A bit vague as in "wide margin" but from the help:
Setup A/B - Setup relief pitchers are the first to come in when a pitcher is removed late (generally during the 7th or later) in a game that is still in doubt. These are usually relief pitchers who are only capable of pitching an inning of relief at maximum effectiveness. Their appearances are usually higher than any other pitching role, while they may not pitch as many total innings as starters or long relief pitchers. Unless settings in the Edit Players Settings page dictate otherwise, the setup A pitcher will be given first priority to enter a game when this situation arises and the score is still close. If there is a wide margin in the score your setup B pitcher will have a better chance of appearing in the game. If a setup pitcher must leave the game during what is still a setup relief situation, first replacement priority will be given to another setup relief pitcher. Setup pitchers are intended to bridge the gap from starters to closers.
I would assume the sim looks at 4 runs as a possible one swing of the bat.