Interventions to Attenuate Cardiovascular Calcification Progression: A Systematic Review of Randomized Clinical Trials

• Published in: Journal of the American Heart Association Vol. 12; no. 23; p. e031676
• Main Authors: Murali, Shashank, Smith, Edward R, Tiong, Mark K, Tan, Sven-Jean, Toussaint, Nigel D
• Format: Journal Article
• Language: English
• Published: England John Wiley and Sons Inc 05.12.2023; Wiley
• Subjects: Antioxidants; cardiovascular risk; coronary artery calcification; Diabetes Mellitus; Disease Progression; Garlic; Humans; Hypoglycemic Agents; Original Research; Phytotherapy; Plant Extracts - therapeutic use; randomized controlled trials; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; systematic review; valvular calcification; vascular calcification; Vascular Calcification - drug therapy; Vascular Calcification - therapy; valvular calcification; cardiovascular risk; coronary artery calcification; randomized controlled trials; systematic review; vascular calcification
• ISSN: 2047-9980; 2047-9980
• DOI: 10.1161/JAHA.123.031676

Cardiovascular calcification, characterized by deposition of calcium phosphate in the arterial wall and heart valves, is associated with cardiovascular morbidity and mortality and is commonly seen in aging, diabetes, and chronic kidney disease. Whether evidence-based interventions could significantly attenuate cardiovascular calcification progression remains uncertain. We conducted a systematic review of randomized controlled trials involving interventions, compared with placebo, another comparator, or standard of care, to attenuate cardiovascular calcification. Included clinical trials involved participants without chronic kidney disease, and the outcome was cardiovascular calcification measured using radiological methods. Quality of evidence was determined by the Cochrane risk of bias and Grading of Recommendations, Assessment, Development, and Evaluations assessment. Forty-nine randomized controlled trials involving 9901 participants (median participants 104, median duration 12 months) were eligible for inclusion. Trials involving aged garlic extract (n=6 studies) consistently showed attenuation of cardiovascular calcification. Trials involving 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (n=14), other lipid-lowering agents (n=2), hormone replacement therapies (n=3), vitamin K (n=5), lifestyle measures (n=4), and omega-3 fatty acids (n=2) consistently showed no attenuation of cardiovascular calcification with these therapies. Trials involving antiresorptive (n=2), antihypertensive (n=2), antithrombotic (n=4), and hypoglycemic agents (n=3) showed mixed results. Singleton studies involving salsalate, folate with vitamin B6 and 12, and dalcetrapib showed no attenuation of cardiovascular calcification. Overall, Cochrane risk of bias was moderate, and the Grading of Recommendations, Assessment, Development, and Evaluations assessment for a majority of analyses was moderate certainty of evidence. Currently, there are insufficient or conflicting data for interventions evaluated in clinical trials for mitigation of cardiovascular calcification. Therapy involving aged garlic extract appears most promising, but evaluable studies were small and of short duration.