Uric acid/HDL-C Ratio May Predict Significant Coronary Artery Stenosis: Intravascular Ultrasonography Study

doi:10.21203/rs.3.rs-4277759/v1

Background: There may be severe difficulties in determining the severity of LMCA lesions. The use of intravascular ultrasound (IVUS) facilitates the decision about the lesion severity in these patients. The aim of this study was to investigate the relationship between UHR and lesion severity in patients who have undergone LMCA IVUS.

Methods: The study included 205 patients who were determined with ICS in LMCA and underwent an IVUS procedure. In the IVUS measurements of these patients, the plaque burden (PB) and the minimal lumen area (MLA) showing lesion severity were measured.

Results: The patients were separated into two groups according to the plaque burden values as those <65% and ≥65%. The UHR values were determined to be significantly higher in the high plaque burden group (479.5 vs. 428.6, p:0.001). When the patients were separated into two groups according to the MLA values (<6mm² and MLA ≥6mm²), the UHR values were determined to be significantly higher in the group with low MLA values (476.8 vs. 414.9, p<0.001). In the ROC analysis performed according to the MLA and plaque burden values, the UHR cutoff value of 450 was found to have similar sensitivity and the same specificity for both parameters.

Conclusions: The results of this study suggested that there is a relationship between the UHR parameter and MLA <6mm² and plaque burden ≥65%, which are independently evaluated as critical in IVUS, and this could predict anatomically significant lesions in patients with a moderate degree of LMCA stricture.

Intravascular ultrasound

coronary artery disease

left main coronary artery

uric acid

high-density lipoprotein cholesterol

Coronary artery disease (CAD) has been determined to be the leading cause of death in developed and developing countries. Coronary angiography (CAG) is a widely used method to evaluate the extent and severity of CAD in clinical practice. However, the interpretation of CAG images can be prevented because of vessels appearing short or overlapping on the imaging, and there can be difficulties in the reliable evaluation of stenosis severity in advanced stage eccentric lesions [1]. When these challenges in the correct evaluation of stricture on angiography are taken into consideration, patients are usually entered in the category named ‘intermediate coronary stenosis’ (ICS). ICS is defined as angiographic stenosis between 30% and 70%, and presents significant clinical difficulty in terms of optimal evaluation and management strategy [2]. Although the prevalence in the general population is not well known, recorded data suggest that ICS could be present in up to 25% of patients undergoing CAG [3]. In addition, left main coronary artery (LMCA) lesions are determined in 5–7% of CAG patients [4] and there are grreat difficulties in determining the severity of LMCA lesions. The use of intravascular ultrasound (IVUS) facilitates the decision about the lesion severity in these patients. However, IVUS cannot be widely used because of the need for extra time for the intervention, an experienced operator, and extra cost.

Some previous studies have shown that some biomarkers show consistency in lesion severity evaluation with the tests that physiologically evalute the severity of coronary lesions [5, 6]. It is also known that uric acid (UA) and high-density lipoprotein cholesterol (HDL-C) disorders are both evaluated as risk factors for CAD [7, 8]. Previous studies have evaluated the ratio of these two parameters with each other and the relationship with some diseases. In those studies, there has been shown to be a relationship of the uric acid to HDL-C ratio (UHR) with hypertension control [9], hepatic steatosis [10], and cardiovascular mortality [11]. The ratio of serum UHR, which has proven cardiovascular effects, may be a good biomarker showing CAD severity and the severity of the lesion in patients with ICS.

The aim of this study was to investigate the relationship between UHR and lesion severity in patients who have undergone LMCA IVUS. This may allow easier determination of lesion severity in patients determined with ICS in LMCA lesions, rather than performing IVUS, which is a costly and time-consuming procedure. To the best of our knowledge, there is no study in the literature that has investigated the relationship between UHR and lesion severity on LMCA IVUS.

Data Collection and Laboratory Analysis

This retrospective, observational study included patients who underwent CAG at a tertiary-level cardiac centre and were diagnosed with CAD, were determined with ICS in the LMCA as a result of CAG, and therefore underwent IVUS measurement. The patients included were those without complications (no ulceration, dissection, or thrombus), determined with ICS and unprotected LMCA lesion. All the patients between January 2020 and June 2023 were included consecutively in the study.

The study inclusion criteria were defined as (i) age in the range of 20–85 years, (ii) indication for CAG with a diagnosis of stable angina pectoris (SAP) or acute coronary syndrome (ACS), and (iii) lesion determined on the LMCA as a result of CAG. The study exclusion criteria were defined as (i)cardiogenic shock, (ii) severe heart valve disease, (iii) active malignancy or active infection, and (iv) incomplete clinical data for uric acid or HDL-C.

A total of 205 patients met the criteria and were included in the study. The patient population was classified according to the IVUS measurements by evaluating 2 criteria. The patients were separated into 2 groups according to the healthy vessel diameter measured on IVUS, as minimal lumen area (MLA) < 6mm² and ͗≥6mm², and as plaque burden (PB) measured on IVUS as < 65% and ≥ 65%. The limits defined for MLA and PB were determined according to the limits determined for IVUS in previous studies [12, 13]. During the study, all the patients were treated in the hospital according to the current guidelines. The basic demographic characteristics of the patients and comorbidities such as hypertension, diabetes mellitus, and hyperlipidemia, together with the laboratory and angiographic findings were retrieved from the hospital electronic database. From a scan of the archived records, data were also obtained for all the patients of previous ECG records and previous drugs used.

Blood samples were taken on presentation of all the patients for analysis including measurements of hemoglobin level, white blood cell count, thrombocyte count and blood glucose level. The HbA1c level was determined using a high-performance liquid chromatography analysis device. The total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol values were determined after 8–12 hours overnight fasting. The eGFR was calculated according to the MDRD formula (eGFR [mL/min/1.73m²] = 186 x [creatinine/88.4]-1.154 x [age]− 0.203 x [0.742 if female, 1.210 if black]) [14].

Coronary Angiography

Standard coronary angiography was performed using a 5 or 6 French Judkins diagnostic catheter (Boston Scientific, MA, USA) and a femoral or radial approach. The reference diameter was taken as the average of angiographically normal segments 10mm in length in the proximal and distal of the lesion. When a normal proximal segment could not be identified (eg. ostial lesion location), only the disttal segment was analyzed.

IVUS Imaging and Analysis

The operators were not blinded to the images. IVUS imaging was performed after the intracoronary administration of 0.2 mg nitroglycerine. The examinations were conducted using the system produced by the Cardiovascular Imaging Systems/Boston Scientific Corporation. The IVUS catheter was advanced to approximately 10mm distal of the lesion, the video recording was started, the transducer retraction device was activated or manual retraction was started, and the coronary artery was imaged retrograde towards the aorto-ostial junction. The examinations were recorded on the integral memory of the Boston device for offline analysis.

Normal coronary anatomy, plaque composition, and measurements determined using IVUS have been reported [15, 16]. The external elastic membrane (EEM) cross-sectional area is measured by following the anterior edge of the adventitia. The lesion region is the cross-sectional slice with the smallest lumen and from the sections with the same lumen area, the section that included the most plaque was selected. If the plaque around the catheter was compressed, the lumen was assumed to be the physical size (not acoustic) of the catheter. For the reference segment, the average was taken of the visually most normal slices (the largest lumen containing the least plaque) from among the main branches 5mm proximal and distal of the lesion. For ostial lesions, the distal reference was used. The IVUS measurements were performed according to the American Cardiology College and European Cardiology Society standards [17].

Using a computer planimeter (TapeMeasure, Indec Systems), the following lesion and reference measurements were performed in diastole: EEM cross-sectional areas (CSA), lumen CSA, MLA and PB ([vessel area – lumen area] /vessel area).

Statistical Analysis

All statistical analyses were performed using SPSS vn. 20 software (Statistical Package for the Social Sciences). Conformity of the data to normal distribution was assessed using the Kolmogorov–Smirnov or Shapiro–Wilk tests. Variables were reported as mean ± standard deviation (SD) or median and interquartile range values. According to the normality test result, the Independent Samples t-test or the Mann Whitney U-test were used for between group comparisons. In the analysis of categorical data, a χ2 test was used or Fisher’s Exact test if any expected cell count was < 5, and descriptive statistics were presented as number (n) and percentage (%). To evaluate the correlations between UHR and anatomically significant atherosclerotic parameters (plaque burden and MLA), Spearman's ρ correlation analysis was performed. ROC curve analysis was applied to determine the cut-off point and the area under the curve (AUC) of UHR for significant anatomic atherosclerosis. The cut-off values of UHR were shown as a prespecified dichotomous variable to facilitate meaningful clinical interpretation of the results. When indicated, analyses performed using UHR as a continuous variable were also reported. Univariate binary logistic regression analysis was used to investigate the relationship between significant anatomic atherosclerosis and UHR (separately for plaque burden and MLA). The effect of UHR on atherosclerosis severity was reported using the odds ratio (OR) and 95% CI. A value of p < 0.05 was considered statistically significant and statistical tests were two-sided.

Ethics Committee Approval

All the procedures in this study were in compliance with the 1964 Helsinki Declaration and later revisions and comparable ethical standards. Approval for the study was granted by the Local Ethics Committee (decision no: 2011- KAEK-25 2023/11 − 02).

The study included 205 patients who underwent CAG for a diagnosis of ACS, USAP, or SAP, and were determined with an LMCA lesion on CAG, so underwent IVUS. The patients comprised 156 (76.1%) males and 49 (23.9%) females with a median (IQR) age of 61 (53–68) years. CAG was performed because of a diagnosis of ACS in 72 (35.1%) patients, USAP in 42 (20.5%), and SAP in 91 (44.4%). When the IVUS results were examined, the mean MLA was calculated as 6.4 (4.8–9.1) mm², and the plaque burden percentage as 58% (46–67%).

The correlations of anatomic atherosclerosis severity with UHR were evaluated using Spearman's ρ correlation analysis. A mild correlation was determined of both plaque burden and MLA with UHR. MLA was negatively associated with UHR, and plaque burden showed a positive correlation (rs = -0.24, p = 0.006; rs = 0.23, p = 0.001,respectively).

The demographic, clinical and laboratory data of the patients were compared in two groups according to the PB percentage of < 65% or ≥ 65% in the LMCA IVUS measurements (Table 1). No significant difference was determined between the groups in respect of demographic characteristics or comorbidities. When the drugs used were compared, more of the patients taking B-blockers and ACE inhibitors were determined to be in the PB ≥ 65% group (p:0.002, p:0.22). In the examination of the laboratory parameters, the uric acid level was determined to be significantly high in the group with high PB (p:0.002). When the continuous variable of the UHR parameter showing the relationship between uric acid and HDL-C was examined, it was determined to be significantly high in the group with high PB (479.5 vs. 428.6, p:0.001).

Table 1

The baseline characteristics and laboratory investigations of all patients according to LMCA plaque burden
		All patients (n = 205)	Plaque Burden ≥%65 (n = 74)	Plaque Burden < 65 (n = 131)	p-value
Demographic characteristics
Age, y		61 (53–68)	60 (55–71)	61 (53–68)	0.186
Male sex, %		156 (76.1)	55 (74.3)	101 (77.1)	0.734
Body mass index, kg/m²		26.8 (24.7–29)	26.2 (24.5–29.3)	26.8 (24.8–28.9)	0.605
Comorbidites
Hypertension, %		129 (62.9)	45 (60.8)	84 (64.1)	0.654
Diabetes mellitus, %		48 (23.4)	19 (25.7)	29 (22.1)	0.608
Hyperlipidemia, %		60 (29.3)	27 (36.5)	33 (25.2)	0.110
Smoking, %		132 (64.4)	47 (63.5)	85 (64.9)	0.880
Chronic kidney disease, %		31 (15.1)	12 (16.2)	19 (14.5)	0.840
Medications
Acetylsalicylic Acid Use, %		204 (99.5)	74 (100)	130 (99.2)	1.000
P2Y12 Inh Use, %	Clopidogrel	103 (50.2)	40 (54.1)	63 (48.1)	0.468
	Ticagrelor	44 (21.5)	22 (29.7)	22 (16.8)
	Prasugrel	16 (7.8)	6 (8.1)	10 (7.6)
B-Blocker Use, %		191 (93.2)	61 (82.4)	131 (100)	0.002
ACE Inh Use, %		175 (85.4)	60(81.1)	123(93.9)	0.022
Statin Use, %		200 (97.6)	73 (98.6)	127 (96.9)	0.656
OAD Use, %		50 (24.4)	24 (32.4)	26 (19.8)	0.062
Clinical Presentation
Acute Coronary Syndrome, %		72 (35.1)	33 (44.6)	39 (29.8)	0.094
Unstable Angina Pectoris, %		42 (20.5)	14 (18.9)	28 (21.4)
Stable Angina Pectoris, %		91 (44.4)	27 (36.5)	64 (48.9)
Laboratory assessment
Hemoglobin, g/dl		13.3 (12.1–14.5)	12.8 (11.7–14.3)	13.6 (12.2–14.6)	0.085
eGFR, ml/min/1.73 m²		90.5 (70-101.6)	92.8 (70-101.5)	90.1 (69.8-102.1)	0.904
Total cholesterol, mmol/L		4.37 (3.74–5.3)	4.25 (3.43–5.30)	4.52 (3.87–5.36)	0.086
Triglycerides, mmol/L		1.56 (1.01–2.41)	1.41 (0.97–2.16)	1.60 (1.06–2.53)	0.279
LDL cholesterol, mmol/L		2.39 (1.78–3.33)	2.31 (1.57–3.07)	2.44 (1.84–3.48)	0.123
HDL cholesterol, mmol/L		1.07 (0.94–1.25)	1.07 (0.91–1.25)	1.08 (0.94–1.26)	0.456
Albumin, g/L		42.1 (39.1–44.5)	41.7 (38.4–44.3)	42.1 (39.1–44.6)	0.115
HbA1c, %		5.78 (5.5–6.4)	5.89 (5.6–6.5)	5.69 (5.4–6.4)	0.430
Uric asid, µmol/L		477.4 (415.5-548.1)	503.9 (459.7-565.8)	468.5 (406.6-539.2)	0.002
UHR, continuous variable		446.3 (366-518.1)	479.5 (400.4–570)	428.6 (357-494.3)	0.001
UHR ≤ 450, categorical variable		109 (53,2)	28 (37.8)	81 (61.8)	0.001
IVUS LMCA MLA, mm²		6.4 (4.8–9.1)	4.9 (3.5–5.8)	8.7 (6.4–10.9)	< 0.001
IVUS LMCA plaque burden, %		58 (46–67)	69 (66–72)	48 (41–56)	< 0.001
Data are presented as median (interquartile range) or number (percentage) of patients. Abbreviations: ACE, angiotensin converting enzyme; eGFR, estimated glomerular filtration rate; HDL, high-density lipoprotein; IQR, interquartile range; IVUS, intravascular ultrasound; LDL, low-density lipoprotein; LMCA, left main coronary artery; MLA, minimal lumen area; OAD, oral antidiabetic; UHR, UA to HDL-C ratio

The results of the Receiver operating characteristic (ROC) analysis performed according to the MLA and PB values of the patients are shown in Table 2. When the ROC analyses were applied separately to the IVUS parameters of MLA and PB with UHR, the UHR cut-off value of 450 for both parameters of anatomic atherosclerosis was determined to have similar sensitivity and the same specificity.

Tablo-2: Comparison of ROC curves of our proposed risk stratification models individually in predicting anatomically significant atherosclerotic lesion A) UHR versus MLA and B) UHR versus plaque burden

Table 3

The baseline characteristics and laboratory investigations of all patients according to LMCA minimum lumen area
Demographic characteristics
		All patients (n = 205)	MLA < 6mm² (n = 92)	MLA ≥ 6mm² (n = 113)	p-value
Age, y		61 (53–68)	60 (55–70)	61 (52–68)	0.158
Male sex, %		156 (76.1)	72 (78.3)	84 (74.3)	0.512
Body mass index, kg/m²		26.8 (24.7–29)	26 (24.2–28.6)	27 (24.9–29)	0.097
Comorbidites
Hypertension, %		129 (62.9)	58 (63)	71 (62.8)	1.000
Diabetes mellitus, %		48 (23.4)	25 (27.2)	23 (20.4)	0.320
Hyperlipidemia, %		60 (29.3)	31 (33.7)	29 (25.7)	0.221
Smoking, %		132 (64.4)	56 (60.9)	76 (67.3)	0.380
Chronic kidney disease, %		31 (15.1)	14 (15.2)	17 (15)	1.000
Medications
Acetylsalicylic Acid Use, %		204 (99.5)	92 (100)	112 (99.1)	1.000
P2Y12 Inh Use, %	Clopidogrel	103 (50.2)	50 (54.3)	53 (46.9)	0.327
	Ticagrelor	44 (21.5)	27 (29.3)	17 (15)
	Prasugrel	16 (7.8)	7 (7.6)	9 (8)
B-Blocker Use, %		191 (93.2)	79 (85.9)	110 (97.3)	0.004
ACE Inh Use, %		175 (85.4)	73 (79.3)	105 (93)	0.003
Statin Use, %		200 (97.6)	91 (98.9)	109 (96.5)	0.382
OAD Use, %		50 (24.4)	27 (29.3)	23 (20.4)	0.145
Clinical Presentation
Acute Coronary Syndrome, %		72 (35.1)	41 (44.6)	31 (27.4)	0.074
Unstable Angina Pectoris, %		42 (20.5)	19 (20.7)	23 (20.4)
Stable Angina Pectoris, %		91 (44.4)	32 (34.8)	59 (52.2)
Laboratory assessment
Hemoglobin, g/dl		13.3 (12.1–14.5)	13.1 (11.9–14.4)	13.6 (12.2–14.5)	0.630
eGFR, ml/min/1.73 m²		90.5 (70-101.6)	92.5 (70-101.5)	88.5 (70-101.6)	0.995
Total cholesterol, mmol/L		4.37 (3.74–5.3)	4.26 (3.44–5.31)	4.53 (3.88–5.37)	0.084
Triglycerides, mmol/L		1.56 (1.01–2.41)	1.41 (0.97–2.16)	1.62 (1.08–2.55)	0.259
LDL cholesterol, mmol/L		2.39 (1.78–3.33)	2.29 (1.55–3.08)	2.47 (1.84–3.51)	0.096
HDL cholesterol, mmol/L		1.07 (0.94–1.25)	1.06 (0.91–1.24)	1.08 (0.96–1.28)	0.107
HbA1c, %		5.78 (5.5–6.4)	5.88 (5.5–6.4)	5.69 (5.3–6.4)	0.353
Uric asid, µmol/L		477.4 (415.5-548.1)	503.9 (446.4-565.8)	468.5 (406.6-521.6)	0.012
UHR, continuous variable		446.3 (366-518.1)	476.8 (405.5–560)	414.9 (349.4–489)	< 0.001
UHR ≤ 450, categorical variable		109 (53.2)	35 (38)	74 (65.5)	< 0.001
IVUS LMCA MLA, mm²		6.4 (4.8–9.1)	4.8 (3.6–5.1)	8.9 (6.7–11.6)	< 0.001
IVUS LMCA plaque burden, %		58 (46–67)	66.5 (64–71)	47 (40–55)	< 0.001
Data are presented as median (interquartile range) or number (percentage) of patients. Abbreviations: ACE, angiotensin converting enzyme; eGFR, estimated glomerular filtration rate; HDL, high-density lipoprotein; IQR, interquartile range; IVUS, intravascular ultrasound; LDL, low-density lipoprotein; LMCA, left main coronary artery; MLA, minimal lumen area; OAD, oral antidiabetic; UHR, UA to HDL-C ratio

The angiographic characteristics and IVUS parameters of the patients were compared according to the UHR levels as ≤ 450 and > 450 (Table 4). The number of critical vessels determined angiographically was seen to be significantly higher in the high UHR group (p:0.039). When the CAG results were compared, the number of patients for whom the decision of CABG was made was significantly higher in the high UHR group (p:0.017). In the IVUS parameters, lumen volume was determined to be significantly low in the high UHR group (p: 0.012). MLA values were determined to be significantly low in the high UHR group (6.7 mm² vs 8.2 mm², p:0.030). When the MLA parameter was examined as a categorical variable, the number of patients with MLA < 6mm² was significantly greater in the high UHR group (57 patients vs.35 patients, p < 0.001). The PB percentage was determined to be significantly higher in the high UHR group (p.0.002). When the PB percentage was examined as a categorical variable, the number of patients with PB > 65% was significantly greater in the high UHR group (p: 0.001).

Table 4

Angiographic and procedural status of patients according to UHR
Procedural data
Angiographic parameters		All patients (n = 205)	UHR ≤ 450 (n = 109)	UHR > 450 (n = 96)	p-value
SYNTAX score		11 ± 10	10 ± 10	12 ± 9	0.061
Critical number of vessels, %	0	46 (22.4)	33 (30.3)	13 (13.5)	0.039
	1	64 (31.2)	33 (30.3)	31 (32.3)
	2	59 (28.8)	26 (23.9)	33 (34.4)
	3	35 (17.1)	16 (14.7)	19 (19.8)
	4	1 (0.5)	1 (0.9)	0
CAG result	Medical follow up	80 (39)	51 (46.8)	29 (30.2)	0.017
	PCI	73 (35.6)	38 (34.9)	35 (36.5)
	CABG	52 (25.4)	20 (18.3)	32 (33.3)
IVUS-based volume parameters in LMCA
EEM volume, mm³		148.9 ± 47	151.3 ± 45.2	146.2 ± 49	0.434
Lumen volume, mm³		66.5 ± 35.7	72.4 ± 36.9	59.8 ± 33.4	0.012
Plaque volume, mm³		82.4 ± 32.1	78.9 ± 28.8	86.4 ± 35.1	0.095
MLA, mm²		7.4 ± 3.8	8.2 ± 3.9	6.7 ± 3.5	0.030
MLA < 6 mm²		92 (44.9)	35 (32.1)	57 (59.4)	< 0.001
Plaque burden, %		55.6 ± 14.5	52.7 ± 14.2	59 ± 14.2	0.002
Plaque burden ≥ 65%		74 (36.1)	28 (25.7)	46 (47.9)	0.001
Data are presented as mean ± SD or number (percentage) of patients. Abbreviations: CABG, coronary artery bypass surgery; CAG, coronary angiography; EEM, external elastic membrane; IVUS, intravascular ultrasound; MLA, minimal lumen area; PCI, percutaneous coronary intervention; SD, standard deviation; SYNTAX, the synergy between percutaneous coronary intervention with taxus and cardiac surgery; UHR, UA to HDL-C ratio.

The results of this study demonstrated that significantly higher UHR values were determined in patients determined with a critical lesion according to the two separate parameters of MLA and plaque burden in the IVUS measurements of patients determined with ICS on LMCA. The UHR showed a negative correlation with MLA, showing lesion severity in the LMCA IVUS measurements, and a positive correlation with PB. The UHR, as a new biomarker combining UA and HDL-C, showed excellent diagnostic capacity for anatomically significant stenosis in patients with the LMCA disease of ICS. To the best of our knowledge, this is the first study in the literature to have investigated the anatomic relationship of ICS with UHR.

Despite advances in the field of interventional cardiology, correct evaluation of ICS in the catheterisation laboratory and the decision for PCI are still a great challenge [18]. This problem has been resolved by determining the plaque burden and lesion severity with MLA limits through comparisons of IVUS measurements in LMCA lesions with distal and proximal vessel diameters. An MLA value <6mm² and plaque burden ≥65% shows anatomically critical LMCA stenosis [12, 13]. However, the IVUS device is not widely used in diagnosis and treatment in clinical practice because of the extra operation time, high costs and the need for an experienced operator [19]. Therefore, there seems to be a need for a biomarker that is reliable in terms of showing lesion severity in ICS lesions. Some biomarkers have been researched in previous studies with the aim of being able to determine lesion severity in patients determined with ICS. However, those studies have focussed more on the functional significance of the stricture. Erdogan M. et al. suggested that the systemic immune inflammation index, calculated as neutrophil*thrombocyte/lymphocyte counts, could predict the fractional flow reserve (FFR) with high sensitivity and specificity [5]. Other studies have also shown that the UA value and modification of some lipid biomarkers could predict the FFR value [6, 20]. In a recent study by Fanqi Li et al., a significant relationship was determined between UHR and FFR severity in patients with ICS [21]. All of these studies concentrated on the functional significance of the stricture and were conducted with the FFR test.

IVUS imaging is the current gold standard method to evaluate LMCA lesions [22]. In intermediate LMCA lesions, the FFR test often causes incorrect classification [23]. In addition, because of the high cost, reimbursement for IVUS imaging is only received for LMCA lesions in Türkiye. Therefore, only patients with LMCA lesions were included in this study.

In the current study population, uric acid values were determined to be signficantly high in the patient group with a high plaque burden. In a previous study on this subject by Ando K. et al., a significant relationship was determined between elevated uric acid and high lipid volume and plaque burden on IVUS [24]. Unlike the current study, that study included IVUS measurements for vessels other than the LMCA, and the effect of uric acid on plaque burden in particular was shown to be independent of gender. In the current study, the uric acid levels were determined to be significantly high in the patient group with MLA <6mm². As there was seen to be a relationship between uric acid levels and a high plaque burden, it was expected that MLA would be low in cases with high uric acid levels.

When the UHR parameter was examined as a continous variable, a significant relationship was determined between the UHR variable and high plaque burden and low MLA values. The HDL-C parameter alone, independently of uric acid, was not found to have a significant effect on these measurements. This result could be associated with being lower in the group with high plaque burden and low MLA value, even if the HDL-C values were not significant. This can explain the significant effect of the HDL-C value on plaque burden and MLA compared to uric acid.

When ROC curve analyses were performed for MLA and plaque burden separately with the UHR parameter, the UHR cut-off value was found to be 450 for both curves. This demonstrated that a value of 450 can be defined as the limit for the UHR parameter. The patient population was then evaluated as subgroups above and below the UHR value of 450. There was determined to be a significantly greater number of patients with MLA <6mm² and plaque burden ≥65% in the patient grooup with high UHR. In a previous study on this subject performed with FFR, the UHR cut-off value was determined to be 310.8 [21]. This was a much lower cut-off value than that of the current study and the difference could be attributed to the measurement methods. The above-mentioned study evaluated the stricture functionally using an FFR device, whereas anatomic stricture evaluation was performed in the current study using IVUS.

The drugs used by the patients in the current study were examined, and there was observed to be a significantly low rate of use of B-blockers and ACE inhibitors in the patient group with MLA <6mm², and in the patients with plaque burden ≥65%. Previous studies in literature have shown that B-blocker use slows the progression of coronary atherosclerosis [25]. It has also been shown that ACE inhibitor use significantly reduces coronary atherosclerosis [26]. Consistent with the findings of those studies, the use of B-blockers and ACE inhibitors was determined to be high in the current study patients with low plaque burden and high MLA.

From these results, it was seen that the UHR parameter can predict vessel stricture, consistent with MLA and plaque burden showing critical vascular narrowing on IVUS measurements in patients with ICS LMCA lesion. Thus it was shown that UHR can predict values of MLA <6mm² and plaque burden ≥65%, which are accepted as critical in IVUS measurements for LMCA.

Study Limitations

There were some limitations to this study to be considered, primarily the single-centre, retrospective design and limited sample size. Only patients with LMCA lesion were included in the study, because IVUS is the gold standard method in LMCA lesions and in Türkiye, reimbursement for use of the IVUS device is only made for LMCA lesions. A further limitation was that the rate of statin use was high in the patient population and this could have affected the HDL-C value in the UHR calculation. However, as there was no significant differencee in the rate of statin use between those with and without critical lesions, statin use was not considered to have affected the results obtained.

The results of this study suggested that there was a relationship between the UHR parameter and MLA <6mm² and plaque burden ≥65%, which are independently evaluated as critical in IVUS, and this could predict anatomically significant lesions in patients with a moderate degree of LMCA stricture.

CAD: Coronary artery disease

CAG: Coronary angiography

ICS: Intermediate coronary stenosis

LMCA: Left main coronary artery

IVUS: Intravascular ultrasound

UA: Uric acid

HDL-C: High-density lipoprotein cholesterol

UHR: Uric acid to HDL-C ratio

SAP: Stable angina pectoris

ACS: Acute coronary syndrome

MLA: Minimal lumen area

PB: Plaque burden

EEM: External elastic membrane

CSA: Cross-sectional areas

SD: Standard deviation

AUC: Area under the curve

OR: Odds ratio

Ethics committee approval and consent to participate

All the procedures in this study including human participants were applied in compliance with the ethical standards of the institutional research committee and the 1964 Helsinki Declaration and subsequent revisions or comparable ethical standards. No animals were used in this study. Approval for the study was granted by the Bursa Yuksek Ihtisas Training and Research Hospital Ethics Committee (Protocol Code: 2011-KAEK-25 2023/11-02)

Consent for publication

Not applicable.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Competing interests

The authors declare that they have no conflict of interests.

Funding

There is no funding source for the research.

Authors' contributions

-ÖFD Conceptualization, writing, review and editing, methodology. AA Conceptualization and resources, MK Project administration, BŞ Review and editing, GD Formal analysis.

Acknowledgements

Not applicable.

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No competing interests reported.

Uric acid/HDL-C Ratio May Predict Significant Coronary Artery Stenosis: Intravascular Ultrasonography Study

Status:

Version 1

Abstract

Introduction

Materials and Methods

Data Collection and Laboratory Analysis

Coronary Angiography

IVUS Imaging and Analysis

Statistical Analysis

Ethics Committee Approval

Results

Discussion

Conclusion

Abbreviations

Declarations

References

Additional Declarations

Status:

Version 1