Albuminuria has traditionally been associated with an elevated risk of cardiovascular events. However, few studies have examined the potential relation between albuminuria and periprocedural risk in percutaneous coronary intervention (PCI). The aim of this study was to evaluate the impact of albuminuria on the incidence of periprocedural myocardial injury (PMI) in patients who underwent PCI. The study included 252 consecutive patients who underwent PCI. The incidence of PMI was significantly higher in patients with albuminuria than in those with normoalbuminuria (31.9% vs 43.3%, respectively, p = 0.014). Even after adjustment for confounders, the presence of albuminuria predicted PMI (odds ratio 2.07, 95% confidence interval 1.08 to 3.97, p = 0.029). Furthermore, patients with albuminuria and preserved estimated glomerular filtration rate had a 4.2-fold higher risk for PMI than did patients with normoalbuminuria and preserved estimated glomerular filtration rate. In conclusion, albuminuria was a strong predictor of PMI in patients who underwent PCI.
Many studies have suggested that microalbuminuria is strongly associated with an increased risk of cardiovascular disease. However, the mechanisms underlying the relation are still unclear but are thought to reflect vascular endothelial vascular damage. Postprocedural cardiac biomarker elevation is now widely known as periprocedural myocardial injury (PMI). In addition, PMI is widely accepted to be related to subsequent mortality and other poor clinical outcomes. Recently, we reported a correlation between chronic kidney disease and the incidence of PMI. However, few studies have evaluated the relation between albuminuria and the periprocedural risk of percutaneous coronary intervention (PCI). Therefore, the aim of this study was to evaluate the impact of albuminuria on the incidence of PMI in patients who underwent PCI.
Methods
This observational study included total 252 patients who treated successfully with PCI at Nagoya University Hospital from September 2011 to June 2013. All patients had stable angina pectoris and documented myocardial ischemia. The exclusion criteria included congestive heart failure, and/or history of chronic hemodialysis treatment, elevated preprocedural cardiac biomarkers, and needed for rotational atherectomy. Written informed consent was obtained from all patients before their procedures, and the study protocols were approved by the institutional ethics committee.
After an overnight fast of 12 hours, blood samples were obtained from all patients. Urinary albumin excretion was expressed as the albumin-to-creatinine concentration ratio (ACR), evaluated in a random morning urine specimen. Immunoturbidometry (TIA-ALBG; Serotec, Chitose, Japan) was used to determine the urinary albumin concentration, and a modified Jaffe method was used to measure the urinary creatinine concentration. Albuminuria was defined as a urinary ACR (UACR) of ≥30 μg/mg: microalbuminuria, as a UACR of 30 to 300 μg/mg, and macroalbuminuria, as a UACR of >300 μg/mg. UACR of <30 μg/mg was defined as normoalbuminuria. Cardiac enzymes were measured just before and at 24 hours after the procedure. An electrochemiluminescence immunoassay (Roche Diagnostics, Tokyo, Japan) was used to measure high-sensitivity troponin T. In this method, the upper normal limit of the reference range was defined as 0.014 ng/ml for high-sensitivity troponin T. In this study, PMI was defined as an increase in high-sensitivity troponin T >5 times (0.070 ng/ml) the upper normal limit at 24 hours after PCI.
All patients had received dual antiplatelet therapy with aspirin (100 to 162 mg/day) and thienopyridine derivatives before PCI. In addition, any statins had been administered for ≥1 month before PCI. Coronary stents were implanted with or without predilation. Procedural success was defined as a reduction of stenosis to <30% residual narrowing without flow-limiting dissection or occlusion of the large side branch (>1 mm) or no-flow/slow-reflow phenomenon during a procedure. The operator, who was blinded to our patients’ characteristics and treatments, selected the position and length of the angioplasty and stent implantation according to angiography and conventional intravascular ultrasound findings.
Hypertension was defined as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg or current antihypertensive medication use. Diabetes mellitus was defined as the use of any antihyperglycemic medication or a current diagnosis of diabetes or having a fasting plasma glucose concentration >126 mg/dl or a glycosylated hemoglobin concentration ≥6.5% (National Glycohemoglobin Standardization Program). Smoking habit was defined as having a current habit or having discontinued cigarette use ≤6 months before PCI. The estimated glomerular filtration rate (eGFR) was calculated according to the new Japanese equation: eGFR (ml/min/1.73 m 2 ) = 194 × serum creatinine − 1.094 × age − 0.287 × 0.739 (in women). Preserved eGFR was defined as ≥60 ml/min/1.73 m 2 , and low eGFR was defined as <60 ml/min/1.73 m 2 .
Continuous variables are expressed as mean ± SD or median (interquartile range) if they were non-normally distributed. Categorical variables are expressed as percentages. Student t test was used to compare continuous variables, and chi-square or Fisher exact test was used to compare categorical variables. To identify independent predictors of PMI, multivariate logistic regression analysis was performed for each parameter used as the dependent variable. A 2-sided p value of <0.05 was considered to indicate statistical significance. SPSS version 18.0 for Windows (SPSS, Inc., Chicago, Illinois) was used to perform all statistical analyses.
Results
Angiographical residual stenosis or large side-branch occlusion was not observed in any patient. In addition, no deaths or critical events occurred during the PCI procedure. Albuminuria was detected in 67 patients (26.6%): 54 (21.4%) had microalbuminuria and 13 (5.2%) had macroalbuminuria. Furthermore, 30 patients (18.2%) with preserved eGFR had albuminuria: 27 (16.4%) had microalbuminuria and 3 (1.8%) had macroalbuminuria.
The clinical characteristics of the patients with and without PMI are listed in Table 1 . Lesion and procedural characteristics are listed in Table 2 . The incidence of PMI was significantly higher in the patients with albuminuria than in those without (31.9% vs 43.3%; p = 0.014). An apparent dose-response relation between the severity of albuminuria and the incidence of PMI was determined. The incidence of PMI increased significantly from 26.5% in the patients with normoalbuminuria to 42.6% in those with microalbuminuria to 46.2% in those with macroalbuminuria (p for trend = 0.037; Figure 1 ).
| Variable | Periprocedural Myocardial Injury | p Value | |
|---|---|---|---|
| No (n = 174) | Yes (n = 78) | ||
| Men | 144 (81%) | 58 (74%) | 0.13 |
| Age (years) | 68.6 ± 9.2 | 73.2 ± 8.7 | <0.001 |
| Body mass index (kg/m 2 ) | 23.9 ± 3.3 | 24.1 ± 4.4 | 0.71 |
| Hypertension | 126 (71%) | 62 (80%) | 0.27 |
| Diabetes mellitus | 69 (39%) | 27 (35%) | 0.49 |
| Current smoker | 48 (27%) | 17 (22%) | 0.36 |
| Previous myocardial infarction | 32 (18%) | 13 (17%) | 0.86 |
| Previous coronary angioplasty | 69 (39%) | 29 (37%) | 0.78 |
| Estimated glomerular filtration rate (ml/min/1.73 m 2 ) | 70.3 ± 18.9 | 61.5 ± 22.7 | 0.002 |
| Albumin-to-creatinine concentration ratio (μg/mg) | 9 (4–19) | 17 (6–61) | 0.005 |
| Low-density lipoprotein (mg/dl) | 91.8 ± 25.4 | 92.6 ± 27.8 | 0.83 |
| High-density lipoprotein (mg/dl) | 43.3 ± 11.4 | 45.7 ± 11.7 | 0.12 |
| Triglycerides (mg/dl) | 113 (82–155) | 112 (78–161) | 0.68 |
| Fasting glucose (mg/dl) | 111.5 ± 29.3 | 110.3 ± 33.4 | 0.77 |
| Hemoglobin A1c (%) | 6.3 ± 0.9 | 6.2 ± 0.9 | 0.75 |
| High-sensitive C-reactive protein (mg/dl) | 0.071 (0.035–0.177) | 0.079 (0.029–0.186) | 0.82 |
| Brain natriuretic peptide (pg/dl) | 30.1 (13.4–81.1) | 45.9 (15.1–128.7) | 0.16 |
| Medications | |||
| Angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers | 95 (53%) | 45 (58%) | 0.68 |
| Ca-channel blocker | 74 (42%) | 34 (44%) | 0.89 |
| β blocker | 56 (32%) | 27 (35%) | 0.77 |
| Diuretics | 28 (16%) | 16 (21%) | 0.47 |
| Antidiabetic drugs | 55 (31%) | 21 (27%) | 0.46 |
| Variable | Periprocedural Myocardial Injury | p Value | |
|---|---|---|---|
| No (n = 174) | Yes (n = 78) | ||
| Coronary lesion location | 0.018 | ||
| Left anterior descending | 90 (52%) | 25 (32%) | |
| Left circumflex | 40 (23%) | 24 (31%) | |
| Right coronary | 43 (25%) | 29 (37%) | |
| Bypass graft | 1 (1%) | 0 | |
| AHA/ACC type B 2 or C | 73 (42%) | 40 (51%) | 0.17 |
| Multivessel coronary disease | 83 (48%) | 37 (47%) | 0.97 |
| Intravascular ultrasound findings | |||
| External elastic membrane volume (mm 3 ) | 224.0 ± 167.5 | 216.9 ± 154.6 | 0.82 |
| Lumen volume (mm 3 ) | 84.0 ± 129.3 | 71.6 ± 53.9 | 0.57 |
| Plaque volume (mm 3 ) | 151.5 ± 117.8 | 145.3 ± 103.8 | 0.77 |
| Procedure | |||
| Number of stents | 1.2 ± 0.5 | 1.4 ± 0.6 | 0.012 |
| Drug-eluting stent use | 65 (37%) | 35 (45%) | 0.27 |
| Direct stenting | 63 (36%) | 26 (33%) | 0.67 |
| Total stent length (mm) | 20.3 ± 10.4 | 24.3 ± 12.9 | 0.011 |
| Maximum pressure inflation (atm) | 16.3 ± 4.4 | 17.2 ± 5.3 | 0.15 |
| Total inflation time (seconds) | 100 (69–160) | 132 (74–215) | 0.10 |
Table 3 lists the results of multiple logistic regression analysis of the relation among the incidences of PMI with multiple risk factors. The presence of albuminuria was an independent predictor of PMI after adjusting for all other variables (p = 0.029), as were age (p <0.001), total stent length (p = 0.011), and high-density lipoprotein cholesterol levels (p = 0.027). We also estimated the combined effects of baseline ACR and eGFR levels on the risk of PMI ( Figure 2 ). After adjusting for multiple risk factors for PMI, the odds ratios (95% confidence interval) of PMI were 4.17 (1.56 to 11.0), 1.92 (0.81 to 4.56), and 2.19 (0.83 to 5.80) for those with albuminuria and preserved eGFR, normoalbuminuria and low eGFR, and albuminuria and low eGFR, respectively.
| Odds Ratio | 95% CI | p Value | |
|---|---|---|---|
| Albuminuria | 2.07 | 1.08–3.97 | 0.029 |
| Age (years) | 1.07 | 1.03–1.11 | <0.001 |
| Total stent length | 1.04 | 1.01–1.06 | 0.011 |
| High-density lipoprotein | 1.03 | 1.00–1.06 | 0.027 |
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