1.
CARDIO-ONCOLOGY
THE LINK BETWEEN CANCER
ANDTHE HEART
Anita M. Arnold, DO FACC MBA
Director: Cardio-Oncology
Lee Health

2.
Objectives
■ To introduce the concept of Cardio-Oncology and why it plays a role in
contemporary cancer therapy
■ To identify risk factors between the 2 most common diseases
■ Compare biological similarities for cancer and cardiovascular disease
■ Discuss common treatments

3.
Disclosures
■ No financial disclosures
■ Board Member: International Cardio-
Oncology Society (ICOS)
– Chair the Education Committee
■ Member of the ACC Council on Cardio-
Oncology
– Outgoing chair of Advocacy Section for
Cardio-Oncology

4.
What exactly is Cardio-Oncology?
New medical subspecialty
of Cardiovascular Medicine
Educates cardiologists with
an interest in oncology
They work with physicians
and others caring for cancer
patients
Monitor CV effects of
therapy to prevent acute
and long term cardiac
dysfunction

5.
Why do we need Cardio-Oncology?
• Increasing numbers of cancer survivors: 13.7 million now, 18 million in 2023.
• 7 year follow up of adult cancer survivors:
30% died of cardiac disease, 50% of which was due to cancer therapy
• Childhood cancer survivors: 80% survival at 5 years
• Mortality is not from recurrent cancer, it’s from cancer treatment related illnesses
• 30 years: cumulative mortality from treatment exceeds recurrent cancer
Ming Hui Chen et al. Circulation Research. 2011;108:619-628

6.
CANCER
PREVALENCE
:THE SILVER
TSUNAMI

7.
WOMEN & CV
DISEASE:
CARDIO
ONCOLOGY
Patnaik JL. Cardiovascular disease competes with breast cancer as the leading cause of death for older females diagnosed with
breast cancer: a retrospective cohort study. Breast Cancer Res. 2011;13(3):R64. Published 2011 Jun 20. doi:10.1186/bcr2901

8.
Which patients need Cardio-Oncology?
Cancer patients who are
undergoing
treatment with potentially
cardiotoxic therapy
(chemo, XRT)
Patients with known
cardiac disease who
develop cancer: to insure
they can withstand the
rigors of treatment
Survivor surveillance,
especially childhood
cancers: 80%, 5-year
survival, with 50% of
subsequent death due to
cardiac disease

9.
Facts about Cardio-Oncology
30% of all cancer patients will develop some
cardiovascular complications due to their treatment
If a man lives more than 5 years after his treatment of
prostate cancer, he is more likely to die of cardiac disease
In general: women are more affected by cancer treatment
cardio-toxicity

10.
Facts about
Cardio-
Oncology
Men are more likely to develop heart failure
that is irreversible
Childhood cancer survivors are 7x more likely
to have heart disease than sibs
22% of childhood cancer survivors treated with
chest radiation have stiffness of their hearts
that can lead to heart failure later in life

11.
How does cancer therapy affect the heart?
• Severe hypertension
• Premature atherosclerosis
• Abnormal cholesterol
• Valvular heart disease (XRT)
• Stroke
• Abnormal EKG: Long Qtc
• Blood vessel abnormalities
• Arrhythmia: Atrial fibrillation
• Heart Failure
• Fibrosis of the heart
• Pericardial disease
• Formation of blood clots:
i. Pulm embolism
ii. Clots to the brain (stroke)
iii. Clots to the heart : MI

12.
Clinical trials and Cardio-toxicity:
How accurate is the data?
■ Pivotal cancer trials have seriously underestimated cardio-toxicity
■ Recent review noted 62% of 189 Phase 2/3 clinical trials reported ANY CV event
■ The rates were BELOW what was expected in the general population suggesting
the need to better clarify the definition of cardio-toxicity and monitoring strategies
during and after therapy
■ This is not new: Herceptin clinical trials noted 2.5% incidence of heart failure, real
world experience later showed up to 20%
■ Better design of FDA trials is being organized
Reporting of CV Events in Clinical Trials Supporting FDA Approval of Contemporary Cancer Therapies
J Am Coll Cardiol. 2020 Feb, 75 (6) 620-628.

13.
Statistics: Cancer and Heart disease
Cancer and Heart
disease are the 2
biggest health care
issues in the US
25% of all Medicare
dollars are spent on
cardiovascular
disease
In the US one out of
every 2 women die of
heart disease or
stroke
One out of every 8
women will get
breast cancer
1/800 men get breast
cancer
If you have one
disease and live long
enough, chances are
you will get the other

14.
What to worry about?

15.
■ You are MORE likely to have cardio-toxicity
from your cancer therapy if you have multiple
risk factors for heart disease, or if you already
have heart disease
■ It is well documented that survivors of cancer
who were treated with any agent that could
cause cardiac toxicity (including XRT) and
especially childhood survivors are at
increased risk of CV disease in their
survivorship years.
■ The longer you are cancer free as a survivor
the more you are at risk of developing heart
disease
Shared risk
factors and
biology for
both!

16.
CLONAL
HEMATOPOIESIS: A
NEWLY RECOGNIZED
LINK BETWEEN
CARDIOVASCULAR
DISEASE AND CANCER
■ Aging causes mutations in
bone marrow cells which can
contribute to “pre-leukemia”
■ Other mutations (TET 2 cells)
can predispose to heart
Failure
■ Inflammatory mediators
MAY affect CHIP cells and
accelerate both cancer and
HF
J Am Heart Assoc. 2020;9:e013754. Doi: 10.1161/JAHA.119.013754.

17.
Shared risk factors: avoid the following
Cardiac: from AHA
■ smoking
■ Physical inactivity
■ Being overweight
■ Eating an unhealthy diet
■ Diabetes
■ High cholesterol
■ High Blood pressure
Cancer: FromWHO
■ > 30% 0f cancer can be avoided
■ tobacco (urban air pollution)
■ obesity
■ unhealthy diets low in fruit and vegetables
■ inactivity
■ alcohol use
■ sexually transmitted human papillomavirus

18.
Shared risk factors: Inflammation
Cardiac
■ Considered the seminal event for
CAD and atherosclerosis
■ 2017 CANTOS: anti-inflammatory
meds for select pts prevented CV
death in 31%
Cancer
■ Chronic inflammation drives certain
cancers: pancreatic, esophageal,
liver, and colon
■ exposure to DNA-damaging
chemicals after inflammation boosts
mutations even more, increasing
cancer risk.
■ colitis, pancreatitis, hepatitis are
linked to greater risk for cancer:
colon, pancreas, and liver.
■ immune cells produce highly
reactive molecules containing
oxygen and nitrogen, which can
damage DNA

19.
Obesity and
cancer
Circulation. 2016;133:1104–1114.

20.
Shared risk factors: Obesity
Cardiac
■ 18 yr of follow upWHI: among
postmenopausal women with normal
BMI:
■ both elevated trunk fat and reduced leg
fat are associated with3-fold increased
risk of CVD
■ Obesity promotes other diseases linked
to CV disease:
– High cholesterol
– High blood pressure
– Impaired glucose tolerance or type-2
diabetes
– Metabolic syndrome
Cancer
■ WHI: higher body fat associated with
risk of invasive breast cancer at 16
years
■ excess body fat increases your risk for
several cancers, including colorectal,
post-menopausal breast, uterine,
esophageal, kidney and pancreatic
cancers.
■ Experts believe it is due to
inflammation caused by visceral fat
surrounds your vital organs.
■ Inflammation then affects how and
when cells divide and die, predisposing
to mutations

21.
Metastatic HER-2(+) Breast cancer: BMI
Body mass index (BMI) is a main indicator of obesity and its association with breast cancer
is well established. Recent international study assessed the influence of BMI on clinical
outcomes of patients treated with pertuzumab and/or trastuzumab emtansine for HER2+
metastatic breast cancer (mBC).
■ In their cohort, a BMI ≥ 30 correlated with worse overall survival in patients with
HER2+ metastatic breast cancer who received pertuzumab and/or trastuzumab
emtansine.
■ The effect of BMI on prognosis was also confirmed in multivariate analysis of overall
survival for the population.
Impact of BMI on HER2+ metastatic breast cancer patients treated with pertuzumab and/or trastuzumab emtansine.
15 January 2020. Journal of Cellular Physiology

22.
Shared risk factors: Diabetes
Cardiac
■ patients withT2D are 2x likely to die
of coronary heart disease as patients
without DM
■ T2D and CAD, have been linked
genetically with the discovery of
numerous risk loci.
■ Data driven by examining thousands
with a particular disease and
scanning their genome to find
similarities.
Cancer
■ 2019 China study:
■ Males: cancer risk increased significantly: #1
Prostate , blood, skin, thyroid, kidney, liver,
pancreas, lung, colorectum, and stomach
■ Males: decrease esophagealCA
■ Women: nasopharynx ,liver, esophagus,
thyroid, lung, pancreas, blood, uterus,
colorectum, breast, cervix, and stomach.
■ Women: decrease gallbladder CA

23.
Shared risk factors: Hypertension
Cardiac
■ Hypertension is a known RF for:
– Heart failure/systolic and
diastolic
– Ischemic heart disease
– LVH thickening of the heart
– Worsening valve disease
– Damage blood vessels:
■ Stroke
■ Aneurysm
■ Organ failure (kidneys)
Cancer
■ 10 studies of association HTN and
cancer mortality in 47,119 subjects.
■ Follow up 9-20 years: HTN was
associated increased cancer
mortality particularly renal cell
carcinoma.
■ The odds ratio for HTN was 1.75:
meaning of pts with RCC they were
1.75 x more likely to have HTN
American Journal of MedicineVol 112 (6) 2002, 479-486

24.
Shared risk factors: High Cholesterol
Cardiac
■ Our bodies need cholesterol!
■ Controversy exists, but most believe
excess cholesterol (LDL) is bad.
■ Multiple studies link cholesterol:
– Heart attack
– Stroke
– Angina
– Dementia
– Vascular disease
Cancer
■ Cholesterol MAY play a role in some
cancers: breast, colon, rectal,
prostatic and testicular cancer
■ directly activate oncogenic
Hedgehog pathway or induce
mTORC1 signaling (cell growth,
invasion and mets)
■ lipid rafts are major platforms for
signaling regulation in cancer
■ There are effective anti-cancer
strategies that disrupt lipid rafts
Am J Cancer Res. 2019; 9(2): 219–227.

25.
Lipid rafts
■ The alternation of cell adhesion and highly migratory behavior are the most prominent
features of cancer cells, which is involved in aggressive invasion and metastatic spread
■ Cholesterol-enriched membrane microdomains called “lipid rafts” have been
implicated in :
– Alzheimer’s, Parkinson’s,
– Cardiovascular diseases
– Immune disorders such as systemic lupus erythematosus
– HIV infection
– Signaling pathways in cancer progression

26.
Lipid rafts
• lipid rafts play a crucial role in the
functionality of a protein, CD44, which
regulates cancer cell adhesion and
migration
• Disrupting of the lipid raft interferes
with cancer cell migration
• Simvastatin, enhances CD44 shedding
and disrupts the lipid rafts
• Has been shown to block the
stimulation of glioma cell migration

27.
Shared risk factors:Tobacco
Cardiac
■ Smoking is the single largest
preventable cause of heart disease.
■ Tobacco smoke contains high levels
of carbon monoxide, causes
irritation, inflammation and
cholesterol deposits in the arteries.
■ People who use tobacco:
– Heart attacks
– High blood pressure
– Blood clots
– Strokes
– Brain hemorrhages
– Aneurysms
Cancer

28.
Shared risk factors: Diet
Cardiac
■ higher intake of vegetables, fruits,
fish, poultry, and whole grains had a
28% lower CV mortality
■ Dietary habits also affect CV risk
factors:
– blood pressure, cholesterol
– glucose levels, and obesity.
Cancer
■ Postmenopausal women (no cancer)
eating a low fat (< 20%) diet vs usual
(30%) followed for 8 years:
■ 21 % lower risk of breast cancer
death
■ 15 % lower risk of death from any
cause.

29.
Shared risk factors: Diet: red meat
Cardiac
■ The current literature does not
support the existence of a clear
relationship between large intake of
red meat and increased risk of heart
disease
■ May also depend on type of fat
involved and processing of the meat
itself.
■ AHA/ACC support a diet higher in
grains, vegetables and plants
Cancer
■ Collectively, evidence for the influence
of meat on breast cancer and CVD risk
is mixed.
■ processed meat intake, (1 -2x/wk) had
a 2.7-fold higher likelihood of
developing breast cancer
■ The fat content, amount of processing
and how cooked all confounds the data
■ Red meat is associated with an
increased risk of colorectal cancer, and
possibly prostate and pancreatic

30.
Shared risk factors: Alcohol
Cardiac
■ There is conflicting evidence but:
■ Several studies report decreased
risk of ischemic heart disease w/
average alcohol intake (2 drinks)
Cancer
■ There are no cancer-related benefits
of modest drinking
■ Alcohol consumption is a risk factor
for breast cancer. Consuming ≥2
alcoholic drinks per day for 5 yrs
confers an 82% increased risk of
breast cancer vs no alcohol intake.
■ variability in defining alcohol intake,
making comparisons difficult

31.
Shared risk factors: Physical inactivity
Cardiac
■ Sedentary behavior is associated with
all-cause mortality including CV.
■ Causes vascular dysfunction
responsible for the increased CVD
incidence and mortality.
■ Mechanism: downregulation of shear
rate and blood flow with changes in
glucose metabolism, inflammation and
oxidative stress causing vascular
dysfunction associated with SB.
■ Exercise decreases: weight,
cholesterol, BP, risk of DM, and
promotes aerobic conditioning.
Cancer
■ Meta-analysis of 43 observational
studies, including over 4 million
individuals and 68,936 cancer cases
■ Comparing the highest and lowest
levels of activity: statistically
significantly higher risk of colon,
endometrial, and lung cancers.
■ For each 2 hrs of sedentary time:
– Risk for colon increased 8%
– Endometrial 10%
– Lung 6%
J Nat Cancer Instit, 106(7), 2014 https://doi.org/10.1093/jnci/dju206

32.
Women & cancer: aging CV system
■ Despite preserved EF, cardio-respiratory
fitness was decreased in early breast cancer
pts a mean of 3 years after Rx compared with
aged matched noncancer women
■ Women with cancer reached an age expected
cardiac decline years before the noncancer
women
■ Their CV system aged faster
Journal of Clinical Oncology,Vol 30, No 36 (December 20), 2012: pp 4458-4461

33.
Shared treatment?

34.
Shared treatment?
Cardiac
■ Aspirin
– Secondary prevention
■ Statins
■ ACE inhibitors
– Lower BP , cardio and renal
protective
■ Beta Blockers
– Cardioprotective after Mi, HF
■ Manage modifiable risks:
– Diabetes
– Obesity
– Blood pressure
– Activity levels
– Diet
Cancer
■ Prostate, Lung, Colorectal, and Ovarian
Cancer ScreeningTrial found that aspirin >
3x/wk w/higher BMI was associated with
reduced risk of all-cause, cancer,
gastrointestinal cancer, and colorectal
cancer mortality.
■ Statins:
– inhibit tumor growth, invasion and
metastasis by blocking production
proteins cancer cells need.
■ ACE inhibitors:
– Pancreatic cancer
■ Beta Blockers:
– Cardioprotective for CMY
■ Manage modifiable risks

35.
Cancer and Statins
■ Prostate cancer: 926 ADT-treated patients, 31% were taking a statin.The median
time to progression was 27.5 months for men on statin, and 17.4 months among those
who were not (P < .001).
– Both statins and precursors of androgens are substrates of the cellular transporter
SLCO2B1, which functions to let hormones and anticancer compounds into cells.
– statins block the uptake of androgen precursors by binding to SLCO2B1
■ Breast Cancer: in some breast cancers, statins increase apoptosis and
radiosensitivity, inhibit proliferation and invasion, and decrease the metastasis.
– WHI, >160,000 postmenopausal 50–79 yrs, by 15 years; however, use of statins was
independently associated with a reduction in late-stage breast cancer diagnoses,
specifically for those with estrogen receptor (ER)-positive cancers
Effect of statins on breast cancer recurrence and mortality: a review, Breast Cancer 2017; 9: 559–565.

36.
Advocacy for cancer patients: WhatYOU can do
What increases your risk for heart disease?
• High blood pressure
• High cholesterol/diet
• Diabetes
• Obesity/sedentary lifestyle
•Tobacco use/alcohol use
• Family history
Tell your doctors if you experience:
• Shortness of breath
• Excessive Fatigue
• Chest pain/pressure
• Irregular heartbeats
• Swelling of legs or ankles
• Syncope
Remember: Late effects of cancer therapy can cause heart problems more than 10-20 years later!

37.
Advocacy for cancer patients: WhatYOU can do
BEFOREAND DURINGTREATMENT
• Discuss your heart health
• Understand how cancer therapies
might affect your heart
Ask about:
• What increases cardiotoxicity
• Tests to check the heart/blood
vessels
• How to protect your heart during
treatment
AFTERTREATMENT
• KNOW what cancer treatments
you’ve had, (dose and duration)
• Know your other risk factors
• Ask about heart checkups
MANAGE: blood pressure, cholesterol,
diabetes, weight, stress
• STOP SMOKING
• START EXERCISING
• EAT RIGHT

38.
Take Home
Message
The extensive overlap in risk factors and disease
prevention for CVD and cancer suggests that
these seemingly diverse diseases have some
common basic molecular pathways.
Chronic inflammation may have a considerable
role because it contributes to both diseases and
occurs in conditions such as obesity, diabetes
mellitus, hypertension, and dyslipidemia.
Controlling CVD risk factors can help reduce the
risk of cancer or cardio-toxicity from cancer
therapy

39.
Take Home
Message
Make sure you advocate for
yourself: BE ARMED and ask about
possible cardiac side effects
Cardio-oncology is an integral part
of cancer care
Certain treatments appear to be
beneficial in both diseases, some
cardio-toxicity can be attenuated

40.
THANKYOU!