Association Between Serum Bilirubin, Lipid Levels, and Prevalence of Femoral and Carotid Atherosclerosis: A Population-Based Cross-Sectional Study

Abstract

Background: Bilirubin may prevent lipid peroxidation and have important antiatherosclerotic effects. We determined associations of serum bilirubin and lipid with peripheral atherosclerosis. Methods: We included 4290 participants (35% men; median age, 60 years) from the southeast China who underwent B-mode ultrasound examination. Increased intima-media thickness or a focal structure encroaching into the arterial lumen by at least 0.5 mm or >50% of the surrounding intima-media thickness value was regarded as having atherosclerosis. Fasting serum bilirubin and lipid levels were measured. Cholesterol/(HDL [high-density lipoprotein] cholesterol+bilirubin), and LDL (low-density lipoprotein cholesterol)/(HDL+bilirubin) ratios were calculated. Unconditional and multinomial logistic regression models were used to examine associations of bilirubin or lipid with prevalence of peripheral atherosclerosis. Mediation analyses were performed to assess the effect of bilirubin on atherosclerosis risk mediated via lipid. Results: Compared with participants with the lowest levels of bilirubin, those with the highest tertile were less likely to have carotid or femoral atherosclerosis (odds ratios were 0.55–0.74). The highest levels of bilirubin significantly reduced the odds of concurrent carotid and femoral atherosclerosis by 35% to 45%. Participants with the highest levels of cholesterol, LDL, cholesterol/(HDL+bilirubin), and LDL/(HDL+bilirubin) ratios had 2.8- to 3.7-fold increased odds of concurrent carotid and femoral atherosclerosis. LDL accounted for 25.65% of the total bilirubin-atherosclerosis association. LDL and cholesterol mediated the associations between direct bilirubin and atherosclerosis (proportion: 20.40%, 9.67%, respectively). Conclusions: Increased serum bilirubin levels are inversely associated with the prevalence of carotid or femoral atherosclerosis. LDL and cholesterol may mediate these associations.

Response by Su and Ye to Letter Regarding Article, “Association Between Serum Bilirubin, Lipid Levels, and Prevalence of Femoral and Carotid Atherosclerosis: A Population-Based Cross-Sectional Study”

“…Third, according to the comment by Zhao et al, we reran multinomial logistic regression models without adjusting for any confounders and could observe that higher HDL (high-density lipoprotein) cholesterol was inversely associated with the odds of atherosclerosis (Q2: 0.95 [0.76–1.19], Q3: 0.83 [0.66–1.04] for only carotid atherosclerosis; Q2: 0.96 [0.77–1.18], Q3: 0.73 [0.59–0.92] for only femoral atherosclerosis; Q2: 0.74 [0.58–0.93], Q3: 0.65 [0.51–0.82] for concurrent carotid and femoral atherosclerosis). However, as shown in Table 2 in our paper, 1 the seemingly inverse associations disappeared after we adjusted for 14 potential confounders. In addition, recent studies have shown a U -shaped association between HDL cholesterol and mortality from cardiovascular disease.…”

“…We appreciate Zhao et al for their great interest and comments on our article. 1 We here respond to the important points raised in their Letter to the Editor.…”

Loss of Anthropometry-Lipids Relationship in Obese Adults: A Cross-Sectional Study in Southern China

“…Fuqing Cohort Study is an ongoing project in Fuqing city, Fujian Province, located in Southern China, which is planned to recruit more than 50,000 residents aged 35–75 years living in several towns across Fuqing city. 11 Two waves of this cohort project have been initiated in Gaoshan Town in 2019 and 2020, respectively. Until the end of June 2021, a total of 10,207 residents in the town have been recruited with baseline assessment.…”

Letter by Zhao et al Regarding Article, “Association Between Serum Bilirubin, Lipid Levels, and Prevalence of Femoral and Carotid Atherosclerosis: A Population-Based Cross-Sectional Study”

“…We have read with great interest the impressive study by Su et al 1 and would like to congratulate the authors for revealing the inversely association between serum bilirubin levels and the prevalence of carotid or femoral atherosclerosis, which could be mediated by LDL (low-density lipoprotein) and cholesterol. Although it seems that the highest levels of bilirubin reduced the odds of concurrent carotid and femoral atherosclerosis with a statistically significant P value, the current analyses should be treated cautiously with 2 concerns to be resolved.…”