Cognitive Decline Common in Heart Failure

November 28, 2019

There is a significant risk of cognitive decline in patients with heart failure, and patients who experience cognitive decline have a higher mortality rate, a new study has shown. 

"Considering the high impact of cognitive impairment on mortality, and the possibility to act on some of its predictors, clinicians who treat patients with heart failure should assess cognitive function frequently," the authors conclude.

"Cognitive function isn't routinely monitored in patients with heart failure at present. This is something we need to pay more attention to," senior author, Marco Di Tullio, MD, Columbia University, New York City, told Medscape Medical News.

The study was published in the December issue of JACC: Heart Failure and was supported by the US National Institute of Neurological Disorders and Stroke.

Cognitive dysfunction is known to affect patients with heart failure but little is known about the time course and factors that may predict cognitive decline over time, Di Tullio said. "There have only been small studies looking at this with few patients and short follow-up, and heart failure treatment has not been optimal in these studies," he said.

"These studies are incredibly difficult to conduct as patients with heart failure and cognitive function tend to have a high rate of nonattendance at follow-up appointments," he noted. "Heart failure patients with cognitive dysfunction die more often and those that survive have more heart failure complications, which means they are less likely to attend follow-up visits. So results of any studies will always underestimate the real effect of cognitive dysfunction in heart failure," he added.  

Despite the fact then that the most severe cases would have been underrepresented in this study, "we did show that a sizeable proportion of patients with heart failurehave cognitive dysfunction," Di Tullio said. "We also showed that those with lower cognitive function had a higher mortality and that mortality increased as cognitive function declined more over time."

For the study, the researchers analyzed data from the Warfarin Versus Aspirin in Reduced Ejection Fraction (WARCEF) trial in patients with heart failure, in which yearly Mini-Mental State Examinations (MMSE) to assess cognitive function were performed. On the MMSE, higher scores indicate better cognitive function.

The current main analysis included the 1846 patients who had a baseline and at least 1 follow-up MMSE measurement.

"The sample size of the present cohort was larger than that of the combined number of patients with heart failure included in previous longitudinal studies," the researchers note.  

The mean baseline MMSE in the study cohort was 28.6, and the mean age of patients was 61 years.

Results showed that Kaplan-Meier estimates of the composite endpoint — a combination of ischemic stroke, intracerebral hemorrhage, or death from any cause — with an MMSE score of 30, 27-29, or < 27 were 25.2%, 34.3%, and 37.9%, respectively (P = .023).

Kaplan-Meier estimates of death rates were 22.0%, 32.2%, and 32.7% with MMSE scores of 30, 27-29, or < 27, respectively.

At 12 months, 13.6% of patients showed a cognitive decline of ≥ 2 points in the MMSE.

"This is a significant and clinically relevant decline in cognitive function," Di Tullio commented.

Among those patients who had at least one MMSE measurement after 12 months and did not show cognitive decline at the 12-month visit, an additional 8.9% showed cognitive decline beyond 12 months.

Kaplan-Meier estimates of death with an MMSE decrease of ≥ 2 points, 1 point, and no decrease were 33.4%, 32.1%, and 27.2% (P = .051), respectively.

In a multivariate analysis, a decline of ≥ 2-points in MMSE score was significantly associated with a higher baseline MMSE score, older age, nonwhite race/ethnicity, lower education level, and also NYHA functional class II or higher.

"Our results on predictors of cognitive decline showed some surprises," Di Tullio said. 

"While there were factors that we would expect to be associated with cognitive decline, such as older age and lower education levels, traditional atherosclerotic risk factors did not seem to be associated with cognitive decline in these heart failure patients," he noted. "And while severity of heart failure was linked to faster cognitive decline, we didn't find any difference between different heart failure medical treatments." 

Normal Cognitive Function at Baseline Still at Risk

"One surprising finding was that better cognitive function at baseline appeared to be a predictor of greater future cognitive decline. Maybe that is because these patients have more to lose," he suggested.

"I think one of the messages from this study is all patients with heart failureare at risk of cognitive decline, and just because patients may have good cognitive function right now, they should not be considered safe from future decline. They can still deteriorate over time," he said.

Noting that this observation contrasts with data from the general population, which show cognitive decline to be worse in individuals with a low baseline MMSE score, the researchers say the present results are plausible from a pathophysiology standpoint because cognitive decline in patients with heart failure is conceivably more related to the interaction between heart and brain than in the general population, which may recognize other predominant risk factors for cognitive decline.

The results also showed that a history of transient ischemic attack or stroke, or reduced renal function, were predictors of worse cognitive decline in patients with heart failure.

"These findings suggest that noncardiovascular comorbidities also play an important role in cognitive decline in patients with heart failure and represent potential targets for interventions," Di Tullio said.

"While we can't say from this study what may help to slow the cognitive decline in these patients, I think it would be reasonable to treat the heart failure more aggressively in patients with more predictors of cognitive decline in an attempt to stave off that cognitive decline," he added.

Although the exact mechanisms linking heart failure and cognitive decline are not known, Di Tullio suggested they could involve hypoperfusion — declining pumping function of the heart will result in less perfusion of blood to the brain — and an increased frequency of atrial fibrillation, which can cause emboli to form and travel to the brain. Also, inflammation and endothelial dysfunction could play a role.

"Our results also provide another reason to manage cardiovascular risk factors closely in younger healthier people, so they don't develop heart failure in the first place, as in addition to the heart failure itself, this also comes with a greater risk of cognitive decline. That's something to be aware of," he added. 

In an accompanying editorial, Andreas P. Kalogeropoulos, MD, PhD, and Hal Skopicki, MD, Stony Brook University, New York, say the current study adds "an important foundational building block to aid in our understanding of cognitive decline among patients with heart failure."

"Despite the lack of definitive interventions, their data invite us to recognize and quantify cognitive decline longitudinally with possible referral of these patients for focused care," they note.

"From a cardiovascular care perspective, these data challenge us to optimize pharmacological and device therapy, with the hope of maintaining the best possible hemodynamic and neurohumoral milieu in the belief that this may be beneficial to the physical, functional, and social keys to optimal patient outcomes," the editorialists conclude.

JACC: Heart Failure. December 2019. Abstract, Editorial

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