Introduction: Limited data are available on the long-term impact of mild renal dysfunction (estimated glomerular filtration rate [eGFR] 60–89 mL/min/1.73 m2) in patients with three-vessel coronary disease (3VD). Methods: A total of 5,272 patients with 3VD undergoing revascularization were included and were categorized into 3 groups: normal renal function (eGFR ≥90 mL/min/1.73 m2, n = 2,352), mild renal dysfunction (eGFR 60–89, n = 2,501), and moderate renal dysfunction (eGFR 30–59, n = 419). Primary endpoint was all-cause death. Secondary endpoints included cardiac death and major adverse cardiac and cerebrovascular events (MACCE), a composite of death, myocardial infarction, and stroke. Results: During the median 7.6-year follow-up period, 555 (10.5%) deaths occurred. After multivariable adjustment, patients with mild and moderate renal dysfunction had significantly higher risks of all-cause death (adjusted hazard ratio [HR]: 1.36, 95% confidence interval [CI]: 1.07–1.70; adjusted HR: 2.06, 95% CI: 1.53–2.78, respectively) compared with patients with normal renal function. Patients after coronary artery bypass grafting (CABG) had a lower rate of all-cause death and MACCE than those undergoing percutaneous coronary intervention (PCI) in the normal and mild renal dysfunction group but not in the moderate renal dysfunction group. Results were similar after propensity score matching. Conclusions: In patients with 3VD, even mild renal impairment was significantly associated with a higher risk of all-cause death. The superiority of CABG over PCI diminished in those with moderate renal dysfunction. Our study alerts clinicians to the early screening of mild renal impairment in patients with 3VD and provides real-world evidence on the optimal revascularization strategy in patients with renal impairment.

Chronic kidney disease (CKD) is a major contributor to global mortality and morbidity and is also a well-recognized independent risk factor for cardiovascular disease (CVD) [1, 2]. Patients with CKD have a high risk of CVD development and cardiac death, which may be due to both high prevalence of traditional risk factors (hypertension, diabetes, dyslipidemia, smoking, etc.) and nontraditional risk factors (inflammation, mineral and bone disorders, endothelial dysfunction, etc.) in CKD patients [3]. Although a threshold of estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 is recommended to indicate CKD and the association between eGFR <60 mL/min/1.73 m2 and risk of death was well established both in general and high-risk populations, it is less clear whether a mildly impaired renal function of eGFR 60–89 mL/min/1.73 m2 was associated with a higher risk of death in patients with coronary artery disease (CAD), especially in patients with multivessel diseases [4‒7].

The evidence for optimal revascularization strategy in patients with mild renal dysfunction is also limited; high-risk patients were routinely excluded in most clinical trials, and the population was often divided according to the eGFR threshold of 60 mL/min/1.73 m2 in the studies comparing the effectiveness of percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABG) in CKD patients [8‒11]. Therefore, we conducted this study to evaluate the impact of mild or moderate renal dysfunction on clinical outcomes and compare the effectiveness of revascularization strategies across renal function status among patients with three-vessel disease (3VD).

Study Design and Population

This study was a post hoc analysis based on a prospective observational cohort of 8,943 patients with 3VD (defined as angiographic stenosis of ≥50% in all three major epicardial coronary arteries). From April 2004 to February 2011, patients with 3VD were consecutively screened and enrolled at Fuwai Hospital, the National Center for Cardiovascular Diseases in China. Patients who met the following criteria were excluded: (1) missing baseline serum creatinine data; (2) eGFR <30 mL/min/1.73 m2, given the small number of these patients (n = 20); (3) without any revascularization procedure after admission; (4) a diagnosis of ST-elevated myocardial infarction (MI) on admission because these patients were more likely to undergo PCI; (5) previous CABG.

This study was approved by the Institutional Review Committee of Fuwai Hospital and followed the Declaration of Helsinki. All participants signed informed consent.

Data Collection and Definitions

Baseline and procedural data of all patients were collected through the electronic record system of Fuwai Hospital by independent clinical research coordinators. Decision on an individual’s therapeutic strategy was made under clinical guidelines [12], cardiologist-team discussion, and patient’s preference. The eGFR was used as the indicator of renal function and was calculated using the Chronic Kidney Disease Epidemiology Collaboration creatinine equation [13]. According to the National Kidney Foundation classification, patients were categorized into three groups based on their eGFR level: normal renal function (≥90 mL/min/1.73 m2), mild renal dysfunction (60–89 mL/min/1.73 m2), and moderate renal dysfunction (30–59 mL/min/1.73 m2) [14].

Follow-Up and Endpoints

Patients were followed by telephone interviews, follow-up letters, or clinical visits. The primary endpoint was defined as all-cause death. Secondary endpoints included cardiac death and major adverse cardiac and cerebrovascular events (MACCE), a composite of death, MI, and stroke. Death was categorized as noncardiac only if an unequivocal noncardiac death could be established. All clinical events were carefully checked by an independent group of clinical physicians.

Statistical Analysis

Summary statistics are described as frequencies and percentages for categorical variables, and as means and standard deviations for normally distributed continuous variables. Student t tests and one-way ANOVA were applied to compare the baseline difference for continuous variables. Pearson χ2 test was applied for comparison of categorical variables. Missing values were imputed as the median for continuous variables or mode for categorical variables, except for the Synergy Between PCI with Taxus and Cardiac Surgery (SYNTAX) scores. Cumulative incidence curves were estimated using the Kaplan-Meier method and were compared by log-rank test. Multivariable Cox proportional regression models were used to estimate the predictive effect of eGFR level and revascularization strategies. Restricted cubic spline analysis with an optimal number of 4 knots was also used to examine the association between continuous eGFR and all-cause death after adjustment. The adjustment model included the following covariates: age, sex, body mass index, hypertension, diabetes, smoking status, dyslipidemia, previous PCI, previous MI, previous stroke, chronic lung disease, peripheral artery disease, left ventricular ejection fraction (LVEF), clinical presentation (stable angina pectoris or acute coronary syndrome), left main artery involvement, SYNTAX score (≤22, 23–32, ≥33), eGFR group, and revascularization strategy. Propensity scores matching was performed for comparison between renal dysfunction groups and normal renal function group, as well as comparison between PCI and CABG in each renal function stratum with similar baseline characteristics, using a 1:1 matching protocol with a caliper width of 0.2 of the SD of the logit of the propensity score. Covariates in the propensity model were listed above. Moreover, subgroup analysis was performed to evaluate the effect of mild renal dysfunction on risk of all-cause death in different groups stratified by age, sex, SYNTAX score, LVEF, and clinical presentation. Statistical significance was defined as a two-tailed p value <0.05. All statistical analysis was performed using R version 4.2.1 (R Foundation for Statistical Computing).

Baseline Characteristics

A total of 5,272 3VD patients undergoing revascularization with baseline eGFR data were included in the final analysis (Fig. 1). Of these patients, 2,352 (44.6%) had normal renal function, 2,501 (47.4%) had mild renal dysfunction, and 419 (8.0%) had moderate renal dysfunction. Baseline characteristics among patients stratified by eGFR were presented in Table 1. Patients with renal dysfunction were older and tended to be female. They were more likely to have lower LVEF and complex coronary anatomy. They also had relatively more comorbidities such as hypertension and peripheral artery disease, and a lower prevalence of smoking history, with less medication at discharge. Baseline characteristics were well-balanced after propensity score matching (online suppl. Table S1; for all online suppl. material, see https://doi.org/10.1159/000534252). Differences in baseline characteristics between patients undergoing PCI and CABG were presented in online supplementary Table S2. More patients in the CABG group had previous CVDs and complex coronary anatomy compared with patients in the PCI group. Prevalence of post-procedure medication prescription was lower in the CABG group.

Fig. 1.

Study flowchart. 3VD, three-vessel disease; CABG, coronary bypass grafting; eGFR, estimated glomerular filtration rate; PCI, percutaneous coronary intervention; STEMI, ST-elevation myocardial infarction.

Fig. 1.

Study flowchart. 3VD, three-vessel disease; CABG, coronary bypass grafting; eGFR, estimated glomerular filtration rate; PCI, percutaneous coronary intervention; STEMI, ST-elevation myocardial infarction.

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Table 1.

Baseline characteristics according to renal function group

eGFR >90 (n = 2,352)eGFR 60–89 (n = 2,501)eGFR 30–59 (n = 419)p value
Age, years 55.7±8.3 64.1±8.5 67.7±7.9 <0.001 
Female 323 (13.7) 581 (23.2) 152 (36.3) <0.001 
Body mass index, kg/m2 26.1±3.1 25.8±3.0 25.7±3.2 <0.001 
Hypertension 1,509 (64.2) 1,769 (70.7) 350 (83.5) <0.001 
Diabetes mellitus 827 (35.2) 809 (32.3) 157 (37.5) 0.04 
Current/former smoker 1,465 (62.3) 1,251 (50.0) 174 (41.5) <0.001 
Dyslipidemia 1,377 (58.5) 1,377 (55.1) 224 (53.5) 0.02 
Previous PCI 261 (11.1) 301 (12.0) 47 (11.2) 0.58 
Previous MI 836 (35.5) 908 (36.3) 151 (36.0) 0.86 
Previous stroke 153 (6.5) 278 (11.1) 58 (13.8) <0.001 
COPD 17 (0.7) 30 (1.2) 6 (1.4) 0.17 
PAD 154 (6.5) 212 (8.5) 45 (10.7) 0.003 
LVEF, % 62.1±11.8 62.5±12.1 59.2±13.9 <0.001 
Clinical presentation    <0.001 
 NSTEMI 162 (6.9) 187 (7.5) 54 (12.9)  
 Unstable angina 975 (41.5) 1,121 (44.8) 213 (50.8)  
 Stable angina 1,215 (51.7) 1,193 (47.7) 152 (36.3)  
Creatinine, μmol/L 71.4±10.6 87.9±12.2 118.1 (20.7) <0.001 
eGFR, mL/min/1.73 m2 100.3±7.5 77.5±8.4 51.5 (7.1) <0.001 
LDL-C, mmol/L 2.6±0.9 2.5±0.8 2.5±0.9 <0.001 
Left main involvement 526 (22.4) 604 (24.2) 114 (27.2) 0.08 
SYNTAX score*    0.04 
 ≤22 910 (38.8) 959 (38.5) 134 (32.1)  
 23–32 869 (37.1) 930 (37.3) 158 (37.8)  
 ≥33 565 (24.1) 605 (24.3) 126 (30.1)  
Revascularization    0.02 
 PCI 1,281 (54.5) 2,311 (52.4) 199 (47.5)  
 CABG 1,071 (45.5) 1,190 (47.6) 220 (52.5)  
Medication at discharge 
 Aspirin 2,290 (97.4) 2,414 (96.5) 394 (94.0) 0.002 
 Clopidogrel 1,303 (55.4) 1,301 (52.0) 205 (48.9) 0.01 
 ACEI 646 (27.5) 760 (30.4) 110 (26.3) 0.04 
 ARB 299 (12.7) 325 (13.0) 69 (16.5) 0.11 
 Nitrates 2,196 (93.4) 2,331 (93.2) 380 (90.7) 0.13 
 β-Blocker 2,126 (90.4) 2,176 (87.0) 356 (85.0) <0.001 
 CCB 800 (34.0) 910 (36.4) 148 (35.3) 0.22 
 Statins 1,323 (56.2) 1,363 (54.5) 229 (54.7) 0.45 
eGFR >90 (n = 2,352)eGFR 60–89 (n = 2,501)eGFR 30–59 (n = 419)p value
Age, years 55.7±8.3 64.1±8.5 67.7±7.9 <0.001 
Female 323 (13.7) 581 (23.2) 152 (36.3) <0.001 
Body mass index, kg/m2 26.1±3.1 25.8±3.0 25.7±3.2 <0.001 
Hypertension 1,509 (64.2) 1,769 (70.7) 350 (83.5) <0.001 
Diabetes mellitus 827 (35.2) 809 (32.3) 157 (37.5) 0.04 
Current/former smoker 1,465 (62.3) 1,251 (50.0) 174 (41.5) <0.001 
Dyslipidemia 1,377 (58.5) 1,377 (55.1) 224 (53.5) 0.02 
Previous PCI 261 (11.1) 301 (12.0) 47 (11.2) 0.58 
Previous MI 836 (35.5) 908 (36.3) 151 (36.0) 0.86 
Previous stroke 153 (6.5) 278 (11.1) 58 (13.8) <0.001 
COPD 17 (0.7) 30 (1.2) 6 (1.4) 0.17 
PAD 154 (6.5) 212 (8.5) 45 (10.7) 0.003 
LVEF, % 62.1±11.8 62.5±12.1 59.2±13.9 <0.001 
Clinical presentation    <0.001 
 NSTEMI 162 (6.9) 187 (7.5) 54 (12.9)  
 Unstable angina 975 (41.5) 1,121 (44.8) 213 (50.8)  
 Stable angina 1,215 (51.7) 1,193 (47.7) 152 (36.3)  
Creatinine, μmol/L 71.4±10.6 87.9±12.2 118.1 (20.7) <0.001 
eGFR, mL/min/1.73 m2 100.3±7.5 77.5±8.4 51.5 (7.1) <0.001 
LDL-C, mmol/L 2.6±0.9 2.5±0.8 2.5±0.9 <0.001 
Left main involvement 526 (22.4) 604 (24.2) 114 (27.2) 0.08 
SYNTAX score*    0.04 
 ≤22 910 (38.8) 959 (38.5) 134 (32.1)  
 23–32 869 (37.1) 930 (37.3) 158 (37.8)  
 ≥33 565 (24.1) 605 (24.3) 126 (30.1)  
Revascularization    0.02 
 PCI 1,281 (54.5) 2,311 (52.4) 199 (47.5)  
 CABG 1,071 (45.5) 1,190 (47.6) 220 (52.5)  
Medication at discharge 
 Aspirin 2,290 (97.4) 2,414 (96.5) 394 (94.0) 0.002 
 Clopidogrel 1,303 (55.4) 1,301 (52.0) 205 (48.9) 0.01 
 ACEI 646 (27.5) 760 (30.4) 110 (26.3) 0.04 
 ARB 299 (12.7) 325 (13.0) 69 (16.5) 0.11 
 Nitrates 2,196 (93.4) 2,331 (93.2) 380 (90.7) 0.13 
 β-Blocker 2,126 (90.4) 2,176 (87.0) 356 (85.0) <0.001 
 CCB 800 (34.0) 910 (36.4) 148 (35.3) 0.22 
 Statins 1,323 (56.2) 1,363 (54.5) 229 (54.7) 0.45 

ACEI, angiotensin-converting enzyme inhibitors; ARB, angiotensin Ⅱ receptor blockers; BMI, body mass index; CABG, coronary bypass grafting; CCB, calcium channel blocker; COPD, chronic obstructive pulmonary disease; eGFR, estimated glomerular filtration rate; LDL-C, low-density lipoprotein cholesterol; LVEF, left ventricular ejection fraction; MI, myocardial infarction; NSTEMI, non-ST-elevation myocardial infarction; PAD, peripheral artery disease; PCI, percutaneous coronary intervention.

*SYNTAX score was calculated using an online calculator (http://www.syntaxscore.com) by a research group blinded to the clinical data.

Impact of Renal Function on Outcomes

The median follow-up period was 7.6 years (interquartile range: 6.0–9.2 years), with a response rate of 82.5%. All patients finished at least one follow-up. During the follow-up time, a total of 555 (10.5%) deaths, 224 (4.2%) cardiac deaths, and 1,185 (22.5%) MACCEs occurred. There were significant differences in crude and propensity score-matched cumulative incidences of all-cause death among three eGFR groups (Fig. 2). When eGFR was analyzed as a continuous variable, adjusted hazard ratio (HR) for all-cause death increased when eGFR was <94 mL/min/1.73 m2 (online suppl. Fig. S1). Multivariable analysis showed that patients with eGFR 60–89 mL/min/1.73 m2 (mild renal dysfunction) and eGFR 30–59 mL/min/1.73 m2 (moderate renal dysfunction) had significantly increased risks of all-cause death compared with patients with eGFR >90 mL/min/1.73 m2 (normal renal function) (HR: 1.36, 95% confidence interval [CI]: 1.07–1.70, p = 0.009; HR: 2.06, 95% CI: 1.53–2.78, p < 0.001, respectively) (Table 2). In terms of secondary endpoints, only eGFR 30–59 mL/min/1.73 m2 was significantly associated with higher risks of cardiac death (HR: 2.58, 95% CI: 1.65–4.05, p < 0.001) and MACCE (HR: 1.34, 95% CI: 1.09–1.66, p = 0.006). These findings were consistent in the cohort after propensity matching (online suppl. Tables S3, S4). Subgroup analysis showed that the adjusted risk of all-cause death with mild renal dysfunction compared with normal renal function was higher in patients who were younger (<65 years) (HR: 1.49, 95% CI: 1.10–2.02, p = 0.009) and female (HR: 3.06, 95% CI: 1.45–6.44, p = 0.003), although the tests for interaction showed no significant results (interaction with age: p = 0.34; interaction with gender: p = 0.08) (online suppl. Table S5).

Fig. 2.

Cumulative incidence curves for all-cause death for comparison among three eGFR groups before matching (a), between eGFR 60–89 mL/min/1.73 m2 and eGFR >90 mL/min/1.73 m2 after matching (b), and between eGFR 30–59 mL/min/1.73 m2 and eGFR >90 mL/min/1.73 m2 after matching (c). eGFR, estimated glomerular filtration rate.

Fig. 2.

Cumulative incidence curves for all-cause death for comparison among three eGFR groups before matching (a), between eGFR 60–89 mL/min/1.73 m2 and eGFR >90 mL/min/1.73 m2 after matching (b), and between eGFR 30–59 mL/min/1.73 m2 and eGFR >90 mL/min/1.73 m2 after matching (c). eGFR, estimated glomerular filtration rate.

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Table 2.

Clinical outcomes stratified by renal function

OutcomesRenal functionEvent (%)Adjusted HR (95% CI)p value
All-cause death eGFR ≥90 133 (5.7) Reference NA 
eGFR 60–89 324 (13.0) 1.36 (1.07–1.70) 0.009 
eGFR 30–59 98 (23.4) 2.06 (1.53–2.78) <0.001 
Cardiac death eGFR ≥90 58 (2.5) Reference NA 
eGFR 60–89 122 (4.9) 1.41 (1.00–2.00) 0.05 
eGFR 30–59 44 (10.5) 2.58 (1.65–4.05) <0.001 
MACCE eGFR ≥90 434 (18.5) Reference NA 
eGFR 60–89 604 (24.2) 1.00 (0.87–1.15) 0.97 
eGFR 30–59 147 (35.1) 1.34 (1.09–1.66) 0.006 
OutcomesRenal functionEvent (%)Adjusted HR (95% CI)p value
All-cause death eGFR ≥90 133 (5.7) Reference NA 
eGFR 60–89 324 (13.0) 1.36 (1.07–1.70) 0.009 
eGFR 30–59 98 (23.4) 2.06 (1.53–2.78) <0.001 
Cardiac death eGFR ≥90 58 (2.5) Reference NA 
eGFR 60–89 122 (4.9) 1.41 (1.00–2.00) 0.05 
eGFR 30–59 44 (10.5) 2.58 (1.65–4.05) <0.001 
MACCE eGFR ≥90 434 (18.5) Reference NA 
eGFR 60–89 604 (24.2) 1.00 (0.87–1.15) 0.97 
eGFR 30–59 147 (35.1) 1.34 (1.09–1.66) 0.006 

CI, confidence interval; eGFR, estimated glomerular filtration rate; HR, hazard ratio; MACCE, cardiac death and major adverse cardiac and cerebrovascular events.

Revascularization Strategy and Renal Function

Compared with PCI patients, CABG patients had a borderline significant lower risk of long-term all-cause death and MACCE in patients with eGFR >90 mL/min/1.73 m2 (normal renal function) and eGFR 60–89 mL/min/1.73 m2 (mild renal dysfunction), but not in patients with eGFR 30–59 mL/min/1.73 m2 (moderate renal dysfunction) (Fig. 3). The results tend to favor CABG over PCI in terms of cardiac death across all eGFR groups. No significant interaction for adverse clinical outcomes was observed between renal function and revascularization strategy. Results were similar in the sensitive analysis using propensity score matching in each eGFR group (online suppl. Table S6).

Fig. 3.

Different clinical outcomes for PCI versus CABG in each renal function group. CABG, coronary bypass grafting; CI, confidence interval; eGFR, estimated glomerular filtration rate; HR, hazard ratio; PCI, percutaneous coronary intervention.

Fig. 3.

Different clinical outcomes for PCI versus CABG in each renal function group. CABG, coronary bypass grafting; CI, confidence interval; eGFR, estimated glomerular filtration rate; HR, hazard ratio; PCI, percutaneous coronary intervention.

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In this prospective large real-world cohort of 3VD patients, our major findings include the following: (1) patients with renal function impairment suffered from more comorbidities and inadequate post-procedure medication; (2) both mild and moderate renal dysfunction were significantly associated with an increased risk of all-cause death, and the association between mild renal dysfunction and risk of all-cause death was stronger in women; (3) compared with PCI, CABG was associated with lower rates of cardiac death across three renal function strata. In terms of all-cause death and MACCE, a trend for benefit of CABG in individuals with normal renal function diminished in those with moderate renal function. As a severe form of CAD, 3VD conferred a substantially increased risk of death and worse risk factor profiles [15]. Thus, it is essential to identify high-risk individuals among these patients, and initiate appropriate intervention strategies to improve their survival. CKD is regarded as a strong risk factor for CAD progression and mortality, as well as a risk multiplier for all-cause mortality in patients with existing severe CAD [16]. In some epidemiological studies, eGFR in the range of 60–89 mL/min/1.73 m2 was also shown to be an independent risk factor of CVD [17, 18]. This effect could be explained by early cardiac remodeling and calcification under the impact of reduced renal function [18]. Our data further extended this result in patients with 3VD, indicating that mild renal dysfunction was significantly associated with risk of death in these patients. Although routine screening of albuminuria and eGFR was recommended in general population according to the ESC 2021 guideline, the range of eGFR of 60–89 mL/min/1.73 m2 was not highlighted [19]. Considering the high proportion of mild renal dysfunction in patients with 3VD, early screening of mild renal dysfunction and active CKD-protective measures are needed to prevent the initial progression of renal impairment in the secondary prevention of multivessel CAD.

Although numeric studies have examined the role of CKD (eGFR <60 mL/min/1.73 m2) in CAD patients, evidence concerning the impact of renal impairment in the categories of mild renal dysfunction (eGFR 60–89 mL/min/1.73 m2) is scarce [20]. In our study, the significant association between moderate renal function and risk of long-term death in patients with 3VD is consistent with several prior studies [7, 21‒23]. However, our results evaluating the impact of mild renal dysfunction differ from previous data. Although a post hoc analysis from the Extended-ESTABLISH trial showed that patients with acute coronary syndrome and mild renal dysfunction were associated with a 2.67-fold increase in long-term MACCE risk even after multivariate adjustment, this association was not observed in several other studies [24]. In a recent analysis of 10,354 patients with multivessel CAD from Korea, Kim et al. [7] found that the association between eGFR 60–89 mL/min/1.73 m2 and increased risk of death became nonsignificant after adjustment of baseline characteristics. Similar result was also observed in a clinical trial and a large-scale cohort [22, 25]. In another post hoc analysis from the SYNTAX trial, no increased rate of long-term death was found in the moderate renal function group [26]. Differences in the study scale, study design, number of diseased coronary vessels, and burden of atherosclerotic risk factors could partially explain the discrepancies. In our observational real-world study, a higher prevalence of several traditional CVD risk factors and high anatomic complexity may accelerate the progression of CKD and CVD sequelae in the early stage of renal dysfunction, which resulted in a higher risk of cardiac or noncardiac death in patients with mild renal dysfunction. Moreover, patients with renal impairment had higher rates of inadequate medication at discharge and potentially worse medication compliance, which could also play a role in worse outcomes.

In the subgroup analysis, we found that the impact of mild renal dysfunction on the risk of all-cause death differed by age and sex. Similar to our results, a meta-analysis including approximately two million subjects concluded a steeper risk relationship between decreased eGFR and all-cause death in women than in men among both general and high-risk populations [27]. This meta-analysis also revealed a “U-shaped” association between eGFR and risk of all-cause death in those with older age (≥65 years), which might be an explanation for the nonsignificant results between mild renal dysfunction and risk of death in the older age subgroup of our analysis. Given the higher death risk associated with mild renal function in the subgroup of older and female patients, more attention should be paid to these patients for risk stratification.

Current evidence for the optimal revascularization strategy in patients with renal dysfunction is controversial and mostly focused on patients with eGFR <60 mL/min/1.73 m2. According to an analysis from the Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial, PCI had a greater risk of long-term death compared with CABG in patients with CKD and left main CAD [9]. Similar results were also found in the analysis from several randomized trials and observational studies performed in patients with multivessel CAD [11, 26, 28‒30]. However, in a large-scale analysis of 5,920 propensity score-matched CAD patients, Bangalore et al. [8] reported that there was no difference in long-term death risk between PCI and CABG. A meta-analysis of randomized clinical trials showed similar results [31]. Moreover, in a pooled analysis of three large randomized clinical trials conducted in patients with stable ischemic heart disease and type 2 diabetes, the benefit of CABG over PCI observed in patients without CKD became nonsignificant in patients with CKD, which is concordant with our findings [10]. In the setting of CKD, the superiority of CABG over PCI in risk of death depends largely on the baseline anatomic and clinical risk, such as left main involvement and prior MI, which might be an explanation for the different results among these studies [32]. In our study, the attenuated superiority of CABG was mainly due to the increase in risk of noncardiac death in the CABG group. As postoperative acute kidney injury is a remarkable risk factor of death in patients undergoing CABG, CABG-related acute kidney injury may lead to the irreversible deterioration of kidney function and eventually a decreased survival rate in CKD patients [33]. Additionally, we compared the outcomes between PCI and CABG in patients with mild renal dysfunction. Similar to the normal function group, patients undergoing CABG had a lower rate of death, cardiac death, and MACCE, indicating that CABG is a preferred option for patients in this renal function category.

Our study has several limitations. First, angiographic and procedural characteristics such as lesion location, stent types, or bypass grafts are not available in our database. Second, this study is based on a prospective cohort. Although multivariable Cox regression analysis and propensity score matching are used for covariate adjustment, potential unmeasured confounders are still inevitable. Third, given that data were collected in a single center during a recruitment period from 2004 to 2011, the generalizability of our results is limited in contemporary procedural practices and other regions. Fourth, eGFR is only a crude measure to evaluate renal function and some other measures such as albuminuria level were lacking. Creatinine for eGFR calculation was measured only once on admission; thus, the impact of eGFR fluctuation over time was unknown. Finally, the small sample size and number of clinical events in the moderate renal function group limit the power to detect meaningful differences in outcomes. As such, our results should be interpreted as hypothesis-generating and further confirmation in a large cohort or randomized trials is needed.

We found that even mild renal dysfunction was significantly associated with a greater risk of all-cause death in patients with 3VD. Compared with PCI, CABG was associated with a borderline significant trend toward lower risk of all-cause death and MACCE in patients with normal renal function and mild renal dysfunction but not in those with moderate renal dysfunction. Therefore, more attention should be paid to early screening and intervention of mild renal dysfunction in 3VD patients, as well as revascularization decision-making in patients with renal impairment.

We appreciate all staff from the department of cardiology and follow-up center in Fuwai Hospital for their contribution to the study.

This study was approved by the Institutional Review Committee of Fuwai Hospital. All participants signed informed consent for participation. All patients enrolled in this study signed informed consent for publication.

The authors declare no conflict of interest.

This work was supported by the National Natural Science Foundation of China (Grant No. 81770365) and the National Key Research and Development Program of China (2016YFC1301300 and 2016YFC1301301).

Lei Song, Jinqing Yuan, Rutai Hui, and Runlin Gao contributed to the study design. Lianjun Xu, Jian Tian, Xinxing Feng, Dong Wang, Jingjing Xu, Ru Liu, Bo Xu, and Wei Zhao contributed to the data collection. Guyu Zeng, Deshan Yuan, Peizhi Wang, Tianyu Li, Lin Jiang, Xueyan Zhao, Yin Zhang, and Kai Sun contributed to the analysis or interpretation of data. Guyu Zeng drafted the manuscript. Deshan Yuan, Lei Song, and Jinqing Yuan critically revised the manuscript. Lei Song and Jinqing Yuan approved the version to be published. All authors read and approved the final submitted version.

Additional Information

Lei Song and Jinqing Yuan contributed equally to this work.

Original datasets in this study are available from the corresponding author after reasonable request.

1.
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