Coronary calcium: Cause or effect?

Here's an interesting observation made by a British research group.

We all know that coronary calcium, as measured by CT heart scans, are a surrogate measure of atherosclerotic plaque "burden," i.e., an indirect yardstick for coronary plaque. The greater the quantity of coronary calcium, the higher the heart scan "score," the greater the risk for heart attack and other unstable coronary syndromes that lead to stents, bypass, etc.

But can calcium also cause plaque to form or trigger processes that lead to plaque formation and/or instability?

Nadra et al show, in an in vitro preparation, that calcium phosphate crystals are actively incorporated into inflammatory macrophages, which then trigger a constellation of inflammatory cytokine release (tumor necrosis factor-alpha, interleukins), fundamental processes underlying atherosclerotic plaque formation and inflammation.

Here's the abstract of the study:
Proinflammatory Activation of Macrophages by Basic Calcium Phosphate Crystals via Protein Kinase C and MAP Kinase Pathways:

A Vicious Cycle of Inflammation and Arterial Calcification?

Basic calcium phosphate (BCP) crystal deposition underlies the development of arterial calcification. Inflammatory macrophagescolocalize with BCP deposits in developing atherosclerotic lesionsand in vitro can promote calcification through the release of TNF alpha. Here we have investigated whether BCP crystals can elicit a proinflammatory response from monocyte-macrophages.BCP microcrystals were internalized into vacuoles of human monocyte-derived macrophages in vitro. This was associated with secretion of proinflammatory cytokines (TNF{alpha}, IL-1ß and IL-8) capable of activating cultured endothelial cells and promoting capture of flowing leukocytes under shear flow. Critical roles for PKC, ERK1/2, JNK, but not p38 intracellular signaling pathways were identified in the secretion of TNF alpha, with activation of ERK1/2 but not JNK being dependent on upstream activation of PKC. Using confocal microscopy and adenoviral transfection approaches, we determined a specific role for the PKC-alpha isozyme.

The response of macrophages to BCP crystals suggests that pathological calcification is not merely a passive consequence of chronic inflammatory disease but may lead to a positive feed-back loop of calcification and inflammation driving disease progression.

This observation adds support to the notion that increasing coronary calcium scores, i.e., increasing accumulation of calcium within plaque, suggests active plaque. As I say in Track Your Plaque, "growing plaque is active plaque." Active plaque means plaque that is actively growing, inflamed and infiltrated by inflammatory cells like macrophages, eroding its structural components, and prone to "rupture," i.e., cause heart attack. Someone whose first heart scan score is, say, 100, followed by another heart scan score two years later of 200 is exposed to sharply increasing risk for cardiovascular events which may, in part, be due to the plaque-stimulating effects of calcium.

Conversely, reducing coronary calcium scores removes a component of plaque that would otherwise fuel its growth. So, people like our Freddie, who reduced his heart scan score by 75%, can be expected to enjoy a dramatic reduction of risk for cardiovascular events.

Less calcium, less plaque to rupture, less risk.

Comments (25) -

  • Mike N

    11/28/2010 3:59:05 PM |

    Does this mean we shouldn't be taking calcium supplements? I've been taking 500 mg per day.

  • Richard Laurence

    11/28/2010 5:54:12 PM |

    Hello Dr Davis, I've read recently that calcium supplements are a bad idea - they increase the risk of cardiovascular disease.

    Does dietary calcium have a similar effect? I would value you opinion.



  • Anonymous

    11/28/2010 5:56:34 PM |

    There is a lot of controversy in Canada currently for a treatment of MS; the opening of blocked or restricted neck veins.  Dr. D, you mentioned dementia, which, to my simple understanding, is either nerve damage or vascular dementia due to a series of small strokes. So my reason for this post is to ask the question; Is the tissue type of veins the same as arteries, and if so, would the same inflammation calcification cycle occur?  If the answer is yes, does that imply vitamin D3 /K2 and wheat elimination has potential for MS sufferers and people trying to avoid vascular dementia in old age?
    Trev (recovering vegetarian)

  • Dr. William Davis

    11/28/2010 6:27:06 PM |

    Mike and Richard--

    I have been advising my patients to take no more than 500 mg calcium per day, given the potential for increased cardiovascular events with higher doses per the studies coming from New Zealand. Also, achieving healthy vitamin D blood levels easily doubles the intestinal absorption of calcium, making supplementation of additional calcium less necessary.

  • Anonymous

    11/28/2010 6:57:46 PM |

    This research was published in 2005.
    Any updates on this?


  • rhc

    11/28/2010 8:20:22 PM |

    Dr. Davis, I hear/read so much about 'inflamation' in the body and 'anti-inflammatory' diets, etc.  So I was wondering if the C-reactive protein test is a reliable way to measure this? If so what is the suggested limit or safe range in YOUR opinion?

  • Anonymous

    11/28/2010 8:35:58 PM |

    Excellent blog! I eat an almost dairy free diet (grass-fed butter is the exception for vitamins K  and A and butyric acid etc and to add fat to overly lean protein)   that includes almonds, filberts, sardines and salmon with bones and greens for calcium. I also eat lots of very dark chocolate/cocoa.  I supplement with vitamin d.  I recently passed a calcium oxalate kidney stone and doc says my dairy free diet is far too rich in oxalates and phytic acid. I have also been plagued with calf and foot cramps. He suggests adding small amounts of cheese or a calcium supplement to block the oxalates.  Despite my magnesium rich diet -- he also says I need a magnesium supplement. It's only been a few days since I've added 2 calcium/mag tablets at night (only contain about 300mg calcium and 180 mag plus additional mag citrate powder in hot water) and my cramps seem to have subsided.  Anyone else get mineral deficiencies eating paleo style with nuts and bones but no supplements?

  • Lori Miller

    11/28/2010 11:11:37 PM |

    Anonymous, I take Mg supplements, too. I seem to have a hard time absorbing minerals.

    The nuts you're eating contain phytic acid, which blocks mineral absorption. The Weston A. Price Foundation recommends soaking and roasting nuts and seeds to neutralize the phytic acid.

  • john

    11/28/2010 11:50:12 PM |

    This is more complicated than the notion that high calcium intake=high "calcification" ...

    ...Blood Ca and its accumulation in soft tissues can increase (from bones) even though less is eaten. Ca metabolism is far more important than magnitude of intake.  It seems that Ca supplementation actually decreases intracellular amounts.

  • Martin Levac

    11/29/2010 2:26:12 AM |

    If the diet is acidic, calcium will be used to buffer this acid which will ultimately be excreted through the urine. On the other hand, if the diet is alkaline, then no calcium is needed for this purpose. So the question is, where does this un-needed calcium go?

    Maybe an alkaline diet isn't such a good thing after all is all I'm saying.

  • Dr. William Davis

    11/29/2010 2:26:24 AM |

    Anon about MS--

    I would be careful about extrapolating the wheat-dementia connection to MS. It would be deeply concerning if there were a connection, but I am not aware of such a connection.

    The one truly compelling observation being made in MS is the vitamin D discussion. To my knowledge, that clinical trial is still underway in Toronto.

  • nightrite

    11/29/2010 3:08:35 AM |

    I too had lots of trouble with kidney stones but no more.  The only change I made was stopping calcium supplements and starting magnesium.  I take 500 mg of mag at bedtime and have not had a kidney stone pain in almost 2 years.

  • Anonymous

    11/29/2010 5:15:36 AM |

    Dr. Davis,

    Wondering how you explain the paradox that statins seems to significantly increase coronary calcium, but to lower coronary events?


  • Pat D.

    11/29/2010 6:31:45 AM |

    Regarding magnesium supplementation - I've read that most magnesium supplements have little to no bio-availability, making it pointless to take them.  There are some on the market which address this concern and I've seen good reviews of them - but they do cost more.  I've also read at multiple nutrition sites that our foods have less and less magnesium as our soils are very depleted.  But almonds, pepitas and nut butters are good sources, as are some other foods, like black beans.  There are lists online.  I've also read that Epsom salt baths are a good source of magnesium.  So I take ES baths and I've made myself a magnesium skin lotion with ES.  Instructions for doing this can be found online.

  • Myron

    11/29/2010 7:00:01 PM |

    Basic Ca phosphate crystal deposition disease: Most pathologic calcifications throughout the body contain mixtures of carbonate-substituted hydroxyapatite and octacalcium phosphate. Because these ultramicroscopic crystals are nonacidic Ca phosphates, the term “basic Ca phosphate” (BCP) is much more precise than “apatite.”

    Nutritionally people eat hydroxyapatite not apatite  BCP

    I guessing the moral of the story is to eat acidic calcium, calcium citrate or hydroxyapatite not apatite.

  • Anand Srivastava

    11/29/2010 7:21:51 PM |

    I have read that Vitamin K2 is very helpful in getting rid of the Calcium.

    Martin Levac also raises a good point. I would think as long as the diet is balanced, then calcium will not stay in the arteries.

    It could be that too alkaline diets might cause this problem. In India several very strict vegetarian (not vegan) societies do not eat onions and garlic. Both are very highly alkaline.

    While Non-vegetarian societies eat a lot of them. I guess the difference may be due to the acid base theory. The over all diet should be very slightly alkaline to be best.

  • Anonymous

    11/30/2010 1:16:14 AM |

    This ACID/BASE diet argument is a little odd sounding to me but even a quick Google leads to the simple explanation that it is the influence of minerals in the diet on blood pH

    "The consumption of animal protein, grain, and high amounts of milk increases the acidity of the body, whereas foods rich in minerals such as green vegetables and fruit increase the alkalinity. Generally, the Western diet induces a chronic, low-grade metabolic acidosis.  This relates to the loss of calcium through excretion in urine.  Here is the link:-

    cool, but is there any link to heart heath?

  • Monique Hawkins

    11/30/2010 2:33:24 AM |

    I see that some readers asked the same question I was thinking related to calcium supplements. For instance, I hear quite a bit how much coral calcium is good for people. I would assume based on what you have said to take no more than 500 mg of that as well per day?

  • Dr. William Davis

    11/30/2010 3:20:33 AM |

    HI, David--

    While statins do not have much effect on slowing the progression of coronary calcium, I know of no data suggesting that they increase coronary calcium.

    Hi, Pat--

    While absorption of magnesium products varies widely, magnesium "salts" like the malate and glycinate are absorbed quite well.

  • Might-o'chondri-AL

    11/30/2010 4:52:20 AM |

    Basicly, calcium concentrated outside a cell has a safe bio-chemical role to perform & magnesium inside that same cell has it's major bio-chemical role. They both have vital cellular functions.

    When calcium "lingers" inside a cell it keeps over-stimulating things; building up in there is even worse. This inflammatory mechanism occurs in many tissues, not just blood vessels.

    Dietary deficiencies of calcium & magnesium naturally trigger a para-thyroid hormone activation. This hormone signal is for getting more calcium available to the body's tissue cells.

    As you get older there is commonly more para-thyroid hormone circulating in your blood. It can form a negative feedback loop with pro-inflammatory factors (like cytokines); as the inflammation keeps calcium inside the cell.

    Cause or effect of calcium being where it's not supposed to be may involve a vicious circle. Rare youngsters with coronary calcium would suggest uncommon genetics.

  • PY

    11/30/2010 9:20:02 PM |

    The preceding paragraph to the above-quoted passage is probably also very relevant to this discussion:

    "It is not clear how or why the claims for high vitamin D levels started, medical experts say. First there were two studies, which turned out to be incorrect, that said people needed 30 nanograms of vitamin D per milliliter of blood, the upper end of what the committee says is a normal range. They were followed by articles and claims and books saying much higher levels — 40 to 50 nanograms or even higher — were needed."

    Can you point us to other studies that point to the efficacy of 30 ng+ concentrations?  

    I am not attempting to be adversarial at all to your views -- I have been following them closely following my own research.  But given that I havea  data-driven bent, this report has given me a reason to reconsider, and I would love your guidance.

  • Anonymous

    12/2/2010 12:01:13 AM |

    I doubt anyone needs calcium or magnesium supplementation. Calcium and magnesium are virtually impossible to avoid - I believe they're in every plant food. I'll stick with D3, MK-7 and hormones.

  • Dr Matti Tolonen

    12/4/2010 1:39:56 PM |

    "Less calcium, less plaque to rupture, less risk."
    It is well known that ethylesterized omega-3 fatty acids, e.g., E-EPA, stabilize arterial plaques. This explains at least partly how these omega-3´s protect the heart and arteries. See for instance J Atheroscler Thromb. Epub ahead of print 2010 Nov 17

  • Leo

    12/5/2010 12:56:06 PM |

    Minä suosittelen K2-vitam.  Se poistaa kalkkia ja ehkäiseen sen kertymistä verisuoniin !!!

  • Anonymous

    12/13/2010 5:23:31 PM |

    Are all OTC omega 3 products ethylesterized? If not, which ones are?