AbstractHigh-altitude polycythemia (HAPC) is a pathological state resulting from maladaptation to prolonged high-altitude exposure, posing significant risks to the cardiovascular health of highlanders. However, its influence on hypertension-mediated organ damages (HMODs) in hypertensive individuals remains unclear. We recruited hypertensive patients residing at altitudes above 2500 m for over 3 years. A case–control matching was conducted in a 1:1 ratio between hypertensive patients with and without HAPC, based on gender and age. Echocardiography, carotid artery ultrasound, and brachial flow-mediated dilation (FMD) were measured as HMODs. A total of 88 hypertensive patients were included in the analysis, with 44 with HAPC and 44 without HAPC. Patients with HAPC showed significantly higher hemoglobin (HGB) levels (217.82 ± 17.34 vs. 160.16 ± 13.25, P<0.001), a larger left atrium (LA) diameter (35.36 ± 4.25 vs. 33.09 ± 3.55, P = 0.008), and a higher proportion of impaired FMD (95.45% vs. 79.55%, P = 0.049) compared to those without HAPC. No significant differences were found between the two groups in diastolic function parameters, left ventricular mass index (LVMI), relative wall thickness (RWT), or intima-media thickness (IMT). After adjusting for age, gender, and other confounding factors, HGB remained significantly associated with LA diameter (β = 0.034, P = 0.023) and impaired FMD (OR = 1.034, 95% CI 1.001–1.069). After matching for age and gender, hypertensive patients with HAPC exhibited a significantly larger LA diameter and a higher prevalence of impaired FMD compared to those without HAPC. Additionally, HGB was identified as an independent risk factor for both increased LA diameter and impaired FMD in hypertensive patients with HAPC.