Low Serum Eicosapentaenoic Acid Levels in Cryptogenic Stroke with Active Cancer

https://doi.org/10.1016/j.jstrokecerebrovasdis.2020.104892Get rights and content

Highlights

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    Low serum EPA levels were associated with cryptogenic stroke with active cancer.

Abstract

Background and Purpose

The increased prevalence of cancer has led to it being considered an important factor in the cause of cryptogenic stroke. In recent years, polyunsaturated fatty acids, particularly omega-3 polyunsaturated fatty acids, have been shown to prevent cancer development and progression. This study aimed to clarify the characteristics of serum polyunsaturated fatty acids in cryptogenic stroke with active cancer.

Methods

The serum levels polyunsaturated fatty acid fractions (eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA; dihomo-gamma-linolenic acid, DHLA; and arachidonic acid, AA) in cases of cryptogenic stroke, sampled within 5 days after admission, were measured. Active cancer was defined as a new diagnosis, treatment, progression or recurrence within 6 months before admission, or metastatic cancer. Multivariate logistic regression analyses were performed to explore the relationship between serum polyunsaturated fatty acids and cryptogenic stroke with active cancer.

Results

Among 123 cases classified as cryptogenic stroke, 27 had active cancer. The serum EPA levels (1.26 ± 0.72 versus 1.89 ± 1.27 umol/l; P = 0.02) were significantly lower in cryptogenic stroke with active cancer, whereas the serum DHA, DHLA and AA levels did not significantly differ. Multivariate logistic analysis revealed that the serum EPA levels were associated with cryptogenic stroke with active cancer independently of age and serum D-dimer levels (odds ratio, 0.974; 95% confidence interval, 0.949–0.999; P = 0.04).

Conclusions

In our study, low serum EPA levels were associated with cryptogenic stroke with active cancer. This suggests that low serum EPA levels may have some involvement in the pathogenesis of cryptogenic stroke with active cancer.

Introduction

Since Armand Trousseau first described migratory superficial thrombophlebitis in 1865, patients with malignant cancer have been known to be in a hypercoagulable state and at risk for the development of cancer-associated thrombosis.1 Approximately 7% of cancer patients have symptomatic cerebrovascular diseases during the clinical course of cancer, and 15% have cerebrovascular lesions at autopsy.2 Previous studies have demonstrated that cancer patients with cryptogenic ischemic stroke often have high serum D-dimer levels and multiple vascular lesions and show cryptogenic stroke etiology, which seems to be due to a hypercoagulable state.3, 4, 5 Regardless of etiology, once a stroke has occurred in a cancer patient, the overall prognosis has been reported as poor.6

In recent years, increasing evidence indicates that omega-3 polyunsaturated fatty acids play a role in cancer risk and progression. Omega-3 polyunsaturated fatty acids play crucial roles in maintaining cellular homeostasis, and perturbations in dietary intake or omega-3 polyunsaturated fatty acid metabolism can result in cellular dysfunction and contribute to cancer risk and progression.7 Therefore, omega-3 polyunsaturated fatty acids might be involved in ischemic stroke associated with cancer. In the present study, we aimed to assess the characteristics of serum polyunsaturated fatty acids in cryptogenic stroke with active cancer.

Section snippets

Methods

Consecutive patients who had an acute symptomatic ischemic stroke and were admitted to or consulted the Department of Neurology, Nara Medical University Hospital, Nara, Japan, within 7 days of onset between March 2014 and December 2019 were studied.

Age, gender, and stroke risk factors, including hypertension, diabetes mellitus, hyperlipidemia, current smoking, arterial fibrillation and past history of stroke, and the period from the stroke onset to admission were recorded for all patients. All

Results

A total of 123 (30%) cases of cryptogenic stroke (85 men, 38 women; mean age, 71.0 ± 13.0 years) among 458 cases of consecutive acute ischemic stroke with admission within 7 days of onset were enrolled in this study. Of the 123 cases of cryptogenic stroke, 27 (22%) (15 men, 12 women; mean age, 70.4 ± 8.67 years) had active cancer, including lung cancer (8, 30 %) stomach cancer (4, 15 %), urinary bladder cancer (3, 11 %), liver, gallbladder, and pancreatic cancer (2, 7 %), and breast, bile duct,

Discussion

To our knowledge, our study has demonstrated, for the first time, that the serum EPA levels were significantly lower in cases of cryptogenic stroke with active cancer than in those cases without cancer, whereas the serum DHA, DHLA, and AA levels did not significantly differ. Furthermore, the low serum EPA levels were associated with cases of cryptogenic stroke with active cancer even after adjusting for the serum D-dimer level, which is considered a strong predictive factor for cryptogenic

Sources of Funding

None

Conflicts of Interest and any Disclosures

The author have no conflicts of interest to disclose concerning the paper.

Acknowledgments

The authors would like to thank Enago for the English language review.

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