The impact of diabetes mellitus and microvascular complications on heart failure biomarkers
CKD
Florina Fringu
1 Abstract
1.1 Background
The prevalence of heart failure (HF) is increased in diabetic patients. Several studies confirmed the prognostic role of ST2 and Galectin-3 (Gal-3) in HF patients, but the relationship between diabetes mellitus (DM) along with its complications and the new biomarkers is still uncertain.
1.2 Methods
88 subjects with decompensated heart failure (NYHA classes III-IV) were enrolled, with a mean age of 69.82 ± 9.5 years, 61.7% of which were men and 47.9% of them with previous DM. All patients were evaluated both clinically and echocardiographically. The entire cohort had serum concentrations of ST2, Gal-3 and NT-proBNP measured upon admission. Patients with DM were divided into two groups: those with DM microvascular complications (retinopathy, nephropathy or polyneuropathy - 58.9%) or without- 41.1%.
1.3 Results
Mean left ventricular ejection fraction (LVEF) was 38.84 ± 11.3%, without significant differences between the two groups (p-NS). Concerning HF biomarkers, the following mean values were obtained: ST2 - 46.32 ± 25.8 ng/ml, Gal 3-15.19 ± 6.7 ng/ml, NT-pro BNP - 3493.04 ± 3884.8 pg/ml. There were no statistically significant differences between patients with or without DM: ST2 : 47.51 ± 28.7ng/ml vs 44.89 ± 23.1 ng/ml; Gal-3: 15.25 ± 7.7ng/ml vs 15.07 ± 5.7ng/ml; NT-proBNP: 3857.42 ± 3844.2 pg/ml vs 3104.28 ± 3940.4 pg/ml. When comparing the two groups of diabetic subjects, only Gal-3 values were found to be consistently higher in subjects with microvascular complications: 16.23 ± 4.9 ng/ml vs 13.74 ± 10.4 ng/ml (p=0.005); ST2 : 53.21 ± 31.9ng/ml vs 39.5 ± 23.3 ng/ml (p-NS); NT-proBNP : 4364.9 ± 4213.9 pg/ml vs 3188.96 ± 3350.0 pg/ml (p=NS). ST 2 levels correlated significantly with NT-proBNP levels (r=0.24; p=0.03), hypocholesterolemia (r= 0.22; p=0.048) and GFR (r=-0.22) in both groups. There was no direct correlation between ST2 levels and the NYHA class (p=0.334). Gal-3 levels also correlated well with LVEF value (r=0.22; p=0.048), NT-pro BNP levels (r=0.40; p < 0.0001) and NYHA class (p <0.0001).
Table 1. Summary of the most relevant paramenters in all groups of patients.
Factor | Levels | no | stage 3 | stage 4-5 | Total | Statistics |
CKD | 19 (30.2%) | 36 (57.1%) | 8 (12.7%) | 63 | ||
Diabetes | 11 (57.9%) | 15 (41.7%) | 4 (50.0%) | 30 (47.6%) | V=0.15 (p=0.513) | |
Diabetes complications | 5 (45.5%) | 11 (78.6%) | 2 (50.0%) | 18 (62.1%) | V=0.33 (p=0.206) | |
Group | control | 8 (42.1%) | 21 (58.3%) | 4 (50.0%) | 33 (52.4%) | V=0.17 (p=0.454) |
DM w/ complic. | 6 (31.6%) | 4 (11.1%) | 2 (25.0%) | 12 (19.0%) | ||
DM with complic. | 5 (26.3%) | 11 (30.6%) | 2 (25.0%) | 18 (28.6%) | ||
Age (years) | Mean ±SD | 67.63 ±9.79 | 71.89 ±9.89 | 73.50 ±9.3 | 70.81 ±9.88 | 1-way ANOVA: p=0.227 |
*M(R) | 65 (51:90) | 71 (45:88) | 72 (63:88) | 70 (45:90) | ||
Sex | F | 6 (31.6%) | 17 (47.2%) | 5 (62.5%) | 28 (44.4%) | V=0.20 (p=0.295) |
M | 13 (68.4%) | 19 (52.8%) | 3 (37.5%) | 35 (55.6%) | ||
ST2 (ng/ml) | Mean ±SD | 31.67 ±16.5 | 48.56 ±21.8 | 57.57 ±43.4 | 48.91 ±26.9 | Kruskal-Wallis: p=0.389 |
*M(R) | 32 (15:48) | 50 (17:100) | 33 (21:130) | 41 (15:130) | ||
Galectin-3 (ng/ml) | Mean ±SD | 11.23 ±1.59 | 16.12 ±5.75 | 15.77 ±5.76 | 15.63 ±5.59 | Kruskal-Wallis: p=0.366 |
*M(R) | 12.1 (9.4:12.2) | 17.6 (7.2:27) | 14 (9.9:26) | 14 (7.2:27) | ||
NT-proBNP (pg/ml) | Mean ±SD | 2112.72 ±2197.9 | 3624.18 ±2845.6 | 4877.88 ±4998.0 | 3333.05 ±3120.5 | Kruskal-Wallis: p=0.087 |
*M(R) | 1088.5 (283:7885) | 3000 (168:13000) | 3144 (675:15000) | 2686 (168:15000) | ||
Weight (kg) | Mean ±SD | 85.83 ±19.8 | 79.50 ±16.9 | 72.50 ±19.4 | 80.47 ±18.3 | 1-way ANOVA: p=0.209 |
*M(R) | 83.5 (45:120) | 79.5 (50:121) | 67.5 (45:107) | 79.5 (45:121) | ||
Height (m) | Mean ±SD | 1.67 ±0.0777 | 1.67 ±0.0719 | 1.63 ±0.0719 | 1.66 ±0.0739 | Kruskal-Wallis: p=0.396 |
*M(R) | 1.68 (1.5:1.8) | 1.68 (1.5:1.84) | 1.62 (1.51:1.7) | 1.68 (1.5:1.84) | ||
BMI (kg/m²) | Mean ±SD | 30.81 ±7.36 | 28.49 ±5.89 | 27.67 ±8.48 | 29.08 ±6.71 | Kruskal-Wallis: p=0.505 |
*M(R) | 28.96 (20:44.08) | 28.91 (18.93:41.02) | 26.6 (17.58:41.8) | 28.91 (17.58:44.08) | ||
Hemoglobin | Mean ±SD | 12.98 ±1.86 | 12.43 ±1.95 | 11.64 ±2.33 | 12.50 ±1.98 | Kruskal-Wallis: p=0.171 |
*M(R) | 13.9 (9.5:15.5) | 12.7 (7.4:16.5) | 11.05 (8.7:15.4) | 13 (7.4:16.5) | ||
Hematocrite | Mean ±SD | 37.66 ±7.65 | 37.69 ±5.66 | 36.16 ±7.26 | 37.49 ±6.43 | Kruskal-Wallis: p=0.619 |
*M(R) | 41 (13.9:45.5) | 38.3 (23.4:48.9) | 36.35 (25.8:45.1) | 38.5 (13.9:48.9) | ||
Cholesterol | Mean ±SD | 166.84 ±59.5 | 156.17 ±43.7 | 132.43 ±66.7 | 156.37 ±52.1 | Kruskal-Wallis: p=0.703 |
*M(R) | 146 (103:317) | 152.5 (92:316) | 128.5 (9.43:204) | 146 (9.43:317) | ||
LDL | Mean ±SD | 94.42 ±45.3 | 87.64 ±33.7 | 100.38 ±42.1 | 91.30 ±38.2 | Kruskal-Wallis: p=0.605 |
*M(R) | 80 (27:222) | 82 (9:190) | 107 (32:146) | 82 (9:222) | ||
HDL | Mean ±SD | 48.11 ±33.1 | 42.42 ±15.1 | 35.75 ±9.25 | 43.29 ±21.7 | Kruskal-Wallis: p=0.677 |
*M(R) | 38 (27:166) | 40.5 (22:94) | 35.5 (19:50) | 38 (19:166) | ||
Triglycerides | Mean ±SD | 124.58 ±74.1 | 116.53 ±50.8 | 134.25 ±61.1 | 121.21 ±59.3 | Kruskal-Wallis: p=0.770 |
*M(R) | 109 (51:361) | 116.5 (53:310) | 115 (69:258) | 111 (51:361) | ||
Uric acid | Mean ±SD | 8.40 ±2.66 | 8.86 ±2.08 | 10.11 ±3.22 | 8.88 ±2.43 | 1-way ANOVA: p=0.253 |
*M(R) | 7.87 (5.09:12.59) | 9.19 (4.82:13.61) | 9.71 (5.63:14.26) | 8.53 (4.82:14.26) | ||
TSH | Mean ±SD | 2.19 ±1.84 | 1.87 ±1.58 | 5.53 ±8.85 | 2.34 ±3.08 | Kruskal-Wallis: p=0.936 |
*M(R) | 1.46 (0.73:6.04) | 1.47 (0.01:7.6) | 1.29 (0.73:18.8) | 1.45 (0.01:18.8) | ||
Glucose | Mean ±SD | 121.16 ±48.6 | 113.00 ±37.4 | 123.88 ±42.2 | 116.84 ±41.2 | Kruskal-Wallis: p=0.731 |
*M(R) | 118 (66:293) | 102 (76:272) | 103 (90:192) | 104 (66:293) | ||
Urea | Mean ±SD | 51.58 ±10.8 | 85.85 ±33.4 | 118.75 ±28.2 | 79.69 ±34.8 | Kruskal-Wallis: p<0.001 |
*M(R) | 56 (30:66) | 80 (30:161) | 120.5 (86:170) | 69 (30:170) | ||
Creatinin | Mean ±SD | 0.977 ±0.16 | 1.51 ±0.294 | 2.52 ±0.996 | 1.48 ±0.621 | Kruskal-Wallis: p<0.001 |
*M(R) | 0.96 (0.65:1.33) | 1.51 (0.96:2.11) | 2.27 (1.76:4.89) | 1.35 (0.65:4.89) | ||
Creatinin clerence | Mean ±SD | 75.24 ±14.0 | 43.69 ±8.34 | 23.86 ±9.13 | 50.69 ±20.3 | Kruskal-Wallis: p<0.001 |
*M(R) | 71.1 (50:97.8) | 42.3 (30.4:59.8) | 23.7 (9.2:41.8) | 47.8 (9.2:97.8) | ||
Iron | Mean ±SD | 38.53 ±9.81 | 38.94 ±13.0 | 35.25 ±11.7 | 38.35 ±11.8 | Kruskal-Wallis: p=0.698 |
*M(R) | 40 (22:55) | 40 (16:64) | 36 (20:50) | 40 (16:64) | ||
Retinopathy | 2 (15.4%) | 5 (33.3%) | 2 (40.0%) | 9 (27.3%) | V=0.22 (p=0.447) | |
Nephopathy | 2 (15.4%) | 11 (73.3%) | 2 (40.0%) | 15 (45.5%) | V=0.54 (p=0.009) | |
PNP | 3 (23.1%) | 8 (53.3%) | 2 (40.0%) | 13 (39.4%) | V=0.28 (p=0.263) | |
AV | Mean ±SD | 78.05 ±18.6 | 75.23 ±18.2 | 66.62 ±11.3 | 74.96 ±17.7 | 1-way ANOVA: p=0.311 |
*M(R) | 75 (48:110) | 75 (30:120) | 71 (45:80) | 75 (30:120) | ||
Hypertension | nu | 3 (15.8%) | 14 (43.8%) | 4 (50.0%) | 21 (35.6%) | V=0.28 (p=0.062) |
II | 13 (68.4%) | 9 (28.1%) | 3 (37.5%) | 25 (42.4%) | ||
III | 3 (15.8%) | 9 (28.1%) | 1 (12.5%) | 13 (22.0%) | ||
ACOMI | 1 (5.3%) | 2 (6.2%) | 2 (25.0%) | 5 (8.5%) | V=0.24 (p=0.195) | |
ICD | 6 (31.6%) | 7 (21.9%) | 0 | 13 (22.0%) | V=0.24 (p=0.195) | |
VS1 | Mean ±SD | 57.26 ±10.7 | 57.94 ±11.0 | 64.25 ±12.0 | 58.55 ±11.1 | Kruskal-Wallis: p=0.248 |
*M(R) | 58 (38:77) | 58 (40:76) | 66.5 (39:77) | 58.5 (38:77) | ||
VS2 | Mean ±SD | 44.32 ±11.4 | 43.74 ±13.4 | 52.12 ±13.1 | 45.00 ±12.9 | Kruskal-Wallis: p=0.229 |
*M(R) | 40 (26:66) | 44 (20:65) | 54.5 (26:65) | 46 (20:66) | ||
E/A | <1 | 2 (22.2%) | 6 (37.5%) | 0 | 8 (28.6%) | V=0.26 (p=0.454) |
≥1 | 5 (55.6%) | 6 (37.5%) | 1 (33.3%) | 12 (42.9%) | ||
≥2 | 2 (22.2%) | 4 (25.0%) | 2 (66.7%) | 8 (28.6%) | ||
Left atrium | Mean ±SD | 48.11 ±7.5 | 46.91 ±6.85 | 54.12 ±7.85 | 48.21 ±7.44 | 1-way ANOVA: p=0.044 |
*M(R) | 50 (28:60) | 46 (35:60) | 52.5 (45:64) | 49 (28:64) | ||
NYHA Class | II | 5 (26.3%) | 4 (12.1%) | 1 (12.5%) | 10 (16.7%) | V=0.18 (p=0.435) |
III | 8 (42.1%) | 21 (63.6%) | 6 (75.0%) | 35 (58.3%) | ||
IV | 6 (31.6%) | 8 (24.2%) | 1 (12.5%) | 15 (25.0%) | ||
Iscaemic cardioathy | 11 (57.9%) | 20 (55.6%) | 4 (50.0%) | 35 (55.6%) | V=0.05 (p=0.931) | |
Fibrilation | 12 (63.2%) | 24 (66.7%) | 8 (100.0%) | 44 (69.8%) | V=0.25 (p=0.133) | |
HTP | 9 (47.4%) | 20 (62.5%) | 5 (62.5%) | 34 (57.6%) | V=0.14 (p=0.547) | |
COPD | 6 (42.9%) | 8 (24.2%) | 4 (57.1%) | 18 (33.3%) | V=0.26 (p=0.167) | |
Asthma | 2 (11.8%) | 1 (3.0%) | 0 | 3 (5.3%) | V=0.19 (p=0.340) | |
VD | Mean ±SD | 34.13 ±8.22 | 31.03 ±7.67 | 34.29 ±4.99 | 32.34 ±7.58 | Kruskal-Wallis: p=0.172 |
*M(R) | 34 (23:49) | 30 (21:48) | 33 (28:42) | 31 (21:49) | ||
PAPS | Mean ±SD | 55.92 ±18.2 | 48.72 ±19.3 | 61.67 ±17.6 | 51.85 ±18.9 | 1-way ANOVA: p=0.368 |
*M(R) | 52 (35:90) | 50 (17:90) | 60 (45:80) | 50 (17:90) | ||
MLHF | Mean ±SD | 59.25 ±7.7 | 62.25 ±5.82 | 63.00 ±NA | 60.57 ±6.85 | 1-way ANOVA: p=0.615 |
*M(R) | 56.5 (50:70) | 62 (52:72) | 63 (63:63) | 60 (50:72) | ||
Diur | 18 (94.7%) | 31 (86.1%) | 7 (87.5%) | 56 (88.9%) | V=0.12 (p=0.620) | |
Nitr | 10 (52.6%) | 15 (41.7%) | 6 (75.0%) | 31 (49.2%) | V=0.22 (p=0.219) | |
IEC | 12 (63.2%) | 18 (50.0%) | 3 (37.5%) | 33 (52.4%) | V=0.16 (p=0.432) | |
Digoxin | 10 (52.6%) | 8 (22.2%) | 1 (12.5%) | 19 (30.2%) | V=0.33 (p=0.033) | |
Bet Bl | 16 (84.2%) | 29 (80.6%) | 5 (62.5%) | 50 (79.4%) | V=0.16 (p=0.429) | |
Antiagr | 5 (26.3%) | 9 (25.0%) | 2 (25.0%) | 16 (25.4%) | V=0.01 (p=0.994) | |
ACO | 13 (68.4%) | 25 (69.4%) | 6 (75.0%) | 44 (69.8%) | V=0.04 (p=0.941) | |
Antiaritmice | 7 (36.8%) | 13 (36.1%) | 4 (50.0%) | 24 (38.1%) | V=0.09 (p=0.758) | |
Sartani | 3 (15.8%) | 15 (41.7%) | 1 (12.5%) | 19 (30.2%) | V=0.29 (p=0.070) | |
Entresto | 1 (5.3%) | 4 (11.1%) | 1 (12.5%) | 6 (9.5%) | V=0.10 (p=0.745) | |
Spirono | 14 (73.7%) | 24 (66.7%) | 5 (62.5%) | 43 (68.3%) | V=0.08 (p=0.810) | |
Statina | 12 (63.2%) | 17 (47.2%) | 3 (37.5%) | 32 (50.8%) | V=0.17 (p=0.385) | |
ADO | 8 (42.1%) | 7 (19.4%) | 3 (37.5%) | 18 (28.6%) | V=0.24 (p=0.175) | |
Insulina | 3 (15.8%) | 8 (22.2%) | 4 (50.0%) | 15 (23.8%) | V=0.24 (p=0.153) | |
*M(R) = Mediana (min:max); MW = Test Mann-Whitney; OR/RR = odds-ratio / risc relativ [cu IC 95%] și p calculat prin testul Fisher); V = Cramer V (p calculat prin testul Chi²). | ||||||
1.4 Conclusions
Biomarkers of HF used for screening the general population are also useful in patients with DM, with Galectin-3 levels being significantly higher in diabetic patients with microvascular complications than in those without.
2 Figures
2.1 ST2-Biomarker Insuf Cardiaca
2.2 Galectina 3- Biomarker Insuf Cardiaca
2.3 BNP
2.4 Fe
3 Figures 2
3.1 Correlations
3.2 Correlations2
3.3 Correlation matrix
3.3.1 All patients
3.3.2 no CKD
3.3.3 Stage 3 CKD
3.3.4 Stage 4 and 5 CKD
4 Extra
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