Those of us who grew up in the 1990s may still remember the plastic container shaped like a happy puppy filled with calcium tablets. Our mothers used to feed us those tablets daily to make our bones stronger. Fast forward two or three decades. In our middle age, the humble calcium pops up again, raising questions about our heart health.
The presence of calcium in our coronary arteries is a marker for plaque formation and arterial blockages, making it an effective indicator for future cardiac complications, including heart attacks, depending on the nature of plaque and other vascular co-morbidities. Before we head further down, we need to keep in mind that this avatar of calcium has nothing to do with its dietary intake.
The calcification of arteries is a result of complex vascular interactions that begin with the formation of lipid-rich plaques, especially due to the cholesterol in our bloodstream. “Calcification is scarring that occurs in plaques in the arteries. It has nothing to do with dietary calcium that is for bone health. This (calcification) is a marker of the buildup of plaque in the arteries of the heart and neck, causing heart attacks and strokes,” says Dr Matthew Budoff, professor of medicine, University of California Los Angeles (UCLA) and endowed chair of preventive cardiology, Lundquist Institute, California, in an online interaction with Happiest Health.
The plaque particles and the subsequent formation of blood clots on its rupture could lead to complete choking of the arteries, thereby triggering heart attacks or brain strokes. This condition leading to choked arteries due to plaque formation is termed atherosclerosis (a variation of the stiffening of arteries affecting blood flow and oxygen in our body). Atherosclerosis manifests not just in the coronary arteries but also in the ones carrying blood to the brain and the upper and lower limbs (peripheral artery disease).
“Calcification usually occurs mostly in men over 40 and women over 50. It is not reversible, but preventable, and we can slow or stop the progression of the condition before it blocks the artery and causes a heart attack or stroke (brain attack),” Dr Budoff adds.
It is not necessary that all lipid plaques get calcified in our coronary artery. Some of them will be non-calcified, consisting of cholesterol and lipid molecules. The formation of these lipid-rich noncalcified plaques is also rated as a high-risk factor for heart attack as they too could rupture and lead to the formation of blood clots in our arteries.
What is calcification?
It is estimated that around 99 percent of the calcium content in the human body is found in our bones and the remaining one percent in our soft tissues, blood and muscles. But when it comes to our cardiac and vascular health, it is this remaining one percent that holds the key. A research article published in the International Journal of Molecular Sciences in April 2020 and later included in the National Institute of Health’s National Library of Medicine, USA, defines vascular calcification as mineral deposition in our body. It is a normal biological process that happens as we age, but certain conditions like diabetes, hypertension, chronic kidney disease and genetic disorders often act as catalysts and enhance its progression.
Plaque formation and subsequent calcification — though considered to be associated with ageing — could start early on in life, sometimes as early as 20, if there are multiple cholesterol-laden lumps along the lines of coronary arteries that cause scarring, lesions and stiffening of the arterial walls. Calcification is one of the main effective clinical markers for atherosclerosis.
“This (calcification) is very variable and depends on genetic factors. In persons with familial hyperlipidemia (excess lipid formation), plaque formation and calcification may already begin at the age of 20 or 30,” says Professor Dr Grigorious Korosoglou, chief physician, department of cardiology and angiology, GRN Clinic, Weinheim, Germany, in an email conversation with Happiest Health.
Vascular comorbidities like diabetes and hypertension apart from chronic kidney disease and adverse cardiac genetic factors when combined with the calcification of coronary arteries could eventually trigger cardiac complications.
“Calcium deposit in our arteries is a marker for heart blockages associated with atherosclerosis. Calcified arteries mean there are high chances of cardiac blockages, especially in those people who are already affected with risk factors like hypertension, diabetes and obesity or have a genetic history of cardiac complications in the family,” says Dr CN Manjunath, cardiologist and director, Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bengaluru.
Ironically, calcium gets deposited on the arterial walls initially as part of the body’s defence mechanism to try and heal the scarring caused by the lipid-rich plaques. This calcium ends up interacting with excess lipid and protein molecules in the plaques and in time becomes calcified plaques, both stable and unstable. It is these unstable plaques that often rupture inside the arteries whose lining has already lost its elastic texture and has become stiffened due to plaque formation. The stable ones, on the other hand, add to the overall plaque burden in the arteries.
“The presence of calcified arteries itself is an indicator that the individual concerned has to take care of their cardiac health. Of course, the extent of medical intervention required or whether just lifestyle alteration is enough, depends on the opinion of an expert cardiologist,” says Dr Partha Sarathi Banerjee, chief interventional cardiologist, Manipal Hospital, Kolkata, in a telephonic interaction with Happiest Health.
One of the earliest descriptions of arterial calcification was documented by German pathologist Johann Monckeberg in 1904, in his study on the formation of calcified plaques during the autopsy of people claimed by rheumatic heart disease and rheumatic fever – killer diseases during those times.
Coronary calcification under the microscope
In 2017, experts at the Cardiovascular Pathology Institute, Maryland, and School of Medicine, Maryland, published a research paper on coronary artery calcification and its progression in the Journal of American College of Cardiology. It has been now included in the open archives of Elsevier since 2018, explaining the progression and complexity of this vascular process. It has been found that plaques with spotty calcifications, rich in lipid content with calcium deposits that emerge as microcalcifications (0.5 to 15 μm), could grow into larger calcium fragments and form a sheet more than 3 mm in thickness adding to the overall plaque burden in the arteries.
“There is a correlation between atherogenic risk factors (formation of fatty deposits in arteries) and calcium score. Calcification within the artery is not reversible. However, calcification itself is usually not the problem since stable plaque in most cases does not rupture. This is, however, not always the case. The pattern of ‘spotty’ calcification or micro-calcification at the beginning of the atherosclerotic process may be associated with a high risk for myocardial infarction (heart attack),” Prof Dr Korosoglou adds.
What causes calcification?
Calcification is classified into two types based on its vascular dynamics – intimal and medial calcification. Intimal calcification is more associated with atherosclerosis in the coronary arteries and valves. Medial calcification is commonly associated with peripheral artery diseases. It has now been pointed out that the earliest signs of calcification are found because of the death of Smooth Muscle Cells (SMC) responsible for ensuring the elasticity of the arterial walls due to plaque formation. This leads to the seepage of macrophages (a type of white blood cell) into the lipid mass as part of the immune reaction of the body to the arterial vascular abnormalities. These macrophages also end up dead in the cholesterol-laden plaque and the subsequent inflammation results in the accumulation of a phospholipid mass within the artery. It is this mass, due to further cell deaths in its vicinity, that changes into mineral deposits of apatite (calcium phosphate) crystals also causing inflammation along the artery, resulting in further cell death. This mass of multiple dead cells together ends up as a necrotic core on the plaque that eventually becomes calcified in the presence of increased levels of calcium and even phosphorous. Some researchers have pointed out calcification leading to osteogenic (formation of bone) like processes where the damaged smooth muscle cells mutate into bone-like structures. But this is comparatively less common in coronary arteries.
Calcification is often regarded as one of the main markers for atherosclerosis and its extent in our coronary arteries. Timely intervention and detection of calcified arteries and plaque formation is a matter of life and death in most atherosclerosis cases.
“The extent of calcification could also be a good indicator when it comes to deciding the nature and intensity of treatment required for the individual, especially the asymptomatic ones. Sometimes if detected early, only lifestyle alteration and health maintenance will be required. Medical intervention would be required if the person is diagnosed with other cardiovascular risk factors,” says Dr S Shanmugasundaram, cardiologist, Billroth Hospital, Chennai.
According to the data compiled by the World Health Organisation, a staggering 17.9 million people die annually of cardiovascular diseases, and Atherosclerotic Cardiovascular Diseases account for at least 85 percent of these deaths.