Blood Pressure Control by Multi-Component Intervention: An Exploratory Mediation Analysis of the SingHypertension Trial

Abstract

Cardiovascular diseases (CVDs) are the leading cause of death and disease burden globally. Hypertension, one of CVDs’ most important risk factors, becomes a global health challenge due to its growing prevalence and severe outcomes. Moreover, controlling blood pressure has been proved an effective way to prevent development of CVDs. The SingHypertension trial demonstrated that a structured system called multicomponent intervention (MCI) was more effective than usual care in reducing systolic blood pressure (SBP) among patients visiting Singapore primary-care clinics for uncontrolled blood pressure. To understand the underlying mechanism, this study performed an exploratory mediation analysis to identify potential mediators for the BP reduction benefit of MCI in the SingHypertension trial. Candidates for potential mediators were obesity status, dietary pattern, physical activity level, tobacco use, and daily dose and number of kinds of antihypertensive medications used. They were selected for being previously proved modifiable risk factors of hypertension and could be affected by one or more components of MCI. A mediation analysis using the product method was conducted. Potential mediators were first evaluated in a single mediator model separately and then analyzed using a parallel model, with or without demographic factors and co-morbidities of chronic diseases adjusted. About 760 samples were included in the mediation analyses. Changes in physical activity level and number of medications used were found statistically significantly mediated the effect, but in different directions. After adjusting for confounders, change in number of medications used mediated 11.34% of the total effect while improvement in physical activity mitigated the direct effect by 25.83%. In parallel models which included all potential mediators, changes in number of medications used mediated 22.62% of the total effect of MCI while improvement in physical activity mitigated 28.10% of the direct effect. In this post-hoc study, number of medication used was identified as a potential mediator of the effect of MCI versus usual care on BP reduction. This provides evidence for BP intervention program design. Further investigation with more appropriate research design and statistical analysis needs to be done to understand the causal relationship between all factors better.