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HHAL MEDICAL NEWS DECEMBER 2010
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HHAL MEDICAL NEWS DECEMBER 2010

Daily Aspirin Associated with Reduced Cancer Mortality in Meta-Analysis

Daily aspirin use confers a reduction in risk for death from several common cancers, in addition to its known benefit on colorectal cancer risk, according to a Lancet meta-analysis.

Researchers pooled data from eight studies including some 25,000 individuals assigned to daily aspirin or control therapy for at least 4 years. (The studies originally investigated aspirin's effects on cardiovascular events.)

Overall, aspirin recipients showed a lower odds ratio for cancer deaths during the trials; when individual patient data were available (on some 23,500 patients), the decrease appeared only after 5 years of aspirin use. The apparent benefit increased with duration of treatment, was not related to daily dose, and seemed confined to adenocarcinomas (e.g., esophageal and lung).

In three U.K. trials, cancer registries were used to extend follow-up to establish 20-year risks, which remained lower among aspirin recipients even after the end of their trial participation.

Lancet article (Free abstract)

Sex Remains Important to Many Elderly Men

Roughly half of elderly men consider sex to be at least somewhat important to them, according to an Annals of Internal Medicine study.

Some 3000 community-dwelling men aged 75 to 95 in Australia completed questionnaires about sexual activity and health conditions. (The men also underwent sex-hormone measurement several years earlier.)

Among the findings:

  • Overall, 30% reported having sex in the previous year; the prevalence was highest among the youngest men (40% among 70- to 79-year-olds vs. 11% among 90- to 95-year-olds).
  • Of those who reported being sexually active, more than half were satisfied with the frequency.
  • Independent predictors of not being active included a diagnosis of prostate cancer, osteoporosis, or diabetes; antidepressant or beta-blocker use; and lack of interest or physical limitations of one's partner.
  • Higher free testosterone levels were associated with increased odds of activity.

Annals of Internal Medicine article (Free abstract)

NIH Issues Guidelines on Managing Food Allergies

An expert panel sponsored by the National Institute of Allergy and Infectious Diseases has published guidelines for diagnosing and managing food allergies in the Journal of Allergy and Clinical Immunology.

Among the recommendations:

  • Food allergy should be considered as a diagnosis in patients presenting with anaphylaxis or a combination of symptoms related to a food-induced allergic reaction (e.g., urticaria, wheezing, angioedema of the lips and tongue) soon after ingesting food.
  • Oral food challenges remain the gold standard for diagnosing a food allergy. The panel also recommends performing a skin puncture test, along with medical history and physical examination.
  • Patients with food allergies should receive nutritional counseling and be trained to read food labels.
  • No medications or allergen-specific immunotherapies are recommended to prevent an allergic reaction.
  • Epinephrine should be the first-line treatment in all instances of anaphylaxis. The guidelines also contain a table summarizing how best to manage anaphylaxis.
  • Patients with a history of anaphylaxis should be given a prescription for two doses of an epinephrine auto-injector and instructions for use.

Summary for clinicians (Free PDF)

The Journal of Allergy and Clinical Immunology article (Free PDF)

Heart and Stroke Groups Update Stroke Prevention Guidelines

Stroke has published updated guidelines on primary prevention of stroke from the American Heart Association and the American Stroke Association. The guidelines take a patient-oriented approach, emphasizing healthy lifestyle choices.

Among the recommendations for clinicians:

  • All patients should have their stroke risk evaluated.
  • Systolic blood pressure should be targeted to below 140 mm Hg, with diastolic under 90 mm Hg. (The goal in diabetics is <130/80.)
  • An angiotensin-receptor blocker (ARB) or an angiotensin-converting–enzyme (ACE) inhibitor can help control blood pressure in adult diabetics.
  • Statins are recommended in patients with coronary heart disease and high-risk conditions such as diabetes.
  • Adjusted-dose warfarin (international normalized ratio target between 2.0 and 3.0) is recommended for high-risk patients with nonvalvular atrial fibrillation (use antiplatelet therapy with aspirin for low-risk afib patients).
  • Patients should reduce sodium intake and increase potassium intake. The DASH diet is recommended.

Stroke article (Free PDF)

Stroke Slips to Fourth Leading Cause of Mortality in U.S.

Stroke has dropped from third to fourth place in the leading causes of U.S. deaths, according to a preliminary CDC report on mortality data from 2008. Rounding out the top five are heart disease (1), cancer (2), chronic lower respiratory diseases (3), and accidents (5).

The number of stroke deaths fell by roughly 20% from 2000 to 2008. American Heart Association president Dr. Ralph L. Sacco says that the reduction can be attributed to a combination of improved prevention, greater use of thrombolytics, and use of drugs that prevent recurrent stroke.

Meanwhile, deaths from chronic lower respiratory diseases increased, partly due to a change in the WHO's classification system.

In addition, American life expectancy decreased slightly, from 77.9 years in 2007 to 77.8 years in 2008.

CDC report (Free PDF)

AHA news release (Free)

Weighty Effects on Breast Cancer Outcomes

Danish data add to the evidence that high body-mass index negatively affects prognosis.

Obesity raises risk for incident breast cancer; moreover, high body-mass index (BMI) can worsen prognosis. In a report based on data from nationwide clinical trials of adjuvant treatment for early-stage breast cancer conducted since 1977, Danish investigators assessed obesity's effects on risk for breast cancer recurrence and death among almost 19,000 women who received treatment for early-stage breast cancer between 1977 and 2006.

Participants with BMIs 30 kg/m2 were older and had more-advanced disease at diagnosis than those with BMIs <25. Cumulative incidence of distant metastasis at 10 years was 24% versus 20% (adjusted hazard ratio, 1.46; P=0.007), and cumulative risk for death from breast cancer at 30 years was 57% versus 46% (AHR, 1.38; P=0.003). However, high BMI was not associated with excess risk for locoregional recurrence. Chemotherapy as well as adjuvant endocrine therapy with tamoxifen or an aromatase inhibitor were less effective after 10 years of follow-up in women with BMIs 30.

http://us.mc812.mail.yahoo.com/mc/showMessage?sMid=0&fid=HHAL%2520news%25201210&sort=date&order=down&startMid=0&filterBy=&.rand=520183479&midIndex=0&mid=1_34808_AG%2FHjkQAAFSXTRktfwVNxWjpl0M&f=1&fromId=jw-nutrition-mailer@alerts.stanford.edu

Eating Chocolate Almost Every Day Keeps the Cardiologist Away

Women who ate chocolate frequently were less likely to be hospitalized for or to die from atherosclerotic vascular disease.

Lewis JR et al. Arch Intern Med 2010 Nov 8; 170:1857

Combined Effect of Healthy Lifestyle Factors on Colorectal Cancer Risk

Nearly one quarter of colorectal cancers were associated with lack of adherence to five lifestyle recommendations.

Kirkegaard H et al. BMJ 2010 Oct 26; 341:c5504

Statins Sharply Lower Cardiovascular Risk Regardless of Baseline LDL Cholesterol

Results of a meta-analysis suggest that guidelines should be reevaluated.

Previous studies and meta-analyses have suggested that vascular risk decreases linearly with reduction in LDL cholesterol (LDL-C) by statins (e.g., 20% reduction in vascular events per 40-mg/dL reduction in LDL-C). A new meta-analysis includes patient-level data from 21 placebo-controlled trials (almost 130,000 patients), and from 5 trials comparing high-dose to low-dose statin therapy (almost 40,000 patients), with average follow-up of 5 years.

In the placebo-controlled trials, statin recipients had a 41-mg/dL greater decline in LDL-C and a significant 22% reduction in first major vascular events (2.8% vs. 3.6% annually). In the high-dose versus low-dose trials, high-dose patients had a 20-mg/dL greater decline in LDL-C and a significant 15% reduction in first major vascular events (4.5% vs. 5.3% annually). Relative risk reductions of about 20% per 40-mg/dL decline in LDL-C were seen in both placebo-controlled and high- versus low-dose trials for all prespecified patient subgroups, and at all baseline LDL-C levels (including <80 mg/dL). Myopathy and rhabdomyolysis were dose-related but occurred infrequently.

The largest study to date of high-dose versus low-dose statin therapy was published simultaneously with — and included in — the meta-analysis. In this manufacturer-funded U.K. trial, >12,000 patients with a history of myocardial infarction were randomized to simvastatin (80 mg or 20 mg daily) and followed for a mean of 6.7 years. The high-dose group had a 14-mg/dL greater average decline in LDL-C and 6% fewer major vascular events than did the low-dose group — a result consistent with the meta-analysis.

Comment: LDL cholesterol reduction with statins seems to predictably and safely lower cardiovascular risk regardless of baseline LDL level, suggesting that current target-based treatment guidelines should be reevaluated. Editorialists note that absolute risk reduction will be small in patients at low cardiovascular risk and urge that priority be given to identifying high-risk patients who will benefit most from statin therapy.

USPSTF Takes New Approach to Recommendations for Care of Elders

The U.S. Preventive Services Task Force is taking a new approach to making recommendations for older patients. In two Annals of Internal Medicine articles, the task force says it is eager to make recommendations relevant to primary care.

Task force members point to the complexity of illness in the aged and to the relative absence of elders in clinical study cohorts.

In its first efforts with the new approach, the USPSTF has assessed the evidence on the ability of specific primary care interventions to prevent falls among elders. The review finds that exercise, physical therapy, and vitamin D supplementation have positive effects. The evidence on benefits from comprehensive fall-prevention programs was less clear, but there was no evidence that they were harmful.

Before publishing its final recommendations, the USPSTF is seeking public comment on its first draft, which it says will be available soon at the website given below.

Annals of Internal Medicine article on new USPSTF approach (Free PDF)

Endothelial dysfunction may trigger development of Alzheimer's disease

Blood vessel dysfunction that is linked to cardiovascular disease may also play a role in the development of neurodegenerative conditions such as Alzheimer's, according to a study that was published in Circulation Research: Journal of the American Heart Association.

The National Institutes of Health predicts that an estimated 5 million Americans have Alzheimer's disease, which has two distinct characteristics. Neurofibrillary tangles often form in the brains of these individuals, as well as amyloid plaques. The development of these buildups has been linked to multiple cardiovascular risk factors, of which a central feature is a deficiency in nitric oxide in the endothelium.

"If you look at any risk factor for cardiovascular disease - the standard risk factors like high cholesterol, diabetes, hypertension, smoking, sedentary lifestyle, aging - all of these have been associated with a loss of nitric oxide in the endothelium, a condition known as enthodelial dysfunction," said senior author and Mayo Clinic researcher Zvonimir S. Katusic.

The team found that inhibiting nitric oxide production triggered a series of biochemical effects that led to an increase in amyloid precursor protein, which is the main component of the amyloid plaques associated with Alzheimer's disease.

Light to moderate alcohol consumption may contribute to heart health

Researchers from the University of Rochester Medical Center have found that a well-known molecule called Notch may be responsible for the protective effects of moderate alcohol consumption on cardiovascular health.

Previous studies have reported that heart disease and cardiac-related mortality are up to 40 percent lower in light to moderate drinkers, compared to those who do not drink alcohol.

"Any understanding of a socially acceptable, modifiable activity that many people engage in, like drinking, is useful as we continue to search for new ways to improve health," Redmond said.

She added that figuring out how alcohol is beneficial at the basic science level does not mean that more doctors will advise their patients to drink. Instead, such a discovery could lead to the development of a new therapy for millions of patients with coronary heart disease.

The protein Notch is key in influencing the growth, migration and death of vascular smooth muscle cells. These processes may have a significant impact on a person's risk for heart attack and stroke.

Moderate amounts of alcohol appeared to decrease Notch signalling, which reduced the production and growth of smooth muscle cells. This left vessels open and relatively free of build-up, a desirable condition for a healthy heart. 

Staying Active Throughout Young Adulthood May Mean Less Weight Gain into Middle Age

Young adults who remain active gain less weight as they enter middle age, according to a 20-year study in JAMA.

Some 3600 individuals aged 18 to 30 were followed for two decades, during which they reported their activity level and were weighed regularly. Overall, men who maintained higher activity levels gained 2.6 fewer kg by middle age than those who were less active, while highly active women gained 6.1 fewer kg than less-active women. In addition, men and women who regularly got 150 minutes of moderate activity per week, as recommended by the U.S. Department of Health and Human Services, had significantly less weight gain than those who did not meet this goal.

The findings were independent of potential confounders, such as weight at baseline and energy intake.

The authors point out that benefits were observed during the 20-year transition into middle age, when the risk of weight gain is highest.

http://jama.ama-assn.org/content/304/23/2603.short

Prevalence of Pain During the Last 24 Months of Life

During the month before death, pain prevalence was 46%.

In surveys of seriously ill patients, their families, and healthcare providers, freedom from pain is rated highly as a contributor to a good death. In a cross-sectional study based on surveys of a nationally representative sample of community-dwelling older U.S. adults from 1994 to 2006, researchers assessed the prevalence of pain as death approached. Surveys were completed by patients or caregivers. No data on treatment of pain were available.

Data were analyzed for 4700 people who died within 24 months of being interviewed; mean age at death was 76. Twenty-six percent of decedents had been "often troubled" by pain of at least moderate severity 24 months before death. The prevalence held steady until it began rising 4 months before death and climbed to 46% during the last month of life. The prevalence of pain during the last month was substantially higher for patients with arthritis than for those without arthritis (60% vs. 26%), but it varied only slightly by terminal diagnosis (cancer, 45%; heart disease, 48%; frailty, 50%; sudden death, 42%; other causes, 47%).

Smith AK et al. Ann Intern Med 2010 Nov 2; 153:563

Medline abstract

Study Suggests Bedtime Might Be Best for Taking Levothyroxine

Taking levothyroxine for hypothyroidism at bedtime improves thyroid hormone levels compared with morning intake, according to an Archives of Internal Medicine study.

Some 100 patients were randomized to take levothyroxine at bedtime and placebo in the morning (30 minutes before breakfast), or placebo at bedtime and levothyroxine in the morning. After 3 months, they crossed over to the opposite treatment schedule for another 3 months.

Compared with morning treatment, bedtime levothyroxine lowered thyrotropin levels and increased free thyroxine and total triiodothyronine levels. Timing of treatment did not, however, affect several secondary outcomes, including quality of life.

The authors note that 30 minutes between morning treatment and breakfast might have been "too short to prevent interference with gastrointestinal absorption of levothyroxine." They conclude that clinicians should inform patients that bedtime levothyroxine is a good alternative to morning intake, as long as the drug is taken on an empty stomach.

Archives of Internal Medicine article (Free abstract)

Radiotherapy and Tamoxifen Show Long-Term Benefits in Locally Excised Ductal Carcinoma In Situ

A Lancet Oncology study confirms that radiotherapy provides long-term benefits to women with locally excised ductal carcinoma in situ (DCIS), and provides new evidence that tamoxifen helps prevent recurrence as well.

In the study, conducted in the U.K., Australia, and New Zealand, some 1700 women who'd undergone complete local excision of DCIS were randomized to radiotherapy, tamoxifen, both, or neither. During roughly 13 years' follow-up, there were 376 breast cancer diagnoses.

Radiotherapy conferred a nearly 60% reduction in diagnoses, compared with no radiotherapy; benefits were limited to decreases in ipsilateral invasive cancer and ipsilateral DCIS, with no effects on contralateral disease. In addition, tamoxifen conferred about a 30% reduction in diagnoses, with benefits seen for ipsilateral DCIS and contralateral disease. Tamoxifen did not appear to benefit women who also received radiotherapy.

A commentator, however, says we may be overtreating DCIS, given that larger, higher-grade tumors pose the greatest recurrence risk. He suggests that for lower-risk disease, "the best course might be to monitor for recurrence and offer adjuvant treatment only as needed."

Lancet Oncology article (Free abstract)

Thigh-High vs. Below-Knee Compression Stockings for DVT Prophylaxis After Stroke

No clear efficacy for preventing deep venous thrombosis with either type of stocking

The CLOTS. Ann Intern Med 2010 Nov 2; 153:553

All-Cause Mortality by Body-Mass Index

A body-mass index between 20 and 25 seems to carry the least risk for all-cause mortality, according to a New England Journal of Medicine report that pooled data from a score of studies totaling some 1.5 million white adults.

The median follow-up was 10 years. Among initially healthy female cohort members who never smoked, the following hazard ratios for all-cause mortality were derived:

BMI Range ________________ HR

15.0 to 18.4 ............................ 1.47

18.5 to 19.9 ............................ 1.14

20.0 to 22.4 ............................ 1.00

22.5 to 24.9 ............................ 1.0 (reference)

25.0 to 29.9 ............................ 1.13

30.0 to 34.9 ............................ 1.44

35.0 to 39.9 ............................ 1.88

40.0 to 49.9 ............................ 2.51

The results among males were similar.

The authors caution that the study's generalizability is limited, given that the data are all from non-Hispanic whites.

NEJM article (Free abstract)

Testosterone Replacement for Women with Chronic Heart Failure

Findings from a small study showed some improvements in functional measures.

Iellamo F et al. J Am Coll Cardiol 2010 Oct 12; 56:1310

Biologically Active Vitamin B12, Homocysteine, and Alzheimer Disease

Baseline serum levels of homocysteine correlated positively and holotranscobalamin levels correlated negatively with AD risk in a population-based, 7-year cohort study.

Studies of the associations among the components of the vitamin B12 cascade and dementia have had inconsistent results (Eur J Neurol 2009; 16:808, Am J Clin Nutr 2007; 85:511, and Neurology 2004; 62:1972). In this study, researchers examined three of the cascade components — homocysteine, holotranscobalamin (holoTC, the biologically active fraction of vitamin B12), and folate — and subsequent risk for Alzheimer disease (AD). Participants were 271 initially nondemented older adults (baseline age range, 65–79) selected from a larger cohort based on the availability of baseline serum samples of these components. After a mean follow-up of 7.4 years, participants underwent a multistep AD screening process.

In a multiple logistic regression model adjusted for known cerebrovascular risk factors (including history of stroke, blood pressure, body-mass index, and smoking) and AD risk factors (including age, education, APOE 4, and Mini-Mental State Exam score), the odds ratios for AD were 1.16 per increase of 1 µmol/L of Hcy and 0.980 per increase of 1 pmol/L of holoTC. Of note, 95% confidence intervals for both calculations did not include 1. The authors report an attenuated link between Hcy and AD when adjusting for holoTC; however, the reported 95% confidence interval for this association included 1 (0.96–1.25). Folate levels were not associated with AD. The authors conclude that further study is needed, in light of the established associations of elevated Hcy with vascular disease and of vitamin B12 deficiency with neurological illness.

Medline abstract (Free)

Diagnosis-Independent Cerebrospinal Fluid Biomarkers of Alzheimer Disease

A CSF signature accurately classified people with and without Alzheimer disease.

De Meyer G et al. Arch Neurol 2010 Aug 67:949

Dementia Associated with Heavy Smoking in Midlife

Midlife cigarette smoking of two packs per day or more portends an elevated risk for overall dementia, Alzheimer disease, and vascular dementia in later life.

Rusanen M et al. Arch Intern Med 2010 Oct 25;

HDL cholesterol may help lower Alzheimer's disease risk
A 1,130-participant study in the Archives of Neurology found that people with low levels of HDL or "good" cholesterol were 60% more likely than those with high levels to develop Alzheimer's disease after age 65. A large number of the participants had other conditions, including obesity and diabetes, leading the researchers to note that the findings may not be applicable to younger and healthier patients. HealthDay News

Study: Home monitors cut patients' need for BP drugs
An analysis in Hypertension of 37 international clinical studies showed that patients with hypertension who were using blood pressure monitors at home experienced a reduction in their blood pressure and were twice as likely to reduce the number of medications they needed compared with those whose blood pressure was being monitored at a medical office. Reuters

Sunscreen use halves melanoma risk in study
Adults who were supervised in using broad spectrum sunscreen regularly were 50% less likely to develop melanoma and had a 73% reduced risk of invasive melanoma 15 years later compared with those who received standard advice on sunscreen use, an Australian study in the Journal of Clinical Oncology showed. Reuters

Survey names Vermont as the healthiest state
The United Health Foundation named Vermont as the healthiest state for the second consecutive year, with its high rate of insured residents, well-funded health services and high availability of primary care providers. Meanwhile, Mississippi placed last for the ninth consecutive time due to high rates of childhood poverty, obesity and preventable hospitalizations. Forbes

The Framingham risk score and chronic psoriasis: Not good news
This study found that patients with psoriasis have an intermediate risk of developing major cardiovascular events, and interventions aimed to correct modifiable cardiovascular risk factors are warranted. The American Journal of Cardiology

Beta-blockers in hypertension? Let's think again
This study concluded that it is time for a re-examination of the clinical evidence for the use of beta-blockers in hypertension, given that there are patients for whom beta-blockers, particularly those with vasodilatory actions, are an appropriate treatment option.

http://www.ajconline.org/article/S0002-9149(10)01631-0/fulltext#sec2.3

 The American Journal of Cardiology

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