Should we all be on statins? (reprise)

Should you be on statins? New guidelines and an online calculator may allow you to answer this question yourself.

Back in 2011, I asked whether we should all be on statins. At the time, it was clear that statins offered benefits for people who had already suffered heart attacks or other serious cardiovascular problems. But for the rest of us, it wasn't clear at all. A number of studies had been published suggesting that millions more people (in the U.S. alone) might benefit from statin therapy, but most of those studies were published by drug companies that made statins. As I wrote at the time, "we need more data from completely unbiased studies."

So has anything changed? Actually, it has. Last year, the U.S. Preventative Services Task Force (USPSTF) reviewed all of the evidence and updated its former (from 2008) recommendations. The evidence now suggests that some people–even those who have never suffered a heart attack–would benefit from statins.

Here's what the current USPSTF recommendations suggest. If you've never had a heart attack and have no history of heart disease, you still might benefit from statins if:

• you're 40-75 years old,
• you have one or more "risk factors" for cardiovascular disease (more about this below), AND
• you have a 10-year risk of cardiovascular disease (CVD) of 7.5%-10%, using a "risk calculator" that I'll link to below.

Now let's look at those risk factors for CVD. There are four of these, and any one of them puts you in the category of people who might benefit from statins: diabetes, high blood pressure (hypertension), smoking, or dyslipidemia.

Most people already know their status for the first 3, but "dyslipidemia" needs a bit more explanation. This is simply an unhealthy level of blood cholesterol, defined by USPSTF as either "an LDL-C level greater than 130 mg/dL or a high-density lipoprotein cholesterol (HDL-C) level less than 40 mg/dL." You can ask your doctor about these numbers, or just look at your cholesterol tests yourself, where they should be clearly marked.

For that last item, how do you calculate you 10-year risk of CVD? Most people should ask their doctor, but if you want to see how it's done, the calculator is at the American College of Cardiology site here. It's quite simple and you can fill it in yourself to see your risk.

A big caveat here, as the USPSTF explains, is that the "risk calculator has been the source of some controversy, as several investigators not involved with its development have found that it overestimates risk when applied to more contemporary US cohorts."

Another problem that I noticed with the risk calculator is that using it for the statin recommendation involves some serious double counting. That's because the risk calculator relies in part on your cholesterol levels and blood pressure, but those same measurements are considered to be separate risk factors for CVD. This puts a lot of weight on cholesterol levels–but on the other hand, statins' biggest effect is to reduce those levels.

The USPSTF is a much more honest broker of statin recommendations than industry-funded drug studies, so we can probably trust these new guidelines. Note that if the risk calculator puts you in the 7.5%-10% range, you will only get a very small benefit from statins–as the USPSTF puts it, "Fewer persons in this population will benefit from the intervention."

Don't rush to go on statins without giving it some serious thought. As Dr. Malcolm Kendrik put it last year (quoted by Dr. Luisa Dillner in The Guardian),

“If I was taking a tablet every day for the rest of my life, I would want to know how long I would have extra to live. If you take statins for five years and you are at higher risk, then you reduce the risk of a heart attack by 36%. But if you rephrase the data, this means on average you will have an extra 4.1 days of life.” 

So no, we shouldn't all be on statins. But until something better comes along (and I hope it will), they are worth considering for anyone who is in a higher-risk group for cardiovascular disease.

An aspirin a day keeps the grim reaper away

Low-dose aspirin is good for you. Any brand of aspirin 

will do, Bayer or otherwise.

Should you take an aspirin every day to prevent some types of cancer? The evidence is growing, and it all points to the same answer: yes.

In 2016, the US Preventive Services Task Force, a science-guided panel that reviews the evidence for a wide range of treatments, recommended regular low-dose aspirin use for people between the ages of 50 and 69 as a way to prevent heart attacks, strokes, and some types of cancer. For people younger than 50 or older than 69, the USPSTF said that the evidence was inconclusive.

The 2016 recommendations came with a caveat: long-term aspirin use carries a slightly increased risk of bleeding in the stomach and intestinal tract, and a small increase in the risk of a hemorrhagic stroke–although it reduces the risk of ischemic strokes. (Ischemic strokes are caused by blood clots in the brain, while hemorrhagic strokes are caused by bleeding. Aspirins reduces the blood's ability to clot, so this tradeoff makes sense physiologically.)

Later in 2016, a study by Yin Cao and colleagues at Harvard found that aspirin use reduced the risk of cancers, especially colon cancer. To be specific, they found a benefit from taking 0.5 to 1.5 aspirin tablets per week for at least 6 years (a standard tablet is 325 mg). For people who followed this regimen, the risk of colon cancer was about 19% lower.

Now, a new study also led by Yin Cao and others at Harvard, just reported in the annual meeting of the American Association for Cancer Research, shows even clearer benefit. They looked at long-term results in a group of 130,000 women (mostly nurses) and men (doctors and other health professionals) who have been followed since the 1980s. Overall, woman had a 7% reduction in the relative risk of dying from any cause and men had a 11% reduction.

Most of the reduction in mortality was due to the reduced risk in dying from colon cancer, breast cancer, and prostate cancer. Just as with the previous study, the benefit appeared in people who took 0.5 to 1.5 aspirin tablets per week for at least six years.

A decrease in the risk of dying by 7-11% seems like a mighty nice benefit from such a simple treatment. For those (like me) whose stomach is upset by aspirin, a low-dose aspirin tablet taken with food may be easier to tolerate. The low-dose pill contains 81mg, one-fourth of a standard tablet, so 2-6 of these per week is equivalent to the 0.5-1.5 tablets that provided a benefit in the latest study.

It's very encouraging when the evidence for a simple, low-cost treatment consistently shows the same benefit. An important caveat is that that if you have any bleeding problems, you should consult your doctor before taking aspirin.

As for me, I've already stocked up on low-dose aspirin. I'm trying the chewable ones first.

Should we test all women for breast cancer-causing mutations?

In this week’s Journal of the American Medical Association, famed geneticist Mary-Claire King argues that all women over age 30 should be tested for cancer-causing mutations in the BRCA1 and BRCA2 genes. King, who made the original discovery of the link between BRCA1 and breast cancer, is one of the world’s leading experts on how mutations in these genes cause cancer.

But her proposed new universal testing policy, which fellow Forbes contributor David Shaywitz calls “audacious,” goes far beyond what other experts recommend. Earlier this year, the highly regarded U.S. Preventative Services Task Force (USPSTF) recommended testing BRCA genes only in women with a family history of breast or ovarian cancer. 

Although there’s no question that King is an expert on BRCA gene testing, I think she’s gone much too far with her latest proposal. She has the science right, but she is far too optimistic about how her recommendation would actually play out. The policy might save some lives, but it would also cause a great deal of pain.

First, it’s worth explaining why King thinks universal BRCA testing is a good idea. In her JAMA article, King and colleagues describe a new study they conducted in Ashkenazy Jews that showed, somewhat surprisingly, that 

“50% of families found to harbor BRCA1 or BRCA2 mutations had no history of breast or ovarian cancer that would have triggered clinical attention." 

In other words, under current policy guidelines, 50% of people who have a damaging mutation in one of these genes will not have their genes tested. Many of them will eventually get breast or ovarian cancer—as King explains, women with harmful BRCA1 mutations have a 60% risk of cancer by age 60, and for BRCA2 the risk is 33% by age 60. That’s a very high risk, though it’s important to keep in mind that many women with these mutations will never get cancer.

With modern DNA sequencing technology, any large-scale genetic BRCA testing program is likely to uncover thousands of mutations that have no harmful effects, and thousands more whose effects are simply unknown. (Aside: each BRCA gene spans about 80-90 thousand nucleotides of DNA, and each of those letters can mutate in 4 ways, changing into one of the other 3 bases or just being deleted. This means there are at least 400,000 mutations possible in each gene, not counting larger deletions. A colleague and I published an article in 2010 describing one such BRCA test.) King is clearly aware that such reporting these mutations to patients would only sow confusion, and she recommends that:

“Testing for BRCA1 and BRCA2 should focus solely on unambiguously loss-of-function mutations with definitive effect on cancer risk…. A VUS [variant of unknown significance] can increase confusion and compromise clinical management; for population-based screening, these variants should not be reported.”

Herein lies one of the biggest problems with King’s idea. We don’t have universal agreement on which mutations have no significance, and even if we did, most physicians are not experts on cancer genetics. In our lawsuit-prone medical culture, there exists an unfortunate tendency to over-treat and over-report everything. 

Thus I fear that if we had wider BRCA testing, clinical labs would report all mutations back to physicians (how could they not?), and physicians in turn would report everything to the patients. The result would be that millions of women would be told "you have a mutation in BRCA1, and we don't know what it means." What's a patient supposed to do with that?

The other problem is that the only treatment to prevent breast and ovarian cancer is surgery to remove a woman’s breasts and ovaries. We don’t have a pill you can take, or lifestyle changes you can adopt, that will dramatically reduce your risk of hereditary cancer. But unlike a cancer diagnosis, the discovery of a BRCA mutation does not mean you have cancer. It simply means you have a risk, possibly a high risk, of getting cancer at a young age. We know from decades of research that people are not very good at evaluating risk. We tend to over-estimate the danger of events that seem very dramatic or visible to us, as cancer is to many people. 

By King’s own estimates, widespread BRCA testing would detect cancer-causing mutations in 250,000 to 415,000 women in the U.S. This estimate assumes the test doesn’t have false positives, which it almost certainly would. All of these women would then be faced with an extremely difficult dilemma: should they have both their breasts removed, or live the rest of their lives in fear of breast cancer? 

This dilemma was famously on display last year, when actress Angelina Jolie revealed in a New York Times article that she’d had a double mastectomy, after discovering that she carried high-risk BRCA mutations. Jolie’s mother died from cancer at the age of 56, and she explained in her article that as a result of the surgery, “ I can tell my children that they don’t need to fear they will lose me to breast cancer.”

King’s proposal is audacious, and it’s well worth debating. But without a better treatment option, telling hundreds of thousands of women that they have a high risk of breast and ovarian cancer carries a potentially enormous cost, both physical and emotional, for these women. Rather than putting huge numbers of women under the surgeon’s knife, we should instead double or triple our investments in research on treatments that may eventually make surgery unnecessary. 

The PSA test for prostate cancer: more harm than good?

Millions of men are tested each year for high levels of prostate-specific antigen, or PSA, which is designed to detect early signs of prostate cancer. The test is covered by insurance, so most men readily agree to it. After all, what's the harm?

Well, plenty. PSA screening, we now know, "leads to a substantial overdiagnosis of prostate tumors." Many of these cancers grow very slowly, and men with slow-growing prostate tumors may never have symptoms. However, once a man is told he has cancer, there is a a strong tendency to treat it, and treatment has serious, often harmful side effects: 20-30% of men treated with surgery and radiation will have long-term incontinence and erectile dysfunction.

There is a furious debate going on right now over the evidence for and against PSA screening. The debate started with a large-scale US study called PLCO, which found no benefit from annual PSA screening. Soon after that, the US Preventive Services Task Force recommending that most men should not get regular PSA tests.  They concluded:

"Many more men in a screened population will experience the harms of treatment than will experience the benefit.... The USPSTF concludes that there is moderate certainty that hte benefits of PSA-based screening for prostate cancer do not outweigh the harms."

The American Academy of Family Physicians agrees, and has adopted a clear recommendation:

"Don't routinely screen for prostate cancer using a prostate-specific antigen (PSA) test or digital rectal exam."

which I wrote about last November.

In contrast, the American Urological Association responsed to the USPSTF report by issuing a statement that it was "outraged and believes that the Task Force is doing men a great disservice." Prostate surgery is big business for urologists, which may have biased their reaction. However, to their credit the AUA modified its guidelines on PSA screening, which now state

"The [AUA] Panel does not recommend routine screening in men between ages 40 to 54 years at average risk."

For men ages 55 to 69, they recommend "shared decision-making," but they still insist that there is a benefit for men in this group. Their 2013 press release says "the highest quality evidence for screening benefit was in men ages 55 to 69 screened at two- to four-year intervals."

Why does the controversy continue? One reason is that a large European study, called ERSPC, reported a small benefit from PSA screening. The European study is actually a combined analysis of 7 studies in 7 countries, each of which was run a bit differently.  Five of the studies reported no benefit, and just two, from Sweden and the Netherlands, showed a benefit.

So what was going on in those two countries? Did they do screening differently, or treatment differently? Well, it seems they did. In a letter published in Uro Today on May 6, Ian Haines and George Miklos lay out an explanation: in the Swedish study, many more patients in the control group (the group that did not receive PSA screening) were treated with androgen deprivation therapy, ADT, which recent evidence indicates may increase the risk of death. Haines and Miklos published a more detailed analysis last October, accompanied by an editorial by Otis Brawley, the Chief Medical Officer of the American Cancer Society.

Brawley pointed out that

"the harms of screening have been consistently demonstrated in all screening trials to date."

He calls for "an objective panel of experts with access to all of the data" to address the controversy over the possible bias in some of the European trials. Carlsson et al. responded last month in the Journal of the National Cancer Institute, defending their methods, but Haines and Miklos fired back in the same issue, arguing that the benefits found in the European study "rests entirely on the ... Goteborg trial from a single city.

Regardlesss of the evidence from that one city, though, the evidence today is strong that until we have much better treatments for prostate cancer, routine screening with PSA tests causes more harm than good. The side effects of surgery can be life-altering and devastating. Guys: unless you have a special reason to be concerned about prostate cancer, tell your doctor "no thanks" if he offers you a PSA test at your next checkup. That's what I did.