CORONARY-ARTERY CALCIFICATION AND CALCIUM SCORE

Studying coronary calcium is the most efficient of any of the commonly tested risk factors as it alone demonstrates a positive predictive value that varies between 20 and 35% and a negative predictive value close to 100%. Coronary Calcification is associated more frequently with the presence of cardiovascular diseases (2,8 times) compared to the maximum carotid thickness (1,3 times). Consequently, the calcium score is more efficient as a subclinical cardiovascular disease predictive index if compared to CIMT (Arch Intern Med. 2008;168(12):1333-1339).

In fact no calcification is present in normal arteries.
La The presence of Coronary Calcification indicates the existence of heart disease and the entity of the calcification corresponds with the entity of the plaque.

Coronary Calcification generally increases with age and tends to be more common in complex plaques, with necroses and haemorrhages.

 Studies have underlined how the number and the severity of coronary stenosis and the frequency of myocardial infarction events are associated with the entity of the calcification.

The entity of Coronary Calcification is greater in male than in female patients and can be expressed by the level of the “calcium score index”.

In multivariate analyses it has been demonstrated that a high calcium score index is an independent risk factor, predictive of cardiac death and/or infarction, even after adjustment because of other coronary risk factors. Patients who demonstrate any amounts of calcium (>0) present an absolute risk of an event equal to 3% per year while the absolute risk for those without calcium, equals 0,12% for each year. Therefore the absence of Coronary-artery Calcification has a strong negative predictive value of 98-100%.

According to Raggi et al. (2001) patients with a calcium score index >160 present a considerable probability of obstructive coronary artery disease with a statistically important increase in cardiac events during the following 30 months.

In addition, calcium screening is a highly sensitive test and moderately specific for predicting the possible presence of important coronary stenosis.

 The exclusion of Coronary Calcification is able to select a considerable group of patients who have a very low probability of having clinically significant coronary stenosis. (Ralph Haberl and Coll.., J Am Coll Cardiol, 2001;37:451–7)

Fig. 2. Results of asymptomatic male calcium screening.

The lowest levels identify the thresholds for the 95% of patients without significant stenosis using conventional coronary angiography.

 The highest levels identify the thresholds for the 90% of patients with significant stenosis . For example if a man of 50 has a score of 56, he is probably not suffering from any coronary disease.
However, with a score level of 217, the same patient would present a high risk of coronary stenosis.

Fig. 3. results of calcium screening in asymptomatic female patients (for explanations, see previous Fig.)

In addition, 47 % of patients with a calcium score index > 400 present a positive myocardial SPECT for reversible ischemia; 20% of patients with a calcium score index > 100 and < 399 present myocardial perfusion defects (SPECT).

On the other hand, only 1% of patients with a calcium score index < 100 present perfusion defects (Wilson and Smith Jr. et al., 2003).

According to the study by MESA (2006) myocardial perfusion reserve is inversely associated with the presence and the severity of Coronary Calcification in asymptomatic adults. This discovery implies that a substantial number of adults, who do not present clinical signs of coronary artery disease, can have a reduced coronary reserve, perhaps caused by the presence of subclinical coronary atherosclerosis.

Calcification is more frequent in Males than in Females.

 Men demonstrate total calcium score values equal to women who are 15 years older in age.

 Coronary Calcification is prevalent in patients with Diabetes Mellitus (type 2) (75%) in smokers (63%) and in those with high blood pressure (50%).

 The probability of suffering from a major cardiac event in patients with Coronary Calcification is 28 times higher than in patients without calcification.

Moreover, smoking adds prognostic value to Coronary-artery Calcification.

In fact, among patients with calcification, smokers present a frequency of cardiac events that are double when compared to that of non-smokers (11%: smokers; 5, 4%: non-smokers).

According to the classifications of the American Heart Association (AHA) the calcified plaque corresponds with Vb type atheroma . The presence of Coronary-artery Calcification, transforms an individual who presents cardiovascular disease risk factors into an individual who has a documented atherosclerotic disease. This is valid, above all, for coronary arteries, but also for carotids and other arteries.

 The presence of small calcified points along the coronary arteries identifies a patient who is suffering from an advanced and complex heart disease.

 In a study published in Circulation in 2004, using intravascular ultrasound (IVUS) Shoichi Ehara and coll., demonstrated how the frequency and type of calcium deposits differ in the ”Culprit Lesion” of patients with acute myocardial infarction, unstable angina, stable angina (P<0.0001).

 The number of small calcified deposits was higher in patients with acute myocardial infarction than with stable angina, but in these latter patients, the deposits were longer and more widespread. Typically in patients with acute myocardial infarction, calcification has non-uniform spotty appearance (Spotty calcifications).

Consequently, the current idea of the vulnerable plaque is uncertain as yet.
Perhaps the true problem is not the lipid core, but the calcium.

When irregular spotty calcification is identified, this probably refers to an unstable coronary segment, complex lesion locations defined in the study quoted above, as the lesion responsible for the coronary syndrome (Culprit Lesion).

Coronary Calcifications are not stable and static. In fact, in one study involving 1064 women subjected to hormonal replacement therapy with estrogen (HRT) for 7.4 years 46% less calcified plaque incidence was discovered, compared to women not treated with estrogen (placebo).

Recent clinical studies demonstrated that Coronary Calcification has a predictive value in elderly patients over 70 years of age. This is obvious both in the “Rotterdam Coronary Calcification study”(Circulation, July 26, 2005, Vol. 112:4, pp. 572-577), as well as in the Raggi ‘s study ( July 2008, Vol. 52:1, pp. 17-23). 

In particular, according to Raggi, the survival of a patient 40 years old, and that of a patient 80 years old with a calcium score > 400 is 88 %, and 19%, respectively. Whereas on 20.562 patients without Coronary Calcification the annual mortality rate was 0,3% in patients between 40 and 49 , and 2,2% in those aged over 70.

This permits the reclassification of patients over 70 years of age who present no Coronary Calcification, and who can be considered as having a lower cardiovascular risk.

Atherosclerotic diseases of the coronary arteries are not pathologies that exclusively affect middle and advanced aged patients. In fact in the PDAY study conducted in 2000, about 19% of Males and about 8% of Females who had died violent deaths between the ages of 30 and 34, showed signs of atherosclerotic stenotic plaques, of about 40% of the left anterior descending artery (LAD).

But the aspect that is truly surprising is that 4% of Males between 15-19 years of age present similar lesions. This is much lower in females in the same category. This involves the need to change our concept of atherosclerotic disease in children, adolescents and young adults.

According to the multi-ethnic study “The Multi-Ethnic Study of Atherosclerosis (MESA)” Coronary Calcification is predictive of coronary events (heart attack, angina p., sudden death) in 4 ethnic groups: White (38.6%), Black (27.6%), Chinese American (11.9%), and Hispanic (21.9%) (New England Journal of Medicine, March 27, 2008, Vol. 358:13, pp. 1336-1345).

Nevertheless, despite the fact that it is currently possible to perform non invasive coronary angiography using CTA, if it is considered still important to determine the calcium score index (CSI).

In fact, where coronary-artery stenosis is present a detected CSI > 75% percentile indicates a risk of 7 to 10 times greater for myocardial infarction or sudden deaths in the 4 following years. At this point, the necessity arises for a more aggressive treatment in order to reduce cardiovascular risk.

Consequently, the total picture of actual cardiovascular risk becomes clear when the CSI has been calculated, also in the presence of CT Coronary Angiography.