Unveiling the Hidden Stroke Threat in Patients With Atrial Fibrillation and Primary Hyperparathyroidism

Abstract

Recent American College of Cardiology (ACC), American Heart Association (AHA), American College of Clinical Pharmacy (ACCP), and Heart Rhythm Society (HRS) guidelines suggest that patients with atrial fibrillation (AF) at intermediate to low annual risk of ischemic stroke can benefit from consideration of factors that might modify their risk of stroke. The role of nontraditional risk factors, such as primary hyperparathyroidism (PHPT), remains unexplored. In our study, we investigated the potential association between PHPT and the risk of ischemic stroke in patients with AF. Using data from the Nationwide Inpatient Sample Database, a retrospective cohort study focused on the adult population with AF, we stratified the participants based on PHPT presence. Demographic information, co-morbidities, and hospitalization details were extracted using International Classification of Diseases, Tenth revision codes. Propensity score matching was applied, encompassing over 20 confounding variables, including the risk factors outlined in the CHA₂DS₂-VASc (Congestive heart failure (C), Hypertension (H), Age ≥75 years (A₂), Diabetes Mellitus (D), Stroke/Transient Ischemic Attack (TIA)/Thromboembolism (S₂), Vascular disease (V), Age 65-74 years (A), Sex category [female] (Sc)) score. Multivariate logistic regression analysis was performed after matching to assess the independent impact of PHPT as an ischemic stroke risk factor. A total of 2,051 of the identified 395,249 patients with AF had PHPT. The PHPT group had an average age of 74 years and consisted of more women (66.1% vs 53.0%). After matching, it was observed that the PHPT group had longer hospital stays (5 vs 4 days) and higher hospitalization charges ($45,126 vs $36,644). This group exhibited higher rates of ischemic stroke (6.0% vs 4.4%) and mortality (6.3% vs 4.9%). The adjusted outcomes showed a 1.4-fold increased risk for ischemic stroke and a 1.32-fold increased risk for mortality in the PHPT cohort. The subgroup analysis showed a higher incidence of mortality in men with a high CHA₂DS₂-VASc score. In conclusion, this study highlights a marked association between PHPT and ischemic stroke in patients with AF, independent of the conventional CHA₂DS₂-VASc score. The potential mechanisms implicated include vascular changes, cardiac dysfunction, and coagulation cascade alterations. The presence of PHPT should be taken into consideration when deciding the assessment of thromboembolic risk.

Keywords: atherosclerosis; atrial fibrillation; cardiovascular risk; primary hyperparathyroidism; stroke.