Arterial stiffness preceding metabolic syndrome in 3,862 adolescents: a mediation and temporal causal longitudinal birth cohort study.

The temporal longitudinal associations of carotid-femoral pulse wave velocity (cfPWV), a measure of arterial stiffness, with the risk of incident metabolic syndrome, were examined in youth. A total of 3,862 adolescents, aged 17.7 yr and followed up for 7 yr, from the Avon Longitudinal Study of Parents and Children were included. cfPWV was assessed by Vicorder at baseline and follow up. Metabolic syndrome was determined by the presence of three or more of dual-energy X-ray absorptiometry-measured trunk fat obesity; decreased high-density lipoprotein cholesterol, elevated triglyceride, hyperglycemia, and elevated/hypertensive blood pressure at both measurement time points. Analyses were conducted using generalized logit mixed-effect models and autoregressive cross-lagged and mediation structural equation models. Among 3,862 adolescents [2,143 (55.5%) female], 5% of male and 1.1% of female participants had metabolic syndrome at baseline, whereas 8.8% of male and 2.4% of female participants had metabolic syndrome at follow-up. In the mixed-model analysis, a 7-yr progressive increase in cfPWV was associated with a cumulatively increased risk of incident metabolic syndrome from baseline through follow-up in the total cohort (odds ratio 1.04 [confidence interval, 1.02-1.06], P = 0.002) and in males (1.09 [1.06-1.12], P < 0.001) but not in females (1.01 [0.95-1.06], P = 0.885). In the cross-lagged model, higher cfPWV at baseline was associated with a higher metabolic syndrome score (β = 0.08, standard error = 0.39, P < 0.0001) at follow-up but metabolic syndrome score at baseline was not associated with cfPWV at follow-up. Cumulatively increased fasting insulin and low-density lipoprotein cholesterol had 12.4 and 9.4% respective mediation effects on the positive relationships between cumulative arterial stiffness and metabolic syndrome score. In conclusion, arterial stiffness temporally preceded incident and progressive metabolic syndrome in youth in a potential causal path, but experimental studies are warranted. NEW & NOTEWORTHY Participants at risk of metabolic syndrome increased twofold during growth from late adolescence to young adulthood. The cumulative increase in arterial stiffness independently predicted the progressive risk of incident metabolic syndrome. Arterial stiffness temporally preceded metabolic syndrome. Increased fasting insulin and low-density lipoprotein cholesterol partly mediated the direct associations between arterial stiffness and metabolic syndrome. Age 17 yr may be an optimal arterial stiffness intervention timing for attenuating metabolic syndrome risks.