It is estimated that there are about 17 million cancer survivors currently living in the US. The population of people who are cancer survivors continues to increase, due to the advancing age of the population as well as the improved response rates to chemotherapy and immunotherapy. However, even with the success of cancer treatment, cancer survivors have a high burden of chronic health conditions as a result of their treatment. Cardiovascular disease is the leading cause of death in cancer survivors.
Before we move on, let’s define some terms:
Cardiovascular disease – a broad term that describes disorders of the heart and blood vessels, usually linked to atherosclerosis.
Atherosclerosis – this describes a thickening and hardening of the arteries caused by a build-up of plaque, and risk factors include high cholesterol, smoking, diabetes and obesity.
Coronary artery disease (also called coronary heart disease) (CAD or CHD) – refers to the thickening of the blood vessels of the heart, which limits blood flow and oxygen to the heart.
Heart disease – refers to a range of disorders that include disease in the blood vessels, but also abnormal heartbeats, called arrhythmias.
Risk of Cardiovascular Disease (CVD) in Cancer Survivors
Some convincing data were recently reported in a study published in the Journal of the American College of Cardiology. A longitudinal study followed 12,414 people who were originally enrolled from 1987-1989, and interviewed every three years, until 2020. Over this time, there were 3,250 cases of cancer. (J AM Coll Cardiol, 2022;80(1):22-32. ARIC Study – Atherosclerosis Risk in the Community).
The incidence of cardiovascular disease per 1000 people was 12 for those who did not have cancer, and 23.1 for those who were cancer survivors. That’s almost double the risk of developing CVD as a cancer survivor compared to the general population. When considering subtypes of CVD, heart failure and stroke were the most statistically significant.
Heart failure has the highest risk in survivors of breast cancer, lung cancer, and blood cancers. One recognized risk factor in this population is the high incidence of radiation to the chest and thoracic cavity, which can cause damage to the valves of the heart and the conduction system of the heart. Individuals with a history of lung cancer had twice the risk of stroke compared to those who did not have lung cancer.
Some researchers have suggested that the reason cancer survivors have a higher risk of CVD is because they had pre-existing conditions. For example, cancer survivors are more likely to have hypertension, diabetes, dyslipidemia, excess weight and a history of smoking than people without cancer. However, not every study has supported this. Instead, much more investigation has been given to the long-term toxicity of chemotherapy and anti-hormone medication (to be further discussed below), and the role that cancer treatment itself may play in the development of CVD. Potential mechanisms include systemic inflammation, a pro-inflammatory and pro-thrombotic state, cardiotoxicity and chest radiation.
The results of the ARIC study support previous longitudinal studies. One of the earliest studies linking a history of cancer to an increased risk of CVD was conducted in Sweden. It followed 820,491 people over time, and found that compared to the cancer-free population, cancer survivors had an elevated risk of stroke and coronary heart disease, which was elevated for 10 years post-diagnosis (Eur J Cancer, 2012;48(1):121). Similarly, a UK-based study followed 108,215 people and found that cancer survivors had an increased risk of heart failure, cardiomyopathy, arrhythmia, coronary heart disease and valvular heart disease for 20 different cancer types, which risk was elevated for 12 years post-diagnosis (Lancet, 2019;394:10203):1041).
Various types of cancer drugs have been linked to an increased risk of cardiovascular disease, including anthracyclines (doxorubicin), selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs), targeted therapies (trastuzumab, kinase inhibitors) and immunotherapy (ipilimumab). Let’s take a further look at hormone medications taken by women with breast cancer, as well as men with prostate cancer.
BREAST CANCER
Estrogen has diverse effects on the body. Estrogen receptors are present in heart muscle and prevent the enlargement of those cells (hypertrophy). Estrogen is also anti-atherosclerotic and reduces inflammation. Two major classes of anti-estrogen medications are most commonly prescribed for breast cancer, which include SERMs, such as Tamoxifen, and AIs, such as Letrozole or Anastrozole.
Some data suggests that Tamoxifen increases body fat percentage, increases triglycerides and increases the risk of diabetes. It may also increase the risk of clots, all of which contribute to the development of cardiovascular disease and increase the risk of stroke. Some studies have also suggested that women who use AIs have an increased risk of heart attack and possibly heart failure compared to those who only use Tamoxifen (Circulation, 2020; 141:549).
Women who use either of the above classes of medications will benefit from increased screening and vigilant preventative measures.
PROSTATE CANCER
Common side effects of androgen deprivation therapy (ADT) in men with prostate cancer show that men have increased fat mass, decreased lean muscle mass, and increased risk of insulin resistance, diabetes, abnormal lipids, and increased arterial wall thickness. All of these findings increase the risk of CVD. (Arterioscler Thromb Vasc Biol, 2020:40:e55). ADT has also been suggested to directly increase the risk of CVD events, such as heart attack, heart failure and arrhythmia.
Testosterone has a number of important biological roles, one being increased muscle mass, bone mass and improved metabolic function. Men with prostate cancer who have been prescribed ADT will benefit from increased screening and more vigilant efforts in CVD prevention.
FRAILTY
If you are a patient of mine, you have heard my rants about building muscle. It is my firm belief that having ample muscle mass is the best thing you can do to live a long and vibrant life. Muscle improves metabolism and helps to prevent weight gain. Muscle prevents us falling as we age and breaking a hip. Muscle gives us more energy. Muscle actually delays the aging process.
Cancer treatment accelerates the aging process, and there is an accelerated decline in both physical and psychosocial measures. This is captured in the concept of frailty and includes measures of energy, speed of gait, weakness, weight, sensory symptoms, mental fitness cardiac fitness, respiratory fitness, immune health and pain.
Cancer survivors not only have increased risk of poor cardiac health, but also have compromised mental health, immune health, poor physical fitness, and greater abnormalities of weight (too high or too low) and pain. High measures of frailty have also been associated with CVD and type II diabetes. (BMC Med, 2023;21:74).
Building muscle is one way to combat frailty. It takes time and dedication, but simple movements and focused nutrition can get you there quickly. In the clinic, you have access to a body composition scale to monitor your gains to keep you motivated.
MONITORING
As a cancer survivor, you should ask for more frequent blood tests for fasting glucose, cholesterol, CRP, cardiac troponin I, as well as frequent blood pressure tests and ECGs. You can self-monitor for weight loss, weight gain, weakness (more tired going up stairs, or walking), poor sleep and inadequate nutrition.
My goal for writing this blog post is to educate my patients and anyone else who is a cancer survivor. Being a cancer survivor poses unique risks for long-term health, and being knowledgable about what measures you might have to take above and beyond the average person is extremely important. Come talk to me about a long-term cardiovascular program so you can live a long and vibrant life.
