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- Incidence and prevalence of thoracic aortic aneurysms: a systematic review and meta-analysis of population-based studiesPublication . Melo, Ryan; Duarte, Gonçalo Silva; Lopes, Alice; Alves, Mariana; Caldeira, Daniel; Fernandes E Fernandes, Ruy; Pedro, Luís MThoracic aortic aneurysms (TAA) may grow asymptomatically until they rupture, with a mortality over 90%. The true incidence and prevalence of this condition is uncertain and epidemiologic data is scarce, understudied and dispersed. Therefore, we aimed to conduct a systematic review and meta-analysis of the incidence and prevalence of TAAs in population-based studies. We searched MEDLINE, EMBASE and CENTRAL from inception to October 2020 for all population-based studies reporting on incidence and/or prevalence of TAAs. Data were pooled using a random effects model. The main outcome was the overall available worldwide incidence and prevalence of TAAs. The secondary outcomes were to evaluate the incidence of ruptured TAAs, differences in the location of these aneurysms (either ascending, arch or descending aorta) and differences in prevalence/incidence across different study designs. Twenty-two studies were included in the review and meta-analysis. The pooled incidence and prevalence of TAAs was 5.3 per 100,000 individuals/year (95% confidence interval [CI]: 3.0; 8.3) and 0.16% (95% CI: 0.12; 0.20), respectively. The pooled incidence of ruptured aneurysms was 1.6 per 100,000 individuals/year (95% CI: 1.3; 2.1). We found a significant difference of the prevalence in autopsy-only studies, which was 0.76% (95% CI: 0.47; 1.13) and the prevalence of TAAs dropped down to 0.07% (95% CI: 0.05;0.11) when these studies were excluded from the overall analysis. The current epidemiologic information provided serve as a base for future public-health decisions. The lack of well-design population-base studies and the limitations encountered serve as calling for future research in this field.
- Aspirin in diabetic patients at primary prevention: insights of the VITAL cohortPublication . Caldeira, Daniel; Alves, Mariana; Ferreira, Joaquim J; Pinto, Fausto J.Purpose: Aspirin use among patients with diabetes in primary prevention is still a matter of debate. We aimed to evaluate the potential cardiovascular risk benefit of aspirin in primary prevention, using data from a contemporary cohort. Methods: Retrospective analysis of the VITAL cohort with > 20,000 individuals at primary prevention who were followed for a median of 5.3 years. The population was evaluated according to the baseline diabetes status, and then aspirin use was evaluated among diabetic patients. Cox regression models were used to estimate the risks of mortality and cardiovascular outcomes. The estimates were reported using adjusted hazard ratio (HR) and 95% confidence intervals (95%CI). Results: Diabetic patients (n = 3549; 13.7%) showed to increase the risk of all-cause mortality (HR 1.61, 95%CI 1.33-1.94), and major adverse cardiovascular events (MACE) (HR 1.36 95%CI 1.11-1.68) than non-diabetic population. Diabetic patients taking aspirin were older, more frequently man, hypertensive, current users of statins, and current smokers compared with diabetic patients who did not use aspirin at baseline. There was no difference between diabetic aspirin users and non-users regarding all-cause mortality (HR 0.80, 95%CI 0.59, 1.10), MACE (HR 0.92, 95%CI 0.64, 1.33), coronary heart disease (HR 0.98, 95%CI 0.67, 1.43), or stroke (HR 0.87, 95%CI 0.48, 1.58). Conclusions: The VITAL data confirmed diabetes as an important risk factor for cardiovascular events in a contemporary cohort but did not show cardiovascular benefits of aspirin in primary prevention among people with diabetes who were shown to be at higher risk of cardiovascular events.
- Cardiovascular and cerebrovascular risk markers in Parkinson’s disease: results from a case−control studyPublication . Alves, Mariana; Pita Lobo, Patrícia; Azevedo Kauppila, Linda; Rebordão, Leonor; Cruz, M. Manuela; Soares, Fátima; Cruz, João; Tornada, Ana; Caldeira, Daniel; Reimão, Sofia; Oliveira, Victor; Ferro, José; Ferreira, Joaquim JBackground: The relationship between Parkinson's disease (PD) and cardiovascular and cerebrovascular disease is not yet well established. Recent data suggest an increased risk of myocardial infarction and stroke in PD patients. Therefore, we designed a study to assess surrogate markers of cardiovascular and cerebrovascular risk in PD. Methods: We conducted a case-control study comparing PD patients recruited from a Movement Disorders Unit with controls randomly invited from a primary healthcare center. All participants underwent a detailed clinical evaluation, including medical history, physical assessment, carotid ultrasound, blood and urine analysis, and 24-h ambulatory blood pressure monitoring. The primary outcome was the carotid intima-media thickness (CIMT). Results: We included 102 participants in each study arm. No significant difference was found in the CIMT among groups (MD: 0.01, 95% CI: -0.02, 0.04). Carotid plaques were more frequent in PD patients (OR: 1.90, 95% CI: 1.02, 3.55), although the lipid profile was more favorable in this group (LDL MD: -18.75; 95% CI: -10.69, -26.81). Nocturnal systolic blood pressure was significantly higher in PD patients (MD: 4.37, 95% CI: 0.27, 8.47) and more than half of the PD patients were non-dippers or reverse dippers (OR: 1.83, 95% CI: 1.04, 3.20). Conclusion: We did not find a difference in CIMT between PD and controls. A higher frequency of carotid plaques and abnormal dipper profile supports the hypothesis that PD patients are not protected from cardiovascular and cerebrovascular disease.
- Synchronous and metachronous thoracic aortic aneurysms in patients with abdominal aortic aneurysms : a systematic review and meta‐analysisPublication . Melo, Ryan; Duarte, Gonçalo Silva; Lopes, Alice; Alves, Mariana; Caldeira, Daniel; Fernandes, Ruy Fernandes e; Pedro, Luís MBackground: The prevalence of thoracic aortic aneurysms (TAA) in patients with known abdominal aortic aneurysms (AAA) is not well known and understudied. Our aim was to conduct a systematic review and meta‐analysis of the overall prevalence of synchronous and metachronous TAA (SM‐TAA) in patients with a known AAA and to understand the characteristics of this sub‐population. Methods and Results: We searched MEDLINE, EMBASE, and CENTRAL (Cochrane Central Register of Controlled Trials) from inception to November 2019 for all population‐based studies reporting on the prevalence of SM‐TAAs in a cohort of patients with AAA. Article screening and data extraction were performed by 2 authors and data were pooled using a random‐effects model of proportions using Freeman‐Tukey double arcsine transformation. The main outcome was the prevalence of SM‐TAAs in patients with AAAs. Secondary outcomes were the prevalence of synchronous TAAs, metachronous TAAs, prevalence of TAAs in patients with AAA according to the anatomic location (ascending, arch, and descending) and the differences in prevalence of these aneurysms according to sex and risk factors. Six studies were included. The pooled‐prevalence of SM‐TAA in AAA patients was 19.2% (95% CI, 12.3–27.3). Results revealed that 15.2% (95% CI, 7.1–25.6) of men and 30.7% (95% CI, 25.2–36.5) of women with AAA had an SM‐TAA. Women with AAA had a 2‐fold increased risk of having an SM‐TAA than men (relative risk [RRs], 2.16; 95% CI, 1.32–3.55). Diabetes mellitus was associated with a 43% decreased risk of having SM‐TAA (RRs, 0.57; 95% CI, 0.41–0.80). Conclusions: Since a fifth of AAA patients will have an SM‐TAA, routine screening of SM‐TAA and their clinical impact should be more thoroughly studied in patients with known AAA.
- Direct oral anticoagulants vs vitamin K antagonist on dementia risk in atrial fibrillation: systematic review with meta-analysisPublication . Branco, Diogo R; Alves, Mariana; Severiano E Sousa, Catarina; Costa, João; Ferreira, Joaquim J; Caldeira, DanielOral anticoagulation significantly reduces the incidence of dementia in atrial fibrillation patients. However, this protective effect has not been compared between Direct Oral Anticoagulants (DOAC) and Vitamin K antagonists' anticoagulants (VKA). We conducted an electronic search for potentially eligible studies through the bibliographic databases MEDLINE, CENTRAL, ClinicalTrials.gov, EMBASE and Web of Science. The outcome of interest was dementia. Random-effects meta-analysis was performed. Nine observational studies were included and 1,175,609 atrial fibrillation patients were enrolled. DOAC therapy was associated with a significant reduction when compared with patients under VKA therapy (hazard ratio 0.89; 95% confidence interval 0.80-0.99). The grade of confidence of our results was very low due to the risk of bias. DOAC therapy is associated with a significant decrease in the risk of dementia when compared with VKA therapy. However, the low certainty of the evidence along with the paucityof clinical trials dedicated to answering this important question underscores a need for global clinical research initiatives.
- Cardiovascular events reported in randomized controlled trials in restless legs syndromePublication . Duarte, Gonçalo Silva; Alves, Mariana; Silva, Maria A.; Câmara, Raquel; Caldeira, Daniel; Ferreira, Joaquim J.Objective: Evaluate the frequency of cardiovascular adverse events reported in randomized controlled trials (RCT) in Restless Leg Syndrome (RLS). Methods: Databases were searched up to October 2015. Randomized, double-blind, placebo-controlled trials of patients with RLS were included if quantitative data were extractable. The primary outcome was cardiovascular adverse events defined as cardiac diseases, blood pressure abnormalities, syncope, cerebrovascular diseases, thromboembolic events, and sudden death. The pooled estimated prevalence of cardiovascular (CV) adverse events (AE) and respective 95% confidence interval (CI) was determined by using a meta-analysis. Results: In sum, 28 RCT (2515 participants in the placebo arm and 4223 participants in the intervention arm) reported CV AE. The pooled estimated prevalence of CV AE was 0.61% (95% CI 0.31 to 0.91; I2 ¼ 0%) in the placebo arm and 0.68% (95%CI 0.40 to 0.96; I2 ¼ 18.25%) in the intervention arm. The frequency of major CV events (myocardial infarction, stroke and peripheral artery disease) was 0.49% (95%CI 0.22 to 0.77; I2 ¼ 0%) and 0.33% (95% CI 0.16 to 0.50; I2 ¼ 0%) in the placebo and intervention arm, respectively. Conclusions: The frequency of major cardiovascular events in the RLS trials is not negligible, particularly when considering the young age of these patients.
- Incidence of acute aortic dissections in patients with out of hospital cardiac arrest: a systematic review and meta-analysis of observational studiesPublication . Melo, Ryan; Machado, Carolina; Caldeira, Daniel; Alves, Mariana; Lopes, Alice; Serrano, Maria; Fernandes E Fernandes, Ruy; Pedro, Luís MObjectives: Acute Aortic dissection (AAD) may present as out-of-hospital cardiac arrest (OHCA). However, the incidence of this presentation is not well known. Our aim was to perform a systematic review and meta-analysis of all observational studies reporting on the incidence of AAD in patients with OHCA. Methods: We searched MEDLINE, CENTRAL, PsycInfo, Web of Science Core Collection and OpenGrey databases from inception to March-2021, for observational studies reporting on the incidence of AAD in patients with OHCA. Data was pooled using a random-effects model of proportions. The primary outcome was the incidence of AAD in OHCA patients. Secondary outcomes were the incidence of type A aortic dissections (TAAD) and type B aortic dissections (TBAD) in OHCA patients, overall mortality following AAD-OHCA and risk of death in AAD-OHCA patients compared to risk of death of non-AAD-OHCA patients. Results: Fourteen studies were included. The pooled calculated incidence of OHCA due to AAD was 4.39% (95 %CI: 2.55; 6.8). Incidence of OHCA due to TAAD was 7.18% (95 %CI: 5.61; 8.93) and incidence of OHCA due to TBAD was 0.47% (95 %CI: 0.18; 0.85). Overall mortality following OHCA due to AAD was 100% (95 %CI: 97.62; 100). The risk of death in AAD-OHCA patients compared with non-AAD-OHCA patients was 1.10 (95 %CI: 0.94; 1.30). Conclusion: AAD as a cause of OHCA is more frequent than previously thought. Prognosis is dire, as it is invariably lethal. These findings should lead to a higher awareness of AAD when approaching a patient with OHCA and to future studies on this matter.
- Anticoagulation after typical atrial flutter ablation: systematic review and meta‐analysisPublication . Ferreira, Afonso Nunes; Alves, Mariana; Lima Da Silva, Gustavo; Cortez-Dias, Nuno; De Sousa, João; Pinto, Fausto J.; Caldeira, DanielBackground: Cavotricuspid isthmus (CTI) ablation in typical atrial flutter (AFL) restores sinus rhythm in 95% of patients, which may lead to the discontinuation of oral anticoagulation during follow-up. Therefore, we aimed to systematically review the clinical impact of oral anticoagulation in the incidence of thromboembolic events (TE) after typical AFL ablation. Methods: We searched for controlled studies evaluating the impact of anticoagulation in the incidence of TE in patients submitted to AFL ablation in MEDLINE, CENTRAL, PsycINFO database (June/2021). The primary outcome was TE events (ischemic stroke or systemic embolism). A meta-analysis was performed deriving risk ratios (RR) and 95% confidence intervals (CI). Statistical heterogeneity was measured through I2 metric. The confidence in the evidence was appraised with Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Results: Eight observational studies with 4870 patients were included. TE events were not significantly reduced (RR 1.18, 95% CI 0.59-2.36; n = 4870; GRADE very low). A meta-regression showed that for each 10% increase in the prevalence of previous AF in the studied population, anticoagulation reduced TE risk in 32%. There were no significant differences regarding bleeding events (RR 2.16, 95% CI 0.43-10.97, I2 = 0%; GRADE low), but there was a lower all-cause mortality (RR 0.24, 95% CI 0.17-0.32, GRADE low). Conclusion: The best available evidence lacks robustness and the data did not definitely associate anticoagulation after typical AFL ablation with reduced TE.
- Low risk of haematomas with intramuscular vaccines in anticoagulated patients: a systematic review with meta-analysisPublication . Caldeira, Daniel; Rodrigues, Bárbara Sucena; Alves, Mariana; Pinto, Fausto J.; Ferreira, Joaquim JIntroduction: The summary of product characteristics of vaccines administered intramuscularly, including the vaccine for coronavirus SARS-CoV-2 (COVID-19) and Influenza, warned for risks of bleeding in patients treated with oral anticoagulants. We aimed to estimate the incidence of major bleeding events in this setting and to compare these risks against other vaccination routes. Methods: This systematic review included all prospective and retrospective studies enrolling anticoagulated patients that received intramuscular vaccination, published until December 2020 in CENTRAL, MEDLINE and EMBASE. The outcomes of interest were major bleeding and haematoma related with vaccination. The incidence of the outcomes was estimated through a random-effects meta-analysis using the Freeman-Turkey transformation. The results are expressed in percentages, with 95%-confidence intervals (95%CI), limited between 0 and 100%. When studies compared intramuscular vaccination vs. other route, the data were compared and pooled using random-effects meta-analysis. Risk ratios (RR) with 95%CI were reported. Results: Overall 16 studies with 642 patients were included. No major bleeding event was reported. The pooled incidence of haematomas following vaccination (mostly against Influenza) in patients treated with oral anticoagulants (mostly warfarin; no data with DOACs / NOACs) was 0.46% (95%CI 0-1.53%). Three studies evaluated the intramuscular vs. subcutaneous route of vaccination. Intramuscular vaccines did not increase the risk of haematoma (RR 0.53, 95%CI 0.10-2.82) compared with subcutaneous route. Conclusions: Intramuscular vaccination in anticoagulated patients is safe with very low incidence of haematomas and the best available evidence suggests that using the intramuscular route does not increase the risk of haematomas compared with the subcutaneous route.
- Atrial fibrillation risk on Parkinson’s disease: a systematic review and meta-analysisPublication . Cereja, Fátima; Alves, Mariana; Ferreira, Joaquim J; Caldeira, DanielThe association of Parkinson's Disease (PD) with atrial fibrillation (AF) is not well established and previous studies' results were heterogeneous. This review aimed to evaluate if patients with PD are at increased risk of having AF. MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science, were searched from inception May 2021. Two reviewers independently selected observational studies with data allowing to estimate the risk of atrial fibrillation in PD patients compared with no-PD controls. Pooled estimates Odds Ratio (OR) and 95% confidence intervals (CIs) were derived through meta-analysis. Heterogeneity was assessed using I2 test. The risk of bias of individual studies was evaluated using the ROBINS-I tool. The study protocol was registered at PROSPERO: CRD42020216572. Seven studies were included: five case-control studies and two cohort studies. Three of the studies included were a population-based study. No significant difference was detected between PD and controls regarding atrial fibrillation (OR 1.10, 95% CI 0.81 to 1.49). Early PD present a significant higher risk of AF (OR 1.55, 95% CI 1.00 to 2.40, I2 98%). The overall risk of bias was serious, with only two studies being considered as having moderate risk. The best evidence available do not support that there is an increased risk of AF in PD patients. Further studies are needed to better conclude if there is a relation between AF and PD.
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