Impact of angiotensin receptor-neprilysin inhibition on cardiovascular function
| Author(s) | Nathaniel, Sangeetha Dianne | |
| Date Accessioned | 2021-01-28T12:39:45Z | |
| Date Available | 2021-01-28T12:39:45Z | |
| Publication Date | 2020 | |
| SWORD Update | 2020-10-13T19:03:22Z | |
| Abstract | Angiotensin Receptor–Neprilysin Inhibitors (ARNi) elicits greater reductions in blood pressure (BP) and is more effective at reducing mortality in heart failure patients with reduced ejection fraction (HFrEF) when compared to patients on conventional treatment including angiotensin converting enzyme inhibitors or angiotensin receptor blockers. The mechanisms contributing to the reduction in mortality are likely beyond the BP lowering effects of ARNi, but remain unclear. Changes in endothelial function and arterial stiffness, as well as BP response to exercise have prognostic value for future cardiovascular events and mortality. Lifestyle interventions and therapeutics have been aimed at improving vascular function and BP in HFrEF, however the impact of ARNi on vascular function and BP response to exercise have yet to be determined. PURPOSE: To test the hypothesis that endothelial function, arterial stiffness, central BPs, and BP response during handgrip exercise would improve after 12 weeks of ARNi in HFrEF. METHODS: HFrEF participants completed experimental visits at baseline and 12 weeks later: 13 participants were prescribed ARNi by their cardiologist [62±10 years, EF: 28±6 %], whereas 10 participants continued on conventional treatment [CON: 60±7 years, EF: 31±5 %; all P=NS]. During each experimental visit, endothelial function was assessed by brachial artery flow‐mediated dilation (FMD), arterial stiffness was assessed via pulse wave velocity (PWV), and central BPs were assessed using radial applanation tonometry. BP responses to isometric handgrip exercise (IHG) were measured at rest, during 2-minutes IHG at 30% maximal voluntary contraction (MVC) followed by post exercise ischemia (PEI) to isolate the metaboreflex. Similarly, BP was measured during 2 minutes of DHG, followed by PEI. Statistical comparisons were performed using 2x2 repeated-measures ANOVA. RESULTS: At baseline, systolic BP (SBP) was not significantly different between ARNi (137±25 mmHg) and CON (120±18 mmHg; P=0.09); 12 weeks of ARNi therapy improved SBP (120±17 mmHg; P<0.01) and there was no change in CON (130±31 mmHg; P=0.07) (ANOVA group P=0.70; time: P=0.39; interaction P<0.01). Diastolic BP (DBP) at baseline in the ARNi group (77±10 mmHg) had higher DBP compared to CON (69±7 mmHg; P=0.04); 12 weeks of ARNi therapy improved DBP (71±9 mmHg; P=0.04) and there was no change in CON (71±10 mmHg; P=0.35) (ANOVA group P=0.28; time P = 0.46; interaction P=0.04). Baseline peripheral mean arterial pressure (MAP) was similar in ARNi (96 ± 13 mmHg) and CON (86 ± 9 mmHg; P=0.06); MAP decreased after 12 weeks of ARNi (87 ± 11 mmHg; P=0.01) but was unchanged in CON (92 ± 17 mmHg; P=0.14) (ANOVA group P=0.65; time P=0.51; interaction P<0.01). At baseline, FMD was similar between ARNi (2.81 ± 2.05%) and CON (4.75 ± 3.75%; P=0.13); however, FMD increased after 12 weeks of ARNi (5.73 ± 1.87%; P<0.001) but not in CON (5.37 ± 3.38%; P=0.33) (ANOVA Time P=0.<0.001, Drug P=0.48, Interaction P=0.01). PWV was similar at baseline in ARNi (8.8 ± 2.5 m/s) and CON (7.0 ± 2.5 m/s; P=0.09); PWV decreased after 12 weeks of ARNi (7.0 ± 1.7 m/s; P<0.01) and was unchanged in CON (7.4 ± 2.4 m/s; P=0.33) (ANOVA Time P=0.09, Drug P=0.40, Interaction P<0.01). When controlling for MAP, the effect of ARNi on PWV remained (ARNi visit 1 vs. visit 2 P<0.01; ANOVA interaction P<0.01). At baseline, central SBP (cSBP) was not significantly different between ARNi (124 ± 21 mmHg) and CON (108 ± 15 mmHg; P=0.08); 12 weeks of ARNi therapy improved cSBP (111 ± 17 mmHg; P<0.01) and there was no change in CON (118 ± 25 mmHg; P=0.08) (ANOVA group P=0.70; time P=0.56; interaction P <0.01). And for central DBP (cDBP), at baseline ARNi group (78 ± 10 mmHg) had higher cDBP compared to CON (69 ± 6 mmHg; P=0.03); 12 weeks of ARNi therapy improved cDBP (72 ± 9 mmHg; P=0.04) and there was no change in CON (73 ± 11 mmHg; P=0.29) (ANOVA group P=0.31; time P = 0.49; interaction P=0.03). A subgroup of participants (ARNi:12 and CON:7) underwent IHG. During IHG, resting MAP (Finometer) was similar between ARNi (97±14 mmHg) and CON (92±12 mmHg; P=0.45) and MAP increased similarly during IHG (ARNi: Δ 14±7 vs. CON: 11±10 mmHg; P=0.52) and PEI (ARNi: Δ 11±10 vs. CON: 8±11 mmHg; P=0.47). Resting MAP was unchanged after 12 weeks of ARNi (96±13 mmHg) and in CON (97±18 mmHg; P=0.75). There was a non-significant attenuation in MAP during IHG (ARNi: Δ 7±13 vs. CON: 13±7 mmHg; P=0.48) and PEI (ARNi: Δ 8±7 vs. CON: 12±6 mmHg; P=0.53) after 12 weeks of ARNi therapy (ANOVA Time P=0.31, Drug P=0.58, Interaction P=0.27). A subgroup of participants completed the DHG protocol (ARNi:10 and CON: 6). At baseline, resting MAP was similar between ARNi (98±2 mmHg) and CON (90±11 mmHg; P=0.28) and MAP increased similarly during DHG (ARNi: Δ 3±4 vs. CON: 8±7 mmHg; P=0.23) and PEI (ARNi: Δ 1±4 vs. CON: 6±4 mmHg; P=0.09). Resting MAP was unchanged after 12 weeks of ARNi (94±12 mmHg) and in CON (98±19 mmHg; P=0.96). The increase in MAP during DHG (ARNi: Δ 5±6 vs. CON: 4±6 mmHg; P=0.97) and PEI (ARNi: Δ 3±4 vs. CON: 3±4 mmHg; P=0.49) after 12 weeks was not impacted by ARNi (ANOVA Time P=0.50; Drug P=0.20; interaction P=0.18). CONCLUSION: These data demonstrate that 12 weeks of ARNi therapy improves endothelial function, reduces arterial stiffness, and reduces central BPs in HFrEF. Preliminary findings do not support an effect of ARNi on lowering BP during IHG in HFrEF, although ARNi demonstrated a greater magnitude drop in BP response to IHG exercise. There was no effect on BP response to DHG in HFrEF using ARNi; additional data are needed to fully characterize the impact of ARNi on BP response to exercise. ☐ Keywords: Heart failure with reduced ejection fraction, Angiotensin Receptor–Neprilysin Inhibitors, Cardiovascular function | en_US |
| Advisor | Wenner, Megan M. | |
| Degree | Ph.D. | |
| Department | University of Delaware, Department of Kinesiology and Applied Physiology | |
| DOI | https://doi.org/10.58088/yv2n-tb80 | |
| Unique Identifier | 1233173824 | |
| URL | https://udspace.udel.edu/handle/19716/28554 | |
| Language | en | |
| Publisher | University of Delaware | en_US |
| URI | https://login.udel.idm.oclc.org/login?url=https://www.proquest.com/dissertations-theses/impact-angiotensin-receptor-neprilysin-inhibition/docview/2455532995/se-2?accountid=10457 | |
| Keywords | Angiotensin receptor-neprilysin inhibitors | en_US |
| Keywords | Arterial stiffness | en_US |
| Keywords | Cardiovascular function | en_US |
| Keywords | Endothelial function | en_US |
| Keywords | Heart failure with reduced ejection fraction | en_US |
| Keywords | Wave reflection | en_US |
| Title | Impact of angiotensin receptor-neprilysin inhibition on cardiovascular function | en_US |
| Type | Thesis | en_US |