Arterial stiffness but not carotid intima-media thickness progression precedes premature structural and functional cardiac damage in youth: A 7-year temporal and mediation longitudinal study

Abstract

Background and aims: The longitudinal relations of cardiac indices with the aorta and carotid vessel and the time sequence for early cardiac disease development are uncharacterized in youth. We examined the temporal longitudinal associations of carotid-femoral pulse wave velocity (cfPWV) and carotid intima-media thickness (cIMT) with left ventricular hypertrophy (LVH) and diastolic dysfunction (LVDD).

Methods: From the Avon Longitudinal Study of Parents and Children, UK birth cohort, 1856 adolescents (1011 females) at a mean (SD) age 17.7 (0.3) years were followed up for 7 years. Vicorder-measured cfPWV and ultrasound-measured cIMT were grouped in tertiles as low (reference), moderate, and high. Echocardiography measured cardiac abnormalities are left ventricular mass indexed for height^2.7 (LVMI^2.7) ≥51 g/m^2.7 as LVH; relative wall thickness ≥44 as hiRWT; LVD function E/A <1.5 as LVD dysfunction (LVDD); and LV filling pressure E/e' ≥8 as hiLVFP. Data were analysed with generalized logit mixed-effect models, cross-lagged path, and mediation structural equation models adjusting for cardiometabolic and lifestyle factors.

Results: Over follow-up, LVH prevalence increased from 3.6% to 7.2% and LVDD from 11.1 to 16.3%. High cfPWV progression was associated with worsening LVH [Odds ratio 1.23 (1.13-1.35); p < 0.001] in the total cohort, males, overweight/obese, and normotensive. High cfPWV progression was associated with worsening hiLVFP in the total cohort, females, and normal weight. Likewise, high cIMT progression was associated with worsening LVH [1.27 (1.26-1.27); p < 0.0001] in the total cohort, overweight/obese and elevated BP/hypertensive. Neither cfPWV nor cIMT progression was associated with worsening hiRWT in the total cohort. In cross-lagged models, higher baseline cfPWV was associated with future LVMI^2.7 (β = 0.06, SE, 5.14, p = 0.035), RWT, LVDF, and LVFP. However, baseline LVMI^2.7, RWT, LVDF, and LVFP were not associated with follow-up cfPWV. Baseline cIMT was not associated with follow-up cardiac indices and vice versa. Cumulative increased systolic blood pressure (34.3% mediation) and insulin resistance (15.1% mediation) mediated the direct associations of cumulative cfPWV with cumulative LVMI^2.7.

Conclusions: Arterial stiffness progression temporally preceded worsening structural and functional cardiac damage in youth with increased systolic blood pressure and insulin resistance partly mediating the relationships. Future interventions aimed at attenuating premature cardiac damage in adolescents and young adults may consider a simultaneous treatment of both arterial stiffness, elevated blood pressure and insulin resistance.

Keywords: Atherosclerosis; Left ventricular diastolic dysfunction; Left ventricular hypertrophy; Metabolic syndrome; Pediatrics.