Role of renin–angiotensin–aldosterone system activation and other metabolic variables in relation to arterial inflammation in HIV
Abstract
Background
Arterial inflammation remains increased among persons with HIV (PWH) compared with persons without HIV (PWOH) even when controlling for traditional risk factors. We sought to understand whether increased renin–angiotensin–aldosterone system (RAAS) activation may be related to arterial inflammation in PWH and when compared with PWOH.
Design
Twenty PWH and 9 PWOH followed a controlled, standardized low and liberal sodium diet to simulate a RAAS-activated and RAAS-suppressed state, respectively. We measured serum lipoprotein-associated phospholipase A2 (LpPLA2) concentrations following both conditions to assess the physiologic dynamics of aldosterone in relation to arterial inflammation.
Results
LpPLA2 levels were significantly higher among PWH versus PWOH during both the RAAS-activated state[5.3(4.2, 6.1) versus 4.0(3.0, 4.8)nmol/L, median(interquartile range),p = .01]) and RAAS-suppressed state[4.4(3.9, 5.3) versus 3.8(3.4, 4.1)nmol/L,p = .01]. Among PWH, but not PWOH, LpPLA2 increased significantly with RAAS activation(p = .03). LpPLA2 levels measured during the RAAS-suppressed state among PWH remained relatively higher than LpPLA2 levels under both conditions among PWOH. Log LpPLA2 was related to log aldosterone during the RAAS-activated state(r = .39,p = .04) among all participants. Log LpPLA2 was correlated with visceral fat(r = .46,p = .04) and log systolic blood pressure(r = .57,p = .009) during a RAAS-activated state when an increase in aldosterone was stimulated in HIV.
Conclusion
LpPLA2 is increased during a RAAS-activated state among PWH, but not among PWOH. Further, LpPLA2 was increased in both RAAS-activated and suppressed states in PWH compared with PWOH. These data suggest a biological link between increased aldosterone and arterial inflammation in this population. Future studies should test RAAS blockade on arterial inflammation as a targeted treatment approach in HIV.
CONFLICTS OF INTEREST
S. S. was the recipient of a Gilead Sciences Research Scholars award. G. K. A. has received consulting fees from Pfizer. S. K. G. has received research funding from KOWA, Gilead, Viiv, and Theratechnologies as well and consulting fees from Theratechnologies and Viiv. All disclosures are unrelated to this manuscript. The remaining authors declare no conflict of interest.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
