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- 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.
- 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.
- 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.
- Direct oral anticoagulants versus vitamin K antagonists in patients with antiphospholipid syndrome: systematic review and meta-analysisPublication . Koval, Nazariy; Alves, Mariana; Plácido, Rui; Almeida, Ana G.; Fonseca, João Eurico; Ferreira, Joaquim J; Pinto, Fausto J.; Caldeira, DanielBackground: Despite vitamin K antagonists (VKA) being the gold standard in the prevention of thromboembolic events in antiphospholipid syndrome (APS), non-vitamin K antagonists oral anticoagulants/direct oral anticoagulants (DOACs) have been used off-label. Objective: We aimed to perform a systematic review comparing DOACs to VKA regarding prevention of thromboembolic events, occurrence of bleeding events and mortality in patients with APS. Methods: An electronic database search was performed through MEDLINE, CENTRAL and Web of Science. After data extraction, we pooled the results using risk ratio (RR) and 95% CI. Heterogeneity was assessed using the I². The outcomes considered were all thromboembolic events as primary, and major bleeding, all bleeding events and mortality as secondary. Evidence confidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Results: We included 7 studies and a total of 835 patients for analyses. Thromboembolic events were significantly increased in DOACs arm, compared with VKA-RR 1.69, 95% CI 1.09 to 2.62, I²-24%, n=719, 6 studies. In studies using exclusively rivaroxaban, which was the most representative drug in all included studies, the thromboembolic risk was increased threefold (RR 3.36, 95% CI 1.53 to 7.37). The risks of major bleeding, all bleeding events and mortality were not significantly different from control arm. The grade of certainty of our results is very low. Conclusions: Current evidence suggests DOACs use, particularly rivaroxaban, among patients with APS, is less effective than VKA since it is associated with 69% increased risk of thromboembolic events.
- N‐Terminal Pro‐B‐type natriuretic peptide levels in Parkinson's diseasePublication . Alves, Mariana; Caldeira, Daniel; Reimão, Sofia; Ferro, José; Ferreira, Joaquim JWe read with interest the study by Choe and colleagues who increases emphasis on the heart–brain axis in Parkinson’s disease (PD). They have studied the relation between subclinical cardiac markers and motor impairment (Unifed Parkinson’s Disease Rating Scale Part III and Hoehn and Yahr stage) and cognition (Montreal Cognitive Assessment[MoCA]) concluding that patients with PD presented higher levels of N-terminal pro-B-type natriuretic peptide(NT-proBNP) compared with healthy controls matched forage, sex, and cardiovascular risk factors; increased levels of NT-proBNP and high-sensitivity troponin I were associated with worse motor impairment (Unifed Parkinson’s DiseaseRating Scale Part III and Hoehn and Yahr stage); and MoCA was inversely associated to high-sensitivity tropo-nin I and NT-proBNP levels only in unadjusted models among patients with PD.The population included were patients with advanced-stage PD (12 years of disease durationin average).
- Aspirin for primary cardiovascular prevention in patients with family history of cardiovascular disease : meta-analysisPublication . Antunes, Miguel M.; Alves, Mariana; Ferreira, Joaquim J; Pinto, Fausto J.; Caldeira, DanielThe use of aspirin, while well established in the secondary prevention of cardiovascular events, remains controversial in the primary prevention of these events in the general adult population. In this setting, aspirin showed a significant but modest decrease of cardiovascular event incidence at the cost of a significantly increased risk of bleeding, a pattern that is also seen in higher risk patients, such as diabetics. It becomes exceedingly important to identify other patient clusters that would benefit from cardiovascular risk reduction at the best benefit/risk ratio.
- Safety of coffee consumption after myocardial infarction : a systematic review and meta-analysisPublication . Ribeiro, Eduardo Matos; Alves, Mariana; Costa, João; Ferreira, Joaquim J; Pinto, Fausto J.; Caldeira, DanielBackground and aims: This systematic review aims to evaluate the impact of coffee consumption in patients with previous myocardial infarction (MI), in relation to all-cause and cardiovascular mortality, as well as other major cardiovascular events (MACE) such as stroke, heart failure, recurrent MI and sudden death. Methods and results: MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science Core Collection, SciELO Citation Database, Current Contents Connect®, KCI Korean Journal Database, African Index Medicus, and LILACS were searched for longitudinal studies evaluating the impact of coffee consumption in patients with previous myocardial infarction. We performed a random-effects meta-analysis to estimate the pooled hazard ratios (HR) with 95% confidence intervals (CI). The statistical heterogeneity was measured by I2. A dose-response analysis was also conducted. Six prospective cohort studies were included in the primary meta-analysis. Consumption of coffee was associated with lower risk of cardiovascular mortality (HR = 0.70; 95% CI 0.54-0.91, I2 = 0%; 2 studies) and was not associated with an increased risk of all-cause mortality (HR = 0.85; 95% CI 0.63-1.13; I2 = 50%; 3 studies), recurrent MI (HR = 0.99; 95% CI 0.80-1.22; I2 = 0%; 3 studies), stroke (HR = 0.97; 95% CI 0.63-1.49; I2 = 39%; 2 studies) and MACE (HR = 0.96; 95% CI 0.86-1.07; I2 = 0%; 2 studies). A significant non-linear inverse dose-response association was found for coffee consumption and all-cause mortality. Conclusions: Consumption of coffee was not associated with an increased risk of all-cause mortality and cardiovascular events in patients with previous myocardial infarction.