The most important medical test you never knew

SOME MONTHS AGO, a case report was published in the Indian Journal of Anaesthesia. Titled ‘Coronary artery calcification on chest computed tomography scan—Anaesthetic implications’, it spoke of a 58-year-old male patient brought in to the Tata Memorial Hospital in Mumbai for a surgery to remove a tumour in the upper lobe of the left lung. He had been suffering from hypertension for the last 10 years but standard preoperative tests, including a 2D Echocardiography, to check for heart health showed nothing of note. After the surgery, an ECG was done which again gave an all-clear. However, 30 minutes later, his heart began to fail but they managed to get him back in three minutes by chest compressions and shocks. Twenty-five days later, a bypass was done, so the story ended well. But it still left the question of the patient’s heart condition not being picked up by doctors despite all the checklists having been ticked. Only one test had given any indication there could be an issue—the Coronary Artery Calcium (CAC) detected in a chest CT scan. The paper asked, ‘In this case, during preoperative evaluation, we failed to detect significant CAD [coronary artery disease] despite following American College of Cardiology/American Heart Association 2014 guidelines for perioperative cardiovascular evaluation for noncardiac surgery. Lack of history of cardiac events, normal echocardiography findings and good effort tolerance masked the underlying CAD. In hindsight, CAC noted in chest CT scan turned out to be the only finding suggestive of CAD.’

Heart ailments are the biggest cause of deaths among humans. According to the World Health Organization (WHO), cardiovascular diseases led to 17.9 million dying in 2016, just under one-third of all deaths. WHO guidelines also specify how to address the ailment, the main preventive strategy being to identify risk and bring it down. It notes, ‘Most cardiovascular diseases can be prevented by addressing behavioural risk factors such as tobacco use, unhealthy diet and obesity, physical inactivity and harmful use of alcohol using population-wide strategies. People with cardiovascular disease or who are at high cardiovascular risk (due to the presence of one or more risk factors such as hypertension, diabetes, hyperlipidaemia or already established disease) need early detection and management using counselling and medicines, as appropriate.’

In cardiovascular diseases, Coronary Artery Disease (CAD) makes up for a majority of deaths. In this, plaque builds up in the arteries related to the heart and when it ruptures, a clot is formed that blocks the vessel cutting off blood supply. Plaques are made up of many substances with calcium being a main component. Looking at the calcium can give information about the density of the plaques. And yet in the first line of risk prediction, the medical profession does not consider it. Instead, the focus is on other risk factors, like cholesterol, which are increasingly found to be less dependable. The Coronary Artery Calcium (CAC) Score is a simple test that can be done at any major pathology laboratory or hospital with a Computerised Tomography (CT or CAT) scanner. It costs around the Rs 5,000 range. The test is non-invasive and takes a few minutes. You go, they push you inside the machine, ask you to take some deep breaths and that is it. By evening, depending on how much calcium is found in the coronary vessels, you get a score starting from 0, which is perfect and indicates that there are no plaques. Between 0 and 100 means CAD has started but there is little to worry at this point if you maintain a heart-healthy lifestyle. From 100 to 400 indicates moderate concern and the need for medication. More than that means CAD is progressing rapidly and you are at serious risk of a heart failure in a few years. If the score is very high, other invasive tests, like an angiography, would be done to find out whether a corrective surgery is necessary.

Dr Ramesh Babu P, founder of Ramesh Hospitals in Vijayawada, is among the few cardiologists in India actively promoting the CAC Score as a life-saving test. Babu says it is far superior in predicting risk and identifying heart disease compared to other tests and risk factors. He even recommends doing a CT Coronary Angiogram, in which the same machine is used but with the addition of a dye being injected into the vein that shows plaque build-up in heart vessels more clearly and early (CT Coronary Angiogram is different from conventional angiography; the former is non-invasive while the latter is invasive, more expensive and involves a little amount of risk.)

It costs around Rs 5,000, takes a couple of minutes in a CT Scan machine and could save millions of lives by informing people about potential heart attacks. But there is little awareness about the coronary artery calcium score test

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“There are so many false positives and false negatives with tests like treadmill, echo cardiogram, routine ECG or stress thallium. These tests and risk factors like hypertension, diabetes, smoking, bad cholesterol, etcetera only provide indirect evidence often found to be fallacious. In CT Coronary Calcium and Angio, we are directly looking into the major coronary vessels,” he says.

Babu thinks it is essential to make these tests the first line of investigation because they have two advantages. First, it will detect heart issues early. “I have seen many patients, even females less than 45 years, in my practice who were absolutely asymptomatic prior to the attack. A heart attack is not a sudden event as many believe. By the time it occurs, there has been a hidden disease for 20-25 years. So, you should identify the disease at that time. The role of identifying it lies with the family physician. They have been missing out because they only look for factors like hypertension and diabetes, and give cholesterol-lowering drugs or blood thinners without knowing whether the disease is there or not, whether it is severe or not. A CAC Test will identify the disease when it is hidden. Treatment can then prevent its progression. Or deaths can be prevented even when there is an attack. For instance, if such identified patients suddenly have a chest pain, it can be immediately recognised as cardiac pain and they can go for treatment within the golden hour. Half the deaths currently happening can be prevented if the disease is identified early,” he says.

The second advantage is the inverse of the above phenomenon—the test could show that there are no heart issues when other tests claim to. And so there will be no reason for taking unnecessary medication like statins, which doctors prescribe to reduce cholesterol. “All around the globe 50 per cent of cholesterol-lowering drugs are unnecessary. They are based on risk factors or some treadmill test that comes positive. If you do the CAC Test and get a low score, you do not need it. In fact, statins may even harm,” he says.

Since 2011, when Babu’s hospital got a 256 slice CT scanning machine, they have done more than 12,000 CT Coronary Angiograms. He remembers one case in the beginning when a man in his forties came to visit his mother in the hospital and even though he had no health issues, decided to get himself scanned. Serious blocks were found in the main heart vessels and the patient could get treatment in time.

Babu suggests that all people who are above 40, are diabetic, hypertensive or have a family history of heart disease should go for CT Coronary Angiogram. In addition, he says that tens of thousands of CT scans are done to screen for cancer and other ailments in government and private hospitals, and a small tweak in the software of the machines could also at the same time get a calcium score. That would save a lot of lives with very little extra effort. “The government should make it a policy,” he says.

A number of peer reviewed studies have shown that the CAC score is a much better predictor of heart health. A 2004 study published in Arteriosclerosis, Thrombosis, and Vascular Biology, a journal of the American Heart Association, took 495 subjects, put them on statins and tracked their CAC scores for between three to four years. Forty-one of them were recorded to have heart attacks during this period. Interestingly, the LDL or bad cholesterol readings of the group that had heart attacks and those that didn’t have weren’t very different. But when it came to the CAC score of the two groups, there was a marked difference. Those with heart attacks had been showing an average increase of 42 per cent in their CAC scores, while those who did not get a heart attack showed only 17 per cent. Having CAC progression made people 17 times likelier to have a heart attack than without CAC progression. The paper said: ‘Continued expansion of CAC may indicate failure of some patients to benefit from statin therapy and an increased risk of having cardiovascular events.’

Another 2012 study published in Circulation: Cardiovascular Imaging, a publication of the American Heart Association, looked at CAC scores of 44,052 individuals with no history of coronary heart disease and without any symptoms. Their others risk factors—smoking, diabetes, lipid readings. hypertension and family history of coronary heart disease—were also noted. The patients were tracked for between 5.5 to 7.5 years. They found that even for patients who had no risk factors, increasing CAC scores led to 3 to 13 times higher mortality risk. It concluded that people who had no risk factors but high coronary artery calcium had more heart attacks than those who had multiple risk factors but no coronary artery calcium.

There have been small Indian studies, too, about CAC. One published in September 2019 in the Cardiology and Cardiovascular Medicine journal, showed that medication might be taken unnecessarily or not taken when necessary if the CAC score was not being considered. In the study, 150 consecutive patients were selected in the OPD of a tertiary Indian hospital. Their probability of having a heart attack over the next 10 years was calculated through the traditional risk factors. They were subcategorised into different grades of low and high risks. These patients were then made to go on a CT scan to get their CAC scores. Once the numbers came out, the researchers found that a substantial percentage would have to be re-stratified for risk. The traditional risk factors said they needed to take medication like cholesterol-lowering statins, but the CAC score said it wasn’t needed. Also, vice versa: ‘17.3 % patients in statin not-needed group might be recommended statins, while 39/75 (52%) patients in statin considered or recommended group, would be considered for risk downgrade… Our study shows that almost one third of the population will be re-stratified regarding their lifetime use if CAC Scoring is used in addition to 10 yr ASCVD Score for use of statins as mode of primary prevention in Indian Population,’ said the paper.

In 2016, a study published in the Medical Journal, Armed Forces India looked at 220 people in a multispecialty zonal hospital with suspected coronary artery disease. They were scanned for coronary calcium and 30 per cent of them were found to have their arteries obstructed with CAD while for another 7 per cent, it was inconclusive. The paper said that these 37 per cent could be referred for further tests ‘to provide definitive disease severity or clarify the diagnosis respectively.’

There was one Indian study which however questioned the efficacy of the calcium score test for our population. Published in the International Journal of Anatomy, Radiology and Surgery in July 2019, in it, 306 patients with chest pain who had been referred to for an angiography in two tertiary hospitals were first asked to get their CAC Scores. They were also questioned to find out the Framingham Risk Score, a widely used predictor of heart disease based on traditional risk factors—for instance, 35 per cent of them had diabetes, 47 per cent had hypertension, 18 per cent dyslipidaemia, and 15 per cent were obese. So, both the CAC score as well as Framingham Score was telling the researchers about what the patient might have. And then the angiography was done to see what the patient did have. Both CAC and Framingham were seen to be faulty. A CAC Score of 0 should indicate that there was no heart disease. But they found that 25 per cent of the subjects with 0 score had coronary artery disease. They said CAC Score had ‘moderate diagnostic accuracy for the detection of significant CAD’. Dr Anitha Kini, a Bengaluru-based radiologist who was part of the study, believes the reason the CAC Score didn’t correlate was because Indians have a gene which predisposes them towards non-calcified plaques (plaques without calcium) in the heart’s arteries. Dr Kini believes studies should be done in different parts of the country too because of the size and diversity of India. “If such studies are done in different parts of the country, we can get consensus criteria about risks,” she says. But between CAC Score and Framingham Score, which uses factors the medical profession uses on patients today, the former still turned out to be a better predictor. As much as 66 per cent males categorised as low-risk by the Framingham Score had coronary artery disease.

Shashikant Iyengar, a 52-year-old resident of Mumbai, found he had diabetes on a Sunday in September 2015. The next day on, he started reading up to look for a cure. It led him in a few months to the low carbohydrate diet which seemed to, if not offer a cure, keep the complications of the disease at bay with minimal or no medication. While diabetes can be the cause for many organs becoming damaged, its major risk is considered to be to the heart.

“Atherosclerosis [plaque formation in heart vessels] basically starts with inflammation which is caused by excess blood sugar and insulin. The blood sugar spike damages the outermost layer of endothelium, the glycocalyx. The body acts to contain the damage, gathers lipids [different forms of cholesterol and fats in blood], platelets, minerals, etcetera, and does the patchwork. Studies have shown that despite very high lipids, if the calcium score is 0 or very low, then the risk of heart disease is much less. If the calcium is very high in spite of lipids being normal, then risk is very high,” he says.

In Iyengar’s lipid readings, LDL, or what is popularly known as bad cholesterol, is high at around 180. But when he took the CAC test a little under a year ago, the score came back as 0. He could therefore safely not take statins even though if he had gone to any doctor with his LDL number, he would have been put on medication. “If you go through studies, you will see CAC very strongly correlates with heart disease. It is not a marker, it actually shows the disease itself, the disease status,” he says.

The CAC Test is becoming popular among the low-carb and keto community for an interesting reason. The diet often leads to high LDL, which is conventionally assumed to be bad for your heart. But among low-carbers high LDL is accompanied by a rise in the good cholesterol HDL and a lowering of Triglycerides, which are good signs. The LDL makes the medical profession wary, so a CAC test helps rule out risk, as happened in Iyengar’s case. He is part of DLife, a forum of low-carb practitioners, and has seen other members, including a cousin of his, who have done the test. “The moment LDL increases, everyone thinks that you will have a heart attack and they look for ways to treat it. Low-carb advocates are big pushers of CAC because they want to show that they are safer in spite of LDL,” he says.

Iyengar became aware of the CAC Score test after listening online to Ivor Cummins, author of the book Eat Rich, Live Long. “He is the biggest advocate of CAC. I have seen practically every video of his. All that he says is based on published papers,” says Iyengar. An Irish biochemical engineer, Cummins got interested in the root causes of modern chronic ailments, particularly cardiovascular diseases, diabetes and obesity, and began research on it in 2012. He is at present the chief programme officer of a charity called Irish Heart Disease Awareness and is probably the world’s best known CAC evangelist. His podcasts and videos, available on his website fatemperor.com, have been seen and heard by millions.

“The CAC is a crucial test because it can take the people who are ‘middle risk’ in the cardiovascular disease risk algorithms, and re-assign 60 to 70 per cent of them to either ‘high risk’ or ‘low risk’. Keep in mind that for middle-aged and older people [where most heart attacks occur]—this ‘middle risk’ group is the largest one. Middle risk is a crazy category in many ways—it is totally ambiguous until you at least look at the actual disease level using CAC. This re-assigning of most ‘middle risk’ people enables the genuinely ‘low risk’ people now identified properly to avoid unnecessary chronic medications and crucially identifies the truly ‘high risk’ who have serious plaque burden, as evidenced now by the CAC score. We can treat these people appropriately to prevent premature heart attack. Middle-risk men over 40 and women over 50 are generally the groups who can benefit hugely from CAC (and official guidelines indicate this demographic),” Cummins says over email.

Cummins terms cholesterol a weak and misleading ‘risk factor’ but the CAC test is superior for other reasons too. “CAC also beats all of the risk factors put together because CAC Score is not a mere ‘risk factor’. It is looking directly at the extent of disease,” he says.

Some years ago, Cummins’ charity had funded a documentary movie called The Widowmaker. It shows something extraordinary—athletes who are in the prime of their health have heart disease in a surprising number and don’t know it. As part of the documentary, they did CAC scans of 45 athletes who were all deemed fit and healthy by their doctors, with no problems identified that required treatment. The documentary was the first to get them to take a CT scan of their heart vessels. “In actual fact 9 of the 45 had seriously high calcification scores. All required follow-up with cardiology for meds/lifestyle change based on their real level of disease,” says Cummins.

One of the reasons cardiologists aren’t enthusiastic about the CAC test is because the prevailing belief is that once coronary artery disease sets in, plaque build-up in heart vessels is progressive and irreversible. At the most, one can stop its progression, but a reversal is not possible. Yet, according to Cummins, there is evidence that this might not be true. He says there has been one study that showed reversal is possible: “We have also seen evidence of reversal in various people around the world, and in an individual in our Irish documentary Extra Time. At the moment the suspicion is that fixing the root causes will stop plaque generation and some calcium will leach back out of the younger, soft plaques. There is still a question over whether with time calcium will leach back out of the older, dense calcified plaque. In any case, the concept of reversing CAC is not liked by the [medical] community. One major reason is that statin drugs are associated with increasing rate of CAC Score. Thus it is very awkward for non-drug interventions to be seen to actually reverse CAC in any way, so much resistance.”

One cardiologist who is at present doing a study to find out whether CAC Score reversal is possible is UK-based Dr Aseem Malhotra, co-author of the book The Pioppi Diet. He says over email, “The evidence for coronary artery disease reversal exists which I’ve seen in my own patients but it hasn’t been tested in the highest quality clinical trials. It’s through a combination of lifestyle factors and we will release the protocol soon. My personal aspiration is to reverse the prevalence of coronary artery disease globally.”

According to Malhotra, the CAC test is the most useful non-invasive test to determine an individual’s extent of coronary artery disease in addition to predicting risk of heart attack over the next 10 years. On why awareness does not exist about it, he says, “A number of reasons. 1. A lack of understanding and knowledge of its use 2. Lack of access in comparison to simple blood tests to assess cholesterol profile, blood glucose status and checking blood pressure which every doctor can easily do in their clinical practice 3. Cost; it’s more expensive than other measures of risk.”

Total cholesterol by itself, he says, is an almost useless marker of risk of heart attack. “That evidence is very clear from my own independent analysis of the data. Also if one is over 60, the higher one’s cholesterol, the less likely you are to die and there is no association with heart disease. The reason this is not so widely acknowledged amongst doctors and cardiologists is because of deliberate misinformation coming from drug companies that profit from the fear of cholesterol. To put it in perspective, total revenues of sales of cholesterol lowering statin drugs are estimated to reach a trillion US dollars by next year.”

In his practice, Malhotra finds the CAC test a useful tool to help patients with very high cholesterol avoid cholesterol-lowering medication. “If they have a zero score then for them cholesterol clearly isn’t a problem. It’s also helpful for patients with a high score to implement a lifestyle change that I prescribe to halt progression or potentially reverse it,” he says.

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Madhavankutty Pillai

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