Search Results (96)

Introduction: Previous studies have reported sex differences in stroke. There are few Asian studies. This study was performed to investigate sex differences in stroke risk factors and mechanisms in a multi-ethnic Asian population. Methods: Data on patients admitted to Raffles Hospital for stroke were analysed. Data were extracted on sex, age, hypertension, diabetes mellitus (DM), hyperlipidaemia, smoking, heart disease, and prior cerebrovascular events (pCeVD). Stroke was subtyped into haemorrhagic stroke (HS) or ischaemic stroke (IS) based on brain scan. IS mechanism was categorised using Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, while the clinical syndrome by Oxfordshire Community Stroke Project (OCSP) classification. Results: Data were collected on 1165 patients, mean age 65.6 ± 12.9 yr; 47.4% female, 83.0% Chinese, with hypertension (63.5%) and hyperlipidaemia (60.3%) being the most common risk factors. HS comprised 23.5%. On regression analysis, compared to males, females had older age (OR 1.03, 95%CI 1.02–10.4) and DM (OR 1.60, 95%CI 1.11–2.30), but less smoking (OR 0.09, 95%CI 0.07–0.13), pCeVD (OR 0.67, 95%CI 0.49–0.93), and HS (OR 0.71, 95%CI 0.51–0.98). There were no differences in HS mechanisms, or IS mechanisms or syndromes. Sex–ethnic differences were found (p < 0.001), with more Chinese and fewer Indians among females compared to males. Conclusions: This study corroborates previous studies of significantly older age and more diabetes mellitus, but less smoking and haemorrhagic stroke among female stroke patients compared to males; differences in HS and IS mechanisms were not found. Novel in this study is that sex–ethnicity differences were found. Future studies should prospectively validate these sex/ethnic differences. Full article

Background: Low selenium intake and age-related decline of coenzyme Q₁₀ (CoQ₁₀) have been associated with an increased risk of cardiovascular disease (CVD) and oxidative stress. In a randomised placebo-controlled trial (RTC) in elderly people with low selenium levels, the supplementation with selenium and CoQ₁₀ reduced CVD and mortality. However, whether the supplementation elicited sex-specific benefits remained to be explored. Methods: Elderly Swedish persons (n = 443; balanced sex ratio) receiving selenium yeast (200 µg/day) and CoQ₁₀ (200 mg/day) combined or a placebo for four years were followed for additional six years. The response to supplementation, cardiovascular (CV) mortality, and risk factors were determined at four and ten years. Kaplan–Meier analyses, ANCOVA, repeated measurements of variance, and Cox proportional hazard regression analyses were performed. Results: The measured 10-year CV mortality rate was lower in females, and supplementation reduced this risk to a greater extent compared to in males. The improved survival rate apparently kicked in later in females than in males. At baseline, males had a higher smoking rate, increased inflammation and oxidative stress, and a higher prevalence of more advanced ischaemic heart disease (IHD) and signs of heart failure. When stratified by sex, in individuals with IHD, the intervention improved CV survival in both sexes, whereas supplementation had a more pronounced effect in females without IHD at inclusion. Supplementation diminished inflammation and oxidative stress, impaired the increase of NT-proBNP, and improved renal function in both sexes. Conclusions: The supplementation improved CV survival, especially in women. The higher prevalence of structural CVD and smoking in males may have contributed to the observed greater supplementation benefits in females. The preventive impact of selenium and CoQ₁₀ supplementation in elderly males and females may be particularly strong and meaningful in the early stages of CVD development. Full article

Background: Matrix metalloproteinase 9 (MMP9) has recently emerged as a risk predictor in patients with cardiovascular diseases (CVD). However, little is known regarding the significance of elevated plasma MMP9 levels in patients during the long-term period following myocardial revascularisation. We aimed to investigate the role of MMP9 in relation to myocardial status before and after myocardial revascularisation and to assess its long-term prognostic value. Methods: This prospective observational study included 200 male patients with ischaemic heart disease. All patients underwent direct myocardial revascularisation on a beating heart (off-pump surgery). Plasma MMP9 levels were analysed preoperatively, at 48 h postoperatively, and during the long-term follow-up period (one year postoperatively). Key echocardiographic parameters, specifically left ventricular ejection fraction (LVEF) and Left Ventricular End-Diastolic Volume (LVEDV), were also assessed. Results: MMP9 levels decreased significantly at 48 h postoperatively (p < 0.0001). During the long-term postoperative period, a clear relationship was demonstrated: higher 1-year MMP9 levels were associated with lower 1-year LVEF, whilst lower 1-year MMP9 levels were associated with higher 1-year LVEF. No significant correlation was observed between preoperative MMP9 levels and age or most other baseline laboratory parameters. Conclusions: Our study established an association between 1-year postoperative MMP9 levels and key parameters of left ventricular function during the long-term follow-up period. This suggests that MMP9 may serve as a novel biomarker for predicting outcomes following myocardial revascularisation. Full article

Introduction: The combination of BRAF and MEK inhibitors (BRAF/MEKi) has significantly improved survival in melanoma patients with BRAF V600 mutations. However, these agents can cause cardiovascular (CV) toxicity, compromising efficacy. This study evaluated the CV adverse events (cAEs) associated with BRAF/MEKi using the U.S. FDA Adverse Event Reporting System (FAERS) to identify new signals of disproportionate reporting (SDRs). Methods: Descriptive and disproportionality analyses were conducted on reports listing dabrafenib (D), vemurafenib (V), encorafenib (E), trametinib (T), cobimetinib (C), or binimetinib (B) as suspects in monotherapy or combination therapy (D + T, V + C, E + B), with melanoma as the indication and at least one cAE. Standardized MedDRA Queries (SMQs) related to cAEs, including bradyarrhythmias and tachyarrhythmias, cardiac failure, cardiomyopathy, thrombotic events, ischaemic heart disease, and myocarditis/pericarditis, were analyzed. Results: Of the 14,077,067 reports retrieved, 18,370 (0.1%) were linked to BRAF/MEKi, with 1591 (8.7%) reporting cAEs, primarily in combination therapy (n = 1268). Disproportionality analysis identified 64 clinically relevant SDRs, most of which were unexpected. Notable findings included bradyarrhythmias, such as QT prolongation with D + T (n = 59; Reporting Odds Ratio, ROR = 5.09, 95% Confidence Interval, CI = 3.94–6.58), cardiac failure with V + C (29; 3.76, 2.6–5.42), and tachyarrhythmias, particularly atrial fibrillation with D + T (99; 2.37, 1.94–2.89). Among embolic and thrombotic events, clinically significant SDRs were observed for disseminated intravascular coagulation with D + T (38; 10.22, 7.42–14.06) and pulmonary embolism with V + C (22; 2.79, 1.83–4.24). Conclusions: Our findings underscore the need for comprehensive CV monitoring in patients receiving BRAF/MEKi therapy to prevent or detect cAEs early and reduce treatment-related risks, particularly in high-risk populations. Full article

Background: Mesenchymal stem cell-based therapy may be indicated in ischaemic heart disease. The use of autologous adipose-derived mesenchymal stromal cells (AdMSCs) offers regenerative potential due to their paracrine effects. The aim of this study was to expand and characterise adult human thymus-derived MSCs harvested during open heart surgery with respect to their stem cell and paracrine properties. Methods: Enzymatically and non-enzymatically isolated human thymic AdMSCs (ThyAdMSCs) were cultured in xeno-free media containing pooled human platelet lysate (pPL). MSC characterisation was performed. Ex vivo expanded ThyAdMSCs were differentiated into three lineages. Proliferative capacity and immunomodulatory properties were assessed by proliferation assays and mixed lymphocyte reaction, respectively. Gene expression analysis was performed by qPCR. Results: Both isolation methods yielded fibroblast-like cells with plastic adherence and high proliferation. Flow cytometry revealed distinct expression of MSC markers in the absence of haematopoietic cell surface markers. Ex vivo expanded ThyAdMSCs could be differentiated into adipocytes, osteocytes, and chondrocytes. Activated peripheral blood mononuclear cells were significantly reduced when co-cultured with ThyAdMSCs, indicating their ability to inhibit immune cells in vitro. Gene expression analysis showed significantly less IFNγ and TNFα, indicating an alteration of the activated and pro-inflammatory state in the presence of ThyAdMSCs. Conclusions: These results demonstrate an efficient method to generate AdMSCs from human thymus. These MSCs have a strong immunomodulatory capacity and are, therefore, a promising cell source for regenerative medicine. The culture conditions are crucial for cells to proliferate in culture. Further research could explore the use of ThyAdMSCs or their secretome in surgical procedures. Full article

Ischaemic heart disease (IHD) is a chronic condition that can cause pathological cardiac remodelling and heart failure (HF). In this study, we sought to determine how cardiac fibroblasts were altered post-experimental myocardial infarction (MI). Female C57BL6 mice underwent experimental MI by permanent left coronary artery ligation. Cardiac fibroblasts were isolated from extracted heart tissue of experimental MI mice and subsequently treated with the pro-fibrotic cytokine, TGF-β, for 24 h and analysed using high throughput LC-MS/MS analysis. Findings were validated using mass spectrometry data generated from human left ventricular tissue analysis, which were collected from patients with ischaemic cardiomyopathy (ISCM) and age/sex-matched patients without clinical HF (NF). Proteomic analysis revealed significant protein expression changes in mouse cardiac fibroblasts after MI. These changes were most pronounced at 1 month post-MI, compared to earlier time points (3 days and 1 week). TGF-β treatment profoundly affected fibroblast cells extracted from MI mice, indicating a heightened sensitivity to pro-fibrotic factors after myocardial injury. Extracellular matrix (ECM) proteins significantly altered in MI fibroblasts following TGF-β treatment were significantly associated with cardiac remodelling. Notably, Lox was significantly changed in both isolated fibroblasts treated with TGF-β from experiment MI mice and human ISCM. Isolated cardiac fibroblasts from MI mice are more susceptible to developing pathogenic traits following TGF-β treatment than isolated fibroblasts from normal heart tissue. ECM proteins associated with these enhanced fibroblast activities and functions are evident. These altered proteins may play a functional role in MI-associated cardiac dysfunction. Full article

Background and Objectives: ST elevation myocardial infarction (STEMI), particularly when complicated by cardiogenic shock (CS), is a critical condition associated with high mortality rates. Identifying predictors of in-hospital mortality can enhance patient management and outcomes. Materials and Methods: This observational, retrospective case–control study included STEMI patients, both complicated and uncomplicated by CS. Additionally, demographics, clinical characteristics, laboratory data and in-hospital mortality rates were analysed for STEMI patients with CS and those without CS. Results: This study included a total of 101 patients with STEMI, of whom 51 (50.5%) had STEMI without CS and 50 (49.5%) had STEMI with CS. No significant differences were observed in demographic characteristics or STEMI risk factors between the two groups. Emergency coronarography was performed in 90.1% of the patients, with successful thrombolysis achieved in 24.5%. Patients with CS exhibited a significantly higher mortality (52%) than those without CS (11.76%). Univariate analysis identified white blood cell counts, CK-MB, CK levels, elevated creatinine and uric acid levels and a reduced left ventricular ejection fraction (LVEF) as predictors of mortality. Logistic regression analysis revealed that LVEF and CK-MB were independent predictors of in-hospital mortality in patients with STEMI and CS. Each 1% increase in LVEF was associated with a reduced mortality risk (HR = 0.89; 95% CI 0.81–0.98; p = 0.018), while elevated CK-MB levels were linked to an increased mortality risk (HR = 1; 95% CI 1–1.01; p = 0.014). Conclusions: Reduced systolic function and elevated CK-MB levels are key predictors of in-hospital mortality and outcomes in STEMI patients with CS. These findings underscore the importance of early identification and support the development of targeted management strategies aimed at improving outcomes in this high-risk population. Full article

Introduction: Percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is a cornerstone of the management of ischemic heart disease. However, in-stent restenosis (ISR) remains a significant clinical challenge, occurring in approximately 5–10% of patients undergoing PCI. This study is designed to compare the efficacy and safety of the primary therapeutic approaches for DES-ISR, specifically drug-coated balloons (DCBs)—paclitaxel-coated balloons (PCBs) and sirolimus-coated balloons (SCBs)—with a new-generation everolimus-eluting stent (EES), contributing to the evolving field of personalized medicine. Methods and Analysis: This prospective, multicentre, randomised, non-inferiority trial aims to enroll 150 patients with DES-ISR, who will be randomised into one of the following: SCB, PCB, or EES. The primary endpoint comparing DCB and EES is late lumen loss (LLL) at 6 months, as measured by quantitative coronary angiography (QCA). Secondary endpoints comparing the three arms include a device-oriented composite endpoint, intraluminal gain, optical coherence tomography (OCT) measured LLL, and correlations between LLL and quantitative flow ratio (QFR). The primary endpoint will be analysed using a non-inferiority design, with a margin set at 0.25 mm, for which the sample size was calculated. Statistical analysis of the primary endpoint will be conducted on an intention-to-treat basis with a one-tailed Mann–Whitney U test with a significance level of 95. Secondary endpoints will be analysed via superiority testing using ANOVA, the Kruskal–Wallis test, logistic regression, or Fisher’s exact test, as appropriate. Ethics and Dissemination: The study protocol has been approved by the Medical Devices Department of the Hungarian National Institute of Pharmacy and Nutrition, ensuring compliance with ethical standards as outlined in the Declaration of Helsinki. All investigators declare no conflicts of interest related to this study. The trial is registered in ClinicalTrials.gov under the ID: NCT04862052. Full article

As snorkelling and breath-hold diving are conducted in a potentially hostile environment by participants with varying skills and health, fatalities occur. In this study, snorkelling and breath-hold diving fatalities were investigated in Australia from 2000 to 2021 to identify causes and countermeasures. The Australasian Diving Safety Foundation database and the National Coronial Information System were searched to identify snorkelling/breath-hold diving deaths from 2000 to 2021. Relevant data were extracted, recorded, and analysed. The median age of the 317 victims was 48 years, two-thirds were overweight or obese, and almost half had health conditions, including ischaemic heart disease (IHD) and left ventricular hypertrophy (LVH), predisposing them to an arrhythmia-related snorkelling incident. One-third of victims were likely disabled by cardiac arrhythmias and at least 137 deaths were from primary drowning, with 34 following apnoeic hypoxia. Pre-existing health conditions, particularly IHD and LVH, predispose to many snorkelling deaths in older participants and may be somewhat mitigated by targeted health screening. Drownings from apnoeic hypoxia persist in younger breath-hold divers who should avoid pushing their limits without close monitoring. Skills practice in a controlled environment, increased focus on the importance of an effective buddy, and improved supervision are necessary to mitigate risk in the inexperienced. Full article

Background: Heart failure (HF) with preserved ejection fraction (pEF) has lacked effective treatments for reducing mortality. However, previous studies have found an association between statin use and decreased mortality in patients with HFpEF. The aim of this study was to analyse whether statin therapy is associated with a reduction in mortality in these patients and whether the effect differs according to the presence or absence of ischaemic heart disease (IHD). Methods: We analysed data from the National Registry of Heart Failure, a prospective study that included patients admitted for HF in Internal Medicine units nationwide. Patients with HFpEF were classified according to the use of statins, and the differences between the two groups were analysed. A multivariable analysis was performed using Cox regression to assess factors independently related to mortality. Results: A total of 2788 patients with HFpEF were included; 63% of them were women with a mean age of 80.1 (±7.8) years. The statin-treated group (40.2%) was younger, with better functional status, and had a more common diagnosis of vascular disease and lower frequency of atrial fibrillation. The most frequent aetiology of HF in both groups was the hypertensive one. Nevertheless, ischaemic HF was more common in those who received statins (24.8% vs. 9.6%; p < 0.001). Multivariable analysis showed lower mortality at the 1-year follow-up in statin-treated patients (OR: 0.74; 95%CI: 0.61–0.89; p = 0.002). This association was observed in patients without IHD (p < 0.001) but not in those with IHD (p = 0.11). Conclusions: Statins are associated with a decrease in total mortality in patients with HFpEF. This benefit occurs mainly in those without IHD. Full article

Background: Ischaemic heart disease is one of the major drivers of cardiovascular death in Europe. Since the first percutaneous coronary intervention (PCI) in 1977, developments and innovations in cardiology have made PCI the treatment of choice for stenotic coronary artery disease. To address the occupational hazards related to chronic exposure to radiation and wear and tear from heavy lead-based radioprotective aprons, the concept of robotically assisted PCI (R-PCI) was introduced in 2005. Aim: To explore the features and limitations of R-PCI, we first discuss the concept and evolution of R-PCI platforms and then systematically review the available clinical data. Methods: A systematic review has been performed across the Pubmed, Embase and Cochrane databases in order to assess the efficacy and safety of R-PCI. Secondary endpoints, such as operator and patient exposure to radiation, contrast volume used and procedural time, were assessed when available. Results: In selected patients, R-PCI provides high technical and clinical success rates, ranging from 81 to 98.8% and from 93.3 to 100%, respectively. In-hospital and 1-year MACE rates ranged from 0 to 10.4% and 4.8 to 10.5%, respectively. R-PCI is able to significantly reduce the operator’s exposure to radiation. Further research analysing the patient’s and cath lab staff’s exposure to radiation is needed. Therapy escalation with R-PCI seems to be limited to complex lesions. R-PCI procedures add approximately 10 min to the procedural time. Conclusions: The efficacy and safety of R-PCI have been proven, and R-PCI is able to significantly reduce occupational hazards for the first operator. The lack of adoption in the community of interventional cardiologists may be explained by the fact that current generations of R-PCI platforms are limited by their incompatibility with advanced interventional devices and techniques needed for escalation in complex interventions. Full article

Background/Objectives: A comprehensive and up-to-date review on cardiovascular disease (CVD) risk in patients with COPD is needed. Therefore, we aimed to systematically review the risk of a range of CVD in patients with COPD. Methods: We searched three databases (Pubmed, Web of Science, SCOPUS) from inception to September 2023 using terms related to COPD and CVD. Observational studies were included if they (1) were conducted in adults with a diagnosis of COPD based on the GOLD criteria, spirometry, physician diagnosis, or review of electronic health records; (2) reported the risk of CVD, namely of myocardial infarction (MI), ischaemic heart disease (IHD), atrial fibrillation (AF), heart failure, cerebrovascular disease, pulmonary hypertension, and peripheral vascular disease, compared with a control population using a measure of risk. A narrative synthesis was used. Results: Twenty-four studies from 2015 to 2023, mainly from Europe (n = 17), were included. A total of 3,485,392 patients with COPD (43.5–76.0% male; 63.9–73.5 yrs) and 31,480,333 (40.0–55.4% male, 49.3–70.0 yrs) controls were included. A higher risk of CVD in patients with COPD was evident regarding overall CVD, MI, IHD, heart failure, and angina. Higher risks of arrhythmia and AF, stroke, sudden cardiac death/arrest, pulmonary embolism, pulmonary hypertension, and peripheral vascular disease were also found, although based on a small amount of evidence. Conclusions: Patients with COPD have a higher risk of CVD than the general population or matched controls. This review underscores the need for vigilant and close monitoring of cardiovascular risk in individuals with COPD to inform more precise preventive strategies and targeted interventions to enhance their overall management. Full article

Furin is an important proteolytic enzyme, converting several proteins from inactive precursors to their active forms. Recently, proteo-genomic analyses in European and East Asian populations suggested a causal association of furin with ischaemic heart disease, and there is growing interest in its role in cardiovascular disease (CVD) aetiology. In this narrative review, we present a critical appraisal of evidence from population studies to assess furin’s role in CVD risk and potential as a drug target for CVD. Whilst most observational studies report positive associations between furin expression and CVD risk, some studies report opposing effects, which may reflect the complex biological roles of furin and its substrates. Genetic variation in FURIN is also associated with CVD and its risk factors. We found no evidence of current clinical development of furin as a drug target for CVD, although several phase 1 and 2 clinical trials of furin inhibitors as a type of cancer immunotherapy have been completed. The growing field of proteo-genomics in large-scale population studies may inform the future development of furin and other potential drug targets to improve the treatment and prevention of CVD. Full article

Background/Objectives: Grafting of LIMA to LAD has long been considered the gold-standard conduit choice for patients undergoing CABG. Despite this, the LSV remains the most used conduit by volume and some patients may not receive even a single arterial conduit. However, the outcomes in this group are not frequently explored. This study, therefore, compares in-hospital outcomes of patients who underwent CABG without any arterial conduits to those who received at least one arterial conduit. Methods: Retrospective propensity-matched database analysis of consecutive patients undergoing CABG in the UK between 1996 and 2019 using data from the National Adult Cardiac Surgery Audit. Results: 335,144 patients underwent CABG, with 6% receiving venous conduits only; matched outcomes are reported for 39,812 patients. In both unmatched and matched groups, we found a significant increase in mortality with the use of veins only (matched mortality 5.3% vs. 3.8%, p < 0.001) with estimated treatment effect for mortality OR 1.43, p < 0.001 (95% CI: 1.31–1.57). We also identified greater rates of post-operative dialysis, IABP insertion, and length of hospital stay in this group. Conclusions: We identified a significant increase in in-hospital mortality with the use of veins only compared to using at least one arterial graft to the LAD. While a single arterial graft should be prioritised wherever possible, venous revascularisation retains a critical role for specific patients. We must, therefore, continue to conduct research addressing the mechanisms underlying and propagating vein graft disease in order better to optimise outcomes for this niche patient group after CABG. Full article

Objectives: Fruit and vegetable (FV) consumption has been inversely associated with cardiovascular disease, but questions remain about the extent to which these results are due to confounding. Methods: From 2006–2010, >0.5 million adults aged 40–69 were recruited to the UK Biobank. Participants free from ischaemic heart disease (IHD) or stroke, with complete information on key covariates, were analysed (n = 452,760). Usual FV intakes were measured by frequency questionnaire, categorised into four groups, and calibrated with a 24-h dietary assessment. Multivariable Cox regression was used to estimate the associations of fruit and/or vegetable intake with IHD, ischaemic stroke, and haemorrhagic stroke, adjusted for socioeconomic status, lifestyle factors, dietary factors, and body mass index. Sequential change in likelihood ratio (LR) ꭕ² was used to quantify the contribution of covariates to model fit. Results: During 12–16 years of follow-up, there were 15,746 IHD events, 5940 ischaemic strokes, and 2154 haemorrhagic strokes. Associations were mostly non-linear. The lowest IHD risk was with the third category of fruit intake (median 216 g/day, HR 0.93 (95% confidence interval 0.90 to 0.97)) and second category of vegetable intake (158 g, 0.95 (0.93, 0.98)). Only the third category of fruit intake and combined FV intake were associated with a lower ischaemic stroke risk (216 g, 0.93 (0.88, 0.99) and 375 g, 0.92 (0.86, 0.97) respectively). Only the highest category of fruit intake (293 g, 0.87 (0.78, 0.98)) and second category of vegetable intake (158 g, 0.89 (0.83, 0.96)) were associated with a lower haemorrhagic stroke risk. Full adjustment reduced the LR ꭕ² of associations with ischaemic disease by 87–92% and haemorrhagic stroke by 66–70%. For IHD and ischaemic stroke, the biggest reductions were with the addition of lifestyle factors in models of FV or fruit intake and socioeconomic status for vegetable intake. Discussion: The relationship between fruit and/or vegetable intake and these cardiovascular outcomes is heavily confounded by socioeconomic, lifestyle, and dietary factors. Residual confounding may explain more of the remaining association. Therefore, caution should be exercised when estimating the burden of disease attributable to low fruit and vegetable intake. Full article