Background: Hypertension or elevated blood pressure (BP) is an important risk factor for aortic dissection (AD); however, few prospective studies on this topic have been published. We investigated the association between hypertension/elevated BP and AD in 2 cohorts and conducted a meta-analysis of published prospective studies, including these 2 studies. Methods: We analyzed data from the J-SHC study (Japan-Specific Health Checkups) and UK Biobank, which prospectively followed up 534 378 and 502 424 participants, respectively. Multivariable Cox regression was used to estimate hazard ratios and 95% CIs for the association of hypertension/elevated BP with AD incidence in the UK Biobank and AD mortality in the J-SHC Study. In the meta-analysis, summary relative risks were calculated with random-effects models. A potential nonlinear dose-response relationship between BP and AD was tested with fractional polynomial models, and the best-fitting second-order fractional polynomial regression model was determined. Results: In the J-SHC study and UK Biobank, there were 84 and 182 ADs during the 4- and 9-year follow-up, and the adjusted hazard ratios of AD were 3.57 (95% CI, 2.17–6.11) and 2.68 (95% CI, 1.78–4.04) in hypertensive individuals, 1.33 (95% CI, 1.05–1.68) and 1.27 (95% CI, 1.11–1.48) per 20–mm Hg increase in systolic BP (SBP), and 1.67 (95% CI, 1.40–2.00) and 1.66 (95% CI, 1.46–1.89) per 10-mm Hg increase in diastolic BP (DBP), respectively. In the meta-analysis, the summary relative risks were 3.07 (95% CI, 2.15–4.38, I ² =76.7%, n=7 studies, 2818 ADs, 4 563 501 participants) for hypertension and 1.39 (95% CI, 1.16–1.66, I ² =47.7%, n=3) and 1.79 (95% CI: 1.51–2.12, I ² = 57.0%, n=3) per 20–mm Hg increase in SBP and per 10–mm Hg increase in DBP, respectively. The AD risk showed a strong, positive dose-response relationship with SBP and even more so with DBP. The risk of AD in the nonlinear dose-response analysis was significant at SBP >132 mm Hg and DBP >75 mm Hg. Conclusions: Hypertension and elevated SBP and DBP are associated with a high risk of AD. The risk of AD was positively dose dependent, even within the normal BP range. These findings provide further evidence for the optimization of BP to prevent AD.

The coronavirus disease 2019 (COVID-19) pandemic remains a source of considerable morbidity and mortality throughout the world. Therapeutic options to reduce symptoms, inflammatory response, or disease progression are limited. This randomized open-label trial enrolled 100 ambulatory patients with symptomatic COVID-19 in Toronto, Canada. Results indicate that icosapent ethyl (8 g daily for 3 days followed by 4 g daily for 11 days) significantly reduced high-sensitivity C-reactive protein (hs-CRP) and improved symptomatology compared with patients assigned to usual care. Specifically, the primary biomarker endpoint, change in hs-CRP, was significantly reduced by 25% among treated patients (−0.5 mg/L, interquartile range [IQR] [−6.9,0.4], within-group p = 0.011). Conversely, a non-significant 5.6% reduction was observed among usual care patients (−0.1 mg/L, IQR [−3.2,1.7], within-group p = 0.51). An unadjusted between-group primary biomarker analysis was non-significant (p = 0.082). Overall, this report provides evidence of an early anti-inflammatory effect of icosapent ethyl in a modest sample, including an initial well-tolerated loading dose, in symptomatic outpatients with COVID-19. ClinicalTrials.gov Identifier: NCT04412018.

Objective Aortic dissection and aortic aneurysm rupture are aortic emergencies and their clinical outcomes have improved over the past two decades; however, whether this has translated into lower mortality across countries remains an open question. The purpose of this study was to compare mortality trends from aortic dissection and rupture between the UK, Japan, the USA and Canada. Methods We analysed the WHO mortality database to determine trends in mortality from aortic dissection and rupture in four countries from 2000 to 2019. Age-standardised mortality rates per 100 000 persons were calculated, and annual percentage change was estimated using joinpoint regression. Results Age-standardised mortality rates per 100 000 persons from aortic dissection and rupture in 2019 were 1.04 and 1.80 in the UK, 2.66 and 1.16 in Japan, 0.76 and 0.52 in the USA, and 0.67 and 0.81 in Canada, respectively. There was significantly decreasing trends in age-standardised mortality from aortic rupture in all four countries and decreasing trends in age-standardised mortality from aortic dissection in the UK over the study period. There was significantly increasing trends in mortality from aortic dissection in Japan over the study period. Joinpoint regression identified significant changes in the aortic dissection trends from decreasing to increasing in the USA from 2010 and Canada from 2012. In sensitivity analyses stratified by sex, similar trends were observed. Conclusions Trends in mortality from aortic rupture are decreasing; however, mortality from aortic dissection is increasing in Japan, the USA and Canada. Further study to explain these trends is warranted.

Background: to investigate the frequency and distribution of new ischemic brain lesions detected by diffusion-weighted imaging on brain magnetic resonance imaging after aortic arch surgery. Methods: This preplanned secondary analysis of the randomized, controlled ACE (Aortic Surgery Cerebral Protection Evaluation) CardioLink-3 trial compared the safety and efficacy of innominate versus axillary artery cannulation during elective proximal aortic arch surgery. Participants underwent pre and postoperative magnetic resonance imaging. New ischemic lesions were defined as lesions visible on postoperative, but not preoperative diffusion weighted imaging. Results: Of the 111 trial participants, 102 had complete magnetic resonance imaging data. A total of 391 new ischemic lesions were observed on diffusion-weighted imaging in 71 (70%) patients. The average number of lesions in patients with ischemic lesion were 5.5±4.9 with comparable numbers in the right (2.9±2.0) and left (3.0±2.3) hemispheres ( P =0.49). Half the new lesions were in the middle cerebral artery territory; 63% of the cohort had ischemic lesions in the anterior circulation, 49% in the posterior circulation, 42% in both, and 20% in watershed areas. A probability mask of all diffusion-weighted imaging lesions revealed that the cerebellum was commonly involved. More severe white matter hyperintensity on preoperative magnetic resonance imaging (odds ratio, 1.80 [95% CI, 1.10–2.95]; P =0.02) and lower nadir nasopharyngeal temperature during surgery (odds ratio per 1°C decrease, 1.15 [95% CI, 1.00–1.32]; P =0.05) were associated with the presentation of new ischemic lesion; older age (risk ratio per 1-year increase, 1.02 [95% CI, 1.00–1.04]; P =0.03) and lower nadir temperature (risk ratio per 1°C decrease, 1.06 [95% CI, 1.00–1.14]; P =0.06) were associated with greater number of lesions. Conclusions: In patients who underwent elective proximal aortic arch surgery, new ischemic brain lesions were common, and predominantly involved the middle cerebral artery territory or cerebellum. Underlying small vessel disease, lower temperature nadir during surgery, and advanced age were risk factors for perioperative ischemic lesions. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02554032.

Objective The purpose of this study is to describe recent mortality trends from aortic stenosis (AS) among eight high-income countries. Methods We analysed the WHO mortality database to determine trends in mortality from AS in the UK, Germany, France, Italy, Japan, Australia, the USA and Canada from 2000 to 2020. Crude and age-standardised mortality rates per 100 000 persons were calculated. We calculated age-specific mortality rates in three groups (<64, 65–79 and ≥80 years). Annual percentage change was analysed using joinpoint regression. Results During the observation period, the crude mortality rates per 100 000 persons increased in all the eight countries (from 3.47 to 5.87 in the UK, from 2.98 to 8.93 in Germany, from 3.84 to 5.52 in France, from 1.97 to 4.33 in Italy, from 1.12 to 5.49 in Japan, from 2.14 to 3.38 in Australia, from 3.58 to 4.22 in the USA and from 2.12 to 5.00 in Canada). In joinpoint regression of age-standardised mortality rates, trend changes towards a decrease were observed in Germany after 2012 (−1.2%, p=0.015), Australia after 2011 (−1.9%, p=0.005) and the USA after 2014 (−3.1%, p<0.001). Age-specific mortality rates in age group ≥80 years had shifts towards decreasing trends in all the eight countries in contrast to other younger age groups. Conclusions While crude mortality rates increased in the eight countries, shifts towards decreasing trends were identified in age-standardised mortality rates in three countries and in the elderly aged ≥80 years in the eight countries. Further multidimensional observation is warranted to clarify the mortality trends.