麻豆传媒

Left ventricular (LV) conduction disease might have been prevented with aggressive blood pressure (BP) control, a post hoc analysis of SPRINT showed.

Individuals randomized to the intensive systolic BP target of <120 mm Hg had significantly less incident LV conduction disease -- counting any fascicular or left bundle-branch block over a median 3.5 years in the trial -- compared with the looser target of <140 mm Hg (HR 0.74, 95% CI 0.56-0.98).

"These results persisted when incident ventricular pacing was included in the outcome and when considering all-cause death as a competing risk," reported Gregory Marcus, MD, MAS, of the University of California San Francisco, and colleagues. Their study was published in .

LV conduction disorders are common and may progress to life-threatening rhythm disturbances, heart failure, or complete heart block requiring a permanent pacemaker. No preventive strategies have been previously identified for these conditions.

"This research was motivated by patients who came in with complete heart block where I put in a pacemaker and they asked, 'Why did this happen to me?'" said Marcus in a press release. "The answer to this question has not been clear, so we wanted to look at the impact that blood pressure might have on the development of their conduction disease."

Marcus and colleagues noted the biological plausibility of a link between hypertension and cardiac conduction disease.

"In hypertension, left ventricular pressure overload may lead to interstitial fibrosis, with subsequent downregulation of gap junctions and impairment in normal electrical cell coupling," they wrote. "Higher systemic blood pressure may also be associated with activation of neurohormonal, cytokine, inflammatory, and oxidative stress signaling pathways that may similarly lead to such fibrosis."

They reported that, in SPRINT, the factors associated with greater risk of conduction disease were older age (HR 1.42 per 10-year increase, 95% CI 1.21-1.67), male sex (HR 2.31, 95% CI 1.63-3.32), and cardiovascular disease (HR 1.46, 95% CI 1.06-2.00).

SPRINT was the impetus for national guidelines 6 years ago revising the BP target down from 140/90 mm Hg to 130/80 mm Hg. The trial found that an even stricter target, below 120 mm Hg, reduced heart attack, stroke, or death in higher-risk older adults, with no excess in falls or orthostatic hypertension in the elderly.

The post hoc findings regarding LV conduction disease were "convincing" in providing a new mechanistic endpoint for managing hypertensive patients with at least one additional cardiovascular risk factor, commented Marco Valgimigli, MD, PhD, an interventional cardiologist at the Istituto Cardiocentro Ticino in Lugano, Switzerland.

"I think clinicians may now want to monitor left ventricular conduction defects even more closely in the follow-up of these patients as possible markers of inadequate (non-sufficiently aggressive) pressure control measures. I think we all would like to see this happening in practice, not only in the setting of a [randomized controlled trial]," said Valgimigli, who was not involved with the present study.

Marcus' group analyzed data from the original SPRINT cohort of older adults with hypertension and at least one other cardiovascular risk factor but excluded those with baseline left ventricular conduction disease, ventricular pacing, or ventricular pre-excitation.

This left them with 7,874 people (mean age 67.6 years, 36% women) across the study arms randomized to BP targets of <140 mm Hg or <120 mmHg.

As expected, in a negative control analysis, standard versus intensive BP control didn't impact right bundle-branch block (HR 0.95, 95% CI 0.71-1.27)

"The negative finding of right bundle-branch block risk demonstrates that the association between intensive BP lowering and lower risk of left ventricular conduction disease was less likely a chance finding or that the changes in left ventricular conduction disease were epiphenomena reflective of some other unknown factor that differed between the randomization groups," the authors said.

Nevertheless, they acknowledged that the post hoc nature of their study precluded any definitive causal conclusions regarding BP control and LV conduction disease.

"One may argue that this is a post-hoc analysis and, as such, subject to uncontrolled type I and type II errors," Valgimigli said, "yet the results are highly consistent, with similar benefits in all possible left ventricular conduction defects, and to me highly credible and plausible."

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