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Cardiovascular Disease Risk in Cancer Survivors Carolyn Miller Reilly, RN, PhD, CHFN, FAHA Assistant Professor Emory University, Nell Hodgson Woodruff School of Nursing Speaker Disclosers Principal Investigator receiving funding for CVD disease research in Cancer Survivors • Internal funding Kennedy Survivorship Pilot Grant Award, Emory University: Novel Testing for Subclinical Cardiovascular Disease in Lymphoma Survivors • Funding from Radiation Therapy Oncology Group sponsored by National Cancer Institute: The Relationship between Radiation Dose Volume and Adverse Cardiovascular Disease Outcomes in Cancer Survivors who Received Therapeutic Thoracic Radiation Objectives • Discuss the growing population of cancer survivors • Present an epidemiological model explaining the elevated CVD risk in cancer survivors. • Differentiate which cancer survivors are at risk for CVD. • Identify screening recommendations. • Discuss effective prevention strategies. Facts and Figures Morbidity and Mortality Weekly Report (MMWR)QuickStats: Age-Adjusted Death Rates for Heart Disease and Cancer --- United States, 1999—2009* Weekly June 3, 2011 / 60(21);713 All-site Cancer Survival Today Percent Surviving 5 years 65.8% Howlader N, Noone AM, Krapcho M, Garshell J, Neyman N, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Cho H, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2010, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2010/, based on November 2012 SEER data submission, posted to the SEER web site, April 2013. What does this mean for Preventive Cardiology Nurses? ARS Question # 1 A 65 year old woman presents for her annual Survivorship Visit following treatment 5 years ago for Stage IIB breast cancer (T2, N1, M0). At that time, she received bilateral mastectomies with axilla lymph node removal and radiation to the left axilla. What will most likely be the cause of her mortality? 0% 0% 0% 0% 1. 2. 3. 4. Breast cancer recurrence Cancer metastasis to brain or bone Cardiovascular disease Cancer metastasis to lung 10 Countdown How the numbers stack up • Risk of CVD death in cancer survivors is higher than the actual risk of tumor recurrence • 7-fold higher mortality than general population • 15-fold increased risk of developing heart failure • 10-fold increased risk ischemia • Higher incidence of hypertension, dyslipidemia, acute coronary syndromes, CVA. Epidemiology of CVD in Cancer Survivors Native Risk Factors Treatment Risk Factors • Genetics • Environmental • • • Chemotherapy Radiotherapy Surgery Cardiovascular Disease Health Behaviors Tobacco, obesity, sedentary lifestyle, metabolic syndrome, insulin resistance Pathophysiology • Cardiomyopathy • Fibrosis Epidemiology of CVD in Cancer Survivors Native Risk Factors Treatment Risk Factors • Genetics • Environmental • • • Chemotherapy Radiotherapy Surgery Cardiovascular Disease Health Behaviors Tobacco, obesity, sedentary lifestyle, metabolic syndrome, insulin resistance Pathophysiology • Cardiomyopathy • Fibrosis Epidemiology of CVD in Cancer Survivors Native Risk Factors Treatment Risk Factors • Genetics • Environmental • • • Chemotherapy Radiotherapy Surgery Cardiovascular Disease Health Behaviors Tobacco, obesity, sedentary lifestyle, metabolic syndrome, insulin resistance Pathophysiology • Cardiomyopathy • Fibrosis Epidemiology of CVD in Breast Cancer Survivors Native Risk Factors Treatment Risk Factors • Genetics • Environmental • • • Chemotherapy Radiotherapy Surgery Cardiovascular Disease Health Behaviors Tobacco, obesity, sedentary lifestyle, metabolic syndrome, insulin resistance Pathophysiology • Cardiomyopathy • Fibrosis Epidemiology of CVD in Breast Cancer Survivors Native Risk Factors • Boerman (2014) Long-term follow-up for CVD after chemotherapy and/or radiation for breast cancer in an unselected population. Support Care Cancer •Haque (2014). Comorbidities and cardiovascular disease risk in older breast cancer survivors. AJMC. Health Behaviors Treatment Risk Factors Cardiovascular Disease Pathophysiology Epidemiology of CVD in Breast Cancer Survivors Native Risk Factors •Boerman (2014) •Haque (2014) •Obi (2014). Determinant of newly diagnosed comorbidities among breast cancer survivors. Journal of Cancer Survivorship. Health Behaviors Treatment Risk Factors Cardiovascular Disease •Obi (2014). Determinant of newly diagnosed comorbidities among breast cancer survivors. Journal of Cancer Survivorship. Pathophysiology ARS Question # 2 A 65 year old woman presents for her annual Survivorship Visit following treatment 5 years ago for Stage IIB breast cancer (T2, N1, M0). At that time, she received bilateral mastectomies with axilla lymph node removal and radiation to the left axilla. True or False: She is at increased risk for CVD because she has been treated for breast cancer? 0% 0% 1. True 2. False 10 Countdown ARS Question # 3 A 65 year old woman presents for her annual Survivorship Visit following treatment 5 years ago for Stage IIB breast cancer (T2, N1, M0). At that time, she received bilateral mastectomies with axilla lymph node removal and radiation to the left axilla. Her increased risk for developing CVD is most influenced by: 0% 0% 0% 1. History of 30 pack year smoker, HTN, hypercholesterolemia, BMI 35, 2. Receipt of left axilla radiation 3. Failure to receive Tamoxifen during her cancer treatment 10 Countdown Audience Query 4: A 45 year old woman presents for her annual Survivorship Visit following treatment 5 years ago for Stage IIB breast cancer (T2, N1, M0). At that time, she received bilateral mastectomies with axilla lymph node removal, chemotherapy with CAF (cyclophosphamide, doxorubicin (Adriamycin), and 5-FU), and radiation to the left axilla. True or False: She is at increased risk for CVD because she has been treated for breast cancer? A. True B. False ARS Question # 4 A 45 year old woman presents for her annual Survivorship Visit following treatment 5 years ago for Stage IIB breast cancer (T2, N1, M0). At that time, she received bilateral mastectomies with axilla lymph node removal, chemotherapy with CAF (cyclophosphamide, doxorubicin (Adriamycin), and 5-FU), and radiation to the left axilla. True or False: She is at increased risk for CVD because she has been treated for breast cancer? 25% 75% 1. True 2. False Known Cardiotoxic Chemotherapies Coronary Ischemia: LV dysfunction: • Fluorouracil (5-FU) • Anthracyclines • Interleukin-2 • Tratuzumab • Sorafenib • Sunitinib Arrhythmias: • Thalidomide • Vandetanib CVD Risk from Radiation • Routine mapping often prevents radiation induced disease now. • When occurs, commonly involves pericardium, aortic valve, vascular diseases, baroreflex failure • Radiation-induced CVD: oxidative stress, fibrosis, and inflammation • Risk factors for radiation- associated CVD: dose > 30-35 GY, dose per fraction> 2 Gy, large volume of irridated heart, younger age at exposure, longer time since exposure, use of cytotoxic chemotherapy, and presence of other CVD risk factors. Epidemiology of CVD in Cancer Survivors Native Risk Factors Treatment Risk Factors • Genetics • Environmental • • • Chemotherapy Radiotherapy Surgery Cardiovascular Disease Health Behaviors Tobacco, obesity, sedentary lifestyle, metabolic syndrome, insulin resistance Pathophysiology • Cardiomyopathy • Fibrosis Epidemiology of CVD in Cancer Survivors Native Risk Factors Treatment Risk Factors • Genetics • Environmental • • • Chemotherapy Radiotherapy Surgery Cardiovascular Disease Health Behaviors Tobacco, obesity, sedentary lifestyle, metabolic syndrome, insulin resistance Pathophysiology • Cardiomyopathy • Fibrosis What about other cancers? Adult and Pediatric Cancers Screening recommendations Screening recommendations • No evidenced-based guidelines for adults! • There is one consensus based clinical practice guidelines: Boveli, Plataniotis and Riola (2010). European Society of Medical Oncology Clinical Practice Guidelines • IOM 2005 Report “From Cancer Patient to Cancer Survivor: Lost in Transition” • Importance of risk-based care with individualized recommendations • Children’s Oncology Group Guidelines: www.survivorshipguidelines.org Screening (condition) US Preventive Services Task Force COG UK Children’s AAP /AHA Cancer Study Group Blood pressure (hypertension) Annually for adults Annually if treatment risk factors present Regularly for all survivors Measured at every healthcare episode if >3yo Fasting lipids (dyslipidemia) Males 20‐34yo / females 20‐44yo with CHD risk 2y after completing therapy and q2y if risk factors present Consider if received chest radiation or BMT All cancer survivors EKG / ECHO N/A (cardiomyopathy) EKG 2y after therapy / ECHO q1‐5 yrs depending exposures ECHO q3‐5 y depending N/A on exposures Fasting glucose (glucose intolerance / diabetes) q2y in cancer survivors exposed to specific treatments Survivors who received BMT Only asymptomatic adults with blood Pressures >135/80mmHg Baseline for all cancer survivors COG, Long Term Follow‐up Guidelines, 2008 Current Clinical Practice of Monitoring • Echocardiogram for baseline and serial assessment of LVEF • BP and weight with survivorship clinic • May or may not get lipid panel with routine labs • No consistency of when these should be measured or how frequent. Purpose 1) to describe the subclinical incidence and calculated risk for the two most prevalent CVDs (HF and CAD), and 2) to examine perceived risk, knowledge and behaviors related to cardiovascular health in the lymphoma cancer survivorship population. Methods A cross-sectional, correlation study, with a purposive sample of 50 asymptomatic patients who are 2 to 10 years post diagnosis and treatment for lymphoma A secondary aim of this study will be to explore patients’ perspectives on the content and delivery approaches of a patient-specific cardiac risk reduction plan developed from the clinical findings collected in this research, integrating survivorship and preventive cardiology services. Instruments & Measures Antecedents and Screening Concepts Demographic/ clinical factors Cognitive Screening Blessed Orientation-Memory-Concentration (BOMC) Previous cardiac events or symptoms Shortened WHO Rose Angina Questionnaire Routine Noninvasive Measures Routine Lab testing: CBC, Chemistry & Lipid panels Calculated CVD risk Novel/ Investigational Biomarkers of inflammation & Measures myocardial injury Atherosclerosis Patient Reported Measures Instruments/ Measures Demographic/ clinical factors Routine Lab testing: CBC, Chemistry & Lipid panels Framingham Risk Assessment Biomarkers: HS-CRP, cTnI, BNP Myocardial Dysfunction Heart Disease Knowledge Coronary Artery Calcification Computed Tomography (CAC-CT) Echocardiogram Heart Disease Knowledge Questionnaire CVD risk-reducing behaviors Health-Promoting Lifestyle Profile II (HPLPII) Physical and psychological symptoms Memorial Symptom Assessment Scale- Heart Failure (MSAS-HF) HRQL SF-36 & EQ-5D Early Evaluation (N=20) Sociodemographic & Risk Variables Value Male Gender 55% Caucasian 80% Working Full-time 70% Low annual income 20% Average Age Heart disease in 1 Degree Relative Smoking 47.5 years Range (29-73) 75% 1 current/ 4 former Exercise minutes per week 91.11 (SD 76) • 150min/ week or greater 35% History • HTN 20% • Hyperlipidemia 25% (0-210) Identification of the Metabolic Syndrome - Any 3 of the Following: Risk Factor Abdominal obesity* Men Women Triglycerides HDL cholesterol Men Women Blood pressure Fasting glucose Defining Level Waist circumference** >102 cm (>40 in) >88 cm (>35 in) 150 mg/dL <40 mg/dl < 50 mg/dl 130/85 mmHg 110 mg/dL Framingham Risk Calculator http://cvdrisk.nhlbi.nih.gov/calculator.asp Early Evaluation (N=20) Concerning CV Findings Waist to hip ratio Value • > .85 in women • >.90 in men Triglycerides > 150 HDL Cholesterol • <40 in men • <50 in women Blood pressure > 130/85 Fasting Glucose >110 mg/dl 50% 80% 25% Total patients with metabolic syndrome 40% 33% 1 (5%) 20% 25% Range (.75-1) (.75-1) Early Evaluation (N=20) Concerning CV Findings Positive Cardiac CT Heart Dysfunction • Systolic Dysfunction • Diastolic Dysfunction Diagnosed with hyperlipidemia Framingham Risk • Moderate (11-19% risk of having event in next 10 years) • High (>30% risk of having even in next 10 years) Value 1 (5%) 2 (10%) 1 (5%) 7 (35%) 3 (15%) 1 (5%) Challenges in cardio-oncology care • Improve the evidence base • Develop, approve, disseminate, and adhere to guidelines • Cost effectiveness? • Limit additional risk • Risk Prediction Prevention Strategies Prevention strategies • Incorporate preventive cardiology within Survivorship Clinics • Support Survivorship Clinics! • Routine monitoring of CVD risk factors and patient centered counseling to address • Start with AHA’s Simple 7 Education AHA’s Simple Seven 1. 2. 3. 4. 5. 6. 7. Get Active Control Cholesterol Eat Better Stop Smoking Manage Blood Pressure Lose Weight Reduce Blood Sugar Source: American Heart Association Effects of Physical Activity Guidelines on Cancer and CVD Mortality: The Cooper Center Longitudinal Study N=53,000 Hazard Ratio 1 0.8 0.6 Cancer Mortality CVD Mortality 0.4 0.2 0 Not Meeting Guidelines Meeting Guidelines Exceeding Guidelines CE Barlow, WL Haskell, SG Lakoski: Meeting the Physical Activity Guidelines and Risk of Cardiovascular Disease and Cancer Mortality: Cooper Center Longitudinal Study. AHA Scientific Sessions (2013), Dallas, TX