Thursday, April 28, 2011

Going Global: New WHO Report on the Rise of Chronic Disease

It's been a trend developing for a number of years: the rising prominence of chronic disease across the globe.  Where diseases like heart disease, stroke, diabetes, and cancer were once the main health concerns of more affluent countries, they've now taken over top spots in developing nations as well - signaling both a shift away from infectious diseases (a good thing) as well as a move toward many unhealthy western habits that promote chronic disease (a bad thing).

According to a new report by the World Health Organization, noncommunicable diseases (NCDs):
"killed 63% of people who died worldwide in 2008. This equals 36 million and nearly 80% of these NCD deaths - equivalent to 29 million people - occurred in low- and middle-income countries, dispelling the myth that such conditions are mainly a problem of affluent societies."
In developing countries, especially, close to a third of people dying from these chronic diseases are under 60 and in their most productive working years.  The cost of treating people with chronic diseases combined with the losses in incomes and productivity by people affected by the diseases delivers a tough blow to the health and economic systems of countries already overburdened.

This new WHO report and those that preceded it, bring into sharp relief the continued problem of income inequality facing global health. The huge income gaps that continue to exist both within and across countries mean that poorer populations now suffering from chronic diseases will die from these diseases at younger ages and in greater numbers than their more affluent counterparts.

Most chronic conditions can be prevented or well controlled with a combination of good health care access, healthy lifestyle, and supportive public policy. Yet, the poorer one is, the less likely one is to have access to, or be able to benefit from, such things. Even within the affluent United States, groups with less income and education smoke more, weigh more, and suffer greater rates of death from heart disease, diabetes, and select cancers.

Narrowing gaps in income both within and between countries will go a long way to combating the new emergence of chronic disease worldwide.

Related Links
WHO: Global status repot on noncommunicable diseases 2010

Thursday, April 14, 2011

Preventing Disease, Saving Billions of Dollars

In the New York Times this week, Mark Bittman highlights the magnitude of our chronic disease burden and the potential for prevention to save our future federal budget billions of dollars (see story).  A small change in diet to reduce heart disease by 10% would save 100 billion dollars. And this is all easy to achieve. Many suggestions are out there and Bittman provides a nice summary of some of the current leading strategies.

In a related new study form the American Cancer Society, McCullough and colleagues report on the benefits of following a healthy lifestyle – in accordance with ACS recommendations (see report).  Focusing on non-smokers since they account for the vast majority of the US population, McCullough followed over 110,000 men and women for 14 years. Some 10,000 men Andover 6500 women died during follow-up. Those who followed ACS cancer prevention guidelines at the beginning of the study: health weight throughout life, limiting alcohol consumption, adequate physical activity, and healthy diet, had 50% reduction in death from cardiovascular disease and 30 percent reduction in death from cancer. So being in the normal weight range (BMI less than 25), being active at the level of one hour per day for at least 5 days per week, drinking no more than one drink per day (for women) or two drinks per day (for men), and eating a healthy diet including higher intake of whole grants and limiting red meat intake gave the greatest benefit.

Following healthy lifestyle will save us billions in health care costs as our population ages and the burden of chronic diseases increases. Its time for everyone to eat well and keep moving! 

Tuesday, April 12, 2011

Radiation, Chernobyl, and the Japanese burden of cancer

The New York Times today reports that the nuclear disaster in Japan is on par with the 1986 Chernobyl explosion (see story). It is appropriate that we consider the impact this will have on disease. In a rigorous review of the epidemiologic evidence following the Chernobyl nuclear accident, Cardis and Hatch provided an update on the impact of that explosion on millions of people in Europe (see article). They document the well-known exposure for children and adolescents from Chernobyl fallout and the associated increase in thyroid cancer. The greatest increase in risk is seen in those youngest at exposure. Deficiency in stable iodine may exacerbate this risk. The data on thyroid cancer risks to other age groups are less definitive.  Studies have also reported increases in both the incidence and mortality from non-thyroid cancers and other diseases. Study of cleanup workers provides evidence of an increased risk of leukemia and other hematologic malignancies. These workers also have increased risk of cataracts and a suggested increased risk of cardiovascular disease following low dose exposures.

In the Times story an accompanying graphic gives a vivid presentation of the distribution of exposures. They present exposure through the air, soil, and water, Over the coming years, given the clear causal relation between radiation exposure and cancer risk, Japan too will experience an increase in thyroid and other cancers. This will be most clearly seen in the first 20 years as an increase in thyroid cancer. Previous follow-up of atomic bomb survivors, also from Japan,  shows that higher radiation exposure in childhood leads to increased risk of breast cancer many years later.

The overall impact of even low-dose radiation a known carcinogen, on the cancer burden in the population is unquestionable. The clear exposure as a consequence of the Japanese tragedy will lead to excess cancers in the years ahead. More rigorous efforts to control exposure in future disasters must be a public health preparedness priority.

Friday, April 8, 2011

Which Screening Tests and When? Two Nice Tools Cover This and More

I was on the Preventive Services Task Force website yesterday to read some new screening recommendations, and I came across a couple neat little widgets that personalize the Task Force's prevention-related guidelines.  One is intended for the public and provides very nice, straightforward recommendations based on a person's gender and age.  The other is intended for doctors and other health professionals but could be of interest to other people interested in delving deeper into things.  It not only summarizes the recommendations but also provides the level of evidence behind the recommendations and other background information.

On the face, these are simple little tools - and I guess they are - but they do a very good job summarizing a lot of important information and in a way not often seen.  

For the public:

For doctors and other health professionals:

More on estrogen as a cause of breast cancer

For more details on our editorial this week in JAMA see the story from the Washington University School of Medicine news office.

We caution physicians and women to consider the broader body of evidence that even use of estrogen alone increases risk of breast cancer. This has been reiterated in several media stories covering the changing tide of evidence on hormones as a cause of breast cancer and factors such as obesity and time since menopause that are well documented to modify the effect of hormone therapy.

To place data on hormone therapy in context our Knol on breast cancer prevention provides a detailed summary.

Have a Family History of Breast Cancer? Keep Up a Healthy Lifestyle

Tuesday, April 5, 2011

Breast Cancer: Balancing Risks and Benefits of Postmenopausal Estrogen Therapy. Caution Still Called For.

When the Women’s Health Initiative (WHI) began in 1993, hormone therapy (HT) was prescribed for a variety of reasons that ranged from the management of menopausal symptoms to the prevention of chronic disease. The WHI was a randomized controlled trail aimed at documenting the risks and benefits of several different approaches to prevention, including estrogen by itself (also called estrogen-alone, or unopposed estrogen) in women who had a hysterectomy; estrogen plus progestin in women who still have their uterus; and vitamin D and other diet changes (like, eating low fat) to reduce risk of breast and other cancers. Many results from the WHI have been published, and we have commented on several of them in previous posts. This week, an important additional report follows women from the estrogen-only component of the trial that documents the risks and benefits of hormone therapy over time after women stopped taking hormones.

The balance of risks and benefits during active intervention for women taking unopposed estrogen was published in 2004 (Anderson, Limacher et al. 2004). Women who were currently taking estrogen had a significantly increased risk of stroke and reduced risk of hip fracture and possibly breast cancer compared with women receiving placebo. There was no overall effect of estrogen on a global index of risks and benefits including coronary heart disease (Anderson, Limacher et al. 2004).

LaCroix and colleagues now report follow-up of women who completed the intervention phase of the WHI estrogen-only study (LaCroix and al 2011). Seventy-eight percent of eligible women gave consent for continued follow-up, through a mean 10.7 years from when the study started. The increased risk of stroke observed when women were current users of estrogen did not persist after they stopped taking it. Likewise, the previously observed significant reduction in hip fractures was eliminated.

The reduced incidence of breast cancer, though, persisted. This finding is inconsistent with a longstanding and extensive body of evidence. (Steinberg, Thacker et al. 1991; Collaborative Group on Hormonal Factors in Breast Cancer 1997) There is growing evidence that important factors modify breast cancer risk among women using hormone therapy. A recent report by Beral et al from the Million Women Study demonstrates an adverse effect of postmenopausal estrogen use on breast cancer risk. Risk is significantly increased among women beginning therapy within 5 years of menopause, and there is little or no increased risk among those beginning therapy 5 or more years after menopause (Beral, Reeves et al. 2011). These findings are based on data from over a million women and 15,759 new cases of breast cancer. Risk increased with duration of use but was stronger among women who began use of estrogen alone within 5 years of menopause. Like usual medical practice, the vast majority of UK women began hormone therapy within 5 years of menopause. Overall the relative risk was 1.43 indicating a significant increase in risk of breast cancer with us of estrogen therapy. Risk was even higher in current users of hormone therapy

Figure 1
Beral and colleagues also noted that obese women using hormone therapy had little additional adverse effect from hormones when they are added to the underlying increased risk due to obesity. Among lean women the relative risk was 1.65 compared to never users (Figure 2). This translates to an increase in risk that is 65% higher than the non-users – this increase is at least comparable to the impact of family history on breast cancer risk. Among overweight and obese women the risk was still elevated at 1.2 times the risk of never users. If women began therapy more than 5 years after menopause the increase in risk was reduced.

Figure 2

In contrast with the majority of clinical practice, sixty-eight percent of women enrolled in the WHI were older than age 60 at randomization to using estrogen or placebo. In fact, 46% of the women were between 60 and 69 at the time they were started on estrogen and over 20% were between 70 and 79. Given this fact and the findings from the Million Women Study, an important question that emerges is whether the WHI population is appropriate for reaching definitive conclusions regarding younger women and the risk of breast cancer associated with hormone thereapy. (Jungheim and Colditz 2011)

As a concensus statement from the Endocrine Society - a collection of leading scientists, researchers and clinicians - says when summarizing the totality of medical science on this issue: “estrogen increases the risk of breast cancer after more than five years of use, particularly evident in those who are using hormones recently after menopause.” (Santen, Allred et al. 2010)

As we note in our editorial in JAMA that accompanies the LaCroix and colleague study (link), the lack of an adverse effect of unopposed estrogen when used for a short period in the WHI does not counter the larger body of evidence of an elevated risk of breast cancer with increasing duration of use (Steinberg, Thacker et al. 1991), the greater adverse effect among leaner women (Beral, Reeves et al. 2011), and randomized, controlled trial evidence that estrogen agonist/antagonists (e.g. tamoxifen) reduce the incidence of estrogen receptor positive breast cancer by more than 50% (LaCroix, Powles et al. 2010; Vogel, Costantino et al. 2010) This body of evidence has led the International Agency for Research on Cancer (IARC) to conclude that unopposed estrogen hormone therapy (International Agency for Research on Cancer 1999) and estrogen plus progestin hormone therapy are carcinogenic (International Agency for Research on Cancer 2008). Hormone therapy should be used with extreme caution, if at all.
Have a Family History of Breast Cancer? Keep Up a Healthy Lifestyle
Oral Contraceptives Reduce Cancer Deaths

Related Links
Breast Cancer Prevention (on Google Knol)

Literature Cited
Anderson, G. L., M. Limacher, et al. (2004). "Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial." Jama 291(14): 1701-1712.
Beral, V., G. Reeves, et al. (2011). "Breast Cancer Risk in Relation to the Interval Between Menopause and Starting Hormone Therapy." Journal of the National Cancer Institute 103(4): 296-305.
Collaborative Group on Hormonal Factors in Breast Cancer (1997). "Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiologic studies of 52,705 women with breast cancer and 108,411 women without breast cancer." Lancet 350: 1047-1059.
International Agency for Research on Cancer (1999). Monograph on the evlaaution of carcinogenic risk to humans. Hormonal Contraception and Post-menopausal Hormonal Therapy. Lyon, France, IARC Press. 72: 660.
International Agency for Research on Cancer (2008). Monograph on the evaluation of carcinogenic risk to humans: Combined estrogen/progestogen contraceptives and combined esteogen/progestogen menopausal therapy. Combined Estrogen-progestogen Contraceptives and Combined Estrogen-progestogen Menopausal Therapy. Lyon, France, IARC Press. 91.
Jungheim, E. and G. Colditz (2011). "Short-term use of unoppsoed estrogen. A balance of inferred risks and benefits." JAMA 305(13).
LaCroix, A. and e. al (2011). "Health Risks and Benefits after stopping the Women's Health Initiative trial of conjugated equine estrogens in postmenopausal women with prior hysterectomy." JAMA 305: 1305-.
LaCroix, A. Z., T. Powles, et al. (2010). "Breast cancer incidence in the randomized PEARL trial of lasofoxifene in postmenopausal osteoporotic women." Journal of the National Cancer Institute 102(22): 1706-1715.
Santen, R. J., D. C. Allred, et al. (2010). "Postmenopausal hormone therapy: an Endocrine Society scientific statement." J Clin Endocrinol Metab 95(7 Suppl 1): s1-s66.
Steinberg, K. K., S. B. Thacker, et al. (1991). "A meta-analysis of the effect of estrogen replacement therapy on the risk of breast cancer." JAMA 265: 1985-1990.
Vogel, V. G., J. P. Costantino, et al. (2010). "Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial: Preventing breast cancer." Cancer Prev Res (Phila) 3(6): 696-706.