Your wifes EAD is valid as long as her I485 is pending. Unless the state dept. of health went to USCIS to get your I140 nulled, I don't see how the terms of your fulfillment of the NIW affect your wifes I485.
You have 6 years to proove 5 years of service. You could use your EAD to deliver pizzas for one of these 6 years.
Read my disclaimer, but in my humble opinion you should be safe if you leave your current job after the 3 years are up and start a new practice even if you have a couple of months of paperwork gap in between (thats what the 6 year rule is for) At the new location, you will have to proove 2 more years of 'full-time' practice with department of health support so you are eligible for adjustment at the end.
Just be sure to have enough business to fulfill the full-time requirement. There was a poster here who essentially saw 3 patients per week at her hpsa practice and made a living doing moonlight gigs in non-hpsa locations. When time came around to file the final compliance report, there was a lot of anxiety whether USCIS would accept the evidence.
5 cents of unsolicited advice regarding opening a practice:
Opening a practice is a major endeavour. Be sure to do your due diligence regarding the practice location. There is a reason these areas are underserved.
There are essentially two options:
1. Staying where you are.
If you do a waiver job, there shouldn't be any restrictive covenant with your current employer preventing you from remaining in the community. If you have the financial wherewithall to open a practice right accross from your current practice, it can be a good option. You have to be conscious of the fact that your former employer might play dirty if you start competing with him. There are many ways he can hurt your practice. (bogus lawsuits about stealing patient records, challenges to your credentials at the local hospital, sending our rumors in the community about your abilities). Patients tend to be loyal to a physician, not necessarily to a practice. If most of your business is independent from insurance panels (which can be a bitch to get onto if you are a new, single physician practice), most of your patients are likely to follow you. This assumes that you are well liked and trusted in your community.
2. Going somewhere else
If you intend on doing that, be very sure about the practice location. If you have a trusted confidant in the community who has a good understanding of the local market it would be ideal (maybe a colleague in a non-competing specialty). If you are new to a community, you have to anticipate a signinifcant 'ramp-up' phase. In a underserved community, this can be expected to be rather short, but still you have to anticipate that you won't make money for a couple of months until insurance payments start trickling in and your patient numbers are high enough to pay the electrical bill.
End of unsolicited advice