Abstract
Background
Survivors of cancer have elevated risk of cardiovascular disease, likely stemming from the negative impact of anticancer therapies on vascular function. Arterial stiffness is a strong indicator of vascular function and independent predictor of cardiovascular disease. The American Heart Association recommends Life's Essential 8 for optimal cardiovascular health. It is currently unknown, however, whether greater adherence to Life's Essential 8 is associated with low arterial stiffness in survivors of cancer.
Methods and Results
This cross‐sectional study included 172 older adult (≥65 years) survivors of cancer (74±6 years; 58% female). Life's Essential 8 100‐point cardiovascular health score, with higher scores indicative of better cardiovascular health, was calculated based on 8 components: diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipids, blood glucose, and blood pressure. Participants were classified as having low (<60), moderate (60–79), or high (≥80) cardiovascular health. Pulse wave velocity (PWV) was used to assess arterial stiffness; with high arterial stiffness defined as a pulse wave velocity ≥10 m/s. The mean cardiovascular health score was 72±11 and 40 survivors (23%) had high arterial stiffness. Compared with low cardiovascular health, the odds ratio of high arterial stiffness was 0.12 (95% CI, 0.03–0.50) and 0.02 (95% CI, 0.003–0.18) for moderate and high cardiovascular health, respectively. Every 10‐point increase in the cardiovascular health score was associated with a 0.43 m/s reduction in pulse wave velocity (P<0.001).
Conclusions
Greater adherence to the American Heart Association's Life's Essential 8 was associated with lower prevalence of high arterial stiffness in older adult survivors of cancer. Prospective studies with larger samples are needed.
Keywords: aging, ideal health, older adult, pulse wave velocity
Subject Categories: Epidemiology, Lifestyle
Nonstandard Abbreviations and Acronyms
- AHA
American Heart Association
- PWV
pulse wave velocity
Clinical Perspective.
What Is New?
This cross‐sectional study found that survivors of cancer with greater adherence to the American Heart Association's Life's Essential 8 for cardiovascular health have lower prevalence of high arterial stiffness.
What Are the Clinical Implications?
Our study suggests that adhering to the Life's Essential 8 for cardiovascular health is linked to lower arterial stiffness, a key mechanism of cardiovascular disease risk and a potential target to improve cardiovascular health and reduce cardiovascular disease burden in the population of cancer survivors.
The findings of this study shed light on the critical need to educate survivors of cancer on the modifiable health factors and behaviors that could affect their cardiovascular health and future cardiovascular disease risk.
Survivors of cancer have a high risk of cardiovascular disease (CVD), partly stemming from the negative impact of anticancer therapies (eg, chemotherapy) on vascular function. 1 , 2 Arterial stiffness is a key indicator of vascular function that quantifies the stiffening of the vascular wall. 3 Importantly, although arterial stiffness naturally increases with age, the increase in arterial stiffness is exaggerated in individuals with cancer and survivors of cancer. 4 , 5 , 6 The presence of this higher arterial stiffness is detrimental as it negatively affects blood pressure (BP) and blood flow delivery to target organs. 3 Indeed, higher arterial stiffness is associated with CVD morbidity and mortality in the general population 7 and survivors of cancer. 8 , 9 Given the strong association between cancer, arterial stiffness, and CVD risk, it is imperative to identify behavioral means of attenuating or preventing increases in arterial stiffness in survivors of cancer to reduce CVD risk in this high‐risk population.
The American Heart Association (AHA) recommends Life's Essential 8 for greater cardiovascular health, 10 which is associated with lower all‐cause and CVD‐specific mortality 11 , 12 and a longer life expectancy free of major chronic disease. 13 , 14 Optimal cardiovascular health is achieved by adhering to 4 ideal health behaviors (diet, physical activity, avoidance of nicotine exposure, and sleep) and achieving optimal levels of 4 ideal health factors (body mass index [BMI], blood lipids, glucose, and BP). Adhering to the AHA Life's Simple 7, a similar cardiovascular health metric that does not include sleep health, has previously been associated with lower arterial stiffness in the general population. 15 , 16 In survivors of cancer, however, it is unclear whether optimal health behaviors, such as adherence to the AHA Life's Essential 8, can beneficially modulate arterial stiffness following the direct effect of anticancer therapy on the vasculature. Additionally, cancer diagnoses and anticancer therapy may indirectly affect diet, physical activity, and other health behaviors 17 , 18 that may uncouple or attenuate the relationship between behavior and arterial stiffness. The purpose of this study was to investigate the association between adherence to the AHA Life's Essential 8 and arterial stiffness in older adult survivors of cancer, a population more susceptible to arterial stiffening. We hypothesized that greater adherence to Life's Essential 8 would be associated with lower prevalence of high arterial stiffness.
METHODS
Study Population
The PAAS (Physical Activity and Aging Study) is an ongoing prospective cohort study of men and women at least 65 years of age. Since 2015, 981 older adults have completed at least 1 examination involving questionnaires and measurement of physical activity, body composition, physical function, and muscular strength. Only participants with a history of cancer were included in the present study (n=230). Among these individuals, 14 were excluded for missing data for the cardiovascular health score and covariates, and 44 were excluded for missing arterial stiffness assessment. The resulting final sample was 172 survivors of cancer. All participants provided written informed consent and the study was approved by the Iowa State University institutional review board (15–430). The data that support the findings of this study are available from the corresponding author upon reasonable request.
Cardiovascular Health Score
The cardiovascular health score was computed following the guidelines set forth by the AHA. 10 Each of the 8 components of the cardiovascular health score was allocated a score of 0 (nonideal) to 100 (ideal), and the average of all 8 components became the overall cardiovascular health score.
In the current study, diet was assessed using the Dietary Screening Tool and scored following standard procedures. 19 Scores on the Dietary Screening Tool range from 0 to 100, with 5 bonus points available for the use of a dietary supplement. Quantiles were then formed (1st–24th, 25th–49th, 50th–74th, 75–94th, and 95th–100th) from the data following AHA recommendations and assigned scores of 0, 25, 50, 80, and 100 points, respectively. The Dietary Screening Tool is significantly correlated with the Healthy Eating Index suggested by the AHA and no consistent bias appears between the 2 dietary assessments. 20
Physical activity levels were determined using the International Physical Activity Questionnaire. 21 Frequency per week and duration of each session were recorded for both moderate and vigorous physical activity. Physical activity time was classified as 0, 1 to 29, 30 to 59, 60 to 89, 90 to 119, 120 to 149, and ≥150 minutes per week, corresponding to 0, 20, 40, 60, 80, 90, and 100 points, respectively.
Nicotine exposure was assessed from 3 self‐report questions: Have you ever smoked at least 100 cigarettes in your lifetime?, Do you currently smoke cigarettes?, and How many years ago did you stop smoking cigarettes? These questions were used to classify individuals into 5 categories including current smoker, former smoker (quit <1 year), former smoker (quit 1 to <5 years), former smoker (quit ≥5 years), and never smoker, corresponding to 0, 25, 50, 80, and 100 points, respectively. Data were not available for secondhand smoke exposure.
The average self‐reported duration of sleep per day was obtained from the Pittsburgh Sleep Quality Index. Sleep hours/night were classified as <4, 4 to <5, 5 to <6, 6 to <7, 7 to <9, and 9 to <10 hours, corresponding to 0, 20, 40, 70, 90, and 100 points, respectively.
Weight measured in kilograms and height in meters were used to calculate BMI. BMI was classified as ≥40.0, 35.0 to 39.9, 30.0 to 34.9, 25.0 to 29.9, and <25.0 kg/m2, corresponding to 0, 15, 30, 80, and 100 points, respectively.
Non‐high‐density lipoprotein cholesterol was obtained from a fasted blood sample. Non‐high‐density lipoprotein cholesterol was classified as ≥220, 190 to 219, 160 to 189, 130 to 159, and <130 mg/dL, corresponding to 0, 20, 40, 60, and 100 points, respectively. If participants self‐reported use of lipid‐lowering medication, 20 points were deducted from the score.
Blood glucose levels were obtained from a fasted blood sample and HbA1c was estimated as (glucose +46.7)/28.7. 22 Participants also self‐reported physician‐diagnosed diabetes. Using fasting glucose, hemoglobin A1c (HbA1c) and diabetes diagnosis, participants were classified into the following groups diabetes with HbA1c≥10%, diabetes with HbA1c of 9.0% to 9.9%, diabetes with HbA1c of 8.0% to 8.9%, diabetes with HbA1c of 7.0% to 7.9%, diabetes with HbA1c <7.0%, no diabetes and fasting glucose 100 to 125 mg/dL, and no diabetes and fasting glucose <100 mg/dL, corresponding to 0, 10, 20, 30, 40, 60, and 100 points, respectively.
Brachial BP was measured using an appropriately sized cuff in the seated position, averaging at least 3 assessments separated by at least 2 minutes. BP was classified as systolic BP (SBP) ≥160 mm Hg or diastolic BP (DBP) ≥100 mm Hg; SBP 140 to 159 or DBP 90 to 99 mm Hg; SBP 130 to 139 or DBP 80 to 89 mm Hg; SBP 120 to 129 and DBP <80 mm Hg; and SBP <120 and DBP <80 mmHg, corresponding to 0, 25, 50, 75, and 100 points, respectively. If participants self‐reported use of a BP lowering medication, 20 points were deducted from the score.
The total cardiovascular health score was calculated as the average of all 8 individual cardiovascular health metric scores. Study participants with a cardiovascular health score <60 were classified as low cardiovascular health, those who scored 60 to 79 were classified as moderate cardiovascular health, and those who scored ≥80 were classified as high cardiovascular health.
Arterial Stiffness
Carotid‐femoral pulse wave velocity (PWV) is a gold standard noninvasive assessment of arterial stiffness. 23 In brief, applanation tonometry and a leg cuff were used to simultaneously collect the carotid and femoral BP waveforms, respectively (SphygmoCor XCEL, AtCor Medical, Naperville, IL, USA). 24 PWV was calculated as the transit distance between the carotid and femoral sites divided by the transit time. At least 2 PWV measurements were performed, and if the first 2 differed by more than 0.5 m/s, a third measurement was taken. The median PWV value was used for analysis. High arterial stiffness was defined as a PWV ≥10 m/s. 23 , 25
Statistical Analysis
Descriptive characteristics are reported across the 3 cardiovascular health categories (low, moderate, and high). The 3 categories were compared using chi‐square analysis for categorical variables and general linear models for continuous variables. Logistic regression models were used to estimate odds ratios (ORs) and 95% CIs of higher arterial stiffness across the 3 categories, with low cardiovascular health as the reference group. Linear trends were determined using the cardiovascular health group as a linear variable within the logistic regression models. The dose–response association was further investigated in 10‐point increments in the cardiovascular health score. Linear regression models were used to examine the association between 10‐point increments in the cardiovascular health score and continuous PWV. Logistic and linear regression models included the following covariates: sex, age (years), heavy alcohol consumption (>7 drinks per week for women, >14 drinks per week for men), education, income, and mean arterial pressure (MAP), calculated from brachial BP as (SBP+2*DBP)/3. MAP was included in the model as a representation of distending pressure on the vasculature to understand if the relationship between the cardiovascular health score and arterial stiffness remained independent of the direct effect of MAP on arterial stiffness.
Sensitivity analyses were run following the AHA recommended cut‐points for the cardiovascular health score, comparing AHA‐defined high cardiovascular health (≥80) to the combined AHA‐defined low (<50) and AHA‐defined moderate (50–79) cardiovascular health scores. 10 Our sample contained only 3 survivors of cancer classified as AHA‐defined low cardiovascular health (2 with high PWV) using the cut‐point of <50, thus not sufficient to serve as the reference group in logistic regression and therefore combined with the moderate cardiovascular health group. We further ran sensitivity analyses to account for the strong relationship between BP and arterial stiffness. We repeated our analyses (1) replacing adjustment for MAP with heart rate; (2) additionally controlling for the presence of hypertension (yes/no), (3) excluding the BP component from the cardiovascular health score; and (4) removing individuals with overt CVD (myocardial infarction, stroke, heart failure) from the analyses. A sensitivity analyses was also performed to examine the robustness of the results after removal of individuals with a prior diagnosis of only melanoma in which only the linear regression was performed due to insufficient numbers for the logistic regression. SAS software (version 9.4) was used for all statistical analyses and a 2‐sided P value <0.05 was deemed statistically significant.
RESULTS
Among 172 older men and women with a history of cancer, we observed 40 cases (23%) of high arterial stiffness. Low, moderate, and high cardiovascular health scores were observed in 13.4%, 57.5%, and 29.0% of the sample, respectively. Descriptive characteristics by cardiovascular health group are presented in Table 1. Cardiovascular health groups were not different in age, sex distribution, and years since diagnosis of cancer. The distribution of the AHA Life's Essential 8 component scores among survivors of cancer with low and high PWV are presented in the Figure. The greatest percentages of low cardiovascular health scores by individual component were observed for BP and diet.
Table 1.
Characteristics of Participants by Categories of Life's Essential 8 Cardiovascular Health Scores
| Characteristic | All | Low (<60) | Moderate (60–79) | High (≥80) | P value |
|---|---|---|---|---|---|
| No. | 172 | 23 | 99 | 50 | |
| Age, y | 74±6 | 74±6 | 74±6 | 75±7 | 0.43 |
| Female sex, n (%) | 99 (57.6) | 14 (60.9) | 51 (51.5) | 34 (68.0) | 0.15 |
| Race or ethnicity | |||||
| Non‐Hispanic White, n (%) | 165 (95.9) | 23 (100.0) | 94 (94.9) | 48 (96.0) | 0.37 |
| Hispanic, n (%) | 1 (0.6) | 0 (0.0) | 0 (0.0) | 1 (2.0) | |
| Other, n (%)* | 6 (3.4) | 0 (0.0) | 5 (5.1) | 1 (2.0) | |
| Cancer type | |||||
| Genitourinary, n (%) | 22 (12.8) | 2 (8.7) | 15 (15.2) | 5 (10.0) | 0.55 |
| Thoracic, n (%) | 5 (2.9) | 1 (4.4) | 3 (3.0) | 1 (2.0) | 0.85 |
| Gastrointestinal, n (%) | 10 (5.8) | 2 (8.7) | 7 (7.1) | 1 (2.0) | 0.37 |
| Hematological, n (%) | 12 (7.0) | 3 (13.0) | 7 (7.1) | 2 (4.0) | 0.37 |
| Gynecological, n (%) | 9 (5.2) | 1 (4.4) | 7 (7.1) | 1 (2.0) | 0.41 |
| Breast, n (%) | 44 (25.6) | 4 (17.4) | 22 (22.2) | 18 (36.0) | 0.12 |
| Melanoma, n (%) | 67 (39.0) | 9 (39.1) | 37 (37.8) | 21 (42.0) | 0.88 |
| Other, n (%) | 31 (18.0) | 5 (21.7) | 17 (17.2) | 9 (18.0) | 0.88 |
| Number of cancers | |||||
| 1, n (%) | 148 (86.1) | 20 (86.7) | 84 (84.9) | 44 (88.0) | 0.74 |
| 2, n (%) | 21 (12.2) | 2 (8.7) | 14 (14.1) | 5 (10.0) | |
| 3+, n (%) | 3 (1.7) | 1 (4.4) | 1 (1.0) | 1 (2.0) | |
| Years since diagnosis (n=149) | 13±12 | 10±9 | 14±12 | 11±11 | 0.19 |
| Pulse wave velocity, m/s | 8.7±1.9 | 9.8±1.7 | 8.9±1.8 | 7.8±1.6 | <0.001 |
| Heavy alcohol drinking, n (%)† | 15 (8.7) | 1 (4.4) | 9 (9.1) | 5 (10.0) | 0.71 |
| Educational attainment | |||||
| High school, n (%) | 23 (13.4) | 7 (30.4) | 11 (11.1) | 5 (10.0) | 0.07 |
| Associate/technical degree, n (%) | 15 (8.7) | 4 (17.4) | 7 (7.1) | 4 (8.0) | |
| Bachelor's degree, n (%) | 55 (32.0) | 3 (13.0) | 34 (34.3) | 18 (36.0) | |
| Graduate/professional degree, n (%) | 79 (46.0) | 9 (39.1) | 47 (47.5) | 23 (46.0) | |
| Income | |||||
| $12000–$24 999, n (%) | 5 (2.9) | 1 (4.4) | 3 (3.0) | 1 (2.0) | 0.04 |
| $25000–$49 999, n (%) | 28 (16.3) | 6 (26.1) | 18 (18.2) | 4 (8.0) | |
| $50000–$74 999, n (%) | 42 (24.4) | 8 (34.8) | 21 (21.2) | 13 (26.0) | |
| $75000–$99 999, n (%) | 42 (24.4) | 7 (30.4) | 18 (18.2) | 17 (34.0) | |
| ≥$100 000, n (%) | 55 (312.0) | 1 (4.4) | 39 (39.3) | 15 (30.0) | |
| Dietary screening tool score | 63±11 | 57±11 | 60±10 | 71±7 | <0.001 |
| Moderate‐to‐vigorous intensity physical activity, min/wk | 304±299 | 182±244 | 319±320 | 330±266 | 0.10 |
| Smoking | |||||
| Current, n (%) | 3 (1.7) | 1 (4.4) | 2 (2.0) | 0 (0.0) | 0.07 |
| Former, n (%) | 45 (26.1) | 10 (43.5) | 27 (27.3) | 8 (16.0) | |
| Never, n (%) | 124 (72.0) | 12 (52.2) | 70 (70.7) | 42 (84.0) | |
| Sleep time, h/night | 7.2±1.1 | 6.5±1.4 | 7.2±1.1 | 7.3±0.8 | 0.01 |
| BMI, kg/m2 | 27.5±4.6 | 31.6±4.0 | 28.4±4.2 | 23.9±3.1 | <0.001 |
| Non‐HDL cholesterol, mg/dL | 127±38 | 140±45 | 125±36 | 124±39 | 0.19 |
| Total cholesterol, mg/dL | 184±43 | 192±45 | 180±41 | 190±46 | 0.26 |
| Low‐density lipoprotein cholesterol, mg/dL | 105±34 | 110±34 | 102±33 | 105±37 | 0.67 |
| HDL cholesterol, mg/dL | 57±17 | 52±16 | 55±15 | 65±17 | 0.001 |
| Antihypercholesterolemia medication, n (%) | 82 (47.7) | 14 (60.9) | 51 (51.5) | 17 (34.0) | 0.05 |
| Fasting glucose, mg/dL | 99±18 | 115±27 | 101±16 | 90±8 | <0.001 |
| Antidiabetic medication, n (%) | 18 (10.5) | 7 (30.4) | 11 (11.1) | 0 (0.0) | 0.001 |
| Systolic BP, mm Hg | 130±17 | 140±14 | 132±17 | 121±14 | <0.001 |
| Diastolic BP, mm Hg | 74±10 | 75±10 | 76±10 | 70±8 | 0.002 |
| Antihypertensive medication, n (%) | 60 (34.9) | 11 (47.8) | 39 (39.4) | 10 (20.0) | 0.02 |
| Life's Essential 8 Score, a.u. | 72±11 | 55±4 | 70±5 | 85±4 | <0.001 |
| Diet score, a.u. | 43±32 | 25±23 | 34±29 | 68±25 | <0.001 |
| Physical activity score, a.u. | 86±27 | 64±38 | 88±26 | 93±16 | <0.001 |
| Nicotine exposure score, a.u. | 92±16 | 85±22 | 91±17 | 96±9 | 0.02 |
| Sleep time score, a.u. | 88±20 | 75±28 | 88±19 | 94±15 | 0.001 |
| BMI score, a.u. | 67±29 | 39±22 | 62±28 | 89±16 | <0.001 |
| Lipid score, a.u. | 69±26 | 60±33 | 68±24 | 73±25 | 0.14 |
| Glucose score, a.u. | 82±24 | 56±23 | 81±24 | 96±12 | <0.001 |
| Blood pressure score, a.u. | 53±33 | 33±29 | 48±32 | 73±28 | <0.001 |
Data presented as mean±SD or n (%). a.u. indicates arbitrary unit; BMI, body mass index; BP, blood pressure; and HDL, high‐density lipoprotein.
Heavy alcohol drinking >7 drinks/week for women and >14 drinks/week for men.
Other includes more than 1 race, or undisclosed race or ethnicity.
Figure 1. Distribution of low, moderate, and high cardiovascular health scores within each of AHA Life's Essential 8 components in survivors of cancer with low (n=132, <10 m/s) and high (n=40, ≥10 m/s) PWV.
Values within each bar correspond to the number of survivors of cancer with that respective score category (eg, 99 survivors with low PWV received a sleep score corresponding to high cardiovascular health). AHA indicates American Heart Association; BMI, body mass index; and PWV, pulse wave velocity.
As shown in Table 2, compared with participants with low cardiovascular health, participants with moderate and high cardiovascular health had lower odds of high arterial stiffness with OR of 0.16 (95% CI, 0.05–0.55, P=0.004) and 0.03 (95% CI, 0.01–0.14, P=<0.001), respectively, after adjustment for potential confounders (Model 2). The significant relationship remained even after further adjustment for MAP (Model 3, P<0.001). The OR for high arterial stiffness per 10‐point increase in cardiovascular health score was 0.41 (95% CI, 0.24–0.70, P=0.001) after controlling for potential confounders and MAP (Model 3). In additional linear regression analyses, a 10‐point increase in the Life's Essential 8 Cardiovascular Health Score was associated with a reduction in PWV of 0.43 m/s (95% CI, −0.65 to −0.21, P<0.001) after adjusting for age, sex, heavy alcohol drinking, education, income, and MAP (R2=0.47; F (7, 164)=20.97; P=<0.001).
Table 2.
Associations of Life's Essential 8 Cardiovascular Health Score With High Arterial Stiffness
| Cardiovascular health score | n | Cases (%) | Odds ratio (95% CI) | ||
|---|---|---|---|---|---|
| Model 1* | Model 2† | Model 3‡ | |||
| Low (<60) | 23 | 12 (52.2) | 1.00 (Ref) | 1.00 (Ref) | 1.00 (Ref) |
| Moderate (60–79) | 99 | 24 (24.2) | 0.20 (0.07–0.59) | 0.16 (0.05–0.55) | 0.12 (0.03–0.50) |
| High (≥80) | 50 | 4 (8.0) | 0.04 (0.01–0.18) | 0.03 (0.01–0.14) | 0.02 (0.003–0.18) |
| P value for linear trend | <0.001 | <0.001 | <0.001 | ||
| Per 10‐unit increase | 0.38 (0.24–0.60) | 0.35 (0.21–0.57) | 0.41 (0.24–0.70) | ||
Model 1 was adjusted for sex and age.
Model 2 was adjusted for Model 1 plus heavy alcohol drinking, education, and income.
Model 3 was adjusted for Model 2 plus mean arterial pressure.
Our sensitivity analysis revealed similar strong associations between high cardiovascular health and lower odds of high arterial stiffness with OR of 0.12 (95% CI, 0.03–0.43 P=0.001) compared with combined low and moderate cardiovascular health according to the AHA‐defined cut‐points, which remained significant after further adjustment for MAP (OR, 0.15 [95% CI, 0.03–0.64], P=0.01). Further, results were similar when adjusting for heart rate instead of MAP in Model 3 (P<0.001); and after excluding the 16 participants with a history of CVD, similar results were observed with lower odds of having high arterial stiffness for participants with moderate (OR, 0.10 [95% CI, 0.02–0.45], P=0.003) and high (OR, 0.01 [95% CI, 0.001–0.12], P=<0.001) cardiovascular health compared with low cardiovascular health, after adjusting for potential confounders and MAP. When additionally adjusting for the presence of hypertension, results remained similar with lower odds of high arterial stiffness for participants with moderate OR, 0.13 [95% CI, 0.03–0.55], P=0.005) and high (OR, 0.03 [95% CI, 0.003–0.20], P=0.001) cardiovascular health compared with low cardiovascular health after adjusting for other potential confounders. In the sensitivity analysis removing BP from the overall score, there was a slight attenuation of the results, with the OR (of high arterial stiffness 0.54 (95% CI, 0.13–2.30, P=0.40) and 0.20 (95% CI, 0.04–0.98, P=0.046) for participants with moderate and high cardiovascular health, respectively, compared with those with low cardiovascular health after adjusting for potential confounders (Model 2). After further adjustment for MAP, the high cardiovascular health group remained significant (OR, 0.10 [95% CI, 0.02–0.68], P=0.02). Upon removal of individual with a prior diagnosis of only melanoma, our linear regression analyses showed consistent results with every 10‐point increase in the cardiovascular health score associated with a 0.64 m/s reduction in PWV (P<0.001) after adjustment for potential confounders and MAP (R2=0.52; F (7,103)=15.78; P=<0.001).
DISCUSSION
In this cohort of 172 older adult survivors of cancer, we observed that having a moderate or high cardiovascular health score was associated with lower prevalence of high arterial stiffness, even after adjustment for MAP. Further, for every 10‐point increase in cardiovascular health scores, we observed a 0.43 m/s lower PWV. These findings suggest that adhering to the AHA Life's Essential 8 for cardiovascular health is linked to lower arterial stiffness, a key mechanism of CVD risk and a potential target to improve cardiovascular health and reduce CVD burden in the population of survivors of cancer, although these results should be confirmed by prospective studies with larger samples.
To our knowledge, this is the first study to evaluate the associations of cardiovascular health defined using the AHA Life's Essential 8 metric with high arterial stiffness in survivors of cancer. We observed significant reductions in the prevalence of high arterial stiffness both by categories of cardiovascular health score and per 10‐point increase in the overall score. The results are consistent with the few prior studies observing associations between cardiovascular health scores and arterial stiffness in the general population. In a 2019 study by Oyenuga et al., 16 lower AHA Life's Simple 7 scores (excluded sleep behavior scoring) in middle‐aged adults were associated with greater arterial stiffening assessed via carotid‐femoral PWV 20 to 30 years later. Crichton et al. 15 show carotid‐femoral PWV decreases in a linear manner across cardiovascular health categories using AHA Life's Simple 7 in 505 adults in the Maine‐Syracuse Longitudinal Study and that individuals with at least 5 health metrics at ideal levels had lower PWV than those with 2 or fewer ideal health metrics (9.8 m/s versus 11.8 m/s). Although not assessing central arterial stiffness via PWV explicitly, several other studies also observe a beneficial effect of greater cardiovascular health with lower brachial‐ankle PWV and other metrics of vascular health in the general population, 26 , 27 , 28 , 29 , 30 and improvement in cardiovascular health scores is associated with lower PWV. 31 , 32 The present study has expanded on the benefits of following the AHA Life's Essential 8 for greater arterial health by showing that adherence is associated with lower prevalence of high arterial stiffness in older adult survivors of cancer, a critical at‐risk population for CVD.
In patients with cancer or survivors, arterial stiffening is associated with greater CVD and all‐cause mortality. 8 , 9 The greater arterial stiffness often observed in this population is likely due to the impact of the anticancer therapy on the vasculature. 4 , 5 , 6 Anticancer therapy elicits increases in oxidative stress and inflammation, which acts on the vasculature by impairing endothelial function and promoting arterial stiffening. 33 However, in the general population, many components of the AHA Life's Essential 8 score for cardiovascular health are linked to arterial stiffness. For example, greater control of health factors such as BP, 34 glucose, 35 and BMI 36 is associated with lower arterial stiffness. Similarly, within the health behaviors, the Mediterranean‐style diet, 37 greater physical activity, 38 and nonsmoking 39 are associated with lower arterial stiffness. The associations between the individual factors and arterial stiffness in summation likely contribute to the associations observed in the present study, even after the removal of BP from the overall score. Thus, many of the factors within the AHA Life's Essential 8 cardiovascular health score could serve as targets for future prospective and interventional studies to improve arterial stiffness and lower CVD risk in the population of survivors of cancer.
The results of the present investigation are of high clinical relevance, suggesting adhering to the cardiovascular health metrics could lower the prevalence of high arterial stiffness. First, data suggest improving cardiovascular health scores is associated with lower prevalence of various CVDs. 32 When investigating the relationship between cardiovascular health and stroke risk, arterial stiffness mediates 9% of this relationship, 29 supporting the mechanistic role of arterial stiffness in the relationship between ideal cardiovascular health and subsequent CVD risk. Thus, the lower arterial stiffness could have potent implications on future CVD and all‐cause mortality risk. In the general population, every 1 m/s increase in PWV is associated with a 14%, 15% and 15% greater risk of a CVD event, CVD mortality, and all‐cause mortality, respectively. 40 In our sample of survivors of cancer, every 10‐point increase in the cardiovascular health score was associated with a 0.43 m/s lower PWV. Improving the cardiovascular health score by 10 points requires modest lifestyle changes, for example, increasing physical activity by 30 minutes/week or increasing sleep duration by 1 hour if averaging <7 hours per night, which may elicit appreciable improvements in cardiovascular risk. Second, our study highlights the critical need for patient education about the modifiable health behaviors and risk factors. Although varying among different types of cancer, only ~29% to 47% of survivors of cancer meet physical activity recommendations and only ~15% to 18% meet dietary recommendations. 17 Further, many survivors of cancer do not incorporate favorable lifestyle changes following diagnosis 18 despite specific physical activity and dietary recommendations for this population provided by the American Cancer Society. 41 This may partially be attributable to the low prevalence of physician recommendations to improve these behaviors 42 and reflected by many survivors stating lack of knowledge and information about healthy lifestyle behaviors (ie, physical activity and diet) as a barrier to lifestyle change. 18 Our findings suggest survivors of cancer have poor dietary habits and lower cardiovascular health scores are observed for the 4 cardiovascular health factors (BP, glucose, BMI, and lipids), similar to prior studies. 43 Thus, monitoring and targeting cardiovascular health factors may be of highest importance for physicians to have long‐term impact on cardiovascular health in this population. Additionally, health behaviors are potentially more modifiable in the short term and can have positive subsequent impact on the health factors. Promotion of adherence to physical activity and dietary recommendations, as well as monitoring health factors, by physicians may help improve cardiovascular health in survivors of cancer. However, future prospective studies in survivors of cancer specifically are warranted to determine the magnitude of benefit of greater cardiovascular health and each of its independent components on lowering CVD risk and potential mechanisms.
The strengths of the present study are the use of the AHA Life's Essential 8 to assess cardiovascular health that includes the metric of sleep, in comparison to prior studies using AHA Life's Simple 7, and application to the population of survivors of cancer. However, our study has some limitations. First, this study is cross‐sectional, thus causal inference cannot be made, and we do not have data available on types of anticancer therapies participants received to perform further sensitivity analyses. Second, our cohort of survivors of cancer had a small number of individuals with low cardiovascular health, which may reflect the lack of diversity in our cohort of older adults who are largely White, highly educated, and living independently. Third, although common among studies evaluating AHA cardiovascular health scores, the health behaviors are self‐report (physical activity, sleep, diet, and nicotine exposure), thus there is an inherent risk of inaccuracy. For example, our participants appear to have higher physical activity levels in comparison to other populations. 16 Additionally, time since the diagnosis may affect the results. 44 In the 149 participants with year of diagnosis data, including time since diagnosis did not significantly alter our results (R2=0.47, F (8,140)=15.7, P=<0.001), with an estimated PWV increase of 0.002 m/s per year since diagnosis (P=0.82). Further stratified analyses of <5 years or ≥5 years since diagnosis revealed no significant interaction term (P=0.19) or group effect (P=0.15) for the odds of high PWV by cardiovascular health status. Thus, time since diagnosis does not appear to have large impact in the present data set. Last, our results can be generalized only to older adult survivors of cancer. Future analyses are required looking at survivors of different age ranges or by specific cancer or treatment types.
CONCLUSIONS
Greater adherence to the AHA Life's Essential 8 for cardiovascular health in this older adult cohort of survivors of cancer is strongly associated with lower prevalence of high arterial stiffness. However, prospective studies are needed to confirm the causal association between adhering to the AHA recommendations for cardiovascular health and arterial stiffness in this at‐risk population of survivors of cancer.
Sources of Funding
None.
Disclosures
None.
Acknowledgments
The authors thank the Physical Activity and Aging Study participants and all research staff at Iowa State University for data collection, entry, and management.
This article was sent to Tiffany M. Powell‐Wiley, MD, MPH, Associate Editor, for review by expert referees, editorial decision, and final disposition.
For Sources of Funding and Disclosures, see page 8.
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