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Frontiers in Endocrinology 2024The global prevalence of cardiovascular diseases (CVD) continues to rise steadily, making it a leading cause of mortality worldwide. Atherosclerosis (AS) serves as a... (Review)
Review
The global prevalence of cardiovascular diseases (CVD) continues to rise steadily, making it a leading cause of mortality worldwide. Atherosclerosis (AS) serves as a primary driver of these conditions, commencing silently at an early age and culminating in adverse cardiovascular events that severely impact patients' quality of life or lead to fatality. Dyslipidemia, particularly elevated levels of low-density lipoprotein cholesterol (LDL-C), plays a pivotal role in AS pathogenesis as an independent risk factor. Research indicates that abnormal LDL-C accumulation within arterial walls acts as a crucial trigger for atherosclerotic plaque formation. As the disease progresses, plaque accumulation may rupture or dislodge, resulting in thrombus formation and complete blood supply obstruction, ultimately causing myocardial infarction, cerebral infarction, and other common adverse cardiovascular events. Despite adequate pharmacologic therapy targeting LDL-C reduction, patients with cardiometabolic abnormalities remain at high risk for disease recurrence, highlighting the importance of addressing lipid risk factors beyond LDL-C. Recent attention has focused on the causal relationship between triglycerides, triglyceride-rich lipoproteins (TRLs), and their remnants in AS risk. Genetic, epidemiologic, and clinical studies suggest a causal relationship between TRLs and their remnants and the increased risk of AS, and this dyslipidemia may be an independent risk factor for adverse cardiovascular events. Particularly in patients with obesity, metabolic syndrome, diabetes, and chronic kidney disease, disordered TRLs and its remnants levels significantly increase the risk of atherosclerosis and cardiovascular disease development. Accumulation of over-synthesized TRLs in plasma, impaired function of enzymes involved in TRLs lipolysis, and impaired hepatic clearance of cholesterol-rich TRLs remnants can lead to arterial deposition of TRLs and its remnants, promoting foam cell formation and arterial wall inflammation. Therefore, understanding the pathogenesis of TRLs-induced AS and targeting it therapeutically could slow or impede AS progression, thereby reducing cardiovascular disease morbidity and mortality, particularly coronary atherosclerotic heart disease.
Topics: Humans; Cardiovascular Diseases; Lipoproteins; Triglycerides; Atherosclerosis; Animals; Dyslipidemias; Risk Factors
PubMed: 38883601
DOI: 10.3389/fendo.2024.1409653 -
BMC Cardiovascular Disorders Jun 2024The role of circular RNAs (circRNAs) as biomarkers of coronary artery disease (CAD) remains poorly explored. This study aimed to identify and validate potential...
BACKGROUND
The role of circular RNAs (circRNAs) as biomarkers of coronary artery disease (CAD) remains poorly explored. This study aimed to identify and validate potential circulating circRNAs as biomarkers for the diagnosis of CAD.
METHODS
The expression profile of circRNAs associated with CAD was obtained from Gene Expression Omnibus (GEO) database. Differential expression analysis, weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operation (LASSO) were employed to identify CAD-related hub circRNAs. The expression levels of these hub circRNAs were validated using qRT-PCR in blood samples from 100 CAD patients and 100 controls. The diagnostic performance of these circRNAs was evaluated through logistic regression analysis, receiver operator characteristic (ROC) analysis, integrated discrimination improvement (IDI), and net reclassification improvement (NRI). Functional enrichment analyses were performed to predict the possible mechanisms of circRNAs in CAD.
RESULTS
A total of ten CAD-related hub circRNAs were identified through WGCNA and LASSO analysis. Among them, hsa_circ_0069972 and hsa_circ_0021509 were highly expressed in blood samples of CAD patients, and they were identified as independent predictors after adjustment for relevant confounders. The area under the ROC curve for hsa_circ_0069972 and hsa_circ_0021509 was 0.760 and 0.717, respectively. The classification of patients was improved with the incorporation of circRNAs into the clinical model composed of conventional cardiovascular risk factors, showing an IDI of 0.131 and NRI of 0.170 for hsa_circ_0069972, and an IDI of 0.111 and NRI of 0.150 for hsa_circ_0021509. Functional enrichment analyses revealed that the hsa_circ_0069972-miRNA-mRNA network was enriched in TGF-β、FoxO and Hippo signaling pathways, while the hsa_circ_0021509-miRNA-mRNA network was enriched in PI3K/Akt and MAPK signaling pathways.
CONCLUSION
Hsa_circ_0069972 and hsa_circ_0021509 were identified by integrated analysis, and they are highly expressed in CAD patients. They may serve as novel biomarkers for CAD.
Topics: Humans; Coronary Artery Disease; RNA, Circular; Case-Control Studies; Predictive Value of Tests; Gene Expression Profiling; Gene Regulatory Networks; Middle Aged; Male; Female; Databases, Genetic; Reproducibility of Results; Algorithms; Genetic Markers; Transcriptome; Aged; Biomarkers
PubMed: 38880872
DOI: 10.1186/s12872-024-03972-2 -
European Journal of Medical Research Jun 2024Ischemic cardio-cerebrovascular disease is the leading cause of mortality worldwide. However, studies focusing on elderly and very elderly patients are scarce. Hence,...
BACKGROUND
Ischemic cardio-cerebrovascular disease is the leading cause of mortality worldwide. However, studies focusing on elderly and very elderly patients are scarce. Hence, our study aimed to characterize and investigate the long-term prognostic implications of ischemic cardio-cerebrovascular diseases in elderly Chinese patients.
METHODS
This retrospective cohort study included 1026 patients aged ≥ 65 years who were categorized into the mono ischemic cardio-cerebrovascular disease (MICCD) (either coronary artery disease or ischemic stroke/transient ischemic attack) (n = 912) and the comorbidity of ischemic cardio-cerebrovascular disease (CICCD) (diagnosed with both coronary artery disease and ischemic stroke/transient ischemic attack at admission) (n = 114). The primary outcome was all-cause death. The mortality risk was evaluated using the Cox proportional hazards risk model with multiple adjustments by conventional and propensity-score-based approaches.
RESULTS
Of the 2494 consecutive elderly patients admitted to the hospital, 1026 (median age 83 years [interquartile range]: 76.5-86.4; 94.4% men) met the inclusion criteria. Patients with CICCD consisted mostly of very elderly (79.2% vs. 66.1%, P < 0.001) individuals with a higher burden of comorbidities. Over a median follow-up of 10.4 years, 398 (38.8%) all-cause deaths were identified. Compared with the MICCD group, the CICCD group exhibited a higher adjusted hazard ratio (HR) (95% confidential interval, CI) of 1.71 (1.32-2.39) for long-term mortality after adjusting for potential confounders. The sensitivity analysis results remained robust. After inverse probability of treatment weighting (IPTW) modeling, the CICCD group displayed an even worse mortality risk (IPTW-adjusted HR: 2.07; 95% CI 1.47-2.90). In addition, anemia (adjusted HR: 1.48; 95% CI 1.16-1.89) and malnutrition (adjusted HR: 1.43; 95% CI 1.15-1.78) are also independent risk factors for all-cause mortality among elderly and very elderly patients.
CONCLUSIONS
Our results thus suggest that elderly patients with ischemic cardio-cerebrovascular disease and anemia or malnutrition may have higher mortality, which may be predicted upon admission. These findings, however, warrant further investigation.
Topics: Humans; Male; Female; Aged; Aged, 80 and over; Propensity Score; Retrospective Studies; China; Risk Factors; Cerebrovascular Disorders; Ischemic Stroke; Coronary Artery Disease; Cause of Death; Prognosis; Comorbidity; East Asian People
PubMed: 38879523
DOI: 10.1186/s40001-024-01929-x -
Journal of the American Heart... Jun 2024The left internal mammary artery (LIMA) is protected from developing atherosclerosis. Perivascular inflammation, which is closely associated with atherosclerosis, can be... (Comparative Study)
Comparative Study
BACKGROUND
The left internal mammary artery (LIMA) is protected from developing atherosclerosis. Perivascular inflammation, which is closely associated with atherosclerosis, can be measured by perivascular adipose tissue attenuation on computed tomography angiography. Whether the absence of atherosclerosis in LIMA is related to the lower level of perivascular inflammation is unknown. This study was performed to compare the level of perivascular inflammation between LIMA in situ and native coronary arteries in patients with coronary artery disease.
METHODS AND RESULTS
A total of 573 patients who underwent both computed tomography angiography and optical coherence tomography imaging were included. The level of perivascular adipose tissue attenuation between LIMA in situ and coronary arteries was compared. Perivascular adipose tissue attenuation around LIMA in situ was significantly lower around the 3 coronary arteries (-82.9 [-87.3 to -78.0] versus -70.8 [-75.9 to -65.9]; <0.001), irrespective of the level of pericoronary inflammation or the number of vulnerable features on optical coherence tomography. When patients were divided into high and low pericoronary inflammation groups, those in the high inflammation group had more target vessel failure (hazard ratio, 2.97 [95% CI, 1.16-7.59]; =0.017).
CONCLUSIONS
The current study demonstrated that perivascular adipose tissue attenuation was significantly lower around LIMA in situ than around native coronary arteries. The lower level of perivascular inflammation may be related to the low prevalence of atherosclerosis in LIMA.
REGISTRATION
URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04523194.
Topics: Humans; Male; Female; Mammary Arteries; Tomography, Optical Coherence; Aged; Middle Aged; Coronary Artery Disease; Coronary Vessels; Computed Tomography Angiography; Coronary Angiography; Adipose Tissue; Retrospective Studies; Inflammation
PubMed: 38879462
DOI: 10.1161/JAHA.123.033224 -
Age and Ageing Jun 2024Peripheral artery disease (PAD) is the lower limb manifestation of systemic atherosclerotic disease. PAD may initially present with symptoms of intermittent... (Review)
Review
Peripheral artery disease (PAD) is the lower limb manifestation of systemic atherosclerotic disease. PAD may initially present with symptoms of intermittent claudication, whilst chronic limb-threatening ischaemia (CLTI), the end stage of PAD, presents with rest pain and/or tissue loss. PAD is an age-related condition present in over 10% of those aged ≥65 in high-income countries. Guidelines regarding definition, diagnosis and staging of PAD and CLTI have been updated to reflect the changing patterns and presentations of disease given the increasing prevalence of diabetes. Recent research has changed guidelines on optimal medical therapy, with low-dose anticoagulant plus aspirin recommended in some patients. Recently published randomised trials highlight where bypass-first or endovascular-first approaches may be optimal in infra-inguinal disease. New techniques in endovascular surgery have increased minimally invasive options for ever more complex disease. Increasing recognition has been given to the complexity of patients with CLTI where a high prevalence of both frailty and cognitive impairment are present and a significant burden of multi-morbidity and polypharmacy. Despite advances in minimally invasive revascularisation techniques and reduction in amputation incidence, survival remains poor for many with CLTI. Shared decision-making is essential, and conservative management is often appropriate for older patients. There is emerging evidence of the benefit of specialist geriatric team input in the perioperative management of older patients undergoing surgery for CLTI. Recent UK guidelines now recommend screening for frailty, cognitive impairment and delirium in older vascular surgery patients as well as recommending all vascular surgery services have support and input from specialist geriatrics teams.
Topics: Humans; Peripheral Arterial Disease; Aged; Endovascular Procedures; Risk Factors; Chronic Limb-Threatening Ischemia; Vascular Surgical Procedures; Age Factors; Practice Guidelines as Topic
PubMed: 38877714
DOI: 10.1093/ageing/afae114 -
BMC Psychiatry Jun 2024Coronary artery disease (CAD) is known as the leading cause of disability and death globally. Anxiety disorders are also recognized as common types of mental disorders...
BACKGROUND
Coronary artery disease (CAD) is known as the leading cause of disability and death globally. Anxiety disorders are also recognized as common types of mental disorders that substantially impact global health. Iran ranks among the countries with a high incidence of CAD and anxiety disorders. Therefore, the present study aims to determine the potential association and epidemiological aspects of anxiety and CAD within the population of Mashhad, the second most popoulos city in Iran.
METHODS
The present study is based on extracted data from the Mashhad stroke and heart atherosclerotic disorder (MASHAD) study which is a 10-year prospective cohort study intended to assess the effects of various CAD risk factors among Mashhad city residents. Anxiety scores were assessed at the baseline using Beck Anxiety Inventory and individuals were classified based on the BAI 4-factor structure model which included autonomic, cognitive, panic, and neuromotor components. Accordingly, the association between baseline anxiety scores and the BAI four-factor model with the risk of CAD events was analyzed using SPSS software version 21.
RESULTS
Based on the results, 60.4% of the sample were female, and 5.6% were classified as having severe forms of anxiety. Moreover, severe anxiety was more prevalent in females. Results showed a 1.7% risk of CAD (p-value < 0.001) over 10 years with one unit increase in anxiety score. Based on the 4-factor model structure, we found that only panic disorder could significantly increase the risk of CAD by 1.1% over the 10-year follow-up (p-value < 0.001).
CONCLUSION
Anxiety symptoms, particularly panic disorder, are independently and significantly associated with an increased overall risk of developing CAD over a 10-year period. Therefore, further studies are warranted to investigate the mechanisms through which anxiety may cause CAD, as well as possible interventions to mitigate these processes.
Topics: Humans; Female; Male; Coronary Artery Disease; Middle Aged; Iran; Prospective Studies; Risk Factors; Adult; Anxiety Disorders; Anxiety; Aged; Prevalence; Psychiatric Status Rating Scales
PubMed: 38877499
DOI: 10.1186/s12888-024-05798-w -
BMC Cardiovascular Disorders Jun 2024Stent restenosis is a relatively common phenomenon among patients with coronary heart disease undergoing percutaneous coronary intervention (PCI). It seems that a set of...
BACKGROUND
Stent restenosis is a relatively common phenomenon among patients with coronary heart disease undergoing percutaneous coronary intervention (PCI). It seems that a set of clinical, laboratory, and even genetic factors make people susceptible to such a phenomenon and in fact, this is multi-factorial. We aimed to first determine the underlying clinical and laboratory risk factors for the occurrence of stent re-stenosis after PCI based on a systematic review study, and after that, through a bioinformatics study, to evaluate the related genes and microRNAs with the occurrence of stent re-stenosis.
MAIN TEXT
In the first step, the manuscript databases including Medline, Web of Knowledge, Google Scholar, Scopus, and Cochrane were deeply searched by the two blinded investigators for all eligible studies based on the considered keywords to introduce clinical and laboratory determinants of stent re-stenosis. In the bioinformatic phase, and following a review of the literature to identify genes and microRNAs involved in restenosis, the interaction of each gene with other genes associated with stent re-stenosis was determined by GeneMANIA network analysis and Cytoscape software. Overall, 67 articles (including 40,789 patients) on clinical and biochemical predictors for stent restenosis and 25 articles on genetic determinants of this event were eligible for the final analysis. The predictors for this event were categorized into four subgroups patient-based parameters including traditional cardiovascular risk profiles, stent-based parameters including type and diametric characteristics of the stents used, coronary lesion-based parameters including several two target lesions and coronary involvement severity and laboratory-based parameters particularly related to activation of inflammatory processes. In the bioinformatic phase, we uncovered 42 genes that have been described to be involved in such a phenomenon considering a special position for genes encoding inflammatory cytokines. Also, 12 microRNAs have been pointed to be involved in targeting genes involved in stent re-stenosis.
CONCLUSIONS
The incidence of stent re-stenosis will be the result of a complex interaction of clinical risk factors, laboratory factors mostly related to the activation of inflammatory processes, and a complex network of gene-to-gene interactions.
Topics: Humans; Percutaneous Coronary Intervention; Coronary Restenosis; Stents; Risk Factors; Computational Biology; Coronary Artery Disease; MicroRNAs; Risk Assessment; Genetic Predisposition to Disease; Treatment Outcome; Female; Male; Gene Regulatory Networks; Middle Aged; Aged
PubMed: 38877398
DOI: 10.1186/s12872-024-03955-3 -
Journal of the American Heart... Jun 2024Cytochrome P450 2C19 (CYP2C19) intermediate and poor metabolizer patients exhibit diminished clopidogrel clinical effectiveness after percutaneous coronary intervention...
BACKGROUND
Cytochrome P450 2C19 (CYP2C19) intermediate and poor metabolizer patients exhibit diminished clopidogrel clinical effectiveness after percutaneous coronary intervention (PCI). However, outcome studies to date have lacked racial diversity. Thus, the impact of genotype on cardiovascular outcomes in patients treated with clopidogrel who identify as Black or African American remains unclear.
METHODS AND RESULTS
Adults among 5 institutions who self-identified as Black or African American, underwent PCI and clinical genotyping, and were treated with clopidogrel were included. Data were abstracted from health records. Major atherothrombotic (composite of death, myocardial infarction, ischemic stroke, stent thrombosis, or revascularization for unstable angina) and bleeding event rates within 1 year after PCI were compared across CYP2C19 metabolizer groups using multivariable Cox regression adjusted for potential confounders and baseline variables meeting a threshold of <0.10. The population included 567 Black patients treated with clopidogrel (median age, 62 years; 46% women; 70% with an acute coronary syndrome indication for PCI). Major atherothrombotic events rates were significantly higher among clopidogrel-treated intermediate and poor metabolizers (24 of 125 [19.2%]) versus patients treated with clopidogrel without a no function allele (43 of 442 [9.7%]; 35.1 versus 15.9 events per 100 person-years; adjusted hazard ratio, 2.00 [95% CI, 1.20-3.33], =0.008). Bleeding event rates were low overall (23 of 567 [4.1%]) and did not differ among the metabolizer groups.
CONCLUSIONS
Black patients with CYP2C19 intermediate and poor metabolizer phenotypes who are treated with clopidogrel exhibit increased risk of adverse cardiovascular outcomes after PCI in a real-world clinical setting. Bleeding outcomes should be interpreted cautiously. Prospective studies are needed to determine whether genotype-guided use of prasugrel or ticagrelor in intermediate and poor metabolizers improves outcomes in Black patients undergoing PCI.
Topics: Aged; Female; Humans; Male; Middle Aged; Acute Coronary Syndrome; Black or African American; Clopidogrel; Coronary Artery Disease; Cytochrome P-450 CYP2C19; Genotype; Hemorrhage; Percutaneous Coronary Intervention; Pharmacogenomic Variants; Platelet Aggregation Inhibitors; Retrospective Studies; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 38874073
DOI: 10.1161/JAHA.123.033791 -
Journal of the American Heart... Jun 2024
Topics: Humans; Female; Coronary Artery Disease; Sex Factors; Prognosis; Multifactorial Inheritance; Risk Assessment; Genetic Predisposition to Disease; Risk Factors; Male
PubMed: 38874071
DOI: 10.1161/JAHA.123.034946 -
EClinicalMedicine Jul 2024Janus kinase (JAK) inhibition is a promising approach for treating vitiligo. We aimed to assess the efficacy and safety of upadacitinib, an oral selective JAK inhibitor,...
Once-daily upadacitinib versus placebo in adults with extensive non-segmental vitiligo: a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-ranging study.
BACKGROUND
Janus kinase (JAK) inhibition is a promising approach for treating vitiligo. We aimed to assess the efficacy and safety of upadacitinib, an oral selective JAK inhibitor, in adults with non-segmental vitiligo.
METHODS
This was a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-ranging study completed at 33 clinical centres in the United States, Canada, France, and Japan. Eligible patients were aged 18-65 years with non-segmental vitiligo and had a Facial Vitiligo Area Scoring Index (F-VASI) ≥0.5 and a Total Vitiligo Area Scoring Index (T-VASI) ≥5. Patients were randomly assigned (2:2:2:1:1) using an interactive response technology to receive upadacitinib 6 mg (UPA6), upadacitinib 11 mg (UPA11), upadacitinib 22 mg (UPA22), or placebo (PBO; preassigned to switch to either UPA11 or UPA22 in period 2) once daily for 24 weeks (period 1). For weeks 24-52 (period 2), patients randomly assigned to upadacitinib continued their treatment, and patients receiving PBO switched to their preassigned upadacitinib dose in a blinded fashion. The primary endpoint was the percent change from baseline in F-VASI at week 24. Efficacy was analysed in the intention-to-treat population, and safety was examined in all randomly assigned patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT04927975.
FINDINGS
Between June 16, 2021, and June 27, 2022, 185 patients (including 115 [62%] who were female and 70 [38%] who were male) were randomly assigned to UPA6 (n = 49), UPA11 (n = 47), UPA22 (n = 43), or PBO (n = 46). At week 24, the LS mean difference versus PBO in the percent change from baseline in F-VASI was -7.60 (95% CI -22.18 to 6.97; p = 0.3037) for UPA6, -21.27 (95% CI -36.02 to -6.52; p = 0.0051) for UPA11, and -19.60 (95% CI -35.04 to -4.16; p = 0.0132) for UPA22. The LS mean difference versus PBO in the percent change from baseline in T-VASI was -7.45 (95% CI -16.86 to 1.96; p = 0.1198) for UPA6, -10.84 (95% CI -20.37 to -1.32; p = 0.0259) for UPA11 and -14.27 (95% CI -24.24 to -4.30; p = 0.0053) for UPA22. Ongoing treatment with upadacitinib induced continuous skin repigmentation over time without reaching a plateau through week 52. The rates for study drug discontinuation and serious treatment-emergent adverse events (TEAEs) were higher in the UPA22 group than in the UPA11 and UPA6 groups. Eight serious TEAEs, including one death of unknown cause and one case of infiltrating lobular breast carcinoma, were reported through 52 weeks; only two serious TEAEs (coronary artery arteriosclerosis [UPA6 (n = 1)] and non-fatal ischemic stroke [UPA11 (n = 1)]) were deemed by the investigator to have a reasonable possibility of being related to study drug. The one case of breast cancer in the UPA11 group was deemed unrelated to study drug, and the one death of unknown cause in the UPA22 group was reviewed and adjudicated and was deemed to be unrelated to study drug. The most common TEAEs were COVID-19, headache, acne, and fatigue. No new safety signals were observed.
INTERPRETATION
Upadacitinib monotherapy led to substantial repigmentation of both facial and total body vitiligo lesions and may offer an effective treatment option for adults with extensive non-segmental vitiligo. Based on these findings, upadacitinib 15 mg is being investigated in adults and adolescents with non-segmental vitiligo in an ongoing phase 3 randomised controlled trial.
FUNDING
AbbVie Inc.
PubMed: 38873632
DOI: 10.1016/j.eclinm.2024.102655