Download PDF
Thromb Haemost 2013; 110(01): 118-123
DOI: 10.1160/TH13-01-0004
Platelets and Blood Cells
Schattauer GmbH

Combined and independent impact of diabetes mellitus and chronic kidney disease on residual platelet reactivity

Usman Baber
1   Zena and Michael A. Wiener Cardiovascular Institute and Marie-Josée and Henry R. Kravis Center for Cardiovascular Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA
,
Jeffrey Bander
1   Zena and Michael A. Wiener Cardiovascular Institute and Marie-Josée and Henry R. Kravis Center for Cardiovascular Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA
,
Rucha Karajgikar
1   Zena and Michael A. Wiener Cardiovascular Institute and Marie-Josée and Henry R. Kravis Center for Cardiovascular Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA
,
Kapil Yadav
1   Zena and Michael A. Wiener Cardiovascular Institute and Marie-Josée and Henry R. Kravis Center for Cardiovascular Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA
,
Ali Hadi
1   Zena and Michael A. Wiener Cardiovascular Institute and Marie-Josée and Henry R. Kravis Center for Cardiovascular Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA
,
Kleanthis Theodoropolous
1   Zena and Michael A. Wiener Cardiovascular Institute and Marie-Josée and Henry R. Kravis Center for Cardiovascular Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA
,
Nilusha Gukathasan
1   Zena and Michael A. Wiener Cardiovascular Institute and Marie-Josée and Henry R. Kravis Center for Cardiovascular Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA
,
Swathi Roy
1   Zena and Michael A. Wiener Cardiovascular Institute and Marie-Josée and Henry R. Kravis Center for Cardiovascular Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA
,
Swapna Sayeneni
1   Zena and Michael A. Wiener Cardiovascular Institute and Marie-Josée and Henry R. Kravis Center for Cardiovascular Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA
,
Stuart A. Scott
2   Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA
,
Jason C. Kovacic
1   Zena and Michael A. Wiener Cardiovascular Institute and Marie-Josée and Henry R. Kravis Center for Cardiovascular Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA
,
Jennifer Yu
1   Zena and Michael A. Wiener Cardiovascular Institute and Marie-Josée and Henry R. Kravis Center for Cardiovascular Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA
,
Samantha Sartori
1   Zena and Michael A. Wiener Cardiovascular Institute and Marie-Josée and Henry R. Kravis Center for Cardiovascular Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA
,
Roxana Mehran
1   Zena and Michael A. Wiener Cardiovascular Institute and Marie-Josée and Henry R. Kravis Center for Cardiovascular Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA
,
Jaime Uribarri
1   Zena and Michael A. Wiener Cardiovascular Institute and Marie-Josée and Henry R. Kravis Center for Cardiovascular Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA
,
Juan J. Badimon
1   Zena and Michael A. Wiener Cardiovascular Institute and Marie-Josée and Henry R. Kravis Center for Cardiovascular Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA
,
Paul Muntner
2   Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA
,
Pedro Moreno
1   Zena and Michael A. Wiener Cardiovascular Institute and Marie-Josée and Henry R. Kravis Center for Cardiovascular Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA
,
Annapoorna S. Kini
1   Zena and Michael A. Wiener Cardiovascular Institute and Marie-Josée and Henry R. Kravis Center for Cardiovascular Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA
,
Samin K. Sharma
1   Zena and Michael A. Wiener Cardiovascular Institute and Marie-Josée and Henry R. Kravis Center for Cardiovascular Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA
› Author AffiliationsFinancial support: This study was partially funded by an investigator-initiated grant from Eli Lilly/Daichii Sankyo. Eli Lilly/Daichii Sankyo did not have any role in the design and conduct of the study, the collection, management, data analysis, or interpretation of the data, or the preparation of the manuscript.
Further Information

Publication History

Received: 03 January 2013

Accepted after major revision: 20 April 2013

Publication Date:
30 November 2017 (online)

Also available at
    Permissions and Reprints

Summary

Patients with both chronic kidney disease (CKD) and diabetes mellitus (DM) are at increased risk for thrombotic events compared to those with one abnormality alone. Whether this can be attributed to changes in platelet reactivity among those with both CKD and DM is unknown. We prospectively studied 438 clopidogrel-naïve patients undergoing percutaneous coronary intervention (PCI). Platelet function tests were performed 4–6 hours after loading with 600 mg of clopidogrel. Platelet reactivity was assessed using the VerifyNow system and expressed as P2Y12 reaction units (PRU). High residual platelet reactivity (HRPR) was defined as PRU > 230. Patients were categorised into four groups by the presence or absence of CKD and DM. Among those without CKD or DM (n=166), DM alone (n=150), CKD alone (n=60) and both CKD and DM (n=62) the mean PRU levels were 201.6 ± 96.3, 220.5 ± 101.1, 254.9 ± 106.7 and 275.0 ± 94.5, respectively (p<0.001). Analogously, the prevalence of HRPR was 42.3%, 50.7%, 63.3% and 75.8%, respectively (p< 0.001). Associations between either CKD or DM alone and HRPR were attenuated after multivariable adjustment while the odds for HRPR associated with both CKD and DM remained significant (OR [95% CI]: 2.61 [1.16 – 5.86]). In conclusion, the presence of both CKD and DM confers a synergistic impact on residual platelet reactivity when compared to either condition alone. Whether more potent platelet inhibitors may improve outcomes among patients with both abnormalities warrants investigation.

Keywords

Cardiology - diabetes mellitus - platelet physiology
 

  • References

  • 1 Schneider CA, Ferrannini E, Defronzo R. et al. Effect of pioglitazone on cardiovascular outcome in diabetes and chronic kidney disease. J Am Soc Nephrol 2008; 19: 182-187.
    CrossrefPubMedGoogle Scholar
  • 2 Best PJ, Lennon R, Ting HH. et al. The impact of renal insufficiency on clinical outcomes in patients undergoing percutaneous coronary interventions. J Am Coll Cardiol 2002; 39: 1113-1119.
    CrossrefPubMedGoogle Scholar
  • 3 Jensen LO, Maeng M, Thayssen P. et al. Long-term outcomes after percutaneous coronary intervention in patients with and without diabetes mellitus in Western Denmark. Am J Cardiol 2010; 105: 1513-1519.
    CrossrefPubMedGoogle Scholar
  • 4 Hakeem A, Bhatti S, Karmali KN. et al. Renal function and risk stratification of diabetic and nondiabetic patients undergoing evaluation for coronary artery disease. JACC Cardiovasc Imaging 2010; 03: 734-745.
    CrossrefPubMedGoogle Scholar
  • 5 Brar SS, ten Berg J, Marcucci R. et al. Impact of platelet reactivity on clinical outcomes after percutaneous coronary intervention A collaborative meta-analysis of individual participant data. J Am Coll Cardiol 2011; 58: 1945-1954.
    CrossrefPubMedGoogle Scholar
  • 6 Li Y, Woo V, Bose R. Platelet hyperactivity and abnormal Ca(2+) homeostasis in diabetes mellitus. Am J Physiol Heart Circ Physiol 2001; 280: H1480-1489.
    CrossrefPubMedGoogle Scholar
  • 7 Winocour PD, Watala C, Perry DW. et al. Decreased platelet membrane fluidity due to glycation or acetylation of membrane proteins. Thromb Haemost 1992; 68: 577-582.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Best PJ, Steinhubl SR, Berger PB. et al. The efficacy and safety of shortand long-term dual antiplatelet therapy in patients with mild or moderate chronic kidney disease: results from the Clopidogrel for the Reduction of Events During Observation (CREDO) trial. Am Heart J 2008; 155: 687-693.
    CrossrefPubMedGoogle Scholar
  • 9 Dasgupta A, Steinhubl SR, Bhatt DL. et al. Clinical outcomes of patients with diabetic nephropathy randomized to clopidogrel plus aspirin versus aspirin alone (a post hoc analysis of the clopidogrel for high atherothrombotic risk and ischemic stabilization, management, and avoidance [CHARISMA] trial). Am J Cardiol 2009; 103: 1359-1363.
    CrossrefPubMedGoogle Scholar
  • 10 Keltai M, Tonelli M, Mann JF. et al. Renal function and outcomes in acute coronary syndrome: impact of clopidogrel. Eur J Cardiovasc Prev Rehabil 2007; 14: 312-318.
    CrossrefPubMedGoogle Scholar
  • 11 Fox CS, Muntner P, Chen AY. et al. Use of evidence-based therapies in shortterm outcomes of ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction in patients with chronic kidney disease: a report from the National Cardiovascular Data Acute Coronary Treatment and Intervention Outcomes Network registry. Circulation 2010; 121: 357-365.
    CrossrefPubMedGoogle Scholar
  • 12 Levey AS, Stevens LA, Schmid CH. et al. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009; 150: 604-612.
    CrossrefPubMedGoogle Scholar
  • 13 Levey AS, Coresh J, Balk E. et al. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med 2003; 139: 137-147.
    CrossrefPubMedGoogle Scholar
  • 14 Martis S, Peter I, Hulot JS. et al. Multi-ethnic distribution of clinically relevant CYP2C genotypes and haplotypes. Pharmacogenomics J. 2012 Epub ahead of print..
    PubMedGoogle Scholar
  • 15 Angiolillo DJ, Bernardo E, Capodanno D. et al. Impact of chronic kidney disease on platelet function profiles in diabetes mellitus patients with coronary artery disease taking dual antiplatelet therapy. J Am Coll Cardiol 2010; 55: 1139-1146.
    CrossrefPubMedGoogle Scholar
  • 16 Almquist T, Jacobson SH, Lins PE. et al. Effects of lipid-lowering treatment on platelet reactivity and platelet-leukocyte aggregation in diabetic patients without and with chronic kidney disease: a randomized trial. Nephrol Dial Transplant 2012; 27: 3540-3546.
    CrossrefPubMedGoogle Scholar
  • 17 Htun P, Fateh-Moghadam S, Bischofs C. et al. Low responsiveness to clopidogrel increases risk among CKD patients undergoing coronary intervention. J Am Soc Nephrol 2011; 22: 627-633.
    CrossrefPubMedGoogle Scholar
  • 18 Park SH, Kim W, Park CS. et al. A comparison of clopidogrel responsiveness in patients with versus without chronic renal failure. Am J Cardiol 2009; 104: 1292-1295.
    CrossrefPubMedGoogle Scholar
  • 19 Angiolillo DJ, Bernardo E, Ramirez C. et al. Insulin therapy is associated with platelet dysfunction in patients with type 2 diabetes mellitus on dual oral antiplatelet treatment. J Am Coll Cardiol 2006; 48: 298-304.
    CrossrefPubMedGoogle Scholar
  • 20 Singla A, Antonino MJ, Bliden KP. et al. The relation between platelet reactivity and glycemic control in diabetic patients with cardiovascular disease on maintenance aspirin and clopidogrel therapy. Am Heart J 2009; 158 784: e1-6.
    CrossrefPubMedGoogle Scholar
  • 21 Leblond F, Guevin C, Demers C. et al. Downregulation of hepatic cytochrome P450 in chronic renal failure. J Am Soc Nephrol 2001; 12: 326-332.
    PubMedGoogle Scholar
  • 22 Noris M, Benigni A, Boccardo P. et al. Enhanced nitric oxide synthesis in uremia: implications for platelet dysfunction and dialysis hypotension. Kidney Int 1993; 44: 445-450.
    CrossrefPubMedGoogle Scholar
  • 23 Sagripanti A, Cupisti A, Baicchi U. et al. Plasma parameters of the prothrombotic state in chronic uremia. Nephron 1993; 63: 273-278.
    CrossrefPubMedGoogle Scholar
  • 24 Plantinga LC, Crews DC, Coresh J. et al. Prevalence of chronic kidney disease in US adults with undiagnosed diabetes or prediabetes. Clin J Am Soc Nephrol 2010; 05: 673-682.
    CrossrefPubMedGoogle Scholar
  • 25 Whaley-Connell AT, Sowers JR, Stevens LA. et al. CKD in the United States: Kidney Early Evaluation Program (KEEP) and National Health and Nutrition Examination Survey (NHANES) 1999-2004. Am J Kidney Dis 2008; 51 (Suppl. 02) S13-20.
    CrossrefPubMedGoogle Scholar