You might want to architect your site to use at least the master / slave replication system. You do not have to configure mysql mailbox replication to start, but you want to create a project for your application so that the database reads a different connection than the records (even if at the beginning both connections were connected to the same db server).
You also need to think very carefully about what your caching strategy will be. I would look at memcache, although with Zend_Cache you could use the cache file at an early stage and change it in memcache if / when you need it. In addition to caching records, you also want to think about partial page-level caching and what strategies you plan / implement there.
You will also want to carefully plan how you will handle storing and retrieving custom media. You will want to easily transfer this material from the main server to a dedicated mailbox in order to serve static content or some kind of CDN (content distribution network).
Also, think about how you are going to handle session management, and make sure that you are not doing anything that will prevent you from using non-file session memory ((dedicated) database or memcache) in the future.
If you think carefully and abstractly save / retrieve data, you will move in a good direction.
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