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.

Subclinical myocardial dysfunction is prevalent among well-treated persons with HIV (PWH). We have previously demonstrated unique renin-angiotensin-aldosterone system physiology among PWH with metabolic dysregulation. Mineralocorticoid receptor blockade may be a targeted treatment strategy for subclinical heart disease in PWH. Forty-six PWH were randomized to receive either eplerenone 50 mg daily or placebo in a 6-month randomized, double-blinded, placebo-controlled trial. We assessed changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP), a biomarker of cardiac stretch, under controlled posture and dietary conditions. The eplerenone- and placebo-treated groups demonstrated a long duration of HIV with good immunological control. NT-proBNP levels were similar between the groups at baseline (41.1 [20.2, 97.9] vs 48.9 [29.2, 65.4] ng/L, P = .80) and decreased significantly more in the eplerenone- vs placebo-treated groups after 6 months (change NT-proBNP -9.6 [-46.8, 0.3] vs -3.0 [-17.0, 39.9] ng/L, P = .02 for comparison of change between groups). Decreases in NT-proBNP were independent of changes in systolic and diastolic blood pressure, and related to decreases in high-sensitivity C-reactive protein (ρ = 0.32, P = .05) and inversely to increases in serum aldosterone (ρ = -0.33, P = .04) among all participants. Treatment with eplerenone for 6 months vs placebo significantly decreases NT-proBNP levels among PWH, independent of eplerenone’s known blood pressure-lowering effects. Further studies should elucidate whether lowering NT-proBNP in this at-risk metabolic population with subclinical heart disease will offer cardioprotection. Clinical Trial Registration NCT01405456

Context The SARS-CoV2 virus is dependent on components of the renin-angiotensin-aldosterone system(RAAS) for infectivity. Primary aldosteronism (PA) is a form of secondary hypertension mediated by autonomous aldosterone production. The intersection of COVID-19 and PA, both which may involve components of the RAAS, remains unknown. Methods We assessed PA as a risk factor for COVID-19 infection and compared management, severity of disease, and outcomes during COVID-19 with a matched population of essential hypertension(EH) patients by conducting a retrospective observational cohort study. Results Of the PA patients, 81 patients had a negative PCR test for COVID-19, while 43 patients had a documented positive PCR test for COVID-19. Those PA patients who tested positive for COVID-19 tended to be female(P = 0.08) and the majority of those with COVID-19 infection identified as non-white race(P = 0.02) and Hispanic ethnicity(P = 0.02). In a subanalysis, 24-hour urine aldosterone upon initial PA diagnosis tended to be higher in the PA group who developed COVID-19 compared to the PA group that did not develop COVID-19[36.5(16.9, 54.3) vs. 22.0(15.8, 26.8)mcg, P = 0.049] and was an independent predictor of COVID-19 infection controlling for sex, race, and ethnicity. ACEi, ARB, and MR use did not differ between those PA patients with and without COVID-19 infection. Comparing those PA and matched EH patients(n = 286) who were COVID-19 PCR positive, there was a significantly higher incidence of cardiovascular complications(12 vs. 2%, P = 0.004) in the PA vs. EH group. Conclusion These data begin to inform us as to whether PA should be a newly identified subpopulation at risk for COVID-19-related cardiovascular disease sequelae.