Table 4.

Risk of cancer therapeutics related cardiac dysfunction (CTRCD) according to baseline levels and changes in arginine-NO metabolite levels

Biomarker (μmol/L)	Baseline (N = 138)†		1 month (N = 124)		2 months (N = 117)
	Adjusted HR‡ (95% CI)	P-value	Adjusted HR‡ (95% CI)	P-value	Adjusted HR‡ (95% CI)	P-value
Arginine	0.93 (0.69, 1.25)	0.61	0.78 (0.64, 0.97)	0.02*	1.23 (0.83, 1.83)	0.29
Citrulline	1.04 (0.58, 1.87)	0.90	0.83 (0.46, 1.50)	0.53	1.35 (0.78, 2.35)	0.28
Ornithine	1.13 (0.74, 1.73)	0.57	1.59 (0.91, 2.77)	0.10	1.70 (0.98, 2.97)	0.06
ADMA	0.77 (0.25, 2.39)	0.65	3.31 (0.88, 12.5)	0.08	3.33 (1.12, 9.96)	0.03*
SDMA	0.61 (0.24, 1.55)	0.30	0.94 (0.39, 2.27)	0.90	0.91 (0.28, 3.01)	0.88
MMA	0.90 (0.53, 1.53)	0.69	0.61 (0.29, 1.27)	0.18	2.70 (1.35, 5.41)	0.005*

Abbreviations: ADMA, asymmetric dimethylarginine; CI, confidence interval; HR, hazard ratio; SDMA, symmetric dimethylarginine; MMA, N-monomethylarginine

^*P<0.05 via the Wald test.

^†This analysis was restricted to the 139 participants with quantitated echocardiography at all time points. 1 participant was dropped from this analysis due to unknown hypertension status.

^‡The estimated hazard ratio (HR) and associated 95% confidence interval (CI) in a model adjusted for treatment regimen, age, race, hypertension, and BMI are shown. Non-baseline models are also adjusted for baseline biomarker value. HRs are shown for the log_1.5-ratio of the biomarker value at baseline relative to the cohort median and the log_1.5-ratio of the biomarker value at 1 and 2 months relative to baseline. HRs can be interpreted as the expected relative increase in the instantaneous risk of CTRCD from a 1.5-fold increase in the biomarker ratio. For example, a 1.5-fold increase in the ADMA level from baseline to 2 months would be expected to lead to a 3.33-fold increase in the rate of CTRCD.