Abstract
IMPORTANCE: Childhood or adolescent intelligence has been linked to major somatic diseases and premature mortality, but the underlying pathways remain unclear. OBJECTIVE: To determine whether adolescent intelligence is associated with atherosclerosis in middle age and whether this association is mediated by the American Heart Association's Life's Essential 8 (LE8) metric of cardiovascular health markers. DESIGN: Population-based prospective cohort study. SETTING: Six university hospitals in Sweden. PARTICIPANTS: Men in the Swedish CArdioPulmonary bioImage Study who underwent mandatory military conscription in adolescence. EXPOSURE: A standardized intelligence test administered at conscription (mean age, 18.3 years; standard deviation [SD], 0.5), assessing logical reasoning, spatial ability, technical skills, and verbal comprehension. Scores were standardized to a mean of 100 (SD, 15). MAIN OUTCOMES AND MEASURES: Atherosclerosis in middle age (mean age 56.6 years; SD, 3.9), assessed using coronary computed tomography angiography (coronary stenosis: 0%, 1-49% and ≥50%) and coronary artery calcium (CAC) scores (0, 1-99, ≥100 Agatston units), and presence of unilateral or bilateral carotid plaque/s via ultrasound. LE8 components assessed in SCAPIS were analyzed as potential mediators. Associations were modeled using multinomial logistic regression, and mediation was estimated using counterfactual mediation analysis. RESULTS: A total of 8,117 men were included in the analysis of coronary stenosis, 7,958 for CAC, and 9,092 for carotid plaque. Higher adolescent intelligence was inversely associated with atherosclerosis in middle age. In analyses with extended adjustments (Model 2) for coronary stenosis, each 15-point (1 SD) increase in adolescent intelligence was associated with 17% lower odds of having ≥50% coronary stenosis (OR: 0.83; 95% CI: 0.75-0.90; P-value: <0.001). An intelligence difference between 70 and 130 corresponded to a prevalence difference of 4.1 percentage points (10.3% vs 6.2%) of coronary stenosis ≥50%. Similar associations were observed for CAC scores and carotid plaque.Mediation via LE8 accounted for 41% to 68% of the association across outcomes; the only direct effect not mediated via LE8 was observed for unilateral carotid plaque. CONCLUSIONS: Higher adolescent intelligence was associated with a lower burden of atherosclerosis in middle age, with a substantial proportion of the association mediated by modifiable cardiovascular health factors.