Abstract
Purpose:
To examine the prevalence of cardiovascular diseases (CVD) among breast cancer (BC) survivors.
Design:
Cross-sectional observational study using the data from the National Health and Nutrition Examination Survey (NHANES) 2003–2018.
Setting:
United States (US).
Subjects:
A nationally representative sample of US women with a history of BC.
Measures:
Self-reported CVD status (i.e., coronary artery disease (CAD), heart failure, and stroke) and time of the CVD diagnosis were used to categorize BC survivors into three groups: No CVD, preexisting CVD, and post-acquired CVD after BC diagnosis.
Analysis:
The prevalence of CVD among BC survivors were estimated by demographic characteristics. Complex sampling design of the NHANES was accounted to estimate the population-level prevalence.
Results:
A total of 658 BC survivors were identified, representing 3.01% (≈3.4 million) of the US women aged ≥18 years old. Of those, ≈6% (≈.2 million) had preexisting CVD and ≈11% (≈.4 million) had at least one CVD diagnosed after BC diagnosis, with an average time elapsed ranging from ≈5 years for heart failure to ≈9 years for CAD and stroke. The prevalence of CVD among BC survivors differed by demographic characteristics including age, education, marital status, menopausal, and physical activity levels.
Conclusion:
Our findings suggest that BC survivors are at risk of suffering from CVD and public health strategies for the long-term management of CVD risk factors in this vulnerable population group is recommended.
Keywords: physical activity, cardiotoxic, cancer survivorship, coronary artery disease
Purpose
Breast cancer (BC) is the second leading cause of cancer death among women in the United States (US).1, Advances in cancer care have led to increasing BC survival rates; yet, adverse cardiotoxic side-effects are frequently induced by cancer treatment (e.g., chemotherapy, radiation therapy).2 These cardiotoxic effects coupled with the shared risk factors (e.g., aging), substantially increase the risk of cardiovascular disease (CVD) among BC survivors.3 The present study examined the population-level prevalence of CVD among BC survivors, with a focus on the CVD developed after BC diagnosis.
Methods
Data and Study Design
We analyzed the National Health and Nutrition Examination Survey (NHANES) data. NHANES examines the health and nutrition status of the US civilian population in 2-year cycles based on a nationally representative sample selected by a multistage, complex sampling design. We combined the eight NHANES cycles (2003–2004 through 2017–2018) to increase the sample size of BC survivors, and the 16-year sampling weights were calculated by following the published analytic guidelines.4
Measures and Data Analysis
During the household interview, NHANES participants were asked to report a range of health and medical conditions by trained interviewers. We used the responses to the questionnaire item asking “has a doctor or other health professional ever told you that you had …” to identify BC survivors and CVD status (i.e., coronary artery disease (CAD), such as coronary heart disease and heart attack, heart failure, and stroke). We also calculated the time difference between self-reported BC and CVD diagnoses among BC survivors with CVD. BC survivors were categorized into three groups: No CVD, pre-existing CVD (i.e., had pre-existing CVD before BC diagnosis), and post-acquired CVD (i.e., CVD diagnosed after BC diagnosis).
The prevalence of CVD status among BC survivors was examined in relation to demographic characteristics (i.e., age in years, race/ethnicity, education, annual household income, marital status, menopausal status, and health insurance coverage) and other health-related characteristics [i.e., smoking status, body mass index (BMI) status, self-reported cardiovascular health (≥40 years old only), and self-reported moderate- and vigorous-intensity physical activity (MVPA) levels]. Weekly time spent in MVPA was estimated from the Global Physical Activity Questionnaire,5 and BC survivors were categorized into the two groups based on the current PA recommendations (sufficient-MVPA≥150 minutes/week vs. insufficient-MVPA<150 minutes/week). The between-group differences in the CVD status by demographic and health-related characteristics were estimated using a linear regression model for a continuous variable and the Rao-Scott x2 test of independence for a categorical variable. The SURVEY procedures in the SAS v9.4 (SAS Institute, Cary, NC) were used to produce the population-level estimates after accounting for the complex sampling design of the NHANES.
Results
A total of 658 BC survivors were identified, representing 3.01% (weighted N = 3,380,013) of the US women aged ≥18 years old (Table 1). The mean age of BC survivors was 65.42 years, with an average of 9.50 years elapsed since first diagnosed with BC. The majority of BC survivors were in the no CVD group (83.05%), while 6.18% (weighted N = 151,238) reported pre-existing CVD and 10.77% (weighted N = 370,693) reported post-acquired CVD.
Table 1.
Descriptive Characteristics of Breast Cancer Survivors By Cardiovascular Disease Status.
| Cardiovascular disease Statusa | |||||
|---|---|---|---|---|---|
| Total | No CVD | Pre-existing CVD | Post-acquired CVD | P-Valueb | |
| Unweighted n | 658 | 546 | 37 | 75 | - |
| Weighted N | 3,380,013 | 2,858,083 | 151,238 | 370,693 | - |
| Weighted population %c | 3.01 (2.72, 3.29) | 2.54 (2.28, 2.81) | .13 (.08, .19) | .33 (.22, .44) | - |
| Weighted %d | - | 83.05 (79.29, 86.81) | 6.18 (3.75, 8.60) | 10.77 (7.30, 14.24) | - |
| Age (years) | 65.42 (64.07, 66.77) | 64.20 (62.76, 65.64) | 70.99 (67.84, 74.14) | 72.59 (69.53, 75.65) | <.001 |
| Years since first diagnosed with BC | 9.50 (8.71, 10.30) | 9.31 (8.43, 10.19) | 5.57 (3.75, 7.40) | 12.59 (10.18, 15.00) | <.001 |
| Race/ethnicity (%) | .123 | ||||
| Non-hispanic white | 82.36 (79.34, 85.39) | 81.82 (78.53, 85.11) | 75.47 (60.47, 90.48) | 89.38 (84.41, 94.36) | |
| Non-hispanic black | 7.93 (6.17, 9.69) | 7.83 (6.02, 9.65) | 14.36 (2.74, 25.97) | 6.05 (2.42, 9.68) | |
| Mexican | 3.03 (1.84, 4.22) | 3.37 (2.04, 4.71) | 1.40 (0, 4.19) | 1.03 (.30, 1.76) | |
| Others | 6.68 (4.88, 8.47) | 6.97 (5.02, 8.92) | 8.77 (0, 18.12) | 3.54 (.54, 6.54) | |
| Education (%) | .026 | ||||
| <High school | 14.74 (11.97, 17.52) | 12.94 (10.23, 15.66) | 19.32 (3.94, 34.69) | 26.76 (15.43, 38.09) | |
| High school diploma | 22.97 (18.45, 27.50) | 21.82 (17.01, 26.63) | 34.74 (19.10, 50.38) | 27.05 (10.20, 43.90) | |
| ≥College or above | 62.28 (57.44, 67.12) | 65.23 (60.17, 70.30) | 45.95 (27.81, 64.08) | 46.19 (28.97, 63.40) | |
| Annual household income (%) | .367 | ||||
| <$25k | 19.23 (15.84, 22.62) | 17.99 (14.66, 21.32) | 30.07 (12.41, 47.72) | 24.39 (13.81, 34.97) | |
| $25k - <$55k | 21.14 (16.94, 25.35) | 21.19 (16.88, 25.49) | 14.83 (3.21, 26.46) | 23.41 (11.38, 35.43) | |
| $55k - <$75k | 31.78 (27.22, 36.35) | 31.03 (26.28, 35.78) | 37.65 (19.32, 55.98) | 35.19 (21.24, 49.15) | |
| ≥$75k | 27.84 (22.69, 33.00) | 29.80 (24.20, 35.39) | 17.46 (1.13, 33.78) | 17.01 (.59, 33.44) | |
| Marital status (%) | .005 | ||||
| Married or living with partner | 56.72 (51.57, 61.87) | 59.74 (54.18, 65.29) | 36.53 (23.12, 49.94) | 41.70 (25.69, 57.71) | |
| Others | 43.28 (38.13, 48.43) | 40.26 (34.71, 45.82) | 63.47 (50.06, 76.88) | 58.30 (42.29, 74.31) | |
| Menopausal status (%) | .039 | ||||
| Postmenopausal | 87.40 (83.51, 91.28) | 85.74 (81.20, 90.28) | 92.54 (78.20, 100) | 98.08 (95.58, 100) | |
| Premenopausal | 12.60 (8.72, 16.49) | 14.26 (9.72, 18.80) | 7.46 (0, 21.80) | 1.92 (0, 4.42) | |
| Smoking status (%) | .781 | ||||
| Currently smoking | 10.99 (8.01, 13.98) | 10.76 (7.5, 14.02) | 9.53 (.49, 18.56) | 13.40 (4.23, 22.56) | |
| Not smoking | 89.01 (86.02, 91.99) | 89.24 (85.98, 92.5) | 90.47 (81.44, 99.51) | 86.60 (77.44, 95.77) | |
| Health insurance (%) | .389 | ||||
| Covered | 87.03 (83.94, 90.12) | 87.16 (84.22, 90.1) | 79.11 (61.87, 96.35) | 89.23 (82.4, 96.05) | |
| Not-covered | 12.97 (9.88, 16.06) | 12.84 (9.90, 15.78) | 20.89 (3.65, 38.13) | 10.77 (3.95, 17.60) | |
| Body mass index (%) | .254 | ||||
| <25 kg/m2 | 30.92 (25.61, 36.23) | 32.36 (26.50, 38.23) | 28.67 (12.44, 44.90) | 20.69 (10.80, 30.57) | |
| 25 - <30 kg/m2 | 34.40 (29.71, 39.10) | 33.62 (28.36, 38.87) | 26.44 (11.50, 41.39) | 43.71 (31.13, 56.29) | |
| ≥30 kg/m2 | 34.68 (30.23, 39.12) | 34.02 (28.99, 39.04) | 44.88 (28.89, 60.87) | 35.60 (20.49, 50.71) | |
| MVPA levels (%)f | .008 | ||||
| S-MVPA (≥150 minutes/week) | 47.54 (42.61, 52.47) | 50.93 (45.79, 56.07) | 29.97 (12.56, 47.38) | 28.61 (12.28, 44.94) | |
| I-MVPA (<150 minutes/week) | 52.46 (47.67, 57.24) | 49.07 (43.93, 54.21) | 70.03 (52.62, 87.44) | 71.39 (55.06, 87.72) | |
Abbreviations: CVD = cardiovascular disease; S-MVPA = sufficient moderate and vigorous-intensity physical activity; I-MVPA = insufficient-MVPA. Values are the mean (95% CI) and percentage (95% CI) for continuous and categorical variables, respectively.
Cardiovascular disease status was determined based on self-reported medical conditions on coronary artery disease (heart attack and coronary heart disease), heart failure, and stroke that were told by a doctor or other health professionals.
P-value is for the between-group differences estimated from a linear regression model for a continuous variable and Rao-Scott x2 test of independence for a categorical variable.
Weighted population % indicates the prevalence estimates among US adult women aged ≥18 years old (weighted N = 112,443,001).
Weighted % indicates the prevalence estimates within breast cancer survivors.
Self-reported cardiovascular health was obtained for adults aged ≥40 years old (n = 645) by asking a series of questions about pain or discomfort in chest.
Self-reported physical activity data was used to determine the level of moderate- and vigorous-intensity physical activity.
BC survivors in pre-existing and post-acquired CVD groups had a higher mean age (71.0 and 72.6, respectively) when compared to those without CVD (≈65 years old). BC survivors with post-acquired CVD had the longest survival time since first diagnosed with BC (12.59 years), followed by BC survivors without CVD (9.31 years) and with pre-existing CVD (5.57 years). There were statistical differences in CVD status by additional demographic characteristics, including education, marital status, and menopausal status. BC survivors with pre-existing and post-acquired CVD had a significantly lower prevalence of sufficient-MVPA (<30%) when compared to those without CVD (50%). Additionally, although not statistically significant, there was a relatively larger proportion of non-Hispanic Black survivors in pre-existing CVD group (14.36%) compared to others (6~8%).
Table 2 presents CVD prevalence in terms of the numbers and types of CVD among BC survivors with pre-existing and post-acquired CVD. Across both groups, ≈20% had two or more CVD’s with CAD (56.84%) being the most frequently reported. Among BC survivors with post-acquired CVD, stroke (34.41%) was the second, followed by heart failure (25.49%). On average, BC survivors with post-acquired CVD reported 8.68 years of latent time until CVD diagnosis. The latent time was shorter for heart failure (5.46 years) compared to stroke (9.15 years) and CAD (9.27 years).
Table 2.
The Prevalence of Cardiovascular Diseases Among Breast Cancer Survivorsa.
| Number of CVDb | Types of cardiovascular disease | |||||
|---|---|---|---|---|---|---|
| Totala | One | Two or More | Coronary Artery Disease | Heart Failure | Stroke | |
| Pre-existing CVDc | ||||||
| Unweighted n | 37 | 29 | 8 | 21 | 14 | 12 |
| Weighted N | 151,238 | 119,684 | 31,554 | 85,966 | 56,565 | 48,633 |
| Weighted %d | - | 79.14 (66.50, 91.77) | 20.86 (8.23, 33.50) | 56.84 (40.97, 72.71) | 37.40 (22.30, 52.50) | 32.16 (15.83, 48.48) |
| Post-acquired CVDe | ||||||
| Unweighted n | 75 | 58 | 17 | 34 | 22 | 29 |
| Weighted N | 370,693 | 291,542 | 79,151 | 190,888 | 94,490 | 127,549 |
| Weighted %d | - | 78.65 (68.63, 88.66) | 21.35 (11.34, 31.37) | 51.50 (36.90, 66.09) | 25.49 (14.25, 36.73) | 34.41 (20.86, 47.96) |
| Years since diagnosis BCf | 8.68 (6.47, 10.88)g | 9.21 (6.64, 11.77) | 6.72 (3.41, 10.03)g | 9.27 (6.21, 12.33) | 5.46 (3.28, 7.64) | 9.15 (4.81, 13.49)> |
Abbreviations: BC = breast cancer, CVD = cardiovascular disease.
Values are the mean (95% CI) and percentage (95% CI) for continuous and categorical variables, respectively.
Cardiovascular disease status was determined based on self-reported medical conditions that were told by a doctor or other health professionals.
The prevalence of breast cancer survivors by the number of cardiovascular diseases reported.
Breast cancer survivors who already had pre-existing cardiovascular diseases before diagnosed with breast cancer.
Weighted % indicates the proportion within each subgroup (pre-existing or post-acquired cardiovascular diseases groups).
Breast cancer survivors who acquired the cardiovascular diseases after diagnosed with breast cancer.
The time elapsed until they were first diagnosed with cardiovascular diseases after they were diagnosed with breast cancer.
When multiple CVDs were reported, the CVD diagnosed first was used to calculate average years.
Discussion
BC survivors are at increased risk of developing CVD in part due to the cardiotoxic effects of anticancer treatment. For instance, anthracycline-based chemotherapy can generate reactive oxygen species causing adverse acute and chronic effects in the cardiovascular system increasing the risk of adverse cardiac events.6 Similarly, radiation therapy on the left chest wall putatively results in oxidative stress and release of pro-inflammatory and profibrotic cytokines with downstream effects on the vasculature and myocardium.7 In the present study, among ≈3.4 million BC survivors in the US, ≈11% (≈.37 million) of survivors developed at least one type of CVD after an average of ≈8 years since first diagnosed with BC. CAD was the most frequently reported post-acquired CVDs with a relatively long latent period (≈9–10 years) when compared to heart failure, which was shown to occur within ≈6 years since BC diagnosis. The delayed manifestation of CAD is consistent with prior studies where CAD is driven by radiation exposure.8 Although our data did not explicitly indicate latent cardiotoxic effects on CVD incidence, the findings are generally aligned with the previous study reporting CVD risks being manifested ≈7 years after BC diagnosis.9 The present findings add prominent preliminary data concerning the long-term prognosis of CVD after BC treatment, suggesting the need for proactive monitoring and management of CVD to reduce the CVD-related burden during long-term survivorship.
Additionally, as shown in the present study, BC survivors are primarily characterized by several key risk factors for CVD, such as aging, postmenopausal status, having overweight/obesity, and being physically inactive,3 which can increase the risk of CVD-related morbidity during their long-term survivorship. Among elderly BC survivors, CVD can pose a more significant threat to their health than the cancer itself, with empirical evidence showing CVD as the leading cause of death in this vulnerable population.10 This implies that public health efforts to provide long-term management of CVD risk factors in addition to the early identification of CVD would offer critical health benefits for BC survivors.
Limitations
The limitations of the present study included that first, medical history used to identify BC survivors and CVD status was self-reported, which is subject to response and non-response biases and risk for misclassification. Further, the NHANES is not designed to sample specific population groups based on medical conditions, and thus, the coverage of the NHANES to produce accurate population-level estimates for BC survivors might be limited. Second, the NHANES did not collect detailed information about medical conditions (e.g., tumor characteristics, stage) and its treatment regimen (e.g., surgery, types of therapy, duration), critical patient-level characteristics associated with CVD prevalence in BC survivors. Third, the present study focused on the cross-sectional prevalence of CVD among BC survivors, and the findings should therefore not be interpreted as causal association of BC with the risk of CVD. Lastly, although we combined the eight cycles of the NHANES, a relatively small sample size of BC survivors resulted in large variation in the estimates and prevented us from subgroup analyses to elucidate the possible disparities in CVD outcomes by demographic characteristics. Thus, the caution is needed when generalizing the present findings to the population-level estimates.
Significance
Nevertheless, our study is one of the few to examine the prevalence of CVD among BC survivors. The results showed that more than 15% of survivors suffered from CVD that were preexisted or post-acquired after BC diagnosis. CVD is a known risk factor elevating the risk of adverse health outcomes and the present study highlights the importance of developing a proactive strategy for long-term care of BC survivors, with a particular emphasis on the monitoring and management of CVD risk factors, to improve longevity and quality of life among BC survivors.
So What?
What Is Already Known on This Topic?
Breast cancer (BC) survivors are at-risk of developing cardiovascular diseases (CVD) due to anticancer-therapy-induced cardiotoxicity, coupled with predis-posing risk factors.
What Is Added by This Report?
The present study provides population-level estimates of CVD prevalence among BC survivors in the United States. We primarily focused on post-acquired CVD after BC diagnosis to provide an implication about the long-term prognosis of CVD after BC treatment.
What are the implications for health promotion practice or research?
The present study supports the importance of providing long-term care services for BC survivors, emphasizing the monitoring and managing of CVD risk factors to reduce the incidence of CVD thereby improving the health and quality of life of this at-risk population.
Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Dr. Sutton is supported by NCI K99CA256038 and the NIH-NCI Cancer Center Support Grant P30 CA016059.
Footnotes
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
References
- 1.Heron M Deaths: Leading causes for 2017. Natl Vital Stat Rep. 2019;68(6):1–77. [PubMed] [Google Scholar]
- 2.Khouri MG, Douglas PS, Mackey JR, et al. Cancer therapy–induced cardiac toxicity in early breast cancer: addressing the unresolved issues. Circulation. 2012;126(23):2749–2763. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Mehta LS, Watson KE, Barac A, et al. Cardiovascular disease and breast cancer: where these entities intersect: a scientific statement from the American Heart Association. Circulation. 2018;137(8):e30–e66. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Johnson CL, Paulose-Ram R, Ogden CL, et al. National health and nutrition examination survey. Analytic guidelines, 1999–2010. Vital Health Stat. 2013;161:1–24. [PubMed] [Google Scholar]
- 5.Armstrong T, Bull F. Development of the world health organization global physical activity questionnaire (GPAQ). J Public Health. 2006;14(2):66–70. [Google Scholar]
- 6.Henriksen PA. Anthracycline cardiotoxicity: An update on mechanisms, monitoring and prevention. Heart. 2018;104(12):971–977. [DOI] [PubMed] [Google Scholar]
- 7.Mitchell JD, Cehic DA, Morgia M, et al. Cardiovascular manifestations from therapeutic radiation: a multidisciplinary expert consensus statement from the international cardiooncology society. Cardio Oncology. 2021;3(3):360–380. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Darby SC, Ewertz M, McGale P, et al. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med. 2013;368(11):987–998. [DOI] [PubMed] [Google Scholar]
- 9.Bradshaw PT, Stevens J, Khankari N, Teitelbaum SL, Neugut AI, Gammon MD. Cardiovascular disease mortality among breast cancer survivors. Epidemiology. 2016;27(1):6–13. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Patnaik JL, Byers T, DiGuiseppi C, Dabelea D, Denberg TD. 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):1–9. [DOI] [PMC free article] [PubMed] [Google Scholar]