Acute respiratory infections, cardiovascular complications, and prevention among people with raised cardiovascular risk

Background: Although acute respiratory infections (ARIs) can lead to cardiovascular complications, the effect of underlying cardiovascular risk on the incidence of ARIs and ARI-related cardiovascular complications in people without established cardiovascular disease (CVD) is unknown. In turn, the benefit of vaccines, such as influenza vaccine, among people with raised cardiovascular risk is unmeasured. Objectives and data sources: The objectives of this thesis were to 1) assess the validity of acute cardiovascular event diagnoses in electronic health record (EHR) data, 2) examine the association of cardiovascular risk with ARIs and ARI-related cardiovascular complications, 3) investigate the association between influenza vaccine and acute cardiovascular events by varying cardiovascular risk level, 4) examine the association of cardiovascular risk with severe COVID-9 outcomes, and 5) investigate the association of COVID-19 and acute cardiovascular events by varying cardiovascular risk level. All analysis to achieve objectives 2-5 used EHR data from the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES). Results: Results from 81 validation studies included in the systematic review suggested EHR recorded acute cardiovascular event diagnoses have a high level of validity, but variable definitions are employed (Chapter 5). Using CPRD and HES data from 6,075,321 individuals aged 40-64 years who are not currently recommended to receive influenza vaccine, I found an increased incidence of ARI among individuals at raised cardiovascular risk (Chapter 6). I also identified a significant association between raised cardiovascular risk and ARI-related cardiovascular complication, which was higher for QRISK2 score (adjusted hazard ratio (aHR) 3.65, 95% confidence interval (CI) 3.42-3.89) than hypertension (aHR 1.98, 95% CI 1.83-2.15). Among 193,900 individuals aged 40-84 years I found a decrease in the season-adjusted relative incidence of first acute cardiovascular events occurring in the days and weeks after influenza vaccination with a tapering over time (Chapter 7). In analysis of raised cardiovascular risk and COVID-19 among 6,059,055 adults aged 40-84 years, I found elevated risk of COVID-19 death, first acute cardiovascular event, and other severe COVID-19 outcomes in those with a QRISK3 score ≥10% (Chapter 8). Hypertension was only associated with risk of acute cardiovascular event. In a self-controlled case series analysis of 1,762 individuals with COVID-19 (Chapter 9), I identified an increased risk of first acute cardiovascular events which was greatest in the first seven days after infection (incidence ratio 7.14, 95% CI 6.06-8.41). Conclusions: People with raised cardiovascular risk are at higher risk of ARI-related cardiovascular complications following infection, including influenza, pneumonia, and COVID-19. Raised cardiovascular risk was more strongly associated with ARI-related cardiovascular complications when cardiovascular risk was measured by QRISK2/3 score compared to hypertension alone. Addressing cardiovascular risk factors could improve outcomes after ARIs. Improved vaccine uptake could contribute to prevention of cardiovascular disease.