Population-based analyses of incidence, prognostic determinants and outcome of aortic dissection

Abstract: Background: Aortic dissection (AD) is a potentially life-threatening disease caused by a tear in the innermost layer of the aortic wall, the intima, resulting in blood flow between the layers of the aortic vessel wall. Main risk factors are hypertension, male sex and smoking. Evidence is mostly based on research including patients treated at specialist centers or from international registers whereas population-based studies are lacking. Hence, true incidence has been hard to determine. Sex differences have seldom been described and predictors of outcome need further attention. Correct classification is crucial in managing patients with AD. Patients with type A dissection (TAD) are mainly managed with open surgical repair (OSR) whereas patients with type B dissection (TBD) are managed medically or with Thoracic EndoVascular Aortic Repair (TEVAR). Pharmacological treatment is of great importance in managing patients with cardiovascular disease but the evidence on the effect of medical treatment in this patient group is limited. Aim: The overall aims of this thesis were to, by means of population-based studies, determine the incidence, describe trends in treatment and survival, characterize prognostic determinants and finally to explore the effect of pharmacological therapy in patients with AD. Method and results: All four studies were population-based. In Study I, all 53 patients treated with TEVAR for acute or subacute complicated TBD in Stockholm County were included. In univariate regression models, treatment within 48 hours from onset of the disease and a false lumen area (FLA) of more than 50% of the total aortic area at the level of the tracheal bifurcation were associated with increased 30-day mortality. Study II was a population-based register study including 8057 patients diagnosed with AD in Sweden during 15 years. The incidence was 7.2 per 100 000 per year, decreasing in men over time. The proportion of patients managed through surgical or endovascular intervention increased and survival improved. A higher proportion of women died outside of hospital than men and among surgically treated patients, women suffered a poorer outcome. Study III included analysis of pharmacological treatment prior to admission and at discharge in 3951 patients diagnosed with AD in Sweden during 10 years. A majority (58%) were treated with antihypertensive medication prior to admission. Treatment with statins at discharge was associated with higher long-term survival whereas there was no association for anticoagulant and antiplatelet therapy. Optimal antihypertensive treatment differed between medically and surgically managed patients. Betablockers and angiotensin 2 receptor blockers were associated with higher long-term survival in surgically managed patients whereas calcium channel blockers and angiotensin converting enzyme inhibitors were associated with highern survival in medically managed patients. Study IV included all 344 patients diagnosed with acute AD in Stockholm County 2012-2016. TAD accounted for 2/3 of the cases. Painless dissection was more common than previously described and was associated with increased mortality. Elevated troponin T, above the upper reference limit, as well as thrombocytopenia at admission was more common in TAD than in TBD. Troponin T elevation was associated with increased early mortality, both in patients with TAD and TBD, respectively, whereas thrombocytopenia was associated with worse outcome in patients with TAD. The DeBakey classification was useful in predicting early mortality, with higher mortality in type I compared to type II and in type IIIB compared to IIIA. Conclusion: This thesis, including four population-based studies, has demonstrated a higher incidence of AD than earlier described. As the frequency of surgical management increased, mortality in hospitalized patients decreased. Highlighting high risk features such as painless dissection, elevated Troponin T, DeBakey I and IIIB at admission as well as a large FLA in patients treated with TEVAR, respectively, may help clinicians predict outcome. Moreover, the use of statins and improved individualization of antihypertensive treatment may possibly improve outcome of AD even further in the future."