Gender differences in risk factors for high plasma homocysteine levels based on a retrospective checkup cohort using a generalized estimating equation analysis

Abstract

Background: Hyperhomocysteinemia (HHcy) is associated with various health problems, but less is known about the gender differences in risk factors for high plasma homocysteine (Hcy) levels.

Methods: In this study, a retrospective study was carried out on 14,911 participants (7838 males and 7073 females) aged 16-102 years who underwent routine checkups between January 2012 and December 2017 in the Health Management Department of Xuanwu Hospital, China. Anthropometric measurements, including body mass index (BMI) and waist-to-hip ratio, were collected. Fasting blood samples were collected to measure the biochemical indexes. The outcome variable was Hcy level, and a generalized estimating equation (GEE) analysis was used to identify the associations of interest based on gender.

Results: Males exhibited increased Hcy levels (16.37 ± 9.66 vs 11.22 ± 4.76 μmol/L) and prevalence of HHcy (37.0% vs 11.3%) compared with females. Hcy levels and HHcy prevalence increased with age in both genders, except for the 16- to 29-year-old group. GEE analysis indicated that irrespective of gender, aspartate aminotransferase, creatinine, uric acid, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels were positively correlated with Hcy levels, and alanine aminotransferase, total cholesterol and glucose were negatively correlated with Hcy levels. However, age, BMI and triglycerides (TGs) were positively correlated with Hcy levels exclusively in females.

Conclusions: Gender differences in risk factors for high plasma Hcy levels were noted. Although common correlational factors existed in both genders, age, BMI and TGs were independent risk factors for Hcy levels specifically in females.

Keywords: Aging; Body mass index; Gender difference; Homocysteine; Hyperhomocysteinemia; Risk factor; Triglycerides.

Fig. 1

Distribution of Hcy levels in the cohort population and age-group distribution profiles in different groups of plasma Hcy levels. a Number of participants, b Age-group distribution of males, c Age-group distribution of females in different Hcy level groups, including normal (≤15 μmol/L), mild HHcy (15 < Hcy ≤ 30 μmol/L), moderate HHcy (30 < Hcy < 100 μmol/L), and severe HHcy (≥100 μmol/L). Hcy, homocysteine; HHcy, hyperhomocysteinemia; Mild-H, mild HHcy; Moderate-H, moderate HHcy; Severe-H, severe HHcy

Fig. 2

Mean Hcy levels in different age groups (16–29, 30–39, 40–49, 50–59, 60–69, 70–79, and ≥ 80 years of age) in males (a) and females (b). Error bar stands for standard error. Significant differences are found between 16 and 29 and 30–39 (P < 0.01), 16–29 and 40–49 (P < 0.01), 16–29 and 50–59 (P < 0.01), 16–29 and 60–69 (P < 0.01), 16–29 and 70–79 (P < 0.05), 30–39 and 70–79 (P < 0.01), 30–39 and ≥ 80 (P < 0.01), 40–49 and 60–69 (P < 0.05), 40–49 and 70–79 (P < 0.01), 40–49 and ≥ 80 (P < 0.01), 50–59 and 70–79 (P < 0.01), 50–59 and ≥ 80 (P < 0.01), 60–69 and 70–79 (P < 0.05), and 60–69 and ≥ 80 (P < 0.01) age groups in males (a). However, in females, significant differences exist in any two groups (P < 0.01) except that there are no statistical differences between 16 and 29 and 40–49, and 70–79 and ≥ 80 age groups (P > 0.05) (b). Hcy, homocysteine

Fig. 3

HHcy prevalence in different age groups (16–29, 30–39, 40–49, 50–59, 60–69, 70–79, and ≥ 80 years of age) in males (a) and females (b). Significant differences in HHcy prevalence are found in any two groups (P < 0.01) except that there are no statistical differences between 16 and 29 and 50–59, 16–29 and 60–69, and 30–39 and 40–49 age groups in males (P > 0.05). Whereas in females, except that no statistical differences are observed between 16 and 29 and 30–39, 16–29 and 40–49, 16–29 and 50–59, and 30–39 and 40–49 age groups (P > 0.05), significant differences exist between any other two groups (P < 0.05 between 70 and 79 and ≥ 80, P < 0.01 between any other pairs). HHcy, hyperhomocysteinemia