IT STARTED in 2014, with a routine health check. I was 44, and fit enough to have completed a string of Olympic-distance triathlons. I exercised most days, at the gym, on a football pitch, running or cycling. Admittedly, my body mass index always came up as “obese”, but that never worried me. I am the very definition of big-boned.
The problems began when a nurse did a finger-prick test of my blood cholesterol. She said I’d have to come back. “The machine seems to be broken,” she said. “I’ve never had a reading this high.”
It wasn’t broken. Further tests confirmed that my blood cholesterol was almost double the healthy level. It was probably genetic, my doctor said. Changing diet and lifestyle wouldn’t help. The only solution was medication: statins.
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So, I was being invited to join the club. In the past 30 years, cholesterol-reducing statins have become some of the most widely prescribed drugs globally – small wonder, when heart disease and strokes are among the world’s biggest killers. In the UK, official guidance is that people with normal levels of cholesterol should take statins if their risk of a stroke or heart attack within 10 years . The American Heart Association’s .
Even so, I’d been vaguely aware of a backlash against statins – and even against the idea that cholesterol really is a bogeyman for your heart. With my own health on the line, I set out to find some clear answers.
In wealthier parts of the world, heart disease and strokes account for over a quarter of deaths. Many factors are at play (see “Cholesterol wars: We may be fighting the wrong enemy“), with conventional wisdom identifying cholesterol as one of the biggest culprits. A fatty biomolecule synthesised primarily in the liver, cholesterol forms cell walls and the myelin sheaths that protect neurons in the brain. It plays a part in biological processes from cell signalling to making vitamin D, and .
But a dark side has long been suspected. In 1913, Russian pathologist Nikolai Anichkov showed that rabbits fed pure cholesterol extracted from egg yolks . Since then we’ve learned how excess cholesterol, carried in the bloodstream by lipoproteins, can stick to artery walls, restricting blood flow and making clots more likely – the condition known as atherosclerosis.
Enter statins
The connection between cholesterol and heart disease became widely accepted in 1984, with the publication of the results of the Lipid Research Clinics Coronary Primary Prevention Trial. This followed about 3800 middle-aged men over seven years, showing that lower levels of “bad” low-density lipoprotein cholesterol correlated with a , or having to undergo heart bypass surgery.
Enter statins. These drugs work by inhibiting the production of an enzyme crucial for making cholesterol in the liver. The first commercial statin received approval in the US in 1987, with plenty more marketed in the next decade. Many trials showed that they reduced heart attacks and strokes in people with high cholesterol or who were otherwise at high risk of heart disease – who smoke, don’t exercise, are overweight and so on.
More recently, studies have extended the benefits to people at lower risk. One key trial known as JUPITER, published in 2008, looked at the effects of taking rosuvastatin on 17,800 people with no known history of heart disease. These people had cholesterol levels below then-recommended thresholds for treatment with statins, but increased levels of a biomarker known to correlate with an increased risk of future heart problems. Over five years, .
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Such results led the American Heart Association to update its advice on who should receive statins in 2013. The UK’s National Institute for Health and Care Excellence (NICE) followed suit in 2014. When my hospital consultant recommended I take a daily “baby dose” of 20 milligrams of atorvastatin to lower my cholesterol levels and prevent future heart problems, he was only following prevailing wisdom.
But right from the start, JUPITER and other similar studies have . For a start, heart attacks may have halved in the JUPITER trial, but the absolute incidence of heart attacks in the study population was low anyway. Only 99 people had a fatal heart attack during the trial period, 31 of whom were taking the statin. Viewed that way, less than 0.5 per cent of the people treated with rosuvastatin benefited, casting a different light on the drug’s effectiveness.
Similar caveats arise in other analyses. As highlighted in a 2014 editorial in the Annals of Internal Medicine, for example, two meta-analyses of studies from 2012 and 2013 , despite the mortality levels they found differing by less than half a per cent.
An alternative measure of a drug’s efficacy is “number needed to treat” (NNT), the number of people that have to be given a therapy for a specified time for one to benefit. Analysis undertaken by , a website run by a consortium of physicians and medical researchers aiming to put a patient’s perspective on research data, suggests that people with existing heart disease clearly benefit by taking statins: (see “Cholesterol wars: We may be fighting the wrong enemy“). In the absence of diagnosed heart disease, however, . A separate meta-analysis in 2013 led by John Abramson at Harvard University, found that “140 low-risk people must be treated with statins for five years to prevent one major coronary event or stroke”. Not only that, but there was .
Such figures mean there should be no blanket prescription of statins, Abramson reckons. “Physicians should discuss these findings with their patients,” he says. “Why would you impose the decision on people when it is at best a judgement call?”
Others beg to differ. Rory Collins leads the based in Oxford, UK, which has access to by far the largest database of statin trials. He points out that even these low NNT figures, extrapolated to whole populations, equate to hundreds of thousands of people avoiding heart attacks. That is worth it, even without life extension. “If you’ve seen someone who’s had a non-fatal heart attack or stroke, you’ll know it completely changes their physical and psychological life,” he says. “To say that coronary death is all that matters is absurd.”
I felt fit as a fiddle at the time of my diagnosis, but better safe than sorry – or dead. So I started popping a daily statin as my consultant recommended. At first it was fine. I even did another triathlon. But a year later, exercise was getting harder. I was slower on the football pitch. I couldn’t lift the weights I used to. If I did a lot of exercise in a day – two hours, say – I would end the evening curled up in a ball on the sofa, in flu-like muscle pain.
Muscle pain, or myalgia, is the most commonly cited side-effect of statins. I didn’t have to look far for another sufferer: my mother had also been put on statins for high cholesterol. “I stop taking them from time to time,” she told me. “I can’t stand the way they make me so weak and achy. They make me feel 10 years older.”
“After exercise I ended up curled up in a ball on the sofa, in flu-like muscle pain”
According to a review paper of clinical trials by Collins, Liam Smeeth at the London School of Hygiene and Tropical Medicine and others that was published last September, statin therapy causes muscle pain in “” – less than one per cent. But other studies – a quarter or a third, and in one study based in Paris, 87 per cent of participants complained of pain. Last year, David Spence and George Dresser at the University of Western Ontario in Canada wrote in the Journal of the American Heart Association that, despite claims from clinical trial data that adverse reactions are vanishingly rare, “in real-world practice, “.
Humans are highly suggestible, meaning reports of muscle pain caused by statins may cause other people to feel it too. But some researchers contend that a flaw in the design of trials so far means those who experience side effects tend to withdraw before a trial’s formal start. Smeeth is conducting a further study on muscle pain and says it simply hasn’t been a prime concern so far. “We’ve done trials in over 100,000 people, but we were worried about people dying, having strokes and heart attacks. Muscle pain and fatigue were just not measured properly,” he says.
Concerns about statins causing diabetes seem less solid. The US Food and Drug Administration advises that “ have been reported with the use of statins”. But of Cochrane, a non-profit organisation that reviews available medical data, thinks this is just an artefact of the way we define diabetes. While statins cause a small rise in blood sugar, this is unlikely to cause the kind of damage we associate with severe, long-standing diabetes. In this respect, he says, the harmful effects of statins are “generally mild and reversible”.
False allegations
I hope he’s right. After two years on statins I had stopped going to the gym. I gave up running. I cut down on swimming. I simply couldn’t bear the pain – or the humiliation of being so weak and sluggish. In the end, I told my doctor I wanted to stop taking statins because they were turning me into a couch potato. Surely that was as bad for me as having high cholesterol?
That echoes concerns of some who think the focus on cholesterol and statins hinders rather than helps heart health (see “Cholesterol wars: We may be fighting the wrong enemy“). Certainly, the questionable benefits of statins for those with no existing heart condition, and their under-studied adverse effects, have led to calls for wider scrutiny of the raw patient data. “When you get an independent look at all the data, including the clinical study reports, you find things that weren’t found before,” says , editor-in-chief of The BMJ.
of the evidence led to a war of words with Collins. His CTT team has access to most of the data, but does not own it – and he says the number of pharmaceutical companies, charities and public bodies involved makes it impossible to get requisite permissions to release it more widely. “The BMJ is making false allegations that we are holding all the adverse event data and not making that available,” Collins says.
New results seem to increase the confusion. Last year, modelling of available data by Judith Finegold at Imperial College London showed that a 50-year-old, non-smoking man without diabetes and with average cholesterol and blood pressure will after starting preventative statin therapy. But that average is highly misleading, Finegold says: it disguises the fact that 7 of that 100 will gain an average of 99 months (8.25 years) of life – while the remaining 93 get nothing at all.
In June 2016, NICE reflected that result by making it clear that . These drugs probably do save some lives – we just can’t ever know which ones, says Smeeth. “And we’ll never know, because the ones who benefit don’t have a heart attack,” he says.
You just have to hope you’re one of the lucky ones, then. I have only played the UK’s national lottery three times, and on none of those occasions did it make sense to do so. But one time I won £5000. Clearly, I’m lucky. But while people with diagnosed heart conditions should keep on popping the pills, it’s far from obvious the rest of us should. I probably shall: when I’m fit again, I’m going to try a different statin. But I certainly won’t see them as the cure-all I once did.
What makes a healthy ticker?
Many factors beyond blood cholesterol determine how healthy your heart is
BEING YOUNG. Muscle tissue tends to degrade with age, making your heart work that little bit harder with every passing year.
BEING FEMALE. Before age 60, . Overconsumption, smoking and work stress have all been blamed – but no one truly knows why.
GOOD GENETICS. Some , although we haven’t singled out what genes are responsible. Lifestyle factors such as smoking or poor diet passed between generations may also contribute to a “hereditary” element.
LOW BLOOD PRESSURE. This reduces the risk of ruptured arteries, dislodged clots or plaque causing a stroke – stress, overeating, smoking and alcohol consumption all play a part in pushing it too high.
HEALTHY BODYWEIGHT. The heart has to work harder in people who are obese. Keeping trim also reduces incidence of type 2 diabetes, another risk factor for heart disease.
REGULAR EXERCISE. Like any other muscle, the heart grows stronger when forced to do a reasonable amount of work. .
This article appeared in print under the headline “Cholesterol wars”
