How low should we go?
One of the country’s most prominent cardiologists wants doctors to be far more aggressive in treating raised cholesterol levels. Is it a good idea?
When Auckland CEO and former coronary care nurse Faye Sumner found her blood pressure and cholesterol levels creeping up as she approached her 60s, it was time for her to tackle her heart risks with more than diet and exercise. As deputy chair of the Heart Foundation, Sumner is well aware of the importance of her lifestyle. She’s always kept fit, eaten a mostly vegetarian diet, has never smoked and has a normal BMI of 23.
But a family history of cardiovascular disease meant her GP was keeping a close eye on her annual check-up results, and when her blood pressure reached 150/90 and her total cholesterol nudged 7 about 10 years ago, she was prescribed both statins and blood-pressure pills.
Sumner is now 69 and her level of “bad” LDL cholesterol has fallen from 4.1 to 2.6, putting her total cholesterol under 5, and her systolic blood pressure is down to about 115 – readings both she and her GP are happy with.
But one of New Zealand’s highest-profile cardiologists, Professor Harvey White, director of coronary care at Auckland City Hospital, says doctors should be treating cholesterol even more aggressively and be aiming to reduce bad cholesterol to below 2. He says our approach is costing lives.
His concerns have been prompted by a consensus paper on heart-disease risk assessment released last year by the Ministry of Health – the first such statement since 2003.
The paper isn’t billed as a guideline document for general practitioners but that’s effectively how it will be used. It recommends for the first time a treatment target for cholesterol lowering – a 40% reduction in LDL in people without a history of heart disease who have a 5-15% risk of having a cardiac event within five years.
White says even a 40% drop can leave levels of LDL cholesterol that are still too high – as in Sumner’s case: she has achieved an almost 40% reduction, but ideally, he says, doctors should be trying to bring her LDL closer to 1.8. “We know lower is better,” he says.
White is a well-known advocate for cholesterol-lowering drugs. He is a member of the international Cholesterol Treatment Trialists’ Collaboration, and has been involved in research and development of the drugs, known as statins. He is regarded as a world authority on their use. He believes everyone should have their cholesterol checked before they’re 20 to pick up those with congenitally high levels (about 1 in 500 people) and says many middle-aged people who would benefit – particularly Māori, who are already at higher risk, and those with a bad family history – are missing out. “Our guidelines don’t recommend cardiovascular checks for women until they reach 55. This kills women. I say screen at 18.”
He says when he’s in the coronary care unit treating patients who have had heart attacks, they’re usually in one of three groups. “They’ve not had their cholesterol measured, it’s been measured and they don’t know the level, or they’ve had it measured and their doctor says it’s okay. A fourth group will know their level, but that’s not many people. It’s just astounding. It’s what causes this epidemic – 18 New Zealanders are dying each day of heart disease and they don’t know what their LDL is. Doctors may measure it, but they’ve never optimised it.”
Patients who’ve had a heart attack or stroke are treated more aggressively than others – doctors try to get their “bad” cholesterol down to 1.6 or even lower. White says above a level of about 0.8, LDL cholesterol has no physiological role to play and there are some cardiologists who are getting levels down to that sort of range. “It’s just toxic and you should really get it out of the body.”
"18 New Zealanders are dying each day of heart disease and they don’t know what their LDL is."
MANAGING RISK
The Health Ministry paper on cardiovascular risk management was written after consultation with an expert advisory group including Heart Foundation medical director, cardiologist Gerry Devlin, and University of Auckland professor Rod Jackson. Jackson devised the “Predict” algorithm based on about 400,000 New Zealand patients, which weighs a number of factors – including blood pressure, cholesterol, smoking, age, diabetes and sex – to determine a percentage risk over five years. At 5-15%, the benefits of drug treatment, including statins and bloodpressure medication, definitively outweigh the harms, and the benefit increases as the
risk rises.
The guidelines say doctors should discuss the benefits and any harms with patients in that risk band, so patients can make an Controlling her cholesterol: Heart Foundation deputy chair Faye Sumner is a former coronary care nurse. informed decision about whether to start treatment. However, White believes that the risk band is too broad, that treatment should be strongly recommended even between 510%, and patients at greater than 10% risk should definitely be treated.
The paper recommends that patients whose blood pressure is over 160/100 or who have a cholesterol ratio higher than 8 (worked out by dividing total cholesterol by HDL, the “good” cholesterol) should be treated regardless of their total risk. But White also takes issue with the ratio of 8, saying treatment should begin at a much lower level than that – an LDL of 4.9 or higher (the cut-off recommended in the United States, for example), which would translate to a ratio of about 6. “A level of 8 is antediluvian,” he says.
Patients who’ve never had a stroke or heart attack who are at 15% or higher risk have the same chance of a coronary event as someone who already has heart disease – and all those patients are aggressively treated, usually with a combination of statins and blood-pressure pills and often with the addition of aspirin.
Devlin and Jackson have defended the new risk-management strategy. Jackson says the Predict equations showed that in recent years, New Zealand doctors have overestimated risk by almost double, because the figures being used were based on old data from the Massachusetts-based Framingham heart study, collated as heart disease rates
People whose blood pressure was higher than 160 were actually at a higher risk than those with a cholesterol ratio of 8.
began to plummet in the late 1960s and early 1970s. Rates have fallen by more than 90% since then and continue to fall.
Predict estimates that 74% of people aged 30-75 have less than a 5% risk of having a cardiovascular event within five years, 24% have a 5-14% risk and just 2% have a risk 15% or higher. Jackson says new research will soon begin to estimate risk for people
older than 75 – they’ve been excluded from the algorithms until now because the Health Ministry focused on first ensuring that people younger than that were having heart checks.
LIFESTYLE vs AGE
But age in and of itself is not a risk factor, Jackson says. “The issue is the amount of time a person has lived with less-than-ideal modifiable risk factors – age is just a proxy for length of time exposed to bad things. So, although age is not modifiable, blood pressure, lipids, smoking, etc are modifiable. To modify the effects of ‘age’ you need to modify the standard risk factors for a longer period of time.”
He says there’s little merit in lowering the 5-15% “intermediate” risk band to 5-10%, as White advocates, because the benefits of treatment are modest and patients have the right to be told of the likely magnitude of the benefit rather than just being advised to start treatment.
Studies show that if your risk is 12% and you are treated with statins, your five-year risk reduces to 8%, Jackson says, “so two people will benefit out of 100 treated for five years. For some people, this benefit will be enough for them to want treatment – for others it won’t be.”
On its own, any single risk factor, such as blood pressure or cholesterol, is not a great predictor of events, unless it is extreme, he says. Predict data showed people whose blood pressure was higher than 160 were actually at a higher risk than those with a cholesterol ratio of 8. Jackson also says the recommended 40% reduction in LDL cholesterol is significant and more likely to be achievable than an LDL of 1.8. “In most trials, patients get less than a 40% reduction. And it’s easier to lower a high LDL than to lower a moderate one, so reducing it from 3 to 2 is a much bigger job than reducing it from 6 to 4.”
“If your LDL is 5 and you’ve got to get it to 2, that’s just not achievable by diet alone.”
However, the big guns come out for people who’ve already had a coronary event. “In those cases, we do our darnedest to get them down as low as possible,
pushing down to 1.5 now. But even 1.8 is hard work.”
The Heart Foundation’s Devlin says the risk-assessment strategy is based on primary prevention – patients who haven’t had a cardiac event or stroke. The next step is for population-based risk assessment to be enhanced by personalised risk, for example with genetic tests or calcium scores. Calcium scores, available privately here, are a CT scan-based assessment of calcium in the coronary arteries – the more the calcium, the higher the risk. A score above 400 is regarded as high risk.
Devlin, who recently became Gisborne Hospital’s first on-site cardiologist, says the hospital is about to start a cardiac CT service and he’s considering research to explore how useful it is in enhancing assessments in people at higher risk of cardiovascular disease, including Māori and Pasifika. People with serious mental illness also have a greater risk of cardiovascular disease but doctors don’t know why. The Heart Foundation is supporting research at Victoria University’s School of Psychology, which is investigating the link between depression, anxiety and heart disease.
DIETARY CONFUSION
Although White says lifestyle changes are important, he says most people would struggle to bring their cholesterol down significantly through dietary modification alone. Most patients achieve about a 10% reduction, although others manage as much as 15% or as little as 5%. “If your LDL is 5 and you’ve got to get it to 2, that’s just not achievable by diet alone.” In groups who eat the same amount of saturated fat, the dif-
Jackson and White fear stories about the alleged health “benefits” of butter and other saturated fats will put progress at risk.
ferences in cholesterol levels will be largely genetic.
Average cholesterol levels have fallen dramatically since the 1960s. Before about 2000, this was almost entirely because of dietary changes, but in recent years, statins have been a substantial contributor. However, Jackson and White fear that stories about the alleged health “benefits” of butter and other saturated fats will put that progress at risk. Jackson doesn’t believe cholesterol levels will start to rise, though, because more people will be being treated. “People have started eating butter again but they’re now also taking statins.”
Their concern about the public’s dietary confusion is shared by international experts,
including renowned Yale physician David Katz, author of a new book The Truth About Food – Why Pandas Eat Bamboo and People Get Bamboozled (see extract, page 20).
Katz, founding director of the Yale-Griffin Prevention Research Centre in Connecticut, says in the book that diets high in saturated fat, notably fatty and processed meats, “tend to produce bad health outcomes. What this does not mean, however, is that saturated fat is or ever was the one thing wrong with modern diets, or that reducing or removing saturated fat from any product would reliably make it ‘good’ for health.”
He told the Listener that the fundamentals of healthy living shouldn’t be controversial. “The only reason they are is because there are amazing forces in modern culture that profit from the confusion. And, frankly, the scientists are in on it themselves because they’re all trying to be heard above the background noise. The more provocative your message the more likely you are to be heard.”
Katz says the net effect of cholesterol in food on blood cholesterol levels is considerably less than that of dietary saturated fat, but also potentially sugar and refined carbohydrates. The greatest effect of dietary cholesterol on blood cholesterol appears in those who don’t eat much saturated fat anyway.
Katz says he’d long believed dietary cholesterol was “a bad actor” and banished eggs from his own diet for more than 20 years. “I only added them back recently when the weight of evidence had clearly tipped the other way. But let’s be clear what that means. Studies large enough to find clear harms of eggs, and dietary cholesterol, did not identify such harm. That’s important, and to me convincing; but it does not mean such studies identified any benefit.”
White, too, says he’s now eating eggs again after avoiding them for about the same period, from the 1980s, for the same reasons. “They’re a great source of protein and easy to cook. The evidence is clear they are not bad, although you cannot say – as with nuts or a Mediterranean diet or olive oil – that they are good.”
SIDE EFFECTS OF STATINS
Retired Hawke’s Bay GP Paddy Twigg, who turned 70 last month, has been on statins and blood-pressure pills for about 10 years. He says he tried to manage his cholesterol levels with diet first. “I switched from butter to margarine and to trim milk, but I was never tempted to stop eating meat.” He managed to reduce his total cholesterol from 7 to about 6 – not low enough to manage without medication. His blood pressure, which was around 160/95, is now 105/65 and his LDL cholesterol, which had been more than 5, is about 1.7.
Twigg is taking Crestor (rosuvastatin), a statin that’s not funded by Pharmac, because he started treatment around the time of heightened publicity about the possible adverse effects of statins, including mental confusion and muscle aches. “I was having a few memory problems – or thought I was – so I decided to switch to a water-soluble drug because fat-soluble statins are absorbed by nerve cells but water-soluble statins are not.”
He says his most memorable heart patients were always those who had attacks despite being at low risk. “They were active, lean, had normal cholesterol and blood pressure – and boom. There’s a further significant risk factor we can’t identify.” That’s thought to be genetic, and the Heart Foundation is supporting research at the University of Otago’s Christchurch Heart Institute by molecular biologist Anna Pilbrow, a PhD in cardiovascular genetics, who is looking for genetic biomarkers in the blood that may be able to predict heart-attack risk.
Twigg also recalls a female patient whose risk he estimated to be around 12-15% – normally the range at which he’d recommend treatment. “She decided to have a calcium score done – it cost her $3000 including a trip to Auckland – but it found she had a very low score so she decided not to go on medication and I supported her in that.”
About half a million New Zealanders are currently on statins, at an annual cost of $5.7 million (down from $28 million in 1998 for around 100,000 patients before
“There are amazing forces in modern culture that profit from the confusion. And, frankly, the scientists are in on it themselves.”
the drugs came off patent and prices fell steeply). White says concerns about their side effects have been overstated. “They’re one of the safest drugs of all – safer than aspirin even.” An international study that was launched several years ago to reinvestigate reported side effects in 200,000 patients involved in 28 clinical trials of statins is not expected to report for another year. White says only about 8% of patients can’t tolerate statins.
THE NOCEBO EFFECT
Muscle-related symptoms are often reported anecdotally, but, White says, in trials involving 88,000 patients, a nonsignificant extra three per 1000 who were on a statin for five years reported muscle symptoms. He says because patients are warned about the possibility of muscle aches, they’re alert to the possibility and over-report them. It’s what is known as a nocebo effect.
“The nocebo effect is best known in ‘voodoo deaths’ when a person is cursed, told they will die and then dies. If patients believe they may have side effects, they often will experience them. This is opposite to the placebo effect, where patients get a benefit and feel better even though the medicine does nothing.”
Nonetheless, doctors accept that patients’ “real life” experience on statins can be very different – and reported side effects have included gastric upsets, elevated liver enzymes and muscle weakness.
However, they remain the single most commonly prescribed treatment in the developed world. A review published in Lancet in 2016 on the effectiveness and safety of statins found their benefits had been underestimated and harms exaggerated.
As a result of her Heart Foundation role, Faye Sumner knows heart specialists will sometimes disagree about how aggressively to treat. She’s happy with her cholesterol levels now and doesn’t intend to ask for any top-ups to her existing medication regime. She’s also aware there’s more to learn about the “jigsaw” of causes of heart disease, and the best thing patients can do is to be aware of their own risk.
She says there are many more tools available now, including online risk calculators (try the Predict tool on chd.bestsciencemedicine.com), home testing machines and wearable devices such as Fitbits, which allow consumers to take control of their own health. “Knowing your numbers – particularly your cholesterol numbers – is huge.”