Systematic investigation of gengetically determined plasma and urinary biomarkers to identify potential detection and intervention targets for vascular calcification
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Background
Vascular calcification (VC) is prevalent among patients with atherosclerosis, hypertension, diabetes, elderly individuals, and those with chronic kidney disease. However, effective diagnostic and therapeutic strategies are lacking. Plasma and urinary biomarkers are commonly used in clinical settings to assess disease progression.
Objective
This study investigates causal relationships between plasma/urinary biomarkers and VC using Mendelian randomization (MR), aiming to identify potential targets for VC intervention, and to assess whether biomarkers mediate the effects of modifiable risk factors on VC.
Methods
We performed two-sample bidirectional MR using large-scale genome-wide association study data (n=363,228 for biomarkers, n=28,654 for VC) to investigate the causal effects of plasma/urinary biomarkers on VC. Then, a literature review was performed to identify common VC risk factors, followed by univariate MR to select risk factors associated with both VC and biomarkers. Finally, mediation analysis was conducted to explored whether biomarkers mediate the effects of modifiable risk factors on VC.
Results
MR analysis identified 7 plasma biomarkers linked to VC, 5 of which were positively correlated. A literature review revealed 856 VC risk factors, with 28 identified through univariate MR analysis, 11 of which correlated with identified biomarkers. Mediation analysis showed that 5 biomarkers (TRIG, GGT, CA, BILD, SHBG) partially mediated the effects of 4 modifiable risk factors on VC.
Conclusion
This study identifies several clinically common used biomarkers for diagnosing and treating VC, suggesting that modulating these biomarkers through lifestyle changes, such as controlling smoking, intake of milk, blood pressure and diabetes, may slow VC progression in patients.
Lay Summary
What is already known about this subject?
Vascular calcification (VC) is prevalent among patients with atherosclerosis, hypertension, diabetes, elderly individuals, and those with chronic kidney disease.
Plasma and urine biomarkers are the most commonly used indicators in clinical practice for assessing disease progression.
However, the potential causal relationship between plasma and urine biomarkers and VC remains unclear.
What are the new findings?
7 clinically used plasma and urine biomarkers are causally linked with VC, while the occurrence of VC affects the expression of Alkaline Phosphatase.
A comprehensive literature review revealed 856 potential risk factors for VC. Univariate MR analysis identified 28 of these risk factors as causally linked to VC, with 11 also associated with specific biomarkers
Mediation analysis revealed that 5 biomarkers (TRIG, GGT, CA, BILD, and SHBG) partially mediated the effects of 4 risk factors on VC.
How might it impact on clinical practice in the foreseeable future?
Our findings suggest that patients may modulate the expression of 5 biomarkers (TRIG, GGT, CA, BILD, and SHBG) by controlling certain risk factors (intake of milk, smoking, diabetes, and systolic blood pressure) in daily life, thereby slowing the progression of VC.
