Using Coronary Calcium Score to Target Statin Treatment in Primary Prevention – The Biolmage Study

Cholesterol-lowering medications are being prescribed to almost 30% of US adults aged 40 and over, most of these are statins drugs (1). The number increases with age, and approximately 48% of adults older than 75 are receiving such treatment.

It has been suggested that treating more older individuals with statins may prevent a substantial number of cardiovascular events, and that, if statins have no adverse effects on functional limitation or cognitive impairment, treating all elderly individuals will be cost-effective (2).

Using Coronary Calcium Score to Target Statin Treatment in Primary Prevention - The Biolmage Study

However, transforming public health targets into clinical practice is easier said than done because clinical medicine is an entirely different ball game, not least because of the human factor. For the clinician, explaining why a lifelong medication with potential side effects makes sense can be a difficult task. Furthermore, the situation gets more complicated if the treating physician realizes that many of those he or she manages to convince will not necessarily derive any benefit.

Three years ago the American College of Cardiology (ACC) and the American Heart Association (AHA) released new guidelines for cardiovascular risk assessment (3). Not unexpectedly, the debate on how to use statins in primary prevention took center stage.

Instead of using cholesterol levels to target treatment a new risk model was introduced, together with an online risk calculator (4). It was based on the assumption that a high level of evidence exists for the use of statin therapy in individuals with a ≥7.5% estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk. The threshold to initiate statin therapy was later supported by risk-benefit and cost-effectiveness analyses (5).

In other words, to decide if a healthy individual should be treated with a statin drug, clinicians are offered an online calculator to assess risk. If the calculator shows that the risk of a cardiovascular event is higher than 7.5% for the next 10 years, statin treatment should be recommended.

The risk calculator itself is relatively user-friendly (6). The variables that have to be entered are race, gender, age, total cholesterol, HDL cholesterol, and systolic blood pressure. Furthermore, whether the individual has diabetes, treatment for hypertension or is a smoker has to be filled in as well. When all this is done, the calculator will report the 10-year ASCVD risk.

Should All Elderly People Be Treated?

What many of us found bizarre when testing the risk calculator was the strong influence of age. It turned out that all healthy individuals will automatically pass the 7.5% 10-year ASCVD risk threshold due to age alone, and thereby qualify for statin therapy, even if other risk factors are optimal. This will happen between age 63 and 71, depending on sex and ethnicity.

So, if we rely on the calculator, everybody will become eligible for statin treatment when they’ve reached a certain age, and everyone older than 70 will be on statins. Of course, this doesn’t make sense. Many elderly individuals will never experience a cardiovascular event. Why should they be given a drug to prevent something that will never happen?

Giving someone the benefit of the doubt can hardly be regarded as good clinical practice. Although statins are by many experts considered to be relatively harmless, adverse effects do occur. The elderly may be more vulnerable to adverse events due to the presence of other diseases and concomitant medication. Furthermore, one of the most feared side effects of statins, functional limitation and cognitive impairment, may easily go undetected among the elderly (7).

So although universal treatment of the elderly may be cost effective, from the patient’s and the clinician’s perspective, such an approach is misguided if not unethical.

How Can We Identify Those Who Benefit (The Biolmage Study)?

Because the use of the risk calculator will lead to unnecessary treatment of a vast number of individuals with statin drugs, the next question inevitably is how we can detect those who truly are at increased risk. By doing so, overtreatment is less likely to occur as treatment will be targeted at only those who are likely to benefit.

One way to do this is to use noninvasive imaging of the coronary or the carotid arteries to detect individuals with subclinical atherosclerosis. Thus, the decision to treat with statins could be guided by the absence (do not treat) or presence (treat) of subclinical atherosclerosis.This hypothesis was tested in the Biolmage Study and recently presented in a paper published in the Journal of the American College of Cardiology (8).

Biolmage was a prospective observational cohort of men 55-80 years of age and women 60 to 80 years old without ASCVD at baseline examination between January 2008 and June 2009. Imaging was performed in 5.805 participants to detect the presence or absence of subclinical atherosclerosis. The mean age of the population was 69 years, and 56% were women.

The purpose of the study was to evaluate a more personalized approach to primary prevention with statins by adding a simple disease guided reclassification step after formal ACC/AHA recommended risk assessment. All study participants underwent CT scanning to determine the coronary artery calcium score (CAC) and carotid ultrasound imaging to detect and quantify carotid plaque.

It turned out that the vast majority of these participants (86%) was eligible for statin therapy because of an estimated 10-year ASCVD risk above 7.5%. However, among those individuals, 28% had no coronary artery calcium, and 20% had no carotid plaque.

There was a strong correlation between subclinical atherosclerosis and clinical events. Event rates were low in participants without subclinical atherosclerosis, including those with diabetes.

According to the authors of the paper, those without subclinical atherosclerosis should be down-classified to non-statin eligible, despite high 10-year ASCVD. The number needed to screen (NNS) to find one person with a CAC of zero was 2.6 among those with a 10-year ASCVD of 7.5-15%.

However, subclinical atherosclerosis was also found in participants with 10-year ASCVD risk below 7.5%. These individuals should be upgraded to statin eligible because of the increased risk associated with subclinical atherosclerosis. The NNS to find one person with a CAC > 100 among participants with 10-year ASCVD risk of <5% and 5% to 7.5% was 10 and 5.3 respectively.

The Take Home Message

The recently published results from the Biolmage study may have several important implications for the practice of cardiovascular prevention.

The 2013 ACC/AHA guidelines support a universal treatment principle for the use of statins because everyone will qualify for treatment if they live long enough. Such an approach will likely lead to overtreatment and is unacceptable from the clinician’s standpoint as well as from the patient’s perspective.

The Biolmage data show that use of non-invasive imaging techniques to reveal the amount of coronary calcium or carotid plaque burden may be useful to reclassify patients as eligible or not eligible for statin treatment based on the presence or absence of subclinical atherosclerosis. In this elderly population assessing coronary artery calcium score (CAC) seemed to perform better than assessing carotid plaque burden.

Limiting primary prevention with statins to those with CAC above zero could spare 1 in 4 elderly from taking life-long medication that will benefit only a few.

The question about how to use statin drugs in primary prevention illustrates a huge gap between public health targets and clinical medicine. From the public health perspective, extending the use of statins, particularly among the elderly may seem an attractive target, not least because of the possible cost-effectiveness. However, due to the risk of side effects and the fact that many of those treated will not derive any benefit, the clinician should not prescribe statin therapy unless there is a high likelihood of benefit. The Biolmage data may have opened the door to new practical tools making it easier for physicians to advise their patients on this thorny issue.

14 thoughts on “Using Coronary Calcium Score to Target Statin Treatment in Primary Prevention – The Biolmage Study”

    • A very good question Evinx.

      If you look at the curves in figure 1 in the original paper you can see that the event rate is also fairly low among those with CAC between 1-99.

      Maybe there has to be an age defined cut-off point. Below age 65, zero may be appropriate. In older individuals, for example above 75 years of age, below 100 might be reasonable. But this is just me thinking out loud. Of course this has to be tested in clinical trials.

  1. I was under the understanding that CAC rose inevitably with age…and that therefore a CAC of 0 was nigh on impossible for an older age group? So I’m also with Evinx, looking for a more reasonable CAC…mine was 8, at age 64…

    • May sound surprising that 32% of the patients had a CAC of zero and 28% of those with 10 – year ASCVD risk score above 7.5%.
      So, almost a third had no signs of coronary atherosclerosis despite a mean age of 69.

    • It’s a very interesting theory Ted and I believe more evidence will be available in the near future. It’s quite possible that intake of vitamin K2 might help to reduce the health risks associated with coronary calcium.

      Vitamin K2 levels are associated with less arterial calcification and arterial stiffening and K2 may lower the risk of vascular damage according to recent data

      Furthermore, vitamin K2 is not very widespread in the modern western diet and almost non-existent in junk food.

      • anecdotally, I have slowed the progression and possibly reversed the increase in coronary calcium using both MK4 and MK7 forms of K2. I also maintain a high level of Vit D which can contribute to calcium. I’m a true believer in K2.

  2. Apologies if a little off-topic for this thread….

    LCHF-er had an acute heart-attack (the two may not be related but “could” be.)

    Dr. Axel: Any take on Lipitor (80mg/day) effect on blood ketones? (AND potential impact on LCHF viability)
    (Mine plunged to 0.3 mmol/L after 2 weeks of Lipitor, besides the usual menu: ACE inhibitors, beta-blockers, blood-thinners but I suspect it’s primarily Lipitor driven). My peak 2 months ago was 2.2 mmol/L and rarely went below 0.9 . But did tank to 0.2 levels for a day or two on rare carb-indulge days… )

    [Long story short…more in the spirit of sharing some observations for the benefit of others…
    – on Ultra-LCHF for 2 years, male, 50 years.
    (35g net-of-fiber carb/day, 80g protein, 100g fat (~30% Saturated); 400g of assorted raw green/non-starch veg for fiber/micro-nutrients)
    – Swimmer of 20 years (2×1.5hr /week) & had just reached my long-term goal of ‘ability to swim 3-hrs in a session’ last month – thanks to Nutritional ketosis and strength training.
    – into weight lifting/strength training past 2 years
    – lost 38 pounds and approx %10 body fat (impedance meter @ home; 26% to 16% bodyfat in two years. )
    – Achieved LCHF-typical Lipid profile: (TG:50, HDL-C:61, LDL-C:141, VLDL-C:11, TC:212, A1C:5.2 [have Beta-thal so true A1c, as a measure of bloodsugar, could be even lower],
    But….. Apo-B:111 (I “think” this holds the key to lot of things but that’s the only time I ever tested it. )
    Readings 2 years ago:TG:194, HDL-C:34, LDL-C:96, VLDL=N/A, TC:170, A1C=6.4, apo-B:N/A.
    Unfortunately but for the single Apo-B read no other data in the particle count dimension. No Lp(a) either. Never thought heart health was critical to me. (always had excellent BP, CIMT year ago showed no plaque. but, it’s all moot at this point (:-( )

    Unfortunately, had a heart-attack,LAD 90% block, stented (rest of the arteries are disease free) right at the gym – 2 weeks ago. Fortunately it started as a dizziness, moderate left chest/shoulder pain, nausea, hyper-ventilation, sweating.. went to Emergency right away. ECG no problem. Awake & quiet 1 hour. Then chest-pain ripped through. NOW ECG shows STEMI! Cath-lab within an hour. Really fortunate given the 5% ish survival rate for the front artery clog (aka the widow maker). More fortunate… no heart muscle/brain damage (Tropin levels were 1, two days after procedure. peaked to 4) that seems not uncommon among survivors.

    No family history of any medical issues. No meds in entire life. Smoked pack-a-day for nealy 23 years. quit 6 years ago. And ate an ultra-high carb(north of 500-750g/day) /low-fat diet most of my life until two years ago. Whole thing is still a mystery. If smoking+utra-high carbs were the drivers it’s a miracle all the other arteries are this clean.

    Continuing on with the Low-carb but moderate fat diet until I get more direction from lipidologists. All the meds is so scary at the current very high dosages. Cardiologists – despite best intentions – seem to be prescribing things targeting the wrong things…and extreme doses…
    Based on my history – assuming smoking/high-carb diet were the main culprits, that does not exist today, I could very well be being treated for the wrong problem.
    Little professional info. on LCHF diet while on these post-heart-attack/stent medications (i.e., secondary prevention as docs call it). (the ketone measurement today was my first shock…indicating LCHF may not be viable.)

  3. “Although statins are by many experts considered to be relatively harmless, adverse effects do occur.”
    In the USA, I wonder how “experts” wind up considering statins to be relatively harmless. After drugs reach the market in the US, no one, and certainly not physicians, is required to report adverse effects.
    A recent NY Times article says that 1/4 of statin users experience muscle pain. Are we to assume that this is benign? Why?
    No one has a financial interest in finding out that statins have common and sometimes even lethal adverse effects, or to what degree this is the case.

  4. Im a 45 year old male, healthy lipid profile (Total Cholesterol: 173 LDL: 102 HDL: 42 Triglycerides: 125, normal blood pressure. Exercise daily

    Chest pains had brought me into the emergency room last month, where they did a bunch of tests to rule out a heart issue. Thankfully it was not heart related. But they did do a CT Scan where my Calcium Score came back at 22.

    The full report on the Scan findings are as follows:

    Left Main Coronary Artery is Patent without obstructive disease
    Left Anterior Decending Artery contains mixed plaque in the mid segment with mild (Approximately 30%) luminal stenosis. The remainder of the LAD appears patent without obstructive disease.
    LCX appears patent without obstructive disease
    RCA appears patent without obstructive disease
    My doctor wants me to start Statins (Lipitor) 20mg/day. He said that although my current profile isn’t too bad, that its more of a preventative measure. Im not sure what to think. Or where I stand in the grand scheme of things for my age and compared to most people, etc.
    Would you consider me to be a high risk?? Not sure if Im doomed here or not. The stress of the uncertainty is actually giving me chest pains. What does this all mean? Is my calcium score really high? And are the findings in the Scan anything to be concerned with?


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