Effects of sequential vs single pneumococcal vaccination on cardiovascular diseases among older adults: a population-based cohort study

Background: Recommendations around the use of 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine (PCV13) seldom focus on potential benefits of vaccine on comorbidities. We aimed to investigate whether sequential vaccination with PCV13 and PPSV23 among older adults would provide protection against cardiovascular diseases (CVD) compared with using a single pneumococcal vaccine. Methods: We conducted a Hong Kong-wide retrospective cohort study between 2012 and 2020. Adults aged >= 65 years were identified as receiving either a single or sequential dual vaccination and followed up until the earliest CVD occurrence, death or study end. To minimize confounding, we matched each person receiving a single vaccination to a person receiving sequential vaccination according to their propensity scores. We estimated the hazard ratio (HR) of CVD risk using Cox regression and applied structural equation modelling to test whether the effect of sequential dual vaccination on CVD was mediated via the reduction in pneumonia. Results: After matching, 69 390 people remained in each group and the median (interquartile range) follow-up time was 1.89 (1.55) years. Compared with those receiving a single vaccine, those receiving sequential dual vaccination had a lower risk of CVD [HR (95% CI): 0.75 (0.71, 0.80), P < 0.001]. Post-hoc mediation analysis showed strong evidence that the decreased CVD risk was mediated by the reduction in all-cause pneumonia. Conclusions: Sequential dual pneumococcal vaccination was associated with lower risk of CVD compared with single-dose PCV13 or PPSV23 in older adults. Such additional CVD benefits should be considered when making decisions about pneumococcal vaccination.