New Cancer Diagnosis Linked to Increased Stroke Risk

January 08, 2015

A diagnosis of cancer — particularly lung, pancreatic, or colorectal cancer — is associated with an increased short-term risk for stroke, a new study suggests.

The study, published online January 7 in the Annals of Neurology, was led by Babak B. Navi, MD, Weill Cornell Medical College, New York, New York.

"The immediate clinical implication of our study is that patients with cancer should be vigilant for symptoms and signs of stroke, and if they think they may be having a stroke to seek immediate medical attention," Dr Navi commented to Medscape Medical News. "They should also pay attention to other stroke risk factors such as diabetes [and] cholesterol blood pressure and make sure these are properly addressed to lower their stroke risk.

"Stroke is particularly relevant to cancer patients because strokes often preclude or delay cancer treatments, resulting in reduced survival," he added.

In the paper, the authors conclude, "[C]ancer may be an underappreciated yet common risk factor for stroke. Future studies will be needed to determine the precise mechanisms by which cancer may be associated with stroke, the need to include a cancer diagnosis in cardiovascular risk prediction instruments, and the optimal strategies to prevent stroke in patients with cancer."

Increased Coagulability

Dr Navi explained that cancer has been suspected to be a risk factor for stroke for some time. "It is known that cancer increases the risk of clots in the venous system — deep vein thrombosis and pulmonary embolism. But there has not been much study of how it may affect the arterial system."

For the current retrospective cohort study, Dr Navi and colleagues used data from the Surveillance, Epidemiology, and End Results (SEER) national cancer registry, which includes around one quarter of all patients with cancer in the United States. This was linked to the Medicare administrative database of patients older than age 65 years in the United States to ascertain stroke diagnoses.

The researchers included patients with five types of cancer: lung, colorectal, breast, and prostate (the four most common cancers) and pancreatic cancer (the one most commonly associated with clotting).

The analysis included 327,389 patients with one of these five cancers. Stroke risk in these patients was then evaluated from the Medicare database. Each patient was matched with a control individual who did not have cancer in terms of age, race, sex, geographic location, and medical comorbidities.

Results showed that patients with cancer had an increased risk for stroke compared with the individuals who did not have cancer, especially in the first 3 months after cancer diagnosis. This was particularly noticeable for patients with lung, colorectal, or pancreatic cancer. The excess risks attenuated over time and were generally no longer present beyond 1 year.

Table. Incidence of Stroke at 3 Months Since Cancer Diagnosis

Type of Cancer Incidence of Stroke in Patients With Cancer (%) Incidence of Stroke in Controls (%)
Breast 1.5 1.1
Colorectal 3.3 1.3
Lung 5.1 1.2
Pancreas 3.4 1.3
Prostate 1.2 1.1

 

Dr Navi said the increased risk within the first 3 months from diagnosis may occur because this is when cancer is most aggressive, before it is brought under control by treatment. "The mechanism by which cancer is associated with clotting is not completely understood, but it is thought to have effects on the fibrinolytic system and may also cause damage to the endothelium of blood vessels," he commented.

Cancer treatments may also be increasing stroke risk, given that the first 3 months after diagnosis is generally when the intensity of chemotherapy, radiation, and other therapies is highest, the authors point out. They are planning a further analysis of the database to examine whether various types of chemotherapy are associated with stroke risk.

The risk for stroke correlated with the aggressiveness of the cancer, the researchers report. For example, risk was highest among patients with lung, pancreas, and colorectal cancers, which are often diagnosed at advanced stages. Patients with breast and prostate cancer, who often have localized tumors, had the lowest stroke risk.

"This finding further supports the biological plausibility of an association between cancer and stroke because cancer-mediated hypercoagulability and thrombotic risk are closely linked to cancer activity," they write.

Prostate cancer, the least aggressive cancer type studied, was only weakly associated with ischemic stroke risk but was strongly associated with hemorrhagic stroke risk, even up to 3 years after diagnosis. "This difference in risk by stroke subtype may reflect the pathophysiological differences between ischemic and hemorrhagic stroke, as well as the effects of the standard course and treatment of prostate cancer," they write.

Dr Navi noted that a previous Swedish study has suggested a link between cancer and stroke and also between cancer and an increased risk for myocardial infarction (MI). "We are going to look at MI as well in our study, but are reporting the stroke results first," he said.

"Our study does need confirmation," Dr Navi acknowledged. "One limitation is that we relied on administrative Medicare data for stroke incidence, rather than a prospectively determined diagnosis. However, Medicare data is very reliable."

The team is planning to validate the results in a prospective study.

This study was supported by grants from the National Institutes of Health (NIH) National Center for Advanced Translational Sciences, the Florence Gould Endowment for Discovery in Stroke, and the NIH National Cancer Institute. The authors have disclosed no relevant financial relationships.

Ann Neurol. Published online January 7, 2015. Abstract

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