Hyperuricemia is associated with altered perioperative neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,and inflammatory responses in patients residing in high-altitude regions who underwent anterior cruciate ligament reconstruction: A cross-sectional study

Abstract

Objective

Hyperuricemia is a common metabolic disorder linked to systemic inflammation; however, its impact on perioperative hematological and inflammatory markers in patients residing in high-altitude regions who have undergone anterior cruciate ligament reconstruction remains unclear. We hypothesized that hyperuricemia is associated with a heightened perioperative inflammatory response.

Methods

This retrospective, cross-sectional study included 83 long-term high-altitude (≥2500 m) residents who underwent anterior cruciate ligament reconstruction between 2019 and 2025. Patients were divided into hyperuricemia (n = 40) and normouricemia (n = 43) groups based on their serum uric acid levels. Inclusion criteria included isolated anterior cruciate ligament injury, complete perioperative laboratory records, and confirmed preoperative hyperuricemia based on serum uric acid levels. Exclusion criteria included systemic inflammatory disease and incomplete data. Perioperative hematological and inflammatory parameters—including platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio—were compared using t-tests and chi-square tests.

Results

Preoperatively, the hyperuricemia group had lower neutrophil-to-lymphocyte ratio (1.17 ± 0.92 vs. 1.91 ± 0.82, p < 0.001) and platelet-to-lymphocyte ratio (101.6 ± 28.4 vs. 116.4 ± 31.9, p = 0.028) but higher lymphocyte count (2.21 ± 0.56 vs. 1.91 ± 0.47, p = 0.009) than the normouricemia group. Postoperatively, compared with the normouricemia group, the hyperuricemia group showed elevated white blood cell count (10.82 ± 2.90 vs. 8.23 ± 2.55, p < 0.001), neutrophil count (7.98 ± 2.88 vs. 5.55 ± 2.23, p < 0.001), and lymphocyte count (2.63 ± 2.36 vs. 1.75 ± 0.52, p = 0.023) but lower platelet-to-lymphocyte ratio.

Conclusion

Hyperuricemia is associated with altered perioperative hematological profiles and amplified inflammatory responses in patients residing in high-altitude regions who have undergone anterior cruciate ligament reconstruction, underscoring the need for targeted perioperative monitoring.

Keywords

Anterior cruciate ligament uric acid hyperuricemia blood cells altitude

Introduction

Anterior cruciate ligament (ACL) injury is one of the most common knee joint injuries.^1,2 In recent years, with the increasing popularity of national fitness programs, the incidence of ACL injuries has shown a rising trend.^3,4 The primary treatment modality is arthroscopic ACL reconstruction (ACLR), which aims to restore knee joint function and facilitate return to sports activities.^5–7 However, postoperative outcomes are influenced by multiple factors, among which hyperuricemia (HUA) has emerged as a significant factor.⁸

HUA is a metabolic disorder characterized by elevated serum uric acid (SUA) levels, primarily due to excessive production or inadequate renal excretion of uric acid.⁹ As the end product of purine metabolism, uric acid can induce inflammatory responses through oxidative stress mechanisms, potentially hindering postoperative recovery.¹⁰ Furthermore, HUA may impair postoperative recovery not only by exacerbating inflammatory responses but also by contributing to vascular dysfunction and thrombogenesis,^11,12 thereby increasing the risk of postoperative complications. In addition, renal impairment in HUA patients may alter the pharmacokinetics of perioperative drugs, which, in combination with HUA, can increase the risk of postoperative complications and delay recovery.⁷

The inflammatory response is a core component of postoperative recovery regulation after ACLR. Determining reliable and easily accessible inflammatory markers is crucial for optimizing perioperative management. In recent years, with the help of convenient and routine peripheral blood tests,¹³ several new inflammatory markers based on peripheral blood counts have been proposed.¹⁴ Among them, the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been found to be associated with clinical outcomes in various diseases, including pneumonia, acute myocardial infarction, and cancer.^15–17 High-altitude regions are generally defined as areas located at an elevation of ≥2500 m and are characterized by hypobaric hypoxia, cold temperatures, strong winds, and intense ultraviolet radiation.¹⁸ This type of environment can exert unique physiological stress on the human body, not only leading to decreased arterial oxygen saturation, increased heart rate, increased blood pressure, and hormonal disorders¹⁹ but also interfering with uric acid metabolism, resulting in increased uric acid production and decreased urate excretion.²⁰ Based on these unique effects, HUA may have a more significant effect on the perioperative inflammatory response of ACLR patients in plateau regions. However, existing studies have neither clarified how HUA affects key inflammatory indicators such as NLR and PLR in ACLR patients in plateau regions nor elucidated the relationship between these indicators and postoperative inflammatory complications, resulting in insufficient theoretical support for preoperative HUA management and postoperative inflammatory monitoring in this population.

This study aimed to investigate the impact of HUA on perioperative hematological and inflammatory markers in patients undergoing ACLR in a plateau region and clarify the relationship between HUA and postoperative inflammatory responses. We hypothesized that compared with individuals with normal uric acid levels, ACLR patients with HUA who reside in plateau regions exhibit significant abnormalities in the perioperative NLR and PLR levels, which are associated with elevated postoperative inflammatory markers such as white blood cell and neutrophil counts, leading to an increased risk of postoperative inflammatory complications.

Materials and methods

Clinical data

A retrospective study design was employed to collect clinical data from patients who were diagnosed with ACL injury, had a history of high-altitude residence, and were admitted to the Department of Orthopedics at the General Hospital of the Western Theater Command of the People’s Liberation Army between January 2019 and January 2025. This was a cross-sectional study. Inclusion criteria were as follows: (a) age 20–60 years (based on the age mentioned on the identity card produced at the time of consultation); (b) confirmed isolated ACL injury on arthroscopy (Figure 1(a)) and knee magnetic resonance imaging, excluding other intra-articular knee injuries such as meniscus tears and posterior cruciate ligament injuries; (c) record of continuous residence at an altitude ≥2500 m for ≥2 years within 3 years prior to consultation, with residence history verified using household registration, residence certificate, or health records; (d) preoperative SUA level meeting the diagnostic criteria for HUA; and (e) no use of medications that affect uric acid metabolism, such as allopurinol and diuretics, for ≥1 month prior to consultation. Medication use was cross-verified using questionnaires and electronic medical records. Exclusion criteria included the following: (a) refusal to undergo arthroscopic ACLR; (b) preoperative functional impairment such as knee deformity or post-traumatic arthritis (Lysholm score <60), which might interfere with treatment and prognosis; (c) inability to cooperate with preoperative examinations, surgery, and postoperative follow-up due to mental illness, cognitive impairment, or severe systemic illness. In total, 83 patients were enrolled and divided into the HUA group (n = 43) and normouricemia (NU) group (n = 40) based on SUA levels. This study was approved by the Ethics Committee of the General Hospital of the Western Theater Command of the People’s Liberation Army (Approval No. 2024EC4-ky013). Findings were reported based on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.²¹ This study was conducted in accordance with the Helsinki Declaration of 1975, as revised in 2013.

Figure 1.

Images showing ACL under arthroscopy. (a) Injured ACL. (b) Central localization of femoral attachment site. (c) Femoral tunnel and (d) reconstructed ACL. ACL: anterior cruciate ligament.

Surgical method

The patient was positioned supine; an arthroscope and instruments were inserted using a conventional medial and lateral approach into the knee joint to explore the joint cavity. A longitudinal incision, approximately 2.5 cm in length, was made two fingerbreadths medial to the tibial tubercle of the lower leg. The sartorius tendon sheath was exposed after layered dissection. The semitendinosus and gracilis tendons were freed, trimmed to an appropriate length, and then braided into five strands. Absorbable oxidized regenerated cellulose hemostatic pads were placed deep within the sartorius aponeurosis at the tendon harvest site to control bleeding. Intraoperative anchor points were established at the tibial and femoral attachments of the ACL (Figure 1(b)), and femoral and tibial tunnels were drilled according to the diameter of the braided tendon (Figure 1(c)). After the braided tendon was placed in both tunnels, the femoral end was fixed with a circumferential titanium plate, and the tibial end was fixed with a compression screw and pin. Postoperative arthroscopic examination demonstrated good tension of the reconstructed ligament (Figure 1(d)), with no impingement of the reconstructed ligament with the intercondylar notch during knee flexion and extension. All ACLRs were performed by the same senior surgical team following a standardized procedure to minimize variability related to surgeon technique.

Data collection

We collected general information from all patients, including age, sex, body mass index (BMI), smoking history, alcohol consumption history, medication history (diuretics and aspirin), and comorbidities (hypertension, hyperlipidemia, diabetes, and coronary heart disease). Blood samples were collected 24 h before and 24 h after the surgery to obtain data on hematological and inflammatory indicators, including preoperative and postoperative erythrocyte sedimentation rate (ESR); high-sensitivity C-reactive protein (hsCRP), blood urea nitrogen (BUN), creatinine (CREA), SUA, albumin (ALB), and hemoglobin (Hb) levels; and white blood cell (WBC), red blood cell (RBC), platelet, neutrophil, and lymphocyte counts, as well as to calculate the PLR and NLR. Information regarding dietary patterns and exercise habits, which may influence the SUA level, was not systematically collected in this study.

Statistical analyses

Statistical analyses were performed using the Statistical Package for Social Sciences (SPSS) software (version 27.0, IBM Corp, Chicago, IL, USA). The normality of continuous variables was assessed using the Shapiro–Wilk test. Categorical data were expressed as numbers and percentages, and intergroup comparisons were performed using the chi-square test. Continuous variables were expressed as mean ± standard deviation (x ± s) values. Normally distributed data were analyzed using independent sample t-tests, while non-normally distributed data were analyzed using Mann–Whitney U tests (two independent sample nonparametric tests). A p-value <0.05 was considered statistically significant.

Results

Comparison of baseline characteristics between the two patient groups

This study included a total of 83 patients. Due to the specific nature of the study, all patients were men; did not have hypertension, hyperlipidemia, diabetes, coronary heart disease, or other related conditions; and had not taken any medications that affect uric acid levels within 1 month prior to admission. In the NU group, the age range of the patients was 21–36 (average: 27.08 ± 3.67) years, and the length of hospital stay was 8–39 (average: 15.43 ± 6.24) days; the average values of other parameters were as follows: BMI, 23.17 ± 1.81 kg/m²; systolic blood pressure, 121.5 ± 13.9 mmHg; and diastolic blood pressure, 74.28 ± 8.07 mmHg. In the HUA group, the age range of the patients was 21–34 (average: 25.65 ± 3.32) years, and the length of hospital stay was 6–55 (average: 16.16 ± 8.03) days; the average values of other parameters were as follows: BMI, 23.97 ± 3.05 kg/m²; systolic blood pressure, 123.49 ± 10.41 mmHg; and diastolic blood pressure, 78.34 ± 8.45 mmHg. There were no statistically significant differences in the age, length of hospital stay, and systolic blood pressure; however, significant differences were noted in the diastolic blood pressure between the two groups, as shown in Table 1.

Table 1.

Comparison of general information.

Variables	NU	95% CI/percentage	HU	95% CI/percentage	X²/t value	p value
Age (years, $\bar{x} \pm$ s)	27.08 ± 3.67	(25.92, 28.24)	25.65 ± 3.32	(24.62, 26.68)	1.852	0.064
Hospitalization days (d, $\bar{x} \pm$ s)	15.43 ± 6.24	(13.48, 17.38)	16.16 ± 8.03	(13.64, 18.62)	0.465	0.068
BMI (kg/m², $\bar{x} \pm s)$	23.17 ± 1.81	(22.63, 23.71)	23.97 ± 3.05	(22.93, 24.99)	1.466	0.147
Drinking history (cases)	17 (39.5%)	39.5%	18 (45.0%)	45.0%	0.254	0.614
Smoking history (cases)	24 (55.8%)	55.8%	17 (42.5%)	42.5%	1.470	0.225
Systolic blood pressure (mmHg, $\bar{x} \pm$ s)	121.5 ± 13.90	(117.21, 125.79)	123.49 ± 10.41	(119.94, 127.04)	0.744	0.459
Diastolic blood pressure (mmHg, $\bar{x} \pm$ s)	74.28 ± 8.07	(71.77, 76.79)	78.34 ± 8.45	(75.74, 80.94)	2.242	0.028

Data are presented as mean ± SD ( $\bar{x} \pm$ s).

NU: normouricemia; CI: confidence interval; HU: hyperuricemia; BMI: body mass index.

Preoperative comparisons

As shown in Table 2, the preoperative lymphocyte counts were significantly higher in the HUA group than in the NU group (mean difference = 0.30 × 10⁹/L, 95% confidence interval (CI): (0.08, 0.52), p = 0.009). In contrast, both PLR and NLR values were higher in the NU group (PLR mean difference = 14.82, 95% CI: (1.65, 27.99), p = 0.028; NLR mean difference = 0.74, 95% CI: (0.36, 1.12), p < 0.001). No significant differences were observed in the ESR; hsCRP, BUN, CREA, ALB, Hb levels; or WBC, RBC, platelet, and neutrophil counts between the two groups. These perioperative differences in PLR and NLR are visually summarized in Figures 2 and 3.

Table 2.

Comparison of preoperative hematological and inflammatory indicators.

Variables	NU	95% CI	HU	95% CI	t value	p value
hsCRP (mg/L, $\bar{x} \pm$ s)	2.66 ± 7.19	(0.46, 4.86)	1.76 ± 5.15	(0.00, 3.56)	0.659	0.512
ESR (mm/h, $\bar{x} \pm$ s)	2.60 ± 2.33	(1.82, 3.38)	2.77 ± 1.82	(1.97, 3.57)	0.366	0.715
BUN (mmol/L, $\bar{x} \pm$ s)	5.03 ± 1.10	(4.68, 5.38)	5.04 ± 1.04	(4.69, 5.39)	0.062	0.951
CREA (μmol/L, $\bar{x}$ ± s)	81.18 ± 10.9	(77.73, 84.63)	83.32 ± 11.1	(79.64, 87.00)	0.886	0.378
SUA (μmol/L, $\bar{x}$ ± s)	362.68 ± 44.38	(348.96, 376.40)	482.72 ± 53.44	(465.99, 501.05)	11.087	<0.001
ALB (g/L, $\bar{x}$ ± s)	44.42 ± 2.01	(43.78, 45.06)	45.16 ± 2.36	(44.37, 45.95)	1.518	0.133
WBC count (×10⁹/L, $\bar{x} \pm$ s)	6.01 ± 1.51	(5.55, 6.47)	6.60 ± 1.64	(6.07, 7.13)	1.710	0.092
RBC count (×10¹²/L, $\bar{x}$ ± s)	5.12 ± 0.49	(5.00, 5.24)	5.27 ± 0.47	(5.15, 5.39)	1.367	0.176
Hb (g/L, $\bar{x} \pm$ s)	156.28 ± 12.27	(152.59, 159.97)	160.09 ± 12.8	(156.13, 164.05)	1.385	0.17
PLT (×10⁹/L, $\bar{x} \pm$ s)	211.05 ± 34.82	(199.93, 222.17)	216.19 ± 54.2	(198.01, 234.37)	0.509	0.612
Neutrophil count (×10⁹/L, $\bar{x} \pm$ s)	3.46 ± 1.09	(3.11, 3.81)	3.73 ± 1.27	(3.24, 4.22)	1.025	0.308
Lymphocyte count (×10⁹/L, $\bar{x} \pm$ s)	1.91 ± 0.47	(1.76, 2.06)	2.21 ± 0.56	(2.04, 2.38)	2.686	0.009
PLR ( $\bar{x} \pm$ s)	116.42 ± 31.94	(105.02, 127.82)	101.6 ± 28.35	(92.68, 110.52)	2.240	0.028
NLR ( $\bar{x}$ ± s)	1.91 ± 0.82	(1.64, 2.18)	1.17 ± 0.92	(0.98, 1.36)	3.871	<0.001

Data are presented as mean ± SD ( $\bar{x} \pm$ s).

NU: normouricemia; CI: confidence interval; HU: hyperuricemia; hsCRP: high-sensitivity C-reactive protein; ESR: erythrocyte sedimentation rate; BUN: blood urea nitrogen; CREA: creatinine; SUA: serum uric acid; ALB: albumin; WBC: white blood cell; RBC: red blood cell; Hb: hemoglobin; PLT: platelet count; PLR: platelet-to-lymphocyte ratio; NLR: neutrophil-to-lymphocyte ratio.

Figure 2.

Perioperative changes in the platelet-to-lymphocyte ratio (PLR) between the normouricemia (NU) and hyperuricemia (HUA) groups. Data are presented as mean ± standard deviation values. *indicates statistical significance with p < 0.05. Statistical comparisons were performed using independent sample t-tests.

Figure 3.

Perioperative changes in the neutrophil-to-lymphocyte ratio (NLR) between the normouricemia (NU) and hyperuricemia (HUA) groups. Data are presented as mean ± standard deviation values. ***indicates statistical significance with p < 0.001. “ns” indicates no statistical significance (p ≥ 0.05), as determined using independent sample t-tests.

Postoperative comparisons

As shown in Table 3, the postoperative WBC and neutrophil counts were significantly higher in the HUA group than in the NU group (WBC mean difference =2.59 × 10⁹/L, 95% CI: (1.34, 3.84), p < 0.001; neutrophil mean difference =2.43 × 10⁹/L, 95% CI: (1.27, 3.59), p < 0.001). Lymphocyte counts were also elevated in the HUA group (mean difference = 0.88 × 10⁹/L, 95% CI: (0.12, 1.64), p = 0.023). In contrast, postoperative PLR remained higher in the NU group (mean difference = 21.48, 95% CI: (1.46, 41.50), p = 0.036). No statistically significant group differences were found for ESR, BUN, CREA, ALB, RBC, Hb, or NLR. The postoperative trends of PLR and NLR are further illustrated in Figures 2 and 3.

Table 3.

Comparison of postoperative hematological and inflammatory indicators.

Variables	NU	95% CI	HU	95% CI	t value	p value
hsCRP (mg/L, $\bar{x} \pm$ s)	11.74 ± 12.24	(7.97, 15.51)	10.38 ± 12.19	(6.49, 14.27)	0.507	0.614
ESR (mm/h, $\bar{x}$ ± s)	4.83 ± 3.88	(2.67, 6.99)	7.21 ± 6.70	(4.74, 9.68)	1.966	0.053
BUN (mmol/L, $\bar{x} \pm$ s)	5.29 ± 0.90	(4.99, 5.59)	5.31 ± 1.36	(4.87, 5.75)	1.20	0.905
CREA (μmol/L, $\bar{x} \pm$ s)	80.80 ± 7.54	(77.98, 83.62)	76.20 ± 17.74	(70.89, 81.51)	1.515	0.134
SUA (μmol/L, $\bar{x} \pm$ s)	344.13 ± 54.69	(327.43, 360.83)	448.42 ± 69.28	(427.87, 468.97)	7.574	<0.001
ALB (g/L, $\bar{x} \pm$ s)	43.18 ± 2.70	(42.34, 44.02)	42.70 ± 2.14	(41.86, 43.54)	0.878	0.383
WBC count (×10⁹/L, $\bar{x} \pm$ s)	8.23 ± 2.55	(7.43, 9.03)	10.82 ± 2.90	(10.03, 11.61)	4.31	<0.001
RBC count (×10¹²/L, $\bar{x} \pm$ s)	4.89 ± 0.49	(4.74, 5.04)	4.90 ± 0.45	(4.76, 5.04)	0.636	0.527
Hb (g/L, $\bar{x} \pm$ s)	148.65 ± 12.82	(144.71, 152.59)	149.86 ± 11.60	(146.24, 153.48)	0.451	0.653
PLT (×10⁹/L, $\bar{x} \pm$ s)	219.10 ± 45.63	(204.77, 233.43)	233.86 ± 56.13	(216.79, 250.93)	1.309	0.194
Neutrophils (×10⁹/L, $\bar{x} \pm$ s)	5.55 ± 2.23	(4.85, 6.25)	7.98 ± 2.88	(7.06, 8.90)	4.274	<0.001
Lymphocyte count (×10⁹/L, $\bar{x} \pm$ s)	1.75 ± 0.52	(1.54, 1.96)	2.63 ± 2.36	(1.98, 3.28)	2.316	0.023
PLR ( $\bar{x}$ ± s)	135.47 ± 45.9	(121.97, 148.97)	113.99 ± 45.61	(99.63, 128.35)	2.137	0.036
NLR ( $\bar{x} \pm$ s)	3.38 ± 1.59	(2.88, 3.88)	3.82 ± 1.84	(3.26, 4.38)	1.148	0.252

Data are presented as mean ± SD ( $\bar{x} \pm$ s) values.

Discussion

The main finding of this study is that both preoperatively and postoperatively, patients with NU exhibited higher PLR, whereas those with HUA had higher lymphocyte counts. These results highlight a paradoxical pattern because HUA is generally considered to promote systemic inflammation.

Although strict selection criteria ensured homogeneity of the study population in terms of age, sex, and other baseline characteristics, certain baseline differences still existed. For example, the diastolic blood pressure in the HUA group was significantly higher than that in the NU group. Urate deposition and oxidative stress can induce inflammation and dysfunction of vascular endothelial cells, leading to vascular sclerosis and increased blood pressure.²² High uric acid levels may increase diastolic blood pressure by affecting renal function and activating the sympathetic nervous system. Uric acid deposition in the kidneys can cause renal tubular damage, compromise renal function, increase blood volume, and raise blood pressure. Furthermore, high uric acid levels may activate the sympathetic nervous system and increase cardiac contractility and vascular resistance, thereby raising diastolic blood pressure.²³ In a recent study, the average BMI of Chinese male HUA patients was 25.73 kg/m², while that of normal male patients was 24.35 kg/m², representing a statistically significant difference.²⁴ These data were based on an analysis of 69,842 samples from 31 provinces and cities in China. Another study supported this finding,²⁵ indicating a positive correlation between high uric acid levels and BMI, especially in patients with gout, whose BMI was significantly higher than that of the normal population. There was no significant difference in BMI between the control and experimental groups in this study, possibly because the participants were mainly young adults. This population generally performed regular physical activity and exhibited relatively strict awareness of weight management. Long-term exercise and autonomous nutritional regulation may have masked the potential impact of HUA on BMI.²⁶

Regarding inflammatory markers, our results demonstrated that the PLR was consistently higher in NU patients, which appears inconsistent with prior evidence linking HUA to systemic inflammation. Several mechanisms may explain this paradox. First, plateau hypoxia exerts dual effects on platelet and lymphocyte homeostasis. Hypoxia can enhance platelet activation and aggregation as an adaptive response to vascular stress, which theoretically increases the PLR.^19,20 In contrast, hypoxia triggers lymphocyte redistribution, with a higher proportion of lymphocytes migrating to hypoxic tissues, leading to a transient decrease in peripheral blood lymphocyte counts.²⁷ In the NU group, patients may have been more sensitive to hypoxia due to the lack of uric acid–related vascular preadaptation, resulting in relatively higher platelet counts and only mild lymphocyte reduction, ultimately leading to a higher PLR. In contrast, long-term HUA might induce vascular remodeling such as mild vascular sclerosis,²² which could attenuate platelet activation under hypoxia. Meanwhile, lymphocyte counts in the HUA group may have decreased more markedly due to chronic inflammatory stress, further contributing to a lower PLR. Second, the hypoxic environment may alter the inflammatory regulatory effect of HUA. At low altitudes, HUA is known to promote systemic inflammation through oxidative stress and urate crystal deposition, thereby elevating the PLR.^10,28 However, at high altitudes, hypoxia activates inflammatory signaling pathways at baseline.²⁹ Therefore, HUA and hypoxia may interact competitively within these pathways, attenuating the proinflammatory effect of HUA observed at low altitudes. Taken together, these hypotheses provide potential explanations for the paradoxical finding of lower PLR in the HUA group at high altitudes. Nonetheless, these interpretations should be viewed with caution, and further mechanistic studies are required to validate the underlying molecular pathways.

Recent studies have shown that an increase in the NLR is associated with an increase in inflammation levels.³⁰ Furthermore, when the body is in an inflammatory stress state, the peripheral blood neutrophil count increases significantly, while the lymphocyte count is known to decrease. Therefore, the ratio of the two indicators changes more significantly in patients with inflammation than in healthy patients. This is consistent with the results of the present study. The average postoperative NLR values of the HUA and NU groups were higher than the preoperative values, which may be attributable to the stress response caused by surgery. HUA can slightly increase the expression of inflammatory factors in the patient’s peripheral blood, causing the patient’s entire body to be in a state of microinflammation.³¹ There was no statistically significant difference in the preoperative neutrophil and WBC counts between the two groups; however, the average postoperative values were significantly greater than the preoperative values, indicating that inflammation persists for a long time. HUA may be an important factor affecting the increase in the neutrophil and WBC counts during surgery, thereby delaying postoperative recovery. Excessive postoperative inflammatory response may increase the possibility of complications such as wound infection and arthritis,³² thereby impairing ligament healing and postoperative functional recovery of patients.

Existing studies have demonstrated that HUA can induce systemic inflammation and impair ACLR prognosis.^10,28 PLR and NLR are reliable inflammatory markers for assessing the prognosis of cardiovascular disease and cancer.^30,33 However, only a few studies have explored the interaction of HUA with PLR and NLR in patients with ACLR, particularly in high-altitude settings. This study fills this research gap and provides innovative insights to this field. First, this is the first study to clearly establish the association of HUA with PLR and NLR in high-altitude residents undergoing ACLR, confirming the association between HUA and PLR (both preoperatively and postoperatively) as well as preoperative NLR reduction and postoperative leukocyte and neutrophil elevation. Second, it expands on the application of PLR and NLR from general surgery and cardiovascular disease to orthopedic surgery in a specific setting (high altitude), providing a new perspective for assessing perioperative inflammation in this population. From the perspective of clinical application, this discovery can guide orthopedic surgeons in the treatment of patients residing in plateau regions by including SUA testing in the routine preoperative evaluation of ACLR patients. For patients with HUA, early implementation of uric acid–lowering interventions can be performed. Furthermore, PLR and NLR can be used as dynamic monitoring indicators of perioperative inflammation for timely identification of inflammatory abnormalities to reduce the risk of postoperative infection and delayed ligament healing. In addition, it provides evidence supporting the formulation of individualized perioperative management plans for ACLR patients residing in plateau regions, thus improving surgical outcomes in this population.

Limitations

This study provides valuable insights; however, certain limitations should be acknowledged. First, the retrospective, single-center design with a relatively small sample size (n = 83) may have introduced selection bias and limited the statistical power. Second, only male patients were included, restricting the generalizability of the findings to female patients residing in high-altitude regions undergoing ACLR. Third, lifestyle factors such as dietary purine intake, physical activity, and altitude acclimatization were not systematically assessed, and perioperative medication use (e.g. nonsteroidal anti-inflammatory drugs, allopurinol, and diuretics) or anesthesia protocols were not controlled, which may have introduced residual confounding. Fourth, only univariate analyses were conducted without adjusting for multiple testing or confounding variables (e.g. BMI, blood pressure, and smoking), which may have increased the risk of spurious associations. Finally, laboratory indicators were monitored only 24 h before and 24 h after surgery, and long-term changes and prognostic impacts were not evaluated. Future multicenter prospective studies with larger cohorts, comprehensive data collection, multivariate modeling, and long-term follow-up are needed to validate and extend these findings.

Conclusion

HUA significantly influences perioperative hematological and inflammatory markers in patients residing in high-altitude regions who underwent ACLR. Compared with patients with NU, those with HUA demonstrated distinct alterations in the PLR and NLR as well as WBC, neutrophil, and lymphocyte counts, suggesting a heightened inflammatory response and immune imbalance. These findings emphasize the importance of monitoring inflammatory indicators and optimizing uric acid management in this population to reduce postoperative risks. Further prospective studies with larger cohorts and longer follow-up are warranted to validate these observations and clarify their prognostic implications.

Supplemental Material

sj-pdf-1-imr-10.1177_03000605251387874 - Supplemental material for Hyperuricemia is associated with altered perioperative neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and inflammatory responses in patients residing in high-altitude regions who underwent anterior cruciate ligament reconstruction: A cross-sectional study

Supplemental material, sj-pdf-1-imr-10.1177_03000605251387874 for Hyperuricemia is associated with altered perioperative neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and inflammatory responses in patients residing in high-altitude regions who underwent anterior cruciate ligament reconstruction: A cross-sectional study by Zheng Xuemei, Chang Mengjing, Tian Wenling, Liu Xiangyue, Liao Dongfa, Yin Li and Cui Lin in Journal of International Medical Research

Footnotes

Acknowledgments

The authors have no acknowledgments to disclose.

Author contributions

All authors contributed to the conception and design of the study. Material preparation and data collection were performed by Chang Mengjing and Tian Wenling. Data analysis was performed by Zheng Xuemei and Liu Xiangyue. The first draft of the manuscript was written by Zheng Xuemei. All authors commented on the previous versions of the manuscript. Cui Lin and Liao Dongfa carefully checked the final manuscript. All authors have read and approved the final manuscript and agreed to be accountable for all aspects of the work.

Compliance with ethical standards

This retrospective chart review study involving human participants was conducted in accordance with the ethical standards of the institutional and national research committees and the 1964 Helsinki Declaration and its subsequent amendments or comparable ethical standards. The Ethics Review Committee of the General Hospital of Western Theater Command approved this study.

Data availability statement

Data are available from the authors upon reasonable request.

Declaration of conflicting interests

The authors have no financial or other forms of conflict of interest to declare.

Ethical approval

Ethical approval was obtained from the Ethics Committee of the General Hospital of the Western Theater Command of the People’s Liberation Army (approval number 2024EC4-ky013).

Funding

This work was supported by grants from relevant Chinese authorities (No. 2023HL065).

ORCID iD

Cui Lin

References

Kaeding

Léger-St-Jean

Magnussen

RA.

Epidemiology and diagnosis of anterior cruciate ligament injuries. Clin Sports Med 2017; 36: 1–8.

Pasquini

Prejbeanu

Russu

, et al. Effect of vitamin D on anterior cruciate ligament injury rates and post-reconstruction function-a systematic review. J Exp Orthop 2025; 12: e70224.

Shi

, et al. Progress in evaluation of return to sports after anterior cruciate ligament reconstruction. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2023; 37: 495–501.

D’Ambrosi

Carrozzo

Meena

, et al. A slight degree of osteoarthritis appears to be present after anterior cruciate ligament reconstruction compared with contralateral healthy knees at a minimum of 20 years: a systematic review of the literature. J Exp Orthop 2024; 11: e12017.

Turk

Shah

Chilton

, et al. Return to sport after anterior cruciate ligament reconstruction requires evaluation of >2 functional tests, psychological readiness, quadriceps/hamstring strength, and time after surgery of 8 months. Arthroscopy 2023; 39: 790–801.e6.

Slater

Hart

Kelly

, et al. Progressive changes in walking kinematics and kinetics after anterior cruciate ligament injury and reconstruction: a review and meta-analysis. J Athl Train 2017; 52: 847–860.

D’Ambrosi

Hewett

TE.

Validity of material related to the anterior cruciate ligament on TikTok. Orthop J Sports Med 2024; 12: 23259671241228543.

Shu

Milne

, et al. Uric acid correlates to oxidation and inflammation in opposite directions in women. Biomarkers 2015; 20: 225–231.

Shen

Zhu

, et al. Demographic, regional and temporal trends of hyperuricemia epidemics in Mainland China from 2000 to 2019: a systematic review and meta-analysis. Glob Health Action 2021; 14: 1874652.

10.

Zhu

Yang

Progress in imaging research of gouty arthritis. Chinese Journal of Medical Imaging 2020; 28: 156–160.

11.

Ejaz

Nakagawa

Kanbay

, et al. Hyperuricemia in kidney disease: a major risk factor for cardiovascular events, vascular calcification, and renal damage. Semin Nephrol 2020; 40: 574–585.

12.

Pan

Shi

, et al. Mechanistic insights of soluble uric acid-related kidney disease. Curr Med Chem 2020; 27: 5056–5066.

13.

Moldovan

Role of serum biomarkers in differentiating periprosthetic joint infections from aseptic failures after total hip arthroplasties. J Clin Med 2024; 13: 5716.

14.

Moldovan

Correlation between peripheric blood markers and surgical invasiveness during humeral shaft fracture osteosynthesis in young and middle-aged patients. Diagnostics (Basel) 2024; 14: 1112.

15.

Lam

Yan

, et al. NLR, MLR, PLR and RDW to predict outcome and differentiate between viral and bacterial pneumonia in the intensive care unit. Sci Rep 2022; 12: 15974.

16.

Tudurachi

Anghel

Tudurachi

, et al. Assessment of inflammatory hematological ratios (NLR, PLR, MLR, LMR and monocyte/HDL-cholesterol ratio) in acute myocardial infarction and particularities in young patients. Int J Mol Sci 2023; 24: 14378.

17.

Misiewicz

Dymicka-Piekarska

Fashionable, but what is their real clinical usefulness? NLR, LMR, and PLR as a promising indicator in colorectal cancer prognosis: a systematic review. J Inflamm Res 2023; 16: 69–81.

18.

Zhang

Jiang

JX.

Practical manual for treatment of plateau combat wounds. Beijing: People’s Medical Publishing House, 2020, pp. 15–19.

19.

Zhang

Wang

Jiang

, et al. Research progress on the damage of plateau hypoxia environment to the body. Journal of Joint Logistics Military Medicine 2024; 38: 813–817.

20.

Zhang

Research progress on changes of red blood cell and blood uric acid concentration in plateau area. Advances in Clinical Medicine 2021; 11: 1460–1464.

21.

Von Elm

Altman

Egger

; STROBE Initiativeet al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Ann Intern Med 2007; 147: 573–577.

22.

Wang

Sun

, et al. Research progress on platelets/lymphocytes and cardiovascular diseases. Clinical Metabolism 2020; 35: 88–91.

23.

Joshi

Bhambhani

Barure

, et al. Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as markers of stable ischemic heart disease in diabetic patients: an observational study. Medicine (Baltimore) 2023; 102: e32735.

24.

Meng

Yan

, et al. Association of neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, and monocyte to lymphocyte ratio with depression: a cross-sectional analysis of the NHANES data. J Affect Disord 2022; 315: 168–173.

25.

Kim

Jung

Suh

CH.

Usefulness of neutrophil-to-lymphocyte ratio as a biomarker for diagnosing infections in patients with systemic lupus erythematosus. Clin Rheumatol 2017; 36: 2479–2485.

26.

Grace

Biggs

Naicker

, et al. Effect of physical activity and nutrition education on body mass index, blood pressure and biochemical variables in overweight and obese adolescents. Ann Glob Health 2021; 87: 9.

27.

Sattiraju

Kang

Giotti

, et al. Hypoxic niches attract and sequester tumor-associated macrophages and cytotoxic T cells and reprogram them for immunosuppression. Immunity 2023; 56: 1825–1843.e6.

28.

Han

Xiao

, et al. Association between serum uric acid level and systemic lupus erythematosus kidney outcome: an observational study in Southern Chinese population and a meta-analysis. Lupus 2023; 32: 83–93.

29.

Zhou

Sun

Jiang

BH.

Research progress in the role of hypoxia-inducible factor 1 in altitude sickness and the mechanisms involved. Sichuan Da Xue Xue Bao Yi Xue Ban 2024; 55: 1424–1435.

30.

Imtiaz

Shafique

Mirza

, et al. Neutrophil lymphocyte ratio as a measure of systemic inflammation in prevalent chronic diseases in Asian population. Int Arch Med 2012; 5: 2.

31.

Guo

Tang

Huang

, et al. Research progress on TLR4/NF-kB signaling pathway in regulating periodontitis and hyperuricemia and their interaction. Chinese Journal of Stomatological Research (Electronic Edition) 2021; 15: 58–62.

32.

Badawy

Jan

Beck

, et al. Contemporary principles for postoperative rehabilitation and return to sport for athletes undergoing anterior cruciate ligament reconstruction. Arthrosc Sports Med Rehabil 2022; 4: e103–e113.

33.

Idowu

Oyeleke

Vitowanu

JM.

Impact of inflammatory cell ratio, biomarkers, activated partial thromboplastin time and prothrombin time on chronic subdural haematoma severity and outcome. Eur J Trauma Emerg Surg 2022; 48: 1085–1092.

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