Impact of geriatric nutritional risk index on prognosis in peripheral artery disease patients undergoing endovascular therapy

Abstract

The prevalence of peripheral artery disease continues to rise, with major amputations and mortality remaining prominent. Frailty is a significant risk factor for adverse outcomes in the management of the vascular disease. The geriatric nutritional risk index has been used to predict adverse outcomes in lower extremity peripheral artery disease and is a nutrition‐based surrogate for frailty. The authors recruited 126 patients with peripheral artery disease who underwent endovascular stent implantation. As in previous reports, malnutrition was diagnosed by the geriatric nutritional risk index. The authors used Kaplan‐Meier and multivariate Cox proportional hazards regression analyses to analyze the risk of major adverse limb events, which included mortality, major amputation, and target limb revascularization. There were 67 major adverse limb events during a median follow‐up of 480 days. Malnutrition on the basis of the geriatric nutritional risk index was present in 31% of patients. Cox regression analysis showed that malnutrition based on the geriatric nutritional risk index was an independent predictor of major adverse limb events. Kaplan‐Meier analysis showed that major adverse limb events increased with worsening malnutrition. Our single‐center, retrospective evaluation of geriatric nutritional risk index (as a synonym for body health) correlates with an increased risk of major adverse limb events. Future directions should focus not only on identifying these patients but also on modifying risk factors to optimize long‐term outcomes.

1. INTRODUCTION

Lower‐extremity peripheral arterial disease (PAD) is the most common situation in clinical practice, and chronic limb‐threatening ischemia (CLTI) is a common lower‐extremity PAD condition. Due to chronic rest pain, CLTI patients are usually anorexic and insomniac, leading to malnutrition. ¹ , ² The incidence of malnutrition in PAD patients undergoing vascular surgery has been reported to be as high as 78%, although endovascular therapy (EVT) is an effective treatment for narrowed arteries. ³

Pre‐operative malnutrition has been associated with a longer length of stay in the hospital, poorer outcomes, and higher costs. ⁴ , ⁵ Many tools, including the Geriatric Nutritional Risk Index (GNRI), the Prognostic Nutritional Index (PNI), and the Controlling Nutritional Status (CONUT) score, have been used to stratify the risk of PAD in the lower extremity. ⁶ , ⁷ , ⁸ Research has suggested that immunological and nutritional status are closely related to cardiovascular progression and prognosis. ⁹ , ¹⁰ Our hypothesis is that the GNRI could be used for the identification of high‐risk patients with poor outcomes. It remains unclear whether GNRI can predict vascular patency in patients undergoing EVT.

Relationship between GNRI and poor clinical outcomes in patients undergoing EVT was investigated in the present study.

2. METHODS

2.1. Patient population

A single‐center, retrospective study evaluating patients with PAD who underwent endovascular stenting as part of limb salvage treatment strategy at our tertiary center between September 2016 and July 2021. PAD was diagnosed using the ankle brachial index (ABI) and computed tomographic angiography. Our cohort consisted of patients with intermittent claudication or tissue loss (Fontaine II–IV symptoms) secondary to arterial insufficiency who underwent endovascular stenting to optimize perfusion. Inadequate arterial perfusion was identified by previous non‐invasive studies such as ABI, duplex ultrasound, or computed tomography angiography, or by a previous invasive angiogram performed by a referring specialist.

2.2. Clinical characteristics

Cardiovascular risk factors were assessed in our patients, including coronary atherosclerosis, heart failure, stroke, hypertension, diabetes mellitus, chronic kidney disease, and smoking status. Hypertension was defined as systolic blood pressure of 140 mmHg, diastolic blood pressure of 90 mmHg, or use of antihypertensive medication; diabetes was defined as fasting blood glucose of 126 mg/dL and glycosylated hemoglobin A1c (HbA1c) of 6.5% (National Glycohemoglobin Standardization Program) or use of antidiabetic medication; and stroke was defined as a group of pathological conditions characterized by sudden, nonconvulsive loss of neurological function.

Before intervention, patients' baseline GNRI was calculated as follows GNRI = 14.89* serum albumin (g/dL) + 41.7*(current weight/ideal weight), where ideal weight (kg) = 22 × height (m) × height (m). If the patient is over ideal weight, weight/ideal weight is set to 1.A low GNRI (GNRI≤98) was defined as malnutrition, whereas a GNRI > 98 was considered to be no nutritional risk. ¹¹

2.3. Revascularization and medical therapy

Endovascular revascularization was performed in the catheterization laboratory in all patients. Dual antiplatelet therapy with aspirin 100 mg and clopidogrel 75 mg daily was continued for at least 6 months (based on follow‐up in the vascular surgery clinic), whichever was longer, as long as there was no evidence of bleeding complications. Patients on other P2Y12 inhibitors for previous percutaneous coronary interventions continued baseline. Patients with other clinical comorbidities (e.g., atrial fibrillation, deep vein thrombosis, or pulmonary embolism) requiring concomitant anticoagulation received either warfarin plus clopidogrel or direct oral anticoagulant plus clopidogrel for 6 months, after which clopidogrel was switched to aspirin 100 mg. The drug treatment was carried out in accordance with the relevant guidelines for patients with high cholesterol levels, high blood pressure, and an abnormal heart rate.

2.4. Follow‐up and study endpoints

After revascularization, patients were assessed at 1, 3, 6, 12, and 24 months with repeat ABI, duplex ultrasonography, or computed tomography angiography in our cardiology clinic. Data on healing, readmission, repeat revascularization, major amputation, or death were obtained from electronic records. We contacted patients by telephone if they were not followed up in time.

The endpoint was major adverse limb events (MALE). MALE was defined as all‐cause mortality, major amputation, and target lesion revascularisation (TLR). Finally, we will also discuss the impact of GNRI on the above indicators.

2.5. Statistical analysis

SPSS 25.0 (IBM SPSS Inc, Chicago, IL, USA) was used for statistical analysis. Continuous data are expressed as mean ± standard deviation, and skewed data are expressed as median with interquartile range (IQR). Continuous and categorical variables were compared using t‐tests and chi‐squared tests, respectively. Data that were not normally distributed were compared using the Mann‐Whitney U test. Kaplan‐Meier curves were used for time‐to‐event analysis. Kaplan‐Meier analysis was used to calculate cumulative event rates for each outcome. Cox proportional hazards analysis was used to identify the independent predictors of the occurrence of MALE. Multivariate analysis using a forward stepwise Cox proportional hazards model was performed to assess the independent predictors of combined MALE. Survival curves were constructed using the Kaplan‐Meier method and compared using the Wilcoxon test.

3. RESULTS

3.1. Baseline characteristics

A total of 250 patients underwent revascularization for Fontaine grade II‐IV symptoms during our study period. A total of 126 patients were included in our primary analysis after excluding those without clinical follow‐up, those who underwent open surgery with drug‐coated balloons, and those without available GNRI (Figure 1). The total duration of the follow‐up period was 16.2 ± 13.2 months.

FIGURE 1.

Flow chart of the selection of study participants.

All patients were grouped by the presence or absence of a postoperative outcome event. The low GNRI group consisted of 39 patients (31%). Twelve patients (30.8%) were classified as Fontaine class II, six patients (15.4%) as Fontaine Class III and 21 patients (53.8%) as Fontaine Class IV. While the high GNRI group comprises 87 patients (69%), 45 patients (51.7%) are classified as Fontaine class II, 25 patients (28.7%) as Fontaine class III and 17 patients (19.5%) as Fontaine class IV. With regard to age, sex, country, site of disease, and some pre‐existing conditions, there were no statistically significant differences between the two groups (Table 1).

TABLE 1.

The baseline study parameters of patients according to GNRI.

Variable	Low GNRI(n = 39)	High GNRI(n = 87)	p‐value
Age(y)	68(64.00–72.00)	66.00(61.00–73.00)	.282 a
Male(n%)	29(74.0)	64(73.6)	.925 c
Country(n%)	15(38.5)	48(55.2)	.083 c
BMI (kg/m2)	21.88 ± 2.37	25.65 ± 2.49	<.001 b
Fontaine grade			.001 c
II	12(30.8)	45(51.7)
III	6(15.4)	25(28.7)
IV	21(53.8)	17(19.5)
Pre‐ABI	0.55 ± 0.15	0.56 ± 0.19	.534 b
Post‐ABI	0.85 ± 0.18	0.90 ± 0.15	.724 b
Stroke	11(28.2)	28(32.2)	.655 c
Hypertension	28(71.8)	57 (65.5)	.487 c
Diabetes	18(46.2)	47(54.0)	.414 c
Smoker	19(48.7)	47(54.0)	.581 c
Drinker	8 (20.5)	11(12.6)	.254 c
ASA			.893 c
1	6(15.4)	12(13.8)
2	22(56.4)	53(60.9)
3	11(28.2)	22(25.3)
The length of the lesion(cm)	19.4(11.1–35.5)	13.9(7–24.4)	.037 a
The location of the lesion
Aortoiliac	13(33.3)	35(40.2)	.461 c
Femoral‐popliteal	30(76.9)	68(78.2)	.877 c
Below the knee	9(23.1)	14(16.1)	.348 c

Abbreviations: ABI, ankle branchial index; ASA, American society of Anesthesiologists; BMI, body mass index.

^a Mann‐Whitney U test; median (interquartile ranges).

^b Student t test; mean ± standart deviation.

^c Pearson chi‐square; number and percent.

Laboratory data showed significant differences between the two groups in neutrophils, red blood cells (RBC), platelets, D‐dimer, and high‐density lipoprotein; other data didn't differ (Table 2).

• a) Malnutrition and Clinical Outcomes

TABLE 2.

The Baseline labortory parameters of patients according to GNRI.

Variable	Low GNRI(n = 39)	High GNRI(n = 87)	p
Neutrophils (109/L),	7.09(4.72–9.18)	4.52(3.66–5.57)	<.001 a
Lymphocytes (109/L),	1.60 ± 0.58	1.95 ± 0.71	.124 b
RBC (109/L),	4.07 ± 0.53	4.46 ± 0.49	<.001 b
Platelet (109/L)	258(186.00–351.00)	231.00(180.00–261.00)	.025 a
HDL (mmol/L)	0.94 ± 0.27	1.03 ± 0.23	.048 b
LDL (mmol/L)	2.62 ± 0.84	2.88 ± 0.92	.131 b
Lipo (a) (mg/L)	347.3(149.57–695.57)	244.6(117.90–481.20)	.143 a
eGFR(ml/min)	85.24(63.19–94.98)	87.35(70.30–95.39)	.310 a
D‐dimer(mg/L)	0.66(0.34–1.07)	0.41 (0.25–0.71)	.010 a
Albumin	33.40(30.20–37.64)	40.60(37.70–42.20)	<.001 a
Total protein	62.70(57.70–65.90)	66.90(64.10–70.70)	<.001 a

Abbreviations: GNRI, geriatric nutritional risk index; HDL, high‐density lipoprotein; LDL, low‐density lipoprotein; RBC, red blood cell.

^a Mann‐Whitney U test; median (interquartile ranges).

^b Student t test; mean ± standart deviation.

^c Pearson chi‐square; number and percent.

To eliminate the influence of possible confounding factors, we included p < .05 in univariate analysis and .05 in multivariate COX regression analysis of factors including BMI, HDL, lesion length, Fontaine grade, neutrophils, RBC, platelets, D‐dimer, and high GNRI to obtain independent risk factors for MALE. When multivariate COX regression analyses were constructed including all these significant univariate predictors, high GNRI (risk ratio, 0.209; 95% confidence interval, 0.056–0.783; p = .020) was found to be a protective factor for MALE, as shown in Table 3. In addition, we plotted KM survival curves for GNRI classification to demonstrate the importance of the above factors in MALE (Figure 2).

TABLE 3.

Multivariate COX regression analysis showing independent predictors of MALE.

Variable	Hazard ratio	95CI%	p value
High GNRI	0.209	0.056–0.789	.020
BMI	1.068	0.896–1.275	.462
Length of lesion	0.989	0.957–1.022	.518
Fontaine grade			.256
III vs. II	2.604	0.941–7.206	.103
IV vs. II	0.997	0.260–3.817	.300
Neutrophils	1.037	0.864–1.244	.697
D‐dimer(mg/L)	0.909	0.698–1.184	.481
RBC	0.842	0.384–1.845	.667
platelet	0.998	0.959–1.261	.431
HDL	0.360	0.064–2.039	.248
Albumin	0.985	0.908–1.068	.707
Total protein	1.096	0.929–1.294	.277

Abbreviations: GNRI, geriatric nutritional risk index; HDL, high‐density lipoprotein; RBC, red blood cell.

FIGURE 2.

Kaplan‐Meier analysis for MALE among patients with GNRI‐based malnutrition status.0:Low GNRI 1:High GNRI.

4. DISCUSSION

The present study demonstrated that immune‐nutritional status was independently associated with MALE based on the GNRI in patients with peripheral artery disease after endovascular stenting.

PAD is a chronic peripheral atherosclerotic disease that can lead to limb‐related complications such as intermittent claudication, ischaemic rest pain, ischaemic ulcers, gangrene, and functional impairment. Complications requiring amputation have a 1‐year mortality rate of ≤50%. ¹² While limb complications are devastating in themselves, peripheral atherosclerosis is often a precursor to obstructive atherosclerotic disease elsewhere, including the brain and coronary arteries. Indeed, patients with peripheral atherosclerosis have an increased incidence of ischaemic stroke, myocardial infarction (MI), and cardiovascular death. ¹³ , ¹⁴ , ¹⁵

Atherosclerosis is a systemic inflammatory disease. ¹⁶ Inflammatory markers such as NLR (Neutrophil‐lymphocyte ratio), PLR (Platelet‐lymphocyte ratio), and CRP (C‐reactive protein) can be used to predict cardiovascular risk in patients with coronary artery disease. Rein and colleagues ¹⁷ reported that patients with PAD have a higher incidence of systemic inflammation than patients with coronary artery disease. PAD is not simply a peripheral atherosclerotic disease, but part of a multivascular disease. ¹⁸ Recently, the concept of a malnutrition‐inflammation‐atherosclerosis syndrome has been proposed, where inflammation tends to promote a catabolic state that inhibits protein synthesis and stimulates protein degradation, leading to malnutrition and reduced GNRI. ¹⁹ , ²⁰ Furthermore, malnutrition is a complex state that includes a decrease in protein reserves and caloric depletion, which can weaken immune defenses. Reduced immune defenses are a key factor in the development of many chronic diseases. Thus, there may be a positive feedback loop between inflammation, malnutrition, immune defenses, and adverse events, resulting in a vicious cycle. ²¹ , ²² , ²³

Conversely, some studies have shown that malnutrition itself can promote atherosclerosis. ²⁴ This vicious circle is known as the “malnutrition‐inflammation‐atherosclerosis syndrome.” The role of nutrition in patient outcomes has been demonstrated in many diseases (several types of cancer, cardiovascular disease), ²⁵ , ²⁶ but such studies are still relatively rare in lower extremity arterial disease.

Previous retrospective studies have shown that GNRI can predict some prognostic indicators after surgery in patients with atherosclerosis. Cheng and colleagues ²⁷ enrolled 699 patients undergoing percutaneous coronary intervention (PCI) to investigate the relationship between GNRI and postoperative all‐cause mortality and major adverse cardiovascular events, and concluded that malnutrition, as assessed by GNRI score at admission, is an independent predictor of adverse cardiovascular events in patients after PCI.

To investigate the correlation between GNRI and PAD in elderly patients with coronary artery disease, Kawamiya studied 228 patients and found that GNRI levels were closely related to PAD in elderly patients with coronary artery disease, which may strengthen the utility of GNRI as a screening tool in clinical practice. ²⁸ Matsuo and colleagues conducted a prospective cohort study of 1219 PAD patients with a median follow‐up of 73 months. Overall survival (OS), Major Adverse Cardiovascular Events(MACE) or MALE in PAD patients were recorded and it was concluded that GNRI was an independent predictor of OS, MACE and MALE in PAD patients. ²⁰

To date, there are few articles that improve the prognosis of PAD patients from a nutritional perspective. Studies have shown that vitamin D deficiency affects the healing of ischaemic ulcers and that supplementation with vitamin D and a high‐protein diet can alter clinical outcomes. ²⁹ , ³⁰ However, studies have shown that nutrient solution supplementation did not significantly improve the healing of diabetic foot ulcers. ³¹ , ³² Although there is no clear evidence that nutritional supplementation affects the long‐term prognosis of PAD patients, we should still pay attention to the role of malnutrition in the prognosis of PAD. It is of great importance to conduct clinical research on nutritional interventions.

Nutrition‐related indicators are used as prognostic indicators and should be included in preoperative assessment to better help patients. We found that malnutrition is very common in patients with peripheral arterial disease and is a risk factor for poor clinical outcomes. This shows that we can follow up preoperatively malnourished patients in time and remind them to come to the hospital regularly. Nutrition therapy will eventually become a new therapeutic target for the treatment of peripheral arterial disease.

5. CONCLUSIONS

Our single‐centre, retrospective evaluation of GNRI correlated with an increased risk of MALE and TLR. Future directions should focus not only on the identification of these patients, but also on risk factor modification to optimize long‐term outcomes.

AUTHOR CONTRIBUTIONS

Dikang Pan, Jiabin Wang, and Yongquan Gu contributed to the study design. Jingyu Wang, Wenzhuo Meng and Zhixiang Su preformed the data analysis. Dikang Pan wrote the manuscript. Yongquan Gu, Jianming Guo, and Xiaoming Shi critically revised and edited the manuscript for important intellectual content. All authors reviewed and approved the final manuscript.

CONFLICT OF INTEREST STATEMENT

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

Pan D, Wang J, Guo J, et al. Impact of geriatric nutritional risk index on prognosis in peripheral artery disease patients undergoing endovascular therapy. J Clin Hypertens. 2023;25:497–503. 10.1111/jch.14659