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Showing posts with label cancer risk. Show all posts
Showing posts with label cancer risk. Show all posts

Friday, August 23, 2013

Research finds ‘raised’ cholesterol to be associated with a reduced risk of death - Briffa

 

In the UK and Europe generally, it is recommended that levels of cholesterol in the blood should not be above 5.0 mmol/l (= about 190 mg/dl). We are given the impression that having levels above this puts us at increased risk of heart disease – a major ‘killer’. However, if this is true, it does not tell the whole story. Because while having a ‘raised’ cholesterol may be associated with an increased risk of heart disease, it might also be associated with a reduced risk of other conditions.
 
It is known, for instance, that higher levels of cholesterol are associated with a reduced risk of cancer. And even last week I wrote about some research which suggests that putting downward pressure on cholesterol levels increases the risk of death due to suicide, accidents and violence.

For these reasons, when assessing the relationship between any lifestyle factor and health, it pays to take as wider a view as possible. This is best done by focusing on the relationship the factor has with overall risk of death.

Such a study published recently in the Scandinavian Journal of Health Care makes for some interesting reading, I think [1]. Here, researchers assessed the levels of cholesterol and risk of death in almost 120,000 adults living in Denmark.

The researchers found that having higher than recommended levels of total cholesterol was associated with a reduced risk of death. For instance, in men aged 60-70, compared with those of total cholesterol levels of less than 5.0 mmol/l, those with total cholesterol levels of 5.00-5.99 had a 32 per cent reduced risk of death. For those with levels 6.0-7.99 mmol/l, risk of death was 33 per cent lower. Even in individuals with levels with 8.00 mmol/l and above, risk of death was no higher than it was for those with levels less than 5.0 mmol/l.

The results were similar for women too. In women aged 60-70, levels of 5.0-5.99 and 6.0-7.99 were associated with a 43 and 41 per cent reduced risk of death respectively.

In individuals aged 70 and over, the results were similar, except here, levels of total cholesterol of 8.00 mmol/l or more were associated with a reduced risk of death too (in both men and women).
Cholesterol in the blood stream is made up of two main types: LDL-cholesterol and HDL-cholesterol, dubbed ‘bad’ and ‘good’ cholesterol respectively. In this study, higher levels of LDL-cholesterol (above 2.5 mmol/l) were consistently associated with a reduced risk of death, irrespective or age or sex.

Together, these findings suggest that the current total cholesterol and LDL recommendations advised by doctors and other health professionals are way off beam. The authors of this study concluded that: “These associations indicate that high lipoprotein levels do not seem to be definitely harmful in the general population.”

Some have suggested that low cholesterol is a marker for ‘frailty’ in the elderly. However, this concept is contradicted by evidence finding that the association between low cholesterol levels and enhanced risk of mortality occurs in younger individuals too [2].

It has also been suggested the relationship between low cholesterol and enhanced risk of mortality is the result of ‘reverse causality’ i.e. that chronic conditions such as cancer can cause lowered cholesterol, rather than the other way round (sometimes referred to as ‘Iribarren’s hypothesis’).
However, evidence refuting this concept comes in the form of a long-term study which found that individuals with a low serum cholesterol maintained over a 20-year period had the worst outlook in terms of overall risk of death [3]. The authors of this study write: “Our present analysis suggests that this [Iribarren’s] hypothesis is implausible and is unlikely to account for the adverse effects of low cholesterol levels over twenty years.”

In the Danish study, the relationship between blood fats known as triglycerides and risk of death was also assessed. In women aged 50-60, higher triglyceride levels were consistently found to be associated with increased risk of death. This was somewhat true for women aged 60-70.

This does not mean that higher triglyceride levels cause heart disease – only that these two things are associated with each other. However, the major driver of triglyceride levels is dietary carbohydrate. And previous studies have found that swapping certain carbohydrates for fat in the diet is associated with an increased risk of cardiovascular disease [4,5].

All-in-all, I’d say this research should cause us to pause before recommending individuals aspire to current cholesterol recommendations. And, I think, we should be particularly wary about recommending that people adopt a lower-fat diet richer in carbohydrate to achieve these goals. There is at least some evidence which suggests that this is likely to do more harm than good.

References:
1.  Association of lipoprotein levels with mortality in subjects aged 50 + without previous diabetes or cardiovascular disease: A population-based register study. Scandinavian Journal of Primary Health Care 2013;31(3):172-180
2.  Ulmer H, et al. Why Eve is not Adam: prospective follow-up in 149650 women and men of cholesterol and other risk factors related to cardiovascular and all-cause mortality. J Womens Health 2004;13(1):41-53
3. Schatz IJ, et al. Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study. Lancet 2001;358(9279):351-5
4. Jakobsen MU, et al. Intake of carbohydrates compared with intake of saturated fatty acids and risk of myocardial infarction: importance of the glycemic index. Am J Clin Nutr 2010;91(6):1764-8
5. Jakobsen MU, et al. Major types of dietary fat and risk of coronary heart disease: a pooled analysis of 11 cohort studies. Am J Clin Nutr 2009;89(5):1425-32
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Read the complete article here.

Friday, November 9, 2012

Do statins really reduce the risk of cancer? - Briffa

Yesterday saw the on-line publication of a study in the New England Journal of Medicine (NEJM) that concerns statins and is getting more than its fair share of media attention. The study, conducted in Denmark, analysed the rates of death from cancer in individuals taking statins, and compared them to those in individuals not taking these drugs. Those taking statins were found to be at a statistically significant reduced risk of dying from cancer. Some seem keen to claim that statins may not only be an answer to heart disease, but our cancer woes too. Take this headline for example which you can find here: ‘Statins cut mortality in cancer patients’. The wording of this title on a website dedicated to the education of doctors strongly suggests that statins actually reduce the risk of death from cancer.

But, not so fast. The NEJM study is what is known as ‘epidemiological’ or ‘observational’ study. The study tells us that statin use is associated with a reduced risk of death from cancer, but it can’t tell us whether or not statins actually cut cancer risk.

One fundamental problem with studies of this nature is that they are subject to what is known as the ‘healthy user effect’. Basically, what this means is that healthier, often more health-conscious individuals are more likely to end up on statins than less healthy, not so health-conscious individuals. Because of this, it’s possible that the apparent benefits of statins with regard to cancer (or anything else) are not to do with the drugs themselves, but the health characteristics of those more likely to take statins.

If we really want to know if statins reduce the risk of cancer death then we need to look to what are known as ‘intervention studies’ in which, usually, roughly equivalent groups of individuals are given statins or placebo. These studies, the gold standard of which are ‘randomised controlled trials’ do have the potential of discerning the true effects of drugs and other treatments.

Single studies such as these can provide useful data, but sometimes it makes sense to amass data from several studies to get a decent overview of the impact of a drug or class of drugs. Such grouping of studies together are referred to as ‘meta-analyses’.

One meta-analysis published in 2009 found that statin use was not associated with a reduced risk of cancer [2]. A more recent meta-analysis published this year found the same thing [3]. Meta-analyses of intervention studies are not perfect, but they are much better than (crappy) single epidemiological studies like the one currently doing the rounds. And it’s perhaps worth bearing in mind that there as been at least some concern about the impact statins might have on cancer risk in the elderly. In one study, statin use (compared to placebo) increased the risk of cancer by 25 per cent (statistically significant) [4].

Put in this context, the frothing enthusiasm exhibited by some regarding this latest study seems inappropriate. And for a website dedicated to the education of doctors to proclaim that ‘Statins cut mortality in cancer patients’ is downright negligent.

References:
1. Nielsen SF, et al. Statin Use and Reduced Cancer-Related Mortality. NEJM published online 8 October 2012
2. Brugts JJ, et al. The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials. BMJ 2009;338:b2376.
3. Cholesterol treatment trialists’ collaboraton. Lack of effect of lowering LDL cholesterol on cancer: meta-analysis of individual data from 175,000 people in 27 randomised trials of statin therapy. PLoS One 2012;7(1):e29849. Epub 2012 Jan 19.
4. Shepherd J, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002;360(9346):1623-30
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Read the complete article here.

Tuesday, October 16, 2012

CT heart scans and radiation: The real story

 
CT heart scans and radiation: The real story “My personal opinion is that many patients today who are receiving multiple CT scans may well be getting at least comparable doses to subjects that have now developed malignancies from x-ray radiation received in the 1930s and '40s. And, similar to those days when the doses were unknown, the dose that patients receive today over a course of years of multiple CT scans is also completely unknown . . .

“I recommend that all healthcare providers become familiar with the concept that 1 in 1000 CT studies of the chest, abdomen, or pelvis may result in cancer.”

Richard C. Semelka, MD
Professor and Vice Chairman, Department of Radiology
University of North Carolina–Chapel Hill

Is this just hype to generate headlines? Or is the truth buried in the enormous marketing clout of the medical device industry, among which the imaging device manufacturers reign supreme?
It’s been over 110 years since radiation was first used for medical imaging. Over those years, it has had its share of misadventures.

In the 1930s and 1940s, before the dangers of radiation were recognized, shoe shoppers had shoes fitted using an x-ray device of the foot to assess fit. High doses of radiation were used to shrink enlarged tonsils and extinguish overactive thyroid glands. Attitudes towards radiation were so lax that doctors commonly permitted themselves to be exposed without protection day after day, year after year, until an unexpected rise in blood cancers like leukemia was observed. As recently as the 1970s and 1980s, cancers like Hodgkins’ disease were treated with high doses of radiation, also leading to radiation-induced diseases decades later.

Not all radiation is bad. Radiation can also be used as a therapeutic tool and even today remains a useful and reasonably effective method to reduce the size, sometimes eliminate, certain types of cancer. Forty percent of people with cancer now receive some form of radiation as part of their treatment (Ron E 2003).

Just how much does medical radiation add to our exposure?  Estimates vary, but most experts estimate that medical imaging provides approximately 15% of total lifetime exposure. In other words, radiation exposure from medical imaging is simply a small portion of total exposure that develops over the years of life. Exposure can be much higher, however, in a specific individual who undergoes repeated radiation imaging or treatment of one sort or another.

For all of us, exposure to medical radiation is part of lifetime exposure from multiple sources, added to the radiation we receive from the world around us. Just by living on earth, we are exposed to radiation from space and naturally-occurring radioactive compounds, and receive somewhere around 3.0 mSv per year (U.S. Nuclear Regulatory Commission). (Doses for radiation exposure are commonly expressed in milliSieverts, mSv, a measure that reflects whole-body radiation exposure.) People living in high-altitude locales like Colorado get exposed to an additional 30–50% ambient radiation (1.0–1.5 mSv more per year).

Much of the information on radiation exposure comes from studies like the Life Span Study that, since 1961, has tracked 120,000 Japanese exposed to radiation from the atomic bombs dropped in 1945 (Preston DL et al 2003). Although regarded as a high-dose exposure study for obvious reasons, there are actually thousands of people in this study who were exposed to lesser quantities of radiation (because of distance from the bomb sites) who still display a “dose-response” increased risk for cancer many years later in life. Radiation exposures of as little as 5–20 mSv showed a slight increase in lifetime risk.

Occupational and excessive medical exposure to radiation also provides a “laboratory” to examine radiation risk. Miners exposed to radon gas; patients exposed to the imaging agent, Thorotrast, containing radioactive isotope thorium dioxide and used as an x-ray contrast agent in the 1930s and 1940s and possesses the curious property of lingering in the body for over 30 years after administration; radium injections administered between 1945 and 1955 to treat diseases like ankylosing spondylitis and tuberculosis, all provide researchers an opportunity to study the long-term effects of various types of radiation exposure over many years (Harrison JD et al 2003).

The excess exposure of workers and several hundred thousand nearby residents to the Mayak nuclear plant in Russia has also revealed a “dose-response” relationship, with increasing exposure leading to more cancers, including leukemia and solid cancers of the bone, liver, and lung (Shilnikova NS et al 2003). Nuclear waste released into the Techa river between 1948 and 1956 contaminated drinking water used by over 100,000 Russians. A plant explosion in 1957 also released an excess of radiation into the atmosphere, yielding exposure via inhalation.

Some sources estimate that at least 272,000 people have been affected by radiation from the Mayak plant. This unfortunate situation has, however, yielded plenty of data on radiation exposure and its long-term effects.

It’s also been known for several decades that people who receive therapeutic radiation for treatment of cancer, even with the reduced doses now employed, are subject to increased risk of a second cancer consequent to the radiation treatment.

From experiences like this, radiation experts estimate that an exposure of 10 mSv increases a population’s risk for cancer by 1 in 1000 (Semelka RC et al 2007).

This question was recently thrust into the spotlight with publication of a study from Columbia University in New York suggesting that a 20-year old woman would be exposed to a lifetime risk of cancer as high as 1 in 143 consequent to the radiation received during a CT coronary angiogram. (Important note: This was estimated risk from a CT coronary angiogram, not a simple heart scan that we advocate for the Track Your Plaque program.) The risk at the low end of the spectrum would be in an 80-year old man (because of the shorter period of time to develop cancer), with a risk of 1 in 5017. If “gating” to the EKG is added (which many scan centers do indeed perform nowadays), risk for a 60-year old woman is estimated at 1 in 715; risk for a 60-year old male, 1 in 1911 (Einstein AJ et al 2007). This study generated some criticism, since it did not directly involve human subjects, but used “phantoms” or x-ray dummies to simulate x-ray exposure. Nonetheless, the point was made: CT coronary angiograms in current practice do indeed expose the patient to substantial quantities of radiation, sufficient to pose a lifetime risk of cancer.

The media frenzy  The NY Times ran an article called With Rise in Radiation Exposure, Experts Urge Caution on Tests in which they stated:

"According to a new study, the per-capita dose of ionizing radiation from clinical imaging exams in the United States increased almost 600 percent from 1980 to 2006. In the past, natural background radiation was the leading source of human exposure; that has been displaced by diagnostic imaging procedures, the authors said."

“This is an absolutely sentinel event, a wake-up call,” said Dr. Fred A. Mettler Jr., principal investigator for the study, by the National Council on Radiation Protection. “Medical exposure now dwarfs that of all other sources.”

Radiation is a widely used imaging tool in medicine. Although CT scans of the brain, bones, chest, abdomen, and pelvis account for only 5% of all medical radiation procedures, they are responsible for nearly 50% of medical radiation used. It’s been known for years that increasing radiation exposure increases cancer risk over many years, but the boom of newer, faster devices that provide more detailed images has opened the floodgates to expanded use of CT scanners.

But before we join in the hysteria, let's first take a look at exposure measured for different sorts of tests:

Typical effective radiation dose values for common tests

Computed Tomography
Head CT 1 – 2 mSv
Pelvis CT 3 – 4 mSv
Chest CT 5 – 7 mSv
Abdomen CT 5 – 7 mSv
Abdomen/pelvis CT 8 – 11 mSv
Coronary CT angiography 5 – 12 mSv

Non-CT
Hand radiograph Less than 0.1 mSv
Chest radiograph Less than 0.1 mSv
Mammogram 0.3 – 0.6 mSv
Barium enema exam 3 – 6 mSv
Coronary angiogram 5 – 10 mSv
Sestamibi myocardial perfusion (per injection) 6 – 9 mSv
Thallium myocardial perfusion (per injection) 26 – 35 mSv
Source: Cynthia H. McCullough, Ph.D., Mayo Clinic, Rochester, MN  A plain, everyday chest x-ray, providing less than 0.1 mSv exposure, provides about the same quantity of radiation exposure as flying in an airplane for four hours, or the same amount of radiation from exposure to our surroundings for 11–12 days. Similar exposure arises from dental x-rays.

If you have a heart scan on an EBT device, then your exposure is 0.5-0.6 mSv, roughly the same as a mammogram or several standard chest x-rays.

With a heart scan on a 16- or 64-slice multidetector device, exposure is around 1.0-2.0 mSv, about the same as 2-3 mammograms, though dose can vary with this technology depending on how it is performed (gated to the EKG, device settings, etc.)

CT coronary angiography presents a different story. This is where radiation really escalates and puts the radiation exposure issue in the spotlight. As Dr. Cynthia McCullough's chart shows above, the radiation exposure with CT coronary angiograms is 5-12 mSv, the equivalent of 100 chest x-rays or 20 mammograms. Now, that's a problem.

The exposure is about the same for a pelvic or abdominal CT. The problem is that some centers are using CT coronary angiograms as screening procedures and even advocating their use annually. This is where the alarm needs to be sounded. These tests, as wonderful as the information and image quality can be, are not screening tests. Just like a pelvic CT, they are diagnostic tests done for legitimate medical questions. They are not screening tests to be applied broadly and used year after year.

It’s also worth giving second thought to any full body scan you might be considering. These screening studies include scans of the chest, abdomen, and pelvis. These scans, performed for screening, expose the recipient to approximately 10 mSv of radiation (Radiological Society of North American, 2007). Debate continues on whether the radiation exposure is justified, given the generally asymptomatic people who generally undergo these tests.

Always be mindful of your radiation exposure, as the NY Times article rightly advises. However, don't be so frightened that you are kept from obtaining truly useful information from, for instance, a CT heart scan (not angiography) at a modest radiation cost.

Heart scans, CT coronary angiograms and the future  Unfortunately, practicing physicians and those involved in providing CT scans are generally unconcerned with radiation exposure. The majority, in fact, are entirely unaware of the dose of radiation required for most CT scan studies and unaware of the cancer risk involved. It is therefore up to the individual to insist on a discussion of the type of scanner being used, the radiation dose delivered (at least in general terms), the necessity of the test, alternative methods to obtain the same diagnostic information, all in the context of lifetime radiation exposure.

Our concerns about radiation exposure all boil down to concern over lifetime risk for cancer, a disease that strikes approximately 20% of all Americans. Many factors contribute to cancer risk, including obesity, excessive saturated fat intake, low fiber intake, lack of vitamin D, repeated sunburns, excessive alcohol use, smoking, exposure to pesticides and other organochemicals, asbestos and other industrial exposures, electromagnetic wave exposure, and genetics. Radiation is just one source of risk, though to some degree a controllable one.

Some people, on hearing this somewhat disturbing discussion, refuse to ever have another medical test requiring radiation. That’s the wrong attitude. It makes no more sense than wearing lead shielding on your body 24 hours a day to reduce exposure from the atmosphere. Taken in the larger context of life, radiation exposure is just one item on a list of potentially harmful factors.

It is, however, worth some effort to minimize radiation exposure over your lifetime, particularly before age 60, and by submitting to high-dose testing only when truly necessary, or when the potential benefits outweigh the risks. Thus, with heart scans and CT coronary angiography, some thought to the potential benefits of knowing your score or the information gained from the CT angiogram need to be considered before undergoing the test. Often the practical difficulty, of course, is that your risk for heart disease simply cannot be known until after the test.

In our view, in the vast majority of instances a simple CT heart scan can serve the simple but crucial role of quantifying risk for heart attack and atherosclerotic plaque. CT heart scans yield this information with less than a tenth of the radiation exposure of a CT coronary angiogram. In people without symptoms and a normal stress test, there is rarely a need for CT coronary angiography with present day levels of radiation exposure. Perhaps as technology advances and the radiation required to generate images is reduced, then we should reconsider.

Early experiences are suggesting that the newest 256-slice scanners, now being developed but not yet available, will cut the dose exposure of 64-slice CT angiograms in half (from 27.8 mSv to 14.1 mSv in a recent Japanese study). The 256-slice scanners will allow scanning that is faster over a larger area in a given period of time.

Thankfully, the scanner manufacturers are increasingly sensitive to the radiation issue and have been working on methods to reduce radiation exposure. However, it still remains substantial.

References: Einstein AJ, Henzlova MJ, Rajagopalan S. Estimating risk of cancer associated with radiation exposure from 64-slice computed tomography coronary angiography. JAMA 2007 Jul 18;298(3):317–323.
Harrison JD, Muirhead CR. Quantitative comparisons of cancer induction in humans by internally deposited radionuclides and external radiation. Int J Radiat Biol 2003 Jan;79(1):1–13.
Hausleiter J, Meyer T, Hadamitzyky M et al. Radiation Dose Estimates From Cardiac Multislice Computed Tomography in Daily Practice: Impact of Different Scanning Protocols on Effective Dose Estimates. Circulation 2006;113:1305–1310.
Kalra MK, Maher MM, Toth TL, Hamberg LM, Blake MA, Shepard J, Saini S. Strategies for CT radiation dose optimization. Radiology 2004;230:619–628.
Mayo JR, Aldrich J, Müller NL. Radiation exposure at chest CT: A statement of the Fleischner Society. Radiology 2003; 228:15–21.
Mori S, Nishizawa K, Kondo C, Ohno M, Akahane K, Endo M. Effective doses in subjects undergoing computed tomography cardiac imaging with the 256-multislice CT scanner. Eur J Radiol 2007 Jul 10; [Epub ahead of print].
Preston DL, Pierce DA, Shimizu Y, Ron E, Mabuchi K. Dose response and temporal patterns of radiation-associated solid cancer risks. Health Phys 2003 Jul;85(1):43–46.
Ron E. Cancer risks from medical radiation. Health Phys 2003 Jul;85(1):47–59.
Shilnikova NS, Preston DL, Ron E et al. Cancer mortality risk among workers at the Mayak nuclear complex. Radiation Res 2003 Jun;159(6):787–798.
Semelka RC, Armao DM, Elias J Jr, Huda W. Imaging strategies to reduce the risk of radiation in CT studies, including selective substitution with MRI. J Magn Reson Imaging 2007 May;25(5):900–9090.

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