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Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition by monoclonal antibodies has been shown to reduce low density lipoprotein (LDL-C) but its effects on cardiovascular (CV) outcomes have not been fully described. The aim of this study is to assess the impact of PCSK9 inhibition on mortality and CV outcomes by pooling data from all available randomized clinical trials (RCT) of PCSK9 inhibitors. We conducted a comprehensive search of electronic databases, up to December 1, 2018, for all RCTs comparing PCSK9 inhibition to placebo or ezetimibe in patients with hypercholesterolemia or coronary artery disease receiving maximally tolerated statin for primary or secondary prevention of mortality and cardiovascular outcomes. We used random-effects meta-analyses to summarize the studies. We retained 23 RCTs having included 88,041 patients in primary and secondary prevention. The follow-up ranged from 6 to 36 months. PCSK9 inhibition was not significantly associated with reductions in total mortality (odds ratio [OR] 0.91, 95% confidence interval [CI] 078 to 1.06; p = 0.22) and CV mortality (OR 0.95, 95% CI 0.84 to 1.07; p = 0.37). In contrast, PCSK9 inhibition was associated with reductions in myocardial infarction (OR 0.80, 95% CI 0.71 to 0.91; p0.0001), stroke (OR 0.75, 95% CI 0.65 to 0.85; p0.0001), and coronary revascularization (OR 0.82, 95% CI 0.77 to 0.88; p0.0001). In conclusion, PCSK9 inhibition was associated with reductions in myocardial infarction, stroke, and coronary revascularization. Future analyses may identify high-risk patients who may benefit more from these agents and longer follow-up of current or new trials may show a mortality benefit.

Background: Stroke is one of the leading causes of mortality worldwide. During the last decade, there have been several improvements in stroke-related care such as raising public awareness for early presentation, lifestyle modification, thrombolytic therapy and endovascular therapy. We aimed to evaluate the potential changes in global stroke-related mortality following these innovations. Methods: We completed a systematic review of all population-based cohort studies published during the last two decades (2000-2020). We retained all studies which reported age-adjusted and sex-specific stroke-related mortality. We grouped the countries into: developed countries with predominant White population* (Canada, United States of America, Western Europe, Australia, New Zealand), Eastern Europe, Latin America, and Asia. For each of the region, we compared the median stroke-related mortality during the decade 2010 to the stroke-related mortality of the 2000 decade. Results: Of 210 articles screened, there were eight studies that reported population-based age-standardized and sex-specific stroke-related mortality in 47 countries. We presented the international secular variations in sex-specific stroke-related mortality in Figure 1. We noted significant temporal decreases in age-standardized stroke-related mortality for both men and women in all regions except for Eastern European women and Asian men. Globally, the stroke-related mortality decreased from 40.0 to 31.7 and from 31.6 to 22.8 per 100,000 for men and women, respectively The reductions of stroke-related deaths approximated 22% and 29%, for men and women, respectively. Conclusion: Despite its temporal decrease in most regions, the lack of reduction in stroke-related mortality of Eastern European women and Asian men are noteworthy. Future research is needed to decrease the stroke-related mortality in these high-risk populations. *: As defined by the International Monetary Fund

Background: Stroke is one of the leading causes of mortality worldwide. We aimed to evaluate the international variations in stroke-related mortality in men and women. Methods: We completed a systematic review of all population-based cohort studies published during the decade 2010-2020. We retained only studies which reported age-adjusted and sex-specific stroke-related all-cause mortality (per 100 000 population). We computed the median sex-specific stroke-related mortality for each of the following group of countries: developed countries (as defined by the International Monetary Fund) with predominantly white population (Canada, United States of America, Western Europe, Australia, New Zealand), Eastern Europe, Latin America, Asia and Africa. We compared stroke-related mortality between women and men and between regions. Results: Of the 210 articles screened, there were seven studies which reported population-based age-standardized and sex-specific stroke-related mortality in 57 countries. We presented the most recent age-adjusted and sex-specific stroke-related mortality medians (and 25 th and 75 th percentiles) in Figure 1. Globally, we observed a significantly lower stroke-related mortality rate in women compared to men (23.6 and 30.8, respectively) (p-value = 0.007). Age-adjusted stroke-related mortality was the highest for both sexes in Eastern Europe, followed by the African rates. Age-adjusted stroke-related mortality was the lowest for both men and women (p Conclusions: There were marked international variations in the age-adjusted stroke-related mortality for both men and women. The high stroke-related mortality in Eastern Europe and Africa should motivate further improvement in stroke care in these regions. Finally, future research is needed to understand and decrease the sex-related difference in stroke-related mortality.

Background: Postoperative atrial fibrillation (POAF) is a frequent occurrence after noncardiac surgery. It remains unclear whether POAF is associated with an increased risk of major adverse events. We aimed to elucidate the risk of stroke, myocardial infarction, and death associated with POAF following noncardiac surgery by a meta-analysis of randomized controlled studies and observational studies. Methods: We searched electronic databases from inception up to August 1, 2019 for all studies that reported stroke or myocardial infarction in adult patients who developed POAF following noncardiac surgery. We used random-effects models to summarize the studies. Results: The final analyses included 28 studies enrolling 2 612 816 patients. At 1-month (10 studies), POAF was associated with an ≈3-fold increase in the risk of stroke (weighted mean 2.1% versus 0.7%; odds ratio [OR], 2.82 [95% CI, 2.15–3.70]; P P ≤0.001) in 8 studies with ≥12-month follow-up. There was a significant overall increase in the risk of stroke and myocardial infarction associated with POAF (weighted mean, 2.5% versus 0.9%; OR, 3.44 [95% CI, 2.38–4.98]; P P P Conclusions: POAF was associated with markedly higher risk of stroke, myocardial infarction, and all-cause mortality following noncardiac surgery. Future studies are needed to evaluate the impact of optimal cardiovascular pharmacotherapies to prevent POAF and to decrease the risk of major adverse events in these high-risk patients.

Background The association between atrial fibrillation and dementia has been described. Whether a specific association exists between atrial fibrillation and Alzheimer's disease remains uncertain. This study aims to assess the association between atrial fibrillation and Alzheimer's disease through a systematic review and meta-analysis of the literature. Methods An exhaustive search of electronic databases up to October 2018 was conducted. Studies that identified patients with and without atrial fibrillation as well as patients with and without Alzheimer's disease and reported results of at least one relevant outcome, including hazard ratio of the association between atrial fibrillation and Alzheimer's disease were included in this analysis. The hazard ratios and their confidence interval were then pooled using a DerSimonian and Laird random effects model. Results Six studies enrolling a total of 56 370 patients were included. At baseline, the mean or median ages ranged from 50 to 78 years with a subsequent follow-up of 3 to 25 years. The random-effect pooled analysis showed a hazard ratio of 1.30 (95% confidence interval 1.01-1.59) and the heterogeneity was not significant, I 48.1%. All of the included studies were rated as good quality. Conclusion Pooled analysis suggest that patients with atrial fibrillation may be exposed to an increased risk of developing new onset of Alzheimer's disease. Given the relevant clinical implications, further studies are required to corroborate these findings.

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice with implications on long-term outcomes. Metabolic disorders including diabetes mellitus and obesity are independent predictors of atrial fibrillation and present therapeutic targets to reduce both the incidence and duration burden of atrial fibrillation. The presence of pericardial fat in direct contact with cardiac structures, as well the subsequent release of proinflammatory cytokines, may play an important role in this connection. Atrial fibrillation is an independent predictor of cognitive impairment and dementia. While clinical stroke is a major contributor, other factors such as cerebral hypoperfusion and microbleeds play important roles. New evidence suggests that atrial fibrillation and cognitive impairment may be downstream events of atrial cardiomyopathy, which may be caused by several factors including metabolic syndrome, obesity, and obstructive sleep apnea. The mechanisms linking these comorbidities to cognitive impairment are not yet fully elucidated. A clearer understanding of the association of AF with dementia and cognitive impairment is imperative. Future studies should focus on the predictors of cognitive impairment among those with AF and aim to understand the potential mechanisms underlying these associations. This would inform strategies for the management of AF aiming to prevent continued cognitive impairment.

Subclinical atrial fibrillation (SCAF) describes asymptomatic episodes of atrial fibrillation (AF) that are detected by cardiac implantable electronic devices (CIED). The increased utilization of CIEDs renders our understanding of SCAF important to clinical practice. Furthermore, 20% of AF present initially as a stroke event and prolonged cardiac monitoring of stroke patients is likely to uncover a significant prevalence of SCAF. New evidence has shown that implanting cardiac monitors into patients with no history of atrial fibrillation but with risk factors for stroke will yield an incidence of SCAF approaching 30–40% at around three years. Atrial high rate episodes lasting longer than five minutes are likely to represent SCAF. SCAF has been associated with an increased risk of stroke that is particularly significant when episodes of SCAF are greater than 23 h in duration. Longer episodes of SCAF are incrementally more likely to progress to episodes of SCAF >23 h as time progresses. While only around 30–40% of SCAF events are temporally related to stroke events, the presence of SCAF likely represents an important risk marker for stroke. Ongoing trials of anticoagulation in patients with SCAF durations less than 24 h will inform clinical practice and are highly anticipated. Further studies are needed to clarify the association between SCAF and clinical outcomes as well as the factors that modify this association.