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1.
Expert Rev Cardiovasc Ther ; 22(8): 353-366, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39258965

ABSTRACT

INTRODUCTION: Lipoprotein(a) [Lp(a)] is linked to higher risks of atherosclerotic cardiovascular disease (ASCVD). Current guideline recommendations are quite liberal on measuring Lp(a) (Class IIa, Level C), and may lead to underuse among (interventional) cardiologists. AREAS COVERED: This case-based narrative review outlines four clinical cases of patients with elevated Lp(a) to illustrate its pathophysiological impact on coronary artery disease (CAD). The expert consensus statements from the American Heart Association (AHA) and European Atherosclerosis Society (EAS) served as the basis of this review. More recent publications, from 2023 to 2024, were accessed through the MEDLINE online library. EXPERT OPINION: We highlighted the importance of routine Lp(a) measurement in identifying patients at high risk for atherosclerosis, necessitating potent risk mitigation. Measuring Lp(a) helps clinicians identify which patients are at highest residual risk, who require potent pharmacological treatment and special attention during catheter interventions. As noninvasive and advanced intravascular imaging modalities evolve, future catheterization laboratories will integrate advanced imaging, diagnostics, and treatment, facilitating tailored patient care. Knowing Lp(a) levels is crucial in this context. While Lp(a)-lowering drugs are currently investigated in clinical trials, it is of paramount importance to know Lp(a) levels and strive toward aggressive management of other modifiable risk factors in patients with elevated Lp(a) and established symptomatic CAD being diagnosed or treated in catheterization laboratories.


Subject(s)
Coronary Artery Disease , Lipoprotein(a) , Humans , Lipoprotein(a)/blood , Coronary Artery Disease/diagnosis , Male , Middle Aged , Female , Recurrence , Aged , Practice Guidelines as Topic , Atherosclerosis/diagnosis , Risk Assessment/methods , Biomarkers/blood
2.
Int J Rheum Dis ; 27(9): e15339, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39278724

ABSTRACT

AIM: To investigate the correlation between T-cell senescence with the atherosclerosis markers in patients with systemic lupus erythematosus (SLE). METHODS: The study participants were 40 female SLE patients aged 18-45 years who met the 2019 EULAR/ACR criteria and 40 healthy individuals. The atherosclerosis markers were investigated using the Doppler ultrasonography examinations to measure the cIMT (carotid intima-media thickness) and flow-mediated dilation (FMD) and serological markers using soluble ICAM-1 and VCAM-1. Flow cytometry of CD4+CD57+, CD8+CD57+, CD4+CD28null, and CD8+CD28null T cells were used to assess the immunosenescence markers. RESULTS: The cIMT (p < .001), sICAM-1 (p < .001), and sVCAM-1 (p < .001) were significantly higher in SLE patients compared with control, while FMD was significantly lower in SLE patients (p < .001). The percentages of all T-cell senescence markers are also significantly higher in SLE patients than in healthy individuals. Positive correlations were shown between cIMT with the CD4+CD57+ (R = .301, p = .005), CD4+CD28null (R = .448, p < .001), and CD8+CD28null (R = .422, p < .001). Conversely, negative correlations were demonstrated between the FMD with CD4+CD57+ (R = -.236, p = .023), CD8+CD57+ (R = -.409, p < .001), CD4+CD28null (R = -.422, p < .001), and CD8+CD28null (R = -.318, p = .003). The soluble markers of sICAM-1 and sVCAM-1 were also positively correlated with the T-cell senescence markers. CONCLUSION: Early sign of atherosclerosis was demonstrated in patients with SLE in this study. T-cell senescence markers had significant correlations with the atherosclerosis markers, including the cIMT, FMD, and soluble adhesion molecules levels. Understanding the link between immunosenescence and atherosclerosis might help to identify a new method for early detection and treatment of atherosclerosis in SLE.


Subject(s)
Atherosclerosis , Biomarkers , Carotid Intima-Media Thickness , Cellular Senescence , Immunosenescence , Lupus Erythematosus, Systemic , Humans , Female , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/complications , Adult , Young Adult , Middle Aged , Atherosclerosis/blood , Atherosclerosis/immunology , Atherosclerosis/etiology , Atherosclerosis/diagnosis , Atherosclerosis/diagnostic imaging , Biomarkers/blood , Case-Control Studies , Adolescent , Intercellular Adhesion Molecule-1/blood , T-Lymphocytes/immunology , Vascular Cell Adhesion Molecule-1/blood , T-Cell Senescence
4.
J Am Heart Assoc ; 13(18): e036318, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39248249

ABSTRACT

BACKGROUND: We conducted a post hoc analysis of the ATAMIS (Antiplatelet Therapy in Acute Mild to Moderate Ischemic Stroke) trial to investigate whether the priority of clopidogrel plus aspirin to aspirin alone was consistent between patients with and without stroke pathogenesis of large-artery atherosclerosis (LAA). METHODS AND RESULTS: Patients with stroke classification randomized to a clopidogrel-plus-aspirin group and aspirin-alone group in a modified intention-to-treat analysis set of ATAMIS were classified into LAA and non-LAA subtypes. The primary outcome was early neurologic deterioration at 7 days, defined as a >2-point increase in National Institutes of Health Stroke Scale score compared with baseline, and safety outcomes were bleeding events and intracranial hemorrhage. We compared treatment effects in each stroke subtype and investigated the interaction. Among 2910 patients, 225 were assigned into the LAA subtype (119 in the clopidogrel-plus-aspirin group and 106 in the aspirin-alone group) and 2685 into the non-LAA subtype (1380 in the clopidogrel-plus-aspirin group and 1305 in the aspirin-alone group). Median age was 66 years, and 35% were women. A lower proportion of early neurologic deterioration was found to be associated with dual antiplatelet therapy in the LAA subtype (adjusted risk difference, -10.4% [95% CI, -16.2% to -4.7%]; P=0.001) but not in the non-LAA subtype (adjusted risk difference, -1.4% [95% CI, -2.6% to 0.1%]; P=0.06). No significant interaction was found (P=0.11). CONCLUSIONS: Compared with the non-LAA subtype, patients with stroke of the LAA subtype may get more benefit from dual antiplatelet therapy with clopidogrel plus aspirin with respect to early neurologic deterioration at 7 days. REGISTRATION: URL: clinicaltrials.gov; UnIque identifier: NCT02869009.


Subject(s)
Aspirin , Clopidogrel , Dual Anti-Platelet Therapy , Ischemic Stroke , Platelet Aggregation Inhibitors , Humans , Female , Male , Aged , Aspirin/administration & dosage , Aspirin/therapeutic use , Aspirin/adverse effects , Clopidogrel/therapeutic use , Clopidogrel/administration & dosage , Clopidogrel/adverse effects , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/administration & dosage , Dual Anti-Platelet Therapy/methods , Dual Anti-Platelet Therapy/adverse effects , Middle Aged , Treatment Outcome , Ischemic Stroke/diagnosis , Ischemic Stroke/prevention & control , Ischemic Stroke/epidemiology , Ischemic Stroke/drug therapy , Ischemic Stroke/etiology , Atherosclerosis/drug therapy , Atherosclerosis/diagnosis , Atherosclerosis/complications , Severity of Illness Index , Drug Therapy, Combination
5.
J Appl Lab Med ; 9(5): 1040-1056, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39225455

ABSTRACT

BACKGROUND: The accurate measurement of blood lipids and lipoproteins is crucial for the clinical management of atherosclerotic disease risk. Despite progress in standardization, there are still significant variations in pre-analytical requirements, methods, nomenclature, and reporting work flows. CONTENT: The guidance document aims to improve standardization of clinical lipid testing work flows. It provides recommendations for the components of the lipid panel, fasting requirements, reporting of results, and specific recommendations for non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein(a) [Lp(a)], apolipoprotein B (apo B), point-of-care lipid testing, and LDL subfraction testing. SUMMARY: Lipid panels should always report non-HDL-C and LDL-C calculations if possible. Fasting is not routinely required except in specific cases. Modern equations should be utilized for LDL-C calculation. These equations allow for LDL-C reporting at elevated concentrations of triglycerides and obviate the need for direct measured LDL-C in most cases.


Subject(s)
Lipids , Lipoproteins , Humans , Lipoproteins/blood , Lipoproteins/analysis , Lipids/blood , Lipids/analysis , Cholesterol, LDL/blood , Apolipoproteins B/blood , Atherosclerosis/blood , Atherosclerosis/diagnosis , Lipoprotein(a)/blood
6.
Front Endocrinol (Lausanne) ; 15: 1437379, 2024.
Article in English | MEDLINE | ID: mdl-39224122

ABSTRACT

Background: The relationship between atherogenic index of plasma (AIP) and triglyceride glucose-body mass index (TyG-BMI) and sarcopenia has not been studied in the United States (US) population. Methods: This research included 4,835 people from the National Health and Nutrition Examination Survey (NHANES) conducted between 2011 and 2018. The relationship between sarcopenia and TyG-BMI, as well as the AIP index, was examined through the utilization of restricted cubic spline (RCS) analysis, subgroup analysis, and multivariate logistic regression analysis. Diagnostic value of AIP and TyG-BMI for sarcopenia was compared by receiver operating characteristic (ROC) curves. Results: In this research, 428 people with sarcopenia were identified among the 4,835 subjects that were included in the experiment. AIP and sarcopenia were positively associated with an odds ratio (OR) of 1.58 and a 95% confidence interval (CI) of (1.07, 2.34) on fully adjusted multivariate logistic regression analysis. Similarly, TyG-BMI and sarcopenia were positively associated with an OR of 8.83 and a 95% CI of (5.46, 14.26). AIP and sarcopenia had a non-linear positive connection (P-value<0.001, P-Nonlinear=0.010), while TyG-BMI and sarcopenia had a linear positive correlation (P-value<0.001, P-Nonlinear=0.064), according to RCS analysis. Subgroup analyses showed a significant interaction between TyG-BMI and sarcopenia due to gender (P = 0.023). ROC curves showed that TyG-BMI (AUC:0.738, 95% CI: 0.714 - 0.761) was more useful than AIP (AUC:0.648, 95% CI: 0.622 - 0.673) in diagnosing sarcopenia. Conclusion: In US adults aged 20-59 years, our study revealed a correlation between elevated AIP and TyG-BMI levels and heightened sarcopenia risk. Moreover, TyG-BMI has better diagnostic validity than AIP.


Subject(s)
Atherosclerosis , Blood Glucose , Body Mass Index , Sarcopenia , Triglycerides , Humans , Sarcopenia/blood , Sarcopenia/diagnosis , Sarcopenia/epidemiology , Female , Male , Cross-Sectional Studies , Middle Aged , Adult , Triglycerides/blood , Blood Glucose/analysis , Atherosclerosis/blood , Atherosclerosis/diagnosis , Atherosclerosis/epidemiology , Young Adult , Nutrition Surveys
7.
RMD Open ; 10(3)2024 Aug 22.
Article in English | MEDLINE | ID: mdl-39179256

ABSTRACT

BACKGROUND: MicroRNAs (miRNAs) can regulate gene expression, controlling numerous cellular processes. Dysregulation of miRNA function is linked to various diseases, making them attractive diagnostic and therapeutic targets. Examples include hsa-miR-92a-3p, hsa-miR-126-3p, hsa-miR-143-3p, hsa-miR-145-5p and hsa-miR-204-5p, which are associated with endothelial function. Their prevalence in Sjögren's disease (SjD) is unknown. We assessed the prevalence of these miRNAs in serum of patients with SjD, correlating levels with cardiovascular risk factors and carotid intima-media thickness (cIMT) to evaluate their utility in risk stratification. METHODS: 199 patients with SjD and 100 age and sex-matched healthy controls (HC) were included in the study. Five different miRNAs (hsa-miR-92a-3p; hsa-miR-126-3p; hsa-miR143-3p; hsa-miR-145-5p; hsa-miR-204-5p) were analysed by quantitative real-time PCR. The miRNA results were compared with known clinical and disease-related parameters. RESULTS: Four miRNAs showed significantly different expressions compared with HC. MiR-92a-3p was upregulated (p=0.025) and miR-126-3p (p=0.044), miR-143-3p (p=0.006) and miR-204-5p (p=0.009) downregulated in SjD compared with HC. The comparison between HC and SjD with/without organ involvement revealed descriptively increased miR-92a-3p levels in patients with SjD with organ involvement (p=0.087). Furthermore, miR-92a-3p levels correlated positively with cIMT as an expression of subclinical atherosclerosis (r=0.148, p=0.04). CONCLUSION: In conclusion, patients with SjD demonstrated differences in their expression of miRNAs linked to regulation of endothelial function. Reduction of specific miRNAs was associated with increased cardiovascular risk, suggesting a potentially protective role for these miRNAs. Furthermore, miR-92a-3p could be helpful for molecular detection of early-stage atherosclerosis and increased cardiovascular risk in SjD.


Subject(s)
Atherosclerosis , Biomarkers , Carotid Intima-Media Thickness , MicroRNAs , Sjogren's Syndrome , Humans , MicroRNAs/genetics , MicroRNAs/blood , Female , Middle Aged , Male , Atherosclerosis/etiology , Atherosclerosis/diagnosis , Atherosclerosis/genetics , Sjogren's Syndrome/complications , Sjogren's Syndrome/diagnosis , Sjogren's Syndrome/genetics , Sjogren's Syndrome/blood , Case-Control Studies , Adult , Gene Expression Profiling , Aged , Gene Expression Regulation
8.
Cardiovasc Diabetol ; 23(1): 301, 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39152490

ABSTRACT

BACKGROUND: The atherogenic index of plasma (AIP) has been shown to be positively correlated with cardiovascular events. However, it remains unclear whether hypertensive patients with long-term high AIP levels are at greater risk of developing heart failure (HF). Therefore, the aim of this study was to investigate the association between AIP trajectory and the incidence of HF in hypertensive patients. METHODS: This prospective study included 22,201 hypertensive patients from the Kailuan Study who underwent three waves of surveys between 2006 and 2010. Participants were free of HF or cancer before or during 2010. The AIP was calculated as the logarithmic conversion ratio of triglycerides to high-density lipoprotein cholesterol. Latent mixed modeling was employed to identify different trajectory patterns for AIP during the exposure period (2006-2010). Cox proportional hazard models were then used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for incident HF among different trajectory groups. RESULTS: Four distinct trajectory patterns were identified through latent mixture modeling analysis: low-stable group (n = 3,373; range, -0.82 to -0.70), moderate-low stable group (n = 12,700; range, -0.12 to -0.09), moderate-high stable group (n = 5,313; range, 0.53 to 0.58), and elevated-increasing group (n = 815; range, 1.22 to 1.56). During a median follow-up period of 9.98 years, a total of 822 hypertensive participants experienced HF. After adjusting for potential confounding factors, compared with those in the low-stable group, the HR and corresponding CI for incident HF in the elevated-increasing group, moderate-high stable group, and moderate-low stable group were estimated to be 1.79 (1.21,2.66), 1.49 (1.17,1.91), and 1.27 (1.02,1.58), respectively. These findings remained consistent across subgroup analyses and sensitivity analyses. CONCLUSION: Prolonged elevation of AIP in hypertensive patients is significantly associated with an increased risk of HF. This finding suggests that regular monitoring of AIP could aid in identifying individuals at a heightened risk of HF within the hypertensive population.


Subject(s)
Biomarkers , Heart Failure , Hypertension , Triglycerides , Humans , Heart Failure/epidemiology , Heart Failure/diagnosis , Heart Failure/blood , Male , Middle Aged , Prospective Studies , Female , Hypertension/epidemiology , Hypertension/diagnosis , Hypertension/blood , Aged , Incidence , Risk Factors , Risk Assessment , Triglycerides/blood , Biomarkers/blood , Atherosclerosis/epidemiology , Atherosclerosis/blood , Atherosclerosis/diagnosis , China/epidemiology , Cholesterol, HDL/blood , Time Factors , Adult , Prognosis , Proportional Hazards Models
10.
Nutr Metab Cardiovasc Dis ; 34(11): 2596-2605, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39168806

ABSTRACT

BACKGROUND AND AIM: Adequate serum vitamin D levels correlate with a more favorable lipid profile compared to deficient levels. Despite the well-established prevalence of vitamin D deficiency in children with obesity, studies investigating its influence on lipid profiles in this population are scarce. We explored the impact of vitamin D status on lipid profiles and markers of atherogenic dyslipidemia in a cohort of children and adolescents with obesity. METHODS AND RESULTS: A total of 271 Caucasian children and adolescents with overweight/obesity and a control group of 54 pediatric patients with normal weight. All participants underwent outpatient visits for the assessment of clinical parameters and venous blood collection for biochemical analysis such as triglycerides (TG)/HDL-C ratio, LDL-C/HDL-C ratio, atherogenic index of plasma AIP), vitamin D level. Individuals with obesity displayed severe vitamin D deficiency (25-OH-D ≤10 ng/ml) at a higher frequency compared to those with normal weight (p = 0.03). In patients with overweight/obesity and low 25-OH-D levels show higher values of glycemia (p = 0.001), insulin resistance (HOMA-IR and TRYG p < 0.001), TG (p < 0.001), TG/HDL-C (p = 0.001), AIP (p < 0.001), SBP (p = 0.01), and DBP (p = 0.04). In normal-weight individuals with low 25-OH- D levels an increased values of glycemia (p = 0.01), insulin resistance (HOMA-IR p = 0.01 and TRYG p = 0.002), TG (p = 0.01), TG/HDL-C (p = 0.02), AIP (p = 0.01). A direct correlation between 25-OH-D levels and metabolic parameters is observed. CONCLUSIONS: A correlation between vitamin D levels and the lipid/atherosclerotic profile was recorded. Vitamin D deficiency may represent a preventable and easily treatable cardiometabolic risk factor, emphasizing the importance of early intervention and preventive measures.


Subject(s)
Atherosclerosis , Biomarkers , Dyslipidemias , Lipids , Pediatric Obesity , Vitamin D Deficiency , Vitamin D , Humans , Child , Male , Female , Adolescent , Vitamin D Deficiency/blood , Vitamin D Deficiency/epidemiology , Vitamin D Deficiency/diagnosis , Vitamin D/blood , Vitamin D/analogs & derivatives , Pediatric Obesity/blood , Pediatric Obesity/diagnosis , Pediatric Obesity/epidemiology , Biomarkers/blood , Dyslipidemias/blood , Dyslipidemias/epidemiology , Dyslipidemias/diagnosis , Lipids/blood , Atherosclerosis/blood , Atherosclerosis/epidemiology , Atherosclerosis/diagnosis , Case-Control Studies , Age Factors , Risk Assessment , Cross-Sectional Studies , Prevalence , Risk Factors
11.
J Diabetes Complications ; 38(10): 108850, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39191064

ABSTRACT

AIMS: Atherogenic indices: Triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, Atherogenic Index of Plasma (AIP), Atherogenic Coefficient (AC), Castelli's Risk Index I and II (CRI-I, CRI-II) are used in clinical studies as surrogates of major adverse cardiac and cerebrovascular events (MACCE). Risk prediction of MACCE in patients with acute myocardial infarction (AMI) has vital role in clinical practice. We aimed to assess prognostic value of these indices following AMI. METHODS: We analyzed patients with AMI with and without T2DM and the prognostic values of atherogenic indices for in-hospital death and MACCE within 12 months after AMI. RESULTS: Of 2461 patients, 152 in-hospital deaths (6.2 %) were reported (74 patients [7.4 %] with T2DM and 78 [5.3 %] without T2DM; p = 0.042). MACCE occurred in 22.7 % of patients (29.7 % with T2DM and 17.9 % without T2DM; p < 0.001). TG/HDL-C and AIP were higher in T2DM patients compared to those without T2DM (p < 0.001). Long-term MACCE was more prevalent in patients with T2DM (p < 0.001). The AUC-ROC for predicting in-hospital death based on TG/HDL-C and AIP was 0.57 (p = 0.002). CONCLUSIONS: None of the atherogenic indices was an independent risk factor for in-hospital death or MACCE at 12-month follow-up in patients with AMI. AIP was an independent risk factor for death at 12-month follow-up.


Subject(s)
Atherosclerosis , Diabetes Mellitus, Type 2 , Myocardial Infarction , Humans , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/mortality , Male , Female , Middle Aged , Prognosis , Aged , Myocardial Infarction/diagnosis , Myocardial Infarction/epidemiology , Myocardial Infarction/complications , Myocardial Infarction/mortality , Myocardial Infarction/blood , Atherosclerosis/complications , Atherosclerosis/epidemiology , Atherosclerosis/diagnosis , Atherosclerosis/blood , Cholesterol, HDL/blood , Hospital Mortality , Triglycerides/blood , Biomarkers/blood , Retrospective Studies , Risk Factors , Predictive Value of Tests , Diabetic Angiopathies/epidemiology , Diabetic Angiopathies/diagnosis , Diabetic Angiopathies/mortality , Diabetic Angiopathies/blood
12.
BMC Cardiovasc Disord ; 24(1): 405, 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39095691

ABSTRACT

BACKGROUND: Atherosclerosis and metabolic syndrome are the main causes of cardiovascular events, but their underlying mechanisms are not clear. In this study, we focused on identifying genes associated with diagnostic biomarkers and effective therapeutic targets associated with these two diseases. METHODS: Transcriptional data sets of atherosclerosis and metabolic syndrome were obtained from GEO database. The differentially expressed genes were analyzed by RStudio software, and the function-rich and protein-protein interactions of the common differentially expressed genes were analyzed.Furthermore, the hub gene was screened by Cytoscape software, and the immune infiltration of hub gens was analyzed. Finally, relevant clinical blood samples were collected for qRT-PCR verification of the three most important hub genes. RESULTS: A total of 1242 differential genes (778 up-regulated genes and 464 down-regulated genes) were screened from GSE28829 data set. A total of 1021 differential genes (492 up-regulated genes and 529 down-regulated genes) were screened from the data set GSE98895. Then 23 up-regulated genes and 11 down-regulated genes were screened by venn diagram. Functional enrichment analysis showed that cytokines and immune activation were involved in the occurrence and development of these two diseases. Through the construction of the Protein-Protein Interaction(PPI) network and Cytoscape software analysis, we finally screened 10 hub genes. The immune infiltration analysis was further improved. The results showed that the infiltration scores of 7 kinds of immune cells in GSE28829 were significantly different among groups (Wilcoxon Test < 0.05), while in GSE98895, the infiltration scores of 4 kinds of immune cells were significantly different between groups (Wilcoxon Test < 0.05). Spearman method was used to analyze the correlation between the expression of 10 key genes and 22 kinds of immune cell infiltration scores in two data sets. The results showed that there were 42 pairs of significant correlations between 10 genes and 22 kinds of immune cells in GSE28829 (|Cor| > 0.3 & P < 0.05). There were 41 pairs of significant correlations between 10 genes and 22 kinds of immune cells in GSE98895 (|Cor| > 0.3 & P < 0.05). Finally, our results identified 10 small molecules with the highest absolute enrichment value, and the three most significant key genes (CX3CR1, TLR5, IL32) were further verified in the data expression matrix and clinical blood samples. CONCLUSION: We have established a co-expression network between atherosclerotic progression and metabolic syndrome, and identified key genes between the two diseases. Through the method of bioinformatics, we finally obtained 10 hub genes in As and MS, and selected 3 of the most significant genes (CX3CR1, IL32, TLR5) for blood PCR verification. This may be helpful to provide new research ideas for the diagnosis and treatment of AS complicated with MS.


Subject(s)
Atherosclerosis , Databases, Genetic , Disease Progression , Gene Expression Profiling , Gene Regulatory Networks , Metabolic Syndrome , Protein Interaction Maps , Humans , Metabolic Syndrome/genetics , Metabolic Syndrome/diagnosis , Metabolic Syndrome/immunology , Atherosclerosis/genetics , Atherosclerosis/immunology , Atherosclerosis/diagnosis , Atherosclerosis/blood , Transcriptome , Male , Predictive Value of Tests , Genetic Markers , Reproducibility of Results , Genetic Predisposition to Disease , Computational Biology , Middle Aged , Female , Gene Expression Regulation
13.
Cardiovasc Diabetol ; 23(1): 314, 2024 Aug 24.
Article in English | MEDLINE | ID: mdl-39182114

ABSTRACT

BACKGROUND: Diabetic kidney disease (DKD) is associated with a higher risk of cardiovascular disease (CVD). Pentoxifylline (PTF), a nonselective phosphodiesterase inhibitor with anti-inflammatory, antiproliferative, and antifibrotic actions, has demonstrated renal benefits in both clinical trials and meta-analyses. The present work aimed to study the effects of PTF on the progression of subclinical atherosclerosis (SA) in a population of patients with diabetes and moderate to severe chronic kidney disease (CKD). METHODS: In this open-label, randomized controlled, prospective single-center pilot study the evolution of carotid intima-media thickness (CIMT) and ankle-brachial index (ABI) were determined in 102 patients with type 2 diabetes mellitus and CKD assigned to PTF, aspirin or control groups during 18 months. We also determined the variations in the levels of inflammatory markers and Klotho (KL), a protein involved in maintaining cardiovascular health, and their relationship with the progression of SA. RESULTS: Patients treated with PTF presented a better evolution of CIMT, increased KL mRNA levels in peripheral blood cells (PBCs) and reduced the inflammatory state. The progression of CIMT values was inversely related to variations in KL both in serum and mRNA expression levels in PBCs. Multiple regression analysis demonstrated that PTF treatment and variations in mRNA KL expression in PBCs, together with changes in HDL, were significant determinants for the progression of CIMT (adjusted R2 = 0.24, P < 0.001) independently of traditional risk factors. Moreover, both variables constituted protective factors against a worst progression of CIMT [OR: 0.103 (P = 0.001) and 0.001 (P = 0.005), respectively]. CONCLUSIONS: PTF reduced SA progression assessed by CIMT variation, a beneficial effect related to KL gene expression in PBCs. TRIAL REGISTRATION: The study protocol code is PTF-AA-TR-2009 and the trial was registered on the European Union Drug Regulating Authorities Clinical Trials (EudraCT #2009-016595-77). The validation date was 2010-03-09.


Subject(s)
Carotid Intima-Media Thickness , Diabetes Mellitus, Type 2 , Disease Progression , Pentoxifylline , Renal Insufficiency, Chronic , Humans , Pilot Projects , Male , Middle Aged , Pentoxifylline/therapeutic use , Female , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/complications , Prospective Studies , Aged , Treatment Outcome , Time Factors , Diabetic Nephropathies/diagnosis , Diabetic Nephropathies/drug therapy , Glucuronidase/blood , Glucuronidase/genetics , Biomarkers/blood , Carotid Artery Diseases/diagnostic imaging , Carotid Artery Diseases/drug therapy , Asymptomatic Diseases , Inflammation Mediators/blood , Phosphodiesterase Inhibitors/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Atherosclerosis/drug therapy , Atherosclerosis/diagnosis , Osteocalcin
15.
Medicine (Baltimore) ; 103(29): e38896, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39029045

ABSTRACT

BACKGROUND: The purpose of this study was to investigate the role of legumain in metabolic dysfunction, diagnosis, and prognosis in patients with atherosclerosis. METHODS: Plasma levels of legumain from patients with atherosclerosis (n = 320) and healthy controls (n = 320), expression of legumain in atheromatous plaque and secreted from monocyte-derived macrophages were measured using enzyme-linked-immunosorbent assay, reverse transcription-polymerase chain reaction, Western blot, immunohistochemistry, and fluorescence. RESULTS: Data demonstrated that atherosclerotic patients had higher plasma level of legumain than healthy controls, which was a diagnostic and prognostic marker and corrected with the degree of atherosclerosis. It found that atheromatous plaque and endothelial cell had higher legumain expression than non-atherosclerotic arteries (controls). Legumain showed significantly increased secretion from pro-inflammatory M1 compared to pro-resolving M2 macrophages during monocyte-derived macrophages, which was localized to structures resembling foam cells. CONCLUSION: In conclusion, our data indicate that legumain expression is upregulated in both plasma and plaques of patients with atherosclerosis, which is associated with metabolic dysfunction of endothelial cell and might be a diagnostic and prognostic marker of atherosclerosis.


Subject(s)
Atherosclerosis , Biomarkers , Cysteine Endopeptidases , Macrophages , Humans , Cysteine Endopeptidases/metabolism , Cysteine Endopeptidases/blood , Male , Female , Atherosclerosis/diagnosis , Atherosclerosis/metabolism , Prognosis , Middle Aged , Macrophages/metabolism , Biomarkers/blood , Biomarkers/metabolism , Plaque, Atherosclerotic/metabolism , Aged , Case-Control Studies , Up-Regulation , Adult
16.
Am J Hypertens ; 37(10): 769-776, 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-38970332

ABSTRACT

BACKGROUND: Previous studies with several limitations have comparatively analyzed the relationship between ambulatory blood pressure (BP) and self-measured BP and biomarkers of organ damage. This study extends this line of research by examining the relationship between ambulatory and self-measured BP and cardiac, renal, and atherosclerotic biomarkers in outpatients at cardiovascular risk. METHODS: In 1,440 practice outpatients who underwent office, ambulatory, and self-measured BP monitoring, we assessed the relationships of each BP with organ damage biomarkers including b-type natriuretic peptide (BNP), echocardiographic left ventricular mass index (LVMI), urine albumin-creatinine ratio (UACR), and brachial-ankle pulse wave velocity (baPWV). RESULTS: In the comparison of correlation, self-measured systolic BP (SBP) was more strongly correlated to log-transformed (Ln) BNP (n = 1,435; r = 0.123 vs. r = -0.093, P < 0.001), LVMI (n = 1,278; r = 0.223 vs. r = 0.094, P < 0.001), Ln-UACR (n = 1,435; r = 0.244 vs. r = 0.154, P = 0.010), and baPWV (n = 1,360; r = 0.327 vs. r = 0.115, P < 0.001) than daytime ambulatory SBP. In the linear regression models including office, ambulatory, and self-measured SBP, only self-measured SBP was significantly related to Ln-BNP (P = 0.016) and LVMI (P < 0.001). In the logistic regression models for the top quartile of LVMI, adding self-measured SBP improved the model predictability (P = 0.027), but adding daytime ambulatory SBP did not. However, adding daytime ambulatory SBP improved the model predictability in the logistic model for the top quartile of baPWV including office and self-measured SBP (P = 0.030). CONCLUSIONS: Our study findings suggested that self-measured BP was associated with cardiac biomarkers independent of ambulatory BP.


Subject(s)
Atherosclerosis , Biomarkers , Blood Pressure Monitoring, Ambulatory , Blood Pressure , Creatinine , Natriuretic Peptide, Brain , Pulse Wave Analysis , Humans , Male , Female , Biomarkers/blood , Biomarkers/urine , Middle Aged , Aged , Natriuretic Peptide, Brain/blood , Atherosclerosis/physiopathology , Atherosclerosis/diagnosis , Creatinine/urine , Creatinine/blood , Ankle Brachial Index , Albuminuria/physiopathology , Albuminuria/diagnosis , Albuminuria/urine , Hypertension/physiopathology , Hypertension/diagnosis , Echocardiography
17.
J Am Heart Assoc ; 13(15): e033990, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39077816

ABSTRACT

BACKGROUND: This study investigated the association of American Heart Association's cardiovascular health guidelines Life's Essential 8 (LE8) and Life's Simple 7 (LS7) with carotid artery outcomes among young adults. METHODS AND RESULTS: This cross-sectional study included 240 young adults (age 24.2±1.6 years) who underwent a carotid ultrasound between 2018 and 2022. LE8 score was calculated from 4 health factors (body mass index, non-high-density lipoprotein cholesterol, fasting glucose, and blood pressure), and 4 health behaviors (dietary intake, physical activity, tobacco use, and sleep). LS7 was calculated from 7 metrics (all LE8 metrics, except for sleep) with a simpler algorithm. Higher LE8 and LS7 scores both indicate better health and better adherence to American Heart Association guidelines. Carotid artery outcomes included carotid artery intima-media thickness, arterial stiffness (eg, distensibility), and echogenicity determined by grayscale median of the intima media complex. Results of linear regression analyses, adjusting for age, sex, ethnicity, and parents' highest degree, indicated that a 1-SD increase in LE8 score was associated with 12.14 µm lower carotid artery intima-media thickness (95% CI, -20.93 to 3.35), 1.17 (10-6×m2/N) greater distensibility (95% CI, 0.09-2.24), suggesting less arterial stiffness, and 2.66 µm greater grayscale median of the intima media complex (95% CI, 0.58-4.75), suggesting less lipid deposition. Analyses using LS7 score demonstrated comparable findings. Health factor metrics demonstrated stronger association with carotid artery outcomes, as compared with behavior metrics. CONCLUSIONS: Greater adherence to the American Heart Association's cardiovascular health guidelines is associated with lower risk for subclinical atherosclerosis in young adults. LE8 and LS7 demonstrated comparable associations with carotid artery outcomes.


Subject(s)
American Heart Association , Carotid Intima-Media Thickness , Humans , Male , Female , Cross-Sectional Studies , Young Adult , United States/epidemiology , Adult , Vascular Stiffness/physiology , Carotid Artery Diseases/epidemiology , Carotid Artery Diseases/diagnostic imaging , Asymptomatic Diseases , Health Behavior , Atherosclerosis/epidemiology , Atherosclerosis/diagnosis , Risk Assessment , Risk Factors , Health Status , Carotid Arteries/diagnostic imaging
18.
Cardiovasc Diabetol ; 23(1): 226, 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38951808

ABSTRACT

BACKGROUND: The atherogenic index of plasma (AIP) is closely associated with the onset of diabetes, with obesity being a significant risk factor for type 2 diabetes mellitus (T2DM). However, the association between the AIP and T2DM in overweight and obese populations has been infrequently studied. Therefore, this study aimed to explore this association in overweight and obese individuals with T2DM. METHODS: This cross-sectional analysis utilized data from 40,633 participants with a body mass index (BMI) ≥ 24 kg/m2 who were screened from January 2018 to December 2023 at Henan Provincial People's Hospital. Participants were categorized into groups of overweight and obese individuals with and without diabetes according to the T2DM criteria. The AIP, our dependent variable, was calculated using the formula log10 [(TG mol/L)/HDL-C (mol/L)]. We investigated the association between the AIP and T2DM in overweight and obese individuals using multivariate logistic regression, subgroup analysis, generalized additive models, smoothed curve fitting, and threshold effect analysis. Additionally, mediation analysis evaluated the role of inflammatory cells in AIP-related T2DM. RESULTS: Overweight and obese patients with T2DM exhibited higher AIP levels than those without diabetes. After adjusting for confounders, our results indicated a significant association between the AIP and the risk of T2DM in overweight and obese individuals (odds ratio (OR) = 5.17, 95% confidence interval (CI) 4.69-5.69). Notably, participants with a high baseline AIP (Q4 group) had a significantly greater risk of T2DM than those in the Q1 group, with an OR of 3.18 (95% CI 2.94-3.45). Subgroup analysis revealed that the association between the AIP and T2DM decreased with increasing age (interaction P < 0.001). In overweight and obese populations, the association between AIP and T2DM risk displayed a J-shaped nonlinear pattern, with AIP > - 0.07 indicating a significant increase in T2DM risk. Various inflammatory cells, including neutrophils, leukocytes, and monocytes, mediated 4.66%, 4.16%, and 1.93% of the associations, respectively. CONCLUSION: In overweight and obese individuals, the AIP was independently associated with T2DM, exhibiting a nonlinear association. Additionally, the association between the AIP and T2DM decreased with advancing age. Multiple types of inflammatory cells mediate this association.


Subject(s)
Biomarkers , Diabetes Mellitus, Type 2 , Obesity , Adult , Aged , Female , Humans , Male , Middle Aged , Atherosclerosis/epidemiology , Atherosclerosis/blood , Atherosclerosis/diagnosis , Biomarkers/blood , Body Mass Index , China/epidemiology , Cholesterol, HDL/blood , Cross-Sectional Studies , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/epidemiology , East Asian People , Obesity/diagnosis , Obesity/blood , Obesity/epidemiology , Overweight/epidemiology , Overweight/blood , Overweight/diagnosis , Overweight/complications , Prognosis , Risk Assessment , Risk Factors , Triglycerides/blood
19.
Cardiovasc Diabetol ; 23(1): 237, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38970008

ABSTRACT

BACKGROUND: Atherogenic index of plasma (AIP) is a non-traditional lipid parameter that can reflect the burden of atherosclerosis. A lipid profile resembling atherosclerosis emerged during pregnancy. Although lipid metabolism is pivotal in diabetes pathogenesis, there is no evidence linking AIP to gestational diabetes mellitus (GDM). Therefore, our objective was to explore the relationship between AIP and GDM and assess AIP's predictive capability for GDM. METHODS: This was a secondary analysis based on data from a prospective cohort study in Korea involving 585 single pregnant women. AIP was calculated as log10 (TG/HDL). We examined the relationship between AIP and GDM using logistic regression models, curve fitting, sensitivity analyses, and subgroup analyses. Receiver operating characteristic (ROC) analysis was also used to determine the ability of AIP to predict GDM. RESULTS: The average age of the participants was 32.06 ± 3.76 years. The AIP was 0.24 ± 0.20 on average. The GDM incidence was 6.15%. After adjustment for potentially confounding variables, AIP showed a positive linear relationship with GDM (P for non-linearity: 0.801, OR 1.58, 95% CI 1.27-1.97). The robustness of the connection between AIP and GDM was demonstrated by sensitivity analyses and subgroup analyses. An area under the ROC curve of 0.7879 (95% CI 0.7087-0.8671) indicates that AIP is an excellent predictor of GDM. With a specificity of 75.41% and sensitivity of 72.22%, the ideal AIP cut-off value for identifying GDM was 0.3557. CONCLUSIONS: This study revealed that the AIP at 10-14 weeks of gestation was independently and positively correlated with GDM risk. AIP could serve as an early screening and monitoring tool for pregnant women at high risk of GDM, thereby optimizing GDM prevention strategies. TRIAL REGISTRATION: ClinicalTrials.gov registration no. NCT02276144.


Subject(s)
Atherosclerosis , Biomarkers , Diabetes, Gestational , Predictive Value of Tests , Humans , Diabetes, Gestational/blood , Diabetes, Gestational/diagnosis , Diabetes, Gestational/epidemiology , Female , Pregnancy , Prospective Studies , Adult , Republic of Korea/epidemiology , Risk Factors , Biomarkers/blood , Atherosclerosis/blood , Atherosclerosis/epidemiology , Atherosclerosis/diagnosis , Risk Assessment , Incidence , Triglycerides/blood
20.
Circulation ; 150(1): 62-79, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38950110

ABSTRACT

Despite data suggesting that apolipoprotein B (apoB) measurement outperforms low-density lipoprotein cholesterol level measurement in predicting atherosclerotic cardiovascular disease risk, apoB measurement has not become widely adopted into routine clinical practice. One barrier for use of apoB measurement is lack of consistent guidance for clinicians on how to interpret and apply apoB results in clinical context. Whereas guidelines have often provided clear low-density lipoprotein cholesterol targets or triggers to initiate treatment change, consistent targets for apoB are lacking. In this review, we synthesize existing data regarding the epidemiology of apoB by comparing guideline recommendations regarding use of apoB measurement, describing population percentiles of apoB relative to low-density lipoprotein cholesterol levels, summarizing studies of discordance between low-density lipoprotein cholesterol and apoB levels, and evaluating apoB levels in clinical trials of lipid-lowering therapy to guide potential treatment targets. We propose evidence-guided apoB thresholds for use in cholesterol management and clinical care.


Subject(s)
Apolipoproteins B , Cholesterol, LDL , Humans , Apolipoproteins B/blood , Cholesterol, LDL/blood , Practice Guidelines as Topic , Cardiovascular Diseases/blood , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/diagnosis , Biomarkers/blood , Atherosclerosis/blood , Atherosclerosis/diagnosis , Atherosclerosis/epidemiology , Apolipoprotein B-100
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