Plasma homocysteine levels and associated factors in community-dwelling adolescents: the EVA-TYROL study

Abstract

Background: Homocysteine (Hcy) has been associated with an adverse cardiovascular risk profile in adolescents. Assessment of the association between plasma Hcy levels and clinical/laboratory factors might improve our understanding of the pathogenesis of cardiovascular disease.

Methods: Hcy was measured in 1,900 14- to 19-year-old participants of prospective population-based EVA-TYROL Study (44.3% males, mean age 16.4 years) between 2015 and 2018. Factors associated with Hcy were assessed by physical examination, standardized interviews, and fasting blood analysis.

Results: Mean plasma Hcy was 11.3 ± 4.5 µmol/L. Distribution of Hcy was characterized by extreme right skew. Males exhibited higher Hcy and sex differences increased with increasing age. Univariate associations with Hcy emerged for age, sex, body mass index, high-density lipoprotein cholesterol, and for factors pertaining to blood pressure, glucose metabolism, renal function, and diet quality, whereas the most important multivariate predictors of Hcy were sex and creatinine.

Discussion: Clinical and laboratory factors associated with Hcy in adolescents were manifold, with sex and high creatinine identified as strongest independent determinants. These results may aid when interpreting future studies investigating the vascular risk of homocysteine.

Keywords: adolescents; cardiovascular risk factors; epidemiology; health prevention; homocysteine.

Figure 1

Distribution of plasma homocysteine by sex. The distribution of homocysteine (Hcy) showed extreme right-skew, which may indicate a mixture distribution including carriers of methylenetetrahydrofolate reductase or other mutations that associate with elevated Hcy. Males tended to feature higher Hcy than females, and this was true for subjects with Hcy ≤ 97th percentile as well as for subjects with very high Hcy > 97th percentile (corresponding to >20 µmol/L). For the latter, individual data points are shown as a dotplot histogram.

Figure 2

Trajectory of plasma homocysteine during adolescence by sex. Although males (dashed lines) compared to females (solid lines) showed higher average Hcy (black lines) throughout adolescence, investigation of Hcy percentiles conditional on age (colored lines) revealed higher male Hcy at the high end of the distribution at all ages, faster increase of Hcy in males than in females, and plateauing of Hcy in females but not in males around age 16.