Startseite Medizin Relationship of resting echocardiography combined with serum micronutrients to the severity of low-gradient severe aortic stenosis
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Relationship of resting echocardiography combined with serum micronutrients to the severity of low-gradient severe aortic stenosis

  • Zhangxin Fan EMAIL logo und Fang Lin
Veröffentlicht/Copyright: 3. November 2025
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Open Medicine
Aus der Zeitschrift Open Medicine Band 20 Heft 1

Abstract

Objective

This study investigated the relationship between serum magnesium, phosphorus, and calcium and low-gradient severe aortic stenosis (LG-AS).

Methods

Dobutamine stress echocardiography (DSE) and resting echocardiography were performed on 73 patients with LG-AS. A projected aortic valve area (AVAproj) ≤ 1 cm2 or indexed AVAIproj < 0.60 cm2/m2 was defined as true-severe AS. Serum magnesium, phosphorus, and calcium were compared. The correlation between serum micronutrients and resting echocardiographic parameters was analyzed. The efficacy of serum micronutrients and resting echocardiographic parameters in predicting true-severe AS in LG-AS was assessed.

Results

DSE diagnosed true-severe AS in 43 patients and pseudo-severe AS in 30 patients. AVA and AVAI were smaller, and the mean pressure gradient (PG) was higher in patients with true-severe AS. Serum calcium and phosphorus were higher, and serum magnesium was lower in patients with true-severe AS. Serum calcium was positively correlated with AVA and AVAI. Serum magnesium had a moderately strong correlation with mean PG. Serum micronutrients had good predictive value for true-severe AS and AVAI, and mean PG improved the predictive value of serum micronutrients.

Conclusion

Serum micronutrients have diagnostic values for true-severe AS in patients with LG-AS.

Keywords: echocardiography; dobutamine stress echocardiography; serum micronutrients; aortic stenosis; low-gradient aortic stenosis

1 Introduction

Aortic stenosis (AS), a prevalent condition affecting the heart valve, markedly reduces life span upon developing symptoms [1,2]. Accurate grading of the severity of AS is critical in determining the appropriate treatment. Echocardiographic evaluation of patients is assessed and categorized according to the Guidelines of the European Association of Cardiovascular Imaging and the American Society of Echocardiography [3]. Severe AS is defined by small aortic valve area (AVA < 1 cm2 or indexed AVI [AVAI] < 0.6 cm2/m2) or high mean pressure gradient (PG > 40 mmHg, manifested by high aortic valve flow velocity). Nonetheless, the severity determined by the aortic valve PG does not consistently align with the severity outlined by AVA. Considering that the aortic valve PG depends on flow dynamics [4,5], severe AS patients with diminished left ventricular ejection fraction (LVEF) or those in a low-flow condition with maintained LVEF, might exhibit a reduced mean PG, known as low-gradient aortic stenosis (LG-AS) [6]. These patients may present with pseudo-severe AS due to incomplete opening of the stenotic valve. Patients with low-gradient AS are broadly categorized into three groups: (1) low-flow, low-gradient AS (LFLG-AS; LVEF < 50%), paradoxical low-flow, low-gradient AS (pLFLG-AS; LVEF ≥ 50% with aN indexed stroke volume, SVI, < 35 mL/m2), or normal flow, low-gradient AS (NFLG-AS; LVEF ≥ 50%, SVI ≥ 35 mL/m2) [7].

Distinguishing true-severe AS from pseudo-severe AS is vital, as individuals with true-severe AS typically gain from aortic valve replacement [8]; whereas, patients with pseudo-severe AS may not benefit from surgical intervention but require intensive pharmacologic therapy and close follow-up [9]. Dobutamine stress echocardiography (DSE) is recommended for the diagnosis of severe AS in LG-AS [10,11]. That is, the projected aortic valve area (AVAproj) at normal transvalvular flow velocity is superior to conventional resting Doppler echocardiographic parameters and can be used to differentiate between pseudo- and true-severe AS [12]. In contrast to the noninvasive nature and easy performance of resting echocardiography, DSE can cause side effects and adverse reactions in patients [13].

Traditionally, magnesium, phosphorus, and calcium are identified as micronutrients linked to maintaining bone health or managing chronic kidney disease [14] and have also been implicated in the risk of cardiovascular disease and subclinical coronary atherosclerosis. There is significant evidence that these elements also influence the occurrence and development of heart valve disease. Aortic valve stenosis, which is primarily caused by calcium deposits narrowing the valve, is the most common valvular heart condition [15]. Multifactorial calcification is caused by mechanical stress, lipid infiltration, and accumulation in inflamed tissue, ultimately causing fibrosis, thickening of the lobules, and calcification [16]. Deficiencies of magnesium may cause impaired cellular metabolic function, mitochondrial dysfunction, and endothelial dysfunction, which further harms the body [17]. Furthermore, cardiovascular diseases may be associated with abnormal phosphorus levels due to vascular calcification, inflammation, and oxidative stress [17]. Many studies have confirmed the role of these trace elements in aortic calcification. For example, elevated serum calcium and phosphorus levels promote AS through vascular calcification [18]. Decreased serum magnesium levels contribute to increased vascular calcification, which increases cardiovascular mortality [19]. Despite the association of these micronutrients with cardiovascular disease, there are limited data on the relationship between these micronutrients and the severity of AS.

This study was to assess the validity of serum magnesium, phosphorus, and calcium levels versus resting echocardiographic parameters in predicting DSE outcomes in patients with LG-AS.

2 Materials and methods

2.1 Patients

This was a cross-sectional cohort study. Patient data were collected at Putian the 95th Hospital. Seventy-three patients (age 66.9 ± 13.8 years, 41 males and 32 females) who underwent DES in Putian the 95th Hospital after echocardiographic diagnosis of LG-AS over a 2-year period (2022.03-2024.03) were studied. LG-AS was defined as an echocardiographic demonstration of a mean PG < 40 mmHg, SVI < 35 mL/m2, AVAI < 0.6 cm2/m2, or AVA < 1 cm2 (3).

The following patients were excluded: (1) atrial fibrillation or atrial tachycardia, (2) ventricular pacing rhythm, (3) mitral stenosis of more than mild severity, (4) moderate or greater aortic, mitral, or tricuspid regurgitation, (5) acute pulmonary edema, and (6) end-stage renal disease.

All patients were diagnosed with LG-AS by initial echocardiography and subsequently diagnosed with true-severe AS (total 43, age 65.2 ± 15.3 years, 23 males and 20 females) and pseudo-severe AS (total 30, age 66.4 ± 12.3 years, 18 males and 12 females) by DSE. This study was approved by the Putian the 95th Hospital Institutional Review Board, and consent was obtained from the patients or their families.

2.2 Collection of general patient information

General information about the patients was collected, including gender, age, height, and weight, and the body surface area was calculated [20]. Information was obtained about patients’ combined diabetes, hypertension, dyslipidemia, coronary artery disease, chronic kidney disease, and use of drugs (corticosteroids, gastric medicine, parathyroid hormone, diuretics, antibiotics, and warfarin) or supplements (gluconate oral solution, vitamin D containing tablets or capsules, sodium glycerophosphate injection, potassium magnesium aspartate tablets, magnesium sulfate injection, etc.) that affect calcium, magnesium, and phosphorus.

2.3 Echocardiography

All echocardiograms were performed following the focused updated current guidelines of the European Association of Cardiovascular Imaging and the American Society of Echocardiography (3). The instruments used were Philips IE33 or Epiq 7C (Philips Healthcare, Andover, MA). All echocardiograms were reviewed by a board-certified echocardiography investigator with no knowledge of all other imaging and clinical findings. The left ventricular diastolic diameter, systolic diameter, and stroke volume were assessed. The data on Doppler flow were collected in pulsed-wave mode from the LV outflow tract (LVOT) area and in continuous-wave mode from the aortic valve, utilizing transducers to achieve peak velocity. The mean PG was calculated using the streamlined Bernoulli’s principle. The left ventricular ejection fraction (LVEF) was measured using the biplane Simpson method. The LVOT diameter was measured in the parasternal long-axis view, and the measurement was used to obtain pulsed-wave Doppler data. The mean transvalvular flow rate (Q), calculated by dividing the stroke volume by the LVEF time, was obtained using the continuity equation to calculate AVA (cm2). AVAI is expressed by dividing by the body surface area (cm2/m2); AVAI < 0.60 was considered severe. For these parameters, measurements from at least three cycles were averaged.

2.4 DSE

DSE was performed by a specialized sonographer in the echocardiography laboratory. Initially, dobutamine was administered at 5 μg/kg/min, increasing to a peak of 20 μg/kg/min every 5 min. At every phase of DSE, measurements of AVA and gradients were taken. The diameter of LVOT was gauged solely in a resting state and was deemed steady throughout the DSE process. Peak stress measurements were recorded at the peak of the mean PG during DSE, which might not align with the last stage of the highest dose of dobutamine. AVAproj at a standard flow rate of 250 mL/s was then calculated. AVAproj was exponentiated by the body surface area. AVAproj ≤ 1 cm2 or an exponentiated AVAIproj < 0.60 cm2/m2 was defined as true severe AS. The AVAproj and AVAIproj equations are as follows (10):

AVA proj = ( AVA peak − AVA rest ) Q peak − Q rest × ( 250 − Q rest ) + AVA rest ,

AVAI proj = AVA proj Body surface area ,

where AVArest and Q rest are AVA and Q at rest, and AVApeak and Q peak are AVA and Q measured by peak load echocardiography.

2.5 Serum micronutrient measurements

Venipuncture was performed early after fasting for at least 12 h. The serum was separated by centrifugation (3,000 rpm for 15 min) at 4°C, all within a 90-min timeframe. For standard testing, samples were dispatched to the lab, while the rest were preserved at −70°C. The levels of calcium, phosphorus, and magnesium in serum were measured employing the Arsenazo III technique (NIPRO, Osaka, Japan), the dicarbonyl blue-I method, and the molybdate blue colorimetric technique (Sekisui Medical, Tokyo, Japan), respectively. Variation coefficients of inter and intra-assays for serum micronutrient concentrations remained below 2.4%. The bromocresol green assay (Wako Pure Chemical Industries, Osaka, Japan) was employed to gauge serum albumin concentrations. Variability coefficients for serum albumin levels, both inter- and intra-assays, remained below 2.8%. Serum calcium was adjusted for serum albumin if serum albumin was less than 4.0 mg/dL using the following formula: Corrected calcium = measured total calcium (mg/dL) + 0.8 × (4.0 serum albumin (g/dL) [21]. All reported results for calcium were based on serum albumin-corrected variables.

2.6 Data statistics

Statistical analyses were performed using SPSS 22.0 software (SPSS Inc., Chicago, IL, USA). The Shapiro–Wilk test was used to determine the normality of the data. Measurement data are shown as mean ± standard deviation (X̅ ± S). t-test (two groups) was used for comparison between two groups for data on continuous variables in a normal distribution; the Mann–Whitney U test was used for comparison between two groups for data on continuous variables in a skewed distribution. Count data are expressed as frequencies (N) and ratios (%), and Chi-square or Fisher’s exact tests were used. Spearman’s test was used to analyze the correlation between serum micronutrients and echocardiograms, and Bonferroni correction was used for multiple comparisons. The sample size of the study was estimated using G*Power software version 3.1.9.2 (Kiel, Germany) with a significance level of α = 0.05, a power of 1 – β = 0.8, and an effect size of d = 0.5, and two-sided tests were performed. P < 0.05 was considered statistically significant. Data were plotted using GraphPad Prism 8 (GraphPad, San Diego, CA, USA). Predictive values of serum micronutrient combinations were obtained using binary logistic analysis. Receiver operating characteristic curves (ROCs) and calculation of the area under the ROC curve (AUC) metrics were used to assess the value of true AS in patients with LG-AS. MedCalc software was used to compare whether there was a statistically significant difference in the AUCs between metrics. A P value of <0.05 was considered statistically significant. AUCs were compared with the AUCs of the different metrics. A P value of <0.05 was considered statistically significant.

  1. Informed consent: Written informed consent was provided by all patients prior to the start of the study.

  2. Ethics statement: The present study was approved by the Ethics Committee of Putian the 95th Hospital (IRB20210302). All procedures were performed in accordance with the ethical standards of the Institutional Review Board and the Declaration of Helsinki, and its later amendments or comparable ethical standards.

3 Results

3.1 Echocardiography of the patients

The mean age of 73 patients was 66.9 ± 13.8 years; 41 were males and 32 were females, of which 3 (4.11%) patients had bicuspid aortic valve. Forty-three (58.90%) of the 73 patients were diagnosed with true-severe AS by DSE, and the remaining 30 (41.10%) were diagnosed with pseudo-severe AS by DSE. Table 1 lists patient characteristics and resting echocardiographic and DSE results in patients with true-severe AS and pseudo-severe AS. Among the resting echocardiographic parameters, AVA and AVAI were smaller in patients with true-severe AS than in those with pseudo-severe AS (0.71 ± 0.19 cm2 vs 0.78 ± 0.16 cm2, P < 0.0001; 0.458 ± 0.084 cm2/m2 vs 0.504 ± 0.074, P < 0.0001). Mean PG was higher in patients with true-severe AS than in patients with pseudo-severe AS (24 ± 7 mmHg vs 21 ± 6 mmHg, P = 0.018). After assessment using DSE, the SVI, flow rate, AVA, AVAI, and mean PG were higher in both groups observed under DSE compared to resting echocardiography (all P < 0.05). There was also a statistically significant difference in the AVA, AVAI, and mean PG observed under DSE, shown to be AVA, and AVAI were smaller in true-severe AS patients than in patients with pseudo-severe AS (0.76 ± 0.21 cm2 vs 1.04 ± 0.18 cm2, P < 0.0001; 0.481 ± 0.061 cm2/m2 vs 0.689 ± 0.064, P < 0.0001). Mean PG was higher in patients with true-severe AS than in patients with pseudo-severe AS (43 ± 8 mmHg vs 32 ± 9 mmHg, P = 0.018). No statistically significant differences in age, gender, body surface area, and comorbid underlying diseases were found between the two groups of patients (all P > 0.05).

Table 1

Patient characteristics and resting echocardiography

True-severe AS (n = 43) Pseudo-severe AS (n = 30) P
Age, years 65.2 ± 15.3 66.4 ± 12.3 0.746
Gender (male/female) 23/20 (53.50/46.50) 18/12 (60.00/40.00) 0.581
Body surface area (m2) 1.56 ± 0.32 1.54 ± 0.29 0.826
Contraindication diseases
Hypertension 29 (67.44) 19 (63.3) 0.716
Diabetes 15 (34.89) 8 (26.67) 0.457
Dyslipidemia 16 (37.21) 6 (20.00) 0.115
Coronary artery disease 17 (39.53) 15 (50.00) 0.375
Chronic kidney disease 7 (16.28) 3 (10.00) 0.443
Medications and supplements
Calcium 1 (2.35) 2 (6.66) 0.564
Magnesium 0 (0.00) 0 (0.00) 1.00
Phosphorus 0 (0.00) 0 (0.00) 1.00
Indexed LV mass (g/m2) 156 ± 40 159 ± 54 0.365
Aortic valve morphology (bicuspid/tricuspid) 16/27 (37.21) 7/23 (23.33/76.67) 0.209
LV diastolic dimension (mm) 48 ± 9 49 ± 11 0.748
LV systolic dimension (mm) 37 ± 11 37 ± 10 0.925
LVEF (%) 50 ± 14 51 ± 15 0.785
Heart rate (bpm) 73 ± 8 74 ± 10 0.426
SVIrest (mL/m2) 36 ± 7 34 ± 9 0.657
Flow raterest (mL/m2) 168 ± 41 162 ± 43 0.642
AVArest, cm2 0.71 ± 0.19 0.78 ± 0.16 0.000
AVAIrest (cm2/m2) 0.458 ± 0.084 0.504 ± 0.074 0.000
Mean PGrest (mmHg) 24 ± 7 21 ± 6 0.018
SVIpeak (mL/m2) 45 ± 9△ 43 ± 9△ 0.385
Flow ratepeak (mL/m2) 251 ± 67△ 253 ± 71△ 0.746
AVApeak, cm2 0.76 ± 0.21△ 1.04 ± 0.18△ 0.000
AVAIpeak (cm2/m2) 0.481 ± 0.061△ 0.689 ± 0.064△ 0.000
Mean PGpeak (mmHg) 43 ± 8△ 32 ± 9△ 0.000

LV: left ventricle; LVEF: left ventricular ejection fraction; SVI: stroke volume index; LVET: left ventricular ejection time; AVA: aortic valve area; AVAI: indexed aortic valve area; PG: pressure gradient; and AS: aortic stenosis. P < 0.05 was statistically significant. △P < 0.05 compared with resting echocardiography.

3.2 Serum micronutrients in the two groups of patients

Data analysis (Table 1) indicates that patients did not take drugs containing phosphorus or magnesium prior to measuring trace elements. A small number of patients took calcium supplements, but there is no statistical significance (P = 0.564). Next, serum calcium, phosphorus, and magnesium levels were measured in these patients, as shown in Figure 1. It was observed that serum calcium and phosphorus levels were higher in patients with true-severe AS than in patients with pseudo-severe AS (9.79 ± 0.27 mg/dL vs 9.52 ± 0.23 mg/dL, P < 0.001, Figure 1a; 3.25 ± 0.30 mg/dL vs 3.09 ± 0.27 mg/dL, P < 0.05, Figure 1b). Serum magnesium levels in true-severe AS patients were lower than those in pseudo-severe AS patients (2.10 ± 0.18 mg/dL vs 2.23 ± 0.22 mg/dL, P < 0.05, Figure 1c). Subgroups were based on median values of serum calcium 9.71 mg/dL, phosphorus 3.21 mg/dL, and magnesium 2.18 mg/dL. Patients with LG-AS, who were ultimately diagnosed with true-severe AS, were used as a risk term. They were categorized into three main groups: low risk, medium risk, and high risk. As shown in Table 2, in 73 patients with LG-AS, the percentages of those who were assessed as low, medium, and high risk based on serum micronutrients were 47.95, 30.13, and 21.92%, respectively. Among the 43 patients with true-severe AS, 14 patients (14/43, 32.56%) were at high risk, which accounted for 87.50% (14/16) of the total number of high-risk individuals, which was significantly higher than that of patients with pseudo-severe AS (2/30, 4.65%) (P = 0.009). There was a statistical difference in the number of patients with true- and pseudo-severe AS assessed as low risk, with the number of low-risk individuals being proportionally higher in patients with pseudo-severe AS (14/43, 9.30% vs 21/30, 48.84, P < 0.001). In particular, this result seems to be mainly attributable to L0 and L3, i.e., all serum micronutrients above the median value (with magnesium ≤ median) and only magnesium ≤ median (L3), which were more prevalent in patients with pseudo-severe AS.

Figure 1 Comparison of serum micronutrients in true-severe AS and pseudo-severe AS. Levels of (a) serum calcium, (b) serum phosphorus, and (c) serum magnesium. *Student’s t-test and #Non-parametric test. *P < 0.05,***P < 0.001, and #P < 0.05. P < 0.05 is statistically significant.
Figure 1

Comparison of serum micronutrients in true-severe AS and pseudo-severe AS. Levels of (a) serum calcium, (b) serum phosphorus, and (c) serum magnesium. *Student’s t-test and #Non-parametric test. *P < 0.05,***P < 0.001, and #P < 0.05. P < 0.05 is statistically significant.

Table 2

Proportion of patients with true-severe AS and pseudo-severe AS in subgroups

True-severe AS Pseudo-severe AS P
Low risk
L0 5 (11.63) 10 (23.23) 0.024
L1 4 (9.30) 0 (0.00) 0.139
L2 1 (2.33) 4 (9.30) 0.152
L3 4 (9.30) 7 (16.28) 0.182
ALL 14 (32.56) 21 (48.84) 0.000
Medium risk
M1 10 (23.26) 2 (4.65) 0.106
M2 3 (6.98) 2 (4.65) 1.000
M3 2 (4.65) 3 (6.98) 0.396
ALL 15 (34.88) 7 (16.28) 0.290
High risk
H 14 (32.56) 2 (4.65) 0.009
ALL 14 (32.56) 2 (4.65) /

Data are expressed as N (%). Grouped according to median serum micronutrient values, low risk (risk of True-severe AS): only serum calcium ≥ median value (L1), only serum phosphorus ≥ median value (L2), or only magnesium ≤ median value (L3), where serum calcium and phosphorus are both < median value and magnesium > median value, were also included in the low-risk group (L0); medium risk: serum calcium and phosphorus both ≥ median value (M1), or magnesium ≤ median value with serum calcium ≥ median value (M2), and magnesium ≤ median value with phosphorus ≥ median value (M3); and high risk: serum calcium and phosphorus both ≥ median value, and magnesium ≤ median value.

3.3 Correlation analysis of serum micronutrients with resting echocardiography

As shown in Figure 2 and illustrated in Table 3, serum calcium had a positive correlation with AVA and AVAI and a strong correlation with AVAI (rs = 0.612, P < 0.001) (Figure 2a). Serum magnesium had a moderately strong correlation with mean PG (rs = −0.489, P < 0.001) (Figure 2b). No significant correlation was observed between serum phosphorus and the above parameters (Figure 2c).

Figure 2 Correlation analysis plots of serum micronutrients with resting echocardiographic parameters. Correlation analysis plots of (a) serum calcium, (b) serum phosphorus, and (c) serum magnesium with resting echocardiographic parameters, including AVA, AVAI, and mean PG, respectively.
Figure 2

Correlation analysis plots of serum micronutrients with resting echocardiographic parameters. Correlation analysis plots of (a) serum calcium, (b) serum phosphorus, and (c) serum magnesium with resting echocardiographic parameters, including AVA, AVAI, and mean PG, respectively.

Table 3

Correlation coefficients between serum micronutrients and resting echocardiographic parameters

Serum calcium (mg/dL) Serum phosphorus (mg/dL) Serum magnesium (mg/dL)
AVA (cm2) 0.249* 0.086 −0.058
AVAI (cm2/m2) 0.612*** 0.102 0.201
Mean PG (mmHg) 0.106 −0.008 −0.489***

Spearman’s correlation coefficient rs was used to show correlation, 0.1–0.3 (weak correlation), 0.3–0.6 (medium strength correlation), and >0.6 strong correlation. All P-values are shown as corrected P-values (FDR program for correction). *P < 0.05 and ***P < 0.001. P < 0.05 is statistically significant.

3.4 Validity of serum micronutrients and resting echocardiographic parameters for assessment of true-severe AS

Next, the predictive values of the three serum micronutrients (calcium, phosphorus, and magnesium) were utilized for ROC curve analysis of true-severe AS. As shown in Figure 3, the combined predictive AUC of the three serum micronutrients was 0.732, 95% CI 0.612–0.852, which had predictive value for true-severe AS in patients with LG-AS (P < 0.001). AVAI combined with serum micronutrients improved the predictive value of serum micronutrients (P = 0.001). Mean PG combined with serum micronutrients also slightly improved the predictive value of serum micronutrients (P = 0.025). AVA combined with serum micronutrients had statistically significant predictive value; however, it did not improve the predictive value of serum micronutrients (P = 0.385).

Figure 3 ROC curve of serum micronutrients versus resting echocardiographic parameters for predicting true-severe AS.
Figure 3

ROC curve of serum micronutrients versus resting echocardiographic parameters for predicting true-severe AS.

4 Discussion

This study analyzed the role of resting echocardiography and serum micronutrients in predicting DSE outcomes in patients with LG-AS. It was found that (1) AVA and AVAI assessed using resting echocardiography were higher, and mean PG was lower in patients with true-severe AS; (2) serum calcium and phosphorus were higher, and serum magnesium was lower in patients with true-severe AS; and (3) using patients with true-severe AS diagnosed by DSE as a risk term and median serum micronutrient values to classify the risk group, the total number of high-risk was 16, with 87.5% (14/16) in the true-severe AS group; and (4) serum micronutrients had good predictive value for true-severe AS in patients with LG-AS, and the resting echocardiographic parameters AVAI and mean PG improved the predictive value of serum micronutrients.

Resting AVA < 1.0 cm2 or AVAI < 0.6 cm2/m2 was used to determine small AVA. Peak aortic valve velocity > 4 m/s and mean PG > 40 mmHg were used to determine high aortic valve velocity and high aortic valve PG, respectively [3]. However, the severity assessed by small AVA and higher mean PG is not always consistent. LG-AS is characterized by the presence of a small AVA but a lower mean PG [7]. Indeed, approximately 10–20% of severe AS have been reported as classic low-flow LG-AS with reduced LVEF, and 10–25% of severe AS with preserved LVEF have been reported as paradoxical low-flow LG-AS [6,22]. Due to its flow-dependent nature, mean PG may underestimate the severity of stenosis, whereas lower AVA or AVAI may overestimate the severity of stenosis due to incomplete opening of the valve. Small AVA due to low-flow status is referred to as pseudo-severe AS (although its actual severity is moderate) and should be differentiated from true-severe AS for the selection of appropriate therapy (8). DSE is recommended in patients with classic low-flow AS to distinguish true-severe AS from pseudo-severe AS [23,24]. A previous study also recommends DSE and AVAproj measurements in pLFLG-AS patients with preserved LVEF [25]. Critical values of AVAproj and AVAIproj are used to predict clinical outcomes between LFLG-AS and pLFLG-AS (1.0 cm2 and 0.6 cm2/m2, respectively) [25]. The significance of DSE seems to be the same in both patients. Nonetheless, DSE presents as a lengthy and challenging diagnostic instrument for doctors and technicians and is not recommended for clinical application. Therefore, our study focused on these two types of patients who underwent resting echocardiography and DSE to differentiate between true and pseudo-severe AS by DSE and to observe the characteristics of the differences in parameters in resting echocardiography. In addition, certain differential parameters of resting echocardiography in combination with serum indices may predict the outcome of DSE in patients with LG-AS.

Aortic calcification is one of the most important etiologic factors of AS. High serum calcium levels may lead to deposition of calcium deposition on the aortic valve, leading to sclerosis of the aortic valve, which will eventually lead to stenosis of the aortic orifice in patients [26]. In patients with end-stage renal disease, increased serum phosphorus levels also promote mitral and aortic valve calcification, whereas serum magnesium concentrations negatively correlate with vascular calcification and may be a compensatory regulatory mechanism that reduces calcium phosphate hydrolysis and vascular calcification [27]. Previous research has demonstrated that the majority of patients with severe aortic valve stenosis and a low mean transvalvular gradient, as assessed by echocardiography, exhibit significant valve calcification [28,29]. In a multiethnic group of patients with atherosclerosis, increased serum phosphorus and urinary phosphorus levels are associated with aortic valve calcification [30]. Serum magnesium is negatively associated with the prevalence of AS [15]. A previous study reports a 1.79-fold increase in the risk of AS per 0.1 mmoL/L increase in calcium concentration and a 1.47-fold increase in the risk of AS per 0.1 mmoL/L increase in phosphorus concentration [31]. In addition, another study shows a 51% increase in the risk of dying from AS for every 0.1 mmoL/L increase in serum calcium [32]. A significant correlation is known to exist between the severity of AS and the risk of death. If severe symptomatic AS is left untreated, the prognosis is poor, with a mortality rate of up to 50% at 1 year after the onset of symptoms and more than 90% at 5 years [33]. Therefore, serum micronutrients are potentially important and reliable markers of AS severity.

In the present study, serum calcium and phosphorus had higher levels, and serum magnesium had lower levels in patients with true-severe AS. This is the first study to confirm the association of serum micronutrients with AS severity. Aortic calcification represents a vascular pathology marked by the accumulation of calcium within the arterial wall. The principal pathological mechanisms contributing to the development of aortic calcification include oxidative stress, inflammation, and endothelial dysfunction. Elevated levels of blood calcium and phosphorus expedite the progression of aortic calcification by facilitating the osteogenic differentiation of vascular smooth muscle cells (VSMCs) and enhancing the expression of calcification-associated factors, such as alkaline phosphatase (ALP) and osteocalcin (OC) [34,35]. A clinical study has demonstrated that the serum calcium–phosphorus product (Ca × P) exhibits a positive correlation with the severity of aortic calcification, thereby reinforcing the critical involvement of calcium and phosphorus in vascular calcification [36]. Furthermore, magnesium ions have been shown to inhibit the proliferation and migration of VSMCs, thereby mitigating their differentiation into osteoblast-like cells. Additionally, magnesium ions can suppress inflammation and oxidative stress, consequently diminishing the damage inflicted by reactive oxygen species on the vascular wall and alleviating endothelial dysfunction [37]. It is worth noting that when endothelial dysfunction occurs, platelet activation and adhesion cannot be effectively inhibited, and thrombi are prone to form. This thrombotic state may not only directly affect the function of the aortic valve but may also indirectly aggravate the symptoms of AS by, for example, blocking blood flow [38]. In addition, in AS, the left ventricle needs to contract more strongly to pump sufficient blood, which may result in a large systolic pressure difference between the left ventricle and the aorta. This pressure difference may result in reduced blood flow to the aorta and coronary arteries, further affecting endothelial cell function and survival [39]. There may be an interaction and vicious circle between endothelial dysfunction and AS. Therefore, the present study attempted to subgroup by serum micronutrient levels. Patients with LG-AS who were eventually diagnosed with true-severe AS by DSE were used as a risk term. The results showed that a total of 16 patients were assessed as high risk, of which 14 were all present in the true-severe AS group. Subsequently, we confirmed a positive correlation of serum calcium with AVA and AVAI, with a particularly strong positive correlation with AVAI (rs = 0.612, P < 0.001). There was a moderately strong correlation between serum magnesium and mean PG (rs = −0.489, P < 0.001). However, we did not observe a significant correlation between serum phosphorus and the above parameters. Therefore, we believe that serum calcium and magnesium are potentially closely correlated with resting echocardiography. Finally, we plotted ROC curves to analyze the predictive value of true-severe AS in patients with LG-AS. As expected, the combination of the three serum micronutrients had predictive values, and the resting echocardiographic parameters AVAI and mean PG improved the predictive value of serum micronutrients.

However, this study also has limitations. First, this study is a cross-sectional cohort study that only establishes an association, not causality. Follow-up of patients over a certain time frame would provide an opportunity to identify changes in valvular gradients associated with serum nutrient elements. Second, the study cohort consisted of a relatively small number of subjects, which may limit the generalizability of the findings. A multifactorial screening for independent correlates would be more favorable to increase the reliability of the diagnostic results of the ROC curves. Finally, our results apply only to calcium, phosphorus, and magnesium.

5 Conclusion

Serum micronutrients are associated with the severity of AS patients. Serum micronutrients are effective in differentiating between LG-AS patients with true-severe AS, and the resting echocardiographic parameters AVAI and mean PG improve the assessment value of serum micronutrients. Based on the results of this study, it can be used as a theoretical basis for the development of predictive models for confirming the diagnosis of true-severe AS among patients with LG-AS and therapeutic strategies for slowing down the disease process in clinical treatment.

  1. Funding information: The authors state no funding involved.

  2. Author contributions: Zhangxin Fan designed the research study, wrote the manuscript, and reviewed the manuscript. Fang Lin performed the research, and provided help and advice on the experiments. Zhangxin Fan and Fang Lin analyzed the data. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript.

  3. Conflict of interest: The authors state no conflict of interest.

  4. Data availability statement: Data are available from the corresponding author on request.

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Received: 2024-07-28
Revised: 2024-11-05
Accepted: 2024-12-05
Published Online: 2025-11-03

© 2025 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  177. Microscopic changes and gross morphology of placenta in women affected by gestational diabetes mellitus in dietary treatment: A systematic review
  178. Review of mechanisms and frontier applications in IL-17A-induced hypertension
  179. Research progress on the correlation between islet amyloid peptides and type 2 diabetes mellitus
  180. The safety and efficacy of BCG combined with mitomycin C compared with BCG monotherapy in patients with non-muscle-invasive bladder cancer: A systematic review and meta-analysis
  181. The application of augmented reality in robotic general surgery: A mini-review
  182. The effect of Greek mountain tea extract and wheat germ extract on peripheral blood flow and eicosanoid metabolism in mammals
  183. Neurogasobiology of migraine: Carbon monoxide, hydrogen sulfide, and nitric oxide as emerging pathophysiological trinacrium relevant to nociception regulation
  184. Plant polyphenols, terpenes, and terpenoids in oral health
  185. Laboratory medicine between technological innovation, rights safeguarding, and patient safety: A bioethical perspective
  186. End-of-life in cancer patients: Medicolegal implications and ethical challenges in Europe
  187. The maternal factors during pregnancy for intrauterine growth retardation: An umbrella review
  188. Intra-abdominal hypertension/abdominal compartment syndrome of pediatric patients in critical care settings
  189. PI3K/Akt pathway and neuroinflammation in sepsis-associated encephalopathy
  190. Screening of Group B Streptococcus in pregnancy: A systematic review for the laboratory detection
  191. Giant borderline ovarian tumours – review of the literature
  192. Leveraging artificial intelligence for collaborative care planning: Innovations and impacts in shared decision-making – A systematic review
  193. Cholera epidemiology analysis through the experience of the 1973 Naples epidemic
  194. Risk factors of frailty/sarcopenia in community older adults: Meta-analysis
  195. Supplement strategies for infertility in overweight women: Evidence and legal insights
  196. Scurvy, a not obsolete disorder: Clinical report in eight young children and literature review
  197. A meta-analysis of the effects of DBS on cognitive function in patients with advanced PD
  198. Protective role of selenium in sepsis: Mechanisms and potential therapeutic strategies
  199. Strategies for hyperkalemia management in dialysis patients: A systematic review
  200. C-reactive protein-to-albumin ratio in peripheral artery disease
  201. 10.1515/med-2025-1251
  202. 10.1515/med-2025-1330
  203. 10.1515/med-2025-1332
  204. Antibiotic prescribing patterns in general dental practice- a scoping review
  205. Clinical and medico-legal reflections on non-invasive prenatal testing
  206. Case Reports
  207. Delayed graft function after renal transplantation
  208. Semaglutide treatment for type 2 diabetes in a patient with chronic myeloid leukemia: A case report and review of the literature
  209. Diverse electrophysiological demyelinating features in a late-onset glycogen storage disease type IIIa case
  210. Giant right atrial hemangioma presenting with ascites: A case report
  211. Laser excision of a large granular cell tumor of the vocal cord with subglottic extension: A case report
  212. EsoFLIP-assisted dilation for dysphagia in systemic sclerosis: Highlighting the role of multimodal esophageal evaluation
  213. Molecular hydrogen-rhodiola as an adjuvant therapy for ischemic stroke in internal carotid artery occlusion: A case report
  214. Coronary artery anomalies: A case of the “malignant” left coronary artery and its surgical management
  215. Combined VAT and retroperitoneoscopy for pleural empyema due to nephro-pleuric fistula in xanthogranulomatous pyelonephritis
  216. 10.1515/med-2025-1362
  217. Rapid Communication
  218. Biological properties of valve materials using RGD and EC
  219. A single oral administration of flavanols enhances short-term memory in mice along with increased brain-derived neurotrophic factor
  220. Letter to the Editor
  221. Role of enhanced external counterpulsation in long COVID
  222. Expression of Concern
  223. Expression of concern “A ceRNA network mediated by LINC00475 in papillary thyroid carcinoma”
  224. Expression of concern “Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway”
  225. Expression of concern “circ_0020123 promotes cell proliferation and migration in lung adenocarcinoma via PDZD8”
  226. Corrigendum
  227. Corrigendum to “Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism”
  228. Corrigendum to “Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis”
  229. Corrigendum to “The progress of autoimmune hepatitis research and future challenges”
  230. Retraction
  231. Retraction of “miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway”
  232. Retraction of: “LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through downregulating SP-A by sponging to miR-424”
  233. Retraction of: “SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways”
  234. Special Issue Advancements in oncology: bridging clinical and experimental research - Part II
  235. Unveiling novel biomarkers for platinum chemoresistance in ovarian cancer
  236. Lathyrol affects the expression of AR and PSA and inhibits the malignant behavior of RCC cells
  237. The era of increasing cancer survivorship: Trends in fertility preservation, medico-legal implications, and ethical challenges
  238. Bone scintigraphy and positron emission tomography in the early diagnosis of MRONJ
  239. Meta-analysis of clinical efficacy and safety of immunotherapy combined with chemotherapy in non-small cell lung cancer
  240. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part IV
  241. Exploration of mRNA-modifying METTL3 oncogene as momentous prognostic biomarker responsible for colorectal cancer development
  242. Special Issue The evolving saga of RNAs from bench to bedside - Part III
  243. Interaction and verification of ferroptosis-related RNAs Rela and Stat3 in promoting sepsis-associated acute kidney injury
  244. The mRNA MOXD1: Link to oxidative stress and prognostic significance in gastric cancer
  245. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part II
  246. Dynamic changes in lactate-related genes in microglia and their role in immune cell interactions after ischemic stroke
  247. A prognostic model correlated with fatty acid metabolism in Ewing’s sarcoma based on bioinformatics analysis
  248. Red cell distribution width predicts early kidney injury: A NHANES cross-sectional study
  249. Special Issue Diabetes mellitus: pathophysiology, complications & treatment
  250. Nutritional risk assessment and nutritional support in children with congenital diabetes during surgery
  251. Correlation of the differential expressions of RANK, RANKL, and OPG with obesity in the elderly population in Xinjiang
  252. A discussion on the application of fluorescence micro-optical sectioning tomography in the research of cognitive dysfunction in diabetes
  253. A review of brain research on T2DM-related cognitive dysfunction
  254. Metformin and estrogen modulation in LABC with T2DM: A 36-month randomized trial
  255. Special Issue Innovative Biomarker Discovery and Precision Medicine in Cancer Diagnostics
  256. CircASH1L-mediated tumor progression in triple-negative breast cancer: PI3K/AKT pathway mechanisms
https://doi.org/10.1515/med-2024-1128
Schlagwörter für diesen Artikel
echocardiography; dobutamine stress echocardiography; serum micronutrients; aortic stenosis; low-gradient aortic stenosis
Creative Commons
BY 4.0

Artikel in diesem Heft

  1. Research Articles
  2. Network pharmacological analysis and in vitro testing of the rutin effects on triple-negative breast cancer
  3. Impact of diabetes on long-term survival in elderly liver cancer patients: A retrospective study
  4. Knockdown of CCNB1 alleviates high glucose-triggered trophoblast dysfunction during gestational diabetes via Wnt/β-catenin signaling pathway
  5. Risk factors for severe adverse drug reactions in hospitalized patients
  6. Analysis of the effect of ALA-PDT on macrophages in footpad model of mice infected with Fonsecaea monophora based on single-cell sequencing
  7. Development and validation of headspace gas chromatography with a flame ionization detector method for the determination of ethanol in the vitreous humor
  8. CMSP exerts anti-tumor effects on small cell lung cancer cells by inducing mitochondrial dysfunction and ferroptosis
  9. Predictive value of plasma sB7-H3 and YKL-40 in pediatric refractory Mycoplasma pneumoniae pneumonia
  10. Antiangiogenic potential of Elaeagnus umbellata extracts and molecular docking study by targeting VEGFR-2 pathway
  11. Comparison of the effectiveness of nurse-led preoperative counseling and postoperative follow-up care vs standard care for patients with gastric cancer
  12. Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis
  13. Adhered macrophages as an additional marker of cardiomyocyte injury in biopsies of patients with dilated cardiomyopathy
  14. Association between statin administration and outcome in patients with sepsis: A retrospective study
  15. Exploration of the association between estimated glucose disposal rate and osteoarthritis in middle-aged and older adults: An analysis of NHANES data from 2011 to 2018
  16. A comparative analysis of the binary and multiclass classified chest X-ray images of pneumonia and COVID-19 with ML and DL models
  17. Lysophosphatidic acid 2 alleviates deep vein thrombosis via protective endothelial barrier function
  18. Transcription factor A, mitochondrial promotes lymph node metastasis and lymphangiogenesis in epithelial ovarian carcinoma
  19. Serum PM20D1 levels are associated with nutritional status and inflammatory factors in gastric cancer patients undergoing early enteral nutrition
  20. Hydromorphone reduced the incidence of emergence agitation after adenotonsillectomy in children with obstructive sleep apnea: A randomized, double-blind study
  21. Vitamin D replacement therapy may regulate sleep habits in patients with restless leg syndrome
  22. The first-line antihypertensive nitrendipine potentiated the therapeutic effect of oxaliplatin by downregulating CACNA1D in colorectal cancer
  23. Health literacy and health-related quality of life: The mediating role of irrational happiness
  24. Modulatory effects of Lycium barbarum polysaccharide on bone cell dynamics in osteoporosis
  25. Mechanism research on inhibition of gastric cancer in vitro by the extract of Pinellia ternata based on network pharmacology and cellular metabolomics
  26. Examination of the causal role of immune cells in non-alcoholic fatty liver disease by a bidirectional Mendelian randomization study
  27. Clinical analysis of ten cases of HIV infection combined with acute leukemia
  28. Investigating the cardioprotective potential of quercetin against tacrolimus-induced cardiotoxicity in Wistar rats: A mechanistic insights
  29. Clinical observation of probiotics combined with mesalazine and Yiyi Baitouweng Decoction retention enema in treating mild-to-moderate ulcerative colitis
  30. Diagnostic value of ratio of blood inflammation to coagulation markers in periprosthetic joint infection
  31. Sex-specific associations of sex hormone binding globulin and risk of bladder cancer
  32. Core muscle strength and stability-oriented breathing training reduces inter-recti distance in postpartum women
  33. The ERAS nursing care strategy for patients undergoing transsphenoidal endoscopic pituitary tumor resection: A randomized blinded controlled trial
  34. The serum IL-17A levels in patients with traumatic bowel rupture post-surgery and its predictive value for patient prognosis
  35. Impact of Kolb’s experiential learning theory-based nursing on caregiver burden and psychological state of caregivers of dementia patients
  36. Analysis of serum NLR combined with intraoperative margin condition to predict the prognosis of cervical HSIL patients undergoing LEEP surgery
  37. Commiphora gileadensis ameliorate infertility and erectile dysfunction in diabetic male mice
  38. The correlation between epithelial–mesenchymal transition classification and MMP2 expression of circulating tumor cells and prognosis of advanced or metastatic nasopharyngeal carcinoma
  39. Tetrahydropalmatine improves mitochondrial function in vascular smooth muscle cells of atherosclerosis in vitro by inhibiting Ras homolog gene family A/Rho-associated protein kinase-1 signaling pathway
  40. A cross-sectional study: Relationship between serum oxidative stress levels and arteriovenous fistula maturation in maintenance dialysis patients
  41. A comparative analysis of the impact of repeated administration of flavan 3-ol on brown, subcutaneous, and visceral adipose tissue
  42. Identifying early screening factors for depression in middle-aged and older adults: A cohort study
  43. Perform tumor-specific survival analysis for Merkel cell carcinoma patients undergoing surgical resection based on the SEER database by constructing a nomogram chart
  44. Unveiling the role of CXCL10 in pancreatic cancer progression: A novel prognostic indicator
  45. High-dose preoperative intraperitoneal erythropoietin and intravenous methylprednisolone in acute traumatic spinal cord injuries following decompression surgeries
  46. RAB39B: A novel biomarker for acute myeloid leukemia identified via multi-omics and functional validation
  47. Impact of peripheral conditioning on reperfusion injury following primary percutaneous coronary intervention in diabetic and non-diabetic STEMI patients
  48. Clinical efficacy of azacitidine in the treatment of middle- and high-risk myelodysplastic syndrome in middle-aged and elderly patients: A retrospective study
  49. The effect of ambulatory blood pressure load on mitral regurgitation in continuous ambulatory peritoneal dialysis patients
  50. Expression and clinical significance of ITGA3 in breast cancer
  51. Single-nucleus RNA sequencing reveals ARHGAP28 expression of podocytes as a biomarker in human diabetic nephropathy
  52. rSIG combined with NLR in the prognostic assessment of patients with multiple injuries
  53. Toxic metals and metalloids in collagen supplements of fish and jellyfish origin: Risk assessment for daily intake
  54. Exploring causal relationship between 41 inflammatory cytokines and marginal zone lymphoma: A bidirectional Mendelian randomization study
  55. Gender beliefs and legitimization of dating violence in adolescents
  56. Effect of serum IL-6, CRP, and MMP-9 levels on the efficacy of modified preperitoneal Kugel repair in patients with inguinal hernia
  57. Effect of smoking and smoking cessation on hematological parameters in polycythemic patients
  58. Pathogen surveillance and risk factors for pulmonary infection in patients with lung cancer: A retrospective single-center study
  59. Necroptosis of hippocampal neurons in paclitaxel chemotherapy-induced cognitive impairment mediates microglial activation via TLR4/MyD88 signaling pathway
  60. Celastrol suppresses neovascularization in rat aortic vascular endothelial cells stimulated by inflammatory tenocytes via modulating the NLRP3 pathway
  61. Cord-lamina angle and foraminal diameter as key predictors of C5 palsy after anterior cervical decompression and fusion surgery
  62. GATA1: A key biomarker for predicting the prognosis of patients with diffuse large B-cell lymphoma
  63. Influencing factors of false lumen thrombosis in type B aortic dissection: A single-center retrospective study
  64. MZB1 regulates the immune microenvironment and inhibits ovarian cancer cell migration
  65. Integrating experimental and network pharmacology to explore the pharmacological mechanisms of Dioscin against glioblastoma
  66. Trends in research on preterm birth in twin pregnancy based on bibliometrics
  67. Four-week IgE/baseline IgE ratio combined with tryptase predicts clinical outcome in omalizumab-treated children with moderate-to-severe asthma
  68. Single-cell transcriptomic analysis identifies a stress response Schwann cell subtype
  69. Acute pancreatitis risk in the diagnosis and management of inflammatory bowel disease: A critical focus
  70. Effect of subclinical esketamine on NLRP3 and cognitive dysfunction in elderly ischemic stroke patients
  71. Interleukin-37 mediates the anti-oral tumor activity in oral cancer through STAT3
  72. CA199 and CEA expression levels, and minimally invasive postoperative prognosis analysis in esophageal squamous carcinoma patients
  73. Efficacy of a novel drainage catheter in the treatment of CSF leak after posterior spine surgery: A retrospective cohort study
  74. Comprehensive biomedicine assessment of Apteranthes tuberculata extracts: Phytochemical analysis and multifaceted pharmacological evaluation in animal models
  75. Relation of time in range to severity of coronary artery disease in patients with type 2 diabetes: A cross-sectional study
  76. Dopamine attenuates ethanol-induced neuronal apoptosis by stimulating electrical activity in the developing rat retina
  77. Correlation between albumin levels during the third trimester and the risk of postpartum levator ani muscle rupture
  78. Factors associated with maternal attention and distraction during breastfeeding and childcare: A cross-sectional study in the west of Iran
  79. Mechanisms of hesperetin in treating metabolic dysfunction-associated steatosis liver disease via network pharmacology and in vitro experiments
  80. The law on oncological oblivion in the Italian and European context: How to best uphold the cancer patients’ rights to privacy and self-determination?
  81. The prognostic value of the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and prognostic nutritional index for survival in patients with colorectal cancer
  82. Factors affecting the measurements of peripheral oxygen saturation values in healthy young adults
  83. Comparison and correlations between findings of hysteroscopy and vaginal color Doppler ultrasonography for detection of uterine abnormalities in patients with recurrent implantation failure
  84. The effects of different types of RAGT on balance function in stroke patients with low levels of independent walking in a convalescent rehabilitation hospital
  85. Causal relationship between asthma and ankylosing spondylitis: A bidirectional two-sample univariable and multivariable Mendelian randomization study
  86. Correlations of health literacy with individuals’ understanding and use of medications in Southern Taiwan
  87. Correlation of serum calprotectin with outcome of acute cerebral infarction
  88. Comparison of computed tomography and guided bronchoscopy in the diagnosis of pulmonary nodules: A systematic review and meta-analysis
  89. Curdione protects vascular endothelial cells and atherosclerosis via the regulation of DNMT1-mediated ERBB4 promoter methylation
  90. The identification of novel missense variant in ChAT gene in a patient with gestational diabetes denotes plausible genetic association
  91. Molecular genotyping of multi-system rare blood types in foreign blood donors based on DNA sequencing and its clinical significance
  92. Exploring the role of succinyl carnitine in the association between CD39⁺ CD4⁺ T cell and ulcerative colitis: A Mendelian randomization study
  93. Dexmedetomidine suppresses microglial activation in postoperative cognitive dysfunction via the mmu-miRNA-125/TRAF6 signaling axis
  94. Analysis of serum metabolomics in patients with different types of chronic heart failure
  95. Diagnostic value of hematological parameters in the early diagnosis of acute cholecystitis
  96. Pachymaran alleviates fat accumulation, hepatocyte degeneration, and injury in mice with nonalcoholic fatty liver disease
  97. Decrease in CD4 and CD8 lymphocytes are predictors of severe clinical picture and unfavorable outcome of the disease in patients with COVID-19
  98. METTL3 blocked the progression of diabetic retinopathy through m6A-modified SOX2
  99. The predictive significance of anti-RO-52 antibody in patients with interstitial pneumonia after treatment of malignant tumors
  100. Exploring cerebrospinal fluid metabolites, cognitive function, and brain atrophy: Insights from Mendelian randomization
  101. Development and validation of potential molecular subtypes and signatures of ocular sarcoidosis based on autophagy-related gene analysis
  102. Widespread venous thrombosis: Unveiling a complex case of Behçet’s disease with a literature perspective
  103. Uterine fibroid embolization: An analysis of clinical outcomes and impact on patients’ quality of life
  104. Discovery of lipid metabolism-related diagnostic biomarkers and construction of diagnostic model in steroid-induced osteonecrosis of femoral head
  105. Serum-derived exomiR-188-3p is a promising novel biomarker for early-stage ovarian cancer
  106. Enhancing chronic back pain management: A comparative study of ultrasound–MRI fusion guidance for paravertebral nerve block
  107. Peptide CCAT1-70aa promotes hepatocellular carcinoma proliferation and invasion via the MAPK/ERK pathway
  108. Electroacupuncture-induced reduction of myocardial ischemia–reperfusion injury via FTO-dependent m6A methylation modulation
  109. Hemorrhoids and cardiovascular disease: A bidirectional Mendelian randomization study
  110. Cell-free adipose extract inhibits hypertrophic scar formation through collagen remodeling and antiangiogenesis
  111. HALP score in Demodex blepharitis: A case–control study
  112. Assessment of SOX2 performance as a marker for circulating cancer stem-like cells (CCSCs) identification in advanced breast cancer patients using CytoTrack system
  113. Risk and prognosis for brain metastasis in primary metastatic cervical cancer patients: A population-based study
  114. Comparison of the two intestinal anastomosis methods in pediatric patients
  115. Factors influencing hematological toxicity and adverse effects of perioperative hyperthermic intraperitoneal vs intraperitoneal chemotherapy in gastrointestinal cancer
  116. Endotoxin tolerance inhibits NLRP3 inflammasome activation in macrophages of septic mice by restoring autophagic flux through TRIM26
  117. Lateral transperitoneal laparoscopic adrenalectomy: A single-centre experience of 21 procedures
  118. Petunidin attenuates lipopolysaccharide-induced retinal microglia inflammatory response in diabetic retinopathy by targeting OGT/NF-κB/LCN2 axis
  119. Procalcitonin and C-reactive protein as biomarkers for diagnosing and assessing the severity of acute cholecystitis
  120. Factors determining the number of sessions in successful extracorporeal shock wave lithotripsy patients
  121. Development of a nomogram for predicting cancer-specific survival in patients with renal pelvic cancer following surgery
  122. Inhibition of ATG7 promotes orthodontic tooth movement by regulating the RANKL/OPG ratio under compression force
  123. A machine learning-based prognostic model integrating mRNA stemness index, hypoxia, and glycolysis‑related biomarkers for colorectal cancer
  124. Glutathione attenuates sepsis-associated encephalopathy via dual modulation of NF-κB and PKA/CREB pathways
  125. FAHD1 prevents neuronal ferroptosis by modulating R-loop and the cGAS–STING pathway
  126. Association of placenta weight and morphology with term low birth weight: A case–control study
  127. Investigation of the pathogenic variants induced Sjogren’s syndrome in Turkish population
  128. Nucleotide metabolic abnormalities in post-COVID-19 condition and type 2 diabetes mellitus patients and their association with endocrine dysfunction
  129. TGF-β–Smad2/3 signaling in high-altitude pulmonary hypertension in rats: Role and mechanisms via macrophage M2 polarization
  130. Ultrasound-guided unilateral versus bilateral erector spinae plane block for postoperative analgesia of patients undergoing laparoscopic cholecystectomy
  131. Profiling gut microbiome dynamics in subacute thyroiditis: Implications for pathogenesis, diagnosis, and treatment
  132. Delta neutrophil index, CRP/albumin ratio, procalcitonin, immature granulocytes, and HALP score in acute appendicitis: Best performing biomarker?
  133. Anticancer activity mechanism of novelly synthesized and characterized benzofuran ring-linked 3-nitrophenyl chalcone derivative on colon cancer cells
  134. H2valdien3 arrests the cell cycle and induces apoptosis of gastric cancer
  135. Prognostic relevance of PRSS2 and its immune correlates in papillary thyroid carcinoma
  136. Association of SGLT2 inhibition with psychiatric disorders: A Mendelian randomization study
  137. Motivational interviewing for alcohol use reduction in Thai patients
  138. Luteolin alleviates oxygen-glucose deprivation/reoxygenation-induced neuron injury by regulating NLRP3/IL-1β signaling
  139. Polyphyllin II inhibits thyroid cancer cell growth by simultaneously inhibiting glycolysis and oxidative phosphorylation
  140. Relationship between the expression of copper death promoting factor SLC31A1 in papillary thyroid carcinoma and clinicopathological indicators and prognosis
  141. CSF2 polarized neutrophils and invaded renal cancer cells in vitro influence
  142. Proton pump inhibitors-induced thrombocytopenia: A systematic literature analysis of case reports
  143. The current status and influence factors of research ability among community nurses: A sequential qualitative–quantitative study
  144. OKAIN: A comprehensive oncology knowledge base for the interpretation of clinically actionable alterations
  145. The relationship between serum CA50, CA242, and SAA levels and clinical pathological characteristics and prognosis in patients with pancreatic cancer
  146. Identification and external validation of a prognostic signature based on hypoxia–glycolysis-related genes for kidney renal clear cell carcinoma
  147. Engineered RBC-derived nanovesicles functionalized with tumor-targeting ligands: A comparative study on breast cancer targeting efficiency and biocompatibility
  148. Relationship of resting echocardiography combined with serum micronutrients to the severity of low-gradient severe aortic stenosis
  149. Effect of vibration on pain during subcutaneous heparin injection: A randomized, single-blind, placebo-controlled trial
  150. The diagnostic performance of machine learning-based FFRCT for coronary artery disease: A meta-analysis
  151. Comparing biofeedback device vs diaphragmatic breathing for bloating relief: A randomized controlled trial
  152. Serum uric acid to albumin ratio and C-reactive protein as predictive biomarkers for chronic total occlusion and coronary collateral circulation quality
  153. Multiple organ scoring systems for predicting in-hospital mortality of sepsis patients in the intensive care unit
  154. Single-cell RNA sequencing data analysis of the inner ear in gentamicin-treated mice via intraperitoneal injection
  155. Suppression of cathepsin B attenuates myocardial injury via limiting cardiomyocyte apoptosis
  156. Influence of sevoflurane combined with propofol anesthesia on the anesthesia effect and adverse reactions in children with acute appendicitis
  157. Identification of hub genes related to acute kidney injury caused by sevoflurane anesthesia and endoplasmic reticulum stress
  158. 10.1515/med-2025-1313
  159. 10.1515/med-2025-1316
  160. Health education pathway for individuals with temporary enterostomies using patient journey mapping
  161. 10.1515/med-2025-1321
  162. 10.1515/med-2025-1324
  163. 10.1515/med-2025-1325
  164. 10.1515/med-2025-1327
  165. 10.1515/med-2025-1331
  166. Effect of timing of cholecystectomy on weight loss after sleeve gastrectomy in morbidly obese individuals with cholelithiasis: a retrospective cohort study
  167. 10.1515/med-2025-1337
  168. 10.1515/med-2025-1347
  169. 10.1515/med-2025-1360
  170. Multiple sclerosis and type 1 diabetes: a Mendelian randomization study of European ancestry
  171. Rapid pathogen identification in peritoneal dialysis effluent by MALDI-TOF MS following blood culture enrichment
  172. Comparison of open and percutaneous A1 pulley release in pediatric trigger thumb: a retrospective cohort study
  173. Impact of combined diaphragm-lung ultrasound assessment on postoperative respiratory function in patients under general anesthesia recovery
  174. Review Articles
  175. The effects of enhanced external counter-pulsation on post-acute sequelae of COVID-19: A narrative review
  176. Diabetes-related cognitive impairment: Mechanisms, symptoms, and treatments
  177. Microscopic changes and gross morphology of placenta in women affected by gestational diabetes mellitus in dietary treatment: A systematic review
  178. Review of mechanisms and frontier applications in IL-17A-induced hypertension
  179. Research progress on the correlation between islet amyloid peptides and type 2 diabetes mellitus
  180. The safety and efficacy of BCG combined with mitomycin C compared with BCG monotherapy in patients with non-muscle-invasive bladder cancer: A systematic review and meta-analysis
  181. The application of augmented reality in robotic general surgery: A mini-review
  182. The effect of Greek mountain tea extract and wheat germ extract on peripheral blood flow and eicosanoid metabolism in mammals
  183. Neurogasobiology of migraine: Carbon monoxide, hydrogen sulfide, and nitric oxide as emerging pathophysiological trinacrium relevant to nociception regulation
  184. Plant polyphenols, terpenes, and terpenoids in oral health
  185. Laboratory medicine between technological innovation, rights safeguarding, and patient safety: A bioethical perspective
  186. End-of-life in cancer patients: Medicolegal implications and ethical challenges in Europe
  187. The maternal factors during pregnancy for intrauterine growth retardation: An umbrella review
  188. Intra-abdominal hypertension/abdominal compartment syndrome of pediatric patients in critical care settings
  189. PI3K/Akt pathway and neuroinflammation in sepsis-associated encephalopathy
  190. Screening of Group B Streptococcus in pregnancy: A systematic review for the laboratory detection
  191. Giant borderline ovarian tumours – review of the literature
  192. Leveraging artificial intelligence for collaborative care planning: Innovations and impacts in shared decision-making – A systematic review
  193. Cholera epidemiology analysis through the experience of the 1973 Naples epidemic
  194. Risk factors of frailty/sarcopenia in community older adults: Meta-analysis
  195. Supplement strategies for infertility in overweight women: Evidence and legal insights
  196. Scurvy, a not obsolete disorder: Clinical report in eight young children and literature review
  197. A meta-analysis of the effects of DBS on cognitive function in patients with advanced PD
  198. Protective role of selenium in sepsis: Mechanisms and potential therapeutic strategies
  199. Strategies for hyperkalemia management in dialysis patients: A systematic review
  200. C-reactive protein-to-albumin ratio in peripheral artery disease
  201. 10.1515/med-2025-1251
  202. 10.1515/med-2025-1330
  203. 10.1515/med-2025-1332
  204. Antibiotic prescribing patterns in general dental practice- a scoping review
  205. Clinical and medico-legal reflections on non-invasive prenatal testing
  206. Case Reports
  207. Delayed graft function after renal transplantation
  208. Semaglutide treatment for type 2 diabetes in a patient with chronic myeloid leukemia: A case report and review of the literature
  209. Diverse electrophysiological demyelinating features in a late-onset glycogen storage disease type IIIa case
  210. Giant right atrial hemangioma presenting with ascites: A case report
  211. Laser excision of a large granular cell tumor of the vocal cord with subglottic extension: A case report
  212. EsoFLIP-assisted dilation for dysphagia in systemic sclerosis: Highlighting the role of multimodal esophageal evaluation
  213. Molecular hydrogen-rhodiola as an adjuvant therapy for ischemic stroke in internal carotid artery occlusion: A case report
  214. Coronary artery anomalies: A case of the “malignant” left coronary artery and its surgical management
  215. Combined VAT and retroperitoneoscopy for pleural empyema due to nephro-pleuric fistula in xanthogranulomatous pyelonephritis
  216. 10.1515/med-2025-1362
  217. Rapid Communication
  218. Biological properties of valve materials using RGD and EC
  219. A single oral administration of flavanols enhances short-term memory in mice along with increased brain-derived neurotrophic factor
  220. Letter to the Editor
  221. Role of enhanced external counterpulsation in long COVID
  222. Expression of Concern
  223. Expression of concern “A ceRNA network mediated by LINC00475 in papillary thyroid carcinoma”
  224. Expression of concern “Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway”
  225. Expression of concern “circ_0020123 promotes cell proliferation and migration in lung adenocarcinoma via PDZD8”
  226. Corrigendum
  227. Corrigendum to “Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism”
  228. Corrigendum to “Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis”
  229. Corrigendum to “The progress of autoimmune hepatitis research and future challenges”
  230. Retraction
  231. Retraction of “miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway”
  232. Retraction of: “LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through downregulating SP-A by sponging to miR-424”
  233. Retraction of: “SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways”
  234. Special Issue Advancements in oncology: bridging clinical and experimental research - Part II
  235. Unveiling novel biomarkers for platinum chemoresistance in ovarian cancer
  236. Lathyrol affects the expression of AR and PSA and inhibits the malignant behavior of RCC cells
  237. The era of increasing cancer survivorship: Trends in fertility preservation, medico-legal implications, and ethical challenges
  238. Bone scintigraphy and positron emission tomography in the early diagnosis of MRONJ
  239. Meta-analysis of clinical efficacy and safety of immunotherapy combined with chemotherapy in non-small cell lung cancer
  240. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part IV
  241. Exploration of mRNA-modifying METTL3 oncogene as momentous prognostic biomarker responsible for colorectal cancer development
  242. Special Issue The evolving saga of RNAs from bench to bedside - Part III
  243. Interaction and verification of ferroptosis-related RNAs Rela and Stat3 in promoting sepsis-associated acute kidney injury
  244. The mRNA MOXD1: Link to oxidative stress and prognostic significance in gastric cancer
  245. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part II
  246. Dynamic changes in lactate-related genes in microglia and their role in immune cell interactions after ischemic stroke
  247. A prognostic model correlated with fatty acid metabolism in Ewing’s sarcoma based on bioinformatics analysis
  248. Red cell distribution width predicts early kidney injury: A NHANES cross-sectional study
  249. Special Issue Diabetes mellitus: pathophysiology, complications & treatment
  250. Nutritional risk assessment and nutritional support in children with congenital diabetes during surgery
  251. Correlation of the differential expressions of RANK, RANKL, and OPG with obesity in the elderly population in Xinjiang
  252. A discussion on the application of fluorescence micro-optical sectioning tomography in the research of cognitive dysfunction in diabetes
  253. A review of brain research on T2DM-related cognitive dysfunction
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Heruntergeladen am 20.12.2025 von https://www.degruyterbrill.com/document/doi/10.1515/med-2024-1128/html?lang=de
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