Cardiovascular Diabetology最新文献

Background: The stress hyperglycemia ratio (SHR), calculated as the ratio of admission blood glucose to estimated average glucose derived from glycated hemoglobin, quantifies the degree of relative hyperglycemia during acute physiological stress. This systematic review and meta-analysis aimed to synthesize the current evidence on the association between SHR and the anatomical severity and clinical prognosis of coronary artery disease (CAD).

Methods: PubMed, EMBASE, Web of Science, and the Cochrane Library were systematically searched for studies published from inception to January 24, 2026. Cross-sectional, retrospective, and prospective cohort studies involving patients with CAD were included. Outcomes related to CAD severity comprised large thrombus burden, multi-vessel disease, non-target lesion progression, and in-stent restenosis. The primary outcome for CAD prognosis was major adverse cardiovascular events (MACE). Data were pooled using random-effects models to estimate hazard ratios (HRs) or odds ratios (ORs) and their 95% confidence intervals (CIs). CAD is classified into acute coronary syndrome (ACS) and chronic coronary syndrome (CCS).

Results: Nine studies evaluating CAD severity and thirty-one studies assessing CAD prognosis met the inclusion criteria. SHR was significantly associated with multiple markers of increased CAD severity. In the ACS subgroup, pooled analysis indicated that the highest SHR levels were significantly associated with an increased risk of MACE (HR: 1.60, 95% CI 1.41-1.81, P < 0.00001; OR: 1.58, 95% CI 1.19-2.11, P = 0.002). This prognostic value was confirmed in continuous variable analyses (HR: 1.59, 95% CI 1.27-2.00; OR: 3.50, 95% CI 1.47-8.32 per unit increment). Similarly, in the CCS subgroup, patients in the highest SHR category exhibited a higher risk of MACE (HR: 1.95, 95% CI 1.50-2.52; P < 0.00001), a finding consistent across continuous analyses (HR: 1.87, 95% CI 1.64-2.12, P <  0.00001 per unit increment). Consistently significant associations were observed across various secondary endpoints and additional subgroups.

Conclusion: The current evidence suggests that SHR can reflect the anatomical complexity of CAD patients and serves as a valuable, easily accessible tool for risk stratification in this population.

Background and objective: Inflammation drives early recurrent cardiovascular risk in type 2 diabetes mellitus (T2DM) patients following acute myocardial infarction (AMI), particularly within 30-90 days post-discharge. Sodium-glucose co-transporter 2 (SGLT2) inhibitors such as empagliflozin (EMPA) provide cardiometabolic benefits, but their anti-inflammatory effects and optimal timing after AMI remain unclear. Given the prognostic role of systemic markers like the neutrophil-to-lymphocyte ratio, we investigated whether early initiation of EMPA modulates NOD-like receptor protein-3 (NLRP3) inflammasome activity and inflammatory responses in monocyte-derived macrophages (MDMs) from T2DM-AMI patients.

Methods: Sixty-six participants were randomised to receive EMPA either at discharge (Arm-A) or following a 90-day delay (Arm B). Clinical data and biological samples were collected over 180 days. CD14+ MDMs and plasma were obtained at days 0, 30, and 90 (EMPA vs. no EMPA), and days 90, 120, and 180 (early vs. delayed). Inflammatory and metabolic markers were assessed using RT-qPCR, luminescence-based caspase-1 and ATP assays, and targeted immunoassays.

Results: Early EMPA administration was associated with reduced NLRP3 priming (IL1β mRNA) and activation (caspase-1 activity), potentially linked to decreased release of ATP, a danger associated molecular pattern (DAMP). In the absence of EMPA, pro-inflammatory cytokines (TNFα, IL6, MCP1) and M1 macrophage markers (e.g., CD80) either increased or remained unchanged over time. Early EMPA treatment appeared to stabilise or reduce their expression. Markers of cell senescence (p21, IL8, BCL2) were also modulated. Plasma levels of senescence-associated markers (MMP9, OPN, Serpin E1) remained largely unchanged, highlighting the importance of evaluating macrophage-specific responses.

Conclusion: Early empagliflozin administration in T2DM-AMI patients was associated with modulation of NLRP3-related inflammatory and senescence pathways in patient-derived macrophages, benefits observed when cells were stimulated ex-vivo with an inflammatory stimulus. These findings provide mechanistic insight into the timing-dependent anti-inflammatory effects of EMPA and underscore its potential for immediate post-AMI use to reduce inflammation and lower residual cardiovascular risk, supporting further clinical investigation.

Background: Epidemiological studies have established that autoimmune diseases (AD) increase cardiovascular disease (CVD) risk. We aimed to elucidate their shared genetic architecture and clinical implications.

Methods: We conducted a cross-trait multivariate genome-wide association study (GWAS) for three autoimmune diseases (type 1 diabetes, systemic lupus erythematosus, and rheumatoid arthritis) and four cardiovascular diseases (coronary artery disease, heart failure, stroke, and peripheral artery disease). We performed both genome-wide and locus-based analysis including fine-mapping, functional annotation, enrichment analyses, transcriptome-wide association studies (TWAS), and proteome-wide and drug-repurposing Mendelian randomization (MR). We constructed a polygenic risk score (PRS) and explored its pleiotropic effects beyond AD and CVD in the UK Biobank population.

Results: In the multivariate GWAS, we identified 259 genome-wide significant association signals that were enriched primarily in arterial tissues and lipid metabolism pathways. Through convergent evidence from TWAS and MR analyses, we prioritized 15 therapeutic targets including TGFB1 and IL6R, and identified histone deacetylase inhibitors as candidate drugs. The polygenic risk score showed discriminative ability in cardiovascular risk stratification among autoimmune patients, with individuals in the highest PRS decile exhibiting significantly elevated CVD risk compared to those in the 2nd-9th deciles (hazard ratios: 1.60 [95% CI: 1.19-2.15] for type 1 diabetes, 2.28 [95% CI: 1.14-4.56] for systemic lupus erythematosus, and 2.33 [95% CI: 1.94-2.80] for rheumatoid arthritis). Additionally, the PRS revealed pleiotropic associations with risk of various health conditions, including polyneuropathy, chronic renal failure, and depressive episodes.

Conclusion: Our study unveils the shared genetic architecture between autoimmune and cardiovascular diseases, providing insights for therapeutic development and risk stratification.

Background: The estimated glucose disposal rate (eGDR), an established measure of peripheral insulin sensitivity, contributes to stratifying the risk of cardio-cerebrovascular events. Nevertheless, the association between long-term eGDR exposure and stroke incidence throughout all stages (0-4) of cardiovascular-kidney-metabolic (CKM) syndrome remains unknown.

Methods: A cohort of 5248 individuals was drawn from the China Health and Retirement Longitudinal Study (CHARLS). For each participant, eGDR values for the years 2012 and 2015 were calculated using the equation: 21.158 - [0.090 × WC (cm)] - [3.407 × HTN (presence = 1)] - [0.551 × HbA1c (%)]. Cumulative eGDR was calculated as (eGDR₂₀₁₂ + eGDR₂₀₁₅)/2* time (2015-2012). K-means clustering was used to analyse eGDR values from both 2012 and 2015 to identify distinct change patterns. To assess associations with stroke risk, we utilised multivariable logistic regression and restricted cubic spline models.

Results: During the 2015-2018 follow-up period, a total of 336 incident stroke cases were documented. Four distinct eGDR change patterns were identified. In fully adjusted models, compared with the participants in the persistent low pattern (Class 2), those in the moderate-high stable (OR 0.43, 95% CI: 0.31-0.58), stable high (OR 0.29, 0.19-0.43), and rapid decrease (OR 0.66, 0.47-0.91) patterns exhibited significantly lower stroke risk. Furthermore, each 1-unit increase in cumulative eGDR was associated with a 5% reduction in stroke odds (OR 0.95, 0.93-0.96). Restricted cubic spline analysis confirmed a linear inverse relationship between cumulative eGDR and stroke risk (P < 0.001; P for nonlinearity = 0.259).

Conclusion: Cumulative eGDR is inversely associated with stroke risk across all CKM syndrome stages (0-4). This observation suggests that prolonged eGDR surveillance may be associated with improved risk stratification in this population.

Background: Diabetes mellitus (DM), which consists of type I and type 2 diabetes (T1D and T2D), is a known risk factor for myocardial infarction (MI) and negatively impacts post-MI outcomes. However, the mechanisms by which DM exacerbates cardiac remodeling in T1D versus T2D have not been well defined. Here, we assessed acute and chronic post-MI outcomes in T1D and T2D mice, focusing on immune and metabolic pathways.

Methods: T1D was induced in adult male mice by a single high dose of streptozotocin (STZ), and T2D induced by high fat/fructose feeding and multiple low STZ doses. Two weeks following STZ administration, MI was induced by permanent coronary artery ligation, and mice were studied at days (D) 0, 3, 7, and 28 post-MI. Cardiac function was assessed by echocardiography.

Results: Compared to non-diabetic mice, T1D and T2D mice had worse cardiac dysfunction after MI, including increased wall thinning and decreased ejection fraction, despite similar infarct sizes. T1D mice also displayed acute pulmonary congestion. By RNA-sequencing analysis, T1D and T2D mice displayed upregulation of genes associated with canonical chemokine/monocyte-mediated inflammatory pathways, and downregulation of genes associated with extracellular matrix remodeling. T1D and T2D delayed activation of M2-like (CD206+) macrophages in the heart, and impaired normal collagen and elastin deposition after MI. T2D also increased expression of genes associated with T cell activation, and increased CD8 + T cells in the infarct. T1D and T2D hearts showed signs of impaired glucose and ketone oxidation, and T1D hearts had increased markers of fatty acid oxidation. Extracted D3 cardiac macrophages from T1D and T2D mice exhibited higher basal oxygen consumption, and increased M1 markers and chemokine expression. Plasma from T1D and T2D mice increased chemokine expression (Ccl2, Ccl7, Cxcl1) in cultured bone marrow macrophages, and T2D plasma impaired mitochondrial function.

Conclusions: DM promotes adverse cardiac remodeling, which is associated with activation of overlapping and unique inflammatory pathways, impaired ECM remodeling, remote metabolic remodeling, and alterations in macrophage metabolism. Our results provide novel insights into potential therapeutic pathways for DM patients suffering from MI.

Background: Markers of insulin resistance, such as the triglyceride-glucose (TyG) index and estimated glucose disposal rate (eGDR), have been extensively linked to cardiometabolic multimorbidity (CMM). However, the roles of lipid metabolism indicators, including the atherogenic index of plasma (AIP) and remnant cholesterol (RC), remain less clearly defined. This study aimed to evaluate both the individual and combined effects of insulin resistance and dyslipidemia on the risk of CMM.

Methods: Data were derived from the English Longitudinal Study of Ageing. A composite metabolic index integrating the TyG, eGDR, AIP, and RC was developed using principal component analysis. The associations of individual and composite indices with incident CMM were examined using multivariable Cox proportional hazards models, while their predictive performance was assessed via receiver operating characteristic (ROC) and net reclassification improvement (NRI) analysis.

Results: Over a 6.8-year follow-up period, 552 cases of CMM occurred among 4232 participants. After multivariable adjustment, each standard deviation (SD) increase in TyG, AIP, and RC was linked to a higher risk of CMM by 30.8% (HR = 1.308; 95% CI: 1.202-1.422), 22.2% (HR = 1.222; 95% CI: 1.117-1.338), and 7.6% (HR = 1.076; 95% CI: 1.025-1.129), respectively. In contrast, eGDR and the composite metabolic index were linked to 35.0% (HR = 0.650; 95% CI: 0.565-0.747) and 37.4% (HR = 0.626; 95% CI: 0.554-0.707) lower risks of CMM. The eGDR and CompositeIndex showed high Population attributable fraction (PAF) of 56.3% (95% CI: 47.3-63.4) and 38.3% (95% CI: 29.8-47.8), respectively. Dose-response analyses showed near-linear relationships for all indices. ROC and NRI analysis further indicated that the CompositeIndex offered highest discrimination with a modest improvement for CMM (AUC = 0.754, 95% CI: 0.737-0.778; NRI = 0.066 (0.027-0.106). The associations were more pronounced among participants younger than 65 years and consistent across sex.

Conclusions: The integrated index combining insulin resistance and lipid dysregulation was associated with incident CMM and provided modest improvements in risk discrimination and reclassification beyond traditional risk factors.

Objective: Cardiometabolic multimorbidity (CMM) is a growing global health challenge. Whether the baseline or cumulative triglyceride glucose and Chinese visceral adiposity index product (TyG-CVAI) can predict incident CMM remains unclear.

Methods: We constructed two prospective cohorts from the China Health and Retirement Longitudinal Study (CHARLS): Cohort 1 (n = 8895 patients) to assess the association of the baseline TyG-CVAI with CMM and Cohort 2 (n = 5839 patients) to assess the association of the cumulative TyG-CVAI with CMM. The cumulative TyG-CVAI was calculated as the average TyG-CVAI between baseline and the 2015 wave multiplied by the exposure time. Incident CMM was confirmed via a self-reported physician diagnosis, medication use, and clinical data. Cox regression models were used to estimate hazard ratios (HRs). Nonlinearity was assessed using restricted cubic splines, and predictive performance was evaluated by performing a receiver operating characteristic (ROC) curve analysis.

Results: During follow-up, 875 and 492 incident CMM cases were documented in Cohort 1 and Cohort 2, respectively. Both the baseline and cumulative TyG-CVAI showed graded, positive associations with the CMM risk. Compared with the lowest quartile, the highest quartile was associated with significantly increased risks (baseline: HR = 1.93, 95% CI = 1.46-2.54; cumulative: HR = 1.76, 95% CI = 1.22-2.53). Significant nonlinear relationships with threshold effects were observed for both indices (P for nonlinearity < 0.001). Furthermore, compared with their individual components (TyG or CVAI), both the baseline and cumulative TyG-CVAI demonstrated superior predictive ability for CMM, as indicated by a larger area under the ROC curve.

Conclusions:  Both the baseline and cumulative TyG-CVAI are independent and nonlinear predictors of incident CMM, outperforming TyG or CVAI alone. This easily obtainable metric may enhance risk stratification and help identify high-risk individuals for early preventive intervention.

Background: Cardiovascular-kidney-metabolic (CKM) syndrome imposes a substantial global health burden, with most adults clustered in early stages 0-3. Insulin resistance (IR), as a core manifestation of metabolic dysfunction, is thought to play a pivotal role in CKM progression and cardiovascular disease (CVD) development, but the relative impact of diverse IR surrogates and the mediating role of biological ageing acceleration remain unclear.

Method: This prospective analysis included 6318 participants with CKM syndrome stages 0-3 from the China Health and Retirement Longitudinal Study (CHARLS). We evaluated twelve insulin resistance surrogates in relation to incident CVD using multivariable-adjusted logistic regression, restricted cubic splines (RCS), and quantile-based models. Mediation analyses assessed whether biological aging acceleration mediated the association between IR indices and new-onset CVD.

Results: 1231 (19.5%) of 6318 participants with CKM stages 0-3 developed new-onset CVD. All IR surrogates demonstrated significant associations with CVD risk, with elevated TyG-derived indices, METS-IR, CTI, and TG/HDL-C showing positive associations whereas eGDR exhibited an inverse relationship (all P-trend < 0.05). RCS analyses revealed nonlinear relationships for METS-IR, CTI, and eGDR. Significant modification effects were observed by biological ageing acceleration, gender, and CKM stage. Mediation analyses indicated that biological aging acceleration accounted for 14.9-16.4% of the TyG-ABSI-CVD association and 1.3-4.2% of other IR-CVD relationships.

Conclusions: Multiple IR surrogate indices independently predict cardiovascular disease in CKM stages 0-3, with biological aging acceleration mediating this association. Integrating these measures into risk stratification could enable early identification and targeted intervention for high-risk individuals.