Yes, altitude makes a difference.
The EFI bikes can adjust the mixture for the altitude, so that's a nice feature of the EFI equipped bikes.
However, compression and breathing still are affected.
With the Iron Barrel engines, we make compression corrections for those people who live in high elevations and won't be likely to ride down to sea level much.
We have some users at 7000' elevation who are using over 9.5:1 compression, and have about the same cranking compression psi as users at sea level with 8.25:1 compression. So, they get about the same power output as the guys at sea level, but need some corrections to be able to do it. And if they come down to lower altitudes, they'd need octane booster to stave off the ping.
But it works.
We are very well-versed in correcting for altitude, and we do it for every Fireball owner as part of their build support.