Sex-specific associations between adipokine profiles and carotid-intima media thickness in the Cameron County Hispanic Cohort (CCHC)

Abstract

Background: Adipokines are hormones secreted from adipose tissue and are associated with cardiometabolic diseases (CMD). Functional differences between adipokines (leptin, adiponectin, and resistin) are known, but inconsistently reported associations with CMD and lack of studies in Hispanic populations are research gaps. We investigated the relationship between subclinical atherosclerosis and multiple adipokine measures.

Methods: Cross-sectional data from the Cameron County Hispanic Cohort (N = 624; mean age = 50; Female = 70.8%) were utilized to assess associations between adipokines [continuous measures of adiponectin, leptin, resistin, leptin-to-adiponectin ratio (LAR), and adiponectin-resistin index (ARI)] and early atherosclerosis [carotid-intima media thickness (cIMT)]. We adjusted for sex, age, body mass index (BMI), smoking status, cytokines, fasting blood glucose levels, blood pressure, lipid levels, and medication usage in the fully adjusted linear regression model. We conducted sexes-combined and sex-stratified analyses to account for sex-specificity and additionally tested whether stratification of participants by their metabolic status (metabolically elevated risk for CMD as defined by having two or more of the following conditions: hypertension, dyslipidemia, insulin resistance, and inflammation vs. not) influenced the relationship between adipokines and cIMT.

Results: In the fully adjusted analyses, adiponectin, leptin, and LAR displayed significant interaction by sex (p < 0.1). Male-specific associations were between cIMT and LAR [β(SE) = 0.060 (0.016), p = 2.52 × 10^-4], and female-specific associations were between cIMT and adiponectin [β(SE) = 0.010 (0.005), p = 0.043] and ARI [β(SE) = - 0.011 (0.005), p = 0.036]. When stratified by metabolic health status, the male-specific positive association between LAR and cIMT was more evident among the metabolically healthy group [β(SE) = 0.127 (0.015), p = 4.70 × 10^-10] (p for interaction by metabolic health < 0.1). However, the female-specific associations between adiponectin and cIMT and ARI and cIMT were observed only among the metabolically elevated risk group [β(SE) = 0.014 (0.005), p = 0.012 for adiponectin; β(SE) = - 0.015 (0.006), p = 0.013 for ARI; p for interaction by metabolic health < 0.1].

Conclusion: Associations between adipokines and cIMT were sex-specific, and metabolic health status influenced the relationships between adipokines and cIMT. These heterogeneities by sex and metabolic health affirm the complex relationships between adipokines and atherosclerosis.

Keywords: Adipokines; Cardiometabolic health; Carotid intima-media thickness; Health disparities; Mexican–American; Population-based cohort; Sex-differences.

Fig. 1

Associations between adipokines and cIMT in both sexes-combined, females, and males. Associations between adipokines and cIMT (continuous) from the fully adjusted linear mixed effects model (Model 5) are demonstrated on the forest plot. Beta coefficients and 95% confidence interval indicate the increase of cIMT levels by every 1-SD increase of adipokines [1-SD: 21.5 ug/mL for adiponectin, 15.3 ng/mL for leptin, 16.5 ng/mL for resistin, 1.15 for LAR, 0.31 for ARI]. Results for sexes-combined and sex-stratified analyses are shown. Significant interaction by sex (p for interaction < 0.1) is indicated (*)

Fig. 2

Associations between adipokines and cIMT stratified by metabolic health status. Associations between adipokines and cIMT levels stratified by metabolic health status from the fully adjusted linear mixed effects model are demonstrated on the forest plot (A. Both sexes-combined, B. Female, and C. Male) Beta coefficients (95% confidence intervals) indicate the increase in cIMT levels by every 1-SD increase of adipokines [1-SD: 21.5 ug/mL for adiponectin, 15.3 ng/mL for leptin, 16.5 ng/mL for resistin, 1.15 for LAR, 0.31 for ARI]. Significant interaction by metabolic health status (p for interaction < 0.1) is indicated by * on the name of adipokines