scholarly journals Growth differentiation factor 15 as an integral marker of the clinical and functional status of patients with non-valvular atrial fibrillation

2021 ◽  
Vol 28 ◽  
pp. 32-38
Author(s):  
T. P. Gizatulina ◽  
L. U. Martyanova ◽  
T. I. Petelina ◽  
E. V. Zueva ◽  
N. E. Shirokov
Keyword(s):  
Atrial Fibrillation ◽  
Blood Serum ◽  
Functional Status ◽  
Linear Regression Analysis ◽  
Prognostic Significance ◽  
Left Ventricular ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
Diastolic Left Ventricular Dysfunction ◽  
Clinical And Functional Status

Aim. To study the relationship between growth differentiation factor 15 (GDF-15) level in blood serum and patient clinical and functional status parameters, and to determine predictors of GDF-15 level in pts with non-valvular atrial fibrillation (AF).Material and methods. Eighty-seven pts (with the mean age of 56.9±9.2 years) with non-valvular AF were studied. A general clinical examination, as well as echocardiography and laboratory tests were performed. These included fasting serum glucose (mmol/l), highly sensitive C-reactive protein (h/s CRP) (mg/l), creatinine level (μmol/l) and subsequent calculation of glomerular filtration rate (ml/min/1.73m2), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (pg/ml). The level of GDF-15 (pg/ml) in blood serum was determined using an enzyme immunoassay with a human ELISA analytical kit.Results. An increase in GDF-15 level was associated with age, ischemic heart disease, severity of hypertension, and heart failure, resulting in a higher risk of stroke, according to the CHA2DS2 -VASc score, carbohydrate metabolism disorders and obesity, increased h/s CRP and NT-proBNP levels, enlargement of the right and left atria, signs of diastolic left ventricular dysfunction and structural remodeling in the form of eccentric hypertrophy. Multiple linear regression analysis revealed 2 independent predictors of GDF-15 levels: age and fasting glucose.Conclusion. GDF-15 is an integral biomarker of age-related metabolic disorders and structural and functional changes in the heart, which opens up prospects for further study of its prognostic significance in pts with non-valvular AF.

scholarly journals Growth differentiation factor 15 as an integral marker of the clinical and functional status of patients with non-valvular atrial fibrillation

2020 ◽  
Vol 27 (3) ◽  
pp. 25-33
Author(s):  
T. P. Gizatulina ◽  
L. U. Martyanova ◽  
T. I. Petelina ◽  
E. V. Zueva ◽  
N. E. Shirokov
Keyword(s):  
Atrial Fibrillation ◽  
Blood Serum ◽  
Functional Status ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
Diastolic Left Ventricular Dysfunction ◽  
Clinical And Functional Status

Introduction. Growth Differentiation Factor 15 (GDF-15) is known to be an independent predictor of cardiovascular and all-cause mortality, as well as major bleeding in patients (pts) with non-valvular atrial fibrillation (AF). Since GDF-15 is expressed by a wide array of cells in response to inflammation and myocardial stress, it is interesting to study which clinical and functional parameters are most associated with the level of GDF-15 in pts with non-valvular AF and preserved left ventricular ejection fraction. Aim. To study the relationship of GDF-15 level in blood serum with parameters of clinical and functional status and to determine independent predictors of GDF-15 level in pts with non-valvular AF. Material and methods. 87 pts with non-valvular AF were studied, with an average age of 56.9±9.2 years. A general clinical examination, echocardiography and laboratory tests were performed, including fasting serum glucose (mmol/l),highly sensitive C-reactive protein (h/s CRP) (mg/l), creatinine level (mkmol/l) and subsequent calculation of glomerular filtration rate (ml/min/1.73m2), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (pg/ml). The level of GDF15 (pg/ml) in blood serum was determined using an enzyme immunoassay with the help of the human GDF-15/MIC-1 ELISA analytical kit (BioVender, Czech Republic). Results. The increase in the GDF-15 level was associated with ageing, ischemic heart disease, severity of arterial hypertension and heart failure, raising the risk of stroke, according to the scale CHA2DS2-VASc, disturbances of carbohydrate metabolism and obesity, increasing the levels h/s CRP and NT-proBNP, enlargement of the right and left atria, signs of diastolic left ventricular dysfunction and structural remodeling in the form of eccentric hypertrophy. Multiple linear regression analysis revealed 2 independent predictors of GDF-15 levels: age and fasting glucose. Conclusion. GDF-15 appears as an integral biomarker of age-related metabolic disorders and structural and functional changes in the heart, which opens up prospects for further study of its prognostic significance in pts with non-valvular AF.

scholarly journals High level of growth differentiation factor 15 and lower left ventricular ejection fraction as predictors of left atrial thrombosis in patients with nonvalvular atrial fibrillation

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
A.V Belokurova ◽  
T.P Gizatulina ◽  
N.Y.U Khorkova ◽  
L.U Martyanova ◽  
T.I Petelina ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ejection Fraction ◽  
Left Atrial ◽  
Roc Analysis ◽  
Left Ventricular ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
Group 2 ◽  
High Level ◽  
Group 1

Abstract Background The presence of left atrial/left atrial appendage (LA/LAA) thrombus is used as a surrogate marker of potential stroke in patients (pts) with atrial fibrillation (AF). Purpose To assess the role of growth differentiation factor 15 (GDF-15) level, clinical and echocardiographic (EchoCG) data as predictors of LA/LAA thrombus in pts with nonvalvular AF. Methods Out of 158 pts with nonvalvular AF admitted to Cardiology Center for radiofrequency ablation or elective cardioversion in 2019–2020 2 groups were formed according to transesophageal EchoCG results: group 1 included pts without LA/LAA thrombus (n=102, mean age 59.5±6.0 years) and group 2 (n=42, mean age 60.9±8.8 years) – pts with LA/LAA thrombus. Arterial hypertension was found in 93 pts of group 1 (91%) and in 40 pts of group 2 (95%, p=0.42), coronary artery disease - in 53 pts (52%) and 29 pts (69%), respectively (p=0.06). Both groups did not differ in frequency and spectrum of oral anticoagulants administration. General clinical assessment, EchoCG, and laboratory tests were performed, including GDF-15 (pg/ml) levels using Human GDF-15/MIC-1 ELISA kit and NT-proBNP (pg/ml) in blood. Results Pts with LA/LAA thrombus more often had persistent AF, while paroxysmal AF was more common in pts without thrombus. There was a tendency to more significant congestive heart failure in group 2. Mean CHA2DS2-VASc score was higher in pts with LA/LAA thrombus, also there was a tendency to a larger proportion of pts with scores ≥3. According to EchoCG data, sizes and volumes of both atria, right ventricle, end-systolic volume, left ventricular (LV) size, pulmonary artery systolic pressure and LV mass index were higher in group 2; LV ejection fraction (LVEF) was normal in both groups, but it was significantly lower in pts with LA/LAA thrombus: 59.1±5.1 and 64.0±7.3, respectively (p<0.001). GDF-15 and NT-proBNP levels were significantly higher in group 2 compared to group 1: p=0.00025 and p=0.ehab724.048801 respectively. According to ROC analysis cut-off were set at level >935.0 pg/ml for GDF-15 (AUC=0.705, 95% CI 0.609–0.800, p<0.001) and >143 pg/ml for NT-proBNP (AUC=0.759, 95% CI 0.670–0.849, p<0.001). Multivariate logistic regression revealed the following variables as independent predictors of LAAT: GDF-15 >935.0 pg/ml (OR=4.132, 95% CI 1.305–13.084) and LVEF (OR=0.859, 95% CI 0.776–0.951). According to ROC analysis, the model had a good quality: AUC=0.776 (p<0.001), sensitivity was 78.3%., specificity - 78.3%. Conclusion High level of GDF-15 (>935.0 pg/ml) along with lower LVEF are independent predictors of LA/LAA thrombus in pts with nonvalvular AF. FUNDunding Acknowledgement Type of funding sources: None.

scholarly journals The association of growth differentiation factor 15 (GDF-15) level with extent of left atrial fibrosis in patients with nonvalvular atrial fibrillation

Kardiologiia ◽  
2020 ◽  
Vol 60 (9) ◽  
pp. 22-29
Author(s):  
T. P. Gizatulina ◽  
L. U. Martyanova ◽  
T. I. Petelina ◽  
E. V. Zueva ◽  
N. E. Shirokov ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Left Atrial ◽  
Low Voltage ◽  
Left Ventricular ◽  
Volume Index ◽  
Blood Levels ◽  
Stepwise Logistic Regression ◽  
Nonvalvular Atrial Fibrillation ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor

Aim To study the relationship between the serum level of growth differentiation factor 15 (GDF-15) and clinical and functional characteristics and severity of left atrial (LA) fibrosis in patients with nonvalvular atrial fibrillation (AF).Material and methods The study included 87 patients with nonvalvular AF (62 patients with paroxysmal AF and 25 patients with persistent AF) aged 27 to 72 years (mean age, 56.9±9.2 years, 32 women). 85 % of these patients had arterial hypertension (AH), 33 % had AH and ischemic heart disease, and 12.6 % had isolated AF and were hospitalized for primary catheter ablation. General clinical evaluation, echocardiography, laboratory tests including measurement of GDF-15 and NT-proBNP concentrations in blood were performed. As a surrogate substrate of LA fibrosis during the electroanatomical voltage mapping, the area of low-voltage (<0.5 mV) zones in LA was calculated, including the total LA fibrosis area (Sf, cm2) and a percentage of fibrosis of the total LA area (Sf%).Results Median concentration of GDF-15 was 767.5 [590.0; 951.0] pg /ml. The GDF-15 level positively correlated with age, presence and severity of AH and chronic heart failure, body mass index, and degree of obesity, CHA2DS2 VASc score, level of NT-proBNP, and LA fibrosis area (Sf and Sf%) and negatively correlated with the indexes of left ventricular diastolic function, e′ septal and e′ lateral. The area of fibrosis increased with increasing GDF-15 concentrations divided into quartiles; Sf% exceeded 20 % at GDF-15 levels higher than median. After a comparative analysis of patients with Sf% ≤20 % and >20 %, statistically significantly different variables were included into a stepwise logistic regression analysis. Two independent predictors of LA fibrosis >20% were identified: a concentration of GDF-15 higher than median (odd ratio (OR), 3.318, 95 % confidence interval (CI): 1.184–9.298) and LA volume index (OR, 1.079, 95 % CI: 1.014–1.147). According to results of the ROC analysis, the area under the curve (AUC) was 0.762 (p=0.000), the model specificity was 72.3 %, sensitivity was 72.4 %, and the prediction accuracy was 72.4 %.Conclusion Blood levels of GDF-15 were associated with the presence and severity of major risk factors for AF and the area of LA fibrosis. In this study, a level of GDF-15 above the median and the LA volume index were independent predictors of LA fibrosis > 20% of the LA area.

scholarly journals The level of growth differentiation factor 15 as a predictor of left atrial thrombosis in patients with nonvalvular atrial fibrillation

Kardiologiia ◽  
2021 ◽  
Vol 61 (7) ◽  
pp. 44-54
Author(s):  
T. P. Gizatulina ◽  
N. Yu. Khorkova ◽  
L. U. Martyanova ◽  
T. I. Petelina ◽  
E. V. Zueva ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Left Atrial ◽  
Roc Analysis ◽  
Left Ventricular ◽  
Nonvalvular Atrial Fibrillation ◽  
Blood Concentrations ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
Group 2 ◽  
Group 1

Aim    To study the role of blood concentration of growth differentiation factor 15 (GDF-15) as a predictor of left atrial/left atrial appendage (LA/LAA) thrombosis in patients with nonvalvular atrial fibrillation (AF).Material and methods    538 patients with nonvalvular AF were admitted to the Tyumen Cardiology Research Center in 2019–2020 for radiofrequency ablation and elective cardioversion. According to findings of transesophageal echocardiography (EcoCG), 42 (7.8%) of these patients had LA/LAA thrombosis and 79 (14.7%) of them had the effect of spontaneous echo contrast (SEC). This comparative, cross-sectional, cohort study included at the initial stage 158 successively hospitalized patients with nonvalvular AF: group 1 (with LA/LAA thrombosis, n=42) and group 2 (without LA/LAA thrombosis and without SEC, n=116). To eliminate significant differences in age between the groups, an additional inclusion criterium was introduced, age from 45 to 75 years. Finally, 144 patients were included into the study: group 1 (with LA/LAA thrombosis, n=42, mean age 60.9±7.2 years) and group 2 (without LA/LAA thrombosis and without SEC, n=116, mean age 59.5±6.0 years). 93 (91%) patients in group 1 and 40 (95%) patients in group 2 had arterial hypertension (p=0.4168); 53 (52%) and 29 (^(%), respectively, had ischemic heart disease (p=0.0611). The groups did not differ in sex, profile of major cardiovascular diseases, or frequency and range of oral anticoagulant treatment. General clinical evaluation, EchoCG, and laboratory tests, including measurements of blood concentrations of GDF-15 and NT-proBNP, were performed.Results    In the group with LA/LAA thrombosis, 1) persistent AF prevailed whereas paroxysmal AF was more frequently observed in patients without thrombosis; 2) a tendency toward more pronounced chronic heart failure was observed; 3) tendencies toward a high median CHA2DS2‑VASc score and toward a greater proportion of patients with scores ≥3 were observed. According to EchoCG findings, group 1 had higher values of sizes and volumes of both atria and the right ventricle, left ventricular (LV) end-systolic volume and size, pulmonary artery systolic blood pressure, and LV myocardial mass index. LV ejection fraction (EF) was in the normal range in both groups but it was significantly lower for patients with LA/LAA thrombosis, 59.1±5.1 and 64.0±7.3, respectively (p=0.00006). Concentrations of GDF-15 (p=0.00025) and NT-proBNP were significantly higher in group 1 than in group 2 (p=0.000001). After determining the threshold values for both biomarkers using the ROC analysis, two independent predictors of LA/LAA thrombosis were obtained by the stepwise multiple regression analysis: GDF-15 >935.0 pg/ml (OR=4.132, 95 % CI 1.305–13.084) and LV EF (OR=0.859, 95 % CI 0.776–0.951). The ROC analysis assessed the model quality as good: AUC=0.776 (p<0.001), sensitivity 78.3 %, specificity 78.3 %.Conclusion    For patients with nonvalvular AF, both increased GDF-15 (>935.0 pg/ml) and LV EF are independent predictors for LA/LAA thrombosis.

scholarly journals New onset of atrial fibrillation in cardiogenic shock

2021 ◽  
Vol 10 (Supplement_1) ◽  
Author(s):  
H Santos ◽  
T Vieira ◽  
J Fernandes ◽  
AR Ferreira ◽  
M Rios ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Cardiogenic Shock ◽  
Linear Regression Analysis ◽  
Clinical Signs ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Coronary Syndrome ◽  
The Impact ◽  
New Onset

Abstract Funding Acknowledgements Type of funding sources: None. Introduction The development of cardiogenic shock (CS) is associated with worse prognosis, and can produce several hemodynamic manifestations. Then, is not surprised the manifestation of new-onset atrial fibrillation (AF) in these patients. Purpose Evaluate the impact of cardiovascular previous history, clinical signs and diagnosis procedures at admission as predictors of new-onset of AF in CS. Methods Single-centre retrospective study, engaging patients hospitalized for CS between 1/01/2014-30/10/2018. 222 patients with CS are included, 40 of them presented new onset of AF. Chi-square test, T-student test and Mann-Whitney U test were used to compare categorical and continuous variables. Multiple linear regression analysis was performed to evaluate predictors of new-onset AF in CS patients. Results CS patients without AF had a mean age of 61.08 ± 13.77 years old, on the other hand new-onset of AF patients in the setting of CS had a mean age of 67.02 ± 14.21 years old (p = 0.016). Nevertheless, no differences between the two groups was detected regarding the sex cardiovascular history (namely arterial hypertension, diabetes, dyslipidemia, obesity, smoker status, alcohol intake, previous acute coronary syndrome, history of angina, previous cardiomyopathy), neoplasia history, cardiac arrest during the CS, clinical signs at admission (like heart rate, blood pressure, respiratory rate), blood results (hemoglobin, leukocytes, troponin, creatinine, C-Reactive protein), left ventricular ejection fraction and the culprit lesion. New-onset of AF in CS patient had not impact in mortality rates. Multiple logistic regression reveals that only age was a predictor of new onset of AF in CS patients (odds ratio 1.032, confident interval 1.004-1.060, p = 0.024). Conclusions Age was the best predictor of new-onset AF in CS patients. The presence of this arrhythmia can have a hemodynamic impact, however, seems not influenced the final outcome.

scholarly journals Left atrial appendage orifice area and morphology is closely associated with flow velocity in patients with nonvalvular atrial fibrillation

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lei Chen ◽  
Changjiang Xu ◽  
Wensu Chen ◽  
Chaoqun Zhang
Keyword(s):  
Atrial Fibrillation ◽  
Flow Velocity ◽  
Left Atrial ◽  
Left Atrial Appendage ◽  
Linear Regression Analysis ◽  
Left Ventricular ◽  
Atrial Appendage ◽  
Mechanical Function ◽  
Orifice Area ◽  
The Relationship

Abstract Background Thromboembolic events are the most serious complication of atrial fibrillation (AF), and the left atrial appendage (LAA) is the most important site of thrombosis in patients with AF. During the period of COVID-19, a non-invasive left atrial appendage detection method is particularly important in order to reduce the exposure of the virus. This study used CT three-dimensional reconstruction methods to explore the relationship between LAA morphology, LAA orifice area and its mechanical function in patients with non-valvular atrial fibrillation (NVAF). Methods A total of 81 consecutive patients with NVAF (36 cases of paroxysmal atrial fibrillation and 45 cases of persistent atrial fibrillation) who were planned to undergo catheter radiofrequency ablation were enrolled. All patients were examined by transthoracic echocardiography (TTE), TEE, and computed tomography angiography (CTA) before surgery. The LAA orifice area was obtained according to the images of CTA. According to the left atrial appendage morphology, it was divided into chicken wing type and non-chicken wing type. At the same time, TEE was performed to determine left atrial appendage flow velocity (LAAFV), and the relationship between the left atrial appendage orifice area and LAAFV was analyzed. Results The LAAFV in Non-chicken wing group was lower than that in Chicken wing group (36.2 ± 15.0 cm/s vs. 49.1 ± 22.0 cm/s, p-value < 0.05). In the subgroup analysis, the LAAFV in Non-chicken wing group was lower than that in Chicken wing group in the paroxysmal AF (44.0 ± 14.3 cm/s vs. 60.2 ± 22.8 cm/s, p-value < 0.05). In the persistent AF, similar results were observed (29.7 ± 12.4 cm/s vs. 40.8 ± 17.7 cm/s, p-value < 0.05). The LAAFV in persistent AF group was lower than that in paroxysmal AF group (34.6 ± 15.8 cm/s vs. 49.9 ± 20.0 cm/s, p-value < 0.001). The LAAFV was negatively correlated with left atrial dimension (R = − 0.451, p-value < 0.001), LAA orifice area (R= − 0.438, p-value < 0.001) and left ventricular mass index (LVMI) (R= − 0.624, p-value < 0.001), while it was positively correlated with LVEF (R = 0.271, p-value = 0.014). Multiple linear regression analysis showed that LAA morphology (β = − 0.335, p-value < 0.001), LAA orifice area (β = −  0.185, p-value = 0.033), AF type (β = − 0.167, p-value = 0.043) and LVMI (β = − 0.465, p-value < 0.001) were independent factors of LAAFV. Conclusions The LAA orifice area is closely related to the mechanical function of the LAA in patients with NVAF. The larger LAA orifice area and LVMI, Non-chicken wing LAA and persistent AF are independent predictors of decreased mechanical function of LAA, and these parameters might be helpful for better management of LA thrombosis.

Abstract P009: Growth Differentiation Factor 15 And The Subsequent Risk Of Atrial Fibrillation: The Atherosclerosis Risk In Communities Study

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Mengkun Chen ◽  
Ning Ding ◽  
Lena Mathews ◽  
Ron C Hoogeveen ◽  
Christie M Ballantyne ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Proportional Hazards ◽  
Troponin T ◽  
Cox Proportional Hazards ◽  
Atherosclerosis Risk In Communities ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
Cox Proportional Hazards Models ◽  
Increased Risk ◽  
Icd 10

Introduction: Growth differentiation factor 15 (GDF-15) is a marker of oxidative stress and inflammation and has been associated with several cardiovascular disease (CVD) phenotypes. However, conflicting results have been reported regarding the association of GDF-15 with incident atrial fibrillation (AF) in the general population. Hypotheses: Higher GDF-15 level is associated with increased risk of incident AF independent of potential confounders. Methods: In 10,101 White and Black ARIC participants (mean age 60 years and 20.9% Blacks) free of AF at baseline (1993-95), we quantified the association of GDF-15 and incident AF using three Cox proportional hazards models. GDF-15 was measured by SOMA scan assay. AF was defined by hospitalizations with AF diagnosis or death certificates (ICD-9 codes: 427.31-427.32; ICD-10 codes: I48.x) or AF diagnosis by ECG at subsequent ARIC visits. Results: There were 2165 cases of incident AF over a median follow-up of 20.7 years (incidence rate 12.1 cases/1,000 person-years). After adjusting for demographic characteristics and cardiovascular risk factors, log GDF-15 was significantly associated with incident AF (hazard ratio 1.42 (1.25-1.63) for top vs. bottom quartile) (Model 1 in Table ). The result was robust even further adjusting for history of other CVD phenotypes and cardiac markers (Models 2 and 3 in Table ). In Model 3, quartiles of high-sensitive cardiac troponin T (hs-cTnT) did not demonstrate significant associations with incident AF. Conclusions: In community-based population, elevated GDF-15 level was independently and robustly associated with incident AF (even more strongly than troponin). These results suggest the involvement of GDF-15 in the development of AF and the potential of GDF-15 as a risk marker to identify individuals at high risk of AF.

scholarly journals Increased Growth Differentiation Factor 15 in Patients with Hypoleptinemia-Associated Lipodystrophy

2020 ◽  
Vol 21 (19) ◽  
pp. 7214 ◽  
Author(s):  
Susan Kralisch ◽  
Annett Hoffmann ◽  
Juliane Estrada-Kunz ◽  
Michael Stumvoll ◽  
Mathias Fasshauer ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Transforming Growth Factor ◽  
Linear Regression Analysis ◽  
Control Group ◽  
Serum Concentrations ◽  
Metabolic Complications ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
Obesity And Diabetes ◽  
The Impact

Objective. Similar to obesity, lipodystrophy (LD) causes adipose tissue dysfunction and severe metabolic complications. Growth differentiation factor 15 (GDF15) belongs to the transforming growth factor β superfamily and is dysregulated in metabolic disease including obesity and diabetes mellitus. Circulating levels in LD and the impact of leptin treatment have not been investigated so far. Material and Methods. GDF15 serum levels were quantified in 60 LD patients without human immunodeficiency virus infection and 60 controls matched for age, gender, and body mass index. The impact of metreleptin treatment on circulating GDF15 was assessed in a subgroup of patients. GDF15 mRNA expression was determined in metabolic tissues of leptin-deficient lipodystrophic aP2-nSREBP1c-Tg mice, obese ob/ob mice, and control C57Bl6 mice. Results. Median GDF15 serum concentrations were significantly higher in LD patients (819 ng/L) as compared to the control group (415 ng/L) (p < 0.001). In multiple linear regression analysis, an independent and positive association remained between GDF15 on one hand and age, patient group, hemoglobin A1c, triglycerides, and C-reactive protein on the other hand. Moreover, there was an independent negative association between GFD15 and estimated glomerular filtration rate. Circulating GDF15 was not significantly affected by metreleptin treatment in LD patients. Gdf15 was upregulated in leptin-deficient lipodystrophic mice as compared to controls. Moreover, Gdf15 mRNA expression was downregulated by leptin treatment in lipodystrophic and obese animals. Conclusions. Serum concentrations of GDF15 are elevated in LD patients and independently associated with markers of metabolic dysfunction. Gdf15 expression is higher in lipodystrophic mice and downregulated by leptin treatment.

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