Blood-Pressure Variability Seen to Predict Cognitive Decline

Pam Harrison

January 15, 2015

DALLAS, TX — Visit-to-visit variation in systolic blood pressure (BP) and mean heart rate (HR) are both independently related to cognitive dysfunction and decline in patients at high cardiovascular risk, and together their predictive effects are additive, suggests research published online January 12, 2015 in Hypertension[1]. Mean systolic BP per se didn't have a significant effect on cognition.

"The take-home message is that HR should be at an optimal rate below 70 bpm, because using beta-blockers [to lower HR] does no harm, especially when a beta-blocker is already indicated as in coronary artery disease or heart failure," Dr Michael Böhm (Universitatsklinikum des Saarlandes, Homburg/Saar, Germany) told heartwire .

Clinicians may find elevated HR to be a useful predictor when assessing patients for their risk of cognitive decline, according to Böhm. And the current study, he said, is the first to identify variability in systolic BP in this high-risk cohort as an independent predictor of cognitive decline, cognitive dysfunction, and cognitive deterioration.

Prospective intervention trials are still needed in high-risk patients to investigate potential drug therapies for improving systolic BP variability and their effect on outcomes, Böhm said.

He and his colleagues pooled data from two studies to evaluate the association of mean systolic BP, visit-to-visit variation in systolic BP, mean HR, and visit-to-visit variation in HR with cognitive decline and cognitive dysfunction in high-risk cardiovascular patients. The studies were the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) and the Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease (TRANSCEND).

In both studies, patients with a history of coronary artery disease, peripheral artery disease, prior transient ischemic attack or stroke, or diabetes mellitus complicated by organ damage were eligible for inclusion. The current analysis included a combined total of 24 593 patients without preexisting cognitive dysfunction.

At each visit in both studies, resting blood pressure and HR were measured and visit-to-visit variation in both BP and HR calculated.

Cognitive function was evaluated by the Mini Mental State Examination (MMSE) at baseline, after 2 years, and at the penultimate visit (usually between 3 and 5 years). About 88% of patients were evaluated at both 3 and 5.5 years.

Cognitive dysfunction was defined as a MMSE ≤24 points at the last available visit and cognitive decline as ≥5-point decrease in the MMSE. Cognitive deterioration was defined as a drop of >1 point per year in the MMSE or a decline to <24 points.

"Cognitive dysfunction was observed in 1857 patients (7.6%) and cognitive decline in 1176 patients (4.8%); 1017 patients (4.1%) fulfilled the criteria for both end points," investigators report.

Separating patients with a mean systolic BP into quintiles, the prevalences of cognitive dysfunction (P<0.0001) and cognitive decline (P=0.0012) increased significantly from the lowest to highest quintiles. Similarly significant effects of visit-to-visit variation in systolic BP on cognitive dysfunction, decline, and deterioration were seen (P<0.0001 for all three). The same pattern applied to heart rate.

In the multivariate model, visit-to-visit variation in systolic BP (P=0.0030) and mean HR (P=0.0008) were the only significant predictors of cognitive dysfunction. The odds ratios [OR] were 1.32 (95% CI 1.10–1.58) and 1.40 (95% CI 1.18–1.66), respectively, for the fifth vs the first quintiles..

Similar effects were observed for both cognitive decline and deterioration and the same two risk features in the adjusted analysis, according to the investigators.

Patients in the highest quintiles of both visit-to-visit variation in SBP and mean HR had an OR of 1.85 (95% CI 1.44–2.38) for cognitive dysfunction. For cognitive decline, the maximum OR at 2.03 (95% CI 1.50–2.75) was seen for those in the fifth quintile of visit-to-visit variation in SBP and the fourth quintile of mean HR.

Results were not affected by a background history of stroke or atrial fibrillation.

"This study demonstrates that long-term SBP variations and mean HR levels are associated with the development of cognitive dysfunction, decline, and deterioration in high-risk patients with atherosclerosis or after stroke or high-risk diabetes mellitus," the authors conclude.

MMSE as the Sole Assessment Instrument

In an accompanying editorial[2], Dr Jurgen Claassen (Radboud University Medical Center, Nijmegen, the Netherlands) suggests that some critics will question MMSE as the sole assessment instrument of cognitive function in the current study, as the MMSE is insensitive to dementia in patients with higher education as well as those with vascular dementia. The MMSE is also sensitive to confounders such as depression.

However, because of the large number of patients included in the analysis as well as the large number of repeated assessments—an average of 11 recordings during a period of 4.5 years—"the patterns of decline in MMSE that emerge in this study . . . most likely truly reflect trends of cognitive decline in this population," Claassen writes.

But how could variability in BP or high heart rate cause dementia, he asks. The brain critically depends on brain perfusion, and instability in BP, present over long periods of time, may jeopardize perfusion, he proposes.

More speculatively, he adds, low HR, based on animal data, may have beneficial effects on atherosclerosis and endothelial function and thus on cerebral blood flow, and these protective effects may be lost with high heart rates.

"All in all, the observations by Böhm et al should stimulate a strong research effort, uniting the cardiovascular and neuroscience fields, aimed at elucidating the links between vascular disease and onset and progression of cognitive decline."

The ONTARGET and TRANSCEND studies were funded by Boehringer Ingelheim. All authors received scientific support from Boehringer Ingelheim. Böhm reported he had no relevant financial relationships; disclosures for the coauthors are listed in the article. Claassen declared relevant financial relationships.


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