Sunday, 30 December 2012

High plasma HDL cholesterol is NOT associated with reduced risk of myocardial infarction

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High plasma HDL cholesterol is associated with reduced risk of myocardial infarction, but whether this association is causal is unclear. Exploiting the fact that genotypes are randomly assigned at meiosis, are independent of non-genetic confounding, and are unmodified by disease processes, mendelian randomisation can be used to test the hypothesis that the association of a plasma biomarker with disease is causal.






Some genetic mechanisms that raise plasma HDL cholesterol do not seem to lower risk of myocardial infarction. These data challenge the concept that raising of plasma HDL cholesterol will uniformly translate into reductions in risk of myocardial infarction.


In summary, our results showed that polymorphisms related to plasma LDL cholesterol were consistently associated with risk of myocardial infarction, whereas this was not the case for variants related to plasma HDL cholesterolA polymorphism in the endothelial lipase gene and a genetic score of 14 common SNPs that specifically raised HDL cholesterol were not associated with myocardial infarction, suggesting that some genetic mechanisms that raise HDL cholesterol do not lower risk of myocardial infarction. Hence, interventions (lifestyle or pharmacological) that raise plasma HDL cholesterol cannot be assumed ipso facto to lead to a corresponding benefit with respect to risk of myocardial infarction.

Cardiovascular Disease Risk Prediction Charts

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Risk charts

How to use the Cardiovascular Disease Risk Prediction Charts* for Primary Prevention

These charts are for estimating cardiovascular disease (CVD) risk (non-fatal myocardial infarction [MI] and stroke, coronary and stroke death and new angina pectoris) for individuals who have not already developed coronary heart disease (CHD) or other major atherosclerotic disease. They are an aid to making clinical decisions about how intensively to intervene on lifestyle and whether to use antihypertensive, lipid lowering medication and aspirin. The use of these charts is not appropriate for the following patients groups.

  • Those with: CHD or other major atherosclerotic disease 
  • Familial hypercholesterolaemia or other inherited dyslipidaemias 
  • Chronic renal dysfunction 
  • Type 1 and 2 diabetes mellitus

The charts should not be used to decide whether to introduce antihypertensive medication when blood pressure (BP) is persistently at or above 160/100 or when target organ damage (TOD) due to hypertension is present. In both cases antihypertensive medication is recommended regardless of CVD risk.

Similarly the charts should not be used to decide whether to introduce lipid-lowering medication when the ratio of serum total to high density lipoprotein (HDL) cholesterol exceeds 7. Such medication is generally then indicated regardless of estimated CVD risk.

To estimate an individual’s absolute 10 year risk of developing CVD choose the table for his or her gender, smoking status (smoker/non-smoker) and age. Within this square define the level of risk according to the point where the coordinates for systolic blood pressure (SBP) and the ratio of total cholesterol to HDL-cholesterol meet. If no HDL cholesterol result is available, then assume this is 1.00mmol/l and the lipid scale can be used for total serum cholesterol alone.

Higher risk individuals (red areas) are defined as those whose 10 year CVD risk exceeds 20%, which is approximately equivalent to the CHD risk of >15% over the same period indicated by the previous version of these charts. As a minimum those at highest CVD risk (greater than 30% shown by the line within the red area) should be targeted and treated now. When resources allow, others with a CVD risk of >20% should be progressively targeted.

The chart also assists in the identification of individuals whose 10 year CVD risk moderately increased in the range 10-20% (orange area) and those in whom risk is lower than 10% over 10 years (green area).

Smoking status should reflect lifetime exposure to tobacco and not simply tobacco use at the time of assessment. For example, those who have given up smoking within 5 years should be regarded as current smokers for the purposes of the charts.

The initial BP and the first random (non-fasting) total cholesterol and HDL cholesterol can be used to estimate an individual’s risk. However, the decision on using drug therapy should generally be based on repeat risk factor measurements over a period of time.

Men and women do not reach the level of risk predicted by the charts for the three age bands until they reach the ages 49, 59, and 69 years respectively. Everyone aged 70 years and over should be considered at higher risk. The charts will overestimate current risk most in the under forties. Clinical judgement must be exercised in deciding on treatment in younger patients. However, it should be recognised that BP and cholesterol tend to rise most and HDL cholesterol to decline most in younger people already possessing adverse levels. Thus untreated, their risk at the age 49 years is likely to be higher than the projected risk shown on the age-less-than 50 years chart.

These charts (and all other currently available methods of CVD risk prediction) are based on groups of people with untreated levels of BP, total cholesterol and HDL cholesterol. In patients already receiving antihypertensive therapy in whom the decision is to be made about whether to introduce lipid-lowering medication or vice versa the charts can act as a guide, but unless recent pre-treatment risk factor values are available it is generally safest to assume that CVD risk is higher than that predicted by current levels of BP or lipids on treatment.

CVD risk is also higher than indicated in the charts for:-

  • Those with a family history of premature CVD or stroke (male first degree relatives aged <55 years and female first degree relatives aged <65 years) which increases the risk by a factor of approximately 1.5 
  • Those with raised triglyceride levels 
  • Women with premature menopause 
  • Those who are not yet diabetic, but have impaired fasting glucose (6.1-6.9mmol/l) 
  • In some ethnic minorities the risk charts underestimate CVD risk, because they have not been validated in these populations. For example, in people originating from the Indian subcontinent it is safest to assume that the CVD risk is higher than predicted from the charts (1.5 times). 
  • The charts may be used to illustrate the direction of impact of risk factor intervention on estimated level of CVD risk. However, such estimates are crude and are not based on randomised trial evidence. Nevertheless, this approach maybe helpful in motivating appropriate intervention. 
  • The charts are primarily to assist in directing intervention to those who typically stand to benefit most. 

*Cardiovascular Disease Risk Prediction Chart reproduced with permission from The University of Manchester Department of Medical Illustration, Manchester Infirmary.

Vaccine developed to protect against norovirus

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by Ian Sample in Vancouver, The Guardian, Friday 17 February 2012 18.00 GMT

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Vaccine developed to protect against norovirus or 'winter vomiting bug' 

A vaccine for norovirus, which is highly infectious and is difficult to kill by cleaning, could be available within five years.

People infected with norovirus (above) can remain infectious for more than three weeks. Photograph: CDC/Phanie/Rex Features 

A vaccine against the highly infectious winter vomiting bug that strikes thousands of people in Britain each year is close to being tested in humans.

Doctors have approached government funders to begin human trials after laboratory tests showed the vaccine could prevent people from succumbing to the infection.

Researchers said the technical issues in formulating the vaccine appeared to be solved, and that regulators now had to assess the treatment's suitability for full-scale clinical trials.

The stomach bug, caused by seasonal norovirus, spreads rapidly between people and is difficult to kill off by cleaning. It has ruined countless holiday cruises, closed hundreds of hospital wards and torn through prisons.

In recent weeks, three US cruise ships have been forced to return early to their ports for deep cleaning after outbreaks of norovirus saw hundreds of passengers and crew struck down with diarrhoea and vomiting. Cruise ships are required to report norovirus outbreaks to the US Centres for Disease Control and Prevention when 3% or more of those onboard go down with the bug.

"When it hits in a situation like a cruise ship, it spreads like wildfire," said Charles Arntzen, co-director of the Centre for Infectious Diseases and Vaccinology at Arizona State University.

Laboratories in England and Wales have confirmed more than 1,100 cases of norovirus in the first four weeks of 2012, according to figures from the Health Protection Agency. So far in this winter season there have been 755 outbreaks in English and Welsh hospitals, leading to 520 ward closures or restrictions on admissions.

Though the illness is generally mild and clears up in two to three days, people can remain infectious for more than three weeks. Most people who are fit and healthy make a full recovery.

"You can have diarrhoea and wash your hands thoroughly afterwards, but if you leave as few as 10 viruses on a door knob, and someone else picks it up, they can get the disease and spread it," Arntzen said. Since the 1980s, a second, more virulent strain of norovirus has emerged and now accounts for around 85% of outbreaks.

To develop the vaccine, scientists working with Arntzen took a gene from norovirus that codes for its protective protein coat and added it to a common tobacco virus. When the virus infected tobacco plants and multiplied inside their cells, it produced thousands of copies of the norovirus protein, which coalesced into virus-like particles. The particles are harmless, but can be used in a vaccine to trigger an immune attack on the virus.

Arntzen's group has teamed up with a group in Kentucky that grows tobacco plants on an industrial scale to manufacture the vaccine. From 1kg of tobacco plant, the researchers can make 10,000 doses of vaccine.

Lab tests of the vaccine showed it was most effective when given as a nasal spray, combined with a dried aloe extract, which made the vaccine stick to mucous membranes in the nose. Vaccine that contained aloe stayed in the nose for around three hours, which is long enough to prime immune defences in other mucous membranes around the body including the gut, where the norovirus strikes.

The results were presented at the annual meeting of the American Association for the Advancement of Science in Vancouver.

The final version of the vaccine is likely to carry virus-like particles from both major strains of norovirus, and possibly some common sub-strains, to ensure it provides broad protection against the bug. A single shot of nasal spray could be effective for six months to two years, Arntzen said.

The vaccine, which could be available in four to five years, may prove popular in children's day care centres and among cruise ship workers, hospital staff, carers in old people's homes, and the military, all of which face regular outbreaks of norovirus.

Crabsallover Lipid & Cholesterol levels

Crabsallover tests: 
November 2006 / 25 November 2008 / 15 July 2010 / 26 January 2011 / 3 November 2011

Crabsallover Serum cholesterol: 
5.1mmol/L, 4.7mmol/L / 5.6mmol/L / 3.5mmol/L / 6.1mmol/L
Conclusion: trend is negative, aim to decrease serum cholesterol by 30% from 5.6 to <3.9mmol/L (target me 26 January 2011) but increased to 6.1mmol/L 3 November 2011

Crabsallover Serum triglycerides: 
Not tested 2.2 mmol/L / 1.5mmol/L (range: 0.5-2.3) / 1.0mmol/L / 2.0mmol/L
Conclusion: trend is positive but aim to decrease triglycerides 26% from 1.5 to <1.1mmol/L

Crabsallover Serum  HDL cholesterol: 
Not tested / 1.18 mmol/L / 1.35mmol/L ./ 1.09mmol/L / 1.4mmol/L
Conclusion: trend is positive but aim to increase HDL 15% from 1.35 to >1.55 mmol/L (@ 15 July 2010)

Crabsallover Serum LDL cholesterol: 
Not tested 2.5 mmol/L / 3.6mmol/L / 2.00mmol/L / 3.8mmol/L
Conclusion: trend is negative for LDL cholesterol, 3.6-3.8mmol/L are borderline high levels - aim for 50% decrease to <1.8mmol/L ie reduce by ~ 2mmol/L @ 3 November 2011

Crabsallover Serum cholesterol/HDL ratio: 
Not tested / 4.0 / 4.1 / 3.2 / 4.4
Conclusion: Lower serum cholesterol/HDL ratio by 27% from 4.1 to 3 - reduce total cholesterol and/or increase HDL @ 15 July 2010.

Overall Lipid & Cholesterol Conclusions: 
Reduce serum cholesterol, triglycerides and LDL cholesterol levels by 30%, 26% and 50% respectively. Increase HDL cholesterol levels by 15% @ 15 July 2010

HeartUK pdf (accessed 30 December 2012)
  • Analyse & reduce / change fats eaten
    • reduce total amount of fat eaten
      • grilled chicken breast without skin contains third less saturated fat than with skin
    • reduce saturated fats (increases LDL cholesterol & risk of narrowed arteries)
      • butter, hard cheese, fatty meat, cream, lard, suet, ghee, coconut oil and palm oil.
    • replace saturated fats with unsaturated fats (lowers LDL & serum cholesterol) 
      • polyunsaturated fats (lowers serum cholesterol & blood triglycerides)
        • Oily fish provides polyunsaturated omega-3 fats 
          • 1.2g omega-3 fats / 100g pilchards
          • omega-3 fats reduces: carotid artery thickness, triglyercides, coronary incidents; increases HDL & reduces LDL cholesterol
      • monounsaturated fats (lowers LDL cholesterol whilst maintaining HDL cholesterol)
        • olive / rapeseed / corn oils
        • nuts and seeds
        • some margarines and spreads
        • cheeses low in fat & saturated fat: cottage cheese, ricotta & half-fat cheddar. 
  • consider Statins if diet modification does not work in a year
Serum Cholesterol

Guidelines for cholesterol levels have been set for healthy people and for those at high risk. High risk means someone with existing heart disease, high blood pressure, diabetes or with a family history of early heart disease. 
Recommendations for Healthy Adults Total cholesterol 5 mmol/l or less
Recommendations for High Risk Adults 4 mmol/l or less

The government recommends that cholesterol levels should be less than 5mmol/L.
In the UK, two out of three adults have a total cholesterol level of 5mmol/L or above. On average, men in England have a cholesterol level of 5.5mmol/L and women have a level of 5.6mmol/L. The UK population has one of the highest average cholesterol concentrations in the world.

To convert mg/dl of HDL or LDL cholesterol to mmol/l, divide by 39.
If you are taking treatment to lower your cholesterol, the target is to lower your total cholesterol to <4 mmol/L (156mg/dl), with a fall of around 20-25%.
Less than 200 mg/dL = 5.1mmol/L = Desirable level that puts you at lower risk for coronary heart disease. A cholesterol level of 200 mg/dL or higher raises your risk.
200 = 5.1mmol/L to 239 mg/dL = 6.1 mmol/L = Borderline high
240 mg/dL = 6.1mmol/L and above High blood cholesterol. A person with this level has more than twice the risk of coronary heart disease as someone whose cholesterol is below 200 mg/dL.

Serum Triglycerides
crabsallover History:

high triglyceride level combined with low HDL cholesterol or high LDL cholesterol seems to speed up atherosclerosis (the buildup of fatty deposits in artery walls). Atherosclerosis increases the risk for heart attack and stroke.
1.5mmol/L x 89 = 133.5 mg/dL
To convert mmol/l of triglycerides to mg/dl, multiply by 89.
Less than 150 mg/dL = 1.68mmol/L =Normal
150–199 mg/dL Borderline high =A triglyceride level of 150 mg/dL or higher is one of the risk factors of metabolic syndrome. Metabolic syndrome increases the risk for heart disease and other disorders, including diabetes.
200–499 mg/dL High
500 mg/dL and above Very high
The mean level of triglycerides for American adults age 20 and older is 144.2 mg/dl (1.6mmol/L)

No figures cited:

Serum HDL cholesterol

Guidelines for cholesterol levels have been set for healthy people and for those at high risk. 
Recommendations for Healthy Adults HDL cholesterol: Men – above 1.0 mmol/l High levels of HDL cholesterol are better than low HDL cholesterol.  The higher your HDL cholesterol level, the lower risk of developing heart disease. There are two ways that HDL cholesterol values are interpreted—as a percent of total cholesterol or as a measured value.  Measured Value: If HDL cholesterol is less than 1.0 mmol/L in men there is an increased risk of heart disease. A desirable level of HDL is greater than 1.0 mmol/L for men and is associated with average risk of heart disease. A good level of HDL is 1.5 mmol/L or more and is associated with a less than average risk of heart disease.

To convert mg/dl of HDL or LDL cholesterol to mmol/l, divide by 39.
HDL Cholesterol Level Category
Less than 40 mg/dL (for men) = Low HDL cholesterol. A major risk factor for heart disease.
60 mg/dL and above = High HDL cholesterol. An HDL of 60 mg/dL and above is considered protective against heart disease.

With HDL (good) cholesterol, higher levels are better. Low HDL cholesterol (less than 40 mg/dL for men, less than 50 mg/dL for women) puts you at higher risk for heart disease. In the average man, HDL cholesterol levels range from 40 to 50 mg/dL. In the average woman, they range from 50 to 60 mg/dL. An HDL cholesterol of 60 mg/dL or higher gives some protection against heart disease. The mean level of HDL cholesterol for American adults age 20 and older is 54.3 mg/dL.
Smoking, being overweight and being sedentary can all result in lower HDL cholesterol. To raise your HDL level, avoid tobacco smoke, maintain a healthy weight and get at least 30-60 minutes of physical activity more days than not.
People with high blood triglycerides usually also have lower HDL cholesterol and a higher risk of heart attack and stroke. Progesterone, anabolic steroids and male sex hormones (testosterone) also lower HDL cholesterol levels. Female sex hormones raise HDL cholesterol levels.

Serum LDL Cholesterol
Guidelines for cholesterol levels have been set for healthy people and for those at high risk. 
High risk means someone with existing heart disease, high blood pressure, diabetes or with a family history of early heart disease.
Recommendations for Healthy Adults LDL cholesterol  3 mmol/l or less
Recommendations for High Risk Adults LDL cholesterol: 2 mmol/l or less Elevated levels of LDL indicate risk for heart disease. Treatment (with diet or drugs) for high LDL aims to lower LDL to a target value of less than 3 mmol/L.
This is especially important if you have other risk factors for heart disease. Risk factors include cigarette smoking, hypertension, low HDL (< 1 mmol/L), family history, age (male 55 or older; female 65 or older), being overweight, and failure to exercise regularly.

“Bad” LDL cholesterol is seen as being worryingly high at 7 mmol/l, more healthy: 4.4mmol/l.  Optiimal: 1 to 3 mmol/L

UK Government advises  LDL should be <3mmol/L

To convert mg/dl of HDL or LDL cholesterol to mmol/l, divide by 39.

Serum Total Cholesterol to HDL ratio High levels of HDL cholesterol are better than low HDL cholesterol.  The higher your HDL cholesterol level, the lower risk of developing heart disease. There are two ways that HDL cholesterol values are interpreted—as a percent of total cholesterol or as a measured value.  
Percent: If HDL is 20% of the total cholesterol, the risk of heart disease is average. If HDL is more than 20% of the total cholesterol, the risk of heart disease is less than average. This is usually expressed as a ratio of cholesterol to HDL. It is desirable for the cholesterol/HDL ratio to be less than 5.

Friday, 28 December 2012

With statins reduce risk of coronary events even if already at low risk

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The Lancet, Volume 380, Issue 9841, Pages 581 - 590, 11 August 2012
Published Online: 17 May 2012

The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials


Statins reduce LDL cholesterol and prevent vascular events, but their net effects in people at low risk of vascular events remain uncertain.


This meta-analysis included individual participant data from 22 trials of statin versus control (n=134 537; mean LDL cholesterol difference 1·08 mmol/L; median follow-up 4·8 years) and five trials of more versus less statin (n=39 612; difference 0·51 mmol/L; 5·1 years). Major vascular events were major coronary events (ie, non-fatal myocardial infarction or coronary death), strokes, or coronary revascularisations. Participants were separated into five categories of baseline 5-year major vascular event risk on control therapy (no statin or low-intensity statin) (<5%, ≥5% to <10%, ≥10% to <20%, ≥20% to <30%, ≥30%); in each, the rate ratio (RR) per 1·0 mmol/L LDL cholesterol reduction was estimated.


Reduction of LDL cholesterol with a statin reduced the risk of major vascular events (RR 0·79, 95% CI 0·77—0·81, per 1·0 mmol/L reduction), largely irrespective of age, sex, baseline LDL cholesterol or previous vascular disease, and of vascular and all-cause mortality. The proportional reduction in major vascular events was at least as big in the two lowest risk categories as in the higher risk categories (RR per 1·0 mmol/L reduction from lowest to highest risk: 0·62 [99% CI 0·47—0·81], 0·69 [99% CI 0·60—0·79], 0·79 [99% CI 0·74—0·85], 0·81 [99% CI 0·77—0·86], and 0·79 [99% CI 0·74—0·84]; trend p=0·04), which reflected significant reductions in these two lowest risk categories in major coronary events (RR 0·57, 99% CI 0·36—0·89, p=0·0012, and 0·61, 99% CI 0·50—0·74, p<0·0001) and in coronary revascularisations (RR 0·52, 99% CI 0·35—0·75, and 0·63, 99% CI 0·51—0·79; both p<0·0001). For stroke, the reduction in risk in participants with 5-year risk of major vascular events lower than 10% (RR per 1·0 mmol/L LDL cholesterol reduction 0·76, 99% CI 0·61—0·95, p=0·0012) was also similar to that seen in higher risk categories (trend p=0·3). In participants without a history of vascular disease, statins reduced the risks of vascular (RR per 1·0 mmol/L LDL cholesterol reduction 0·85, 95% CI 0·77—0·95) and all-cause mortality (RR 0·91, 95% CI 0·85—0·97), and the proportional reductions were similar by baseline risk. There was no evidence that reduction of LDL cholesterol with a statin increased cancer incidence (RR per 1·0 mmol/L LDL cholesterol reduction 1·00, 95% CI 0·96—1·04), cancer mortality (RR 0·99, 95% CI 0·93—1·06), or other non-vascular mortality.


In individuals with 5-year risk of major vascular events lower than 10%, each 1 mmol/L reduction in LDL cholesterol produced an absolute reduction in major vascular events of about 11 per 1000 over 5 years. This benefit greatly exceeds any known hazards of statin therapy. Under present guidelines, such individuals would not typically be regarded as suitable for LDL-lowering statin therapy. The present report suggests, therefore, that these guidelines might need to be reconsidered.

11 per 1000 over 5 years = 2.2 per 100 over 10 years, for 1mmol/L reduction in LDL cholesterol. My risk would reduce from 8 to 6 per 100 over 10 years or from 4% to 3% over 5 years if I take statins and reduce LDL cholesterol from 3.1 (3/1/13 result) to 2.1mmol/L.


British Heart Foundation; UK Medical Research Council; Cancer Research UK; European Community Biomed Programme; Australian National Health and Medical Research Council; National Heart Foundation, Australia.

Thursday, 27 December 2012 measures risk of heart attack or stroke in next 10 years

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Weight 10stone


NICE guidelines on Lipid Management & Statins being updated

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Following on from the CTT 2012 report, NICE are investigating new guidelines for use of statins for people with a <=10% risk of heart attack or stroke in next 10 years.

NICE guidelines on lipid management and use of Statins are being updated. See the scope and 2nd meeting (October 2012) minutes.

The risk assessment stage of the NHS Health Check (formerly known as the Vascular Check Programme) uses a risk engine for people aged 40–74 years to calculate their 10-year risk of CVD. Blood lipids, including cholesterol, are a modifiable risk factor for CVD. The risk of CVD is directly related to blood cholesterol levels and it is estimated that more than 50% of CVD in developed countries is a result of blood cholesterol levels higher than 3.8 mmol/litre. Blood cholesterol and other lipid components can be modified by drugs, physical activity and dietary changes; a multifactorial approach is likely to yield most benefit. (pg 2 of scope)

Key clinical issues that will be covered a) The most appropriate risk tool system to estimate a person’s absolute risk of developing CVD for: people without diabetes – for example, age alone, QRISK and Framingham risk assessment tools (10-year or lifetime risk)

Lipid modification strategy: for example, fixed dose or treating to a target lipid level.

c) Pharmacological interventions
(1) to reduce the risk of developing CVD (primary prevention) and (2) for secondary prevention in people with established CVD:
First-line treatment: statins.
Second-line treatment (alone or in combination with statins):
fibrates, anion-exchange resins, nicotinic acid group, omega-3 fatty acids.

5.1.1 NICE guidance to be updated
This guideline will update and replace the following NICE guidance:
Lipid modification. NICE clinical guideline 67 (2008).
Statins for the prevention of cardiovascular events. NICE technology appraisal guidance 94 (2006).

Wednesday, 26 December 2012

Statins - MRC

reposted from:
updated October 2007
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Statins save thousand of lives and diminish hospitalisation costs. The MRC has funded studies that show cholesterol-lowering statin treatment reduces the risk of heart attacks and strokes by at least one third, as well as lowering the need for arterial surgery, angioplasty and amputations.
In the 1970s, scientists suspected that cholesterol was important in heart disease and that the higher the level of blood cholesterol, the higher the risk of heart disease. This led to the suggestion that, if cholesterol was lowered, the risk may be reduced. When cholesterol-lowering statin drugs became available in the next couple of decades, researchers decided that large studies, involving several thousands of patients, were needed to test them properly.
The biggest of these was the MRC-funded Heart Protection Study (HPS), a randomised and double-blind eight-year trial that was designed, coordinated and analysed by the Clinical Trial Service Unit in Oxford1. It began in 1987. As well as being the largest ever trial of cholesterol-lowering drugs, the HPS was the first to include a substantial number of women, elderly people, people with diabetes, and those with lower than average cholesterol. The trial used simvastatin (Zocor®), which was the first statin to become available in the UK; Merck & Co Inc helped fund the trial along with the MRC, the British Heart Foundation and Roche Vitamins Ltd.

Statins benefit everyone

To examine the effects of such drugs in detail, the investigators of all trials formed a group called the Cholesterol Treatment Trialists (CTT) Collaboration, also supported by the MRC. The group published a protocol in 1995 and agreed to look at all the results in a standard way. The first report from this group was published in 2005 in The Lancet, combining data from more than 90,000 participants2. It showed that, among people at increased risk, statins work quickly to reduce the risk of heart disease and stroke and the need for operations to restore blood flow in the arteries surrounding the heart. These benefits were similar, irrespective of a person’s initial cholesterol level.
For example, if someone has a cholesterol level of 6 millimoles per litre, which is high but not uncommon for a middle-aged person, a moderate dose of statin would lower it to 4.5 within weeks, with a maximum effect at between four and six weeks. For every one millimolar decrease in blood cholesterol concentration, the risk of heart disease and stroke decreases by about a quarter. About five years of statin treatment typically prevents major vascular events in 100 of every 1,000 people who have previously had a heart attack. Over the longer term, statins become even more effective. Serious side effects are extremely rare.

Cost savings

Treating people with statins leads to large savings – 22 per cent – in hospitalisation costs for all vascular events among a wide range of high-risk individuals. The drugs have substantially reduced in price after their patents expired in 2003 and now cost pence rather than pounds per day, which markedly increases their cost-effectiveness.
The HPS showed that a daily dose of statins is cost-effective for a wider range of people with vascular disease than was previously thought, but the analysis estimated cost-effectiveness during the study treatment period only3. The HPS team published a new model in the British Medical Journal in 2006, which extrapolated the HPS results to a wider spectrum of people and beyond the five-year treatment period4. They concluded that statin therapy should be considered routinely for more people at a lower risk of vascular events than previously thought.
The MRC team used the data from the 20,536 participants of the HPS and found that, at current generic prices, lifetime treatment with statins is cost-effective (costs less than £2,500 per life year gained) for people aged between 35 and 85 with risks of major heart attacks or strokes at one per cent a year.
The National Institute for Health and Clinical Excellence (Nice) published guidance at the beginning of 2006 saying that adults who have a 20 per cent or greater risk of developing heart disease over the next decade should be offered statins. Draft guidance in June 2007 stated that millions of people should be assessed to find out how many more would benefit from taking statins. A month later, Roger Boyle, the National Director for Heart Disease and Stroke, said that a ‘blanket approach’ to give everyone above a certain age a daily dose of statins would save lives, NHS funding and doctors’ time.
Based on the numbers of people with coronary heart disease, stroke and diabetes, the World Health Organization has estimated that if an extra 10 million high-risk people were to start statin treatment, this would save about 50,000 lives each year and would prevent similar numbers from suffering non-fatal heart attacks or strokes. Statins can benefit people even after they stop taking them – five years of treatment was associated with a significant reduction in coronary events for a subsequent ten years in men with high cholesterol who did not have a history of suffering from heart attacks5.


1. Heart Protection Study Collaborative Group (2002). MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebo controlled trial. The Lancet360, 7.
2. CTT collaborators (2005). Efficacy and safety of cholesterol-lowering treatment: prospective meta-analyis of data from 90 056 participants in 14 randomised trials of statins. The Lancet, DOI:10.1016/S0140-6736(05)67394-1.
3. Heart Protection Study Collaborative Group (2005). Cost-effectiveness of simvastain in people at different levels of vascular disease risk: economic analysis of a randomised trial in 20 536 individuals. The Lancet,365, 1779.
4. Heart Protection Study Collaborative Group (2006). Lifetime cost effectiveness of simvastatin in a range of risk groups and age groups derived from a randomised trial of 20 536 people. BMJ,DOI:10.1136/bmj.38993.731725.BE.
5. Ford et al. (2007). Long-term follow-up of the West of Scotland Coronary Prevention Study. N Engl J Med357, 1543.
MRC, December 2006, updated October 2007 crabsallover heart score

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Riskscore - Heart attacks

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ASSIGN number is the risk percent of cardiovascular disease over ten years

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ASSIGN score: 10

The ASSIGN number is the risk percent of cardiovascular disease over ten years, based on the recent SHHEC study. ASSIGN 20 means 20% risk. The actual risk is probably now less than that number. What matters more is what somebody's score is in relation to other ASSIGN scores, and therefore their priority or ranking for action to lower their risk.

ASSIGN score below 20 is not currently high risk, implying general preventive measures (nobody is free of risk) Repeat the scoring in 5 years or earlier, depending how high the current score is.

Cholesterol-lowering medicines, statins - NHS Choices

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GBD 2010: understanding disease, injury, and risk

reposted from: The Lancet, Volume 380, Issue 9859, Pages 2053 - 2054, 15 December 2012 doi:10.1016/S0140-6736(12)62133-3 pdf download.

Complete pdf download

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GBD 2010: understanding disease, injury, and risk

Publication of the Global Burden of Disease Study 2010 (GBD 2010) is a landmark event for this journal and, we hope, for health. The collaboration of 486 scientists from 302 institutions in 50 countries has produced an important contribution to our understanding of present and future health priorities for countries and the global community.

What is the GBD 2010? Launched in 2007, it is a consortium of seven partners: Harvard University; the Institute for Health Metrics and Evaluation (IHME) at the University of Washington, Seattle; Johns Hopkins University; the University of Queensland; Imperial College London; the University of Tokyo; and WHO.

GBD 2010 is the first systematic and comprehensive assessment of data on disease, injuries, and risk since 1990. That initial exercise was commissioned by the World Bank. This latest round was supported by the Bill & Melinda Gates Foundation. The project has dramatically expanded in scope. In 1990, 107 diseases and injuries, together with ten risk factors, were assessed. For 2010, 235 causes of death and 67 risk factors are included.

What are the headline findings? First, although 52·8 million deaths occurred in 2010 (in 1990, the figure was 46·5 million deaths), great progress is being made in population health. Life expectancies for men and women are increasing. A greater proportion of deaths are taking place among people older than 70 years. The burdens of HIV and malaria are falling. Far fewer children younger than 5 years are dying. Infectious diseases are increasingly being controlled. In some parts of the world, there has been substantial progress in preventing premature deaths from heart disease and cancer.

But this hopeful picture is being challenged by old and new threats. Huge gaps remain in progress for some regions of the world. Tuberculosis and malaria are estimated to have killed around 1·2 million people each in 2010. 8 million people died from cancer in 2010, over a third more deaths than 20 years ago. One in four deaths was from heart disease or stroke. 1·3 million deaths were due to diabetes. Deaths from road traffic injuries increased by almost half. Blood pressure is the biggest global risk factor for disease, followed by tobacco, alcohol, and poor diet. And young adults are emerging as a new and neglected priority in global health: GBD 2010 finds that young adults, especially men, are dying in far higher numbers than previously appreciated. But the most afflicted continent remains Africa. Here, maternal, newborn, and child mortality, along with a broad array of vaccine-preventable and other communicable diseases, remain urgent concerns.
GBD 2010 also puts an important spotlight on disability—from, for example, mental health disorders, substance use, musculoskeletal disease, diabetes, chronic respiratory disease, anaemia, and loss of vision and hearing. Disability from disease and injury will become an increasingly important issue for all health systems. More people will be spending more years of their lives with more illnesses. Women are hit especially hard by disability. Women aged 15—65 years lose more healthy life to disability than men. Yet disability has been almost ignored as a central policy priority during the era of the Millennium Development Goals.

What should happen next? These reports should add energy and momentum to efforts to improve the measurement of health, especially commitments to strengthen civil registration and vital statistics systems in countries. There is also every prospect that, instead of the GBD being a single event every few years, it will evolve into a continuous process of reviewing and updating data as new and more reliable information, together with better methods, become available. The 1990 GBD reports led to important shifts in health priorities. Non-communicable diseases, especially mental ill-health, justifiably achieved much greater prominence. The success of the GBD, then and now, is that it provides a level playing field to assess independently (and dispassionately) the health priorities that face countries.

In the meantime, everyone concerned with health—health workers and policy makers, those working in technical agencies (across the UN system), development partners, civil society, and the research community—should use these latest findings to sharpen understanding of trends in disease, injury, and risk. We should use them to spark global, regional, and national debates about their meaning for policy and practice. We should use them to hold one another accountable for progress towards internationally agreed development goals and to plan for the post-2015 era of sustainable development, where the scope of health as an indispensable part of human development will be broadened still further. And, finally, we should use them as a platform to advocate ever more vigorously for the growing consensus that universal health coverage could be the third great global health transition.1 GBD 2010 is an extraordinary collaboration. Our collective responsibility is to turn it into an extraordinary opportunity.


1 Rodin J, de Ferranti D. Universal health coverage: the third global health transition. Lancet 2012; 380: 861-862. Full Text | PDF(379KB) | CrossRef | PubMed

Tuesday, 25 December 2012

Anti-cholesterol drugs [Statins] may prevent cancer deaths

reposted from:
crabsallover highlightskey pointscomments / links.

Can Statins Be Used to Prevent or Treat Cancer?

The safety and efficacy of statins, coupled with the recognition of the importance of maintaining low LDL cholesterol to prevent cardiovascular disease, has resulted in these medicines becoming some of the most widely prescribed drugs of all time. Millions of patients have been taking statins for as long as two decades and, as a result, an enormous database exists in terms of the long-term benefits and risks these agents might have. This information continues to be mined resulting in various hypotheses of other potential effects that statins may have beyond lowering LDL cholesterol. A study last week, reported in the New England Journal of Medicine is typical. These Danish authors believed that since cholesterol is essential for cell proliferation, perhaps statins could reduce cholesterol availability thereby leading to decreased proliferation and migration of cancer cells (metastasis).

To test their theory, these scientists assessed cancer mortality among patients in the entire Danish population who received a diagnosis of cancer between 1995 and 2007, with a follow-up until the end of 2009. They found that 18,721 (out of 277,204) of these cancer patients had used statins regularly and that these patients were 15% less likely to die from their disease than their non-statin treated counterparts. The study didn’t look at whether statins could prevent cancer, but only at the results after cancer has been diagnosed.

This is not the first hint that statins may have a beneficial impact in the treatment of cancer. At this year’s American College of Gastroenterology meeting in Las Vegas, researchers at the Mayo Clinic spoke of their meta-analysis of 13 studies involving a total of 1,132,969 patients of which 9,285 were diagnosed with esophageal cancer. Those who were on statins were 28% less likely to get esophageal cancer than those not on statins.

However, anyone experienced in the conduct of clinical trials will be able to tell you that meta-analyses just provide a signal, not a conclusion. Because they are retrospective in nature, meta-analyses have flaws. For example, in these studies patients are also taking other drugs, so you don’t know if he observation is due to the statin or the other drugs also being administered. Similarly, statin users may be people who tend to take better care of themselves in terms of diet and exercise and so the beneficial effects may not have anything to do with the statin use. This is why you cannot get FDA approval for a drug indication based on meta-analyses. Rather, you need to carry out highly controlled clinical trials so that the ONLY variable in the study is statin use vs. non-statin use. Only then will you be able to ascertain whether statins are delivering a benefit.

So, are there any clinical trials underway to test whether statins can, in fact, be useful in cancer treatment? Actually, the National Cancer Institute (NCI) is funding a variety of studies in this area. A check of shows there are at least a dozen such studies ongoing. One example, a study being carried out at the M.D. Anderson Cancer Center, is exploring the use of atorvastatin (Lipitor) in preventing breast cancer in women at high-risk for getting this disease. Another is a trial studying rosuvastatin (Crestor) in the prevention of colorectal cancer recurrence in patients whose cancer was surgically removed. Studies are also underway exploring statins in others cancers including prostate, melanoma and acute leukemia.

The downside to all of this is that these studies won’t be completed for a number of years. However, if any of these trials are successful, it is possible that relatively inexpensive generic drugs designed to reduce heart attacks and strokes could turn out to be an important addition to battling a tough disease.