Mutual effect of homocysteine and uric acid on arterial stiffness and cardiovascular risk in the context of predictive, preventive, and personalized medicine

Abstract

Background: Arterial stiffness is a major risk factor and effective predictor of cardiovascular diseases and a common pathway of pathological vascular impairments. Homocysteine (Hcy) and uric acid (UA) own the shared metabolic pathways to affect vascular function. Serum uric acid (UA) has a great impact on arterial stiffness and cardiovascular risk, while the mutual effect with Hcy remains unknown yet. This study aimed to evaluate the mutual effect of serum Hcy and UA on arterial stiffness and 10-year cardiovascular risk in the general population. From the perspective of predictive, preventive, and personalized medicine (PPPM/3PM), we assumed that combined assessment of Hcy and UA provides a better tool for targeted prevention and personalized intervention of cardiovascular diseases via suppressing arterial stiffness.

Methods: This study consisted of 17,697 participants from Beijing Health Management Cohort, who underwent health examination between January 2012 and December 2019. Brachial-ankle pulse wave velocity (baPWV) was used as an index of arterial stiffness.

Results: Individuals with both high Hcy and UA had the highest baPWV, compared with those with low Hcy and low UA (β: 30.76, 95% CI: 18.36-43.16 in males; β: 53.53, 95% CI: 38.46-68.60 in females). In addition, these individuals owned the highest 10-year cardiovascular risk (OR: 1.49, 95% CI: 1.26-1.76 in males; OR: 7.61, 95% CI: 4.63-12.68 in females). Of note, males with high homocysteine and low uric acid were significantly associated with increased cardiovascular risk (OR: 1.30, 95% CI: 1.15-1.47), but not the high uric acid and low homocysteine group (OR: 1.02, 95% CI: 0.90-1.16).

Conclusions: This study found the significantly mutual effect of Hcy and UA on arterial stiffness and cardiovascular risk using a large population and suggested the clinical importance of combined evaluation and control of Hcy and UA for promoting cardiovascular health. The adverse effect of homocysteine on arteriosclerosis should be addressed beyond uric acid, especially for males. Monitoring of the level of both Hcy and UA provides a window opportunity for PPPM/3PM in the progression of arterial stiffness and prevention of CVD. Hcy provides a novel predictor beyond UA of cardiovascular health to identify individuals at high risk of arterial stiffness for the primary prevention and early treatment of CVD. In the progressive stage of arterial stiffness, active control of Hcy and UA levels from the aspects of dietary behavior and medication treatment is conducive to alleviating the level of arterial stiffness and reducing the risk of CVD. Further studies are needed to evaluate the clinical effect of Hcy and UA targeted intervention on arterial stiffness and cardiovascular health.

Supplementary information: The online version contains supplementary material available at 10.1007/s13167-022-00298-x.

Keywords: Arterial stiffness; Brachial-ankle pulse wave velocity; Cardiovascular risk; Homocysteine; Mutual effect; Predictive preventive and personalized medicine (PPPM / 3PM); Uric acid.

Fig. 1

Adjusted associations of one-SD increase in Hcy/UA with baPWV stratified by UA/Hcy levels. Abbreviations: Hcy homocysteine, UA uric acid, baPWV brachial-ankle pulse wave velocity, SD standard deviation. The SD of UA and Hcy in males was 78.65 µmol/L and 7.64 µmol/L; SD of UA and Hcy in females was 69.22 µmol/L and 3.98 µmol/L. β refers to the regression coefficients in the multi-variable linear regression model after adjusted for age, education, BMI, physical activity, smoking, drinking, health status, systolic pressure, glucose, triglyceride, HDL-C

Fig. 2

Adjusted linear regression lines of Hcy/UA and baPWV stratified by UA/Hcy levels. Abbreviations: Hcy homocysteine, UA uric acid, baPWV brachial-ankle pulse wave velocity. High level Hcy was defined as > 14 µmol/L in male and > 10 µmol/L in female; and high level UA was defined as > 420 µmol/L in male and > 320 µmol/L in female. The regression lines were plotted after adjusting for age, education, BMI, physical activity, smoking, drinking, health status, systolic pressure, glucose, triglyceride, HDL-C using R package ‘effects’. A: linear regression lines of Hcy and baPWV stratified by UA levels in male; B: linear regression lines of UA and baPWV stratified by Hcy levels in male; C: linear regression lines of Hcy and baPWV stratified by UA levels in female; D: linear regression lines of UA and baPWV stratified by Hcy levels in female

Fig. 3

Adjusted mutual associations of serum Hcy and UA with baPWV in subgroups according to age, BMI, hypertension, diabetes, and smoking. Abbreviations: Hcy homocysteine, UA uric acid, baPWV brachial-ankle pulse wave velocity. High level Hcy was defined as > 14 µmol/L in males and > 10 µmol/L in females; and high level UA was defined as > 420 µmol/L in males and > 320 µmol/L in females. Age was divided in to ≤ 60 and > 60 years; BMI was divided in to ≥ 28.0 and < 28.0 kg/m² according to the standard for Chinese population