Relationship Between Baseline Characteristics and the Number of Biomarkers Elevated
| All (n=345) | No biomarkers elevated (n=79) | One biomarker elevated (n=96) | Two biomarkers elevated (n=87) | Three biomarkers elevated (n=83) | p Value | |
|---|---|---|---|---|---|---|
| Biomarker levels | ||||||
| GDF15 (pg/mL) | 2023 (1427, 2885) | 1252 (851,1514) | 1684 (1352,2059) | 2469 (2016,3294) | 3276 (2607, 4323) | <0.001 |
| sST2 (ng/mL) | 33 (24,46) | 20 (15,27) | 30 (22,40) | 36 (27,49) | 48 (40,63) | <0.001 |
| MPO (ng/mL) | 75 (53,128) | 76 (53,154) | 68 (51,112) | 75 (53,140) | 76 (55,116) | 0.68 |
| NTproBNP (pg/mL) | 1402 (580,3583) | 465 (189,816) | 1018 (495,1668) | 1956 (1095,4142) | 5166 (2610,8966) | <0.001 |
| Galectin-3 (ng/mL) | 19 (14,25) | 15 (12,19) | 18 (14,22) | 20 (14,26) | 24 (19,30) | <0.001 |
| hs-cTnT (pg/mL) | 25 (16,42) | 14 (12,19) | 22 (16,32) | 31 (20,44) | 43 (27,66) | <0.001 |
| hsCRP (mg/L) | 3.7 (1.7,7.8) | 2.9 (1.5,5.4) | 2.7 (1.6,7.5) | 3.8 (2.1,7.7) | 5.9 (3.0,15.2) | <0.001 |
| MCP-1 (pg/mL) | 204 (169,245) | 183 (152,221) | 197 (164,224) | 222 (173,255) | 215 (181,276) | <0.001 |
| Clinical characteristics | ||||||
| Age (years) | 78 (11) | 71 (11) | 78 (10) | 82 (9) | 82 (9) | <0.001 |
| Female | 151 (44%) | 36 (46%) | 45 (47%) | 33 (38%) | 37 (45%) | 0.63 |
| Body mass index (kg/m2) | 28.8 (6.5) | 30.1 (6.2) | 29.8 (6.7) | 28.0 (6.4) | 27.1 (6.0) | 0.005 |
| SBP (mmHg) | 133 (23) | 137 (16) | 132 (22) | 135 (25) | 128 (25) | 0.031 |
| STS score | 7.5 (5.8) | 3.6 (3.3) | 6.4 (5.1) | 9.0 (6.1) | 10.7 (5.5) | <0.001 |
| Atrial arrhythmia | 110 (32%) | 4 (5%) | 28 (29%) | 35 (40%) | 43 (52%) | <0.001 |
| Coronary disease | 248 (72%) | 48 (62%) | 66 (69%) | 62 (71%) | 72 (87%) | 0.002 |
| Previous CABG | 116 (34%) | 19 (24%) | 26 (27%) | 34 (39%) | 37 (45%) | 0.014 |
| Prior myocardial infarction | 86 (25%) | 15 (19%) | 15 (16%) | 24 (28%) | 32 (39%) | 0.003 |
| Obstructive lung disease | 155 (45%) | 28 (35%) | 40 (42%) | 43 (49%) | 44 (53%) | 0.10 |
| Peripheral vascular disease | 191 (55%) | 27 (34%) | 52 (54%) | 53 (61%) | 59 (71%) | <0.001 |
| Diabetes | 123 (36%) | 21 (27%) | 31 (32%) | 32 (37%) | 39 (47%) | 0.048 |
| Syncope | 38 (11%) | 11 (14%) | 7 (7%) | 11 (13%) | 9 (11%) | 0.50 |
| Angina | 107 (31%) | 30 (38%) | 29 (30%) | 24 (28%) | 24 (29%) | 0.49 |
| NYHA class III/IV | 253 (73%) | 40 (51%) | 70 (73%) | 67 (77%) | 76 (92%) | <0.001 |
| GFR (mL/min/1.73m2) | 70 (27) | 85 (21) | 74 (21) | 66 (32) | 58 (24) | <0.001 |
| Medications (%) | ||||||
| ASA or antiplatelet | 242 (70%) | 58 (73%) | 66 (69%) | 59 (68%) | 59 (71%) | 0.86 |
| βblockers | 204 (59%) | 44 (56%) | 53 (55%) | 50 (57%) | 57 (69%) | 0.23 |
| ACE-I or ARB | 156 (45%) | 35 (44%) | 50 (52%) | 38 (44%) | 33 (40%) | 0.41 |
| Calcium channel blocker | 96 (28%) | 25 (32%) | 33 (34%) | 13 (15%) | 25 (30%) | 0.013 |
| Statins | 227 (66%) | 59 (75%) | 63 (66%) | 53 (61%) | 52 (63%) | 0.25 |
| Loop diuretic | 172 (50%) | 15 (19%) | 46 (48%) | 47 (54%) | 64 (77%) | <0.001 |
| Aldosterone antagonist | 29 (8%) | 2 (3%) | 7 (7%) | 9 (10%) | 11 (13%) | 0.07 |
| Echocardiography | ||||||
| AVA index (cm2/m2) | 0.38 (0.10) | 0.41 (0.10) | 0.39 (0.09) | 0.36 (0.10) | 0.37 (0.10) | 0.004 |
| Mean gradient (mmHg) | 42 (13) | 41 (11) | 42 (13) | 43 (14) | 41 (14) | 0.52 |
| Peak gradient (mmHg) | 68 (20) | 67 (18) | 69 (20) | 70 (20) | 67 (23) | 0.49 |
| Ejection fraction (%) | 58 (15) | 64 (13) | 60 (14) | 57 (15) | 49 (15) | <0.001 |
| LVED dimension (cm) | 4.6 (0.7) | 4.4 (0.8) | 4.5 (0.7) | 4.6 (0.7) | 4.7 (0.7) | 0.035 |
| LVES dimension (cm) | 3.1 (0.9) | 2.8 (1.0) | 2.9 (0.8) | 3.2 (0.9) | 3.5 (1.0) | <0.001 |
| LV mass index (g/m2) | 119 (38) | 119 (39) | 110 (32) | 125 (40) | 124 (41) | 0.07 |
| e' (cm/s) | 5.4 (1.7) | 5.7 (1.9) | 5.4 (1.6) | 5.1 (1.4) | 5.4 (1.9) | 0.27 |
| E/e' | 20 (11) | 17 (9) | 20 (9) | 21 (12) | 22 (11) | 0.008 |
| Moderate/severe MR | 37 (11%) | 2 (3%) | 5 (5%) | 14 (16%) | 16 (19%) | <0.001 |
| PASP (mmHg) | 41 (13) | 35 (10) | 37 (12) | 44 (13) | 48 (13) | <0.001 |
| Treatment and outcome | ||||||
| TAVR (%) | 183 (53%) | 26 (33%) | 42 (44%) | 57 (66%) | 58 (70%) | <0.001 |
| Died (%) | 91 (26%) | 7 (9%) | 15 (16%) | 31 (36%) | 38 (46%) | <0.001 |
Data shown as n (%), mean (SD), or median (25th, 75th percentiles).
The three biomarkers considered for elevation included GDF15, sST2 and NTproBNP (based on their median values).
Continuous variables were evaluated for differences using an overall F-test from an analysis of variance; Fisher's exact test was used to identify differences in distributions among levels of categorical data; non-normal and ordinal data were compared using the Kruskal–Wallis test.
ARB, angiotensin receptor blocker; ASA, aspirin; AVA, aortic valve area; CABG, coronary artery bypass grafting; GDF15, growth differentiation factor 15; GFR, glomerular filtration rate; hsCRP, high-sensitivity C reactive protein; LVED, LV end-diastolic dimension; LVES, LV end-systolic dimension; MPO, myeloperoxidase; MR, mitral regurgitation; NTproBNP, amino-terminal pro-B-type natriuretic peptide; NYHA, New York Heart Association; PASP, pulmonary artery systolic pressure; SBP, systolic blood pressure; sST2, soluble ST2; STS, Society of Thoracic Surgeons; TAVR, transcatheter aortic valve replacement.