Purpose: Here we investigate the hypothesis that PCSK9 inhibition improves impaired CEF in PLWH and in patients with dyslipidemia (DL).
Methods: Cine 3T MRI was used to noninvasively measure CEF, assessed as the change in coronary cross-sectional area (CSA) from rest to isometric handgrip exercise (IHE), a known endothelial-dependent vasodilator. Eight HIV+ subjects on stable highly active antiretroviral therapy and with undetectable HIV RNA (mean age 53±9 yrs, LDLC 98±18 mg/dL, 38% on statins) and ten patients with dyslipidemia (DL) without HIV receiving evolocumab for clinical reasons (mean age 56±10 yrs, LDLC 130±28 mg/dL, 50% on statins) underwent MRI studies before and six weeks following the initiation of evolocumab 420 mg. MRI readers were blinded to group and timepoint. MRI data are presented as mean±SD for % change rest vs IHE.
Results: Prior to evolucumab, resting CSA in the two groups did not differ and IHE did not induce normal coronary vasodilation in either group; mean stress-induced CSA changes were -2.1±6.4% in HIV (p=0.27) and -0.6±4.1% in DL (p=0.46). Notably, CEF significantly improved following six weeks of evolocumab with IHE-induced CSA changes of 7.6±5.7% (p=0.006) and 5.0±3.6% (p=0.002) in the HIV and DL groups, respectively. The %-LDLC reduction with evolocumab was profound and comparable in the HIV and DL groups, 73±5% and 60±6% (p=0.19 HIV vs. DL). There was no significant correlation between the extents of LDLC reduction and of CEF improvement in either of these modest sized groups.
Conclusion: PCSK9 inhibition with evolocumab significantly improves abnormal coronary endothelial function after only six weeks in HIV+ people with normal LDLC and in HIV- people with DL. To our knowledge, these data represent the earliest (6 weeks) evidence for improvement in human coronary artery health by PCSK9 inhibition.