Table 4.
Blood pressure, heart rate, and heart rate variability metrics in patients with lipodystrophy before and after initiation or withdrawal of metreleptin
| Initiation | Withdrawal | Combined | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline (n = 14) | 24 h (n = 13) | 2 weeks (n = 13) | 6 months (n = 10) | P * | Baseline (n = 7) | 24 h (n = 7) | 2 weeks (n = 7) | P * | Off (n = 21) | On (n = 20) | P | |
| Systolic BP (mmHg) | 135 ± 14 | 136 ± 14 | 133 ± 12 | 132 ± 18 | 0.9 | 133 ± 14 | 126 ± 10f | 129 ± 8 | 0.4 | 133 ± 12 | 133 ± 13 | 0.6 |
| Diastolic BP (mmHg) | 77 ± 8 | 77 ± 10 | 75 ± 7 | 73 ± 9 | 0.7 | 73 ± 6 | 71 ± 3f | 70 ± 8 | 0.6 | 75 ± 8 | 75 ± 7 | 0.8 |
| Heart rate (beats/ min) | 84 ± 15a | 85 ± 13 | 81 ± 12b | 75 ± 13c | 0.002 | 73 ± 7 | 79 ± 8 | 75 ± 6 | 0.07 | 81 ± 13e | 78 ± 11g | 0.2 |
| SDNN (msec) | 68 ± 27a | 69 ± 29 | 76 ± 27b | 76 ± 21c | 0.0026m | 95 ± 18 | 87 ± 25 | 87 ± 29 | 0.0324hr | 75 ± 28e | 84 ± 27g | 0.02 |
| VLF (msec2) | 1576 ± 1063a | 1525 ± 1166 | 1845 ± 1330b | 1977 ± 1129 c | 0.03 | 2612 ± 748 | 2346 ± 1074 | 2096 ± 961 | 0.07 | 1758 ± 1034e | 2174 ± 1263g | 0.03 |
| LF (msec2) | 504 (346 1468)a | 517 (343 1760) | 677 (452 2755)b | 878 (634 1644) c | 0.026m | 1570 (586 1728) | 1455 (300 1917) | 1424 (347 1715) | 0.1 | 665 (357 1574)e | 679 (563 2112)g | 0.003 |
| HF (msec2) | 257 (121 969)a | 189 (92 901) | 488 (144 1463)b | 265 (133 1101) c | 0.08 | 473 (309 1492) | 643 (116 1461) | 609 (155 2645) | 0.1 | 293 (150 1426)e | 473 (203 1492)g | 0.004 |
| LF/HF | 3.3 ± 1.7a | 3.3 ± 1.7 | 3.0 ± 1.6b | 3.8 ± 1.8c | 0.5 | 3.7 ± 2.1 | 3.5 ± 1.4 | 3.0 ± 1.4 | 0.2 | 3.2 ± 1.5e | 3.2 ± 1.8g | 0.6 |
| Sleeping heart rate (beats/min) | 75 ± 14a | 73 ± 13 | 71 ± 12b | 66 ± 10d | 0.1 | 68 ± 12 | 65 ± 10 | 66 ± 7 | 0.7 | 72 ± 13e | 70 ± 12g | 0.5 |
| Sleeping SDNN (msec) | 81 ± 41a | 79 ± 38 | 87 ± 36b | 87 ± 17d | 0.4 | 101 ± 25 | 109 ± 53 | 100 ± 37 | 0.7 | 88 ± 40e | 92 ± 32g | 0.5 |
| Sleeping VLF (msec2) | 2015 ± 1636a | 1727 ± 1056 | 2076 ± 1311b | 2273 ± 690d | 0.2 | 3636 ± 1619 | 3312 ± 2089 | 2710 ± 1405 | 0.4 | 2259 ± 1559e | 2651 ± 1588g | 0.2 |
| Sleeping LF (msec2) | 762 (370 1815)a | 529 (325 2856) | 838 (445.9 3424)b | 833 (636 2878)d | 0.1 | 1974 (586 2391) | 2469 (383 2888) | 2110 (432 2851) | 0.6 | 1138 (438 2354)e | 1024 (586 2407)g | 0.2 |
| Sleeping HF (msec2) | 366 (143 1331)a | 408 (123 1611) | 688 (149 1986)b | 412 (159 1505)d | 0.1 | 822 (245 1653) | 1282 (162 2952) | 1224 (209 4112) | 0.7 | 466 (193 1922)e | 822 (212 1653)g | 0.6 |
| Sleeping LF/HF | 2.8 ± 1.8a | 2.5 ± 2.2 | 2.5 ± 2.0b | 3.6 ± 2.4d | 0.6 | 3.4 ± 2.8 | 2.3 ± 1.2 | 2.3 ± 1.2 | 0.4 | 2.6 ± 1.6e | 2.8 ± 2.3g | 1 |
| Waking heart rate (beats/min) | 87 ± 14a | 89 ± 13 | 84 ± 12b | 76 ± 13c | 0.00046m | 75 ± 6 | 83 ± 8 | 77 ± 6 | 0.1 | 84 ± 13e | 80 ± 11g | 0.1 |
| Waking SDNN (msec) | 63 ± 23a | 65 ± 23 | 74 ± 28b | 75 ± 22c | 0.0026mo | 93 ± 17 | 81 ± 21 | 84 ± 27 | 0.029 24hr | 71 ± 26e | 81 ± 26g | 0.03 |
| Waking VLF (msec2) | 1366 ± 926a | 1375 ± 1002 | 1871 ± 1510b | 1937 ± 1252c | 0.6 | 2316 ± 823 | 2092 ± 886 | 1920 ± 902 | 0.8 | 1560 ± 934e | 2035 ± 1292g | 0.1 |
| Waking LF (msec2) | 456 (326 1369)a | 514 (290 1416) | 669 (386 2548)b | 905 (592 1487)c | 0.0042w, 6mo | 1349 (609 1516) | 1362 (342 1772) | 1027 (392 1525) | 0.8 | 555 (346 1424)e | 750 (512 1684)g | 0.01 |
| Waking HF (msec2) | 214 (99 870)a | 141 (84 713) | 312 (123 1346)b | 252 (133 1024)c | 0.016mo | 376 (328 1318) | 474 (104 1069) | 439 (140 1752) | 0.7 | 229 (115 1291)e | 341 (198 1318)g | 0.2 |
| Waking LF/HF | 3.4 ± 1.8a | 3.5 ± 1.7 | 3.1 ± 1.6b | 3.8 ± 1.7c | 0.1 | 3.8 ± 2.0 | 3.9 ± 1.6 | 3.3 ± 1.5 | 0.2 | 3.4 ± 1.6e | 3.4 ± 1.7g | 0.5 |
Data show the mean ± SD for normally distributed metrics and median (interquartile range) for nonnormally distributed metrics. Patients in the initiation cohort have data prior to initiation of metreleptin (baseline) and after 2 weeks and 6 months of metreleptin administration. Patients in the withdrawal cohort have data during metreleptin treatment (baseline) and after 2 weeks of metreleptin withdrawal. The combined cohort includes baseline and 2 week data in both groups, categorized by on or off metreleptin status.
Abbreviations: BP, blood pressure; HF, high-frequency component is associated with parasympathetic regulation; LF, low-frequency component is associated with both sympathetic and parasympathetic regulation; LF/HF ratio is associated with sympathetic regulation; SDNN, standard deviation of the normal-to-normal interbeat interval is a measure of overall heart rate variability; VLF, very low frequency component of heart rate variability power spectrum is associated with renin/angiotensin regulation of heart rate variability. *Overall P-value for linear mixed-effects regression is shown. 24hrP < 0.05 for baseline vs 24 h. 2wP < 0.05 for baseline vs 2 weeks. 6mP < 0.05 for baseline vs 6 months.
a n=13.
b n=12.
c n=8.
d n=7.
e n=20.
f n=6.
g n=19.