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Circulating Angiotensin II is Associated with Pro-Inflammatory Cytokines, Myocardial Stress, and Dyslipidemia Independent of Traditional Risk Factors in a High-HIV Population

Lwiindi, P. C.; Wandira, N.; Hamooya, B. M.; Povia, J. P.; Kirabo, A.; Masenga, S. K.

2025-12-09 pathology
10.64898/2025.12.08.25341856 medRxiv
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BackgroundWeve known Angiotensin II (Ang II) as a vasoconstrictor associated with hypertension and inflammation. However, its relationship with specific subclinical cardiovascular, lipid, kidney and inflammatory markers in populations of African ancestry with high HIV burden is not known. MethodsWe conducted a cross-sectional analysis of 220 participants attending routine care at a tertiary hospital from the general medical clinic. We collected sociodemographic information and blood specimens to assay for kidney, hormonal, hemodynamics, cardiovascular, metabolic and inflammatory profile. We used spearmans correlations and linear regression models to determine the correlates of Ang II. A p-value of <0.05 was considered significant. We used statcrunch to analyze data. ResultsThe median age in the population was 50 years, with a female preponderance (67.3%). The majority were living with HIV (PLWH), and 29.5% had hypertension. In simple linear regression, Ang II showed strong positive association with renin ({beta}=0.808, p<0.0001), aldosterone ({beta}=0.690, p<0.0001), inflammatory markers (IL-6: {beta}=46.099, p<0.0001; TNF-: {beta}=0.183, p<0.0001; IL-17A: {beta}=0.914, p<0.0001; IL-5: {beta}=1.7, p<0.0001; d-Dimer: {beta}=0.02, p<0.0001; IgE: {beta}=0.0007, p=0.0008; Soluble ST2: {beta}=107.9, p<0.0001), hs-CRP ({beta}=0.003, p=0.028), plasma potassium ({beta}=0.690, p<0.0001), plasma chloride ({beta}=166.2, p<0.0001), white blood cell count ({beta}=227.617, p=0.022), microalbumin ({beta}=6.62, p=0.029), and lipid ratios (Cholesterol/HDL: {beta}=400.352, p=0.022 and LDL/HDL ratio: {beta}=426.517, p=0.026). Inverse associations were observed with left ventricular mass ({beta}=-8.628, p=0.015), left ventricular diameter in diastole ({beta}=-709.064, p=0.048), and plasma sodium ({beta}=-203.474, p=0.014). In multiple linear regression adjusted for HIV, hypertension, BMI, and sex, renin ({beta}=0.476, p<0.0001), aldosterone ({beta}=0.577, p<0.0001), IL-6 ({beta}=21.000, p<0.0001), TNF- ({beta}=0.134, p<0.0001), IL-17A ({beta}=0.535, p<0.0001), Soluble ST2 ({beta}=78.3, p<0.0001), d-Dimer ({beta}=0.01, p=0.0005), Cholesterol/HDL ratio ({beta}=348.410, p=0.013), and plasma potassium ({beta}=11.285, p=0.040) remained significantly associated with Ang II. ConclusionCirculating Ang II is independently and strongly associated with key pro-inflammatory cytokines, markers of myocardial stress, coagulation, and atherogenic dyslipidemia, in a population with high HIV burden beyond traditional risk factors. The role of Ang II in this population remains to be investigated in large prospective studies.

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