BEAM trial analyses

Project aims

In this randomized, placebo-controlled double-blind trial, we aimed to investigate the impact of oral butyrate treatment on BP in patients with hypertension. The primary outcome was daytime systolic blood pressure as measured with an ambulatory blood pressure device.

Paper

A paper with more details on the methodology can be found here: [insert link].

Trial design

We included Dutch participants, aged 40 to 65, with untreated grade I hypertension (office systolic BP between 140 and 160 mmHg or diastolic BP between 90 and 100 mmHg), or the use of one BP lowering drug, and BMI lower than 27 kg/m2. Included participants were randomized using a stratified alternating block randomization (1:1 ratio) performed in the data collection system Castor EDC. Block sizes were 4, 6, or 8 with two strata for age (=<50 years and >50 years) and sex, to ensure that the two groups had similar baseline risk and were balanced in numbers. Physicians and study participants were blinded to treatment allocation, until the statistical analyses were completed in a blinded fashion.

RStudio and renv

The analyses were performed in RStudio (v.2023.9.1.494) using R (v.4.2.1). We used renv and uploaded a lockfile in this repository to reconstruct the renv.

ToC: scripts

The scripts shared in this repository are numbered, and are discussed below in the same order:

Data cleaning (1_data_cleaning.R).
Tables (2_tables.R): for table 1, and some descriptives for adverse events and compliance numbers. Results (in csv) can be found in results folder.
Dietary data: linear mixed models in 3-dietary-analysis.R (plot can be found in Supplements)
Linear mixed models of blood pressure outcomes:

Plots and linear mixed models of office and ambulatory blood pressure in 4a-bp-analyses.R (Figure 1)
Adjusted linear mixed models for ambulatory blood pressure in 4b-bp-lmm-adjusted.R (Figure 2)

Neurohumoral balance:

Nexfin analyses (heart rate variability, baroreceptor sensitivity, etc) in 5a-nexfin-analyses.R
Body impedance analysis (BIA), including total body water, in 5b-bia-analyses.R
Fractional excretion of sodium in 5c-frac-excretion.R
Renin and aldosterone plasma concentrations in 5d-reninaldo.R. This script also includes a ggarrange function that uses outputs of scripts 5a-5c above and results in Figure 3 in the manuscript.

SCFA and serotonin analyses:

Plasma and fecal SCFA analyses, plots and adjusted LMMs in 6a-scfa-analyses which is Figure 4 in the manuscript.
Serotonin plasma level analysis in 6b-serotonin-analysis. This plot can be found in the Supplements.

Gut microbiota composition:

Preparation of phyloseq object in 7a-processing-phyloseq.R - make, root and add tree after multiple sequence alignment, make nice taxonomy.
Compositional plot at genus level in 7b-compositional-plots.R
Ordination and diversity plots in 7c-ordination-plots.R - this script also includes a ggarrange function that uses the compositional plot of 7b.
Linear mixed models for separate ASVs in 7d-lmm-asvs.R (plot can be found in Supplements)

Monocyte and inflammatory markers analyses: