Hyperlipidaemia - what you need to know
Chemical pathologist Dr Robert Cramb answers GP Dr Pam Brown’s questions on statins and the metabolic syndrome, stanols and the pros and cons of high- and low-dose simvastatin
Chemical pathologist Dr Robert Cramb answers GP Dr Pam Brown's questions on statins and the metabolic syndrome, stanols and the pros and cons of high- and low-dose simvastatin
1. What common causes of raised triglycerides should we exclude when we identify someone with hypertriglyceridaemia? Do mildly raised and severely raised levels have possible different causes?
It's important to take a careful history with regard to excess alcohol consumption – some patients are reluctant to reveal the extent of their drinking. Also remember that others, despite not drinking excessive amounts of alcohol, can be exquisitely sensitive to it and develop hypertriglyceridaemia very easily.
Patients with undiagnosed diabetes often have concurrent raised triglyceride concentrations, which may or may not be apparent in a careful history but can be easily identified through a simple venous blood test.
Obesity is an obvious factor but visceral obesity, where the fat is mainly found abdominally rather than subcutaneously, is a particularly potent source of plasma triglycerides. Subcutaneous fat is much more likely to be adequately controlled by normal insulin production and poses less of a risk for hypertriglyceridaemia.
Increases in plasma triglyceride concentrations are highly variable and all of these common causes of hypertriglyceridaemia can produce mild, moderate and sometimes spectacular increases in triglyceride concentrations.
2. Should the presence of metabolic syndrome in the absence of type 2 diabetes influence our threshold for treating with a statin for primary prevention?
There is a lot of debate over whether metabolic syndrome is a true entity or merely an epiphenomenon associated with diabetes. But post-hoc analyses of many of the major statin trials have shown that patients who have the markers associated with metabolic syndrome are more at risk of cardiovascular disease. The decision on whether to use lipid-lowering agents is – rightly or wrongly – currently based around Framingham risk data, in the absence of defined familial disease.
The single major factor defining metabolic syndrome is waist size – that is, visceral obesity. I would not use the metabolic syndrome as a reason for lowering the threshold at which to start a statin. But I would use it to focus the attention of the patient on reviewing their dietary and exercise habits before considering any use of a statin.
Obviously, if the patient is being treated for secondary prevention of cardiovascular disease the presence or absence of metabolic syndrome is irrelevant.
3. What is the role of stanols and sterols in lipid lowering? Are there any downsides to our patients choosing to use these, apart from the cost?
Stanols or sterols at 2g per day in patients who have already made dietary and exercise changes are likely to lower total cholesterol concentrations by up to 10%. Although stanols and sterols can be obtained in a variety of products, the yogurt drinks contain about 2g of these agents, and consuming amounts greater than 2g of them is unlikely to produce any more significant lipid lowering.
One advantage of the yogurt drinks is that they have a defined amount of stanol or sterol and a relatively low number of calories. In patients who have weight problems this does mean that they might find it easier to regulate their total calorie consumption using these products.
4. I've had some patients ask about co-enzyme Q10 supplements and CV disease plus a lot has been written about the impact of statins on co-enzyme Q10 levels. Should patients on statins be encouraged to take supplements?
Anecdotally it is often reported that co-enzyme Q10 supplements can prevent myalgia often associated with statins.
But there are no convincing data to show that supplements of Q10 are associated with any improvement in symptoms in large-scale trials.
Some patients appear to have a significant reduction in symptoms while taking them but, although they or their doctor may find their use beneficial, there's no evidence that we should be recommending the widespread use of these supplements to anyone taking a statin.
5. When is it appropriate to prescribe omega 3 fatty acid supplements to improve lipid profile?
Omega 3 fatty acids are useful in patients with hypertriglyceridaemia. But the effect is variable and even though they can produce a very brisk reduction in triglycerides in some, in others this may be less beneficial. High doses of omega 3 fatty acid capsules (up to four capsules a day) may be required to produce any measurable triglyceride-lowering effect and some patients do not react well to excessive omega 3 consumption as fish oils.
6. NICE recommends starting therapy with simvastatin 40mg in primary and secondary prevention but suggests using lower doses if 40mg is not tolerated. In which patients is it appropriate to start at a lower dose?
I'm more inclined to start simvastatin at a low dose and titrate upwards in all patients.
The biggest reduction in cholesterol concentration is found with the initial dose of any of the statins and thereafter any doubling dose of statins elicits about a 6% reduction in total cholesterol for every doubling dose.
This dose increase can be carried out monthly and some patients who suffer problems at 40mg may be well controlled with the use of 10mg and achieve reductions in cholesterol that are appropriate to meet current targets and elicit a good reduction in cholesterol.
At least 80% of patients will be able to tolerate full-dose simvastatin, particularly if they are titrated to these levels. It is the remaining 20% of patients that may require a review of their lipid-lowering therapy to include supplementary drugs with lower doses of statins.
7. If we prescribe 80mg simvastatin to patients whose total cholesterol and HDL remain above 4 or 2 respectively, how many patients are likely to be intolerant of the higher dose?
Personally, I wouldn't recommend increasing simvastatin to 80mg in any circumstances. Although the guidance from NICE suggests this as a way forward there is a much greater risk of myopathy and rhabdomyolysis as a result of the use of increased doses of simvastatin. Although in percentage terms this may only affect a very small number of patients, the risk is sufficiently high for me to never use an 80mg dose.
8. What baseline level of transaminases should prevent us initiating statin therapy? NICE recommends checking LFTs at three and 12 months. What absolute level or increase should make us consider stopping the statin?
The use of statins in patients with raised LFT levels will depend on the aetiology of the raised transaminases.
In patients who are drinking excessively, attention should be given to their alcohol consumption rather than progressing with statin therapy.
The level of transaminases on their own is not a good guide to overall liver function. If patients' INR is abnormal then further investigations of their liver function should be undertaken before considering a statin.
But if patients have raised transaminase levels – for instance, as a result of fatty liver or previous viral infection – this is not an absolute contraindication.
The statins should carry on at the lowest possible dose with a review of transaminases after two or three weeks.
In many patients with fatty liver, statins titrated slowly can improve transaminase levels, but high doses of potent statins can increase transamimases and the effect will remain until the statin is stopped.
A very small number of patients can be exquisitely sensitive to statins but they may have underlying causes of liver disease that require further investigation.
As a general rule, continuing rises in transaminases should suggest that patients have the drugs discontinued, and increases of between three and five times the starting levels of the transaminases would be an indication to discontinue their use immediately.
9. What are the important drug interactions with statins?
Important reactions are in part dependent on the statin used. But the key interactions of which we must be aware are:
• increased risk of myopathy with erythromycin – particularly simvastatin and atorvastatin
• potential interaction with anticoagulants – with atorvastatin transiently reducing the effect of warfarin, and fluvastatin potentially enhancing its anticoagulant effect
• myopathy – increased when statins are given with antifungal agents, especially with simvastatin
• additional problems of myopathy can be found with cyclosporin and concomitant use of statins and fibrates do require care and monitoring
• grapefruit juice consumption – contraindicated while taking simvastatin; it may also increase the plasma concentration of atorvastatin.
10. At what age is it appropriate to screen children or young adults at risk of familial hyperlipidaemia? At what age should therapy commence?
In children at risk of familial hypercholesterolaemia, tests should be carried out by the age of 10 or at the earliest opportunity. Ideally, genetic analysis with an appropriate DNA test if the family mutation is known is the ideal test, although this is not currently widely available.
Otherwise a full lipid profile, including triglycerides, HDL and LDL, should be ordered and reviewed.
If the total cholesterol and LDL cholesterol fall within the diagnostic areas, children should be referred to an appropriate specialist with expertise in managing children with familial hypercholesterolaemia. It is for these specialists to advise the appropriate age at which to start therapy.
More details can be found in a recent Ten Top Tips on familial hypercholesterolaemia.
11. Which patients with hyperlipidaemia should we consider referring?
Unfortunately it's never clear which patients are going to benefit from referral to secondary care. But patients in whom there is a question mark over their diagnosis, those with profound hypertriglyceridaemia and those who are intolerant of statins, and sometimes other drugs, may benefit from the expertise of specialists with an interest in hyperlipidaemia.
It's also worth remembering that the NICE guidance for familial hypercholesterolaemia suggests healthcare professionals with an interest and expertise in treating this disease be used to follow those patients that have a clear diagnosis. All children with FH should be referred to specialist children's units.
12. What is the likely magnitude of benefits from changes in physical activity or diet on the various lipid fractions? What dietary advice can we give patients with hyperlipidaemia in the absence of specialist dietetic advice?
The benefits from changes in physical activity and diet depend on how little physical activity is currently undertaken and the overall quality of the current diet.
Patients with a diet high in total and saturated fat and refined carbohydrate who change to one with less than 30% of calories coming from fat and more from monounsaturated and polyunsaturated fats – as well as a shift to less refined carbohydrate and more soluble fibre – can make spectacular lipid reductions.
Decreases of 15% in total cholesterol can be achieved and for those patients who have a lack of physical activity and a poor diet, the changes in triglycerides can be even more marked.
Dietary advice should be kept relatively simple and focus on the areas in which excess fat and refined carbohydrates are easily found in the diet. Patients should:
• cut down their consumption of full cream milk substituting this with semi-skimmed or skimmed milk
• reduce cheese consumption, particularly cheeses with a very high fat content such as stilton and many cheddars
• reduce intake of red meat and substitute this with white meat or fish (reminding patients that battered, deep-fried fish is not the ideal substitute)
• avoid excessive consumption of cakes, chocolates, pastries, crisps, ice-creams and confectionery
• increase their consumption of fruit and vegetables, using the five-a-day guide as a minimum.
An area that is often ignored is that of carbonated sweetened drinks and, paradoxically, excessive amounts of smoothies or fruit juices should be avoided as they provide large amounts of relatively easily obtainable carbohydrate.
Dr Robert Cramb is a consultant chemical pathologist at University Hospital, Birmingham, chair of HEART UK's laboratory subcommittee and a member of the charity's medical, scientific and research committee. This article reflects the personal views of the author, not necessarily those of HEART UK and its committees
Competing interests: none declared
HEART UK – The Cholesterol Charity is committed to raising awareness of the risks of high cholesterol, lobbying for better detection of those at risk, funding research into improved treatment and supporting health professional training. Healthcare professional membership of the charity includes a variety of benefits including lipid news updates in the quarterly magazine, reduced registration at the charity's annual conference and invitations to educational workshops. For more information please visit the HEART UK website.Xanthalesma in a hyperlipidaemic patients Xanthalesma in a hyperlipidaemic patients What I will do now What I will do now
Dr Pam Brown considers the responses to her questions
I've always been enthusiastic about helping my patients make small, incremental changes to their diet and physical activity if they have hyperlipidaemia, hypertension or diabetes and I will continue to do this.
I'll also continue to discuss use of stanols and sterols with those patients who do not qualify for statin therapy but who have raised TC and LDL.
Perhaps we should all be more vigilant about warning patients to avoid grapefruit juice when they are taking simvastatin – many of them may not read the patient leaflet fully or be warned by their pharmacist.
I will encourage patients on warfarin to have their INR checked shortly after starting fluvastatin in case they need a dose reduction.
There is a tendency to start simvastatin directly at 40mg in patients with diabetes – perhaps it is worth titrating up rather than starting with this dose.
I will arrange for children to be tested much younger if there is confirmed familial hypercholesterolaemia.
Dr Pam Brown is a GP in Swansea