Cancer Boosts Stroke Risk

Pam Harrison

November 12, 2012

Patients with cancer who have none of the conventional stroke risk factors are at increased risk for stroke due to cancer-related hypercoagulation, new research shows.

Christopher Schwarzbach, MD, and colleagues from the University of Heidelberg, Mannheim, Germany, found unidentified stroke etiology was significantly more frequent in patients with cancer than controls.

Conversely, conventional risk factors, such as hypertension and hyperlipidemia, were significantly more prevalent in controls than in patients with cancer who had also had a stroke.

"Our study is the largest on this topic including a matched control group so far and the data strengthen the concept of cancer-associated hypercoagulation as an important stroke etiology in cancer patients," study investigator Dr. Schwarzbach told Medscape Medical News.

"Clinicians should be aware of this potential and important stroke mechanism, even in elderly patients with usual risk factors for atherosclerosis," he added.

The study was published in the November issue of Stroke.

Hypercoagulable State

Cancer is often considered a hypercoagulable state. However, as Dr. Schwarzbach noted, only a few studies have explored the relationship between cerebral ischemic events as a manifestation of hypercoagulation, and results have been contradictory.

For the study, data on 140 patients with ischemic stroke and the additional diagnosis of solid or active malignancy were prospectively collected between 2002 and 2011.

The same number of sex- and age-matched patients who presented with ischemic infarction served as controls.

Patients were phenotypically categorized according to the American Society of Clinical Oncology (ASCO) classification of stroke and were assigned to a conventional stroke etiology (CSE) group with an ASCO score grade of 1 or 2 or an unidentified/cancer-associated stroke etiology (UCE) group with an ASCO score grade of 3 or 0.

Patients with cancer and CSE and those with UCE were analyzed separately.

Unidentified stroke etiology was significantly more frequent in the cancer group (48%) than in controls (27%) (P < .001).

The prevalence of deep-vein thrombosis and pulmonary embolism was similarly significantly higher in patients with cancer than in controls: 8% vs 1% (P < .01).

D-dimer levels, a measure of activation of the coagulation cascade and thrombus formation, were again significantly higher in the UCE group than the CSE group of patients with cancer (P < .05).

"Metastatic disease itself was significantly more frequent in patients with cancer with unidentified and/or stroke-associated stroke etiology (59%) than in patients with cancer with conventional stroke etiology (28%; P < 0.05)," the investigators add.

When they compared stroke lesion patterns between patients with cancer and controls, infarction in multiple vascular territories (P < 0.05) and small embolic infarction (P < 0.001) were also significantly more frequent in those with cancer.

"The significantly higher prevalence of infarction in multiple vascular territories in patients with cancer compared with control subjects as well as in the UCE compared with the CSE group of patients with cancer...supports the concept of proximal embolism potentially due to cancer-associated hypercoagulation," the investigators write.

They added that "patients with suspected cancer-associated hypercoagulability screened for other thromboembolic complications such as deep vein thrombosis which is of utmost therapeutic relevance."

Important Contribution

Marc Lazzaro, MD, from the Medical College of Wisconsin, Milwaukee, and a member of the American Academy of Neurology, told Medscape Medical News that this latest report is of the largest case-control study to date that suggests cancer-associated hypercoagulability is an important risk factor for stroke.

"This is an important contribution to understanding stroke etiology and the management of stroke patients," Dr. Lazzaro added, "[as] accurate identification of stroke etiology is essential to optimally reduce the risk of recurrent events. This study sharpens our understanding of ischemic stroke."

Dr. Lazzaro also noted that the results of this study highlight the importance of evaluating select stroke patients for malignancy, especially those without an identified etiology.

"Findings further support the need for prospective therapy trials to guide treatment of cancer patients with stroke related to cancer-associated hypercoagulability," he said.

The authors and Dr. Lazzaro have disclosed no relevant financial relationships.

Stroke. 2012;43:3029-3034. Abstract