Warfarin Accelerates Aortic Calcification by Upregulating Senescence-Associated Secretory Phenotype Maker Expression.

Area of Science:

• Cardiovascular Research
• Vascular Biology
• Pharmacology

Background:

• Arterial calcification (AC) is a significant risk factor for cardiovascular disease.
• Warfarin, a vitamin K antagonist (VKA), has been implicated in promoting AC.
• The role of warfarin in AC, especially concerning age, requires further elucidation.

Purpose of the Study:

• To investigate the relationship between warfarin use and arterial calcification.
• To examine the influence of age on warfarin-associated AC.
• To explore the underlying mechanisms of warfarin-induced AC in different age groups.

Main Methods:

• A case-cohort study using data from the Multi-Ethnic Study of Atherosclerosis (MESA) involving 6655 participants.
• Analysis of AC in relation to age, vitamin K, and systemic inflammation markers (IL-6, TNF-α).
• In vitro studies to assess warfarin's effect on phosphate-induced AC in vascular cells across different ages.

Main Results:

• AC was associated with age and vitamin K, with higher scores linked to increased IL-6 and TNF-α.
• Warfarin users exhibited significantly more calcified coronary plaques than non-VKA users.
• Warfarin's dose-time response correlated with AC and IL-6 in patients < 65 years, but not in older patients. In vitro studies showed warfarin exacerbated early-stage calcification in young VSMCs.

Conclusions:

• Aging and warfarin treatment are independent risk factors for increased arterial calcification.
• Younger patients appear more susceptible to warfarin-related AC than older patients.
• Warfarin-induced cellular senescence may explain the heightened sensitivity in younger individuals.