Over the last few decades, medical progress has led to the survival of many more people with cancer. However, a new study published in The Lancet shows that this cohort has a higher risk of cardiovascular disease (CVD) than controls without cancer, due to a number of reasons.
These include the use of chemotherapeutic agents that have direct toxic effects on the heart, the effects of the cancer itself on the blood and vascular system, and risk factors common to both, such as obesity and dietary factors.
Interventional cardiologist. Image Credit: MAD.vertise / Shutterstock
A few randomized trials have shown that certain specific CVDs are associated with certain cancer therapies, over the short- to medium-term. Some observational studies indicated a greater risk of CVDs in people who survived cancer in adolescence and young adulthood compared to age-matched or general population controls. However, not much is known about the absolute increase in risk in cancer survivors as compared to individuals without cancer. Moreover, the outcome studied in most cases is CVD as a combined outcome, which suggests that only survivors of some cancers have a higher CVD risk. In contrast, other studies indicate that different cancers are associated with different types of CVD.
The current study takes advantage of the long-term cancer survival data now available to study a number of outcomes: specific CVD outcomes following a wide range of specific cancers, and the effect of risk factors that are common to both conditions. The aim is to identify what factors increase the CVD risk in survivors of different cancers.
The researchers retrieved large-scale data from the linked electronic health records databases from a number of UK sources. These included primary care centers, hospitals and cancer registries. The subjects included survivors of the 20 leading cancers which account for over 90% of cancers, and five times as many controls, matched for age and sex. The cancer survivors were classified into 20 groups.
The CVD outcomes observed were:
- Coronary artery disease, including myocardial infarction, angina, revascularization procedures, cardiac arrest
- Stroke, whether ischemic or hemorrhagic
- Cardiac arrhythmia
- Venous thromboembolism (VTE), including pulmonary embolism and deep vein thrombosis
- Cardiac failure and cardiomyopathy
- Valvular heart disease
- Disease of the peripheral blood vessels
The study looked at over 100,000 adult cancer patients who had survived at least one year after diagnosis, and more than 520,000 controls. Patients were followed up until one of the following occurred:
- End of study/ study-associated follow-up
- Any of the study outcomes occurred
The data was analyzed for the incidence of each of these CVD outcomes, and then adjusted for common risk factors and demographic factors like education and income. Certain other conditions were also compensated for as they could affect the final outcome in specific cohorts (e.g., cancers limited to women, lung cancers), namely, hysterectomy, history of preceding hormone replacement therapy, chronic liver disease, immunosuppression, chronic obstructive pulmonary disease and sclerosis. The effect modification of cancer survival itself on the risk of CVD was also investigated, as well as the role of cancer treatment.
What were the results?
The main findings were that in 18 of these cancers, survivors had a 2-9 times higher risk of VTE, or blood clots formed in the veins. The greatest increase was with pancreatic cancer survivors who were at more than 9 times higher risk compared to controls, while prostate cancer patients were at 70% increased risk. The risk declined over time but was still higher than in the controls at 5 years after diagnosis.
To put this in perspective, breast cancer survivors could expect six and 12 more cases of VTE per 1,000 women per year, under and over the age of 60 years respectively, which is twice as high as that in controls. Even at 10 years post-diagnosis, the venous thromboembolism risk is still higher compared to the controls, for colorectal cancer, NHL, and melanoma.
In 10 out of 20 cancers, including blood, esophagus, lung, ovarian and kidney cancers, the risk of heart failure and cardiomyopathy (permanently weakened heart muscle) was increased. The risk ranged from about 60% higher in ovarian cancer to over 300% higher in multiple myeloma.
The increase in risk for heart failure was most marked in patients who survived non-Hodgkin lymphoma, breast and lung cancer, especially younger patients who had no past history of cardiovascular disease. NHL survivors under 60 and over 80 years experienced four and 21 more cases of heart failure per 1,000, compared to controls. For VTE, a similar pattern was found following breast and colorectal cancer.
Other cardiovascular events that were observed to occur more often in certain cohorts include cardiac arrhythmias in cancer survivors with a high BMI, following colorectal cancer or non-Hodgkin lymphoma (NHL). Peripheral vessel disease was not obviously linked to any cancer. Blood cancer survivors showed increased risk over all CVD categories, unlike other cohorts who tended to show higher risk in one or more specific categories. Over time, there was an age-linked increase in risk overall, and this was greatest following a history of chemotherapy.
Lead author Helen Strongman says, “Over recent decades cancer treatment and management have improved substantially. Around half of those diagnosed with cancer in developed countries are now expected to survive for more than 10 years. However, there are concerns that there may be increased long-term risks of cardiovascular disease following cancer diagnosis."
Thus most cancer survivors showed an increase in risk for at least one cardiovascular disease over the medium to long term, compared to the general population. The actual increase was dependent upon the site of the cancer. It is important to note that the overall risk remains low, especially for younger patients, but still needs to be addressed.
The study is hoped to provide evidence that will spur research into evolving measures to benefit patients at high risk of CVD following cancer treatment. Early prevention is imperative because of the particularly high mortality in cancer survivors who develop CVD, and this requires greater awareness of risk from the GP level onwards.
Senior author Krishnan Bhaskaran says, “With treatment for cancer becoming more effective, we must start thinking about living beyond cancer and improving the health of survivors. If patients, primary care doctors, and specialists are more aware of the potential for increased cardiovascular risks in this patient group, we might detect problems earlier and improve outcomes.”
Medium and long-term risks of specific cardiovascular diseases in survivors of 20 adult cancers: a population-based cohort study using multiple linked UK electronic health records databases, Helen Strongman, Sarah Gadd, Anthony Matthews, Kathryn E Mansfield, Susannah Stanway, Alexander R Lyon, et al., Published:August 20, 2019, https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31674-5/fulltext