Effect of cytochrome P4502C19(CYP2C19)gene polymorphism and clopidogrel reactivity on long term prognosis of patients with coronary heart disease after PCI

Objective To investigate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity and its association with longterm clinical outcome in patients with coronary heart disease(CHD)undergoing percutaneous coronary intervention(PCI).Methods In total,675 patients were enrolled.Based on the platelet inhibition rate,patients were categorized into two groups:clopidogrel low responsiveness(CLR)and normal clopidogrel responsiveness(NCR).The CLR group was divided into ticagrelor and clopidogrel group based on the antiplatelet drugs used in the follow-up treatment.Patients were classified into three groups(normal metabolizer,intermediate metabolizer,and poor metabolizer)based on the CYP2C19 genotype.We aimed to evaluate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity.The cumulative rates of 12-month all-cause deaths,major adverse cardiovascular events(MACCEs),and bleeding events were calculated.Results CLR was observed in 44.4%of the overall population.Significant differences were observed in the platelet inhibition rate of clopidogrel among the three metabolic genotypes(P<0.05).At the 12-month follow-up,13 patients(1.9%)died and 96 patients(14.2%)experienced MACCEs.Patients with CLR(9.6%vs.11.7%vs.22.1%,P<0.05)or poor metabolizer(10.7%vs.16.4%vs.22.6%,P=0.026)experienced a higher rate of MACCEs.A MACCEs risk score between zero and two was calculated.The highest incidence of MACCEs significantly increased with the 2-positive results,and the area under the curve(AUC)was 0.712(95%CI:0.650-0.774,P<0.05).There was no significant difference between the group with a score of one and the occurrence of MACCEs(P>0.05).Conclusions Low response to clopidogrel in CHD patients is correlated with CYP2C19 gene polymorphism.CYP2C19 genotyping combined with platelet reactivity is an independent predictor of 12-months MACCEs in patients with clopidogrel treatment after PCI,which is better than either test alone.

The relation between serum phosphorus levels and long-term mortality in Chinese patients with ST-segment elevation myocardial infarction

Background Elevated serum phosphorus levels may be associated with adverse outcomes in cardiovascular disease. This study aimed to investigate the relation between serum phosphorus levels and risk of all-cause mortality in Chinese patients with ST-segment elevation myocardial infarction (STEMI) who had preserved renal function at baseline. Methods We enrolled patients with STEMI who had preserved renal function at baseline in Xuanwu Hospital from January 2011 to December 2016. Those patients were divided into four groups based on serum phosphorus levels. All-cause mortality rates were compared between groups. Mean duration of follow up was 54.6 months. We used Cox proportional-hazards models to examine the relation between serum phosphorus levels and all-cause mortality after adjustment for potential confounders. Results 1989 patients were involved and 211 patients (10.6%) died during follow-up. Based on serum phosphorus levels, patients were categorized into the following groups:< 2.50 mg/dL (n = 89), 2.51–3.50 mg/dL (n = 1066), 3.51–4.50 mg/dL (n = 672) and > 4.50 mg/dL (n = 162), respectively. The lowest mortality occurred in patients with serum phosphorus levels between 2.51–3.50 mg/dL, with a multivariable-adjusted hazard ratio of 1.19 (95% CI: 0.64–1.54), 1.37 (95% CI: 1.22–1.74), and 1.46 (95% CI: 1.35–1.83) in patients with serum phosphorus levels of < 2.50 mg/dL, 3.51–4.50 mg/dL and > 4.50 mg/dL, respectively. Conclusions Elevated serum phosphorus levels were associated with all-cause mortality in Chinese patients with STEMI who had preserved renal function at baseline.