Patients With Cancer at Increased Risk for Cardiovascular Death

Alexander M. Castellino, PhD

November 26, 2019

In a population-based study that included more than 3 million patients over a 40-year span, 1 in 10 cancer patients did not die of cancer but of cardiovascular disease (CVD). Cancer-related deaths occurred in 4 of 10 patients.

This finding comes from an analysis of data from the Surveillance, Epidemiology, and End Results (SEER) database. The study was published online November 24 in the European Heart Journal.

In an accompanying editorial, cardio-oncologist Joerg Herrmann, MD, from the Mayo Clinic, Rochester, Minnesota, writes that this "important work...confirms that cancer patients have an on average 2–6 times higher CVD mortality risk than the general population....

"A reactive management approach that comes into play solely when clinical presentations and complications arise is no longer in order," he comments. He advocates for a proactive approach that should begin before a patient receives any cancer treatment and that continues for a lifetime.

Cancer Patients at Higher Risk

"As the number of cancer survivors rise, the rate of cardiovascular deaths will continue to rise," senior author Nicholas G. Zaorsky, MD, a radiation oncologist, and Kathleen Sturgeon, MD, both at the Penn State College of Medicine, Hershey, Pennsylvania, commented in a statement.

"The foundational evidence provided by this investigation is a seminal characterization of 28 cancer sites for CVD mortality risk and provides insight on the scope of CVD mortality risk in cancer patients that has not yet been fully reported," Zaorsky and colleagues write.

"This study fills an important gap in the literature both for PCPs [primary care physicians] and specialists as we highlight both historical trends and observations regarding basic clinical presentations...which together may influence patient-level decisions on cardiovascular care," they add.

For their study, the team compared the US general population to 3,234,256 US cancer survivors from the SEER database for the period 1973 to 2012. The period covered in the analysis does not reflect key developments that have occurred regarding immunotherapies, the authors note. "This analysis lags behind and does not reflect the present-day environment in its entirety," Herrmann notes in his editorial.

Across 28 cancer types, 38% (1,228,328 patients) died from cancer and 11.3% (365,689 patients) from CVD. Of the CVD-related deaths, 76.3% were due to heart disease.

For all cancers combined, the team reports the following:

  • Increased age at cancer diagnosis is associated with increased risk for death from CVD.

  • The younger a cancer survivor is diagnosed, the higher is the risk for heart disease.

  • For survivors diagnosed before age 55 years, the risk for CVD mortality is 10-fold higher than that of the general population.

  • The greatest number of deaths from CVD occur during the first year following a cancer diagnosis.

  • Deaths from CVD for all cancer survivors are higher than for those in the general population.

The team assessed the different cancer types. They found higher-than-average (>11.3%) CVD-related deaths among patients with bladder (19.4%), larynx (17.3%), prostate (16.6%), corpus uteri (15.6%), colorectal (13.7%), and breast (11.7%) cancers.

Several trends for CVD-related deaths in cancer patients and survivors were noted. Nine cancers were associated with higher rates of index-cancer deaths and low rates of death from CVD (<10%). These include cancers of the lung, liver, brain, stomach, gallbladder, pancreas, esophagus, and ovary, as well as multiple myeloma.

"These cancers are all associated with high mortality from index-cancer," Sturgeon and colleagues write.

For eight of the cancers that are associated with improved prognosis (soft tissue, nasopharynx, anal, oropharynx, colorectal, non-Hodgkin lymphoma, kidney, and cervix), the researchers note that CVD-related risk for death increases even though index-cancer death is >10% higher than death from CVD.

For the remaining 11 cancers, over the time span of analysis, death from the index cancer is on par with (<10% or higher) or is higher than death from CVD. These include cancers of the breast, larynx, thyroid, testis, prostate, bladder, and penis, as well as endometrial cancer, melanoma, and Hodgkin lymphoma.

Peak in First Year After Cancer Diagnosis

In his editorial, Herrmann notes that in general, cancer patients face a lifetime risk for CVD mortality. That risk peaks in the first year following a cancer diagnosis. He suggests that the increased risk during this "acute cancer phase" represents the interplay of preexisting CVD, potential cardiovascular toxicities of cancer therapies, and cardiovascular risk associated with tumor burden.

"Recognizing this phase is extremely important and has not been made this evident across a multitude of cancers in the past," he writes.

The acute phase is followed by the chronic phase, which falls in the survivorship period, notes Herrmann. He comments that this chronic phase has not been detailed in one given dataset for a variety of cancers.

"In view of such grave and persistent consequences, a reactive management approach that comes into play solely when clinical presentations and complications arise is no longer in order," Herrmann writes.

Cardio-oncology is important for all cancer patients but is most important for those in whom cancer mortality and CVD mortality are on par, Herrmann writes.

He advocates for a proactive approach for cardio-oncology that starts before any therapy is given and that continues for a lifetime.

Herrmann is a director of cardio-oncology clinic, and he believes that this specialty will increase over time as its importance continues to be recognized.

One of the study authors has received research funding from Novocure. Herrmann has disclosed no relevant financial relationships.

Eur Heart J. Published November 24, 2019. Abstract, Editorial

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