Abstract: Objective To investigate the association between whole blood iron, copper and their interaction with cardiovascular diseases (CVD). Methods A cohort-based case control study was conducted. Cases were 93 males with CVD in the Kailuan cohort who participated in the follow-up in 3 hospitals in 2017-2018. During the same period, 372 males with non-CVD who were 1∶4 individual matched by age and labor type were selected as controls. The concentration of blood iron and copper was determined by inductively coupled plasma mass spectrometry. Conditional logistic regression models were used to estimate the association between blood iron and copper and CVD, respectively and elastic-Net regression models to estimates interaction between the two metals and CVD. Results The whole blood iron concentration in the cases was significantly higher than the controls, while blood copper concentration was lower than the controls (both P＜0.001). After adjusting for age, smoking, drinking, overweight, hypertension, diabetes, anemia, hyperlipidemia, and high sensitivity C-reactive protein, the participants with higher iron increase 3.17 times (OR=4.17, 95% CI: 2.23-7.79, P＜0.001) risk of CVD than those with lower iron, and those with lower copper increase 3.26 times (OR=4.26, 95% CI: 1.73-10.45, P＜0.01) risk than those with the higher copper. Adaptive Elastic-net regression analysis showed that it under the simultaneous exposure of higher iron and lower copper, the risk of CVD with environment risk score ＞0.232 was 8.96 times (OR=8.96, 95% CI: 4.47-17.95, P＜0.001) than the score ≤0.232. Conclusions Higher iron and copper deficiency may be independent risk factors for CVD. Environment risk score could be a good indicator of simultaneous exposure of blood iron and copper, which should have a better predictive value of CVD.

Key words: whole blood iron, whole blood copper, cardiovascular diseases (CVD), case control studies