Cognitive Impairment Tied to Increased Cardiovascular Disease Risk in Type 2 Diabetes

Hertzel Gerstein, MD

New research is calling attention to an often-overlooked aspect of overall health in these patients: cognitive impairment.

An analysis of data from the REWIND trial, results of the study, which was funded by Eli Lilly and Company, suggest presence of cognitive impairment among patients with diabetes was associated with a 1.6 times greater risk of major adverse cardiovascular events and a 1.8 times greater risk of stroke or mortality compared to their counterparts without cognitive.

“Our study found low scores on cognitive tests predicted heart disease in people with diabetes and other heart risk factors,” said study investigator Hertzel C. Gerstein, MD, professor of medicine in the Faculty of Health Sciences at McMaster University, in a statement. “Although the explanation for this remains unclear, proven heart medications should be offered to these patients to reduce their future risk of a heart attack or stroke.”

While previous research has clearly outlined the associations between low cognitive scores or poor cognitive health with increased risk of adverse cardiovascular events, it is unknown whether the relationship of the association could be assessed more accurately using novel cognitive indices. With this in mind, Gerstein and an international team of investigators designed the current study as an analysis of the Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) trial.

A multicenter, randomized, double-blind, placebo-controlled trial comparing dulaglutide against placebo therapy in patients from 371 sites in 24 countries, the trial provided investigators with information related to a cohort of 9901 individuals with type 2 diabetes and additional cardiovascular risk factors with a follow-up lasting a median of 5.4 years.

After limiting the original REWIND cohort to only those who had completed both the Montreal Cognitive Assessment (MoCA) and the Digit Substitution Test (DSST), investigators were left with a cohort of 8772 individuals for inclusion in their analyses, including 905 with substantive cognitive impairment at baseline.

The primary outcome of interest for the investigators’ analyses was the association between cognitive score measures and incident major adverse cardiovascular events and either stroke or death. For the purpose of analysis, substantive cognitive impairment was defined as a baseline score on either the MoCA or DSST equal to or greater than 1.5 standard deviations below the country-specific mean.

Compared to their counterparts without baseline substantive cognitive impairment, those with cognitive impairment had higher incidence of major adverse cardiovascular events (HR, 1.34 [95% CI, 1.11-1.62]; P=.003) and stroke or death (HR, 1.60 [95% CI, 1.33-1.91]; P <.001) in unadjusted analyses. Investigators pointed out this relationship with major adverse cardiovascular events remained significant but was attenuated after adjustment for age, sex, education, prior stroke or TIA, systolic blood pressure, HbA1c and tobacco use (HR, 1.22 [95% CI 1.01-1.48]; P=.043) and became nonsignificant after adjustment for albuminuria, eGFR, and retinopathy.

Further analysis indicated stronger relationships were observed with country-specific mean substantive cognitive impairment score and major adverse cardiovascular events (HR, 1.61 [95% CI, 1.28-2.01]; P <.001), and stroke or death (HR, 1.85 [95% CI, 1.50-2.30]; P <.001). Investigators pointed out the relationships with country-specific mean score and major adverse cardiovascular events and stroke or death remained significant in models that adjusted for up to 10 substantive cognitive impairment risk factors.

This study, “Novel Indices of Cognitive Impairment and Incident Cardiovascular Outcomes in the REWIND Trial,” was published in the Journal of Clinical Endocrinology and Metabolism.