Epidemiological and biological associations between cardiovascular disease and kidney stone formation: A systematic review and meta-analysis.

Previous studies find kidney stone formers (KSF) are at greater risk of developing cardiovascular disease (CVD). The underlying mechanisms are poorly understood, and many clinicians are unaware of this connection. We will: 1 Provide an up-to-date review of epidemiological data. 2 Clearly define CVD outcomes to understand conditions associated with kidney stone formation (KSF). 3 Review hypothesised biological pathways to further understand the relationship. Our systematic review is registered with PROSPERO (ID CRD42021251477). We searched epidemiological and biological data. The epidemiological search generated 669 papers, narrowed down to 15. There were 4,259,869 participants (230,720 KSFs). KSF was associated with 25% higher risk of coronary artery disease (CAD) (95% confidence interval (CI): 15, 35%), 17% higher risk of stroke/transient ischemic attacks (TIA) (CI:10, 25%) and 39% higher risk of arterial disease (AD) (CI: 17 65%). Significant heterogeneity was found. Female-identifying KSFs had a higher risk of stroke (ratio = 1.10) and CAD (1.20). The biological search generated 125 papers, narrowed down to 14. Potential underlying mechanisms were extracted and discussed, including intimal/medial vascular calcification, oxidative stress via osteopontin (OPN), cholesterol-induced pathology, and endothelial dysfunction. There is a significant association between KSF and CVD, supporting the consideration of KSF as a systemic, calcium-mediated disease. Clinicians will benefit from being aware of this connection. [Display omitted] • Largest systematic review on the topic of cardiovascular disease and kidney stones. • Increased risk of coronary artery disease, stroke, and peripheral arterial disease. • Relationship was stronger for female-identifying kidney stone formers. • First time epidemiological and biological review have been combined in this field. • Strengthened a poorly understood, clinically relevant relationship. [ABSTRACT FROM AUTHOR]