Comorbidities Related to Clinical Outcomes in Patients With Acute Ischemic Stroke Undergoing Mechanical Thrombectomy: Review of Literature and Experience at a Single Comprehensive Stroke Center

DISCUSSION

The comparative analysis of age, BMI, and comorbid conditions with outcomes in our population showed a statistically significant correlation to functional nonindependence in patients who presented with chronic hypertension, peripheral artery disease, and younger age at presentation. Our results agreed with those of Le Bouc et al that showed improved outcome with advanced age.⁴ However, our results differed from the findings of the DAWN trial that showed age >80 years (given a prespecified infarct volume) was associated with worse functional outcomes.² One difference between our study and the Le Bouc et al and the DAWN studies is that we analyzed age as a continuous variable, whereas the Le Bouc et al and DAWN trials set thresholds for advanced age (50 years and 80 years, respectively).^2,4 We did not dichotomize age because of a general lack of evidence for a threshold effect and to prevent overfitting. Consequently, our results show a different age effect.

In our study, peripheral artery disease had a significant correlation with not achieving functional independence at 90 days. We suggest multiple possible explanations for this correlation. We theorize that the presence of diffuse atherosclerosis may make the vascular beds more prone to intraprocedural rupture or injury, potentially promoting rethrombosis and limiting recovery potential. Additionally, vascular disease may make the procedure more technically challenging and the removal of blood clots less successful. Finally, patients with vascular disease have less compliant blood vessels, potentially diminishing the ability of the vasculature to preserve flow to the brain during the ischemic period and, in turn, reducing the benefit of MT.

The only study we found assessing the impact of peripheral artery disease was the Kurre et al study that analyzed the outcomes of patients ≥80 years with chronic disease states.³ The authors did not find a significant correlation between peripheral artery disease and the outcomes of MT, a result the authors attributed to the unrigorous characterization of the sample population, unreported comorbidities, and lack of prospective design. Furthermore, the authors explained that their study did not consider the severity of each premorbid condition.

Our data also show that hypertension is a variable likely to impact outcomes following MT. Goyal et al looked at the effect of hypertensive crisis during and after MT but did not examine hypertension as a comorbidity impacting long-term outcomes.⁷ Our study adds evidence that hypertension is an outcome-determining variable not only when it occurs periprocedurally but also when it is a preexisting comorbidity.

Our finding that hypertension and peripheral artery disease are variables impacting the outcomes of MT is important considering the prevalence of these chronic conditions. According to Centers for Disease Control and Prevention data published in 2016, the overall prevalence of hypertension was 29.0%, and the prevalence increased with age: 18-39 years, 7.5%; 40-59 years, 33.2%; and ≥60 years, 63.1%.⁸ Because of the high prevalence of hypertension, we suggest that prospective studies be conducted to validate our finding as we anticipate that the majority of patients who have a stroke and are evaluated for candidacy of MT will have hypertension.

Peripheral artery disease is present in approximately 8.5 million people in the United States including 12%-20% of individuals >60 years.⁹ Risk factors for peripheral artery disease include smoking, hyperlipidemia, hypertension, and diabetes.⁹ While our study did not show correlations between hyperlipidemia and diabetes (we did not assess smoking) and MT outcomes, our study did show a correlation with peripheral artery disease.

Lu et al showed that patients with a prior history of diabetes mellitus had significantly lower odds of functional independence.⁵ Conversely, Kurre et al did not find a statistically significant impact of diabetes on functional nonindependence after MT.³ Our study supports the finding of Kurre et al.

The other risk factors evaluated in our study—BMI, HbA1c, and hyperlipidemia—showed no statistically significant correlations. While this result may reflect an actual lack of correlation between these diagnoses and outcomes in this population, we suggest that the result could instead be attributable to low sample sizes for each of these diagnoses, as well as underdocumentation in the EMR. Our study has additional limitations. First, the study is retrospective. Prospective studies with large sample sizes that rigorously ensure proper diagnoses of comorbid conditions and their severity are needed to confirm our results. Second, our study did not have a formal control as we did not compare our cohort to a non-MT group. Randomized controlled trials that compare treatment and nontreatment groups are needed to validate our results. Third, we obtained comorbidities from the EMR based on the documentation of diagnosis codes. Physicians and nurses manually enter these diagnoses at various times throughout patient care, possibly resulting in a great deal of variability in the accuracy of this documentation. Despite these concerns, our data add to the growing evidence related to existing comorbidities and the outcomes of patients with acute ischemic stroke who are undergoing MT.