Novel Insights into Salt-Sensitivity of Blood Pressure in African Adults with and without HIV: Comprehensive Inflammatory, renal and Cardiometabolic Profiling in a Zambian Cohort

BackgroundSalt sensitivity of blood pressure (SSBP) amplifies cardiovascular risk in hypertension. Although we previously found that SSBP was more prevalent in people with HIV (PWH) compared to the HIV-uninfected, yet its determinants in PWH remain understudied in sub-Saharan Africa. In this study, we hypothesized that chronic inflammation and cardiometabolic disturbances would be uniquely associated with SSBP in Zambian adults with and without HIV. MethodsWe performed a cross-sectional SSBP assessment in 366 adults (269 PWH, 97 without HIV [PWTH]). We also performed echocardiography, carotid ultrasonography, flow-mediated dilation, lipid profiles, renal function, inflammatory markers, taste perception, and 24-hour dietary recalls. SSBP was defined as a [&ge;]10mmHg mean arterial pressure increase between high-salt and low-salt intervention. Multivariate logistic regression models were used to identify independent correlates of SSBP in the overall population (adjusted for age, sex, and HIV status) and separately in PWH and PWTH (adjusted for age and sex). ResultsIn the overall population multivariate analysis, hypertension (AOR=12.28), IPROS (AOR=5.70), peripheral artery disease (AOR=2.63), left ventricular hypertrophy (AOR=2.31), and higher cardiovascular risk scores were independently associated with SSBP. PWH were older (49 {+/-} 12 vs. 44 {+/-} 17 years, p= 0.015) and exhibited lower BMI (25.04 vs. 26.44 kg/m{superscript 2}, p=0.045) and waist circumference (83.79 vs. 87.76 cm, p= 0.037) than PWTH. PWH demonstrated elevated salt-taste recognition thresholds (0.467 vs. 0.233 g/0.5L, p= 0.0014) and dysregulated metabolic/inflammatory profiles, including higher triglycerides, d-dimer, high-sensitivity C-reactive protein (hs-CRP), IL-6, and hormonal profile including renin, aldosterone, angiotensin II, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (p< 0.05). Hypertension strongly predicted SSBP in both groups in univariate (PWH: OR = 13.08, 95% CI 6.62-25.81; PWTH: OR = 28.33, 95% CI 7.69-104.35, p<0.001) and multivariate analysis (PWH: AOR = 10.27, 95% CI 5.02-21.00; PWTH: AOR = 24.68, 95% CI 5.45-111.73, P<0.0001). In multivariate analysis, an immediate pressor response to oral salt (IPROS) was independently associated with SSBP in PWH (AOR = 19.90, 95% CI 6.61-59.91) and PWTH (AOR = 18.49, 95% CI 2.14-159.28). In a comprehensive multivariate model, larger waist circumference was associated with reduced odds of SSBP (AOR=0.94 per cm, p=0.016), while greater left ventricular posterior wall thickness was associated with increased odds (AOR=21.44, p=0.027) among PWH. Left ventricular mass index, atherosclerotic cardiovascular disease (ASCVD) risk and plasma creatinine were additional correlates in PWH (p< 0.01) but not in PWTH. In PWTH, atrial natriuretic peptide (AOR=1.00, 95% CI 1.00-1.00, p=0.021) and peripheral artery disease (AOR= 5.39, 95% CI 1.20-24.06, p=0.027) were the only unique factors associated with SSBP compared to PWH. ConclusionSSBP in this Zambian cohort is associated with a complex interplay of traditional and HIV-specific factors. The strong independent association of IPROS with SSBP across all analyses supports its potential utility as a clinical screening tool. The distinct correlates in PWH, particularly the prominent role of cardiac structural changes and the unexpected association with marital status, highlight the need for HIV-specific approaches to salt sensitivity assessment and management.