Predictors of Carotid Intima-Media Thickness Progression in Adolescents-The EVA-Tyrol Study

Abstract

Background Cardiovascular disease depends on the duration and time course of risk factor exposure. Previous reports on risk factors of progression of carotid intima-media thickness (cIMT) in the young were mostly restricted to high-risk populations or susceptible to certain types of bias. We aimed to unravel a risk factor signature for early vessel pathology based on repeated ultrasound assessments of the carotid arteries in the general population. Methods and Results Risk factors were assessed in 956 adolescents sampled from the general population with a mean age of 15.8±0.9 years, 56.2% of whom were female. cIMT was measured at baseline and on average 22.5±3.4 months later by high-resolution ultrasound. Effects of baseline risk factors on cIMT progression were investigated using linear mixed models with multivariable adjustment for potential confounders, which yielded significant associations (given as increase in cIMT for a 1-SD higher baseline level) for alanine transaminase (5.5 μm; 95% CI: 1.5-9.5), systolic blood pressure (4.7 μm; 0.3-9.2), arterial hypertension (9.5 μm, 0.2-18.7), and non-high-density (4.5 μm; 0.7-8.4) and low-density lipoprotein cholesterol (4.3 μm; 0.5-8.1). Conclusions Systolic blood pressure, arterial hypertension, low-density and non-high-density lipoprotein cholesterol, and alanine transaminase predicted cIMT progression in adolescents, even though risk factor levels were predominantly within established reference ranges. These findings reemphasize the necessity to initiate prevention early in life and challenge the current focus of guideline recommendations on high-risk youngsters. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03929692.

Keywords: atherosclerosis; cardiovascular disease; intima‐media thickness; risk factors.

Figure 1. Predictors of carotid intima‐media thickness progression in adolescents.

Predictors are shown on the y‐axis and change in cIMT after 22.5 months of follow‐up on the x‐axis as points (main estimate) and horizontal ranges (95% CI). Effects are given for a 1‐SD higher level for continuous variables and vs the reference category for categorical variables. Model 1: adjustment for baseline cIMT, age, and sex; Model 2: adjustment for baseline cIMT, age, sex, and for the following variables both at baseline and at follow‐up: systolic and diastolic blood pressure, BMI Z score, LDL‐cholesterol, fasting glucose, smoking status (never vs ever smoker) and Family Affluence Scale score (except for highly correlated variables, see Methods section for details), and alcohol consumption in grams/week (only for liver parameters). Only predictors but not the adjustment variables of Model 1 and Model 2 are shown on the y‐axis. Under multivariable adjustment (Model 2), systolic blood pressure, arterial hypertension, LDL cholesterol, non‐HDL cholesterol, and alanine transaminase were significantly associated with cIMT progression. Central obesity was defined as a waist circumference at or above the 90th age‐ and sex‐specific percentile. Arterial hypertension was defined as a systolic blood pressure ≥130 mm Hg, a diastolic blood pressure ≥80 mm Hg, or any of the 2 at or above the age‐ and sex‐specific 95th percentile. Elevated ALT was defined as an ALT ≥22 U/L in girls and ≥26 U/L in boys. *Never‐smokers were excluded for this analysis. ALT indicates alanine transaminase; BMI, body mass index; cIMT, carotid intima‐media thickness; HDL, high‐density lipoprotein; HOMA‐IR, Homeostatic Model Assessment for Insulin Resistance; and LDL, low‐density lipoprotein. ^†Categorical variable.