Sex-Based Outcomes of Dual-Antiplatelet Therapy After Percutaneous Coronary Intervention: A Pairwise and Network Meta-Analysis.

BACKGROUND: Although dual antiplatelet therapy (DAPT) improves the outcomes of patients undergoing percutaneous coronary intervention (PCI), sex-specific differences in efficacy and safety of DAPT remain unresolved. We compared sex differences for DAPT outcomes and DAPT durations (1-3 months [short-term], 6 months [mid-term], and >12 months [extended] vs. 12 months). METHODS: We searched databases through 31 December 2023 for trials reporting DAPT after PCI. The endpoints were major adverse cardiovascular and cerebrovascular events (MACCE), net adverse clinical and cerebrovascular events (NACCE), and any bleeding. Extracted data were pooled in a frequentist network and pairwise, random-effects meta-analysis. RESULTS: Twenty-two trials (99,591 participants, 25.2% female) were included. Female sex was significantly associated with a higher 1-year MACCE risk (hazard ratio 1.14 [95% confidence interval 1.02-1.28]) and bleeding (1.13 [1.00-1.28]), but not NACCE (1.12 [0.96-1.31]). In sub-analyses, the association between female sex and MACCE was related to use of clopidogrel as the second antiplatelet agent (1.11 [1.03-1.20]), whereas higher bleeding events were related to newer P2Y12 inhibitors (P2Y12i) (1.58 [1.01-2.46]). For DAPT duration, short-term DAPT followed by P2Y12i monotherapy was non-inferior for MACCE in females and males (0.95 [95% CI 0.83-1.10; and 0.96 [0.80-1.16]) but tended to be superior in males for NACCE versus 12-month DAPT (0.96 [0.91-1.01]); mid-term DAPT tended to be associated with a lower bleeding risk in males (0.43 [0.17-1.09]). CONCLUSIONS: Female sex is associated with higher MACCE and bleeding when newer P2Y12i agents are used. Short-term DAPT followed by P2Y12i monotherapy is safe and effective in both sexes undergoing PCI. CLINICAL TRIALS REGISTRATION: PROSPERO ID: CRD42021278663.

The impact of age, sex, cardio-respiratory fitness, and cardiovascular disease risk on dynamic cerebral autoregulation and baroreflex sensitivity.

BACKGROUND: Humans display an age-related decline in cerebral blood flow and increase in blood pressure (BP), but changes in the underlying control mechanisms across the lifespan are less well understood. We aimed to; (1) examine the impact of age, sex, cardiovascular disease (CVD) risk, and cardio-respiratory fitness on dynamic cerebral autoregulation and cardiac baroreflex sensitivity, and (2) explore the relationships between dynamic cerebral autoregulation (dCA) and cardiac baroreflex sensitivity (cBRS). METHODS: 206 participants aged 18-70 years were stratified into age categories. Cerebral blood flow velocity was measured using transcranial Doppler ultrasound. Repeated squat-stand manoeuvres were performed (0.10 Hz), and transfer function analysis was used to assess dCA and cBRS. Multivariable linear regression was used to examine the influence of age, sex, CVD risk, and cardio-respiratory fitness on dCA and cBRS. Linear models determined the relationship between dCA and cBRS. RESULTS: Age, sex, CVD risk, and cardio-respiratory fitness did not impact dCA normalised gain, phase, or coherence with minimal change in all models (P > 0.05). cBRS gain was attenuated with age when adjusted for sex and CVD risk (young-older; ß = - 2.86 P < 0.001) along with cBRS phase (young-older; ß = - 0.44, P < 0.001). There was no correlation between dCA normalised gain and phase with either parameter of cBRS. CONCLUSION: Ageing was associated with a decreased cBRS, but dCA appears to remain unchanged. Additionally, our data suggest that sex, CVD risk, and cardio-respiratory fitness have little effect.

Incidence and predictors of sudden cardiac death in arrhythmogenic right ventricular cardiomyopathy: a pooled analysis.

AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC), an inherited heart muscle abnormality, is a major cause of sudden cardiac death (SCD). However, the burden of SCD and risk factors in ARVC are not clearly described. Thus, we estimated the rates and predictors of SCD in ARVC in a meta-analysis. METHODS AND RESULTS: PubMed, Embase, and Web of Science were searched through 7 April 2021. Prospective studies reporting SCD from ARVC cohorts were included. Data were independently extracted by two reviewers and pooled in a random-effects meta-analysis. Fifty-two studies (n = 5485 patients) with moderate-to-low risk of bias were included. The pooled annualized rates of SCD were 0.65 per 1000 [95% confidence interval 0.00-6.43, I2 0.00%] in those with an implantable cardioverter-defibrillator (ICD) and 7.21 (2.38-13.79, I2 0.0%) in non-ICD cohorts: 7.14 in probands and 8.44 for 2010 Task Force Criteria (TFC). Multivariable predictors of life-threatening arrhythmic events including SCD were: age at presentation [adjusted hazard ratio 0.98 (0.97-0.99)], male sex [2.08 (1.29-3.36)], right ventricular (RV) dysfunction [6.99 (2.17-22.49)], QRS fragmentation [6.55 (3.33-12.90)], T-wave inversion [1.12 (1.02-1.24)], syncope at presentation [2.83 (2.40-4.08)], previous non-sustained ventricular tachyarrhythmia [2.53 (1.44-4.45)], and the TFC score [1.96 (1.02-3.76)], (P < 0.05). Predictors of appropriate ICD therapy were RV dysfunction, syncope, and inducible ventricular arrhythmia (P < 0.01). CONCLUSION: This meta-analysis demonstrates a high burden of SCD in ARVC patients, especially among probands and ARVC defined by the modified TFC. Better strategies are required to improve patient management and prevent SCD in ARVC. PROSPERO ID: CRD42020211761.

Impact of green tea on the deleterious cardiometabolic effects of 7-days unhealthy lifestyle in young healthy males.

PURPOSE: The aim of this study was to examine if catechin-rich green tea abrogates the negative effects of 7-days of physical inactivity and excessive calorie-intake on insulin homeostasis and peripheral vascular function. METHODS: Using a randomized, double-blind, crossover design, twelve healthy men (29 ± 6 yrs) underwent 7-days unhealthy lifestyle (UL), including physical inactivity (-50% steps/day) and overfeeding (+50% kcal/day). This was combined with green tea consumption (UL-tea; 3 doses/day) or placebo (UL-placebo). Before and after each intervention, we examined postprandial blood glucose and insulin (3-h after a 1,202 kcal meal) and upper and lower limb vascular function (flow-mediated dilation (FMD%)) and carotid artery reactivity (CAR%). RESULTS: UL-placebo increased postprandial glucose and insulin, while UL-tea decreased postprandial glucose and insulin (Time*Intervention interaction effects: both p < 0.05). UL-placebo decreased CAR% and femoral FMD%, while UL-tea prevented these effects (Time*Intervention interaction effects of p < 0.04 and p < 0.001, respectively). There was no main effect of Time or Time*Intervention interaction (both p > 0.05) for brachial FMD%. CONCLUSION: Seven days of physical inactivity and overfeeding impair insulin homeostasis and vascular function. These effects were mitigated by a daily intake of catechin-rich green tea.

The Role of MSC Therapy in Attenuating the Damaging Effects of the Cytokine Storm Induced by COVID-19 on the Heart and Cardiovascular System.

The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has led to 47 m infected cases and 1. 2 m (2.6%) deaths. A hallmark of more severe cases of SARS-CoV-2 in patients with acute respiratory distress syndrome (ARDS) appears to be a virally-induced over-activation or unregulated response of the immune system, termed a "cytokine storm," featuring elevated levels of pro-inflammatory cytokines such as IL-2, IL-6, IL-7, IL-22, CXCL10, and TNFα. Whilst the lungs are the primary site of infection for SARS-CoV-2, in more severe cases its effects can be detected in multiple organ systems. Indeed, many COVID-19 positive patients develop cardiovascular complications, such as myocardial injury, myocarditis, cardiac arrhythmia, and thromboembolism, which are associated with higher mortality. Drug and cell therapies targeting immunosuppression have been suggested to help combat the cytokine storm. In particular, mesenchymal stromal cells (MSCs), owing to their powerful immunomodulatory ability, have shown promise in early clinical studies to avoid, prevent or attenuate the cytokine storm. In this review, we will discuss the mechanistic underpinnings of the cytokine storm on the cardiovascular system, and how MSCs potentially attenuate the damage caused by the cytokine storm induced by COVID-19. We will also address how MSC transplantation could alleviate the long-term complications seen in some COVID-19 patients, such as improving tissue repair and regeneration.

Vascular Manifestations of COVID-19 - Thromboembolism and Microvascular Dysfunction.

The coronavirus pandemic has reportedly infected over 31.5 million individuals and caused over 970,000 deaths worldwide (as of 22nd Sept 2020). This novel coronavirus, officially named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), although primarily causes significant respiratory distress, can have significant deleterious effects on the cardiovascular system. Severe cases of the virus frequently result in respiratory distress requiring mechanical ventilation, often seen, but not confined to, individuals with pre-existing hypertension and cardiovascular disease, potentially due to the fact that the virus can enter the circulation via the lung alveoli. Here the virus can directly infect vascular tissues, via TMPRSS2 spike glycoprotein priming, thereby facilitating ACE-2-mediated viral entry. Clinical manifestations, such as vasculitis, have been detected in a number of vascular beds (e.g., lungs, heart, and kidneys), with thromboembolism being observed in patients suffering from severe coronavirus disease (COVID-19), suggesting the virus perturbs the vasculature, leading to vascular dysfunction. Activation of endothelial cells via the immune-mediated inflammatory response and viral infection of either endothelial cells or cells involved in endothelial homeostasis, are some of the multifaceted mechanisms potentially involved in the pathogenesis of vascular dysfunction within COVID-19 patients. In this review, we examine the evidence of vascular manifestations of SARS-CoV-2, the potential mechanism(s) of entry into vascular tissue and the contribution of endothelial cell dysfunction and cellular crosstalk in this vascular tropism of SARS-CoV-2. Moreover, we discuss the current evidence on hypercoagulability and how it relates to increased microvascular thromboembolic complications in COVID-19.

Reproducibility of four frequently used local heating protocols to assess cutaneous microvascular function.

BACKGROUND: Skin microvascular responses to local heating are frequently used to assess microvascular function. Several local heating protocols have been developed, all varying slightly in execution. The aim of this study was to determine the inter-day reproducibility of the four most commonly used local heating protocols in healthy young subjects. METHODS: Fifteen, healthy males (28±5yrs, BMI 25±2kg/m2) attended two experimental trials 2-7days apart. During each trial, baseline and maximal thermally stimulated forearm skin responses were examined simultaneously at four sites on the dominant forearm using laser Doppler flowmetry (LDF). The following heating protocols were adopted: 1. Rapid 39°C (0.5°C/5s), 2. Rapid 42°C (0.5°C/5s) 3. Gradual 42°C (0.5°C/2min 30s) and 4. Slow 42°C (0.5°C/5min). The coefficient of variation (CV) was calculated for absolute flux, cutaneous vascular conductance (CVC; flux/mean arterial pressure, MAP) and CVC expressed as a percentage of maximal CVC at 44°C (%CVCmax) at three different time points; baseline (33°C), plateau (39/42°C) and maximal (44°C). RESULTS: Reproducibility of baseline flux, CVC and %CVCmax was 17-29% across all protocols. During the plateau, Rapid, Gradual and Slow 42°C demonstrated a reproducibility of 13-18% for flux and CVC and 5-11% for %CVCmax. However, Rapid 39°C demonstrated a lower reproducibility for flux, CVC and %CVCmax (all 21%). Reproducibility at 44°C was 12-15% for flux and CVC across all protocols. CONCLUSION: This is the first study examining inter-day reproducibility across four local heating protocols. The good-to-moderate reproducibility of the Rapid, Gradual and Slow 42°C protocols support their (simultaneous) use to assess microvascular function. Using Rapid 39°C may require a greater number of subjects to detect differences within subjects.