Maximum prevention of cardiovascular disease [CVD] – the safety and usefulness of statins
This matters because CVD is a major killer: both cardiovascular death or hospitalisation [Major Adverse Cardiovascular Events = MACE] are almost entirely preventable by lowering blood pressure <120/80, avoiding smoking, and reducing apolipoprotein B concentration [ApoB-‘bad cholesterol’ most of which is LDL-C – this being what is usually measured]. Few if any of you will be smokers in 2023, but many of you have non-optimal BP [see previous InfoSheet on this] and less than perfect cholesterol patterns.
Statins remain the first line of defence but there is a whole conspiracy theory industry telling an untrue negative story about these drugs -do not be persuaded! Equally important is our medical system’s approach to treatment - too little and too late to achieve maximum benefit.
I want to put you straight on both of those.
What good looks like …
If you were a slim active hunter-gatherer, you would have low LDL. As we get fatter and more sedentary, or our glucose metabolism becomes less than perfect, Some people have an increased risk because of hereditary tendency to abnormal lipid patterns: first a raised lipoprotein(a), discussed below and second, familial hypercholesterolaemia. Both mean a higher risk of MACE and events occurring a lot earlier in life – so a risk of premature death.
Although Health Systems focus on those with established problems eg previous MACE or those with high LDL this is not optimal for health prevention. For you, personally the aim should be to have the lipid pattern of a fit young hunter gatherer. As with raised BP, the arterial damage occurs cumulatively as a product of [raised LDL x the time it has been raised]. There is significant gain and no harm in total optimisation now. Clearly there is harm in bumbling along with ‘borderline’ or ‘slightly raised’ LDL
Low-density lipoproteins (LDLs), make up 90-95% of all apoB-containing lipoprotein particles so LDL cholesterol (LDL-C) is frequently used to estimate apoB. This is the key measure [rather than total cholesterol] The balance of HDL to LDL gives further information and high tryclycerides are an independent risk factor for MACE.
“If you are a teenager with ‘normal’ cholesterol it will be of the order of 1.6 mmol/L (60 mg/dL). This is the level of the hunter gatherer you can aspire to be. The ‘normal’ quoted in guidelines is 2.59 mmol/L (100mg/dL), which is rather generous. As it is the apolipoprotein B/ LDL-C that causes the problem you cannot have too low a level and aiming as low as you can comfortably achieve is worthwhile. Triglycerides are an additional risk and if very high may cause pancreatitis. Best studied fasting, a level of 1.13mmo/L would be a good cut off. However men have a higher risk from elevated triglycerides than women.
A word about cholesterol triglycerides and diet
Almost all of the cholesterol in your blood stream has been manufactured by your liver. It has not come from diet [eg how many eggs you eat]. It is a metabolic issue. This means that dietary modification is a poor way to control LDL and it is not worth delaying starting statins to try this out.
Triglycerides are fat molecules but they are principally the eay that excess sugar intake is stored – not an indication to reduce fat intake.
Where are you on this…?
The critical thing is to get tested. A test 3 or 4 years ago doesn’t count. Although high risk individuals show up on non-fasting tests and your doctor or clinic may say you don’t need to fast, I advise you to book a test in the morning and have breakfast after the test [no milky drinks, but black tea or coffee or water is OK]. Then you get clean results not influenced by a meal and you can truly optimise..
You are not convinced?
Landmark randomized controlled trials show statins reduce the risk of death ie all-cause mortality and MACE i.e., heart attack, stroke, and cardiovascular death. This is true both in primary prevention [someone who has no previous heart disease] and secondary prevention [treatment after MACE]. It is interesting that statins reduce ALL causes of death. This probably reflects the second way in which they work: as well as lowering lipids and triglycerides they have an anti-inflammatory capability.
The absolute benefits of statin therapy depend on both an individual’s absolute risk of vascular events and the absolute reduction in LDL cholesterol that is achieved.
Eg, suppose we lower LDL cholesterol by 2 mmol/L for 5 years in 10,000 patients with pre-existing occlusive vascular disease. This prevents MACE in 1000 individulas (ie, 10% absolute benefit).
If we take people with increased risk but no events – this prevents MACE in 500 individuals (ie, 5% absolute benefit) who are at increased risk but have not yet had a vascular event .
Statin therapy has been shown to reduce vascular disease risk further during each year it continues to be taken, so larger absolute benefits would accrue with more prolonged therapy, and these benefits persist long term. Simply as far as lipids go “the lower the better”.
You fear statins - What about risks?
The risks of statins have been exaggerated in the media. A major review in the Lancet in 2017 looked very critically at over 20 years of research. The review tested the quality of the studies, possible misinterpretations of data and answered all of the Qs that have come up during these 20 years .
There are rare cases of myopathy (muscle pain or weakness combined with large increases in blood concentrations of creatine kinase), cases of new-onset diabetes mellitus, and, a slight increase in the risk of haemorrhagic stroke [but overall stroke benfit].
Myopathy: treatment of 10 000 patients for 5 years with an effective regimen (eg, atorvastatin 40 mg daily) would cause about 5 cases of myopathy (one of which might progress, if the statin therapy is not stopped, to the more severe condition of rhabdomyolysis). This is specific diagnosable condition [raised blood creatinine kinase is definitive]. However muscle pain or weakness is reported in 50–100 patients (ie, 0.5–1.0%) per 10 000 treated for 5 years. The placebo-controlled randomised trials show definitively that these symptomatic adverse events that are attributed to statin therapy in routine practice are not actually caused by it. GPs and patients believe that statins cause these problems but actually they are just as common inn older individuals who don’t take statins.
Stroke: the context here is important – 13% of strokes are haemorrhagic and are the result of bleeding from a pre-existing weakness inn a blood vessel. Any blood ‘thinning’ agent will increase the risk of bleeding eg ibuprofen, aspirin, anticoagulants or a statin. Typically, , 50–100 new cases of diabetes, and 5–10 haemorrhagic strokes. However, any adverse impact of these side-effects on major vascular events has already been taken into account in the estimates of the absolute benefits. Statin therapy may cause symptomatic adverse events (eg, (ie, they represent misattribution). The large-scale evidence available from randomised trials also indicates that it is unlikely that large absolute excesses in other serious adverse events still await discovery. The principal statins used are atorvastatin, rosuvastatin and simvastatin. Various other are available globally but are not used in the UK and are ‘me too ‘ drugs with no particular benefit.
Simvastatin in high dose has a higher risk of side effects. I recommend starting on atorvastatin.
Summary
The benefits of statins are substantial and scientifically watertight. The risks of statins are minor and can usually be overcome by modification of type and dose. In difficult cases, including if triglycerides do not fall sufficiently on a statin, alternative drugs are now available.
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