The correlation between a cardiovascular event and an undiagnosed cancer continues to gain evidentiary support. A strong link was identified in a study recently conducted by researchers at Weill Cornell Medicine and Memorial Sloan Kettering Cancer Center in New York. The research found that older adults with cancer are nearly 70 percent more likely to experience a stroke or myocardial infarction in the year prior to cancer diagnosis compared to peers who don't have cancer (Blood 2018; doi:10.1182/blood-2018-06-860874).
“In the 5 months before cancer is officially diagnosed, there is an increased risk of arterial thromboembolic events, and the closer the patient gets to diagnosis, the higher the associated risk,” said Babak B. Navi, MD, MS, lead author of the study and Chief of the Division of Stroke and Hospital Neurology at Weill Cornell Medicine. “These findings support the notion that cancer is not just a risk factor for venous thromboembolism. It's also a risk factor for arterial events and oncologists should be attuned to that.”
Study Background & Design
This study is one of several that have examined cardiovascular risk in the presence of cancer. Past research conducted by Navi and others has established that cancer patients face an increased risk for arterial thromboembolism. In these studies, cardiovascular risk was documented after cancer diagnosis. The study published in December 2018 in Blood evaluated for the first time the cardiovascular risk that is present before cancer diagnosis.
Navi and his co-investigators linked data from the Surveillance, Epidemiology, and End Results (SEER) registry with Medicare claims filed between 2004 and 2013. The SEER-Medicare program encompasses multiple population-based cancer registries in the U.S., and because these registries are linked to Medicare enrollment and claims files, they provide detailed clinical information about a diverse population of patients with cancer. Using these data, the researchers evaluated risks for arterial thromboembolic events that occurred in the year before patients were diagnosed with cancer. They restricted this evaluation to records for patients aged 67 years and older who had been diagnosed with breast, lung, prostate, colorectal, bladder, non-Hodgkin lymphoma, uterine, pancreatic, or gastric cancers between Jan. 1, 2005, and Dec. 1, 2013.
The SEER data system includes approximately 28 percent of all patients diagnosed with cancer in the U.S. and provides data from a 5 percent random sample of Medicare enrollees without cancer who live in the SEER geographic areas. This enabled the researchers to compare arterial thromboembolic event risk in patients with incident cancer with control patients who did not have cancer.
The cancers selected for evaluation (breast, lung, prostate, colorectal, bladder, non-Hodgkin lymphoma, uterine, pancreatic, and gastric) were chosen because they reflect the five most common overall and solid tumor cancers, the most common hematologic and gynecologic cancers, and the two cancers most often associated with thromboembolism (pancreatic and gastric). In total, these cancers account for about two-thirds of all incident cancer diagnoses in the U.S.
All patients with cancer were individually matched to a control patient without cancer according to year of birth, sex, race (white or nonwhite), SEER registry (surrogate for geographic region), Charlson Comorbidity Index (trichotomized into 0, 1, and ≥2), and the diagnoses of hypertension and atrial fibrillation within 365 to 730 days prior to study entry. The diagnoses of hypertension and atrial fibrillation were individually matched because they are important cardiovascular risk factors not included in the Charlson Comorbidity Index.
Navi and his co-investigators identified 374,331 pairs of cancer patients and matched controls without cancer who met the eligibility criteria established for the study. The records of more than 700,000 Medicare beneficiaries were reviewed. The mean age of the eligible patients was 76 years; 52 percent were women and 48 percent were men. At the time of diagnosis, 30 percent of the cancers were in stage III or stage IV. The most common cancer types, accounting for 77 percent of the cases, were prostate, breast, lung, and colorectal.
The analysis determined that in the 151-360 days prior to cancer diagnosis, the 30-day interval risks for arterial thromboembolic events were similar between cancer patients and matched controls. But in the 1-150 days prior to cancer diagnosis, the 30-day interval risks for arterial thromboembolic events were higher in cancer patients versus matched controls. This risk increased progressively as the cancer diagnosis date approached and peaked in the 30 days immediately before cancer diagnosis.
The study concluded that in the 360 days before a cancer diagnosis, the risk of an arterial thromboembolic event increased nearly 70 percent. This risk first rose about 5 months prior to cancer diagnosis and increased progressively until it peaked the month before cancer diagnosis. By that time, the risk had increased more than fivefold.
“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 wrote. “Of the cancer types studied, lung and colorectal cancer were the most likely to be preceded by an arterial thromboembolic event.”
The findings of the study suggest that some myocardial infarction and ischemic stroke events may be triggered or potentially caused by occult cancers.
“Future research is needed to identify clinically useful biomarkers for occult cancer in patients with arterial thromboembolic events and to determine the utility of cancer screening strategies in these patients, particularly among those with cancer risk factors or unexplained ‘cryptogenic’ events,” the authors wrote. “In the meantime, we recommend that patients with acute myocardial infarction and ischemic stroke be up-to-date with their age- and gender-appropriate cancer screening, and that their clinicians pay close attention to, and have a low threshold to investigate, any symptoms or signs consistent with occult cancer, such as unexplained anemia or weight loss.”
In an interview with Oncology Times, Navi explained that his work as a stroke neurologist led to his research interest in the association between cancer and arterial thromboembolism. “Not infrequently, I will see a patient with acute ischemic stroke who is diagnosed with cancer in the days to weeks afterward,” he explained. “It's a natural extension of my clinical experience and research to determine when this risk starts.”
Navi said he and his co-investigators, along with others studying the link between cardiovascular disease and cancer, will next work to identify biomarkers and characteristics that may signal an occult cancer in patients with an acute stroke or myocardial infarction. In the meantime, he hopes that this study raises awareness within the medical community about the link between cancer and arterial thromboembolism risk.
“These data provide more evidence connecting cancer to arterial thromboembolism risk,” Navi said. “Oncologists should be cognizant of this association and they should ensure that their patients' cardiovascular risk factors are being adequately addressed. Oncologists are great at risk stratifying and preventing venous thromboembolism, but there seems to be less emphasis on preventing arterial events, even though arterial events are generally more disabling and lethal.”
Michelle Perron is a contributing writer.