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Abstract Background Diabetic macroangiopathy has been the main cause of death and disability in diabetic patients. The mechanisms underlying smooth muscle cell transformation and metabolic reprogramming other than abnormal glucose and lipid metabolism remain to be further explored. Method Single-cell transcriptome, spatial transcriptome and spatial metabolome sequencing were performed on anterior tibial artery from 11 diabetic patients with amputation. Multi-omics integration, cell communication analysis, time series analysis, network analysis, enrichment analysis, and gene expression analysis were performed to elucidate the potential molecular features. Result We constructed a spatial multiomics map of diabetic blood vessels based on multiomics integration, indicating single-cell and spatial landscape of transcriptome and spatial landscape of metabolome. At the same time, the characteristics of cell composition and biological function of calcified regions were obtained by integrating spatial omics and single cell omics. On this basis, our study provides favorable evidence for the cellular fate of smooth muscle cells, which can be transformed into pro-inflammatory chemotactic smooth muscle cells, macrophage-like smooth muscle cells/foam-like smooth muscle cells, and fibroblast/chondroblast smooth muscle cells in the anterior tibial artery of diabetic patients. The smooth muscle cell phenotypic transformation is driven by transcription factors net including KDM5B, DDIT3, etc. In addition, in order to focus on metabolic reprogramming apart from abnormal glucose and lipid metabolism, we constructed a metabolic network of diabetic vascular activation, and found that HNMT and CYP27A1 participate in diabetic vascular metabolic reprogramming by combining public data. Conclusion This study constructs the spatial gene-metabolism map of the whole anterior tibial artery for the first time and reveals the characteristics of vascular calcification, the phenotypic transformation trend of SMCs, and the transcriptional driving network of SMCs phenotypic transformation of diabetic macrovascular disease. In the perspective of combining the transcriptome and metabolome, the study demonstrates the activated metabolic pathways in diabetic blood vessels and the key genes involved in diabetic metabolic reprogramming. Graphical abstract

Abstract Background Although the Healthy Eating Index (HEI) is widely recommended to reduce the risk of cardiovascular disease and all-cause death, there are significant differences in physiological and nutritional factors between the sexes. The potential impact of sex on adult dietary health is still poorly understood. The study was designed to assess whether the health benefits of diet differed by sex. Methods In a prospective study of 39,567 U.S. adults (51.2% female, age 46.8 ± 17.6 years), we examined sex-specific, multivariable-adjusted associations of HEI with all-cause mortality and cardiovascular disease mortality. Restricted cubic splines (RCS), subgroup analysis, propensity score matching (PSM), random forest feature importance, and sensitivity analysis were also used. Results During 328,403 person-years of follow-up, a total of 4754 all-cause deaths were recorded, including 1481 cardiovascular deaths. Compared to the lowest quartile of HEI, the all-cause mortality rate of females and males in the highest quartile array decreased by 34% (HR 0.66 [95% CI 0.55–0.8]) and 15% (HR 0.85 [95% CI 0.73–0.99]), respectively. The restricted cubic spline showed a linear inverse association between baseline HEI and all-cause mortality and CVD mortality, with similar sex-specific results. Similarly, component scores were sex-specific for mortality risk, with females benefiting more from diet. The benefits of dairy products, vegetables, and sodium scores on the risk of all-cause death were higher in males and females. However, the benefits of vegetable, sodium, and fatty acid scores on the risk of cardiovascular death were different. Conclusions In the adult population of the U.S., there are more opportunities for females to reduce the risk of all-cause mortality and cardiovascular mortality from the same dose of healthy dietary intake than males. These findings could reduce the risk of death by motivating the population, especially females, to consume healthy dietary components, especially vegetables and dairy products.

Abstract Background Dyslipidemia and abnormal cholesterol metabolism are closely related to coronary artery calcification (CAC) and are also critical factors in cardiovascular disease death. In recent years, the atherogenic index of plasma (AIP) has been widely used to evaluate vascular sclerosis. This study aimed to investigate the potential association of AIP between CAC and major adverse cardiovascular events (MACEs). Methods This study included 1,121 participants whose CACs were measured by multislice spiral CT. Participants’ CAC Agatston score, CAC mass, CAC volume, and number of vessels with CACs were assessed. AIP is defined as the base 10 logarithm of the ratio of triglyceride (TG) concentration to high-density lipoprotein-cholesterol (HDL-C) concentration. We investigated the multivariate-adjusted associations between AIP, CAC, and MACEs. The mediating role of the AIP in CAC and MACEs was subsequently discussed. Results During a median follow-up of 31 months, 74 MACEs were identified. For each additional unit of log-converted CAC, the MACE risk increased by 48% (HR 1.48 [95% CI 1.32–1.65]). For each additional unit of the AIP (multiplied by 10), the MACEs risk increased by 19%. Causal mediation analysis revealed that the AIP played a partial mediating role between CAC (CAC Agatston score, CAC mass) and MACEs, and the mediating proportions were 8.16% and 16.5%, respectively. However, the mediating effect of CAC volume tended to be nonsignificant (P = 0.137). Conclusions An increased AIP can be a risk factor for CAC and MACEs. Biomarkers based on lipid ratios are a readily available and low-cost strategy for identifying MACEs and mediating the association between CAC and MACEs. These findings provide a new perspective on CAC treatment, early diagnosis, and prevention of MACEs.

Abstract Backgroud The association between caffeine intake and mortality in prediabetes and diabetes is not well defined. This study was designed to investigate the association between caffeine intake and all-cause mortality and cardiovascular disease (CVD) mortality in adults with prediabetes and diabetes in the United States. Methods This analysis included 18,914 adult patients with diabetes and prediabetes from the National Health and Nutrition Examination Survey (NHANES) 2003–2018. Follow-up extended to December 31, 2019. Weighted Cox proportional hazards regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for all-cause mortality and CVD mortality. Results During 142,460 person-years of follow-up, there were 3,166 cases of all-cause mortality and 1,031 cases of CVD mortality recorded. In the fully adjusted models, caffeine intake showed a significant dose-response association with the risk of all-cause mortality and CVD mortality in individuals with diabetes and prediabetes. When comparing extreme quartiles of caffeine intake, the multivariable-adjusted hazard ratio for all-cause mortality was 0.78 (0.67–0.91) (P for trend = 0.007); however, there was no significant association with the risk of CVD mortality. Results remained consistent in stratified analyses by sex, age, race/ethnicity, education level, family income-poverty ratio, BMI, hypertension, smoking status, alcohol intake, and HEI-2015. Conclusions This study suggests that caffeine intake is significantly inversely associated with the risk of all-cause mortality in individuals with diabetes and prediabetes. In individuals with prediabetes, there is also a significant inverse association between caffeine intake and CVD events, but this association is not present in those with diabetes. Graphical Abstract

Abstract Background Pulmonary hypertension (PH) is a rare disease characterized by proliferation and occlusion of small pulmonary arterioles, which has been associated with a high mortality rate. The pathogenesis of PH is complex and incompletely understood, which includes both genetic and environmental factors that alter vascular structure and function. Methods Thus we aimed to reveal the potential genetic etiology of PH by targeting 143 tag SNPs of 14 candidate genes. Totally 208 individuals from Chinese Han population were enrolled in the present study, including 109 non-idiopathic PH patients and 99 healthy controls. Results The data revealed that 2 SNPs were associated with PH overall susceptibility at p