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Page 6 of 12 Baker et al. J Cancer Metastasis Treat 2020;6:24 I http://dx.doi.org/10.20517/2394-4722.2020.36

Table 2. Patient frequency of abnormal readings at baseline, 12 months, and 24 months after enrollment
Variable Normal Range Abnormal (%), Baseline Abnormal (%), 12M Abnormal (%), 24M
2
BMI (kg/m ) ≤ 30 28% (17/60) 18% (6/34) 27% (6/22)
ALT (IU/L) ≤ 30 35% (18/52) 23% (7/31) 14% (3/21)
AST (IU/L) ≤ 35 10% (5/52) 6% (2/31) 5% (1/21)
LDL (mg/L) ≤ 135 9% (5/58) 6% (2/33) 10% (2/21)
HDL (mg/L) ≥ 40 15% (9/59) 3% (1/33) 10% (2/21)
Total cholesterol (mg/dL) ≤ 200 19% (11/59) 21% (7/33) 19% (4/21)
Triglycerides (mg/dL) ≤ 200 15% (9/59) 6% (2/33) 29% (6/21)
hsCRP (mg/L) ≤ 2 51% (29/57) 61% (20/33) 57% (12/21)
Glucose (mg/dL) ≤ 100 20% (12/59) 18% (6/33) 52% (11/21)
Creatinine (mL/min) ≥ 88 45% (26/58) 41% (14/34) 43% (9/21)
SBP (mmHg) ≤ 130 28% (17/61) 32% (11/34) 45% (10/22)
DBP (mmHg) ≤ 80 13% (8/61) 9% (3/34) 14% (3/22)

BMI: body mass index; ALT: alanine aminotransferase; AST: aspartate aminotransferase; LDL: low-density lipoprotein cholesterol;
HDL: high-density lipoprotein cholesterol; hsCRP: high-sensitivity C-reactive protein; SBP: systolic blood pressure; DBP: diastolic blood
pressure

was 42 years (range 18-82). Twenty-eight patients (46%) were between the ages of 18 and 39 at the time
of the first clinic visit and 64% (n = 39) were diagnosed at age 39 years or younger. All patients received
doxorubicin adjuvant chemotherapy (by definition of our study population), 89% had cancer surgery, and
49% received external radiation (adjuvant, neoadjuvant). The median number of years between diagnosis
and baseline visit was 15 years (range 4-42).

Laboratory measurements taken at each visit (baseline, one year, and two years) that fell outside the
corresponding reference range and were therefore considered abnormal are summarized in Table 2.
Excluding missing values, the measurements with the largest percentage of abnormal values were hsCRP,
with 51% (29/57) having a measurement of 2.0 mg/L or greater at baseline, and creatinine clearance, with
45% (25/55) having a measurement below 88 mL/min. Among the patients with a 1-year (12-month) or
2-year (24-month) visit, the percentages of abnormal hsCRP measurements increased slightly to 61 and
57%, respectively, and the percentages of abnormal creatinine clearance measurements increased slightly to
48 and 47%, respectively.

Figures 1 and 2 plot the baseline distribution of risk factors for major cardiovascular events, stratified by
age group. From Figure 1, 16 (26%) patients had at least three risk factors, and 30 (49%) had at least two.
Nineteen patients aged 40 or older (58%) had at least two CVD risk factors identified, and 12 (36%) had three
or more risk factors. In 9 out of these 12 patients, one of the contributing risk factors was hsCRP ≥ 2.0 mg/L.
Among patients aged 18-39, 11 (39%) had at least two CVD risk factors identified, and four (14%) patients
had three or more risk factors. In all four of these patients, one of the contributing risk factors was hsCRP ≥
2.0 mg/L. Figure 2 indicates that the prevalence of high BMI, high total cholesterol, and type 2 diabetes was
comparable between patients aged 18-39 and ≥ 40. Among patients aged 18-39, hypertension was present in
4 (14%) patients. The biomarker hsCRP, indicative of inflammation and a recognized CAD risk enhancer ,
[20]
was recorded in 26 patients aged 18-39; in 10 of these patients (38%), it was measured at levels > 2 mg/dL,
and in 6 patients (23%), it was measured at levels > 10 mg/dL, presented in Figure 3.

DISCUSSION
Retrospective cohort studies of childhood cancer survivors have shown that exposure to anthracycline
chemotherapy and external radiation that included the heart in the field at a young age are compounded
[5,7]
by conventional risk factors, such as obesity, hypertension, and lipid disorders . A retrospective study of
adult cancer survivors similarly identified poorer overall survival for patients who subsequently developed
CVD as well as a relationship between therapeutic exposure and the development of CVD . Our cohort
[31]