[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 34.237.76.91. Please contact the publisher to request reinstatement.
[Skip to Content Landing]
Figure.
Temporal Trends in In-Hospital Reperfusion and In-Hospital Mortality
Temporal Trends in In-Hospital Reperfusion and In-Hospital Mortality

Includes recipients of renal transplants with ST-segment elevation myocardial infarction. CABG indicates coronary artery bypass grafting; PCI, percutaneous coronary intervention.

aP < .001 for trend.

bP = .002 for trend.

cP = .004 for trend.

dP = .27 for trend.

Table 1.  
Baseline Demographics, Comorbidities, and Hospital Characteristics of Patients With STEMIa
Baseline Demographics, Comorbidities, and Hospital Characteristics of Patients With STEMIa
Table 2.  
Use of In-Hospital Reperfusion and In-Hospital Outcomes of STEMI in the Study Groups
Use of In-Hospital Reperfusion and In-Hospital Outcomes of STEMI in the Study Groups
Table 3.  
Age- and Sex-Stratified Analysis of In-Hospital Mortality After STEMI in Non-CKD, Stage 5D CKD, and Renal Transplant Groups
Age- and Sex-Stratified Analysis of In-Hospital Mortality After STEMI in Non-CKD, Stage 5D CKD, and Renal Transplant Groups
Table 4.  
Temporal Trends in In-Hospital Reperfusion and Outcomes in Recipients of Renal Transplants With STEMI
Temporal Trends in In-Hospital Reperfusion and Outcomes in Recipients of Renal Transplants With STEMI
1.
Gupta  T, Harikrishnan  P, Kolte  D,  et al.  Trends in management and outcomes of ST-elevation myocardial infarction in patients with end-stage renal disease in the United States.  Am J Cardiol. 2015;115(8):1033-1041.PubMedGoogle ScholarCrossref
2.
Saran  R, Li  Y, Robinson  B,  et al.  US Renal Data System 2015 annual data report: epidemiology of kidney disease in the United States.  Am J Kidney Dis. 2016;67(3)(suppl 1):S1-S305.PubMedGoogle ScholarCrossref
3.
Kasiske  BL, Maclean  JR, Snyder  JJ.  Acute myocardial infarction and kidney transplantation.  J Am Soc Nephrol. 2006;17(3):900-907.PubMedGoogle ScholarCrossref
4.
Hypolite  IO, Bucci  J, Hshieh  P,  et al.  Acute coronary syndromes after renal transplantation in patients with end-stage renal disease resulting from diabetes.  Am J Transplant. 2002;2(3):274-281.PubMedGoogle ScholarCrossref
5.
Silkensen  JR.  Long-term complications in renal transplantation.  J Am Soc Nephrol. 2000;11(3):582-588.PubMedGoogle Scholar
6.
Aakhus  S, Dahl  K, Widerøe  TE.  Cardiovascular morbidity and risk factors in renal transplant patients.  Nephrol Dial Transplant. 1999;14(3):648-654.PubMedGoogle ScholarCrossref
7.
Herzog  CA, Littrell  K, Arko  C, Frederick  PD, Blaney  M.  Clinical characteristics of dialysis patients with acute myocardial infarction in the United States: a collaborative project of the United States Renal Data System and the National Registry of Myocardial Infarction.  Circulation. 2007;116(13):1465-1472.PubMedGoogle ScholarCrossref
8.
Wolfe  RA, Ashby  VB, Milford  EL,  et al.  Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant.  N Engl J Med. 1999;341(23):1725-1730.PubMedGoogle ScholarCrossref
9.
Healthcare Cost and Utilization Project. Overview of the National (Nationwide) Inpatient Sample (NIS). http://www.hcup-us.ahrq.gov/nisoverview.jsp. Modified November 29, 2016. Accessed May 20, 2016.
10.
Trend Weights for HCUP NIS Data. https://www.hcup-us.ahrq.gov/db/nation/nis/trendwghts.jsp. Modified May 12, 2015. Accessed May 20, 2016.
11.
Gupta  T, Paul  N, Kolte  D,  et al.  Association of chronic renal insufficiency with in-hospital outcomes after percutaneous coronary intervention.  J Am Heart Assoc. 2015;4(6):e002069.PubMedGoogle ScholarCrossref
12.
Massie  AB, Kucirka  LM, Segev  DL.  Big data in organ transplantation: registries and administrative claims [published correction in Am J Transplant. 2014;14(11):2673].  Am J Transplant. 2014;14(8):1723-1730.PubMedGoogle ScholarCrossref
13.
Becerra  BJ, Becerra  MB, Safdar  N.  A nationwide assessment of the burden of urinary tract infection among renal transplant recipients.  J Transplant. 2015;2015:854640.PubMedGoogle ScholarCrossref
14.
Elixhauser  A, Steiner  C, Harris  DR, Coffey  RM.  Comorbidity measures for use with administrative data.  Med Care. 1998;36(1):8-27.PubMedGoogle ScholarCrossref
15.
Healthcare Cost and Utilization Project. HCUP NIS description of data elements. http://www.hcup-us.ahrq.gov/toolssoftware/comorbidity/comorbidity.jsp. Modified October 6, 2016. Accessed May 20, 2016.
16.
Austin  PC, Mamdani  MM.  A comparison of propensity score methods: a case-study estimating the effectiveness of post-AMI statin use.  Stat Med. 2006;25(12):2084-2106.PubMedGoogle ScholarCrossref
17.
Mamdani  M, Sykora  K, Li  P,  et al.  Reader’s guide to critical appraisal of cohort studies, 2: assessing potential for confounding.  BMJ. 2005;330(7497):960-962.PubMedGoogle ScholarCrossref
18.
Gupta  T, Harikrishnan  P, Kolte  D,  et al.  Outcomes of acute myocardial infarction in patients with hypertrophic cardiomyopathy.  Am J Med. 2015;128(8):879-887.e1.PubMedGoogle ScholarCrossref
19.
Khera  S, Kolte  D, Gupta  T,  et al.  Temporal trends and sex differences in revascularization and outcomes of ST-segment elevation myocardial infarction in younger adults in the United States.  J Am Coll Cardiol. 2015;66(18):1961-1972.PubMedGoogle ScholarCrossref
20.
Abbott  KC, Bucci  JR, Cruess  D, Taylor  AJ, Agodoa  LY.  Graft loss and acute coronary syndromes after renal transplantation in the United States.  J Am Soc Nephrol. 2002;13(10):2560-2569.PubMedGoogle ScholarCrossref
21.
Herzog  CA, Ma  JZ, Collins  AJ.  Poor long-term survival after acute myocardial infarction among patients on long-term dialysis.  N Engl J Med. 1998;339(12):799-805.PubMedGoogle ScholarCrossref
22.
Alvares  S, Mota  C, Soares  L,  et al.  Cardiac consequences of renal transplantation changes in left ventricular morphology.  Rev Port Cardiol. 1998;17(2):145-152.PubMedGoogle Scholar
23.
Rigatto  C, Foley  RN, Kent  GM, Guttmann  R, Parfrey  PS.  Long-term changes in left ventricular hypertrophy after renal transplantation.  Transplantation. 2000;70(4):570-575.PubMedGoogle ScholarCrossref
24.
Nakamura  S, Ishibashi-Ueda  H, Niizuma  S, Yoshihara  F, Horio  T, Kawano  Y.  Coronary calcification in patients with chronic kidney disease and coronary artery disease.  Clin J Am Soc Nephrol. 2009;4(12):1892-1900.PubMedGoogle ScholarCrossref
25.
Généreux  P, Madhavan  MV, Mintz  GS,  et al.  Ischemic outcomes after coronary intervention of calcified vessels in acute coronary syndromes: pooled analysis from the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) and ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trials.  J Am Coll Cardiol. 2014;63(18):1845-1854.PubMedGoogle ScholarCrossref
26.
Luft  FC.  Renal disease as a risk factor for cardiovascular disease.  Basic Res Cardiol. 2000;95(suppl 1):I72-I76.PubMedGoogle ScholarCrossref
27.
Kasiske  BL, Chakkera  HA, Roel  J.  Explained and unexplained ischemic heart disease risk after renal transplantation.  J Am Soc Nephrol. 2000;11(9):1735-1743.PubMedGoogle Scholar
28.
Collins  AJ, Foley  RN, Chavers  B,  et al.  US Renal Data System 2013 annual data report.  Am J Kidney Dis. 2014;63(1)(suppl):A7.PubMedGoogle ScholarCrossref
29.
Coles  AH, Fisher  KA, Darling  C,  et al.  Recent trends in post-discharge mortality among patients with an initial acute myocardial infarction.  Am J Cardiol. 2012;110(8):1073-1077.PubMedGoogle ScholarCrossref
30.
Yeh  RW, Sidney  S, Chandra  M, Sorel  M, Selby  JV, Go  AS.  Population trends in the incidence and outcomes of acute myocardial infarction.  N Engl J Med. 2010;362(23):2155-2165.PubMedGoogle ScholarCrossref
31.
Herzog  CA, Ma  JZ, Collins  AJ.  Long-term survival of renal transplant recipients in the United States after acute myocardial infarction.  Am J Kidney Dis. 2000;36(1):145-152.PubMedGoogle ScholarCrossref
32.
Quan  H, Li  B, Saunders  LD,  et al; IMECCHI Investigators.  Assessing validity of ICD-9-CM and ICD-10 administrative data in recording clinical conditions in a unique dually coded database.  Health Serv Res. 2008;43(4):1424-1441.PubMedGoogle ScholarCrossref
Original Investigation
March 2017

Management and Outcomes of ST-Segment Elevation Myocardial Infarction in US Renal Transplant Recipients

Author Affiliations
  • 1Division of Cardiology, Department of Medicine, Westchester Medical Center and New York Medical College, Valhalla, New York
  • 2Division of Cardiology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York
  • 3Division of Cardiology, Warren Alpert Medical School, Brown University, Providence, Rhode Island
  • 4Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota
  • 5Division of Cardiology, Ronald Reagan–UCLA (University of California, Los Angeles) Medical Center
  • 6Brigham and Women’s Hospital Heart and Vascular Center, Harvard Medical School, Boston, Massachusetts
JAMA Cardiol. 2017;2(3):250-258. doi:10.1001/jamacardio.2016.5131
Key Points

Question  What are the differences in in-hospital reperfusion rates and outcomes of ST-segment elevation myocardial infarction among renal transplant recipients, patients without chronic kidney disease, or those with stage 5D chronic kidney disease?

Findings  In this retrospective nationwide analysis of approximately 2.3 million patients with ST-segment elevation myocardial infarction, renal transplant recipients were less likely to receive reperfusion compared with patients without chronic kidney disease, but had similar risk-adjusted in-hospital mortality. In contrast, compared with patients with stage 5D chronic kidney disease, renal transplant recipients were much more likely to receive reperfusion and had markedly lower in-hospital mortality rates.

Meaning  In-hospital mortality rates in renal transplant recipients with ST-segment elevation myocardial infarction are more favorable compared with those in patients with stage 5D chronic kidney disease and are similar to those in the general population.

Abstract

Importance  Renal transplantation is associated with reduction in the risk for myocardial infarction (MI) in patients with chronic kidney disease requiring long-term dialysis (stage 5D CKD). Whether outcomes of MI differ among renal transplant recipients vs patients with stage 5D CKD or those without CKD has not been well examined.

Objectives  To compare in-hospital reperfusion rates and outcomes of ST-segment elevation MI (STEMI) in renal transplant recipients vs the stage 5D CKD group or the non-CKD group.

Design, Setting, and Participants  The National Inpatient Sample database was queried to identify patients 18 years or older who were hospitalized with the principal diagnosis of STEMI. All hospitalizations for STEMI in the United States from January 1, 2003, to December 31, 2013, were included. Codes from International Classification of Diseases, Ninth Revision, Clinical Modification, were used to identify patients in the non-CKD, stage 5D CKD, or prior renal transplant groups. Data were analyzed from March to May 2016.

Main Outcomes and Measures  In-hospital mortality.

Results  From 2003 to 2013, 2 319 002 patients in the non-CKD group (34.7% women; 65.3% men; mean [SD] age, 64.2 [14.4] years), 30 072 patients in the stage 5D CKD group (45.0% women; 55.0% men; mean [SD] age, 66.9 [12.5] years), and 2980 patients in the renal transplant group (27.3% women; 72.7% men; mean [SD] age, 57.5 [11.1] years) were identified who were hospitalized with STEMI. Of these, 68.9% of the patients in the non-CKD group, 39.5% in the stage 5D CKD group, and 65.2% in the renal transplant group received in-hospital reperfusion for STEMI. The renal transplant group was more likely to receive reperfusion compared with the stage 5D CKD group (adjusted odds ratio [AOR], 1.83; 95% CI, 1.67-2.01; P < .001) but less likely compared with the non-CKD group (AOR, 0.75; 95% CI, 0.68-0.83; P < .001). Risk-adjusted in-hospital mortality among the renal transplant group with STEMI was markedly lower compared with the stage 5D CKD group (AOR, 0.37; 95% CI, 0.33-0.43; P < .001) but similar compared with the non-CKD group (AOR, 1.14; 95% CI, 0.99-1.31; P = .08). Among renal transplant recipients with STEMI, the use of reperfusion increased from 53.7% in the 2003-2004 interval to 81.4% in the 2011-2013 interval (AOR, 1.33; 95% CI, 1.25-1.43; P < .001 for trend), whereas risk-adjusted in-hospital mortality remained unchanged during the study period, from 8.9% in the 2003-2004 interval to 6.1% in the 2011-2013 interval (AOR, 0.94; 95% CI, 0.85-1.05; P = .27 for trend).

Conclusions and Relevance  In-hospital mortality rates in renal transplant recipients with STEMI are more favorable compared with those of patients with stage 5D CKD and approach those of the general population with STEMI.

Introduction

Cardiovascular disease (CVD) is the leading cause of death in patients with stage 5 chronic kidney disease requiring long-term dialysis (stage 5D CKD).1 Approximately 45% of deaths in patients with stage 5D CKD have cardiac causes, with approximately 15% of these deaths attributable to acute myocardial infarction (AMI).2 Although renal transplantation has been shown to be associated with a reduced risk for CVD in patients with stage 5D CKD,3,4 CVD is still a major cause of morbidity and the leading cause of death in renal transplant recipients.5,6

Previous studies7 have shown that compared with the general population, patients with stage 5D CKD are less likely to receive reperfusion therapy for AMI and have more than a 2-fold higher in-hospital mortality rate. Renal transplant recipients have an all-cause mortality benefit compared with patients with stage 5D CKD8; whether this benefit extends to mortality after AMI has not been well examined. In this study, we compare the use of reperfusion (thrombolysis, percutaneous coronary intervention [PCI], and coronary artery bypass grafting [CABG]) and in-hospital outcomes of ST-segment elevation myocardial infarction (STEMI) in renal transplant recipients (renal transplant group) vs patients without CKD (non-CKD group) and patients with stage 5D CKD (stage 5D CKD group). We also describe the temporal trends in rates of in-hospital reperfusion and outcomes of STEMI in the renal transplant group.

Methods
Data Source

Data were obtained from the National Inpatient Sample (NIS) data files from January 1, 2003, to December 31, 2013. The design of the NIS has been described previously9 (eMethods in the Supplement). Briefly, the NIS is the largest publicly available all-payer inpatient health care database in the United States and provides national estimates of hospital stays. The NIS approximates a 20% stratified sample of all discharges from US community hospitals and is drawn from all states participating in the Healthcare Cost and Utilization Project, representing more than 95% of the US population.9 Patient- and hospital-level weights were provided to obtain national estimates.10 This study was deemed exempt from institutional review board approval and the need for informed consent by the institutional review board of New York Medical College because the Healthcare Cost and Utilization Project NIS is a publicly available database containing deidentified patient information.

Study Population

From 2003 to 2013, a total of 86 305 292 discharge records were included in the NIS, corresponding to a national estimate of 424 020 120 hospitalizations in the United States. We used codes 410.01, 410.11 to 410.61, 410.81, and 410.91 from the International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) to identify all patients 18 years or older hospitalized with the principal diagnosis of STEMI (n = 2 912 897). Patients in the stage 5D CKD group (n = 30 072) were identified using the ICD-9-CM diagnosis code for CKD requiring long-term dialysis (585.6) or the ICD-9-CM procedure code for hemodialysis (39.95) or peritoneal dialysis (54.98), except when dialysis was performed for acute kidney injury (584.5-584.9). Patients in the renal transplant group (n = 2980) were identified using the ICD-9-CM diagnosis code V42.0; those who had developed graft failure requiring dialysis were excluded from this group. Of the remaining 2 879 845 patients with STEMI, those in the non-CKD group (n = 2 319 002) were identified as those without documented ICD-9-CM diagnosis codes for CKD (585.1-585.5 and 585.9) (eFigure in the Supplement). This approach has been used by previous studies with the NIS database to identify patients with no CKD, stage 5D CKD, and a functional renal transplant.1,11-13 Also, because the V42.0 diagnosis code has not been extensively validated in the past, we compared the number of overall hospitalizations for AMI in patients with renal transplants captured in the NIS 2013 data vs the US Renal Data System annual data report and found them to be similar.2 Patients with STEMI who underwent thrombolysis (ICD-9-CM codes 99.10 and V45.88), coronary angiography (ICD-9-CM codes 88.55, 88.56, 37.22, and 37.23), PCI (ICD-9-CM codes 00.66, 36.01, 36.02, 36.05, 36.06, 36.07, and 17.55), and CABG (ICD-9-CM code 36.1x) were identified using the respective ICD-9-CM codes.

Outcomes Measured

Our primary outcome of interest was all-cause, in-hospital mortality, defined by the variable “died” in the NIS database. The mean length of stay (LOS) (in patients surviving to hospital discharge) was used as a secondary outcome.

Patient and Hospital Characteristics

We defined the following baseline patient characteristics: demographics, primary expected payer, weekday vs weekend admission, median household income for the patient’s zip code, all Elixhauser comorbidities (except chronic renal failure),14,15 and other clinically relevant comorbidities (smoking, dyslipidemia, known coronary artery disease [CAD], family history of CAD, atrial fibrillation, prior MI, prior PCI, prior CABG, and carotid artery disease). A list of ICD-9-CM and Clinical Classification Software codes used to identify comorbidities is given in the eTable 1 in the Supplement. Hospital-level variables included the census region, bed size, location, and teaching status.

Statistical Analysis

Data were analyzed from March to May 2016. Weighted data were used for all statistical analyses. For descriptive analyses, patient demographics, comorbidities, and hospital characteristics were compared using the Pearson χ2 test for categorical variables and 1-way analysis of variance for continuous variables. In addition, we used absolute standardized differences (ASD), calculated as the difference in means or proportions divided by a pooled estimate of the SD, to compare baseline characteristics among the 3 groups. Compared with traditional significance testing, ASD is not as sensitive to sample size and is useful in identifying clinically meaningful differences.16,17 An ASD of greater than 10% is conventionally considered meaningful.

We used multivariable logistic or linear regression models to compare treatment strategy (thrombolysis, coronary angiography, PCI, and CABG), in-hospital mortality, and LOS between the renal transplant group and the non-CKD group or the stage 5D CKD group. All regression models were constructed using generalized estimating equations with exchangeable working correlation matrix to account for clustering of outcomes within hospitals. Variables included in the regression models were age, sex, primary expected payer, weekday vs weekend admission, median household income for the patient’s zip code, all Elixhauser and other clinically relevant comorbidities, and hospital characteristics. These variables were selected a priori because they are known to influence STEMI outcomes and in-hospital mortality in administrative databases in general.14,18,19 Because LOS had a positively skewed distribution, log-transformed LOS was used as the dependent variable in the regression models. For in-hospital outcomes, after adjusting for all these variables, we performed additional adjustment for the use of thrombolysis, PCI, and CABG to determine whether differences in treatment could explain outcome differences between the study groups.

To study temporal trends in reperfusion and outcomes of STEMI among renal transplant recipients, we divided the study period into the following intervals: 2003-2004, 2005-2006, 2007-2008, 2009-2010, and 2011-2013. For trend analyses, Cochrane-Armitage test was used for categorical variables and linear regression for continuous variables. Multivariable logistic or linear regression models adjusting for all the previously mentioned variables were used to assess whether the use of thrombolysis, coronary angiography, PCI, or CABG, in-hospital mortality, or LOS in renal transplant recipients with STEMI has changed over time.

Statistical analysis was performed using SPSS Statistics software (version 21.0; IBM Corp). All P values were 2 sided with a significance threshold of less than 0.05. Categorical variables are expressed as percentage and continuous variables as mean (SD). Odds ratios (OR) and 95% CIs are used to report the results of logistic regression.

Results
Baseline Characteristics

From January 1, 2003, to December 31, 2013, we identified 2 319 002 patients in the non-CKD group (34.7% women; 65.3% men; mean [SD] age, 64.2 [14.4] years), 30 072 in the stage 5D CKD group (45.0% women; 55.0% men; mean [SD] age, 66.9 [12.5] years), and 2980 in the renal transplant group (27.3% women; 72.7% men; mean [SD] age, 57.5 [11.1] years) 18 years or older hospitalized with STEMI. Compared with the non-CKD group, patients in the renal transplant group were more likely to be younger, less likely to be women, less likely to be white, and more likely to be African American or Hispanic. Patients in the renal transplant group had a higher prevalence of prior CABG, uncomplicated or complicated diabetes, hypertension, and deficiency anemia but were less likely to be smokers or to have chronic pulmonary disease. Compared with the stage 5D CKD group, the patients in the renal transplant group were younger, less likely to be women or African American, and more likely to be white. Patients in the renal transplant group had a lower prevalence of most comorbid conditions, including prior MI, prior PCI, prior CABG, atrial fibrillation, heart failure, diabetes with chronic complications, hypertension, peripheral vascular disease, deficiency anemia, chronic pulmonary disease, fluid and electrolyte disorders, and coagulopathy. Dyslipidemia and known CAD were conditions more prevalent in the renal transplant group compared with the stage 5D CKD group (ASD>10% for all comparisons) (Table 1 and eTable 2 in the Supplement).

In-Hospital Reperfusion

The renal transplant group with STEMI had lower overall reperfusion rates compared with the non-CKD group (65.2% vs 68.9%; unadjusted OR, 0.85; 95% CI, 0.79-0.91; adjusted OR [AOR], 0.75; 95% CI, 0.68-0.83; P < .001). We found no difference in rates of thrombolysis between the renal transplant and non-CKD groups (3.5% vs 4.0%; AOR, 1.01; 95% CI, 0.84-1.23; P = .89). However, the renal transplant group was less likely to receive coronary angiography (71.8% vs 72.6%; AOR, 0.87; 95% CI, 0.84-1.23; P = .007), PCI (56.2% vs 58.5%; AOR, 0.89; 95% CI, 0.82-0.97; P = .01), or CABG (5.5% vs 6.3%; AOR, 0.72; 95% CI, 0.61-0.85; P < .001) (Table 2).

On the contrary, compared with the stage 5D CKD group, the renal transplant group was much more likely to receive reperfusion therapy for STEMI (65.2% vs 39.5%; unadjusted OR, 2.87; 95% CI, 2.65-3.10; AOR, 1.83; 95% CI, 1.67-2.01; P < .001). Thrombolysis was performed in 3.5% of the renal transplant group vs 2.1% of the stage 5D CKD group (AOR, 1.49; 95% CI, 1.17-1.90; P = .001). Coronary angiography was performed in 71.8% of the renal transplant group vs 50.5% of the stage 5D CKD group (AOR, 1.64; 95% CI, 1.49-1.80; P < .001) and PCI in 56.2% of the renal transplant group vs 32.2% of the stage 5D CKD group (AOR, 1.65; 95% CI, 1.51-1.80; P < .001). Rates of CABG use were similar in the renal transplant and stage 5D CKD groups (5.5% vs 6.3%; AOR, 0.96; 95% CI, 0.79-1.16; P = .66) (Table 2).

In-Hospital Outcomes

The renal transplant group with STEMI had similar risk-adjusted in-hospital mortality compared with the non-CKD group (8.5% vs 8.4%; AOR, 1.14; 95% CI, 0.99-1.31; P = .08). Even after additional adjustment for differences in the use of thrombolysis, PCI, and CABG, we found no difference in in-hospital mortality between the renal transplant and non-CKD groups (AOR, 1.12; 95% CI, 0.97-1.30; P = .12). Likewise, the mean LOS was rather similar between the renal transplant and non-CKD groups (4.8 vs 4.6 days; adjusted parameter estimate, 0.98; 95% CI, 0.97-0.99; P < .001) (Table 2).

In contrast, the renal transplant group had significantly lower risk-adjusted in-hospital mortality compared with the stage 5D CKD group (8.5% vs 23.5%; AOR, 0.37; 95% CI, 0.33-0.43; P < .001), which was not explained by differences in rates of reperfusion between the 2 groups (AOR, 0.40; 95% CI, 0.35-0.46; P < .001). Mean LOS was also shorter in the renal transplant group (4.8 days vs 7.2 days; adjusted parameter estimate: 0.93; 95% CI, 0.92-0.94; P < .001) (Table 2). Age- and sex-stratified analysis for in-hospital mortality showed largely similar results (Table 3).

STEMI Trends in Renal Transplant Recipients With STEMI

From 2003 to 2013, 2980 renal transplant recipients were hospitalized with the principal diagnosis of STEMI. The number of annual STEMI hospitalizations in the renal transplant group declined from 370 in 2003 to 275 in 2013 (P < .001 for trend). From the 2003-2004 to 2011-2013 intervals, prevalence of most cardiovascular comorbidities increased, including smoking, dyslipidemia, known CAD, prior MI, atrial fibrillation, hypertension, and obesity (P < .05 for trend for all) (eTable 3 in the Supplement). Overall, the use of reperfusion increased from 53.7% in the 2003-2004 interval to 81.4% in the 2011-2013 interval (unadjusted OR, 1.35; 95% CI, 1.28-1.42; AOR, 1.33; 95% CI, 1.25-1.43; P < .001). Specifically, the use of thrombolysis (from 5.0% in 2003-2004 to 3.1% in 2011-2013; AOR, 0.72; 95% CI, 0.58-0.90; P = .004 for trend) and CABG (from 5.3% in 2003-2004 to 4.9% in 2011-2013; AOR, 0.84; 95% CI, 0.75-0.94; P = .002 for trend) decreased, whereas that of coronary angiography (from 61.5% in 2003-2004 to 83.0% in 2011-2013; AOR, 1.37; 95% CI, 1.27-1.47; P < .001 for trend) and PCI (from 43.4% in 2003-2004 to 73.3% in 2011-2013; AOR, 1.38; 95% CI, 1.30-1.47; P < .001 for trend) increased (Figure). We found no significant change in risk-adjusted in-hospital mortality (from 8.9% in 2003-2004 to 6.1% in 2011-2013; AOR, 0.94; 95% CI, 0.85-1.05; P = .27) (Figure) or mean LOS (from 4.9 days in 2003-2004 to 5.1 days in 2011-2013; adjusted parameter estimate, 0.99; 95% CI, 0.99-1.00; P = .05 for trend) during the study period (Table 4).

Discussion

This large, multicenter, nationwide, observational cohort study of patients with STEMI in the United States has several important findings. First, the renal transplant group had modestly lower in-hospital reperfusion rates for STEMI compared with patients without CKD but had similar risk-adjusted in-hospital mortality and mean LOS. Second, compared with the stage 5D CKD group, the renal transplant group was much more likely to receive reperfusion and had markedly lower risk-adjusted in-hospital mortality and shorter mean LOS. Finally, from the 2003-2004 to 2011-2013 intervals, we observed an increase in the use of reperfusion among renal transplant recipients with STEMI. However, risk-adjusted in-hospital mortality and mean LOS remained unchanged during the study period.

Previous studies3,4,20,21 have shown that the risk for AMI is lower after renal transplantation compared with patients undergoing dialysis. Using data from the US Renal Data System, Hypolite et al4 showed that patients with stage 5D CKD due to diabetes enrolled in the transplant list had a 62% lower risk for acute coronary syndromes after renal transplant. Similarly, among Medicare beneficiaries with stage 5D CKD placed on the transplant list, Kasiske et al3 showed that renal transplant was associated with a 17% lower adjusted risk for AMI. Abbott et al20 also showed that renal transplant recipients who develop graft loss requiring dialysis have more than a 2-fold increase in the risk for AMI. However, data on the outcomes of AMI in renal transplant recipients vs patients with stage 5D CKD are scarce. Similar to our findings, in a study of 34 189 patients with stage 5D CKD and 3079 renal transplant recipients with AMI identified from the US Renal Data System from 1977 to 1995, Herzog et al21 showed that the adjusted risk of in-hospital mortality was almost 3-fold higher in patients undergoing dialysis vs renal transplant recipients.

Several possible mechanisms suggest how renal transplantation may be associated with better outcomes after STEMI compared with patients undergoing dialysis. Renal transplant recipients are not subject to variations in intravascular volume as are patients undergoing maintenance dialysis. Studies have shown that echocardiographic variables, such as left ventricular mass index, left ventricular end-systolic and diastolic diameters, and left atrial dimension, normalize in most patients undergoing dialysis after renal transplantation.22,23 Secondary hyperparathyroidism and frequent calcium supplementation in patients undergoing dialysis is associated with increased calcium-phosphate product levels, leading to coronary calcification and more calcified plaques.11,24,25 Also, dialysis status is associated with a generalized inflammatory state that is associated with endothelial dysfunction and accelerated atherosclerosis, leading to greater extent of CAD.26 Renal transplantation is associated with at least partial correction of these metabolic abnormalities, potentially contributing to a decreased risk for and better outcomes after AMI.4

Although renal transplant recipients are at lower risk for CVD than patients with stage 5D CKD, they are more prone to develop CVD compared with the general population. Traditional risk scoring systems such as the Framingham risk score underestimate the risk for CAD in renal transplant recipients.27 To our knowledge, no published data have assessed the outcomes of AMI in renal transplant recipients compared with patients without CKD. We found that despite lower rates of PCI and CABG compared with the non-CKD group, the renal transplant group had similar risk-adjusted in-hospital mortality and mean LOS after STEMI. However, the US Renal Data System data describe 2-year survival rates after AMI in renal transplant recipients to be approximately 50%,28 whereas, 2-year survival rates after AMI in the general population are reported to be approximately 75%.29 These data suggest that despite similar in-hospital mortality rates, as noted in our study, renal transplant recipients still have a greater long-term mortality hazard after AMI compared with patients without CKD.

Consistent with changes in the general population with STEMI,30 we observed a temporal decrease in the use of thrombolysis and CABG and an increase in the use of coronary angiography and PCI among the renal transplant group. Herzog et al31 previously showed a 45% reduction in risk-adjusted all-cause mortality in renal transplant recipients with AMI in 1990 to 1996 compared with 1977 to 1984. In our study, we observed that risk-adjusted in-hospital mortality in renal transplant recipients with STEMI remained unchanged from the 2003-2004 to 2011-2013 intervals. Still, in-hospital mortality among the renal transplant group with STEMI in our study (8.5%) compares favorably with reported in-hospital mortality rates of approximately 12% in renal transplant recipients with AMI (STEMI and non-STEMI) in the 1980s and 1990s,21,31 suggesting that outcomes in these patients have improved over time. The temporal change in in-hospital mortality in renal transplant recipients with STEMI is also in stark contrast to the observed change in patients with stage 5D CKD in whom risk-adjusted mortality after STEMI has increased during the past few years.1

Limitations

Our study has several limitations that must be acknowledged. Comparison of renal transplant recipients vs patients with stage 5D CKD is subject to some degree of selection bias that is unlikely to be corrected even after extensive multivariable adjustment. Patients who have undergone renal transplant are likely to have undergone some form of screening for CAD and subsequent revascularization as appropriate during the pretransplant workup, which could partly contribute to better outcomes. A more accurate comparison would be between patients undergoing dialysis who are listed for transplant vs those after transplant, but these data were not available in the NIS database. We could not determine the interval between renal transplant and the STEMI event or whether it influences treatment choice or outcomes. Comorbidities were extracted using ICD-9-CM codes, and no adjustment could be made for severity of comorbid conditions. Given the lack of direct access to laboratory data, we could not estimate glomerular filtration rates and relied on ICD-9-CM coding for documentation of CKD. The ICD-9-CM diagnosis of CKD, although highly specific, has a modest sensitivity of approximately 80%32; therefore, some patients with milder stages of CKD may have been classified as not having the disease. No data were available on the use of guideline-recommended adjunctive medical therapies for STEMI. Last, given the observational design of our study, residual measured or unmeasured confounding could have accounted at least partly for our findings.

Conclusions

Compared with patients with stage 5D CKD, renal transplant recipients with STEMI were more likely to undergo reperfusion and had lower risk-adjusted in-hospital mortality. Of note, despite lower reperfusion rates, risk-adjusted in-hospital mortality in renal transplant recipients with STEMI was similar to that in patients without CKD. Among renal transplant recipients with STEMI, we observed a temporal increase in rates of coronary angiography and PCI; however, risk-adjusted in-hospital mortality remained unchanged during the study period. Future investigations are needed to confirm our findings and explore the mechanisms that contribute to improved STEMI outcomes in renal transplant recipients vs those remaining on dialysis.

Back to top
Article Information

Corresponding Author: Deepak L. Bhatt, MD, MPH, Brigham and Women’s Hospital Heart & Vascular Center, Harvard Medical School, 75 Francis St, Boston, MA 02115 (dlbhattmd@post.harvard.edu).

Accepted for Publication: October 28, 2016.

Published Online: January 11, 2017. doi:10.1001/jamacardio.2016.5131

Author Contributions: Drs Gupta and Bhatt had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Gupta, Kolte, Khera, Fonarow, Bhatt.

Acquisition, analysis, or interpretation of data: Gupta, Kolte, Bhatt.

Drafting of the manuscript: Gupta, Bhatt.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Gupta, Kolte.

Administrative, technical, or material support: Gupta, Bhatt.

Study supervision: Gupta, Bhatt.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Fonarow reports serving as a consultant to Amgen, AstraZeneca, Eli Lilly, and Janssen. Dr Bhatt reports serving on the advisory boards of Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, and Regado Biosciences; serving on the board of directors of the Boston Veterans Affairs Research Institute and Society of Cardiovascular Patient Care; serving as the chair of the American Heart Association Quality Oversight Committee; serving on the data monitoring committees of Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, and Population Health Research Institute; receiving honoraria from American College of Cardiology as the senior associate editor of Clinical Trials and News, ACC.org, from Belvoir Publications as the editor in chief of Harvard Heart Letter, from Duke Clinical Research Institute for work on clinical trial steering committees, from Harvard Clinical Research Institute for work on the clinical trial steering committee, from HMP Communications as the editor-in-chief of Journal of Invasive Cardiology, from the Journal of the American College of Cardiology as guest editor and associate editor, from Population Health Research Institute for work on the clinical trial steering committee, from Slack Publications as the chief medical editor of Cardiology Today’s Intervention, from the Society of Cardiovascular Patient Care for work as secretary and treasurer, and from WebMD for work on continuing medical education steering committees; serving as deputy editor of Clinical Cardiology; serving as chair of the National Cardiovascular Data Registry–ACTION Registry Steering Committee; serving as chair of the Veterans Affairs Clinical Assessment Reporting and Tracking Research and Publications Committee; receiving research funding from Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Forest Laboratories, Ischemix, Medtronic, Pfizer, Roche, Sanofi Aventis, and The Medicines Company; receiving royalties from Elsevier for editorship of Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease; serving as site coinvestigator for Biotronik, Boston Scientific, and St Jude Medical; serving as a trustee for the American College of Cardiology; and performing unfunded research for FlowCo, PLx Pharma, and Takeda. No other disclosures were reported.

Meeting Presentation: This paper was presented in part at the 65th Annual Scientific Sessions of the American College of Cardiology; April 4, 2016; Chicago, Illinois.

References
1.
Gupta  T, Harikrishnan  P, Kolte  D,  et al.  Trends in management and outcomes of ST-elevation myocardial infarction in patients with end-stage renal disease in the United States.  Am J Cardiol. 2015;115(8):1033-1041.PubMedGoogle ScholarCrossref
2.
Saran  R, Li  Y, Robinson  B,  et al.  US Renal Data System 2015 annual data report: epidemiology of kidney disease in the United States.  Am J Kidney Dis. 2016;67(3)(suppl 1):S1-S305.PubMedGoogle ScholarCrossref
3.
Kasiske  BL, Maclean  JR, Snyder  JJ.  Acute myocardial infarction and kidney transplantation.  J Am Soc Nephrol. 2006;17(3):900-907.PubMedGoogle ScholarCrossref
4.
Hypolite  IO, Bucci  J, Hshieh  P,  et al.  Acute coronary syndromes after renal transplantation in patients with end-stage renal disease resulting from diabetes.  Am J Transplant. 2002;2(3):274-281.PubMedGoogle ScholarCrossref
5.
Silkensen  JR.  Long-term complications in renal transplantation.  J Am Soc Nephrol. 2000;11(3):582-588.PubMedGoogle Scholar
6.
Aakhus  S, Dahl  K, Widerøe  TE.  Cardiovascular morbidity and risk factors in renal transplant patients.  Nephrol Dial Transplant. 1999;14(3):648-654.PubMedGoogle ScholarCrossref
7.
Herzog  CA, Littrell  K, Arko  C, Frederick  PD, Blaney  M.  Clinical characteristics of dialysis patients with acute myocardial infarction in the United States: a collaborative project of the United States Renal Data System and the National Registry of Myocardial Infarction.  Circulation. 2007;116(13):1465-1472.PubMedGoogle ScholarCrossref
8.
Wolfe  RA, Ashby  VB, Milford  EL,  et al.  Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant.  N Engl J Med. 1999;341(23):1725-1730.PubMedGoogle ScholarCrossref
9.
Healthcare Cost and Utilization Project. Overview of the National (Nationwide) Inpatient Sample (NIS). http://www.hcup-us.ahrq.gov/nisoverview.jsp. Modified November 29, 2016. Accessed May 20, 2016.
10.
Trend Weights for HCUP NIS Data. https://www.hcup-us.ahrq.gov/db/nation/nis/trendwghts.jsp. Modified May 12, 2015. Accessed May 20, 2016.
11.
Gupta  T, Paul  N, Kolte  D,  et al.  Association of chronic renal insufficiency with in-hospital outcomes after percutaneous coronary intervention.  J Am Heart Assoc. 2015;4(6):e002069.PubMedGoogle ScholarCrossref
12.
Massie  AB, Kucirka  LM, Segev  DL.  Big data in organ transplantation: registries and administrative claims [published correction in Am J Transplant. 2014;14(11):2673].  Am J Transplant. 2014;14(8):1723-1730.PubMedGoogle ScholarCrossref
13.
Becerra  BJ, Becerra  MB, Safdar  N.  A nationwide assessment of the burden of urinary tract infection among renal transplant recipients.  J Transplant. 2015;2015:854640.PubMedGoogle ScholarCrossref
14.
Elixhauser  A, Steiner  C, Harris  DR, Coffey  RM.  Comorbidity measures for use with administrative data.  Med Care. 1998;36(1):8-27.PubMedGoogle ScholarCrossref
15.
Healthcare Cost and Utilization Project. HCUP NIS description of data elements. http://www.hcup-us.ahrq.gov/toolssoftware/comorbidity/comorbidity.jsp. Modified October 6, 2016. Accessed May 20, 2016.
16.
Austin  PC, Mamdani  MM.  A comparison of propensity score methods: a case-study estimating the effectiveness of post-AMI statin use.  Stat Med. 2006;25(12):2084-2106.PubMedGoogle ScholarCrossref
17.
Mamdani  M, Sykora  K, Li  P,  et al.  Reader’s guide to critical appraisal of cohort studies, 2: assessing potential for confounding.  BMJ. 2005;330(7497):960-962.PubMedGoogle ScholarCrossref
18.
Gupta  T, Harikrishnan  P, Kolte  D,  et al.  Outcomes of acute myocardial infarction in patients with hypertrophic cardiomyopathy.  Am J Med. 2015;128(8):879-887.e1.PubMedGoogle ScholarCrossref
19.
Khera  S, Kolte  D, Gupta  T,  et al.  Temporal trends and sex differences in revascularization and outcomes of ST-segment elevation myocardial infarction in younger adults in the United States.  J Am Coll Cardiol. 2015;66(18):1961-1972.PubMedGoogle ScholarCrossref
20.
Abbott  KC, Bucci  JR, Cruess  D, Taylor  AJ, Agodoa  LY.  Graft loss and acute coronary syndromes after renal transplantation in the United States.  J Am Soc Nephrol. 2002;13(10):2560-2569.PubMedGoogle ScholarCrossref
21.
Herzog  CA, Ma  JZ, Collins  AJ.  Poor long-term survival after acute myocardial infarction among patients on long-term dialysis.  N Engl J Med. 1998;339(12):799-805.PubMedGoogle ScholarCrossref
22.
Alvares  S, Mota  C, Soares  L,  et al.  Cardiac consequences of renal transplantation changes in left ventricular morphology.  Rev Port Cardiol. 1998;17(2):145-152.PubMedGoogle Scholar
23.
Rigatto  C, Foley  RN, Kent  GM, Guttmann  R, Parfrey  PS.  Long-term changes in left ventricular hypertrophy after renal transplantation.  Transplantation. 2000;70(4):570-575.PubMedGoogle ScholarCrossref
24.
Nakamura  S, Ishibashi-Ueda  H, Niizuma  S, Yoshihara  F, Horio  T, Kawano  Y.  Coronary calcification in patients with chronic kidney disease and coronary artery disease.  Clin J Am Soc Nephrol. 2009;4(12):1892-1900.PubMedGoogle ScholarCrossref
25.
Généreux  P, Madhavan  MV, Mintz  GS,  et al.  Ischemic outcomes after coronary intervention of calcified vessels in acute coronary syndromes: pooled analysis from the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) and ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trials.  J Am Coll Cardiol. 2014;63(18):1845-1854.PubMedGoogle ScholarCrossref
26.
Luft  FC.  Renal disease as a risk factor for cardiovascular disease.  Basic Res Cardiol. 2000;95(suppl 1):I72-I76.PubMedGoogle ScholarCrossref
27.
Kasiske  BL, Chakkera  HA, Roel  J.  Explained and unexplained ischemic heart disease risk after renal transplantation.  J Am Soc Nephrol. 2000;11(9):1735-1743.PubMedGoogle Scholar
28.
Collins  AJ, Foley  RN, Chavers  B,  et al.  US Renal Data System 2013 annual data report.  Am J Kidney Dis. 2014;63(1)(suppl):A7.PubMedGoogle ScholarCrossref
29.
Coles  AH, Fisher  KA, Darling  C,  et al.  Recent trends in post-discharge mortality among patients with an initial acute myocardial infarction.  Am J Cardiol. 2012;110(8):1073-1077.PubMedGoogle ScholarCrossref
30.
Yeh  RW, Sidney  S, Chandra  M, Sorel  M, Selby  JV, Go  AS.  Population trends in the incidence and outcomes of acute myocardial infarction.  N Engl J Med. 2010;362(23):2155-2165.PubMedGoogle ScholarCrossref
31.
Herzog  CA, Ma  JZ, Collins  AJ.  Long-term survival of renal transplant recipients in the United States after acute myocardial infarction.  Am J Kidney Dis. 2000;36(1):145-152.PubMedGoogle ScholarCrossref
32.
Quan  H, Li  B, Saunders  LD,  et al; IMECCHI Investigators.  Assessing validity of ICD-9-CM and ICD-10 administrative data in recording clinical conditions in a unique dually coded database.  Health Serv Res. 2008;43(4):1424-1441.PubMedGoogle ScholarCrossref
×