Monday, September 16, 2013

Blood Vessel Calcification (or Part III of Should I take calcium?)

Here's the heart of the calcium supplement debate. Does taking extra calcium for prevention and treatment of bone loss associated with aging hasten the calcification of blood vessels, a process which is also associated with aging. That which is normal and healthy for your skeleton, namely the incorporation of calcium crystals into its structure, is neither normal nor healthy within your arteries.  Studies of aging humans and their whole body CT scans suggest that virtually all men and women have some demonstrable vascular calcium by age 70.(1)  Furthermore, the calcification was widespread in 80% of men and 60% of women by that age, and extensive calcification is known to correlate with a high degree of atherosclerosis more commonly known as 'hardening of the arteries'.(2)

This sort of dilemma--a basically good physiological process gone rogue--takes us into a lot of science on calcium, injury, hormones, aging, and inflammation.  The CT scanning study cited above not only confirmed that calcification, and therefore atherosclerosis, is definitely correlated with aging and increases as the years progress, it also, once again, found that menopause with its attendant loss of estrogen is also a time of accelerated progression of vascular disease.  Women under 50 years of age were much less likely than men to have calcium, but the prevalence of calcified vessels greatly increased between 50 and 60, and the gals were as likely as the guys to have calcifications by age 70 (just not as extensive).  Whether or not hormone therapy can slow down this vascular deterioration is another complicated story for another post.

Of note in this discussion, however, is the immune system's response to the presence of calcium crystals in developing atherosclerotic lesions in arteries.  Cells called macrophages which are first responders to bodily harm show up early in the course of blood vessel injury and set immediately to work eating foreign invaders Pac-Man style.  As they gobble up various harmful substances such as oxidized LDL cholesterol or basic calcium phosphate (BCP) crystals, they send out proinflammatory cytokines which are chemical messenger molecules that further activate an immune response.  This is a good thing with regards to incoming foreign bodies such as bacteria or dirt from the sidewalk when you've fallen and scraped your knee, but not so good when it's an ongoing assault from various environmental insults such as LDL-cholesterol, trans-fats, cigarette smoke, or...too much calcium (more on this later).  The inflammation from BCP crystals in activated macrophages "may lead to a positive feed-back loop of calcification and inflammation driving disease progression."(3)  In other words, once blood vessels are disturbed by calcification, the immune response invites the deposition of more calcium.

Here's one more puzzle to set your head reeling (mine is already so why not join me?).  There is a known clinical association between vascular calcification and osteoporosis.  In other words, those of us dealing with loss of bone mineral density are the very people that need to worry most about gaining unwanted vascular mineralization in the form of calcium in our arterial walls.  This suggests a link between bone and vascular metabolism.  Either vascular calcification promotes bone mineral loss, bone loss hastens vascular calcification, or there's a common underlying pathology to both processes.  The latter seems the most likely scenario, and the underlying normal and abnormal physiology of calcification in the body finally leads to some answers about whether or not calcium supplements are a good idea.

More on that in the next post.

1) Matthew A, et al. Patterns and Risk Factors for Systemic Calcified Atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology.                                   
2) Solberg LA, Eggen DA.  Localization and sequence of development of atherosclerotic lesions in the carotid and vertebral arteries. arteries. Circulation; 1971.
3) Nadra, I, et al. Proinflammatory Activation of Macrophages by Basic Calcium Phosphate Crystals via Protein Kinase C and MAP Kinase Pathways. Circulation Research. 96: 1248-1256.