MI, Stroke Risks Rise Months Before Cancer Diagnosis

Pam Harrison

December 26, 2018

The risk of having a myocardial infarction (MI) or an ischemic stroke increases 5 months before patients receive a diagnosis of cancer and peaks 1 month before, according to a retrospective, matched, case-control study.

"We have established that cancer is a strong risk factor for arterial thrombosis, and this study focused on when this risk starts, and it seems like it starts about 5 months before cancer is diagnosed," Babak Navi, MD, neurologist at Weill Cornell Medicine and Memorial Sloan Kettering Cancer Center in New York City, explained to Medscape Medical News.

The new study was published online December 21 in Blood.

Do the findings mean that clinicians should screen older patients for cancer after they experience these arterial thromboembolic events?

Navi cautioned that investigators have to first determine the utility of screening older patients who have had an MI or an ischemic stroke for the presence of an occult cancer. There are downsides to screening, including exposure to radiation, cost, and incidental findings that might lead to more testing.

But he also said it was a good idea for some patients.

"On a case-by-cases basis, if someone has a stroke or a heart attack, particularly if it is otherwise unexplained — meaning the patient had no reason to have it — and if there are any symptoms or signs of cancer, such as unexplained anemia, weight loss, enlarged lymph nodes, recent blood in the stool, or cough, then they should be considered for screening. And by screening, I mean generally a CT scan of the chest, abdomen, and pelvis, which are easy enough to get," Navi told Medscape Medical News.

In the new study, the authors reviewed the population-based Surveillance Epidemiology and End Results (SEER)–Medicare linked dataset and identified 374,331 cancer patients aged 67 years or older who had one of nine cancer types.

Cancer patients were then matched to individual control persons, who were without cancer, by year of birth, sex, race, and the presence of some other comorbidities, such as atrial fibrillation. The participants in the analysis totaled 748,662 overall.

"We defined an arterial thromboembolic event as the composite of myocardial infarction or ischemic stroke," Navi and colleagues note.

The mean age of the cohort was 76 years, and slightly more than half were women.

At the time of diagnosis, 30% of the cancers were of stage III or IV, they also note.

The risk for either MI or ischemic stroke was then assessed in 30-day intervals from 360 days to the day prior to that on which patients received a cancer diagnosis.

"From 360 to 151 days before cancer diagnosis, the 30-day interval risks of arterial thromboembolic events were similar between cancer patients and matched controls without cancer," the investigators report.

However, the 30-day interval risk of having an MI or an ischemic stroke from day 150 to day 1 prior to being diagnosed was consistently higher in cancer patients compared with cancer-free control persons. This risk progressively increased as the cancer diagnosis date approached.

At 30 days prior to being diagnosed with cancer, the risk of developing an arterial thromboembolic event was more than 5.5-fold higher than it was for control persons, at 0.62% vs 0.11% (P < .001).

When investigators analyzed the data for the full 360 days before a cancer diagnosis, the risk of developing an arterial thromboembolic event was 69% higher among those who were later diagnosed with cancer compared with control persons, at 1.75% vs 1.05% (P < .001).

Cancer patients with the highest risk of having an arterial thromboembolic event in the 360 days preceding their diagnosis were most likely to be diagnosed with lung cancer, followed by colorectal cancer.

The risk of having an arterial thromboembolic event also remained elevated for cancer patients compared with cancer-free control persons when analyses were restricted to patients who did not have a comorbid diagnosis of atrial fibrillation.

"The relative risks of myocardial infarction alone and ischemic stroke alone were similar, although myocardial infarction was slightly more common than ischemic stroke," the researchers observe.

Table. Risk for MI and Ischemic Stroke Prior to Cancer Diagnosis

Time Before Dx Cancer Patients Cancer-Free Control Persons P Value
Myocardial infarction      
1 - 30 days 0.38 0.06 <.001
31 - 60 days 0.09 0.05 <.001
61 - 90 days 0.07 0.05 <.001
91 - 120 days 0.06 0.05 .009
121 - 150 days 0.06 0.05 .03
Ischemic stroke      
1 - 30 days 0.26 0.05 <.001
31 - 60 days 0.08 0.05 <.001
61 - 90 days 0.06 0.04 <.001
91 - 120 days 0.05 0.05 .17
121 - 150 days 0.05 0.04 .02

Cancer Stage and Event Risk

The stage of cancer at the time of diagnosis was associated with the likelihood of patients having an arterial thromboembolic event in the 360 days prior to their diagnosis, with the risk increasing as cancer stage increased.

For example, the risk was 32% higher for cancer patients with stage I cancer compared with control persons, 55% higher for cancer patients with stage II cancer compared with control persons, and more than twofold higher for those whose cancer was stage II at diagnosis relative to control persons.

For those with stage IV cancer at diagnosis, the risk of having an arterial thromboembolic event was slightly more than twofold higher than it was for control persons.

Navi noted that the propensity for cancer to cause blood clots is likely directly triggering at least some of the arterial thromboembolic events seen in those who were eventually diagnosed with cancer.

In their previous SEER-Medicare study of 279,719 patients diagnosed with eight common cancers, the risk of patients having an arterial thromboembolic event in the 6 months after a diagnosis of cancer shot up by 120% compared to matched control persons who did not have cancer.

However, Navi pointed out, the period after a cancer is diagnosed is somewhat complex, and there are factors besides cancer that could contribute to the heightened risk for arterial thrombosis in this setting, including surgery and chemotherapy, a well-known risk factor for thrombotic events.

In addition, patients who undergo chemotherapy can experience a decrease in platelet counts that necessitates stopping anticoagulant therapy. All of these factors could confound the association.

"But before a cancer is diagnosed, there is no cancer treatment, so you are cutting out some of those confounding factors," Navi said.

The study was supported by research funding from the National Institutes of Health and the Florence Gould Endowment for Discovery in Stroke. The authors have disclosed no relevant financial relationships.

Blood. Published online December 21, 2018. Abstract

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