Vascular calcification is the deposition of calcium in soft tissues, specifically within the walls of arteries and veins, commonly described as a hardening of the arteries. Although once viewed as a simple degenerative consequence of age, current scientific understanding confirms this is an active, highly regulated biological process. The abnormal buildup of mineral deposits strongly predicts future cardiovascular problems, including heart attack and stroke.
Defining Vascular Calcification
Vascular calcification involves the pathological deposition of mineral within the vascular system, primarily calcium phosphate crystals known as hydroxyapatite. This crystalline substance is chemically similar to bone mineral, but its presence in the vessel wall causes a loss of elasticity. The process is not passive precipitation, but an active, cell-mediated process tightly regulated by inhibitors and inducers. When protective mechanisms fail, calcium phosphate accumulates. This buildup is distinct from typical atherosclerotic plaque, though it often occurs alongside it, affecting various parts of the circulation.
Intimal Versus Medial Calcification
The location of mineral deposits within the artery wall dictates the type of calcification and its clinical impact. Calcification can occur in the inner layer, the intima, or the middle layer, the media. Intimal calcification is closely associated with atherosclerosis, where fatty plaques accumulate beneath the vessel lining. This form is typically focal and localized within atherosclerotic plaques, leading to vessel narrowing and potential blockage. Calcified plaques in the intima increase the risk of plaque rupture, which can trigger a heart attack or stroke.
Medial calcification, often called Mönckeberg’s sclerosis, occurs in the tunica media, the middle layer rich in vascular smooth muscle cells. This type is typically diffuse and circumferential, spreading around the entire vessel wall. Medial calcification is non-obstructive, meaning it does not narrow the vessel lumen to cause immediate blockages. Its main consequence is a loss of arterial elasticity, leading to arterial stiffness. While both types are associated with cardiovascular disease, medial calcification is primarily linked to stiffness and is common in specific systemic diseases.
The Biological Process of Calcification
The cellular mechanism underlying vascular calcification is a complex process similar to bone formation. This involves a phenotypic conversion where vascular smooth muscle cells (VSMCs) lose their normal contractile function. These VSMCs transform into cells resembling osteoblasts or chondrocytes, which build bone or cartilage. This transformation is marked by the expression of specific bone-related proteins, such as Runx2 and alkaline phosphatase, normally silenced in healthy blood vessels.
These transformed cells actively promote the mineralization of the surrounding extracellular matrix, turning the vessel wall into bone-like tissue. VSMCs also release matrix vesicles, which act as nucleation sites to initiate the formation and growth of hydroxyapatite crystals. The balance between factors that promote mineralization, like high phosphate levels, and natural inhibitors determines whether this process progresses. Passive precipitation of crystals can also occur when calcium and phosphate concentrations exceed a certain threshold, compounding the active cellular process.
Systemic Conditions That Increase Risk
Several systemic conditions accelerate vascular calcification, transforming it from a slow aging phenomenon into a rapidly progressing disease. Chronic Kidney Disease (CKD) is a primary driver, as impaired kidney function disrupts the body’s ability to regulate mineral balance. This disruption leads to hyperphosphatemia, an excess of phosphate in the blood, which promotes the osteogenic transformation of vascular cells. CKD patients frequently experience a more severe and widespread form of calcification.
Diabetes Mellitus is another risk factor, as chronic high blood sugar and associated inflammation contribute to vascular damage. Diabetes is particularly associated with medial calcification, causing severe arterial stiffness in the peripheral arteries. Advanced age is a non-modifiable risk factor, with most individuals over 60 showing some evidence of mineral deposits. Other risk factors include persistent inflammation, dyslipidemia, and abnormalities in Vitamin D and K metabolism.
Clinical Impact on Vessel Function
The presence of vascular calcification increases the risk of adverse cardiovascular events. The hardening of the arteries, particularly due to medial calcification, leads to a loss of arterial elasticity and compliance. This loss results in increased pulse wave velocity, meaning the pressure wave travels faster along the stiffened arteries. The faster wave returns to the heart at an unfavorable time, increasing the workload on the heart muscle and causing higher systolic blood pressure, which can lead to ventricular hypertrophy.
Intimal calcification contributes to the instability and progression of atherosclerotic plaques. While the calcium deposits may not cause a complete blockage, they indicate the overall atherosclerotic burden and plaque vulnerability. The calcified deposits within the plaque can predispose it to rupture, releasing clot-forming material into the bloodstream. This rupture is the direct cause of most acute events, such as a heart attack or an ischemic stroke.