Growth Differentiation Factor 15 in Severe Aortic Valve Stenosis: Relationship with Left Ventricular Remodeling and Frailty
Abstract
:1. Introduction
2. Methods
2.1. Study Population
2.2. Frailty Assessment
2.3. Echocardiography
2.4. GDF15 and Other Plasma Biomarkers
2.5. Statistical Analyses
3. Results
3.1. Correlation of GDF15 with Echocardiographic Data
3.2. Correlations with Frailty
3.3. Correlations with Follow-Up Outcomes
4. Discussion
- Higher GDF15 levels in AVS patients compared to age- and sex-matched controls;
- An association between age, NYHA functional class, renal function and GDF15 levels;
- A differential distribution of GDF15 levels according to parameters of systolic function (GLS) and structure (LAVi; LV mass);
- A differential distribution of GDF15 according to the frailty score (Katz index), with higher GDF15 levels in more frail patients, independent of other clinical, structural and bio-humoral parameters.
4.1. GDF15 in Aortic Valve Disease
4.2. GDF15 and Frailty Before Aortic Valve Replacement
5. Limitations
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Population (n = 62) | Controls (n = 15) | GDF15 T1-T2 (754–1643 ng/L) (n = 23) | GDF15 T3 (2255–2725 ng/L) (n = 39) | T1-T2 vs. T3 | ||||||
---|---|---|---|---|---|---|---|---|---|---|
N (Median/Mean) | % (95% CI) | N (Median/Mean) | % (95% CI) | p * | N (Median/Mean) | % (95% CI) | N (Median/Mean) | % (95% CI) | p | |
Gender (Female) | 34 | 54.8% | 8 | 55% | ns | 12 | 52.1% | 22 | 56.4% | 0.5 |
Age (years) | 79.3 | 77.3–81.3 | 78.2 | 76.5–80.2 | ns | 76.2 | 73.3–79.2 | 81 | 79.4–82.5 | 0.004 |
BMI (kg/m2) | 26.6 | 25.6–27.6 | 25.5 | 25.2–27.7 | ns | 26.6 | 25–28.2 | 26.6 | 25.2–27.9 | 0.9 |
BSA (m2) | 1.8 | 1.81–1.95 | 1.75 | 1.71–1.96 | ns | 1.88 | 1.8–1.96 | 1.81 | 1.75–1.87 | 0.2 |
Heart Rate (bpm) | 74 | 69.3–78.7 | 71 | 68.1–79.6 | ns | 72.1 | 67.9–76.3 | 77.3 | 73–81.7 | 0.1 |
Atrial Fibrillation | 6 | 9.6% | 0 | 0% | NA | 1 | 4.3% | 5 | 12.8% | 0.06 |
SAP (mmHg) | 140.2 | 132.9–147.5 | 140.2 | 132.9–147.5 | ns | 135.6 | 128.9–142.3 | 140.2 | 133.2–147.2 | 0.4 |
DAP (mmHg) | 71.1 | 67.2–74.9 | 71.8 | 67–75.3 | ns | 71 | 66.9–75.1 | 71.3 | 67.1–75.4 | 0.9 |
Smokers | 17 | 27.4% | 0 | 0% | NA | 7 | 30.4% | 10 | 25.6% | 0.07 |
Anemia | 20 | 32.2% | 0 | 0% | NA | 6 | 26% | 14 | 35.8% | 0.08 |
Diabetes Mellitus | 17 | 27.4% | 0 | 0% | NA | 7 | 30.4% | 10 | 25.6% | 0.07 |
Hypertension | 57 | 92% | 13.5 | 90% | ns | 21 | 91.3% | 36 | 92.3% | 0.07 |
Coronary Artery Disease | 19 | 30.6% | 0 | 0% | NA | 7 | 30% | 12 | 30.7% | 0.6 |
COPD | 15 | 24.1% | 0 | 0% | NA | 4 | 17.3% | 11 | 28.2% | 0.06 |
NYHA class I/II | 38 | 61.2% | 15 | 100% | <0.0001 | 20 | 86.9% | 18 | 46.1% | 0.03 |
NYHA class III | 24 | 38.7% | 0 | 0% | NA | 7 | 30% | 17 | 43.6% | 0.04 |
Katz Frailty Score ≥5 | 52 | 83.8% | NA | NA | NA | 22 | 95.6% | 30 | 77% | 0.05 |
Katz Frailty Score <5 | 10 | 16.1% | NA | NA | NA | 1 | 4.3% | 9 | 23% | 0.0001 |
eGFR (mL/min/1.73 m2) | 63.3 | 56.6–70 | 73.3 | 68.8–75.4 | <0.0001 | 69.4 | 62.2–73.6 | 54.2 | 47.6–60.9 | 0.0001 |
Euroscore II (%) | 3.8 | 2.7–4.9 | NA | NA | NA | 3.4 | 1.2–5.7 | 4 | 2.9–5.2 | 0.6 |
GDF-15 (pg/mL) | 1772.4 | 1573.5–1971.3 | 774.9 | 599.5–950.2 | <0.0001 | 1253.8 | 1115.5–1392.2 | 2490.4 | 2255–2725.7 | <0.0001 |
NT-pro-BNP (ng/L) | 918 | 588.2–1433.6 | 33.7 | 16.7–50.6 | 0.0001 | 140 | 78–251.2 | 1048.5 | 510.2–1371.4 | <0.0001 |
TnT-Hs (ng/L) | 89.5 | 20.4–110.7 | 4.8 | 4–5.6 | 0.04 | 24.8 | 4.8–44.8 | 54.1 | 49.5–98.8 | 0.0001 |
Albumin (g/dl) | 3.8 | 3–4.4 | 4.2 | 4–4.6 | ns | 3.5 | 2.9–3.8 | 3.6 | 3.1–4.1 | 0.8 |
Population (n = 62) | Controls (n = 15) | GDF15 T1-T2 (754-1643 ng/L) (n = 23) | GDF15 T3 (2255-2725 ng/L) (n = 39) | |||||||
---|---|---|---|---|---|---|---|---|---|---|
N (Median/Mean) | % (95% CI) | N (Median/Mean) | % (95% CI) | p * | N (Median/Mean) | % (95% CI) | N (Median/Mean) | % (95% CI) | p | |
LV EDVi (mL/m2) | 53 | 48.6–57.4 | 56 | 49.6–59.4 | ns | 50 | 44.3–56.9 | 54.3 | 48.3–60.4 | 0.4 |
LV ESVi (mL/m2) | 28.1 | 24.3–31.9 | 26.1 | 23.3–33.9 | ns | 26.9 | 22.3–31.6 | 28.8 | 23.2–34.3 | 0.6 |
EF (%) | 60.7 | 57.5–63.8 | 62.7 | 58.5–65.8 | ns | 62.7 | 59.9–65.4 | 59.9 | 56.6–63.3 | 0.2 |
GLS (%) | 13.9 | 12.9–15 | 17.2 | 15.9–19 | <0.0001 | 15.9 | 14.7–17.2 | 13.7 | 12.7–15.1 | 0.01 |
RWT | 0.50 | 0.47–0.53 | 0.38 | 0.35–0.42 | <0.0001 | 0.5 | 0.46–0.53 | 0.51 | 0.48–0.54 | 0.5 |
LVMi (g/m2) | 130.1 | 119.6–140.5 | 80.2 | 65.4–88.3 | <0.0001 | 111.4 | 101.2–121.6 | 132.5 | 124.3–140.7 | 0.001 |
LAVi (cm2/m2) | 44.1 | 37–47 | 26 | 22.2–31.1 | <0.0001 | 41.7 | 35.1–46.4 | 47.3 | 41.3–50.2 | 0.04 |
E/A | 0.8 | 0.6–0.9 | 1 | 0.8–1.2 | ns | 0.7 | 0.6–0.8 | 0.8 | 0.7–0.9 | 0.8 |
E/e’average | 15.8 | 13.1–17.9 | 11.5 | 9.1–13.2 | 0.04 | 16.3 | 13.4–19.1 | 16.9 | 14.4–19.4 | 0.7 |
Stroke Volume index (mL/m2) | 35 | 31.4–38.6 | 49 | 45–65 | <0.0001 | 36.7 | 31.9–41.5 | 33.4 | 30.2–36.5 | 0.2 |
AVAi (mL/m2) | 0.36 | 0.34–0.4 | NA | NA | NA | 0.4 | 0.35–0.43 | 0.38 | 0.33–0.41 | 0.4 |
Peak Trans-aortic velocity (m/s) | 4.4 | 4.2–4.6 | 1.6 | 1.5–2.1 | <0.0001 | 4.4 | 4.2–4.7 | 4.3 | 4.2–4.5 | 0.4 |
Maximum pressure gradient (mmHg) | 79.9 | 73.6–86.3 | NA | NA | NA | 82.5 | 73.8–91.1 | 77.5 | 73.1–82.4 | 0.3 |
Mean pressure gradient (mmHg) | 49.7 | 45.7–53.8 | NA | NA | NA | 50.3 | 44.7–55.9 | 47.7 | 44.6–50.7 | 0.4 |
ZVa (mmHg/mL/m2) | 5.4 | 4.9–5.8 | NA | NA | NA | 5.2 | 4.5–5.8 | 5.4 | 4.9–5.8 | 0.6 |
Estimated sPAP | 33.1 | 29.8–32.4 | 28.8 | 27.9–31.3 | 0.03 | 30.5 | 27.9–33 | 33.9 | 30.1–37.7 | 0.2 |
TAPSE (mm) | 19 | 16.7–24 | 20 | 18.3–25.2 | 0.04 | 18 | 17.5–23.3 | 17 | 16.8–22.8 | 0.6 |
Independent Variables | OR | 95% CI | p | OR | 95%CI | p |
---|---|---|---|---|---|---|
GLS% | 1.062 | 1.002–1.112 | 0.04 | 0.07 | ||
Age (years) | 1.065 | 1.002–1.114 | 0.05 | 0.08 | ||
GDF-15 (pg/mL) | 1.2 | 1001–1.324 | 0.02 | 1.06 | 1–1.123 | 0.03 |
LVMi (g/m2) | 0.9 | 0.8–0.987 | 0.04 | 0.1 | ||
NYHA class | 0.85 | 0.78–0.943 | 0.03 | 0.2 | ||
eGFR (mL/min/1.73 m2) | 1.12 | 1.004–1.253 | 0.038 | 0.09 |
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Fabiani, I.; Santoni, T.; Angelillis, M.; Petricciuolo, S.; Colli, A.; Pellegrini, G.; Mazzei, D.; Pugliese, N.R.; Petronio, A.S.; De Caterina, R. Growth Differentiation Factor 15 in Severe Aortic Valve Stenosis: Relationship with Left Ventricular Remodeling and Frailty. J. Clin. Med. 2020, 9, 2998. https://doi.org/10.3390/jcm9092998
Fabiani I, Santoni T, Angelillis M, Petricciuolo S, Colli A, Pellegrini G, Mazzei D, Pugliese NR, Petronio AS, De Caterina R. Growth Differentiation Factor 15 in Severe Aortic Valve Stenosis: Relationship with Left Ventricular Remodeling and Frailty. Journal of Clinical Medicine. 2020; 9(9):2998. https://doi.org/10.3390/jcm9092998
Chicago/Turabian StyleFabiani, Iacopo, Tatiana Santoni, Marco Angelillis, Serena Petricciuolo, Andrea Colli, Giovanni Pellegrini, Deborah Mazzei, Nicola Riccardo Pugliese, Anna Sonia Petronio, and Raffaele De Caterina. 2020. "Growth Differentiation Factor 15 in Severe Aortic Valve Stenosis: Relationship with Left Ventricular Remodeling and Frailty" Journal of Clinical Medicine 9, no. 9: 2998. https://doi.org/10.3390/jcm9092998
APA StyleFabiani, I., Santoni, T., Angelillis, M., Petricciuolo, S., Colli, A., Pellegrini, G., Mazzei, D., Pugliese, N. R., Petronio, A. S., & De Caterina, R. (2020). Growth Differentiation Factor 15 in Severe Aortic Valve Stenosis: Relationship with Left Ventricular Remodeling and Frailty. Journal of Clinical Medicine, 9(9), 2998. https://doi.org/10.3390/jcm9092998