Should the health of these two senators force them to step down, the political consequences could be hugely consequential. Arizona would have two Senate seats in play in 2018. Democrats have already targeted the seat of retiring Republican Jeff Flake, finding encouragement in the narrow results of Arizona’s presidential contest (Donald Trump won with a 3.5 percent plurality, contrasted with Mitt Romney’s 9-point win in 2012). Capturing both seats could be enough to put Democrats in control of the Senate (assuming they hold all of the seats they’re defending next year—10 of them in states Trump won).

While Mississippi is deep red, Cochran barely survived a 2014 primary challenge from state Senator Chris McDaniel. The Tea Party favorite actually ran slightly ahead of Cochran in the first primary, then lost the runoff by only 7,500 votes. An open seat in Mississippi could trigger an intense fight that could wind up with a fringe candidate sufficiently unappealing to put that safe GOP seat in play. Just ask Alabama.