Reducing Inflammation with statins, aspirin, flu jab cuts cancer and heart disease - David Agus

reposted from: http://www.youtube.com/watch?v=GZ6I3T1RAnQ&feature=relmfu

crabsallover highlights, key points, comments / links.




Reducing Inflammation with statins, aspirin, flu jab cuts cancer and heart disease - David Agus

Fever - we don't know if a fever is good or bad. But fever is caused by inflammation.

3:50s - 5:00 Statins block synthesis of LDL cholesterol, lowered death from heart disease and stroke
JUPITER trial (I assume Agus is talking about this trial) - statins reduced incidence of cancer by 40% in people who don't have high cholesterol, also delayed heart attack and stroke by 12 years. Statins work by reducing inflammation which reduces deposition of cholesterol and also reduces cancer.

5:40 how can we measure inflammation? Types of inflammation - some is causal, other is not. How to optimise bad inflammation?

6:40s - 7:15s Taking a flu jab not only reduces the chances of a nasty flu for 5 days but also reduces the chance of getting cancer or heart disease in 10 years time by reducing inflammation

Aspirin: 8.20s - aspirin reduces inflammation which reduces heart disease and cancer

Statins effective prevents of heart attacks in persons with low cholesterol but high C-reactive protein (CRP)

reposted from: http://www.westhertshospitals.nhs.uk/whc/archive/evidence/01%20prevention/AFCAPS%20CRP-NEJM%202001.pdf
Published: June 2001

crabsallover highlights, key points, comments / links.

As highlighted by David Agus in 'The end of Illness' (2012), the JUPITER study (wikipedia) suggested that high CRP may indicate risk of future heart attack up to 8 years in advance, even if cholesterol levels are low.

ABSTRACT 

Background Elevated levels of C-reactive protein, even in the absence of hyperlipidemia, are associated with an increased risk of coronary events. Statin therapy reduces the level of C-reactive protein independently of its effect on lipid levels. We hypothesized that statins might prevent coronary events in persons with elevated C-reactive protein levels who did not have overt hyperlipidemia.

Methods 

The level of C-reactive protein was measured at base line and after one year in 5742 participants in a five-year randomized trial of lovastatin for the primary prevention of acute coronary events.

Results 

The rates of coronary events increased significantly with increases in the base-line levels of C-reactive protein. Lovastatin therapy reduced the C-reactive protein level by 14.8 percent (P<0.001), an effect not explained by lovastatin-induced changes in the lipid profile. As expected, lovastatin was effective in preventing coronary events in participants whose base-line ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol was higher than the median ratio, regardless of the level of C-reactive protein (number needed to treat for five years to prevent 1 event, 47; P=0.005). However, lovastatin was also effective among those with a ratio of total to HDL cholesterol that was lower than the median and a C-reactive protein level higher than the median (number needed to treat, 43; P=0.02). In contrast, lovastatin was ineffective among participants with a ratio of total to HDL cholesterol and a C-reactive protein level that were both lower than the median (number needed to treat, 983; P=0.87).

Conclusions 

Statin therapy may be effective in the primary prevention of coronary events among persons with relatively low lipid levels but with elevated levels of C-reactive protein. (N Engl J Med 2001;344:1959-65.)

Do heart benefits of statins outweigh diabetes risk?

reposted from: http://www.nhs.uk/news/2012/08august/Pages/Do-heart-benefits-of-statins-outweigh-diabetes-risk.aspx

crabsallover highlights, key points, comments / links.

Fri Aug 10, 2012 11:00 Share

‘Heart benefits of statins outweigh diabetes risk’, The Daily Telegraph says.

Statins are a type of medication widely used to lower blood cholesterol levels. While statins have proved reasonably effective in preventing cardiovascular disease (CVD), concerns have been raised that they could be associated with an increased risk of type 2 diabetes.

The Telegraph’s story is based on a large, five-year study from the US that was seeking to clarify the ‘risk-benefit balance’ between:

• statin use
• reduced risk of CVD
• increased risk of type 2 diabetes

The key findings of the study were that:

• in people with no pre-existing risk factors for diabetes (such as obesity) statins decreased the risk of a major CVD outcome (such as a heart attack or a stroke) by 52%, but did not increase the risk of diabetes
• in people with one or more risk factors for diabetes, there was a 28% increase of diabetes, but this has to be balanced against a 39% decrease in a major CVD outcome

The researchers calculated that by treating the (roughly) 11,000 people in this trial who had risk factors for diabetes, 134 CVDs or deaths would be avoided for every 54 extra cases of diabetes caused.

The findings of this trial will need to be evaluated alongside other evidence, but do suggest the benefits of statins outweigh the potential risks.

Where did the story come from?

The study was carried out by researchers from the Center for Cardiovascular Disease Prevention and the Division of Cardiovascular Medicine at Brigham and Women’s Hospital, Harvard Medical School, USA, and was funded by the drug company AstraZeneca. The study was published in the peer-reviewed medical journal, The Lancet.

The Telegraph accurately reported the main findings of this study, but it may have been more useful to readers if it had provided the actual numbers of people who might benefit. This would help both health professionals and patients to make a more informed decision about whether the benefits of statins are worth the risk.

What kind of research was this?

This was a randomised controlled trial which aimed to look at the benefit of statins in reducing the risk of cardiovascular events, and look at whether they increased the risk of type 2 diabetes, compared to an inactive placebo drug. The study population were people with no history of cardiovascular disease events; that is, the study was looking at the use of statins for primary prevention of cardiovascular disease (use of statins in people who have already had a heart attack or stroke would be secondary prevention).

A randomised controlled trial is the best way of looking at the risks and benefits of any intervention compared to a comparator. This particular trial further benefits from being of a large size, and including a reasonable length of follow-up (five years).

What did the research involve?

The JUPITER (Justification for Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) trial included 17,802 men and women (average age 66 years) who were randomised to take either 20mg daily of rosuvastatin or an inactive placebo drug for five years.

All participants were healthy, without known heart disease or diabetes, although 65% did have one or more major risk factor for diabetes, including:

• metabolic syndrome (a combination of risk factors that increase risk of diabetes and other cardiovascular disease)
• body mass index (BMI) of 30 or higher (having a BMI of 30 or above is considered to be clinically obese)
• impaired fasting glucose and /or elevated glycated haemoglobin (a longer term measure of blood glucose control): the elevated levels suggest there are ‘warning signs’ that diabetes may develop in the future

Participants were followed over the course of the five years, and the main outcome of interest was a combined cardiovascular outcome, such as:

• any first events of heart attack
• stroke
• admission to hospital for unstable angina (similar to a heart attack but without the typical features on blood tests and ECG – suggests that a cardiac artery was blocked but has cleared by itself and that the person may be at risk of full heart attack)
• arterial revascularisation (surgery to unblock an artery)
• death resulting from a cardiovascular cause

Other outcomes of interest were doctors' diagnosis of diabetes, or venous thromboembolism (blood clot in the veins).

The trial was double blind, meaning that neither participants nor researchers knew whether statin or placebo had been taken.

After exclusion of those who were found to have diabetes at study start or who had missing data, 17,603 (99%) were included in the analyses. People with one or more major risk factor for diabetes (11,508) and those without (6,095) were analysed separately.

What were the basic results?

Overall, in all participants of the trial there were 270 reports of diabetes in people randomised to take rosuvastatin compared to 216 in the placebo group – a risk increase of 25% (hazard ratio [HR] 1.25, 95% confidence interval  (CI) 1.05 to 1.49). The average time from randomisation to diagnosis of diabetes was 84.3 weeks in the rosuvastatin group vs. 89.7 weeks in the placebo group: an acceleration of 5.4 weeks.

When analysed separately by group, for people with one or more risk factor for diabetes, statin treatment gave:

• a 39% reduced risk of any of the major cardiovascular outcomes of trial (HR 0.61, 95% CI 0.47 to 0.79)
• a 28% increased risk of diabetes (HR 1.28, 95% CI 1.07 to 1.54)
• no significant effect on risk of venous thromboembolism or all-cause death

People without diabetes risk factors had:

• a 52% reduced risk of any of the major cardiovascular outcomes of trial (HR 0.48, 95% CI 0.33 to 0.68)
• no significant effect on risk of diabetes, venous thromboembolism or all-cause death

The researchers calculated that if the number of people in this trial who had diabetes risk factors take a statin, then 134 cardiovascular events or deaths would be avoided for every 54 new cases of diabetes diagnosed. If the number of people in this trial without diabetes risk factors take a statin, 86 cardiovascular events or deaths would be avoided with no new cases of diabetes diagnosed.

How did the researchers interpret the results?

The researchers conclude from their trial that the cardiovascular benefits of taking a statin outweigh the risk of diabetes, even in people at high risk of diabetes.

Conclusion

This is a well conducted trial intending to weigh up the cardiovascular benefit against the diabetes risk of taking a statin. The large trial benefits from being double blind (neither participants nor researchers aware of study treatment) and including a reasonable length of follow-up.

Overall, the researchers find that amongst roughly 11,000 people with diabetes risk factors (such as metabolic syndrome or raised fasting glucose levels in the blood) 134 cardiovascular events or deaths would be avoided for every 54 extra cases of diabetes caused by taking a statin.  Amongst roughly 6,000 people without diabetes risk factors who take a statin, 86 cardiovascular events or deaths would be avoided with no new cases of diabetes diagnosed.

These are important findings which add to the evidence on the benefit of statins for reducing cardiovascular events, and to the risk increase for diabetes.

It must be noted that the trial was examining the use of one statin for ‘primary prevention’ – that is, in people who have not suffered a cardiovascular event such as heart attack or stroke. It has not examined use of statins for secondary prevention in people who have already had a cardiovascular event, although the researchers say that in this group the diabetes risk is considered to be low compared with the reduced risk of having another cardiovascular event.

Also, the study has only examined one statin – rosuvastatin – though previous research has suggested that all statin drugs are associated with a similar small increased risk. The study has also only examined the medium dose of 20mg, and other research suggests that the risks may be dose-dependent and higher doses may be associated with higher risk.

When prescribing any drug its benefits and potential risks need to be taken into account. The findings of this trial will need to be evaluated alongside other evidence of the risks and benefits of statins at different doses and in different treatment groups. However, overall the findings confirm the net benefits of statins.

Analysis by NHS Choices. Follow Behind the Headlines on twitter.

Links To The Headlines

‘Heart benefits of statins outweigh diabetes risk: experts’. The Daily Telegraph, August 10, 2012

Links To Science

Ridker PM, Pardhan A, MacFayden JG, et al. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. The Lancet. Published online, August 10, 2012

C-reactive protein concentration and the vascular benefits of statin therapy

reposted from: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)62174-5/abstract

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The Lancet, Volume 377, Issue 9764, Pages 469 - 476, 5 February 2011

<Previous Article|Next Article>

doi:10.1016/S0140-6736(10)62174-5Cite or Link Using DOI

Published Online: 28 January 2011

C-reactive protein concentration and the vascular benefits of statin therapy: an analysis of 20 536 patients in the Heart Protection Study

Heart Protection Study Collaborative Group ‡

Summary

Background

It has been suggested that inflammation status, as assessed by C-reactive protein (CRP) concentration, modifies the vascular protective effects of statin therapy. In particular, there have been claims that statins might be more beneficial in people with raised CRP concentrations, and might even be ineffective in people with low concentrations of both CRP and LDL cholesterol. This study aimed to test this hypothesis.

Methods

In 69 UK hospitals, 20 536 men and women aged 40—80 years at high risk of vascular events were randomly assigned to simvastatin 40 mg daily versus matching placebo for a mean of 5·0 years. Patients were categorised into six baseline CRP groups (<1·25, 1·25—1·99, 2·00—2·99, 3·00—4·99, 5·00—7·99, and ≥8·00 mg/L). The primary endpoint for subgroup analyses was major vascular events, defined as the composite of coronary death, myocardial infarction, stroke, or revascularisation. Analysis was by intention to treat. This study is registered, number ISRCTN48489393.

Findings

Overall, allocation to simvastatin resulted in a significant 24% (95% CI 19—28) proportional reduction in the incidence of first major vascular event after randomisation (2033 [19·8%] allocated simvastatin vs 2585 [25·2%] allocated placebo). There was no evidence that the proportional reduction in this endpoint, or its components, varied with baseline CRP concentration (trend p=0·41). Even in participants with baseline CRP concentration less than 1·25 mg/L, major vascular events were significantly reduced by 29% (99% CI 12—43, p<0·0001; 239 [14·1%] vs 329 [19·4%]). No significant heterogeneity in the relative risk reduction was recorded between the four subgroups defined by the combination of low or high baseline concentrations of LDL cholesterol and CRP (p=0·72). In particular, there was clear evidence of benefit in those with both low LDL cholesterol and low CRP (27% reduction, 99% CI 11—40, p<0·0001; 295 [15·6%] vs 400 [20·9%]).

Interpretation

Evidence from this large-scale randomised trial does not lend support to the hypothesis that baseline CRP concentration modifies the vascular benefits of statin therapy materially.

Introduction

Inflammation is thought to contribute to the pathogenesis of coronary heart disease.1 C-reactive protein (CRP), an acute phase reactant synthesised by the liver, is the most extensively studied systemic marker of inflammation. Results from a meta-analysis2 of individual participant data from 54 prospective observational studies showed that CRP concentration was associated with the risk of coronary heart disease, ischaemic stroke, and vascular and non-vascular mortality. However, associations with ischaemic vascular diseases were explained largely by conventional risk factors (eg, CRP is positively correlated with smoking, diabetes, physical inactivity, blood pressure, body-mass index, non-HDL cholesterol, and triglycerides2), and so they might not reflect causality (which is supported by genetic-epidemiological studies3). Nonetheless, the ability of CRP to predict vascular risk means that it might still be useful as a biomarker to identify individuals who would particularly benefit from therapies to reduce risk.4

Some,5, 6 but not all,7 subgroup analyses undertaken in previous randomised trials of statin therapy have suggested that the vascular benefits might be greater in the presence of inflammation than in its absence. It has even been suggested that people who have low concentrations of both LDL cholesterol and CRP might not benefit much from statin therapy.8 The JUPITER trial9randomly allocated 17 802 apparently healthy men and women with LDL cholesterol concentrations less than 130 mg/L (3·4 mmol/L) but CRP concentrations 2·0 mg/L or greater to receive either rosuvastatin 20 mg daily or matching placebo. Allocation to rosuvastatin reduced LDL cholesterol at 1 year by about 50% (ie, 1·2 mmol/L) and CRP by about 40% (1·3 mg/L) and, during median treatment duration of about 2 years, there was a significant 44% reduction in the primary composite endpoint of myocardial infarction, stroke, arterial revascularisation, admission to hospital for unstable angina, or death from cardiovascular causes.9 It has been suggested that this large relative risk reduction is greater than might have been expected given the achieved LDL cholesterol reduction,9, 10 raising the possibility that the benefits of statins might be proportionally greater in people with high CRP concentrations. Secondary analyses of the JUPITER trial did not record any evidence that the effect of rosuvastatin on vascular events differed according to baseline CRP concentration,11 but these analyses included only three baseline groups for CRP (because of the relatively small number of events) and were not able to assess the effect in people with CRP concentration less than 2·0 mg/L (because they were not eligible for the trial).

The Heart Protection Study (HPS) is, to date, the largest randomised trial of statin therapy and was undertaken in high-risk patients in whom large numbers of major vascular events occurred during the study treatment period. This study tested the hypothesis that the effects of statin therapy differ according to baseline concentrations of CRP and LDL cholesterol.