Abstract
BACKGROUND AND OBJECTIVES: Recent literature suggests no elevated risk of cardiovascular disease in patients having nonfocal transient neurologic attacks (TNAs), yet the origin of these attacks remains unclear. Therefore, we investigated their incidence and potential risk factors in a prospective cohort study, hypothesizing associations with cardiovascular risk factors. METHODS: Within the Dutch population-based Rotterdam Study, community-living individuals aged 45 years or older underwent assessment for demographic and cardiovascular risk factors in study cohorts initiated in 1990, 2000, and 2006. Participants were subsequently followed until January 1, 2021, for disease incidence through automated linkage of the study database with medical records from participants' general practitioners. For this study, participants free from TNA at baseline were selected and followed up for the outcome of a nonfocal TNA. The risk of nonfocal TNA was determined through age-specific incidence rates (IRs). Potential risk factors of nonfocal TNA were identified using cause-specific, multivariable, Cox proportional hazard modeling accounting for age, sex, education (university or higher vocational vs lower education level), cardiovascular risk factors, ultrasound markers of carotid atherosclerosis, antithrombotic medication use, and a history of vascular diseases. Sensitivity analyses consisted of conducting this regression among participants without any history of vascular disease at study entrance. RESULTS: After 204,474 person-years of follow-up in 14,096 participants (mean [SD] age 65.5 [10.3] years, 59.0% female), 518 index nonfocal TNAs (3.7%) occurred. The incidence of nonfocal TNA increased with age, with an IR in those aged between 55 and 59 years of 65.5 (95% CI 33.6-116.2) per 100,000 person-years of follow-up to 424.0 (95% CI 348.0-512.0) in those aged 85 years or older. Older age (hazard ratio [HR] 1.08, 95% CI 1.07-1.09), a lower education level (HR 1.62, 95% CI 1.15-2.29), plaque presence on carotid ultrasound (HR 0.80, 95% CI 0.65-1.00), and the use of antithrombotics (HR 0.59, 95% CI 0.39-0.90) were all independently associated with the risk of nonfocal TNA. After restricting analyses to the 12,499 individuals without history of vascular disease, only the associations of age and a higher maximum attained education level with the risk of nonfocal TNA remained statistically significant. DISCUSSION: Nonfocal TNAs predominantly affect older adults and those with lower educational attainment, suggesting that these attacks originate from socioeconomic determinants rather than from established cardiovascular risk factors.