Authors: Chih-Cheng Lai, Meng-tse Gabriel Lee, Wan-Chien Lee, Christin Chih-Ting Chao, Tzu-Chun Hsu, Si-Huei Lee, Chien-Chang Lee
Summary: Background: Patients are at increased risk of cardiovascular complications while recovering from sepsis. We aimed to study the temporal change and susceptible periods for cardiovascular complications in patients recovering from sepsis by using a national database.
Methods: In this retrospective population-based cohort study, patients with sepsis were identified from the National Health Insurance Research Database in Taiwan. We estimated the risk of myocardial infarction (MI) and stroke following sepsis by comparing a sepsis cohort to a matched population and hospital control cohort. The primary outcome was first occurrence of MI or stroke requiring admission to hospital during the 180-day period following discharge from hospital after sepsis. To delineate the risk profile over time, we plotted the weekly risk of MI and stroke against time using the Cox proportional hazards model. We determined the susceptible period by fitting the 2 phases of time-dependent risk curves with free-knot splines, which highlights the turning point of the risk of MI and stroke after discharge from the hospital.
Results: We included 42,316 patients with sepsis; stroke developed in 831 of these patients and MI developed in 184 within 180 days of discharge from hospital. Compared with population controls, patients recovering from sepsis had the highest risk for MI or stroke in the first week after discharge (hazard ratio [HR] 4.78, 95% confidence interval [CI] 3.19 to 7.17; risk difference 0.0028, 95% CI 0.0021 to 0.0034), with the risk decreasing rapidly until the 28th day (HR 2.38, 95% CI 1.94 to 2.92; risk difference 0.0045, 95% CI 0.0035 to 0.0056) when the risk stabilized. In a repeated analysis comparing the sepsis cohort with the non-sepsis hospital control cohort, we found an attenuated but still marked elevated risk before day 36 after discharge (HR 1.32, 95% CI 1.15 to 1.52; risk difference 0.0026, 95% CI 0.0013 to 0.0039). The risk of MI or stroke was found to interact with age, with younger patients being associated with a higher risk than older patients (interaction p = 0.0004).
Interpretation: Compared with the general population with similar characteristics, patients recovering from sepsis had a markedly elevated risk of MI or stroke in the first 4 weeks after discharge from hospital. More close monitoring and pharmacologic prevention may be required for these patients at the specified time.
Sepsis, life-threatening organ dysfunction caused by pathogen-induced systemic inflammation, is a leading cause of death and morbidity worldwide. From 2009 to 2011, sepsis contributed to more than half of all deaths from infectious diseases in Canada. In 2011, sepsis was the 12th leading cause of death in Canada and responsible for 1 in 18 deaths.1 In addition to the number of patient deaths attributable to sepsis, recent evidence has shown that there is an increased risk of cardiovascular complications in patients who are recovering from sepsis. Various mechanisms have been proposed to account for the increased risk of cardiovascular complications after sepsis, including endothelial dysfunction, demand ischemia, disseminated intravascular coagulation, myocardial depression and platelet activation.
However, there is a paucity of research on risk of cardiovascular complications during the recovery period for those with a diagnosis of sepsis. We aimed to quantify the temporal change of risks of cardiovascular complications after sepsis by comparing a cohort of patients in hospital who were diagnosed with sepsis with matched community and hospital control cohorts, that included patients without a diagnosis of sepsis. Our second goal was to determine a susceptible period for myocardial infarction (MI) and stroke after sepsis. Third, we aimed to assess the risk of post-sepsis MI and stroke after sepsis in several predefined subpopulations.
Source: Canadian Medical Association Journal, 2018; 190 (36): E1062