular and quantitative gavage of Rothia can relieve bone loss in mice with OVX-induced osteoporosis by repairing the intestinal mucosal barrier injury, optimizing the intestinal permeability, inhibiting the release of pro-inflammatory cytokines, and improving the disorder of gut microbiota.

Empagliflozin ameliorates vascular calcification in diabetic mice through inhibiting Bhlhe40-dependent NLRP3 inflammasome activation.

Type 2 diabetes mellitus (T2DM) patients exhibit greater susceptibility to vascular calcification (VC), which has a higher risk of death and disability. However, there is no specific drug for VC therapy. NLRP3 inflammasome activation as a hallmark event of medial calcification leads to arterial stiffness, causing vasoconstrictive dysfunction in T2DM. Empagliflozin (EMPA), a sodium-glucose co-transporter 2 inhibitor (SGLT2i), restrains hyperglycemia with definite cardiovascular benefits. Given the anti-inflammatory activity of EMPA, herein we investigated whether EMPA protected against VC in the aorta of T2DM mice by inhibiting NLRP3 inflammasome activation. Since db/db mice receiving a normal diet developed VC at the age of about 20 weeks, we administered EMPA (5, 10, 20 mg·kg-1·d-1, i.g) to 8 week-old db/db mice for 12 weeks. We showed that EMPA intervention dose-dependently ameliorated the calcium deposition, accompanied by reduced expression of RUNX2 and BMP2 proteins in the aortas. We found that EMPA (10 mg·kg-1·d-1 for 6 weeks) also protected against VC in vitamin D3-overloaded mice, suggesting the protective effects independent of metabolism. We showed that EMPA (10 mg·kg-1·d-1) inhibited the abnormal activation of NLRP3 inflammasome in aortic smooth muscle layer of db/db mice. Knockout (KO) of NLRP3 significantly alleviated VC in STZ-induced diabetic mice. The protective effects of EMPA were verified in high glucose (HG)-treated mouse aortic smooth muscle cells (MOVASs). In HG-treated NLRP3 KO MOVASs, EMPA (1 µM) did not cause further improvement. Bioinformatics and Western blot analysis revealed that EMPA significantly increased the expression levels of basic helix-loop-helix family transcription factor e40 (Bhlhe40) in HG-treated MOVASs, which served as a negative transcription factor directly binding to the promotor of Nlrp3. We conclude that EMPA ameliorates VC by inhibiting Bhlhe40-dpendent NLRP3 inflammasome activation. These results might provide potential significance for EMPA in VC therapy of T2DM patients.

Risk factors for peripheral artery disease and diabetic peripheral neuropathy among patients with type 2 diabetes.

AIMS: To investigate the prevalence of peripheral artery disease (PAD) and diabetic peripheral neuropathy (DPN) and the associated risk factors among Chinese patients with type 2 diabetes mellitus. METHODS: A cross-sectional study was conducted using data between November 1, 2018, and December 31, 2022. PAD was defined as ABI ≤ 0.9. DPN diagnosis involved specialized physician assessments using questionnaires and vibration perception threshold tests. Logistic regression analysis was used to identify related factors. We also evaluated the association between the clustering of risk factors and disease incidence. RESULTS: The study population comprised 13,315 patients (mean age: 63.3 years). 4.9 % of the patients had PAD and 43.9 % had DPN. Multivariate regression analysis revealed advanced age, smoking, hypertension, coronary heart disease, dyslipidemia, elevated HbA1c, and uric acid levels as independent risk factors for PAD. For DPN, independent risk factors included advanced age, female gender, hypertension, coronary heart disease, elevated total cholesterol, triglycerides, lipoprotein(a), fasting plasma glucose, HbA1c, alkaline phosphatase, cystatin C, albumin-to-creatinine ratio, and elevated homocysteine levels, whereas apolipoprotein A was a protective factor. The clustering of risk factors was prevalent and associated with higher disease risk. CONCLUSIONS: Our study contributed to identifying high-risk individuals and improving lower limb health among diabetic individuals.

Global, regional, and national time trends in cancer mortality attributable to high fasting plasma glucose: an age-period cohort analysis.

BACKGROUND: High fasting plasma glucose (HFPG) is the fastest-growing risk factor for cancer deaths worldwide. We reported the cancer mortality attributable to HFPG at global, regional, and national levels over the past three decades and associations with age, period, and birth cohort. METHODS: Data for this study were retrieved from the Global Burden of Disease Study 2019, and we used age-period-cohort modelling to estimate age, cohort and period effects, as well as net drift (overall annual percentage change) and local drift (annual percentage change in each age group). RESULTS: Over the past 30 years, the global age-standardized mortality rate (ASMR) attributable to HFPG has increased by 27.8%. The ASMR in 2019 was highest in the male population in high sociodemographic index (SDI) areas (8.70; 95% CI, 2.23-18.04). The net drift for mortality was highest in the female population in low SDI areas (2.33; 95% CI, 2.12-2.55). Unfavourable period and cohort effects were found across all SDI quintiles. Cancer subtypes such as "trachea, bronchus, and lung cancers", "colon and rectal cancers", "breast cancer" and "pancreatic cancer" exhibited similar trends. CONCLUSIONS: The cancer mortality attributable to HFPG has surged during the past three decades. Unfavourable age-period-cohort effects on mortality were observed across all SDI quintiles, and the cancer mortality attributable to HFPG is expected to continue to increase rapidly in the future, particularly in lower SDI locations. This is a grim global public health issue that requires immediate attention.

Efficacy and safety of PCSK9 inhibitors in patients with diabetes: A systematic review and meta-analysis.

AIMS: Individuals with diabetes have increased cardiovascular risk. Although PCSK9 inhibitors bring about a wide reduction in lipids, there is uncertainty about the effects for diabetic patients. We conducted a systematic review and meta-analysis to assess the efficacy and safety of PCSK9 inhibitors for diabetes. DATA SYNTHESIS: We performed a meta-analysis comparing treatment with PCSK9 inhibitors versus controls up to July 2022. Primary efficacy endpoints were percentage changes in lipid profile parameters. We used random effects meta-analyses to combine data. Subgroups of diabetic patients (by diabetes type, baseline LDL-C, baseline HbA1c and follow-up time) were also compared. We included 12 RCTs comprising 14,702 patients. Mean reductions in LDL-C were 48.20% (95% CI: 35.23%, 61.17%) in patients with diabetes. Reductions observed with PCSK9 inhibitors were 45.23% (95% CI: 39.43%, 51.02%) for non-HDL-cholesterol, 30.39% (95% CI: 24.61%, 36.17%) for total cholesterol, 11.96% (95% CI: 6.73%, 17.19%) for triglycerides, 27.87% (95% CI: 22.500%, 33.17%) for lipoprotein(a), 42.43% (95% CI: 36.81%, 48.06%) for apolipoprotein B; increases in HDL-C of 5.97% (95% CI: 4.59%, 7.35%) were also observed. There was no significant difference in fasting plasma glucose (FPG) (WMD: 2.02 mg/mL; 95% CI: -1.83, 5.87) and HbA1c (WMD: 1.82%; 95% CI: -0.63, 4.27). Use of a PCSK9 inhibitor was not associated with increased risk of treatment-emergent adverse event (TEAE) (p = 0.542), serious adverse event (SAE) (p = 0.529) and discontinuations due to AEs (p = 0.897). CONCLUSIONS: PCSK9 inhibitor therapy should be considered for all diabetic individuals at high risk of atherosclerotic cardiovascular disease. REGISTRATION CODE IN PROSPERO: CRD42022339785.

Neutrophil membrane biomimetic delivery system (Ptdser-NM-Lipo/Fer-1) designed for targeting atherosclerosis therapy.

Atherosclerosis is a progressive inflammatory disease characterised by excessive lipid accumulation and inflammatory cell infiltration and is the basis of most cardiovascular diseases and peripheral arterial diseases. Therefore, an effectively targeted delivery system is urgently needed to deliver ferroptosis-specific inhibitors to the site of arterial plaque and the inflammatory microenvironment. Inspired by the fact that neutrophils can be recruited to arterial plaques under the action of adhesion molecules and chemokines, the authors developed a neutrophil membrane hybrid liposome nano-mimetic system (Ptdser-NM-Lipo/Fer-1) that delivers Ferrostatin-1 (Fer-1) to the atherosclerotic plaque effectively, which is composed of Fer-1-loaded Ptdser-modified liposomes core and neutrophils shell. Fer-1 was released at the AS plaque site to remove reactive oxygen species (ROS) and improve the inflammatory microenvironment. In vitro ROS clearance experiments have shown that 50 µmol/ml Fer-1 can significantly remove ROS produced by H2 O2 -induced MOVAS cells and Ptdser-NM-Lipo/Fer-1 revealed a 3-fold increase in the inhibition rate of ROS than free Fer-1 in induced-RAW264.7, demonstrating its superior ROS-cleaning effect. Based on the interaction of adhesion molecules, such as vascular cell adhesion molecule 1, ICAM-1, P-selectin, E-selectin, and chemokines released in the inflamed site, the aorta in NM-Lipo-treated mice displayed 1.3-fold greater radiant efficiency than platelet membrane-Lipo-treated mice. Meanwhile, due to the modification of the Ptdser, the aorta in Ptdser-NM-Lipo/Fer-1-treated mice exhibited the highest fluorescence intensity, demonstrating its excellent targeting ability for atherosclerosis. Therefore, we present a specific formulation for the treatment of atherosclerosis with the potential for novel therapeutic uses.

Trends in lipid profiles and control of LDL-C among adults with diabetes in the United States: An analysis of NHANES 2007-2018.

BACKGROUND AND AIM: To determine trends in lipid profiles and lipid control in US adults with diabetes and assess variation in these trends across sex and race/ethnicity from 2007 to 2018. METHODS AND RESULTS: Serial cross-sectional analysis of data from diabetic adults participating in the National Health and Nutrition Examination Survey (NHANES; 2007-2008 to 2017-2018). Among the 6116 participants included (weighted mean age, 61.0 years; 50.7% men), age-adjusted TC (p for trend < 0.001), LDL-C (p for trend < 0.001), TG (p for trend = 0.006), TG/HDL-C (p for trend = 0.014) and VLDL-C (p for trend = 0.015) decreased significantly. Age-adjusted LDL-C levels were consistently higher in women than in men over the study period. Age-adjusted LDL-C improved significantly for diabetic whites and blacks but did not change significantly for the other races/ethnicity. Lipid parameters improved for non-coronary heart disease (CHD) diabetic adults, except for HDL-C, while no lipid parameter significantly changed for diabetic adults with concomitant CHD. Among diabetic adults receiving statin therapy, age-adjusted lipid control remained unchanged from 2007 to 2018, as did adults with concomitant CHD. However, age-adjusted lipid control improved significantly for men (p for trend < 0.01) and diabetic Mexican Americans (p for trend < 0.01). In 2015-2018, female diabetic participants receiving statins had lower odds of achieving lipid control (OR: 0.55; 95% CI: 0.35-0.84; P = 0.006) than men. Differences in lipid control across different races/ethnicities no longer existed. CONCLUSIONS: Lipid profiles improved in the US adults with diabetes from 2007 to 2018. Although rates of lipid control did not improve nationally in adults receiving statins, these patterns varied by sex and race/ethnicity.

Association of Systemic Immune Inflammation Index with All-Cause, Cardiovascular Disease, and Cancer-Related Mortality in Patients with Cardiovascular Disease: A Cross-Sectional Study.

Objective: Our research was designed to investigate the relationship between systemic immune inflammation (SII) index and all-cause, cardiovascular disease (CVD), and cancer-related mortality in patients with CVD. Methods: We used the National Health and Nutrition Examination Survey data from 1999 to 2018 to conduct this study. The association between SII index and all-cause, CVD, and cancer-related mortality in patients with CVD was examined using restricted cubic splines (RCS), Cox proportional hazard models, and subgroup analysis, respectively. CVD was defined as a composite of five outcomes of CVD, including coronary heart disease (CHD), congestive heart failure (CHF), angina pectoris, myocardial infarction, and stroke. Additionally, the link between SII index and all-cause, CVD, and cancer-related mortality in patients with a composite of five outcomes of CVD was also explored. Results: In total, 5329 participants were included. The RCS also showed a U-curve correlation between SII index and the all-cause, CVD, and cancer-related mortality in patients with CVD. As compared with the individuals with lowest quartile of SII index, hazard ratios with 95% confidence intervals for all-cause, CVD, and cancer-related mortality across the quartiles were (1.202 (0.981, 1.474), 1.184 (0.967, 1.450), and 1.365 (1.115, 1.672)), (1.116 (0.815, 1.527), 1.017 (0.740, 1.398), and 1.220 (0.891, 1.670)), and (1.202 (0.981, 1.474), 1.184 (0.967, 1.450), and 1.365 (1.115, 1.672)), respectively, in the full-adjusted model. The SII index also had a U-shaped relationship with all-cause, CVD, and cancer-related mortality in patients with CHD, angina, and myocardial infarction. Additionally, the U-shaped relationship between SII index and all-cause, and cancer-related mortality also exists in CHF, and stroke. However, there was a positive linear correlation between SII index and CVD mortality in patients with CHF, and stroke. Conclusion: In the United States general population, the correlation between SII index and all-cause, CVD, and cancer-related mortality showed a U-shaped curve in patients with CVD.

Association of Systemic Immune Inflammation Index with Estimated Pulse Wave Velocity, Atherogenic Index of Plasma, Triglyceride-Glucose Index, and Cardiovascular Disease: A Large Cross-Sectional Study.

In the U.S. general population, there is a lack of understanding regarding the association between the systemic immune inflammation (SII) index and estimated pulse wave velocity (ePWV), atherogenic index of plasma (AIP), and triglyceride-glucose (TyG) index and cardiovascular disease (CVD). As a result, the objective of our research was to investigate the association between the SII index and ePWV, AIP, and TyG index and incident CVD. We used the National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2018 to conduct this study. The correlation between the SII index and ePWV, AIP, and TyG index was examined using generalized additive models with smooth functions. In addition, the association between SII index and triglyceride (TC), high-density lipoprotein cholesterol (HDL-C), and fast glucose (FBG) also were explored. Finally, we further performed multivariable logistic regression analysis, restricted cubic spline (RCS) plots, and subgroup analysis to study the connection between the SII index and CVD. Our analysis included 17389 subjects from the NHANES database. A substantial positive association existed between SII, WV, and the TyG index. In addition, with the increase of the SII index, AIP showed a trend of decreasing first, then rising, and then decreasing. The SII index was inversely and linearly associated with triglyceride (TG), while positively and linearly associated with fast glucose (FBG). However, high-density lipoprotein cholesterol (HDL-C) had a tendency of first declining, then climbing, and finally falling with the rise in the SII index. After adjusting for potential confounders, compared with the lowest quartiles, the odds ratios with 95% confidence intervals for CVD across the quartiles were 0.914 (0.777, 1.074), 0.935 (0.779, 1.096), and 1.112 (0.956, 1.293) for SII index. The RCS plot showed an inverse U-shaped curve relationship between the SII index and CVD. Overall, this study found a strong correlation between a higher SII index and ePWV and the TyG index. Additionally, these cross-sectional data also revealed a U-shaped connection between the SII index and CVD.

Association between daily eating frequency and mortality in people with diabetes: Findings from NHANES 1999-2014.

Background: Previous studies have shown that increasing the frequency of eating is beneficial in terms of cardiovascular metabolic risk factors; however, limited evidence is available for the association between daily eating frequency and mortality, especially in people with diabetes. Therefore, we aimed to explore the association between eating frequency and long-term mortality in populations with diabetes. Methods: We selected 4,924 individuals suffering from diabetes (mean age: 57.77 years; 51.3% men) from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2014. Daily eating frequency was used as the exposure factor in this study. We extracted the mortality data from the National Death Index records and matched them with the population of NHANES. All participants were followed up from the date of getting enrolled in NHANES to 31 December 2015. Multivariate Cox proportional hazards regression, Kaplan-Meier survival curves, and restricted cubic spline were used to assess the associations between eating frequency and all-cause and cause-specific mortality among people with diabetes. Results: During 34,950 person-years of follow-up, 1,121 deaths were documented, including 272 cardiovascular disease (CVD)-related deaths and 156 cancer-related deaths. After adjusting for confounding factors, the daily eating frequency was linearly inversely associated with all-cause and CVD-related mortality, and the HR (95% CIs) for per one-time increment of eating frequency was 0.88 (0.80-0.98) and 0.77 (0.63-0.93), respectively. Sensitivity analyses showed that the main results and statistical significance were still stable. Conclusion: Higher eating frequency was independently related to lower all-cause and CVD-related mortality in people with diabetes, which can be used as a potential strategy for daily-diet management among populations suffering from diabetes.

Association of lipoprotein(a) with coronary severity in patients with new-onset acute myocardial infarction: A large cross-sectional study.

BACKGROUND: Although current evidence suggests a causal association between lipoprotein(a) [Lp(a)] and cardiovascular disease, there is still no consensus on its association with coronary severity in new-onset acute myocardial infarction (AMI). We explored the association of Lp(a) with coronary severity. METHODS: In this large cross-sectional study, we enrolled 2,740 patients with new-onset AMI from the Zhongda Hospital affiliated to Southeast University. Lp(a) was considered as an exposure variable. Gensini score, left main disease and three-vessel disease were used to assess coronary severity. Multivariate logistic regression, restricted cubic spline (RCS) models and threshold effects were used to analyze the association of Lp(a) with coronary severity. RESULTS: Multivariate adjusted models showed that Lp(a) was independently associated with Gensini score (≥100), left main disease and three-vessel disease [Q4 vs Q1, OR (95 % CI), P value: 2.301 (1.770, 2.992), P < 0.001; 1.743 (1.174, 2.587), P = 0.006; 1.431 (1.128, 1.816), P = 0.003; respectively], and the associations persisted in sensitivity analyses and most subgroups (P < 0.05). Additionally, the RCS showed that Lp(a) was nonlinearly associated with Gensini score (continuous variable), Gensini score (≥100) and three-vessel disease (P for nonlinearity < 0.05). Threshold effects analysis showed that Lp(a) above the inflection point was positively associated with Gensini score (continuous variable) as well as the risk of Gensini score (≥100) and three-vessel disease. CONCLUSION: Lp(a) was closely associated with coronary severity represented by Gensini score, left main disease and three-vessel disease in patients with new-onset AMI.

Association of lipoprotein(a) with left ventricular hypertrophy in patients with new-onset acute myocardial infarction: A large cross-sectional study.

BACKGROUND: The association of lipoprotein(a) [Lp(a)] with echocardiography-estimated left ventricular hypertrophy (LVH) in high-risk population remains uncertain, so we assessed the association between Lp(a) with echocardiography-derived LVH in patients with new-onset acute myocardial infarction (AMI). METHODS: In this large, single-center, cross-sectional observational study, we enrolled 2,096 patients with new-onset AMI. Lp(a) was used as the independent variable and LVH was used as the dependent variable. Logistic regression, subgroup and sensitivity analysis were performed to test the association of Lp(a) with LVH. RESULTS: The concentration of Lp(a) was higher in LVH group compared with the non-LVH group (P < 0.001). Multivariate logistic regression analysis showed that higher Lp(a) was strongly associated with higher risk of LVH, independently of traditional cardiovascular risk factors (Fully adjusted model, Q4 vs Q1, OR: 1.941, 95% CI: 1.343-2.803, P < 0.001). Subgroup analysis showed that the association of Lp(a) with LVH persisted in the subgroups of age (<60 and ≥60 years), sex (male and female), smoking (yes and no), diabetes (yes), hypertension (yes), hyperlipidemia (yes), and chronic kidney diseases (yes and no). Further sensitivity analysis indicated that Lp(a) remained significantly associated with LVH after further adjusting for high-sensitivity C-reactive protein or excluding patients with estimated glomerular filtration rate < 30 ml/min/1.73 m2 or dividing Lp(a) into multiple dichotomous variables. CONCLUSION: Lp(a) was closely associated with LVH in patients with new-onset AMI.

Oleoylethanolamide alleviates hyperlipidaemia-mediated vascular calcification via attenuating mitochondrial DNA stress triggered autophagy-dependent ferroptosis by activating PPARα.

Vascular calcification, a prevalent pathological alteration in metabolic syndromes, is tightly related with cardiometabolic risk events. Ferroptosis, a newly iron-dependent programmed cell death, induced by palmitic acid (PA), the major saturated free fatty acid in hyperlipidemia, is a vital mechanism of vascular calcification. Recent studies reported that ferroptosis is a distinctive type of cell death dependent on autophagy, with the lipotoxicity of PA on cell viability being closely linked with autophagy. Oleoylethanolamide (OEA), an endogenous bioactive mediator of lipid homeostasis, exerts vascular protection against intimal calcification, atherosclerosis; however, its beneficial effect on vascular smooth muscle cell (VSMC)-associated medial calcification has not been investigated. Our aim was to characterize the effect of OEA on vascular calcification and ferroptosis of VSMCs under hyperlipidaemia/PA exposure. In vivo, vascular calcification model was induced in rats by high-fat diet and vitamin D3 plus nicotine; in vitro, VSMCs ferroptosis was induced by PA or plus ß-glycerophosphate mimicking vascular calcification. The calcium deposition in hyperlipidaemia-mediated rat thoracic aortas, the PA-induced ferroptosis and subsequent calcium deposition in VSMCs, were suppressed by OEA treatment. Additionally, CGAS-STING1-induced ferritinophagy, the main molecular mechanism of PA-triggered ferroptosis of VSMCs, was activated by mitochondrial DNA damage; however, early administration of OEA alleviated these phenomena. Intriguingly, overexpression of peroxisome proliferator activated receptor alpha (PPARα) contributed to a decrease in PA-induced ferroptosis, whereas PPARɑ knockdown inhibited the OEA-mediated anti-ferroptotic effects. Collectively, our study demonstrated that OEA serves as a prospective candidate for the prevention and treatment of vascular calcification in metabolic abnormality syndromes.

Intakes of omega-3 fatty acids and risks of all-cause and cause-specific mortality in people with diabetes: a cohort study based on NHANES 1999-2014.

AIMS: Intake of omega-3 fatty acids is associated with several health benefits, but the specific benefits in populations with diabetes have yet to be elucidated. Therefore, this study aimed to explore the relationship between intake of omega-3 fatty acids and mortality in people with diabetes. METHODS: This was a prospective cohort study and included 4854 participants with diabetes (mean age, 57.92 years; 50.9% male) from the National Health and Nutrition Examination Survey (1999-2014). Eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid intake were used as alternative markers of omega-3 fatty acids intake and calculated based on the sum of the 24-h dietary recall interviews and dietary supplements. Mortality data were ascertained by linkage to National Death Index records by December 31, 2015. Cox proportional hazard models and restricted cubic spline were used to assess the relationship between EPA and DHA intake and all-cause and cause-specific mortality. Statistical analyses were performed using R 4.2.0 software. RESULTS: Compared with participants with a lower EPA + DHA intake, participants who had a higher EPA + DHA intake tended to be Non-Hispanic Black; were more likely to be obese; and had higher daily energy intake and family income. During 34,386 person-years of follow-up, 1102 deaths were documented, including 266 cardiovascular disease deaths and 152 cancer deaths. In multivariable regression analyses with adjustment of confounding factors, higher EPA + DHA intake was significantly and linearly related to lower all-cause mortality: there was a 25% reduced risk of all-cause mortality. CONCLUSIONS: Higher omega-3 fatty acid intake was independently related to lower all-cause mortality in individuals with diabetes, suggesting an adequate intake of omega-3 fatty acids may prevent premature death among the population with diabetes.

Lead exposure is non-linearly associated with subclinical myocardial injury in the general population without cardiovascular disease.

Background and aims: Growing studies have focused on the effect of lead exposure on human circulatory system, while the relationship between lead exposure and subclinical myocardial injury (SC-MI) is still poorly known. Therefore, this study was to explore the effect of lead exposure on SC-MI. Methods: The study included 6,272 individuals aged 40 and older without cardiovascular disease (CVD) from the third National Health and Nutrition Examination Survey. Blood lead was used as an alternative marker of lead exposure. Multivariable logistic regression models, restricted cubic spline and threshold effect analyses were performed to investigate the effect of blood lead on SC-MI. Results: After adjusting for age, sex, race, diabetes, hypertension, systolic blood pressure, body mass index, waist-to-hip ratio, triglycerides, total cholesterol, creatinine, fasting plasma glucose and hemoglobin Alc, higher blood lead level was independently related to higher risk of SC-MI (OR 1.047, 95% CI [1.018, 1.077]; P = 0.003). Restricted cubic spline curve showed that there was a non-linear correlation between blood lead and SC-MI. Threshold effect analysis determined that the inflection point of blood lead was 3.8 ug/dl. When the blood lead level was higher than 3.8 ug/dl, there was an independent positive correlation between blood lead level and the risk of SC-MI (OR 1.031, 95% CI [1.009, 1.053]; P < 0.01). And similar associations were also observed among subgroups of male, ≤60 years, >60 years, never smoker, non-Hispanic White, non-Hispanic Black or without hypertension and diabetes. Conclusions: Blood lead was non-linearly related to SC-MI in population free from CVD.