Table 3.
Clinical Characteristics and Biomarkers by Neprilysin Tertiles
| Variable | sNEP ≤1.4 (n=516) | sNEP 1.5–22.6 (n=514) | sNEP >22.6 (n=506) | Unadjusted Trend P Value | BMI‐Adjusted Trend P Value | Adjusted Trend P Valuea |
|---|---|---|---|---|---|---|
| Clinical characteristics | ||||||
| Age at exam, y | 63.52±10.35 | 62.16 ±10.41 | 62.79±10.83 | 0.27 | 0.25 | 0.16 |
| Female | 270 (52) | 275 (54) | 258 (51) | 0.67 | 0.59 | 0.11 |
| BMI, kg/m2 | 28.30±5.30 | 28.76±5.54 | 27.99±5.05 | 0.37 | … | 0.30 |
| BMI >30, kg/m2 | 166 (32) | 186 (36) | 139 (27) | 0.11 | … | 0.08 |
| Increased WCb | 165 (32) | 183 (36) | 158 (31) | 0.79 | … | 0.91 |
| Smoking status | <0.001 | <0.001 | <0.001 | |||
| Never | 217 (42) | 254 (50) | 286 (57) | |||
| Former | 234 (45) | 214 (42) | 192 (38) | |||
| Current | 64 (12) | 43 (8) | 27 (5) | |||
| Current/former smoker | 298 (58) | 257 (50) | 219 (43) | <0.001 | <0.001 | <0.001 |
| Diabetes mellitus | 41 (8) | 37 (7) | 36 (7) | 0.61 | 0.73 | 0.86 |
| Hypertension | 164 (32) | 144 (28) | 131 (26) | 0.04 | 0.05 | 0.09 |
| AF/flutter | 31 (6) | 25 (5) | 27 (5) | 0.63 | 0.62 | 0.82 |
| CAD | 60 (12) | 64 (12) | 58 (11) | 0.94 | 0.96 | 0.48 |
| Prior MI | 25 (5) | 23 (4) | 26 (5) | 0.83 | 0.80 | 0.50 |
| Prior stroke | 13 (3) | 4 (1) | 8 (2) | 0.24 | 0.24 | 0.34 |
| Metabolic syndrome | 103 (20) | 127 (25) | 97 (19) | 0.77 | 0.91 | 0.71 |
| SDP, mm Hg | 134.17±21.97 | 131.79±21.00 | 132.53±21.40 | 0.22 | 0.28 | 0.49 |
| DBP, mm Hg | 74.10±10.55 | 73.29±10.30 | 73.26±9.76 | 0.19 | 0.24 | 0.17 |
| Total cholesterol | 204.79±33.22 | 202.23±34.61 | 203.32±36.98 | 0.50 | 0.48 | 0.66 |
| Antilipemic therapy | 96 (20) | 88 (18) | 71 (15) | 0.03 | 0.04 | 0.07 |
| Creatinine | 0.80 (0.70–1.00) | 0.80 (0.70–0.90) | 0.80 (0.70–1.00) | 0.28 | 0.26 | 0.31 |
| Estimated GFR mL/minc | 85.01±24.79 | 85.38±24.38 | 82.85±21.65 | 0.25 | 0.25 | 0.17 |
| GFR <60 mL/min | 54 (10) | 57 (11) | 59 (12) | 0.54 | 0.55 | 0.45 |
| Insulin (μU/mL) | 4.80 (3.50–7.50) | 5.50 (3.80–8.40) | 5.00 (3.40–7.40) | 0.94 | 0.68 | 0.51 |
| Serum glucose | 95.00 (89.00–101.00) | 94.00 (89.00–102.00) | 93.00 (88.00–100.00) | 0.21 | 0.28 | 0.52 |
| Cardiac structure and function | ||||||
| EF | 62.76±7.21 | 62.94±7.19 | 62.65±7.25 | 0.80 | 0.80 | 0.63 |
| EF <45% | 14 (3) | 10 (2) | 11 (2) | 0.56 | 0.56 | 0.78 |
| MS DD | 42 (9) | 37 (8) | 26 (6) | 0.04 | 0.04 | 0.08 |
| Mild/MS DD | 151 (33) | 130 (28) | 121 (27) | 0.02 | 0.02 | 0.06 |
| MS DD except EF <45% | 38 (9) | 30 (7) | 24 (5) | 0.06 | 0.05 | 0.07 |
| Mild/MS DD except EF <45% | 141 (32) | 121 (27) | 115 (26) | 0.04 | 0.04 | 0.07 |
| LVH | 134 (35) | 128 (32) | 133 (35) | 0.28 | 0.32 | 0.52 |
| E/A ratio | 1.09±0.43 | 1.12±0.44 | 1.10±0.37 | 0.90 | 0.97 | 0.40 |
| E/e′ | 8.59±3.08 | 8.75±3.05 | 8.61±3.15 | 0.93 | 0.90 | 0.60 |
| Left atrial size | 3.94±0.67 | 3.89±0.63 | 3.93±0.72 | 0.68 | 0.93 | 0.79 |
| Estimated PASP | 23.03±5.20 | 22.60±5.11 | 22.52±5.09 | 0.18 | 0.21 | 0.39 |
| Serum biomarkers | ||||||
| Aldosterone | 4.90 (2.50–7.90) | 4.30 (2.50–7.80) | 4.90 (2.70–8.30) | 0.84 | 0.79 | 0.71 |
| NT‐proANP | 2284.0 (1469.0–3554.0) | 2077.0 (1329.0–3122.0) | 2375.0 (1436.0–3433.0) | 0.53 | 0.46 | 0.77 |
| NT‐proBNP | 75.36 (31.84–153.80) | 62.30 (24.59–133.80) | 68.52 (28.60–141.70) | 0.61 | 0.56 | 0.88 |
| BNP | 15.70 (6.30–33.80) | 13.70 (4.70–28.80) | 15.85 (6.70–32.30) | 0.85 | 0.86 | 0.57 |
| ANP | 11.60 (7.40–17.60) | 12.05 (7.10–16.50) | 11.65 (7.10–15.40) | 0.19 | 0.20 | 0.31 |
| sNEP | 0.65 (0.40–0.96) | 4.11 (2.13–8.80) | 119.00 (43.68–576.20) | … | … | … |
| Adiponectin | 9.80 (6.60–15.40) | 9.40 (6.40–14.30) | 9.60 (6.40–14.05) | 0.65 | 0.47 | 0.77 |
| Outcomesd | ||||||
| Death, K–M (no. of events) | 0.007 | 0.008 | 0.24 | |||
| 1 y | 0.99 (3) | 1.00 (2) | 0.99 (3) | |||
| 5 y | 0.94 (29) | 0.95 (27) | 0.95 (25) | |||
| 10 y | 0.86 (69) | 0.88 (60) | 0.87 (64) | |||
| HF, K–M (no. of events) | 0.80 | 0.85 | 0.28 | |||
| 1 y | 0.98 (12) | 0.98 (8) | 0.97 (13) | |||
| 5 y | 0.93 (34) | 0.94 (27) | 0.92 (36) | |||
| 10 y | 0.86 (62) | 0.88 (52) | 0.87 (58) | |||
Data are shown as mean±SD, number (percentage), or median (interquartile range). AF indicates atrial fibrillation; ANP, A‐type natriuretic peptide; BMI, body mass index; BNP, brain (B‐type) natriuretic peptide; CAD, coronary artery disease; DD indicates diastolic dysfunction; EF, ejection fraction; GFR, glomerular filtration rate; HF, heart failure; K–M, Kaplan–Meier; LVH, left ventricular hypertrophy; MI, myocardial infarction; MS, moderate or severe; NT‐pro, N‐terminal pro; PASP, pulmonary artery systolic pressure; sNEP, serum neprilysin; WC, waist circumference.
Adjusted for age, sex, BMI, and smoking.
Increased WC defined by as >102 cm in men, and >88 cm in women.
By Modification of Diet in Renal Disease.
Outcome data presented showing K–M survival estimates and number of observed events at 1, 5, and 10 y.