Visit-to-Visit BP Variability Linked to Coronary Plaque Progression, Adverse Outcomes

Patients with CAD who have bigger swings in blood pressure between trips to the doctor are more likely to have progression of coronary atheromas and adverse cardiovascular outcomes, according to a study that provides insight into the previously identified link between BP variability and CVD.

The relationships were strongest for variability in systolic BP, which was associated with annualized change in percent atheroma volume measured by IVUS in a post hoc look at seven randomized trials (P = 0.007), researchers led by Donald Clark III, MD (University of Mississippi Medical Center, Jackson), report.

Moreover, through 24 months of follow-up, MACE risk rose in lockstep with increases in systolic BP variability, from 6.1% in the patients with the most stable BP readings to 12.0% in those with the most widely fluctuating readings (P < 0.001 for trend).

The findings, published online April 10, 2019, ahead of print in JAMA Cardiology, “establish a mechanistic link underlying a body of literature demonstrating an association between BP variability and CVD risk and suggest maintaining stable BP levels may be important to further improve outcomes in patients with coronary disease,” the authors write.

To TCTMD, senior author Rishi Puri, MD, PhD (Cleveland Clinic, OH), pointed out that fluctuations in control of other risk factors, like LDL cholesterol, have been seen in other studies, and he added that treatment compliance does not seem to be a major explanation for the phenomenon.

“Variability in these risk factors could be because there’s some factors related to the biology of that patient that result in fluctuating responses to the therapies we use,” Puri said. “We don’t know what the mechanism is, but from this particular analysis, we’re able to [suggest]—although not prove—that cyclical variability of your systolic blood pressure probably does have a proatherosclerotic effect. And when people demonstrate plaque progression, we know that correlates with greater clinical events.”

Evidence That BP Variability Is Harmful

BP readings that fluctuate widely from visit to visit have been tied to poor outcomes in multiple studies. In one study of US military veterans, for example, higher systolic BP variability was associated with heightened risks of coronary heart disease, stroke, end-stage renal disease, and all-cause mortality.

BP variability has been shown to correlate with arterial stiffness and endothelial dysfunction, but the mechanisms underlying the relationships with clinical outcomes are still not well understood.

In this study, the investigators explored the possible contribution of coronary atheroma progression as an explanation for the findings. They performed a post hoc, patient-level analysis of seven randomized trials of various antiatherosclerotic or antihypertensive therapies. The analysis included a total of 3,912 adults (mean age 58 years; 28% women) who had CAD and underwent serial IVUS measurements.

Most patients (78%) had hypertension, which was generally well controlled. Mean achieved levels of systolic, diastolic, and pulse pressure were 129, 77, and 52 mm Hg, respectively.

During follow-up of up to 2 years, there was no overall change in mean percent atheroma volume, but patients with greater visit-to-visit variation in BP—particularly systolic—were more likely to have atheroma progression (OR 1.09; 95% CI 1.01-1.17). Relationships with variability in diastolic or pulse pressure were not significant.

“The stronger association with systolic BP variability may be linked to the relatively older age of participants included in this analysis,” the authors explain. “Systolic BP, as compared with diastolic BP or pulse pressure, is known to have more prognostic importance with increasing age.”

Risk of MACE (death, MI, stroke, urgent revascularization for ACS, and hospitalization for unstable angina) tended to increase with greater variability for all three measures of BP, but the relationship was strongest for systolic BP.

“The synergistic findings at the arterial level and the findings at a clinical level tell us that we need to understand this concept of variability a little more,” Puri said.

‘More Questions Than Answers’

What this all means for the treatment of patients with CAD remains unclear, Puri said, noting that there are no therapies proven to reduce BP variability.

In their paper, the investigators note that because statins have been shown to slow or even reverse plaque progression, they might represent a potential treatment for patients with high BP variability.

Also, now that renal denervation appears to be making a comeback, it will be interesting to look at whether lowering BP in that fashion will result in less variability compared with medical therapy, Puri said.

For now, for patients with swings in BP, “all we can do is harp on compliance,” Puri said. “We know that’s easier said than done. But other than that, there are no therapies strictly directed at variability.”

Future research into the causes of variability in risk factor control might help clarify what to do when it occurs and present an opportunity for more personalized treatments to reduce cardiovascular risk, Puri said. “I think individual variability is something that we may look at in the future as we look for incremental gains in lowering residual risk in our patients.”

But, he said, there’s still a lot to learn. “We need to go back to the biology and understand this better, and the future will be about teasing out these mechanisms and understanding if we can actually treat this or not. We don’t know whether we can,” Puri said. “So this is essentially just a mechanistic study posing perhaps more questions than answers.”