My thoughts are fairly simple: Don't do it!
Leave font selection and line spacing etc. up to the reader (person and device). Most devices allow the users to adjust text for themselves and it can be really annoying to have an ebook that forces its own choices on you.
Disclaimer: the above is based on the assumption that this is narrative text. For some non-fiction situations there may be reason to force adjustments.
As for doing it whether it's a good idea or not: I'm not familiar with Vellum, but you could use Sigil (or, I assume, the Calibre ebook editor) to adjust the relevant CSS styles. Perhaps Vellum offers direct editing of the styles too?
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