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Abstract

Background:

Contrast-induced nephropathy is a prevalent cause of hospital-acquired renal insufficiency and increases adverse events in older patients undergoing angiography and percutaneous coronary intervention. The Mehran risk score has been widely used in Vietnam to assess contrast-induced nephropathy risk in patients before coronary angiography and percutaneous coronary intervention. Recently, there has been a shift toward the adoption of simpler risk prediction models, such as the contrast volume-to-glomerular ﬁltration rate ratio. This study aimed to (1) determine the incidence of contrast-induced nephropathy in older patients undergoing coronary angiography and/or percutaneous coronary intervention, and (2) compare the validity of the contrast volume-to-glomerular ﬁltration rate ratio and the Mehran score in predicting contrast-induced nephropathy.

Method:

This is a prospective cohort study conducted at a hospital in Vietnam from September 2019 to May 2020. Consecutive patients aged ⩾60 years who underwent coronary angiography and/or percutaneous coronary intervention were recruited. The contrast volume-to-glomerular ﬁltration rate ratio and the Mehran score were evaluated for their predictive utility regarding contrast-induced nephropathy risk. The receiver operator characteristic was employed to calculate the area under the curve for both the contrast volume-to-glomerular ﬁltration rate ratio and the Mehran score in predicting contrast-induced nephropathy.

Results:

The study included 170 participants with a mean age of 70 years and 33.1% were female. Contrast-induced nephropathy was diagnosed in 9.4% of the participants. Participants with contrast-induced nephropathy exhibited a higher prevalence of chronic kidney disease, anemia, and heart failure. There was no significant difference between the area under the curves of the contrast volume-to-glomerular ﬁltration rate ratio (0.79, 95% CI: 0.65–0.92), and the Mehran score (0.65, 95% CI: 0.51–0.82) in predicting contrast-induced nephropathy.

Conclusion:

Our findings indicate that contrast-induced nephropathy was prevalent among older patients following percutaneous coronary intervention. The contrast volume-to-glomerular ﬁltration rate ratio demonstrated a good prognostic value for predicting contrast-induced nephropathy comparable to that of the Mehran score. Further research is needed to identify optimal cutoff values for the contrast volume-to-glomerular ﬁltration rate ratio in older patients.

Keywords

Contrast-induced nephropathy coronary heart disease percutaneous coronary intervention elderly risk prediction

Introduction

The prevalence of coronary heart disease increases with age and older patients accounted for a large proportion of patients presenting with coronary heart disease.¹ Advancement in percutaneous coronary intervention (PCI) has contributed to reduced mortality in patients with coronary artery disease.² However, coronary angiography and percutaneous intervention have also increased the risk of developing contrast-induced nephropathy (CIN), especially in older patients with multimorbidity.^2–4 CIN is an acute kidney injury (defined as a 25% increase in serum creatinine from baseline or 0.5 mg/dL absolute increase in serum creatinine) occurring within 48–72 h post IV contrast administration.^3–5 It is an iatrogenic acute kidney injury with potentially severe outcomes. CIN is the third common cause of hospital-acquired renal insufficiency and can negatively impact the treatment effect and increase mortality in patients undergoing PCI.^3–6

Over ten risk assessment tools have been developed to predict CIN.⁷ Among these, the Mehran risk score has been the most commonly used in Vietnam.⁸ Introduced by Mehran and colleagues in 2004, the Mehran score has been widely applied in many studies to predict CIN as well as short- and long-term clinical outcomes in patients with ST elevation myocardial infarction.⁸ Although the Mehran score has been demonstrated to be clinically helpful for the prediction of CIN, the complexity of this score may hinder its application in resource-limited settings. In recent years, there has been a shift toward the adoption of simpler risk prediction models, such as the contrast volume-to-glomerular ﬁltration rate ratio (CV/GFR ratio). The CV/GFR ratio, calculated as the ratio of contrast medium quantity to glomerular ﬁltration rate (GFR), was proposed as a predictor of the development of CIN in patients after PCI.^9,10

Vietnam is a middle-income country in Southeast Asia and is one of the countries with the highest number of older people in the region (11 million people aged ⩾ 60, representing approximately 12% of the population in 2017, and it is estimated that in 2038 older people will represent approximately 20% of the Vietnamese population).¹¹ In Vietnam, cardiovascular disease was responsible for approximately one-third of annual deaths.¹² There is an increasing trend in number of older adults undergoing coronary angiography and percutaneous interventions. Therefore, our study aimed to (1) determine the incidence of CIN in older people undergoing coronary angiography/PCI, and (2) compare the validity of the CV/GFR ratio and the Mehran score in predicting CIN.

Methods

Study design

This prospective observational study was conducted at the Department of Interventional Cardiology, Thong Nhat Hospital in Ho Chi Minh City, Vietnam.

Participants

Consecutive patients were recruited from September 2019 to May 2020. The inclusion criteria were: (1) age 60 years or older, (2) undergoing coronary angiography and/or PCI, and (3) with recorded serum creatinine levels before and in 48 h after angiography. The exclusion criteria included: (1) concurrent use of other nephrotoxic medications, (2) transfer to another hospital, discharge, or death within 48 h after the procedure, or (3) not providing consent.

The study was approved by the Ethics Committee of Thong Nhat Hospital in Ho Chi Minh City (No. 18/2020/BVTN-HDYD). Written informed consent was obtained from all participants.

Data collection

Collected information encompassed demographic characteristics, height, weight, medical history, comorbidities, laboratory results during hospitalization including serum creatinine levels, and the contrast volume (iohexol) used during the procedure. Age and sex were recorded from the participants’ medical records. Body mass index (BMI, kg/m²) was calculated from measured weight (kg) and height (m), and categorized into four groups: underweight (BMI < 18.5 kg/m²), normal (BMI: 18.5–22.9 kg/m²), overweight (BMI: 23–24.9 kg/m²), and obese (BMI ⩾ 25.0 kg/m²).¹³ Smoking status was categorized based on self-reporting as non-smoking or smoking (including current smokers or ex-smokers who quit less than 1 year ago).

Outcome variable: CIN was defined as a 25% increase in serum creatinine from baseline or 0.5 mg/dL absolute increase in serum creatinine occurring within 48 h post IV contrast administration.

CIN risk prediction models

The CV/GFR ratio: The CV/GFR ratio was calculated as the ratio of contrast quantity received to the patient’s GFR. The GFR was estimated using the Cockcroft–Gault method: 140 – age (years) × weight (kg)/(72 × serum creatinine (mg/dl) (×0.85 for female participants).¹⁴ In a large observational study in the USA involving 3179 consecutive patients undergoing PCI (mean age 64 ± 12), a CV/GFR ratio > 3.7 was a significant and independent predictor of an early abnormal increase in serum creatinine after PCI.¹⁰

The Mehran score, developed by Mehran and colleagues in 2004, is a risk assessment tool for predicting CIN. The score is calculated based on the following factors: hypotension (if systolic blood pressure is less than 80 mmHg for at least 1 h requiring inotropic support: 5 points), use of intra-aortic balloon pump (5 points), congestive heart failure (if class III/IV by New York Heart Association classification¹⁵ or history of pulmonary edema: 5 points), older than 75 years: 4 points), anemia (if hematocrit less than 39% for men and less than 36% for women: 3 points), diabetes mellitus (3 points), contrast media volume (1 point per 100 mL), and estimated glomerular filtration rate (GFR; measured in mL/min per 1.73 m²; 2 points if GFR 60–40; 4 points if GFR 40–20; 6 points if GFR < 20). A risk score < 5 indicated low CIN risk, while 6–15 indicated intermediate, and 16 or more indicated high risk.⁸

Power analysis: The sample size for this study was estimated using a single population proportion formula: n = Z² _1−α/2 * [p*(1−p)/d²], with n = the required sample size, Z_1−α/2 = 1.96 (with α = 0.05 and 95% confidence interval), p = estimated rate of CIN in older patients after PCI, and d = precision (assumed as 0.05). Our literature search found only one previous study in Vietnam reporting an incidence of approximately 13% in older adults (mean age 68.9 ± 9.9) after PCI.¹⁶ Therefore, the estimated sample size is approximately 170 participants.

Statistical analysis

The data analysis for our study was conducted using SPSS for Windows (version 27.0, IBM Corp., Armonk, NY, USA) and R 4.1.1. Continuous variables are expressed as means accompanied by standard deviations (SDs), while categorical variables were depicted as frequencies and percentages. Group comparisons were performed employing the Chi-square test or Fisher’s exact test for categorical variables and either Student’s t-test or Mann–Whitney test for continuous variables.

The receiver operator characteristic (ROC) was used to assess the area under the curve (AUC) for the CV/GFR ratio and the Mehran score in predicting CIN, and to determine the cutoff points of the scores. Comparison in the AUCs was conducted via MedCalc using the method by Hanley and McNeil.^17,18 A higher AUC value suggests a better diagnostic ability. An AUC of 0.5 suggests no discrimination (i.e., ability to diagnose patients with and without CIN based on the test), 0.7–0.8 is considered acceptable, 0.8–0.9 is considered excellent, and more than 0.9 is considered outstanding.¹⁹

Results

There were 170 participants in this study. The mean age of the participants was 70 years (SD: 9.2), and 33.1% of them were women. Of these 170 participants, 16 (9.4%) had CIN.

The characteristics of participants are described in Table 1. The prevalence of chronic kidney disease (31.3% vs 2.6%, p < 0.001), heart failure (50.0% vs 26.6%, p = 0.049), and anemia (75.0% vs 42.9%, p = 0.014) was higher in participants with CIN compared to those without CIN, respectively. Participants with CIN were also more likely to be underweight (18.8% vs 5.2% in those without CIN, p = 0.027). The mean contrast volume injected was 202.5 ± 133.8 mL in all participants, significantly higher in those with CIN than in those without CIN (371.3 ± 163.7 mL vs 184.9 ± 117.7 mL, p < 0.001).

Table 1.

Participant characteristics.

Characteristics	All (n = 170)	Participants with CIN (n = 16)	Participants without CIN (n = 154)	p-Value
Age (years)	70.0 ± 9.2	71.3 ± 9.3	69.7 ± 9.2	0.507
Sex
Male	113 (66.5%)	10 (62.5%)	103 (66.9%)	0.724
Female	57 (33.5%)	6 (37.5%)	51 (33.1%)	0.724
Smoking	43 (25.3%)	2 (12.5%)	41 (26.6%)	0.216
Body mass index
Normal	75 (44.1%)	10 (62.5%)	65 (42.2%)	0.027
Underweight	11 (6.5%)	3 (18.8%)	8 (5.2%)
Overweight	38 (22.4%)	2 (12.5%)	36 (23.4%)
Obese	46 (27.1%)	1 (6.3%)	45 (29.2%)
SBP at admission (mmHg)	126.7 ± 19.4	125.0 ± 21.9	126.9 ± 19.2	0.717
DBP at admission (mmHg)	75.4 ± 9.1	74.1 ± 9.2	75.5 ± 9.2	0.540
Heart rate at admission (beats per min)	76.8 ± 14.7	76.7 ± 13.8	76.8 ± 14.8	0.982
Ejection fraction (%)	62.2 ± 10.9	56.8 ± 11.0	62.8 ± 10.8	0.036
Blood glucose level (mmol/L)	7.6 ± 3.4	8.1 ± 4.8	7.6 ± 3.2	0.590
Lipid profile (mmol/L)
Total cholesterol	4.5 ± 1.3	4.4 ± 0.8	4.5 ± 1.4	0.861
LDL cholesterol	2.6 ± 1.1	2.6 ± 0.7	2.6 ± 1.1	0.927
HDL cholesterol	1.0 ± 0.3	1.0 ± 0.3	1.0 ± 0.3	0.962
Triglyceride	1.9 ± 1.6	1.8 ± 1.1	2.0 ± 1.7	0.556
Hypertension	170 (100%)	16 (100%)	154 (100%)	N/A
Diabetes	63 (37.1%)	8 (50.0%)	55 (35.7%)	0.260
Heart failure	49 (28.8%)	8 (50.0%)	41 (26.6%)	0.049
Anemia	78 (45.9%)	12 (75.0%)	66 (42.9%)	0.014
Chronic kidney disease	9 (5.3%)	5 (31.3%)	4 (2.6%)	<0.001
Procedure
Angiography only	47 (27.6%)	7 (43.8%)	40 (26.0%)	0.201
Scheduled PCI	89 (52.4%)	5 (31.3%)	84 (54.5%)
Emergency PCI	34 (20.0%)	4 (25.0%)	30 (19.5%)
Contrast volume (mL)	202.5 ± 133.8	371.3 ± 163.7	184.9 ± 117.7	<0.001
⩽50 mL	33 (19.4%)	1 (6.3%)	32 (20.8%)	0.018
51–150 mL	28 (16.5%)	0 (0%)	28 (18.2%)
151–200 mL	33 (19.4%)	2 (12.5%)	31 (20.1%)
>200 mL	76 (44.7%)	13 (81.3%)	63 (40.9%)

CIN: contrast-induced nephropathy; SBP: systolic blood pressure; DBP: diastolic blood pressure; LDL: low-density lipoprotein; HDL: high-density lipoprotein; PCI: percutaneous coronary intervention.

Figure 1 presents the mean values of serum creatinine at baseline, after 24 and 48 h, stratified by CIN status. The mean values of the Mehran score and CV/GFR ratio are presented in Figure 2.

Figure 1.

Serum creatinine level at baseline, after 24 and 48 h, stratified by contrast-induced nephropathy (CIN) status.

Figure 2.

Mean values of the Mehran score and the contrast volume-to-glomerular ﬁltration rate (CV/GFR) ratio.

Figure 3 presents the ROC showing AUC of the CV/GFR ratio and the Mehran score. The AUC of the CV/GFR ratio in predicting CIN was 0.79 (95% CI: 0.65–0.92), and that of the Mehran score in predicting CIN was 0.65 (95% CI: 0.51–0.82). The difference between these two AUCs was not statistically significant (p = 0.23).

Figure 3.

ROC showing areas under the curve (AUCs) of the CV/GFR ratio and the Mehran score.

Table 2 presents the sensitivity and specificity for several potential cutoff points of the CV/GFR ratio and Mehran score. Consistent with previous studies, Mehran > 5 shows good sensitivity and acceptable specificity in this studied population. Regarding the CV/GFR ratio, we found that a cutoff point of 4.7 shows better specificity than 3.7 in this study’s participants.

Table 2.

The sensitivity and specificity for various cutoff points of the CV/GFR ratio and Mehran score.

Risk score	Cutoff point	Sensitivity (%)	Specificity (%)
Mehran	>5	81	53
Mehran	>6	75	63
Mehran	>7	50	73
CV/GFR ratio	>3.7	81	58
CV/GFR ratio	>4.7	81	71
CV/GFR ratio	>5.0	75	75

Discussion

In this study in 170 older participants undergoing coronary angiography and intervention, we found that 9.4% of them developed CIN after the procedures. Participants with CIN were more likely to have a history of chronic kidney disease, heart failure, anemia, underweight, and received a higher dose of contrast.

The incidence of CIN in our studies is consistent with the literature. In a recent systematic review and meta-analysis of 120 studies, the pooled proportion for CIN after angiography was 9.1% (95% CI: 8.5–9.6%).²⁰ In several studies in Asian populations, the reported incidence of CIN was varied. In a study of 152 patients (mean age 58.5 ± 23.0) with coronary heart disease undergoing PCI in Nepal from February 2010 to July 2010, 13.2% of the participants developed CIN after the procedure.²¹ In a study in 1331 patients (mean age 67.0 ± 7.6 in the CIN group, 61.5 ± 8.5 in the non-CIN group) undergoing PCI in China from January 2017 to January 2020, the incidence of CIN was 15.3%.²² A retrospective analysis of the Malaysia National Cardiovascular Database PCI Registry in 248 patients who underwent PCI in 2019 showed that 4.4% of them had CIN.²³ CIN incidence is usually higher in emergency PCI for acute coronary syndrome, up to 28% according to a study in 338 patients with acute ST-segment elevation myocardial infarction or unstable angina/non–ST-segment elevation myocardial infarction (mean age 67 ± 11 in the CIN group, 65 ± 10 in the non-CIN group) in Japan.²⁴

Contrast-induced nephropathy is a common and concerning complication of coronary intervention, particularly in older patients.²⁵ Many studies have shown that CIN increased adverse outcomes for patients after PCI. A recent meta-analysis of 22 studies (n = 32,781) revealed that in patients with acute coronary syndrome undergoing PCI, CIN increased by 216%, 455%, 49%, and 50% relative risk for all-cause mortality, short-term all-cause mortality, major adverse cardiac events, and stent restenosis, respectively.²⁶ Our finding supports the need for further research into CIN in older people, and on how to reduce the risk of CIN in this vulnerable population. Older patients usually have multiple comorbidities, including those diseases that have been shown to increase the risk of CIN such as chronic kidney disease, diabetes, and heart failure.^23,25,27 Chronic kidney disease, for instance, compromises renal function, making kidneys less capable of handling the nephrotoxic effects of contrast media used during angiography and PCI.²⁸ Similarly, diabetes can lead to microvascular damage, further impairing renal function, while heart failure affects the overall perfusion and can contribute to renal congestion and injury.^23,25,27 The interaction of these conditions necessitates meticulous preoperative evaluation and management to minimize the incidence of CIN in older patients. It is essential for clinicians to take appropriate preventive measures to reduce the risk of developing CIN in these patients. Older patients should receive careful preoperative evaluation and management to minimize the risk of developing CIN. Physicians need to consider the use of preventative measures such as pre-hydration therapy, contrast volume limitation, and the use of low osmolar contrast media in clinical decision-making to minimize the risk of CIN associated with the procedure.²⁹ Post-procedure care is equally important. Close monitoring of renal function immediately after PCI can facilitate early detection and management of CIN if it develops. Prompt treatment of any emerging renal impairment, along with adjusting medications that may exacerbate renal dysfunction, is vital to improving outcomes.²⁹ By implementing these approaches, clinicians can significantly improve the prognosis and quality of life for older patients undergoing coronary interventions.

Regarding the risk prediction scores, we observed that both the CV/GFR ratio and the Mehran score had good prognostic value for predicting CIN in the study participants. In a recent systematic review and meta-analysis of six studies (n = 16,899 patients) examining the predictive value of the CV/GFR for CIN after PCI, the authors concluded that the CV/GFR ratio could be considered a reliable predictor for the development of CIN in patients undergoing PCI (odds ratio 2.67, 95% CI: 1.88–3.78).³⁰ However, it is important to note that the cutoff values for the CV/GFR ratio varied considerably across the studies included in this review: >2.44, >2.88, >2.86, >3, >4, and >6.15.³⁰ This variability highlights a key area for future investigation. Determining the most appropriate cutoff values, particularly for older patients who are usually at higher risk of CIN, is crucial. Such research could lead to more precise and individualized risk assessment tools and ultimately improving patient outcomes. Further studies are, therefore, essential to standardize these cutoff values, and to enhance the predictive accuracy of the CV/GFR ratio, ensuring that it can be effectively used in clinical settings to mitigate the risk of CIN.

Our study provided useful insights into CIN among older patients with coronary heart disease in Vietnam. The findings are significant as they highlight the incidence rate of CIN in this older population, contributing to a better understanding of how to manage and prevent this condition in vulnerable older patients. However, this study has several limitations. First, it is important to note that the study was conducted at a single hospital. Hence, the results may not be representative of the broader population in Vietnam and should be interpreted with caution. The limitation of conducting the study in a single urban hospital means that the study sample may not encapsulate the diversity found across different regions and healthcare settings in Vietnam. Older patients from other hospitals might have different demographic profiles, socioeconomic statuses, or health conditions that could affect the incidence and risk factors associated with CIN. Therefore, multicenter studies are necessary to validate these findings and provide a more comprehensive overview of CIN and its risk assessment tools in older patients with coronary heart disease across the country. Second, information regarding the indications of angiography/PCI for each participant, as well as their pre- hydration and post-hydration treatments, was not collected for this study. Another important consideration is the hemodynamic status of the participants. Most participants in this study had stable hemodynamic status at the time of their procedures. As a result, the study may not adequately represent elderly patients with unstable hemodynamics, who are potentially at a higher risk for CIN. Unstable hemodynamics can exacerbate renal impairment due to fluctuations in blood pressure and perfusion to the kidneys, so further research should focus on this subgroup to determine if and how they differ in terms of CIN risk and outcomes.

Conclusion

Our study indicates that CIN was prevalent among older patients following coronary angiography and PCI. The CV/GFR ratio demonstrated a good prognostic value for predicting CIN comparable to that of the Mehran score. Further research is needed to identify optimal cutoff values for the CV/GFR ratio in older patients in Vietnam. Continued research and clinical trials are crucial to develop new preventive measures.

Footnotes

Acknowledgements

Not applicable.

Author notes

An abstract based on this work was presented at the European Society of Cardiology—Asia Conference in Singapore in 2022 and was published in the European Heart Journal 2023, volume 44 (Suppl_1). DOI: 10.1093/eurheartj/ehac779.114.

Author contributions

Study conception and design: Tan Van Nguyen and Tu Ngoc Nguyen. Ethics application, recruitment, data acquisition: Tan Van Nguyen and Nhi Tuyet Quang. Project management: Tan Van Nguyen and Ngo Thi Kim Trinh. Statistical analysis: Weber Liu and Tu Ngoc Nguyen. Drafting of the manuscript: Tu Ngoc Nguyen, Tan Van Nguyen, and Weber Liu. All authors were involved in interpretation of data and revised the manuscript critically for important intellectual content. All authors read and approved the final manuscript.

Availability of data and materials

The study data are available from the corresponding author upon request.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Ethics approval

Ethical approval for this study was obtained from *The Ethics Committee of Thong Nhat Hospital in Ho Chi Minh City (No. 18/2020/BVTN-HDYD)*.

Informed consent

Written informed consent was obtained from all subjects before the study.

Trial registration

Not applicable.

ORCID iD

Tu Ngoc Nguyen

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