What is coronary artery calcification?
Arterial calcification is a process that sees the hardening of your arteries as calcium crystals build up within the blood vessel walls. This is a gradual process that occurs as you age. There are two main types of arterial calcification, intimal and medial.1
Intimal calcification is caused by calcium crystals building up on the innermost layer of the arterial wall. Intimal calcification is the end stage of the atherosclerosis cascade. Atherosclerosis causes coronary heart disease, which occurs when cholesterol-rich fatty plaques are deposited on the inner wall of the blood vessel, narrowing the artery so less blood can travel through it to reach the heart and provide it with the proper amount of oxygen and nutrients it needs. After these plaques form, they are calcified, making them hard and rigid.
Medial calcification is the build-up of calcium crystals in the middle layer of the artery wall. This layer is made mostly of smooth muscle cells, which are susceptible to deposition of calcium in this area which hardens the vessel. Medial calcification is less common but is associated with chronic kidney disease and diabetes.
Arterial calcification is dangerous because your muscular arteries are designed to be elastic and flexible, able to narrow and widen on demand and respond well to high blood pressure. These traits are lost when calcium crystals populate an area of an artery, making the vessels rigid and immovable, and increasing blood pressure. Increased blood pressure is troublesome because it puts extra strain on your cardiovascular system causing wear and tear to the heart and vessels. Vessel injury in turn triggers atherosclerotic plaque formation on top of the injury site that further increases calcification and increases the risk of a heart attack.
Ages affected and more prone to coronary artery calcification
Calcification is a frequent finding in the arteries of the elderly, with incidence increasing as you age. In a study of patients aged 80 and above, calcification was evident in 81% of patients!2 This may be because as you age, all the factors in place that inhibit the release of calcium at the artery wall area are less effective. 3 On the flip side, as you age, more osteogenic pathways (that stimulate bone deposition) are turned on,4 especially in the setting of diabetes, inflammation, oxidative stress and high cholesterol (all traits of ageing bodies).
As you age, with each cell division, the telomeres (ends of your DNA) shorten. This causes loss of cell functionality and ability to divide, leading to cell death. If this occurs in the endothelial cells that make up the inner lining of your arteries, they will not be able to repair in response to vessel damage. This increases the likelihood of vessel injury that sparks atherosclerosis (so indirectly triggers intimal calcification). Dying cells and vessel wall injury will cause inflammatory signals to be released. Inflammation is a key driver of calcification. An inflamed vessel environment causes the conversion of vascular wall cells into bone cells that will deposit calcium crystals. Lastly, dying cells undergo apoptosis, and apoptotic bodies can trigger pro-calcific signalling cascades that will alter gene expression to harden blood vessels.5
Oxidative stress is another hallmark of ageing. Reactive oxygen species (ROS) build up in your cells over time and cause irreparable damage to DNA and mitochondria. Alterations to DNA due to ROS damage can change the genes expressed in vascular smooth muscle cells and contribute to their conversion into bone cells causing calcification. ROS can cause cell death, increasing vessel injury and inflammation to indirectly encourage calcification.6 The metabolic abnormalities of diabetic cells cause the increased production of the ORS superoxide in the cells that line your blood vessels’ inner walls where it can exert its pro-calcific damage.7 Incidence of type-2 diabetes increases with age.
Furthermore, with age comes increased susceptibility to other diseases like obesity and Type-2 diabetes and chronic kidney disease. Obesity increases calcification risk because levels of cholesterol circulating in the blood will increase. Cholesterol is the main component of the fatty deposits that appear on the arterial walls to block them during atherosclerosis and what will get calcified. Furthermore, blood pressure increases during obesity because the heart must work harder to pump blood around the body, high blood pressure poses a danger to the vascular system, increasing the chances of injury (and atherosclerosis). Diabetes increases calcification risk because, during times of high blood sugar, signalling is unbalanced promoting calcification-activating signalling.8 Lastly, chronic kidney disease disrupts the delicate extracellular ion balance present in the body, increasing phosphate circulating in the body contributes to the formation of calcium phosphate crystals on the vessel walls.9
Symptoms, causes and treatment
Symptoms of coronary artery calcification
Calcification is often asymptomatic, so it is hard to know if you have it until a cardiovascular event occurs. Due to calcification being intimately linked to atherosclerosis and the narrowing of blood vessels, symptoms will overlap with classic coronary heart disease symptoms of angina such as:
- Chest pain that can spread to your arms, back, neck and abdomen
- Dizziness/Light-headedness and breathlessness - as a result of reduced blood to the heart due to narrowing calcified arteriesHowever, it is hard to distinguish angina episodes that can be relatively harmless from the experience of a heart attack which sees all of the same symptoms. Therefore, it is better to be safe than sorry, and contact medical help straight away by calling 999 if you experience any combination of these symptoms. You may be experiencing a major cardiac event10
Causes of coronary artery calcification
Intimal and medial calcification can have different causes. Intimal calcification is primarily a stage of atherosclerosis so classical risk factors for such (indirectly increasing the probability for intimal calcification) include:
- High blood pressure
- High cholesterol
- Poor diet
- Physical inactivity
- Alcohol consumption
Medial calcification is caused by the conversion of smooth muscle cells that make up the middle arterial layer into bone cells. This is mostly caused by high blood sugar as a symptom of diabetes and excess phosphate levels in the blood, as a symptom of improper blood filtering from chronic kidney disease.11
Both of these conditions that cause calcification have an age-bias, disfavouring older people and making them more susceptible to calcification.
Coronary artery calcification treatment
There isn’t one set clinical regime to treat all cases of arterial calcification. Classic coronary artery disease treatment procedures like a coronary angioplasty (inserting a balloon or stent into the narrowed vessel to widen it) and a coronary bypass graft (rerouting the blood flow with a new vessel to avoid the narrowed artery) are more dangerous and less effective when a patient has severe arterial calcification. Surgeons can instead perform an atherectomy (either rotational, orbital or laser) where the plaque and calcium crystals built up in the artery wall is shaved down.12
Medically, to treat arterial calcification, what you are prescribed depends on the type of calcification you have. If you have medial calcification as a side effect of chronic kidney disease you will have to take potassium supplements to rebalance your ion levels and stop calcification. Alternatively, if you are a heart disease patient, with calcified regions due to atherosclerotic plaque build-up then statins (to lower blood cholesterol) and blood pressure-lowering medications can be prescribed. Lastly, there are drugs available to stop bone cell conversion, action and survival so that less calcium is deposited onto the arterial walls, these include Bisphosphonate drugs.13
Diagnosis and prevention
How is coronary artery calcification diagnosed
The first and most used diagnostic method to identify coronary artery calcification is computed tomography coronary angiography (CTCA). Calcified vessels will appear on the CTCA scans so physicians can visualise the calcium-based cardiac burden and give a coronary artery calcification score to quantify the severity of the calcification. The values will fall into one of the three groups, 0–100, 101–400, and more than 400. Which numerical score group you fall into dictates the risk you are of a heart attack and the urgency of treatment.14
Intravascular ultrasound is an alternative method used to diagnose coronary artery calcification. It is highly sensitive and specific. The ultrasound wand is inserted into the blood vessels via a catheter so the arteries can be visualised and the degree of calcification found.15
How can we prevent coronary artery calcification
Though coronary arterial calcification is an unfortunate and inevitable symptom of ageing (an independent risk factor in its own right), many other risk factors will speed its development and increase its severity. Therefore, even in older patients, the same advice is given to build a preventative lifestyle with a balanced diet, reduced stress and increased exercise.
If you are in a high-risk demographic for coronary arterial calcification(diabetic, elderly, have circulatory issues, have a family history of heart disease or calcification or have chronic kidney disease), the best way to prevent severe calcification from forming is to identify it early to begin a treatment course. Therefore, it is always important to stay vigilant to your cardiovascular health. You may be able to have your calcification score screened, even with no symptoms if you have a strong predisposition for the pathology.
Surprisingly, dietary levels of calcium do not influence vascular calcification (despite the name). Instead, coronary arterial calcification is associated with conventional cardiovascular risk factors including:
- Family history
- Chronic kidney disease
- Poor diet
- Physical inactivity
- High cholesterol
- High blood pressure
- Alcohol consumption
When to see a doctor
If you are worried generally about your heart health because you are a member of an at-risk group for calcification, talk to your GP for screening options and advice. If you are experiencing a combination of the heart symptoms mentioned, contact an ambulance straight away. Although these symptoms could be angina caused by a partially limited blood supply to the heart, they also could be the symptoms of a heart attack which is a serious medical emergency.
Coronary artery calcification is a process of hardening of your arteries into bone-like structures as calcium crystals build up within the blood vessel walls with age. It normally develops silently, and is more common in individuals with certain risk factors. Therefore it is important to be attentive towards it (especially as you age) to get as early a diagnosis as possible to improve treatment odds.
This article was written to increase your awareness so that you can do just that.
- O'neill WC, Lomashvili KA. Recent progress in the treatment of vascular calcification. Kidney international. 2010 Dec 2;78(12):1232-9. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3184001/
- Roberts WC, Shirani J. Comparison of cardiac findings at necropsy in octogenarians, nonagenarians, and centenarians. The American journal of cardiology. 1998 Sep 1;82(5):627-31. Available from: https://pubmed.ncbi.nlm.nih.gov/9732892/
- Sage AP, Tintut Y, Demer LL. Regulatory mechanisms in vascular calcification. Nature Reviews Cardiology. 2010 Sep;7(9):528-36. Available from: https://pubmed.ncbi.nlm.nih.gov/20664518/
- Boström KI, Rajamannan NM, Towler DA. The regulation of valvular and vascular sclerosis by osteogenic morphogens. Circulation research. 2011 Aug 19;109(5):564-77. Available from: https://pubmed.ncbi.nlm.nih.gov/21852555/
- Abedin M, Tintut Y, Demer LL. Vascular calcification: mechanisms and clinical ramifications. Arteriosclerosis, thrombosis, and vascular biology. 2004 Jul 1;24(7):1161-70. Available from: https://pubmed.ncbi.nlm.nih.gov/15155384/
- Chiao YA, Lakatta E, Ungvari Z, Dai DF, Rabinovitch P. Cardiovascular disease and aging. Advances in geroscience. 2016:121-60. Available from: https://www.researchgate.net/publication/295259668_Cardiovascular_Disease_and_Aging
- Rota M, LeCapitaine N, Hosoda T, Boni A, De Angelis A, Padin-Iruegas ME, Esposito G, Vitale S, Urbanek K, Casarsa C, Giorgio M. Diabetes promotes cardiac stem cell aging and heart failure, which are prevented by deletion of the p66shc gene. Circulation research. 2006 Jul 7;99(1):42-52. Available from: https://pubmed.ncbi.nlm.nih.gov/16763167/
- Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circulation research. 2010 Oct 29;107(9):1058-70. Available from: https://pubmed.ncbi.nlm.nih.gov/21030723/
- Shanahan CM, Crouthamel MH, Kapustin A, Giachelli CM. Arterial calcification in chronic kidney disease: key roles for calcium and phosphate. Circulation research. 2011 Sep 2;109(6):697-711. Available from: https://pubmed.ncbi.nlm.nih.gov/21885837/
- Amann K. Media calcification and intima calcification are distinct entities in chronic kidney disease. Clinical Journal of the American Society of Nephrology. 2008 Nov 1;3(6):1599-605. Available from: https://pubmed.ncbi.nlm.nih.gov/18815240/
- Liu W, Zhang Y, Yu CM, Ji QW, Cai M, Zhao YX, Zhou YJ. Current understanding of coronary artery calcification. Journal of geriatric cardiology: JGC. 2015 Nov;12(6):668. Available from: https://pubmed.ncbi.nlm.nih.gov/26788045/
- 13. Wu M, Rementer C, Giachelli CM. Vascular calcification: an update on mechanisms and challenges in treatment. Calcified tissue international. 2013 Oct;93(4):365-73. Available from: https://pubmed.ncbi.nlm.nih.gov/23456027/
- Achenbach S. Computed tomography coronary angiography. Journal of the American College of Cardiology. 2006 Nov 21;48(10):1919-28. Available from: https://pubmed.ncbi.nlm.nih.gov/17112978/
- Mintz GS, Popma JJ, Pichard AD, Kent KM, Satler LF, Chuang YC, Ditrano CJ, Leon MB. Patterns of calcification in coronary artery disease: a statistical analysis of intravascular ultrasound and coronary angiography in 1155 lesions. Circulation. 1995 Apr 1;91(7):1959-65. Available from: https://pubmed.ncbi.nlm.nih.gov/7895353/