Toxic effects of herbal supplements on endothelial and vascular system among rural Thai patients: A multicenter cohort study

BACKGROUND: The use of herbal supplements among elderly Thais has increased from 65.7% to 73.9% (2022-2024). Evidence regarding cardiovascular safety remains limited, particularly regarding interactions with potentially inappropriate medications (PIMs) in patients with multimorbidity and polypharmacy. This study investigated the association and incidences between herbal supplement use and vascular as well as endovascular diseases (VEDs) among elderly Thai patients. METHODS: A retrospective, propensity score-matched cohort study was carried out. Data were collected from electronic medical records at 12 community hospitals in Sakon Nakhon Province, Thailand (January 2022-December 2024). The cohort included 38,240 adults aged ≥60 years without baseline VEDs. Using 1:1 propensity score matching, we created matched cohorts of 11,587 pairs balanced for age, sex, comorbidities, and polypharmacy. We compared herbal supplement users (documented through prescription records, patient self-reports, and pharmacy data) to non-users. The primary outcome was incident VEDs, a composite of cerebrovascular disease, peripheral vascular disease, and acute coronary syndrome, identified via ICD-10 codes. We used Cox proportional hazards regression adjusted for baseline characteristics. RESULTS: During the follow-up with 38,240 person-years, 2,792 incident VEDs occurred. Herbal supplement use was significantly associated with increased VED risk (aHR 1.52, 95% CI 1.39-1.67). A clear dose-response relationship emerged: 2 years (aHR 2.24; P-trend