Excess cardiovascular risk associated with community-acquired lower respiratory tract infections: a population-based nested self-controlled case-series

BACKGROUND: Lower respiratory tract infections (LRTI) are common and can trigger acute cardiovascular events. Previous studies focussing on this association only reported relative effect measures, leaving the population impact largely unknown.

METHODS: This population-based study was based on routine health care data of the Julius General Practitioners' Network in the Netherlands and included patients aged ≥40 years presenting with an LRTI to general practice between 2016-2019. The burden of acute cardiovascular events following LRTI was assessed in three consecutive steps. First, 90-day incidence rates of acute cardiovascular events following LRTI were mapped for major adverse cardiac and cerebrovascular events (MACCE), venous thromboembolism (VTE), and new-onset atrial fibrillation (nAF). Second, incidence rate ratios (IRR) within 90 days following LRTI were estimated per cardiovascular event type, using a self-controlled case-series analysis. Third, excess cardiovascular risk associated with LRTI was calculated.

RESULTS: In total, 11,065 patients contributed 16,497 LRTI episodes. The 90-day incidence rate per 1000 LRTI patients was 4.2 (3.3 to 5.3, n = 69) for MACCE, 2.7 (1.9 to 3.6, n = 44) for VTE, and 6.6 (5.4 to 8.1, n = 96) for nAF. Incidence rate ratios (IRR) of cardiovascular events within 90 days following LRTI were 1.3 (1.0 to 1.8) for MACCE, 6.8 (4.4 to 10.4) for VTE, and 2.9 (2.3 to 3.7) for nAF. For all cardiovascular event types, IRRs were highest in the first week following LRTI. Per 1000 LRTI patients, 0.5 (-0.5 to 1.6) to 1.1 (0.1 to 2.4) excess MACCE, 2.1 (1.1 to 3.6) to 3.0 (1.8 to 4.9) excess VTE, and 2.3 (1.1 to 3.7) to 4.4 (2.9 to 6.2) excess nAF diagnoses were associated with LRTI.

CONCLUSIONS: The temporal increase in cardiovascular risk following LRTI culminates in approximately five to nine excess acute cardiovascular events per 1000 LRTI patients aged ≥40 years. Given the large number of LRTI patients during seasonal outbreaks, this implies a need for targeted preventative interventions and patient-focussed campaigns to increase seasonal vaccine uptake.