Health knowledge about symptoms of heart attack and stroke in adult survivors of childhood acute lymphoblastic leukemia

James Gurney

Janet Donohue

Kirsten Ness

Maura O’Leary

Stephen Glasser

K Baker

Purpose

Children with acute lymphoblastic leukemia (ALL), the most common pediatric malignancy, have a 5-year survival rate of better than 80%. Long-term survivors of childhood ALL, however, carry an elevated risk of early mortality from cardiac events and stroke, and a disproportionately high prevalence of dyslipidemia and obesity, presumably as an adverse effect of treatment.

Methods

As part of a clinical follow-up study of 70 young adult survivors of childhood ALL, we evaluated the degree to which this high risk group differed in knowledge about symptoms of heart attack and stroke from that of a population-based comparison group frequency-matched by age, sex, and body mass index. Questions from the Behavioral Risk Factor Surveillance System were used to assess health knowledge.

Results

Survivors of ALL scored considerably worse on symptom knowledge than did their population counterparts. The strongest association was observed for chest pain as a symptom of a heart attack: ALL survivors were 14-fold more likely than the comparison group to answer the question incorrectly. Seventy-seven percent of survivors failed to identify pain in the jaw, neck or back as a heart attack symptom.

Conclusions

These results indicate an important gap in knowledge, and underscore the need for health education among survivors of childhood leukemia that includes information about symptoms of myocardial infarction and stroke.

Introduction

With cardiac and vascular diseases accounting for more than 871,000 deaths annually and reigning as the leading causes of mortality among adults in the United States (1), one might expect a fairly high level of health knowledge for symptoms of heart attack and stroke, at least among persons with a high risk profile. Long-term childhood cancer survivors in general, and acute leukemia survivors in particular, have a substantially elevated risk of cardiovascular disease and stroke as a late effect of treatment (2–6). Among survivors of pediatric acute lymphoblastic leukemia (ALL), the most common malignancy of childhood (7), potentially cardiotoxic effects of anthracylines and high dose cyclophosphamide (8) are compounded by a disproportionately high prevalence of metabolic syndrome or its components, particularly dyslipidemia and obesity (9–15), thus reflecting a poor cardiac risk profile leading into adulthood. As part of a clinical follow-up study of young adult survivors of childhood ALL (9), we asked participants to complete a module of the Center for Disease Control and Prevention’s Behavioral Risk Factor Surveillance Study (BRFSS; http://www.cdc.gov/brfss/) that asked health knowledge questions about symptoms of heart attack and stroke. We evaluated the degree to which adult survivors of childhood ALL differed in symptom knowledge from that of a population-based, frequency matched comparison group who completed the same module of the BRFSS.

Methods

Described in detail elsewhere (9), we recruited and evaluated 75 adult survivors of childhood ALL in 2004–2005 who received their leukemia treatment at one of three children’s hospitals in the Minneapolis/St. Paul area and who participated in the Childhood Cancer Survivor Study (16). None of the subjects had a history of a cardiac event or stroke. Subjects completed a variety of clinical and laboratory examinations in the General Clinical Research Center at the University of Minnesota and completed several questionnaires, including Module 10 of the 2002 BRFSS which asked questions “about your knowledge of the signs and symptoms of a heart attack and stroke.” Written informed consent was obtained for each subject as approved by the Human Subjects Review Committees at the University of Minnesota and Children’s Hospitals and Clinics of Minneapolis/St. Paul. For this analysis, we selected a comparison group from among Minnesota respondents of the 2003 BRFSS who answered the same questions on symptom knowledge of heart attack and stroke as that of study subjects using a frequency matching algorithm to produce a balanced distribution of 3 controls to each subject by age, sex, and body mass index. We excluded 5 subjects because of missing responses or problems with matching appropriate controls. Unconditional logistic regression, controlling for the three matching variables (age and body mass index as continuous variables) and educational level, was used to compare the relative odds of answering a question incorrectly. There were 12 questions that asked about heart attack or stroke, worded as follows: “Which of the following do you think is a symptom of a [heart attack/stroke]? For each, tell me yes, no, or you’re not sure.” We considered ‘not sure’ answers to be incorrect.

Results

Mean age for both the 70 ALL subjects and the 210 adults in the population comparison group was 29 years (range 18–45), both groups were 59% female, and the distribution of body mass index for both groups was 43% at <25, 24% at 25–29, and 33% at ≥30. Survivors were slightly less likely to be a current smoker (17.1%) than were those in the comparison group (18.6%). The Table shows the wording of each question, a comparison of the percentage of incorrect answers for each question, and the adjusted odds ratios with corresponding 95% confidence intervals quantifying the strength of the association for answering incorrectly between ALL survivors and the comparison group. With only two exceptions, one each for heart attack and stroke, ALL survivors scored worse on symptom knowledge than did their population counterparts. The strongest association was observed for chest pain as a symptom of a heart attack, in which ALL survivors (5.7%) were 14-fold more likely than the comparison group (0.5%) to not answer the question correctly as a symptom. The highest percentage of incorrect answers by ALL survivors (77%) was for the question asking if pain in the jaw, neck or back was a heart attack symptom. Differences in results were not observed between the ALL survivors who received cranial irradiation during their treatment course and those who did not receive cranial irradiation.

Table

Comparison of symptom knowledge^{of myocardial infarction and stroke between 70 young adult survivors of childhood acute lymphoblastic leukemia and 210 frequency matched controls}

	Percentage who answered incorrectly
“Which of the following do you think is a symptom of a [heart attack/stroke]? For each, tell me yes, no, or you’re not sure.”	ALL Survivors	Controls	OR^*	95% CI
Heart attack symptoms
Pain or discomfort in the jaw, neck or back	77.1	55.2	2.8	1.5 – 5.2
Feeling weak, lightheaded, or faint	38.6	21.9	2.3	1.2 – 4.1
Chest pain or discomfort	5.7	0.5	14.0	1.5 – 131
Sudden trouble seeing in one or both eyes^a	55.7	70.1	0.5	0.3 – 0.9
Pain or discomfort in the arms or shoulders	24.3	6.2	5.2	2.3 – 11.6
Shortness of breath	15.7	5.7	3.3	1.3 – 8.1

Stroke symptoms
Sudden confusion or trouble speaking	28.6	10.0	3.8	1.8 – 7.9
Sudden numbness or weakness of face, arm, or leg, especially on one side	8.6	4.3	2.2	0.7 – 6.7
Sudden trouble seeing in one or both eyes	44.3	26.7	2.1	1.2 – 3.8
Sudden chest pain or discomfort^a	61.4	61.0	0.98	0.5 – 1.7
Sudden trouble walking, dizziness, or loss of balance	34.3	7.6	6.6	3.1 – 13.7
Severe headache with no known cause	61.4	37.6	2.6	1.5 – 4.6

^{From the Behavioral Risk Factor Surveillance System}

^{Decoy symptom}

^{Odds ratios and confidence intervals adjusted for age, sex, body mass index, and educational level}

Discussion

These results indicate that young adult survivors of childhood ALL have less accurate knowledge about symptoms of myocardial infarction and stroke than a normative population, despite their treatment-related elevated risk for mortality from cardiac and vascular events.

Although we cannot explain the unexpected findings, these data suggest a need for effective health education about symptoms of myocardial infarction and stroke, and by inference, about the elevated risk for adverse cardiac and vascular sequelae among long-term survivors of childhood leukemia and other pediatric cancers that include cardiotoxic therapy or are associated with treatment-potentiated obesity. Moser and colleagues (17) emphasize the need for early identification and treatment of acute coronary events and stroke, and note, as have others (18–21), that patient delay in seeking medical intervention is a major factor limiting delivery of definitive treatment. Reflecting the remarkable improvements in survival rates for most childhood cancers over the past several decades (22), especially ALL (23), the National Cancer Institute’s SEER Program estimates that nearly 228,000 persons aged 27 years or younger have or had cancer during childhood (24). This high prevalence supports the growing understanding that health service issues affecting childhood cancer survivors, particularly as they relate to cardiovascular health, are significant as they progress into age groups with increasing risk of adverse health outcomes (25–31). Although our results do not allow assessment of health outcomes as a function of health knowledge, the poor general understanding of heart attack and stroke symptoms among these ALL survivors highlights the need for special efforts to increase awareness of risk factors for potential adverse health outcomes related to cancer and its treatment, both for the survivors themselves and for the primary care providers who follow them as adults after transition from pediatric cancer care (32).

Acknowledgments

NIH Research Funding Support: R21-CA106778; M01-RR00400; U24-CA55727; K23-CA85503

^{Child Health Evaluation and Research Unit, Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI 48109-0456}

^{Department of Epidemiology and Cancer Control, St. Jude Children’s Research Hospital, Memphis, TN 38105}

^{Children’s Oncology Group/Curesearch, Bethesda MD 20814}

^{Division of Preventive Medicine, University of Alabama-Birmingham Medical School, Birmingham, AL 35205}

^{Division of Hematology/Oncology/Bone Marrow Transplantation, Department of Pediatrics, University of Minnesota Medical School, MN 55455}

Correspondence to: James G. Gurney Ph.D., University of Michigan, Department of Pediatrics, 300 N.Ingalls St., Room 6E02, Ann Arbor, MI 48109, E-mail: ude.hcimu@nrugemaj; Phone: 734-615-8145; Fax: 734-764-2599

Publisher's Disclaimer

Abstract

Purpose

Methods

Results

Conclusions

Keywords: Cancer, myocardial infarction, health education, adverse late effects

Abstract

Footnotes

Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Footnotes

References

1. Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K, Haase N, Ho M, Howard V, Kissela B, Kittner S, Lloyd-Jones D, McDermott M, Meigs J, Moy C, Nichol G, O’Donnell CJ, Roger V, Rumsfeld J, Sorlie P, Steinberger J, Thom T, Wasserthiel-Smoller S, Hong Y. Heart Disease and Stroke Statistics--2007 Update. A Report From the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2007;115(5):e69–171.[PubMed]
2. Mertens ACCause of mortality in 5-year survivors of childhood cancer. Pediatr Blood Cancer. 2007;48(7):723–6. PMID: 17226844 [PubMed - indexed for MEDLINE] [[PubMed][Google Scholar]
3. Mertens AC, Yasui Y, Neglia JP, Potter JD, Nesbit ME, Jr, Ruccione K, Smithson WA, Robison LLLate mortality experience in five-year survivors of childhood and adolescent cancer: the Childhood Cancer Survivor Study. J Clin Oncol. 2001;19(13):3163–72.[PubMed][Google Scholar]
4. Bowers DC, Liu Y, Leisenring W, McNeil E, Stovall M, Gurney JG, Robison LL, Packer RJ, Oeffinger KCLate-occurring stroke among long-term survivors of childhood leukemia and brain tumors: a report from the Childhood Cancer Survivor Study. J Clin Oncol. 2006;24(33):5277–82.[PubMed][Google Scholar]
5. Gurney JG, Kadan-Lottick NS, Packer RJ, Neglia JP, Sklar CA, Punyko JA, Stovall M, Yasui Y, Nicholson HS, Wolden S, McNeil DE, Mertens AC, Robison LLEndocrine and cardiovascular late effects among adult survivors of childhood brain tumors: Childhood Cancer Survivor Study. Cancer. 2003;97(3):663–73.[PubMed][Google Scholar]
6. Bowers DC, McNeil DE, Liu Y, Yasui Y, Stovall M, Gurney JG, Hudson MM, Donaldson SS, Packer RJ, Mitby PA, Kasper CE, Robison LL, Oeffinger KCStroke as a late treatment effect of Hodgkin’s Disease: a report from the Childhood Cancer Survivor Study. J Clin Oncol. 2005;23(27):6508–15.[PubMed][Google Scholar]
7. Gurney JG, Davis S, Severson RK, Fang JY, Ross JA, Robison LLTrends in cancer incidence among children in the U.S. Cancer. 1996;78(3):532–41.[PubMed][Google Scholar]
8. Adamson PC, Balis FM, Berg S, Blaney SM. General Principles of Chemotherapy. In: Pizzo PA, Poplack DG, editors. Principles and Practice of Pediatric Oncology. 5. Philadelphia: Lippincott Williams & Wilkins; 2006. pp. 290–365. [PubMed]
9. Gurney JG, Ness KK, Sibley SD, O’Leary M, Dengel DR, Lee JM, Youngren NM, Glasser SP, Baker KSMetabolic syndrome and growth hormone deficiency in adult survivors of childhood acute lymphoblastic leukemia. Cancer. 2006;107(6):1303–12.[PubMed][Google Scholar]
10. Nuver J, Smit AJ, Postma A, Sleijfer DT, Gietema JAThe metabolic syndrome in long-term cancer survivors, an important target for secondary preventive measures. Cancer Treat Rev. 2002;28(4):195–214.[PubMed][Google Scholar]
11. Talvensaari K, Knip MChildhood cancer and later development of the metabolic syndrome. Ann Med. 1997;29(5):353–5.[PubMed][Google Scholar]
12. Talvensaari KK, Lanning M, Tapanainen P, Knip MLong-term survivors of childhood cancer have an increased risk of manifesting the metabolic syndrome. J Clin Endocrinol Metab. 1996;81(8):3051–5.[PubMed][Google Scholar]
13. Oeffinger KC, Buchanan GR, Eshelman DA, Denke MA, Andrews TC, Germak JA, Tomlinson GE, Snell LE, Foster BMCardiovascular risk factors in young adult survivors of childhood acute lymphoblastic leukemia. J Pediatr Hematol Oncol. 2001;23(7):424–30.[PubMed][Google Scholar]
14. Oeffinger KC, Mertens AC, Sklar CA, Yasui Y, Fears T, Stovall M, Vik TA, Inskip PD, Robison LLObesity in adult survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. J Clin Oncol. 2003;21(7):1359–65.[PubMed][Google Scholar]
15. Sklar CA, Mertens AC, Walter A, Mitchell D, Nesbit ME, O’Leary M, Hutchinson R, Meadows AT, Robison LLChanges in body mass index and prevalence of overweight in survivors of childhood acute lymphoblastic leukemia: role of cranial irradiation. Med Pediatr Oncol. 2000;35(2):91–5.[PubMed][Google Scholar]
16. Robison LL, Mertens AC, Boice JD, Breslow NE, Donaldson SS, Green DM, Li FP, Meadows AT, Mulvihill JJ, Neglia JP, Nesbit ME, Packer RJ, Potter JD, Sklar CA, Smith MA, Stovall M, Strong LC, Yasui Y, Zeltzer LKStudy design and cohort characteristics of the Childhood Cancer Survivor Study: a multi-institutional collaborative project. Med Pediatr Oncol. 2002;38(4):229–39.[PubMed][Google Scholar]
17. Moser DK, Kimble LP, Alberts MJ, Alonzo A, Croft JB, Dracup K, Evenson KR, Go AS, Hand MM, Kothari RU, Mensah GA, Morris DL, Pancioli AM, Riegel B, Zerwic JJReducing delay in seeking treatment by patients with acute coronary syndrome and stroke: A scientific statement from the American Heart Association Council on Cardiovascular Nursing and Stroke Council. Circulation. 2006;114(2):168–182.[PubMed][Google Scholar]
18. Centers for Disease Control and Prevention. Awareness of stroke warning signs--17 states and the U.S. Virgin Islands, 2001. MMWR Morb Mortal Wkly Rep. 2004;53(17):359–62.[PubMed]
19. Centers for Disease Control and PreventionPlace of death after stroke--United States, 1999–2002. MMWR Morb Mortal Wkly Rep. 2006;55(19):529–532.[PubMed][Google Scholar]
20. Lacy CR, Suh D-C, Bueno M, Kostis JBDelay in presentation and evaluation for acute stroke: Stroke Time Registry for Outcomes Knowledge and Epidemiology (S.T.R.O.K.E) Stroke. 2001;32(1):63–69.[PubMed][Google Scholar]
21. McGinn AP, Rosamond WD, Goff JDC, Taylor HA, Miles JS, Chambless LTrends in prehospital delay time and use of emergency medical services for acute myocardial infarction: Experience in 4 US communities from 1987–2000. American Heart Journal. 2005;150(3):392–400.[PubMed][Google Scholar]
22. Gurney JG, Bondy ML. Epidemiology of Childhood Cancer. In: Pizzo PA, Poplack DG, editors. Principles and Practice of Pediatric Oncology. 5th edition. Philadelphia: Lippincott Williams & Wilkins; 2006. pp. 1–13. [PubMed]
23. Smith MA, Ries LAG, Gurney JG, Ross JA. Leukemia. In: Ries LAG, Smith MA, Gurney JG, Linet M, Tamra T, Young JL, et al., editors. Cancer Incidence and Survival among Children and Adolescents: United States SEER Program 1975–1995. NIH Pub. No. 99-4649. Bethesda, MD: National Cancer Institute; 1999. pp. 17–34. [PubMed]
24. Ries LAG, Harkins D, Krapcho M, Mariotto A, Miller BA, Feuer EJ, Clegg L, Eisner MP, Horner MJ, Howlader N, Hayat M, Hankey BF, Edwards BK SEER Cancer Statistics Review, 1975–2003. Bethesda, MD: National Cancer Institute; 2006. [PubMed][Google Scholar]
25. Aziz NMCancer survivorship research: challenge and opportunity. J Nutr. 2002;132(11 Suppl):3494S–3503S.[PubMed][Google Scholar]
26. Bhatia S, Meadows ATLong-term follow-up of childhood cancer survivors: future directions for clinical care and research. Pediatr Blood Cancer. 2006;46(2):143–8.[PubMed][Google Scholar]
27. Hawkins MMLong-term survivors of childhood cancers: what knowledge have we gained? Nat Clin Pract Oncol. 2004;1(1):26–31.[PubMed][Google Scholar]
28. Hudson MMA model for care across the cancer continuum. Cancer. 2005;104(11 Suppl):2638–42.[PubMed][Google Scholar]
29. Landier W, Wallace WHB, Hudson MMLong-term follow-up of pediatric cancer survivors: education, surveillance, and screening. Pediatr Blood Cancer. 2006;46(2):149–58.[PubMed][Google Scholar]
30. Meadows ATPediatric cancer survivorship: research and clinical care. J Clin Oncol. 2006;24(32):5160–5.[PubMed][Google Scholar]
31. Shaw AK, Pogany L, Speechley KN, Maunsell E, Barrera M, Mery LSUse of health care services by survivors of childhood and adolescent cancer in Canada. Cancer. 2006;106(8):1829–37.[PubMed][Google Scholar]
32. Ginsberg JP, Hobbie WL, Carlson CA, Meadows ATDelivering long-term follow-up care to pediatric cancer survivors: transitional care issues. Pediatr Blood Cancer. 2006;46(2):169–73.[PubMed][Google Scholar]