Susceptible period for cardiovascular complications in patients recovering from sepsis

Abstract

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 nonsepsis 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.

Figure 1:

Flow diagram of the study population. Note: LHID = Longitudinal Health Insurance Database, MI = myocardial infarction.

Figure 2:

Risk profile over time of myocardial infarction and stroke in participants after discharge from hospital. Comparison of participants with sepsis with participants without sepsis in the population control group (upper panel). Comparison of participants with sepsis with participants without sepsis in the hospital control group (lower panel). Note: CI = confidence interval, MI = myocardial infarction.

Figure 3:

Risk of MI or stroke in participants recovering from sepsis compared with the population control cohort. Note: CI = confidence interval, MI = myocardial infarction. *Significant result.