Exploring mitochondrial DNA copy number in circulating cell-free DNA and extracellular vesicles across cardiovascular health status: A prospective case-control pilot study.

Cardiovascular disease (CVD) is a leading global cause of mortality, difficult to predict in advance. Evidence indicates that the copy number of mitochondrial DNA (mtDNAcn) in blood is altered in individuals with CVD. MtDNA released into circulation may act as a mediator of inflammation, a recognized factor in the development of CVD, in the long distance. This pilot study aims to test if levels of mtDNAcn in buffy coat DNA (BC-mtDNA), in circulating cellfree DNA (cf-mtDNA), or in DNA extracted from plasma extracellular vesicles (EV-mtDNA) are altered in CVD patients and if they can predict heart attack in advance. A group of 144 people with different CVD statuses (50 that had CVD, 94 healthy) was selected from the LifeLines Biobank according to the incidence of new cardiovascular event monitored in 6 years (50 among controls had heart attack after the basal assessment). MtDNAcn was quantified in total cf-DNA and EV-DNA from plasma as well as in buffy coat. EVs have been characterized by their size, polydispersity index, count rate, and zeta potential, by Dynamic Light Scattering. BC-mtDNAcn and cf-mtDNAcn were not different between CVD patients and healthy subjects. EVs carried higher mtDNAcn in subject with a previous history of CVD than controls, also adjusting the analysis for the EVs derived count rate. Despite mtDNAcn was not able to predict CVD in advance, the detection of increased EV-mtDNAcn in CVD patients in this pilot study suggests the need for further investigations to determine its pathophysiological role in inflammation.

Risk prediction of cardiovascular disease in the Asia-Pacific region: the SCORE2 Asia-Pacific model.

BACKGROUND AND AIMS: To improve upon the estimation of 10-year cardiovascular disease (CVD) event risk for individuals without prior CVD or diabetes mellitus in the Asia-Pacific region by systematic recalibration of the SCORE2 risk algorithm. METHODS: The sex-specific and competing risk-adjusted SCORE2 algorithms were systematically recalibrated to reflect CVD incidence observed in four Asia-Pacific risk regions, defined according to country-level World Health Organization age- and sex-standardized CVD mortality rates. Using the same approach as applied for the original SCORE2 models, recalibration to each risk region was completed using expected CVD incidence and risk factor distributions from each region. RESULTS: Risk region-specific CVD incidence was estimated using CVD mortality and incidence data on 8,405,574 individuals (556,421 CVD events). For external validation, data from 9,560,266 individuals without previous CVD or diabetes were analysed in 13 prospective studies from 12 countries (350,550 incident CVD events). The pooled C-index of the SCORE2 Asia-Pacific algorithms in the external validation data sets was 0.710 (95% confidence interval [CI] 0.677-0.745). Cohort-specific C-indices ranged from 0.605 (95% CI 0.597-0.613) to 0.840 (95% CI 0.771-0.909). Estimated CVD risk varied several-fold across Asia-Pacific risk regions. For example, the estimated 10-year CVD risk for a 50-year-old non-smoker, with a systolic blood pressure of 140 mmHg, total cholesterol of 5.5 mmol/L, and high-density lipoprotein-cholesterol of 1.3 mmol/L, ranged from 7% for men in low-risk countries to 14% for men in very-high-risk countries, and from 3% for women in low-risk countries to 13% for women in very-high-risk countries. CONCLUSIONS: The SCORE2 Asia-Pacific algorithms have been calibrated to estimate 10-year risk of CVD for apparently healthy people in Asia and Oceania, thereby enhancing the identification of individuals at higher risk of developing CVD across the Asia-Pacific region.

Polygenic risk score adds to a clinical risk score in the prediction of cardiovascular disease in a clinical setting.

BACKGROUND AND AIMS: A cardiovascular disease polygenic risk score (CVD-PRS) can stratify individuals into different categories of cardiovascular risk, but whether the addition of a CVD-PRS to clinical risk scores improves the identification of individuals at increased risk in a real-world clinical setting is unknown. METHODS: The Genetics and the Vascular Health Check Study (GENVASC) was embedded within the UK National Health Service Health Check (NHSHC) programme which invites individuals between 40-74 years of age without known CVD to attend an assessment in a UK general practice where CVD risk factors are measured and a CVD risk score (QRISK2) is calculated. Between 2012-2020, 44,141 individuals (55.7% females, 15.8% non-white) who attended an NHSHC in 147 participating practices across two counties in England were recruited and followed. When 195 individuals (cases) had suffered a major CVD event (CVD death, myocardial infarction or acute coronary syndrome, coronary revascularisation, stroke), 396 propensity-matched controls with a similar risk profile were identified, and a nested case-control genetic study undertaken to see if the addition of a CVD-PRS to QRISK2 in the form of an integrated risk tool (IRT) combined with QRISK2 would have identified more individuals at the time of their NHSHC as at high risk (QRISK2 10-year CVD risk of ≥10%), compared with QRISK2 alone. RESULTS: The distribution of the standardised CVD-PRS was significantly different in cases compared with controls (cases mean score .32; controls, -.18, P = 8.28×10-9). QRISK2 identified 61.5% (95% confidence interval [CI]: 54.3%-68.4%) of individuals who subsequently developed a major CVD event as being at high risk at their NHSHC, while the combination of QRISK2 and IRT identified 68.7% (95% CI: 61.7%-75.2%), a relative increase of 11.7% (P = 1×10-4). The odds ratio (OR) of being up-classified was 2.41 (95% CI: 1.03-5.64, P = .031) for cases compared with controls. In individuals aged 40-54 years, QRISK2 identified 26.0% (95% CI: 16.5%-37.6%) of those who developed a major CVD event, while the combination of QRISK2 and IRT identified 38.4% (95% CI: 27.2%-50.5%), indicating a stronger relative increase of 47.7% in the younger age group (P = .001). The combination of QRISK2 and IRT increased the proportion of additional cases identified similarly in women as in men, and in non-white ethnicities compared with white ethnicity. The findings were similar when the CVD-PRS was added to the atherosclerotic cardiovascular disease pooled cohort equations (ASCVD-PCE) or SCORE2 clinical scores. CONCLUSIONS: In a clinical setting, the addition of genetic information to clinical risk assessment significantly improved the identification of individuals who went on to have a major CVD event as being at high risk, especially among younger individuals. The findings provide important real-world evidence of the potential value of implementing a CVD-PRS into health systems.

Epitaxial Growth of Two-Dimensional Nonlayered AuCrS2 Materials via Au-Assisted Chemical Vapor Deposition.

Two-dimensional (2D) nonlayered transition metal dichalcogenide (TMD) materials are emergent platforms for various applications from catalysis to quantum devices. However, their limited availability and nonstraightforward synthesis methods hinder our understanding of these materials. Here, we present a novel technique for synthesizing 2D nonlayered AuCrS2 via Au-assisted chemical vapor deposition (CVD). Our detailed structural analysis reveals the layer-by-layer growth of [AuCrS2] units atop an initial CrS2 monolayer, with Au binding to the adjacent monolayer of CrS2, which is in stark contrast with the well-known metal intercalation mechanism in the synthesis of many other 2D nonlayered materials. Theoretical calculations further back the crucial role of Cr in increasing the mobility of Au species and strengthening the adsorption energy of Au on CrS2, thereby aiding the growth throughout the CVD process. Additionally, the resulting free-standing nanoporous AuCrS2 (NP-AuCrS2) exhibits exceptional electrocatalytic properties for the hydrogen evolution reaction.

Toward Controlled Synthesis of 2D Crystals by CVD: Learning from the Real-Time Crystal Morphology Evolutions.

The rich morphology of 2D materials grown through chemical vapor deposition (CVD), is a distinctive feature. However, understanding the complex growth of 2D crystals under practical CVD conditions remains a challenge due to various intertwined factors. Real-time monitoring is crucial to providing essential data and enabling the use of advanced tools like machine learning for unraveling these complexities. In this study, we present a custom-built miniaturized CVD system capable of observing and recording 2D MoS2 crystal growth in real time. Image processing converts the real-time footage into digital data, and machine learning algorithms (ML) unveil the significant factors influencing growth. The machine learning model successfully predicts CVD growth parameters for synthesizing ultralarge monolayer MoS2 crystals. It also demonstrates the potential to reverse engineer CVD growth parameters by analyzing the as-grown 2D crystal morphology. This interdisciplinary approach can be integrated to enhance our understanding of controlled 2D crystal synthesis through CVD.

Controlled Growth of Submillimeter-Scale Cr5Te8 Nanosheets and the Domain Wall Nucleation Governed Magnetization Reversal Process.

Two-dimensional (2D) ferromagnets have attracted widespread attention for promising applications in compact spintronic devices. However, the controlled synthesis of high-quality, large-sized, and ultrathin 2D magnets via facile, economical method remains challenging. Herein, we develop a hydrogen-tailored chemical vapor deposition approach to fabricating 2D Cr5Te8 ferromagnetic nanosheets. Interestingly, the time period of introducing hydrogen was found to be crucial for controlling the lateral size, and a Cr5Te8 single-crystalline nanosheet of lateral size up to ∼360 µm with single-unit-cell thickness has been obtained. These samples exhibit a leading role of domain wall nucleation in governing the magnetization reversal process, providing important references for optimizing the performances of associated devices. The nanosheets also show notable magnetotransport response, including nonmonotonous magnetic-field-dependent magnetoresistance and sizable anomalous Hall resistivity, demonstrating Cr5Te8 as a promising material for constructing high-performance magnetoelectronic devices. This study presents a breakthrough of large-sized CVD-grown 2D magnetic materials, which is indispensable for constructing 2D spintronic devices.

Distinct Inflammatory Phenotypes Are Associated With Subclinical and Clinical Cardiovascular Disease in People With Human Immunodeficiency Virus.

Despite inflammation being implicated in cardiovascular disease (CVD) in people with human immunodeficiency virus (PWH), considerable heterogeneity within populations of PWH exists. Stratifying CVD risk based on inflammatory phenotype could play an important role. Using principal component analyses and unsupervised hierarchical clustering, we examined 38 biomarkers to identify inflammatory phenotypes in 2 independent cohorts of PWH. We identified 3 distinct inflammatory clusters present in both cohorts that were associated with altered risk of both subclinical CVD (cohort 1) and prevalent clinical CVD (cohort 2) after adjusting for CVD risk factors. These data support precision medicine approaches to enhance CVD risk assessment in PWH.

Low LCAT activity is linked to acute decompensated heart failure and mortality in patients with CKD.

Chronic kidney disease (CKD) is often associated with decreased activity of lecithin-cholesterol acyltransferase (LCAT), an enzyme essential for HDL maturation. This reduction in LCAT activity may potentially contribute to an increased risk of cardiovascular mortality in patients with CKD. The objective of this study was to investigate the association between LCAT activity in patients with CKD and the risk of adverse outcomes. We measured serum LCAT activity and characterized lipoprotein profiles using nuclear magnetic resonance spectroscopy in 453 non-dialysis CKD patients from the CARE FOR HOMe study. LCAT activity correlated directly with smaller HDL particle size, a type of HDL potentially linked to greater cardiovascular protection. Over a mean follow-up of 5.0 ± 2.2 years, baseline LCAT activity was inversely associated with risk of death (standardized HR 0.62, 95% CI 0.50-0.76; P < 0.001) and acute decompensated heart failure (ADHF) (standardized HR 0.67, 95% CI 0.52-0.85; P = 0.001). These associations remained significant even after adjusting for other risk factors. Interestingly, LCAT activity was not associated with the incidence of atherosclerotic cardiovascular events or kidney function decline during the follow-up. To conclude, our findings demonstrate that low LCAT activity is independently associated with all-cause mortality and ADHF in patients with CKD, and is directly linked to smaller, potentially more protective HDL subclasses.

Dyslipidaemia as a target for atherosclerotic cardiovascular disease prevention in children with type 1 diabetes: lessons learned from familial hypercholesterolaemia.

In the last few decades, atherosclerotic cardiovascular disease (ASCVD) risk has decreased dramatically among individuals affected by familial hypercholesterolaemia (FH) as a result of the early initiation of statin treatment in childhood. Contemporaneously important improvements in care for people with diabetes have also been made, such as the prevention of mortality from acute diabetic complications. However, individuals with type 1 diabetes still have a two to eight times higher risk of death than the general population. In the last 20 years, a few landmark studies on excess mortality in people with type 1 diabetes, in particular young adults, have been published. Although these studies were carried out in different populations, all reached the same conclusion: individuals with type 1 diabetes have a pronounced increased risk of ASCVD. In this review, we address the role of lipid abnormalities in the development of ASCVD in type 1 diabetes and FH. Although type 1 diabetes and FH are different diseases, lessons could be learned from the early initiation of statins in children with FH, which may provide a rationale for more stringent control of dyslipidaemia in children with type 1 diabetes.

Cardiovascular Health and Life Expectancy Among Adults in the United States.

BACKGROUND: Cardiovascular disease may be the main reason for stagnant growth in life expectancy in the United States since 2010. The American Heart Association recently released an updated algorithm for evaluating cardiovascular health (CVH)-Life's Essential 8 (LE8) score. We aimed to quantify the associations of CVH levels, estimated by the LE8 score, with life expectancy in a nationally representative sample of US adults. METHODS: We included 23 003 nonpregnant, noninstitutionalized participants aged 20 to 79 years who participated in the National Health and Nutrition Examination Survey from 2005 to 2018 and whose mortality was identified through linkage to the National Death Index through December 31, 2019. The overall CVH was evaluated by the LE8 score (range, 0-100), as well as the score for each component of diet, physical activity, tobacco/nicotine exposure, sleep duration, body mass index, non-high-density lipoprotein cholesterol, blood glucose, and blood pressure. Life table method was used to estimate life expectancy by levels of the CVH. RESULTS: During a median of 7.8 years of follow-up, 1359 total deaths occurred. The estimated life expectancy at age 50 years was 27.3 years (95% CI, 26.1-28.4), 32.9 years (95% CI, 32.3-33.4), and 36.2 years (95% CI, 34.2-38.2) in participants with low (LE8 score <50), moderate (50≤ LE8 score <80), and high (LE8 score ≥80) CVH, respectively. Equivalently, participants with high CVH had an average 8.9 (95% CI, 6.2-11.5) more years of life expectancy at age 50 years compared with those with low CVH. On average, 42.6% of the gained life expectancy at age 50 years from adhering to high CVH was attributable to reduced cardiovascular disease death. Similarly significant associations of CVH with life expectancy were observed in men and women, respectively. Similarly significant associations of CVH with life expectancy were observed in White participants and Black participants but not in Mexican participants. CONCLUSIONS: Adhering to a high CVH, defined as the LE8 score, is related to a considerably increased life expectancy in US adults, but more research needs to be done in other races and ethnicities (eg, Hispanic and Asian).

Toward the Production of Super Graphene.

The quality requirements of graphene depend on the applications. Some have a high tolerance for graphene quality and even require some defects, while others require graphene as perfect as possible to achieve good performance. So far, synthesis of large-area graphene films by chemical vapor deposition of carbon precursors on metal substrates, especially on Cu, remains the main way to produce high-quality graphene, which has been significantly developed in the past 15 years. However, although many prototypes are demonstrated, their performance is still more or less far from the theoretical property limit of graphene. This review focuses on how to make super graphene, namely graphene with a perfect structure and free of contaminations. More specially, this study focuses on graphene synthesis on Cu substrates. Typical defects in graphene are first discussed together with the formation mechanisms and how they are characterized normally, followed with a brief review of graphene properties and the effects of defects. Then, the synthesis progress of super graphene from the aspects of substrate, grain size, wrinkles, contamination, adlayers, and point defects are reviewed. Graphene transfer is briefly discussed as well. Finally, the challenges to make super graphene are discussed and a strategy is proposed.

Quantum-Sized Co Nanoparticles with Rich Vacancies Enabled the Uniform Deposition of Lithium Metal and Fast Polysulfide Conversion.

The notorious polysulfide shuttling and uncontrollable Li-dendrite growth are the main obstacles to the marketization of Li-S batteries. Herein, a dual-functional material consisting of vacancy-rich quantum-sized Co nanodots anchored on a mesoporous carbon layer (v-Co/meso-C) is proposed. This material exposes more active sites to improve its reaction performance and simultaneously realizes excellent lithiophilicity and sulfiphilicity characteristics in Li-S electrochemistry. As Li metal deposition hosts, v-Co/meso-C shows small nucleation overpotential, low polarization, and ultra-long cycling stability in both half and symmetric cells, as confirmed by experimental studies. On the S cathode side, experimental and theoretical calculations demonstrate that v-Co/meso-C enhances the adsorption of polysulfides and boosts their catalytic conversion rate. This, in turn, suppresses the shuttle effect of polysulfides and improves sulfur utilization efficiency. Finally, a shuttle-free and dendrite-free v-Co/meso-C@Li//v-Co/meso-C@S full cell is fabricated, exhibiting excellent rate performance (739 mAh g-1 at 5.0 C) and good cyclability (capacity decay rate is 0.033% and 0.035% per cycle at 2.0 and 5.0 C, respectively). Even a pouch cell with high sulfur loading (5.5 mg cm-2) and lean electrolyte/sulfur (4.8 µL mg-1) can still work 50 cycles with 80% capacity retention rate. This study shows far-reaching implications in the design of dendrite-free, shuttle-free Li-S batteries.

Synthesis of Ultrathin FeS Nanosheets via Chemical Vapor Deposition.

Fe-based 2D materials exhibit rich chemical compositions and structures, which may imply many unique physical properties and promising applications. However, achieving controllable preparation of ultrathin non-layered FeS crystal on SiO2/Si substrate remains a challenge. Herein, the influence of temperature and molecular sieves is reported on the synthesis of ultrathin FeS nanosheets with a thickness as low as 2.3 nm by molecular sieves-assisted chemical vapor deposition (CVD). The grown FeS nanosheets exhibit a non-layered hexagonal NiAs structure and belong to the P63/mmc space group. The inverted symmetry broken structure is confirmed by the angle-resolved second harmonic generation (SHG) test. In particular, the 2D FeS nanosheets exhibit exceptional metallic behavior, with conductivity up to 1.63 × 106 S m-1 at 300 K for an 8 nm thick sample, which is higher than that of reported 2D metallic materials. This work provides a significant contribution to the synthesis and characterization of 2D non-layered Fe-based materials.

Macrophage-based therapeutic approaches for cardiovascular diseases.

Despite the advances in treatment options, cardiovascular disease (CVDs) remains the leading cause of death over the world. Chronic inflammatory response and irreversible fibrosis are the main underlying pathophysiological causes of progression of CVDs. In recent decades, cardiac macrophages have been recognized as main regulatory players in the development of these complex pathophysiological conditions. Numerous approaches aimed at macrophages have been devised, leading to novel prospects for therapeutic interventions. Our review covers the advancements in macrophage-centric treatment plans for various pathologic conditions and examines the potential consequences and obstacles of employing macrophage-targeted techniques in cardiac diseases.

CVD phenotyping in oncologic disorders: cardio-miRNAs as a potential target to improve individual outcomes in revers cardio-oncology.

With the increase of aging population and prevalence of obesity, the incidence of cardiovascular disease (CVD) and cancer has also presented an increasing tendency. These two different diseases, which share some common risk factors. Relevant studies in the field of reversing Cardio-Oncology have shown that the phenotype of CVD has a significant adverse effect on tumor prognosis, which is mainly manifested by a positive correlation between CVD and malignant progression of concomitant tumors. This distal crosstalk and the link between different diseases makes us aware of the importance of diagnosis, prediction, management and personalized treatment of systemic diseases. The circulatory system bridges the interaction between CVD and cancer, which suggests that we need to fully consider the systemic and holistic characteristics of these two diseases in the process of clinical treatment. The circulating exosome-miRNAs has been intrinsically associated with CVD -related regulation, which has become one of the focuses on clinical and basic research (as biomarker). The changes in the expression profiles of cardiovascular disease-associated miRNAs (Cardio-miRNAs) may adversely affect concomitant tumors. In this article, we sorted and screened CVD and tumor-related miRNA data based on literature, then summarized their commonalities and characteristics (several important pathways), and further discussed the conclusions of Cardio-Oncology related experimental studies. We take a holistic approach to considering CVD as a risk factor for tumor malignancy, which provides an in-depth analysis of the various regulatory mechanisms or pathways involved in the dual attribute miRNAs (Cardio-/Onco-miRNAs). These mechanisms will be key to revealing the systemic effects of CVD on tumors and highlight the holistic nature of different diseases. Therefore, the Cardio-miRNAs should be given great attention from researchers in the field of CVD and tumors, which might become new targets for tumor treatment. Meanwhile, based on the principles of precision medicine (such as the predictive preventive personalized medicine, 3PM) and reverse Cardio-oncology to better improve individual outcomes, we should consider developing personalized medicine and systemic therapy for cancer from the perspective of protecting cardiovascular function.

Cardiovascular disease risk in people of African ancestry with HIV in the United Kingdom.

OBJECTIVES: Our objective was to describe the prevalence of cardiovascular disease (CVD) risk factors in people of African ancestry with HIV in the UK. METHODS: We conducted a cross-sectional analysis of CVD risk factors in Black people with HIV aged ≥40 years and estimated the 10-year CVD risk using QRISK®3-2018. Correlations between body mass index (BMI) and CVD risk factors were described using Pearson correlation coefficients, and factors associated with 10-year CVD risk ≥5% were described using logistic regression. RESULTS: We included 833 Black people with HIV and a median age of 54 years; 54% were female, 50% were living with obesity (BMI ≥30 kg/m2), 61% had hypertension, and 19% had diabetes mellitus. CVD risk >5% ranged from 2% in female participants aged 40-49 years to 99% in men aged ≥60 years, and use of statins ranged from 7% in those with CVD risk <2.5% to 64% in those with CVD risk ≥20%. BMI was correlated (R2 0.1-0.2) with triglycerides and diastolic blood pressure in women and with glycated haemoglobin, systolic and diastolic blood pressure, and total:high-density lipoprotein (HDL) cholesterol ratio in men. In both female and male participants, older age, blood pressure, diabetes mellitus, and kidney disease were strongly associated with CVD risk ≥5%, whereas obesity, total:HDL cholesterol, triglycerides, and smoking status were variably associated with CVD risk ≥5%. CONCLUSIONS: We report a high burden of CVD risk factors, including obesity, hypertension, and diabetes mellitus, in people of African ancestry with HIV in the UK. BMI-focused interventions in these populations may improve CVD risk while also addressing other important health issues.

The association between the triglyceride-glucose index and the risk of cardiovascular disease in US population aged ≤ 65 years with prediabetes or diabetes: a population-based study.

BACKGROUND: The relationship between the triglyceride-glucose (TyG) index and the risk of cardiovascular disease (CVD) in the U.S. population under 65 years of age with diabetes or prediabetes is unknown. The purpose of this study was to investigate the relationship between baseline TyG index and CVD risk in U.S. patients under 65 years of age with diabetes or prediabetes. METHODS: We used data from the 2003-2018 National Health and Nutrition Examination Survey (NHANES). Multivariate regression analysis models were constructed to explore the relationship between baseline TyG index and CVD risk. Nonlinear correlations were explored using restricted cubic splines. Subgroup analysis and interaction tests were also conducted. RESULTS: The study enrolled a total of 4340 participants with diabetes or pre-diabetes, with a mean TyG index of 9.02 ± 0.02. The overall average prevalence of CVD was 10.38%. Participants in the higher TyG quartiles showed high rates of CVD (Quartile 1: 7.35%; Quartile 2: 10.04%; Quartile 3: 10.71%; Quartile 4: 13.65%). For CVD, a possible association between the TyG index and the risk of CVD was observed. Our findings suggested a linear association between the TyG index and the risk of CVD. The results revealed a U-shaped relationship between the TyG index and both the risk of CVD (P nonlinear = 0.02583) and CHF (P nonlinear = 0.0208) in individuals with diabetes. Subgroup analysis and the interaction term indicated that there was no significant difference among different stratifications. Our study also revealed a positive association between the TyG index and comorbid MetS in the U.S. population under 65 years of age with prediabetes or diabetes. CONCLUSIONS: A higher TyG index was linked to an increased likelihood of CVD in the U.S. population aged ≤ 65 years with prediabetes and diabetes. Besides, TyG index assessment will contribute to more convenient and effective screening of high-risk individuals in patients with MetS. Future studies should explore whether interventions targeting the TyG index may improve clinical outcomes in these patients.

Association between the triglyceride-glucose index and all-cause and CVD mortality in the young population with diabetes.

BACKGROUND: Although studies have demonstrated the value of the triglyceride-glucose (TyG) index for cardiovascular disease (CVD) and cardiovascular mortality, however, few studies have shown that the TyG index is associated with all-cause or CVD mortality in young patients with diabetes. This study aimed to investigate the association between the TyG index and all-cause and CVD mortality in young patients with diabetes in the United States. METHODS: Our study recruited 2440 young patients with diabetes from the National Health and Nutrition Examination Survey (NHANES) 2001-2018. Mortality outcomes were determined by linking to National Death Index (NDI) records up to December 31, 2019. Cox regression modeling was used to investigate the association between TyG index and mortality in young patients with diabetes. The nonlinear association between TyG index and mortality was analyzed using restricted cubic splines (RCS), and a two-segment Cox proportional risk model was constructed for both sides of the inflection point. RESULTS: During a median follow-up period of 8.2 years, 332 deaths from all causes and 82 deaths from cardiovascular disease were observed. Based on the RCS, the TyG index was found to have a U-shaped association with all-cause and CVD mortality in young patients with diabetes, with threshold values of 9.18 and 9.16, respectively. When the TyG index was below the threshold value (TyG index < 9.18 in all-cause mortality and < 9.16 in CVD mortality), its association with all-cause and CVD mortality was not significant. When the TyG index was above the threshold (TyG index ≥ 9.18 in all-cause mortality and ≥ 9.16 in CVD mortality), it showed a significant positive association with all-cause mortality and CVD mortality (HR 1.77, 95% CI 1.05-2.96 for all-cause mortality and HR 2.38, 95% CI 1.05-5.38 for CVD mortality). CONCLUSION: Our results suggest a U-shaped association between TyG index and all-cause and CVD mortality among young patients with diabetes in the United States, with threshold values of 9.18 and 9.16 for CVD and all-cause mortality, respectively.

Association between the triglyceride glucose-body mass index and future cardiovascular disease risk in a population with Cardiovascular-Kidney-Metabolic syndrome stage 0-3: a nationwide prospective cohort study.

BACKGROUND: The American Heart Association (AHA) has recently introduced the concept of Cardiovascular-Kidney-Metabolic (CKM) syndrome, which is the result of an increasing emphasis on the interplay of metabolic, renal and cardiovascular diseases (CVD). Furthermore, there is substantial evidence of a correlation between the triglyceride glucose-body mass index (TyG-BMI ) and CVD as an assessment of insulin resistance (IR). However, it remains unknown whether this correlation exists in population with CKM syndrome. METHODS: All data for this study were obtained from the China Health and Retirement Longitudinal Study (CHARLS). The exposure was the participants' TyG-BMI at baseline, which was calculated using a combination of triglycerides (TG), fasting blood glucose (FBG) and body mass index (BMI). The primary outcome was CVD, which were determined by the use of a standardised questionnaire during follow-up. To examine the relationship between TyG-BMI and CVD incidence in population with CKM syndrome, both Cox regression analyses and restricted cubic spline (RCS) regression analyses were performed. RESULTS: A total of 7376 participants were included in the final analysis. Of these, 1139, 1515, 1839, and 2883 were in CKM syndrome stages 0, 1, 2, and 3, respectively, at baseline. The gender distribution was 52.62% female, and the mean age was 59.17 ± 9.28 (years). The results of the fully adjusted COX regression analyses indicated that there was a 6.5% increase in the risk of developing CVD for each 10-unit increase in TyG-BMI,95% confidence interval (CI):1.041-1.090. The RCS regression analyses demonstrated a positive linear association between TyG-BMI and the incidence of CVD in the CKM syndrome population (P for overall < 0.001, P for nonlinear = 0.355). CONCLUSIONS: This cohort study demonstrated a positive linear association between TyG-BMI index and increased CVD incidence in a population with CKM syndrome stage 0-3. This finding suggests that enhanced assessment of TyG-BMI index may provide a more convenient and effective tool for individuals at risk for CVD in CKM syndrome stage 0-3.

Circulating palmitoyl sphingomyelin levels predict the 10-year increased risk of cardiovascular disease death in Chinese adults: findings from the Da Qing Diabetes Study.

BACKGROUND: Higher levels of palmitoyl sphingomyelin (PSM, synonymous with sphingomyelin 16:0) are associated with an increased risk of cardiovascular disease (CVD) in people with diabetes. Whether circulating PSM levels can practically predict the long-term risk of CVD and all-cause death remains unclear. This study aimed to investigate whether circulating PSM is a real predictor of CVD death in Chinese adults with or without diabetes. METHODS: A total of 286 and 219 individuals with and without diabetes, respectively, from the original Da Qing Diabetes Study were enrolled. Blood samples collected in 2009 were used as a baseline to assess circulating PSM levels. The outcomes of CVD and all-cause death were followed up from 2009 to 2020, and 178 participants died, including 87 deaths due to CVD. Cox proportional hazards regression was used to estimate HRs and their 95% CIs for the outcomes. RESULTS: Fractional polynomial regression analysis showed a linear association between baseline circulating PSM concentration (log-2 transformed) and the risk of all-cause and CVD death (p < 0.001), but not non-CVD death (p > 0.05), in all participants after adjustment for confounders. When the participants were stratified by PSM-tertile, the highest tertile, regardless of diabetes, had a higher incidence of CVD death (41.5 vs. 14.7 and 22.2 vs. 2.9 per 1000 person-years in patients with and without diabetes, respectively, all log-rank p < 0.01). Individuals with diabetes in the highest tertile group had a higher risk of CVD death than those in the lowest tertile (HR = 2.73; 95%CI, 1.20-6.22). CONCLUSIONS: Elevated PSM levels are significantly associated with a higher 10-year risk of CVD death, but not non-CVD death, in Chinese adults with diabetes. These findings suggest that PSM is a potentially useful long-term predictor of CVD death in individuals with diabetes.