Research Project 1 Background. The incremental predictive value of high inflammatory status and high on-treatment platelet reactivity (HPR) on the occurrence of periprocedural myocardial infarction (PMI) after percutaneous coronary intervention (PCI) has not been characterized. Methods. 500 PCI patients (pts) treated with clopidogrel had preprocedural measurement of CRP levels and platelet reactivity (PR) using VerifyNow P2Y12 assay. Elevated inflammatory status was defined as CRP >3 mg/L and HPR as P2Y12 reactivity units (PRU) =240. Results. Rates of PMI were increased in pts with CRP levels >3 mg/L (10.9% vs 4.6%, OR 2.4, 95% CI 1.2 to 4.5, P = 0.015) and in pts with HPR (11% vs 5.5%, OR 2.2, 95% CI 1.2-4.4, P = 0.018). The occurrence of PMI was highest in the subgroup with HPR and high inflammatory status (16.6% vs 3.6%, OR 4.3, 95% CI 1.5 to 12.6, P = 0.008). Conclusions. In pts who undergo PCI, baseline stratification according to PR and inflammatory status may identify those at higher risk for PMI. Research Project 2 Background. Growing evidence suggests that PR may predict bleeding. We investigate the incremental value of PR in predicting bleeding PCI via the femoral approach over a validated bleeding risk score (BRS). Methods and Results. 800 PCI pts were included. PR was measured before PCI with the VerifyNow P2Y12 assay and low PR was defined as a =178. Calculation of the BRS included the following: age, sex, intra-aortic balloon pump, glycoprotein IIb/IIIa inhibitors, chronic kidney disease, anemia, and low-molecular-weight heparin within 48-hour pre-PCI. A new risk score including low PR (BRS-PR) was developed and validated in an independent cohort of pts (n = 310). Bleeding events at 30 days after PCI were defined according to the REPLACE-2, and BARC criteria. Both BRS and PR showed high discriminatory power for bleeding (AUC >0.7 for all definitions). In the validation set, BRS-PR showed higher discriminatory power for TIMI bleeding than BRS alone (AUC = 0.788 versus 0.709; P = 0.036). Conclusions. PR has incremental predictive value on bleeding events after PCI via the femoral approach over a BRS. Research Project 3 Background. No comprehensive data are available on role of platelet indices (PI) in periprocedural risk stratification of pts undergoing PCI. Methods. 502 PCI pts had preprocedural measurement of PI and PR, the latter assessed by the point-of-care VerifyNow P2Y12 assay and expressed as PRU. Study endpoints were HPR and PMI according to tertiles of PI. Results. Incidence of PMI was 6.6%. Rates of PMI were not different among PI tertiles: platelet count (I: 6.0%, II: 7.1%, III: 6.5%; P = 0.74), mean platelet volume (I: 6.6%, II: 7.3%, III: 5.8%; P = 0.86), platelet distribution width (I: 7.2%, II: 7.2%, III: 5.4%; P = 0.74), MPV/P ratio (I: 6.6%, II: 6.0%, III: 7.1%; P = 0.91). A significant difference in the occurrence of PMI was identified among PRU tertiles (I: 3 %, II: 5.4 %, III: 11.4 %; P = 0.006). Conclusion. This study showed no relation between PI and PMI in PCI pts, but confirms association of HPR with increased incidence of PMI. Research Project 4 Background. Leptin is an adipose tissue derived hormone, which is involved in the regulation of food intake and energy balance. No data are available on relation of leptin and PR and cardiovascular outcome in pts undergoing PCI. Methods. 155 PCI pts were enrolled in the study and had preprocedural measurement of plasma leptin levels and PR. Leptin levels were assessed by ELISA. Hyperleptinemia was defined as leptin levels =14 ng/ml. PR was evaluated by the VerifyNow P2Y12 assay and expressed as PRU. Pts were divided in three groups based on PRU values: LPR for PRU =178; NPR for PRU between 178 and 239; HPR for PRU =239. All pts were followed every 12 months for up 8 years. Results. Leptin plasma levels were significantly different among groups of PR (P = 0.047). In particular leptin levels were significantly higher in pts with HPR (12.61 ± 16.58 ng/ml) compared to LPR (7.83 ± 8.87 ng/ml, P = 0.044) and NPR (7.04 ± 7.03 ng/ml, P = 0.01) group. Incidence of PMI in the study was 8%. Rate of PMI was higher among hyperleptinemic pts (15.1% vs 6.5%, P = 0.22). Clinical long-term follow-up was complete in 140 pts (90.3%). Incidence of MACE was 40% in hyperleptinemic group and 21% in the normoleptinemic group. Pts with hyperleptinemia experienced a significantly higher rate of MACE compared with those in the normoleptinemic group (HR 2.3; CI 95% 1.14-4.6, P = 0.02). Conclusions. The present study suggests that high levels of leptin are associated with HPR and with a worse clinical outcome in pts treated with clopidogrel undergoing PCI.

Role of platelet reactivity and leptin in cardiovascular outcome of patients undergoing percutaneous coronary interventions / Elisabetta Ricottini , 2017 Oct 30. 27. ciclo

Role of platelet reactivity and leptin in cardiovascular outcome of patients undergoing percutaneous coronary interventions

2017-10-30

Abstract

Research Project 1 Background. The incremental predictive value of high inflammatory status and high on-treatment platelet reactivity (HPR) on the occurrence of periprocedural myocardial infarction (PMI) after percutaneous coronary intervention (PCI) has not been characterized. Methods. 500 PCI patients (pts) treated with clopidogrel had preprocedural measurement of CRP levels and platelet reactivity (PR) using VerifyNow P2Y12 assay. Elevated inflammatory status was defined as CRP >3 mg/L and HPR as P2Y12 reactivity units (PRU) =240. Results. Rates of PMI were increased in pts with CRP levels >3 mg/L (10.9% vs 4.6%, OR 2.4, 95% CI 1.2 to 4.5, P = 0.015) and in pts with HPR (11% vs 5.5%, OR 2.2, 95% CI 1.2-4.4, P = 0.018). The occurrence of PMI was highest in the subgroup with HPR and high inflammatory status (16.6% vs 3.6%, OR 4.3, 95% CI 1.5 to 12.6, P = 0.008). Conclusions. In pts who undergo PCI, baseline stratification according to PR and inflammatory status may identify those at higher risk for PMI. Research Project 2 Background. Growing evidence suggests that PR may predict bleeding. We investigate the incremental value of PR in predicting bleeding PCI via the femoral approach over a validated bleeding risk score (BRS). Methods and Results. 800 PCI pts were included. PR was measured before PCI with the VerifyNow P2Y12 assay and low PR was defined as a =178. Calculation of the BRS included the following: age, sex, intra-aortic balloon pump, glycoprotein IIb/IIIa inhibitors, chronic kidney disease, anemia, and low-molecular-weight heparin within 48-hour pre-PCI. A new risk score including low PR (BRS-PR) was developed and validated in an independent cohort of pts (n = 310). Bleeding events at 30 days after PCI were defined according to the REPLACE-2, and BARC criteria. Both BRS and PR showed high discriminatory power for bleeding (AUC >0.7 for all definitions). In the validation set, BRS-PR showed higher discriminatory power for TIMI bleeding than BRS alone (AUC = 0.788 versus 0.709; P = 0.036). Conclusions. PR has incremental predictive value on bleeding events after PCI via the femoral approach over a BRS. Research Project 3 Background. No comprehensive data are available on role of platelet indices (PI) in periprocedural risk stratification of pts undergoing PCI. Methods. 502 PCI pts had preprocedural measurement of PI and PR, the latter assessed by the point-of-care VerifyNow P2Y12 assay and expressed as PRU. Study endpoints were HPR and PMI according to tertiles of PI. Results. Incidence of PMI was 6.6%. Rates of PMI were not different among PI tertiles: platelet count (I: 6.0%, II: 7.1%, III: 6.5%; P = 0.74), mean platelet volume (I: 6.6%, II: 7.3%, III: 5.8%; P = 0.86), platelet distribution width (I: 7.2%, II: 7.2%, III: 5.4%; P = 0.74), MPV/P ratio (I: 6.6%, II: 6.0%, III: 7.1%; P = 0.91). A significant difference in the occurrence of PMI was identified among PRU tertiles (I: 3 %, II: 5.4 %, III: 11.4 %; P = 0.006). Conclusion. This study showed no relation between PI and PMI in PCI pts, but confirms association of HPR with increased incidence of PMI. Research Project 4 Background. Leptin is an adipose tissue derived hormone, which is involved in the regulation of food intake and energy balance. No data are available on relation of leptin and PR and cardiovascular outcome in pts undergoing PCI. Methods. 155 PCI pts were enrolled in the study and had preprocedural measurement of plasma leptin levels and PR. Leptin levels were assessed by ELISA. Hyperleptinemia was defined as leptin levels =14 ng/ml. PR was evaluated by the VerifyNow P2Y12 assay and expressed as PRU. Pts were divided in three groups based on PRU values: LPR for PRU =178; NPR for PRU between 178 and 239; HPR for PRU =239. All pts were followed every 12 months for up 8 years. Results. Leptin plasma levels were significantly different among groups of PR (P = 0.047). In particular leptin levels were significantly higher in pts with HPR (12.61 ± 16.58 ng/ml) compared to LPR (7.83 ± 8.87 ng/ml, P = 0.044) and NPR (7.04 ± 7.03 ng/ml, P = 0.01) group. Incidence of PMI in the study was 8%. Rate of PMI was higher among hyperleptinemic pts (15.1% vs 6.5%, P = 0.22). Clinical long-term follow-up was complete in 140 pts (90.3%). Incidence of MACE was 40% in hyperleptinemic group and 21% in the normoleptinemic group. Pts with hyperleptinemia experienced a significantly higher rate of MACE compared with those in the normoleptinemic group (HR 2.3; CI 95% 1.14-4.6, P = 0.02). Conclusions. The present study suggests that high levels of leptin are associated with HPR and with a worse clinical outcome in pts treated with clopidogrel undergoing PCI.
30-ott-2017
Role of platelet reactivity and leptin in cardiovascular outcome of patients undergoing percutaneous coronary interventions / Elisabetta Ricottini , 2017 Oct 30. 27. ciclo
File in questo prodotto:
File Dimensione Formato  
DT_201_RicottiniElisabetta.pdf

accesso aperto

Tipologia: Tesi di dottorato
Licenza: Creative commons
Dimensione 2.92 MB
Formato Adobe PDF
2.92 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12610/68855
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact