The out-of-the-blue reference triggered questions about the vice president’s role in the latest mess and the unusual relationship between the pair of leaders. If Trump falls alone, Pence becomes the 46th president of the United States — a development many mainstream Republicans would prefer. If Trump and Pence go down together or in quick succession, it’s President Nancy Pelosi — a prospect that would not be lost on Senate Republicans voting on whether to oust their party’s leaders.

Trump’s offhand remark was a stark reminder of the eternal risks to the people in his orbit, particularly as the notoriously unpredictable president navigates the delicate politics of impeachment.

Responding to a question about the president’s U.N. news conference, Tom LoBianco, author of the new Pence book “Piety and Power,” asked, “You mean when he gutted Pence on live TV?”

“He tends to flash this paranoia every now and then that Pence is after the job," Lobianco said. "It’s like joking not-joking. But I was shocked that he was so out in the open this time.”

Pence allies say there’s no reason to think the president will toss his No. 2 under the bus — something Trump has done to past advisers, Cabinet secretaries and White House aides.

“Trump is very loyal to people who have been loyal to him,” former Sen. Jim DeMint (R-S.C.) said. “You look back where there’s been separations, and it’s often where someone has gone off in a different policy direction and been public about it.”

Some people close to Pence, who spoke with POLITICO on the condition of anonymity, saw the president’s recent comment as nothing more than Trump’s typical stream of consciousness — an innocent statement meant to convey that neither he nor the vice president are guilty of wrongdoing.

“He’s largely above reproach. No one ever accuses the vice president of doing anything like that,” said one person close to Pence, referring to the allegations at the center of House Democrats’ impeachment inquiry that Trump pressured Ukrainian President Volodymyr Zelensky to investigate Joe Biden and his son Hunter.

“The president was trying to put himself on the same ground as that,” this person said.

A senior administration official dismissed the notion that Trump would throw Pence under the bus if he ever sensed disloyalty. “That is silly. It’s the opposite, meaning that [Pence's] calls are fine, too,” the official said of Trump's latest remark. “Think this through: POTUS and VP are gone and Pelosi becomes president? Please.”

The past several weeks have been a minefield of loyalty tests for Pence, culminating with the whistleblower complaint that prompted Pelosi to embrace impeachment after months of cautioning her progressive colleagues not to rush toward it.

Pence met with Zelensky on Sept. 1 during a last-minute trip to Poland. He told reporters afterward he did not mention Biden during their conversation but did communicate his “great concerns about issues of corruption” in Ukraine. The vice president was not a participant on the July 25 call between the president and Zelensky, according to a senior administration official, who pushed back against a report saying he urged Trump not to release a transcript of the conversation earlier this week.

Before the Ukraine scandal burst into public view, Pence was recovering from a series of other controversies that put his allegiance to Trump on full display.

On Sept. 9, the president claimed he had nothing to do with Pence’s stay at a Trump-owned property in Doonbeg, Ireland, far away from meetings the vice president had planned in Dublin. Trump’s denial of involvement in the arrangement contradicted a prior explanation provided by Pence chief of staff Marc Short, who said the president had suggested his resort as an overnight accommodation. When Short and Pence later said the vice president made the decision on his own — because of his family ties to Doonbeg — it was widely seen as an attempt to rescue Trump from accusations of emoluments clause violations.

That same afternoon, Pence and his team found themselves in cleanup mode again. This time, the vice president pushed back on reports that he had disagreed with Trump’s decision to invite Taliban leaders and the president of Afghanistan to Camp David for a secret round of peace negotiations.

“More Fake News!” Pence tweeted in distinctly Trumpian prose.

Pence’s reaction was consistent with how those in his inner circle expect him to behave as the impeachment inquiry unfolds on Capitol Hill: with a mix of caution and chameleonic performances that endear him to the president.

Indeed, Pence’s first public defense of the president amid reports of the whistleblower complaint came in a fiery interview Monday night on Fox News’ “Hannity” — a prime-time program Trump watches religiously.

“Here we go again. The assume-the-worst media takes one report, runs with it. Democrats on Capitol Hill immediately start to denounce the president before anybody has the facts,” the vice president said.

Pence also came to Trump’s defense on Wednesday in a series of statements from his official Twitter account that landed right as the president was calling attention to his conversations with Ukrainian officials. Quoting from an interview he did with Fox Business Network’s Lou Dobbs, the vice president — who wasn't at Trump’s news conference in New York — denounced Democrats’ “reckless accusations.” He also repeated the president’s erroneous claim that Biden threatened to withhold U.S. aid from Ukraine if a prosecutor — whom Trump has falsely claimed was investigating Hunter Biden — weren't removed from his position.

“The vice president is just as solid and loyal as he can get,” DeMint said. “He is just very thoughtful and strategic and over the next few weeks, he will be the president’s top adviser.”

The co-dependency between Trump and Pence has long been demonstrated by their policy portfolios, their synchronized talking points and the role both men play in energizing their MAGA base. Trump, a political neophyte with major character flaws in the eyes of his most ardent evangelical supporters, has allowed his vice president, a devout Christian, to assume powerful roles on foreign policy, health care and religious freedom. As long as Pence remains his dutiful deputy and greatest defender, he gains an automatic head start for his own presidential ambitions in the post-Trump era.

“He would never take out Trump because if you are ever seen trying to kill the king, you lose the base,” LoBianco said.

But even after three years of Pence’s obedience and nonstop flattery, there have been signs that Trump is unwilling to reciprocate the same degree of loyalty.

Earlier this summer, the president began soliciting advice from close friends on whether Pence should remain his running mate in 2020 amid reports that he was facing pressure from his daughter Ivanka Trump and her husband, Jared Kushner, to swap out the vice president for a female running mate.

And when Trump was pressed in a June “Fox & Friends” interview to endorse Pence as his natural successor, he attempted to dodge the question.

“Well, it’s — I love Mike; we are running again. You’re talking about a long time, so you can’t put in that position,” Trump said, adding he was merely willing to give it “very strong consideration.”

Daniel Lippman contributed to this report.