Atherosclerotic cardiovascular diseases (ASCVD) remain the leading cause of mortality and morbidity among diabetic patients, particularly those with type 2 diabetes mellitus (T2DM) [1]. Reducing the burden of ASCVD in diabetic patients is a critical clinical necessity to lower mortality, prevent related morbidities, and improve quality of life [2]. Structural changes in the arterial wall caused by diabetes negatively affect the elastic properties of arteries [3,4]. Furthermore, it is known that prediabetic states similarly lead to impairments in aortic elastic properties [4,5]).
Studies have demonstrated significant associations between increased total fat mass and its distribution with insulin resistance, glucose intolerance, and heightened risks of diabetes and cardiovascular diseases [6]. Body fat distribution, even in normal-weight elderly adults, is closely linked to metabolic syndrome [7]. While anthropometric measurements such as body mass index (BMI) and waist-to-hip ratio (WHR) are commonly used to define abdominal obesity, numerous body composition indices have been developed. However, it remains unclear which parameter is most effective in predicting and defining cardiovascular risk and metabolic disorders [8].
This study investigates the aortic elastic parameters in newly diagnosed T2DM patients and explores their association with various body composition indices.
The study included 273 patients (Group 1; 129 males, 149 females; mean age: 50.7 ± 12.2 years) newly diagnosed with diabetes based on evaluations conducted after presenting to our cardiology and internal medicine outpatient clinics for various complaints. Additionally, 139 control subjects (Group 2; 49 males, 90 females; mean age: 47.1 ± 8.5 years) with no identified diseases during their assessments were included. Detailed medical histories were obtained for all participants, and current and previous medication use information was recorded. Comprehensive physical examinations were performed for each subject. Blood pressure was measured using a sphygmomanometer after 5 minutes of rest in a seated position, and pulse rates were documented.
The diagnosis of diabetes was based on the following criteria: fasting glucose ≥7.0 mmol/L (≥126 mg/dL), HbA1c ≥48 mmol/mol (≥6.5%), or 2-hour glucose during an oral glucose tolerance test (OGTT) ≥11.1 mmol/L (≥200 mg/dL). Electrocardiograms (ECGs) were obtained for all participants. In the presence of symptoms suggestive of coronary artery disease, patients were examined for the presence of coronary artery disease. Patients whose test results suggested the presence of coronary artery disease were excluded from the study.
The diagnosis of diabetes was confirmed with one laboratory test in the presence of symptoms or with two separate laboratory tests in the absence of symptoms [9].
Venous blood samples were collected from all participants after 8 hours of fasting. The following parameters were measured: fasting blood glucose, urea, creatinine, lipid panel (total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein), liver enzymes (aspartate aminotransferase, alanine aminotransferase), and C-reactive protein using the Roche Diagnostics Cobas 8000 c702 analyzer. HbA1c levels were measured with the Arkray ADAMS™ A1c HA-8180V Analyzer, while insulin levels were determined using the Roche Diagnostics Cobas 8000 c602 system. Additionally, complete blood counts were measured with the Mindray BC-6800 Plus analyzer.
Insulin resistance was quantified using the Homeostatic Model Assessment (HOMA-IR) formula:
Informed consent was obtained from all participants. Study was approved by the local ethics committee of our hospital (approval number: 397).
All participants' height, weight, waist circumference, and hip circumference were measured. Waist circumference was measured at the level of the umbilicus while the patient stood upright with arms extended laterally, using a measuring tape to combine the midpoint of the subcostal margin on each side. Hip circumference was measured by aligning the tape around the most prominent part of the gluteal region and the symphysis pubis.
Body Mass Index (BMI) was calculated as weight in kilograms divided by the square of height in meters:
The waist-to-height ratio (WHtR) and waist-to-hip ratio (WHR) were calculated from the waist and hip measurements. Other body composition indices were computed using the following formulas:
Tri-Ponderal Mass Index (TMI)
Visceral Adiposity Index (VAI):
For men:
For women:
Body Shape Index (BSI):
Body Roundness Index (BRI):
Body Adiposity Index (BAI):
Additionally, the Cardiometabolic Index (CMI), a relatively novel marker for assessing cardiovascular risk, was calculated as: CMI = WtHR × TG (mmol L−1)/HDL-C (mmol L−1) [15]
All transthoracic echocardiographic examinations were performed using the Philips EPIQ 7 echocardiography system (Philips Healthcare, 3000 Minuteman Road, Andover, MA, USA) with a 2.5–3.5 MHz transducer. M-mode recordings were conducted at 50 mm/s, and Doppler recordings at 100 mm/s. Evaluations were carried out in the left lateral decubitus position, and measurements included LV internal dimensions, wall thickness and EF measured with the biplane Simpson method were assessed according to recent guidelines for chamber quantification [16]. Tissue Doppler imaging parameters (S', systolic; E,' early diastolic; A,' late diastolic myocardial velocities) were measured at the lateral, septal, and tricuspid annuli. All measurements were recorded as the average of two separate measurements.
To obtain aortic elastic parameters, ascending aortic M-mode echocardiographic recordings were acquired from the parasternal long-axis view, approximately 3 cm above the aortic valve. The systolic aortic diameter (AoS) was measured when the aortic valve was fully open. At the same time, the diastolic aortic diameter (AoD) was measured at the end of the diastole, at the peak of the QRS complex on the ECG, using the distances between the inner edges of the anterior and posterior walls of the vessel. Aortic elastic parameters were calculated using aortic diameters and systolic (SBP) and diastolic blood pressure (DBP) values with the following formulas:
Aortic strain (%)
Aortic stiffness index
Aortic distensibility (cm2/dyn/103)
All data were recorded in the “IBM SPSS (Statistical Package 27 Social Sciences) Statistics 25” program. The suitability of the variables to normal distribution was examined using histogram graphics and the Kolmogorov-Smirnov test. Mean, standard deviation and median values were used when presenting descriptive analyses. An independent T-test was used to compare continuous variables between groups if the distribution was expected, and the Mann-Whitney U test (MU) was used if the distribution was abnormal. Spearman correlation tests were used in the comparative analysis of the measurement data. In order to eliminate the lack of balance between the groups, demographic characteristics, body composition parameters and aortic elastic properties, which are among the variables predicting new diabetes mellitus diagnosis in binary regression analysis, were evaluated with univariate analysis. Those with significant p values were evaluated with multivariate analysis. Odds ratio (OR) and 95% confidence interval (CI) were calculated In order to identify independent determinants of aortic elasticity parameters, multivariate linear regression analyses were performed. Results with a P-value below 0.05 were considered statistically significant.
Table 1 compares demographic data between groups. In Group 1, age, systolic and diastolic blood pressure, and heart rate were significantly higher compared to Group 2. All body composition indices, except for BSI, were significantly higher in Group 1 (Table 1). Additionally, the rates of female sex, hypertension, hyperlipidemia, and obesity were significantly higher in Group 1 (Table 1). Among diabetic patients, 153 were classified as obese and 78 as overweight.
Comparison of demographic, laboratory and body composition parameters between the groups
| Group 1 (n=273) | Group 2 (n=139) | p | |
|---|---|---|---|
| Age (year) | 50.6 ± 10.2 | 44.1 ± 8.6 | <0.001 |
| Gender (F, n-%) | 144 – 52.7 | 90 – 64.7 | 0.020 |
| Obesity (n-%) | 153 – 56 | 2 – 1.4 | <0.001 |
| Smoking (n-%) | 99 – 36.3 | 62 – 44.6 | 0.101 |
| BMI (kg/m2) | 30.9 ±5.6 | 235.6 ± 2.9 | <0.001 |
| WC (cm) | 107.2 ±11.5 | 89.1 ±11.3 | <0.001 |
| HC (cm) | 109.9 ±11.0 | 99.7 ± 7.2 | <0.001 |
| Waist to Height ratio | 0.65±0.08 | 0.53±0.06 | <0.001 |
| Waist to Hip ratio | 0.97±0.06 | 0.89±0.08 | <0.001 |
| TPI | 18.8±3.9 | 14.2±2.0 | <0.001 |
| VAI | 4.14±8.35 | 1.43±0.85 | <0.001 |
| BSI | 0.08±0.05 | 0.08±0.02 | 0.368 |
| BRI | 6.74±2.01 | 4.12±1.35 | <0.001 |
| BAI (%) | 40.3±9.3 | 28.5±4.5 | <0.001 |
| CMI | 3.86±8.90 | 1.01±0.64 | <0.001 |
| SBP (mm/Hg) | 138.7 ±19.5 | 120.8 ±15.3 | <0.001 |
| DBP (mm/Hg) | 84.2 ±12.5 | 73.8 ±12.1 | <0.001 |
| Heart Rate (/dk) | 84.9 ±12.8 | 78.5±8.5 | <0.001 |
| Glucose (mg/dL) | 184.9 ± 79.3 | 90.8 ± 7.1 | <0.001 |
| Urea (mg/dL) | 27.7 ±8.1 | 26.9 ± 8.2 | 0.427 |
| Creatinine (mg/dL) | 0.72 ±0.16 | 0.72 ±0.14 | 0.837 |
| AST (U/L) | 21.8 ±13.1 | 18.5 ±8.3 | 0.025 |
| ALT (U/L) | 30.2 ±26.8 | 17.2 ±11.5 | <0.001 |
| Total Cholesterol (mg/dL) | 211.7 ± 58.7 | 194.3 ±37.6 | 0.090 |
| HDL (mg/dL) | 45.2 ±13.9 | 56.8 ±13.5 | <0.001 |
| LDL (mg/dL) | 127.9 ±40.5 | 117.8 ±33.2 | 0.0360 |
| Triglyceride (mg/dL) | 201.3 ±149.0 | 97.5±41.1 | <0.001 |
| HbA1c (%) | 8.78 ±2.35 | 5.39 ±0.29 | <0.001 |
| Insulin (mU/L) | 12.9 ± 8.3 | 8.1 ± 4.4 | 0.004 |
| Homa-IR | 5.37 ± 3.72 | 1.85 ±1.06 | <0.001 |
| CRP (mg/L) | 6.84±6.95 | 2.10±2.57 | <0.001 |
| WBC ( 109 /L) | 8.05 ±2.32 | 6.80 ±1.97 | 0.011 |
Abbrevations: BMI: Body mass index, WC: Waist circumference, HC: Hip circumference, TPI: Tri ponderal index, VAI: Visceral adiposity index, BSI: Body shape index, BRI: Body roundness index, BAI: Body adiposity index, CMI: Cardiometabolic index, SBP: Systolic blood pressure, DBP: Diastolic blood pressure, AST: Aspartate Transaminase, ALT: Alanine Transaminase, LDL: Low Density Lipoprotein, HDL: High Density Lipoprotein, HbA1c: Glycated Hemoglobin, CRP: C-Reactive Protein, , Homa-IR: Homeostatic Model Assessment-Insulin Resistance, WBC: White Blood Cell,
When laboratory parameters were evaluated, glycemic parameters were predictably worse in the diabetic group (Table 1). Total cholesterol (TC), triglycerides (TG), and LDL-C levels were significantly higher in Group 1, while HDL-C levels were significantly lower (Table 1). AST and ALT levels were also significantly higher in Group 1 compared to Group 2. While urea and creatinine levels were similar between groups, CRP was significantly higher in Group 1 (Table 1).
Echocardiographic parameters revealed that left ventricular wall thickness and left atrial diameter were significantly higher in Group 1 compared to Group 2 (Table 2). Among parameters reflecting diastolic function, the E/A ratio was significantly lower in Group 1, while lateral and septal E/E ratios were significantly higher (Table 2). The ejection fraction was also significantly lower in Group 1 compared to Group 2.
Comparison of conventional echo parameters, diastolic and systolic functions, aortic elastic properties in newly diagnosed type 2 DM patients and control groups
| Group 1 (n=273) | Group 2 (n=139) | p | |
|---|---|---|---|
| EF (%) | 62.7 ±2.5 | 68.6 ± 1.8 | <0.001 |
| LVESD (cm) | 2.58 ±0.43 | 2.42 ±0.32 | <0.001 |
| LVEDD (cm) | 4.59 ±0.42 | 4.51 ±0.38 | 0,068 |
| IVS (cm) | 1.11 ±0.19 | 0.85 ±0.14 | <0.001 |
| PW (cm) | 1.10 ±0.47 | 0.86 ±0.13 | <0.001 |
| Aortic root diameter (cm) | 2.70 ±0.33 | 2.45 ±0.30 | <0.001 |
| Left atrium diameter (cm) | 3.51 ±0.38 | 3.12 ±0.38 | <0.001 |
| Mitral E (m/sec) | 0.65 ±0.15 | 0.72 ±0.17 | <0.001 |
| Mitral A (m/sec) | 0.78 ±0.15 | 0.668 ±0.16 | <0.001 |
| Mitral EDT (ms) | 234.7 ±59.6 | 186.9 ±37.7 | <0.001 |
| E/A | 0.87 ±0.29 | 1.38 ±0.20 | <0.001 |
| E/E’ lateral | 7.63 ±2.54 | 6.47 ±1.74 | <0.001 |
| E/E’ septal | 10.40 ±2.83 | 8.33 ±1.82 | <0.001 |
| Aortic strain (%) | 6.53±3.98 | 14.8±6.02 | <0.001 |
| Aortic stiffness index | 1.15±0.93 | 0.39±0.19 | <0.001 |
| Aortic distensibility (cm2/dyn1/103) | 2.61±1.87 | 6.56±3.24 | <0.001 |
EF: Ejection Fraction, LVESD: Left Ventricular End Systolic Diameter, LVEDD: Left Ventricular End Diastolic Diameter, IVS: Interventicular Septum, PW: Posterior Wall, EDT: E Wave Deceleration Time, E’: Early Diastolic Forward Flow Velocity
When aortic elastic parameters were evaluated, aortic strain and aortic distensibility were significantly lower in Group 1 than in Group 2, whereas the aortic stiffness index was significantly higher in Group 1 (Table 2).
Spearman correlation analysis demonstrated that aortic elastic parameters were significantly correlated with almost all body composition indices except for BSI. The highest correlation was observed with TPI (Table 3). Additionally, aortic elastic parameters were significantly correlated with glycemic parameters (Table 3).
Spearman correlation of aortic elastic properties with body composition and glycemic parameters
| AS | Rho | P | ASI | Rho | P | AD | Rho | P |
|---|---|---|---|---|---|---|---|---|
| BMI (kg/m2) | −0.365 | <0.001 | 0.317 | <0.001 | −0.383 | <0.001 | ||
| WC | −0.375 | <0.001 | 0.320 | <0.001 | −0.390 | <0.001 | ||
| HC | −0.265 | <0.001 | 0.214 | <0.001 | −0.269 | <0.001 | ||
| WtHeightR | −0.366 | <0.001 | 0.316 | <0.001 | −0.384 | <0.001 | ||
| WtHipR | −0.352 | <0.001 | 0.316 | <0.001 | −0.366 | <0.001 | ||
| TPI | −0.490 | <0.001 | 0.456 | <0.001 | −0.516 | <0.001 | ||
| VAI | −0.383 | <0.001 | 0.334 | <0.001 | −0.366 | <0.001 | ||
| BSI | −0.010 | 0.978 | −0.110 | <0.001 | −0.005 | <0.001 | ||
| BRI | −0.366 | <0.001 | 0.318 | <0.001 | −0.385 | <0.001 | ||
| BAI | −0.361 | <0.001 | 0.317 | <0.001 | −0.345 | <0.001 | ||
| CMI | −0.441 | <0.001 | 0.392 | <0.001 | −0.432 | <0.001 | ||
| HbA1c (%) | −0.471 | <0.001 | 0.442 | <0.001 | −0.481 | <0.001 | ||
| Glucose | −0.474 | <0.001 | 0.437 | <0.001 | −0.476 | <0.001 |
Abbrevations: BMI: Body mass index, WC: Waist circumference, HC: Hip circumference, TPI: Tri ponderal index, VAI: Visceral adiposity index, BSI: Body shape index, BRI: Body roundness index, BAI: Body adiposity index, CMI: Cardiometabolic index
Parameters that can predict diabetes were included in the univariate analysis as age, gender, SBP, DBP, body composition parameters, aortic elastic properties (ASI, AS, AD). Significant results are given in Table 4. Multivariate analysis was performed on the parameters that were significant in univariate. In the multivariate logistic regression analysis, ASI (Odds ratio (OR): 1.884, 95% confidence interval (CI): 1.295–2.741, p = 0.001)) and BMI (Odds ratio (OR): 1.752, 95% confidence interval (CI): 1.215–2.526, p = 0.003)) were found to be independent predictors of newly diagnosed diabetes (Table 4).
Binary regression analysis in order to eliminate potential bias in regard to demographic characteristics between the groups
| Univariate | Multivariate | |||||
|---|---|---|---|---|---|---|
| OR | 95% CI | P value | OR | 95% CI | P value | |
| Age | 1.039 | 1.016 – 1.062 | 0.001 | 0.818 | 0.640 – 1.046 | 0.109 |
| Gender, female | 0.608 | 0.399 – 0.926 | 0.021 | |||
| Aortic stiffness index | 1.729 | 1.501 – 1.979 | <0.001 | 1.884 | 1.295 – 2.741 | 0.001 |
| Aortic strain | 0.966 | 0.959 – 0.972 | <0.001 | |||
| Aortic distensibility | 0.931 | 0.917 – 0.945 | <0.001 | |||
| SBP | 1.064 | 1.048 – 1.081 | <0.001 | |||
| DBP | 1.072 | 1.051 – 1.093 | <0.001 | |||
| WC | 1.158 | 1.125 – 1.192 | <0.001 | |||
| HC | 1.136 | 1.101 – 1.172 | <0.001 | |||
| BMI | 1.478 | 1.363 – 1.601 | <0.001 | 1.752 | 1.215 – 2.526 | 0.003 |
| Waist to Height ratio | 8.905 | 5.695 – 13.923 | <0.001 | |||
| Waist to Hip ratio | 5.005 | 3.434 – 7.293 | <0.001 | |||
| VAI | 3.248 | 2.411 – 4.376 | <0.001 | |||
| BRI | 2.648 | 2.162 – 3.244 | <0.001 | |||
| BAI | 1.303 | 1.191 – 1.425 | <0.001 | |||
Abbrevations: SBP: Systolic blood pressure, DBP: Diastolic blood pressure, BMI: Body mass index, WC: Waist circumference, HC: Hip circumference, TPI: Tri ponderal index, VAI: Visceral adiposity index, BSI: Body shape index, BRI: Body roundness index, BAI: Body adiposity index, CMI: Cardiometabolic index
The multivariate linear regression analysis identified TPI, WC, and HC as independent risk factors for all aortic elasticity parameters. Moreover, waist-to-hip ratio and BRI were independent risk factors for aortic stiffness, BRI and BAI for aortic distensibility, and BAI for aortic strain (Table 5).
Linear regression analysis to determine the relation between aortic elastic properties with body composition parameters
| Table Multivariate Linear Regression Analysis for Aortic Elasticity Parameters | |||||
| B | Standard Error | Beta | |||
| Variables | Dependent variable | Aortic stiffness | t | P | |
| TPI | 0.073 | 0.011 | 0.745 | 6.802 | <0.001 |
| Waist to Hip ratio | −24.854 | 9.764 | −1.882 | −2.545 | 0.012 |
| BRI | −0.174 | 0.083 | −0.432 | −2.105 | 0.037 |
| WC (cm) | 0.281 | 0.099 | 4.151 | 2.831 | 0.005 |
| HC (cm) | −0.255 | 0.089 | −3.177 | −2.874 | 0.005 |
| Dependent variable | Aortic strain | ||||
| TPI | −0.458 | 0.83 | −0.649 | −5.537 | <0.001 |
| VAI | −0.799 | 0.418 | −0.152 | −1.911 | 0.058 |
| BRI | 3.141 | 1.672 | 1.075 | 1.878 | 0.062 |
| BAI | −0.725 | 0.355 | −0.796 | −2.042 | 0.043 |
| WC (cm) | −0.507 | 0.232 | −1.034 | −2.183 | 0.031 |
| HC (cm) | −0.507 | 0.172 | 0.873 | 2.945 | 0.004 |
| Dependent variable | Aortic distensibility | ||||
| TPI | −0.243 | 0.042 | −0.666 | −5.743 | <0.001 |
| Waist to Hip ratio | 74.469 | 40.498 | 1.507 | 1.839 | 0.068 |
| BRI | 2.256 | 0.965 | 1.495 | 2.337 | 0.021 |
| BAI | −0.499 | 0.201 | −1.061 | −2.487 | 0.014 |
| WC (cm) | −1.062 | 0.462 | −4.191 | −2.297 | 0.023 |
| HC (cm) | 0.968 | 0.403 | 3.222 | 2.402 | 0.018 |
Abbrevations: BMI: Body mass index, WC: Waist circumference, HC: Hip circumference, TPI: Tri ponderal index, VAI: Visceral adiposity index, BSI: Body shape index, BRI: Body roundness index, BAI: Body adiposity index, CMI: Cardiometabolic index
The main findings of our study indicate that aortic elastic functions are impaired in newly diagnosed type 2 diabetic (T2DM) patients compared to the normal population. These impaired functions are associated with glycemic parameters and are significantly related to body composition indices, with the strongest correlation observed for the Tri-Ponderal Mass Index (TPI).
The factors determining the elastic functions of the aorta are primarily the balance between elastin and collagen content in the arterial wall. A shift in this balance toward collagen leads to increased arterial stiffness, one of the earliest indicators of atherosclerosis in the vascular wall [18,19]. Several mechanisms contribute to the deterioration of arterial elasticity, including endothelial dysfunction and impaired nitric oxide-mediated vasodilation originating from the endothelium. In T2DM, insulin resistance, and hyperglycemia activate the renin-angiotensin-aldosterone system, increasing the expression of type 1 angiotensin receptors in vascular tissues, which promotes arterial wall hypertrophy and fibrosis [20,21,22,23]. Furthermore, the non-enzymatic glycation of proteins in the arterial wall during chronic hyperglycemia leads to structural and functional changes in the vascular wall [24].
Several studies have investigated elastic functions in diabetic patients. Toutouzas et al. demonstrated that aortic elastic functions were impaired in diabetic patients and that this impairment was associated with the duration of diabetes and fasting blood glucose levels [25].
Similarly, Badran et al. reported that increased aortic stiffness in patients with type 2 diabetes is an early event that may explain cardiovascular complications in patients with diabetes. Poor glycemic control and duration of diabetes have negative effects on aortic elastic properties [26]. Chen Y et al. found a weak correlation between aortic elastic parameters and HbA1c levels [27]. In another study, Fang et al. concluded that variability in HbA1c levels was associated with the progression of aortic stiffness [28]. Dang et al. also demonstrated that longer diabetes duration was associated with higher arterial stiffness and lower aortic strain [4]. Similarly, another study showed that aortic elastic functions were more impaired in patients with diabetes for more than seven years compared to those with a shorter diabetes duration [29]. In another study by Song et al., they showed that aortic elastic functions were impaired in type 2 diabetics and that this impairment was associated with epicardial adipose tissue, independent of glucose levels [30].
In our study, we focused on newly diagnosed diabetic patients and showed that aortic elastic functions were already impaired at the time of diagnosis compared to the normal population. Additionally, aortic elastic properties were moderately correlated with fasting glucose and HbA1c levels.
Socioeconomic status, smoking, hypertension, sedentary lifestyle, and obesity during adolescence are known to be associated with diabetes [31]. Obesity is considered one of the most critical indicators [31]. While body mass index (BMI) is the most commonly used measurement to define overweight and obesity, its value in reflecting metabolically detrimental body fat is limited [32]. This limitation has led to the development of new body composition indices.
In a study conducted on Brazilian children and adolescents, Ueda et al. demonstrated that TPI better predicted excessive body fat accumulation compared to BMI [30], which is consistent with the findings of Wang et al. Similarly, De Lorenzo et al. showed that TPI not only better reflects body fat percentage but also more effectively defines adiposity compared to BMI [33].
Since T2DM patients are often overweight or obese, a clear body composition parameter to define adiposity in this group has yet to be established [34]. Alfaraidi et al. found that TPI correlated better with adiposity and metabolic parameters [34]. In a study conducted in Taiwan, adolescents with persistent increases in TPI were found to have a higher risk of developing diabetes, independent of initial obesity status. The importance of TPI in monitoring growth trajectories in both obese and non-obese young children was also highlighted [35].
Our study demonstrated that aortic elastic functions are impaired in newly diagnosed T2DM patients compared to the normal population, even at the time of diagnosis. These elastic functions may represent an early marker of atherosclerosis in diabetic individuals. In the screening of aortic elastic functions in diabetic patients, monitoring body composition indices in addition to glycemic parameters is essential. Among these indices, TPI appears to be the most reliable parameter. TPI could serve as a screening tool not only for aortic elastic functions but also for the development of other atherosclerotic processes. Further large-scale studies are needed on this topic.