Association of Raynaud's phenomenon after bleomycin etoposide cisplatin (BEP) chemotherapy for testicular cancer (TC) with accelerated atherosclerosis.

Abstract

4631 Background: Cross-sectional studies showed that treatment with BEP for TC causes a higher rate of cardiovascular disease. We investigated longitudinal changes in clinical and vascular parameters, to explore their role as early biomarkers for accelerated atherosclerosis. Methods: In consecutive TC patients (pts), cardiovascular morbidity, risk factors, plasma markers for endothelial activation (soluble inter cellular adhesion molecule [sICAM-1], von Willebrand factor [vWF]) and inflammation (high sensitivity C reactive protein [hsCRP]), and carotid intima media thickness (IMT; a subclinical atherosclerosis marker) were evaluated twice after BEP completion. Results: 50 pts underwent evaluations median 11 months and 6.5 years after BEP. During follow-up 2% had clinical cardiovascular morbidity; 28% had secondary Raynaud’s phenomenon. sICAM-1 and IMT increased (Table). At 6.5 years, IMT in TC pts equalled healthy males (n=45, median 0.59 mm [0.38-0.97]; p=0.93). In linear regression the age-related IMT increase was higher in TC pts (b=0.09 [SE=0.02], P<0.0001] than controls [b=0.06 [SE=0.02], P=0.003). Changes in IMT related to increases in serum lipids. Pts with Raynaud’s phenomenon had a higher age-related IMT increase (Raynaud: b=0.12 [SE=0.004], P=0.009; no Raynaud: b=0.006 [SE=0.002], P=0.002). Conclusions: Subclinical signs for atherosclerosis increase during follow-up after BEP for TC, with an accelerated age-related IMT progression compared to controls. The relationship between IMT and Raynaud’s phenomenon suggests that this symptom may be a clinical biomarker to identify survivors with augmented atherosclerosis, who may benefit from intervention. 11 months (8-15) 6.5 years (3.2-10.1) Median Range N abnormal Median Range N abnormal Blood pressure Systolic mmHg 125 100–170 3 124 100–180 13 Diastolic 74 60–100 80* 60–105 Body mass index kg/m2 25.3 18.9–38.0 4 25.5 20.2–41.7 7 Cholesterol mmol/L 4.7 3.2–7.8 0 4.8 3.4–7.3 6 Glucose mmol/L 4.7 2.6–5.8 0 5.5* 3.6–7.4 1 sICAM-1 ng/mL 373 159–727 423* 260–823 vWF % 87 52–237 99 37–204 hsCRP mg/L 0.7 0.2–8.9 0.8 0.2–4.7 IMT mm 0.53 0.41–0.90 0.59* 0.44–0.94 * P < 0.05, Wilcoxon signed rank