HHAL MEDICAL NEWS APRIL 2010

Atrial fibrillation find to be the mortality predictor
Despite being associated with an apparently lower likelihood of myocardial ischemia, atrial fibrillation was found by these authors to be an independent predictor of all-cause mortality in patients with known or suspected coronary artery disease referred for exercise stress testing.

In conclusion, despite being associated with an apparently lower likelihood of myocardial ischemia, AF was an independent predictor of all-cause mortality in patients with known or suspected CAD referred for exercise stress testing.

http://www.ajconline.org/article/S0002-9149(09)02912-9/fulltext

CDC: 45% of U.S. adults have risk factors for heart disease
About 45% of American adults who participated in a CDC survey were found to have at least one of three main risk factors for heart disease, stroke and other cardiovascular ailments. Among those polled, 30.5% had high blood pressure, 26% had high blood cholesterol levels and 9.9% had diabetes.

http://www.healthday.com/Article.asp?AID=638408

Genes Tie Blood Fat(triglyceride) to Heart Disease
Mutation can increase risk by up to 40 percent, researchers say

http://www.healthday.com/Article.asp?AID=638884

How does vitamin D relate to coronary risk?
According to these authors, low 25-hydroxyvitamin D3 levels are associated with markers of endothelial dysfunction and inflammatory activation, representing potential mechanisms for incremental coronary

Conclusion

Low 25-hydroxyvitamin D3 levels are associated with markers of endothelial dysfunction and inflammatory activation, representing potential mechanisms for incremental coronary risk.

http://www.amjmed.com/article/S0002-9343(09)01014-6/fulltext

The meaning of a high heart rate: Good or bad?
This study found that healthy longevity depends on preservation of autonomic function, in particular, HRV (heart rate variability)-parasympathetic function, despite the early age-related decrease. The eighth decade reversal of the decrease in HRV-parasympathetic function and its subsequent increase are key determinants of longevity. Persistently high HRV in the elderly represents a marker predictive of longevity.

http://www.ajconline.org/article/S0002-9149(09)02852-5/fulltext

The growing dangers of hepatitis C
Approximately 20% of patients infected by hepatitis C develop cirrhosis in about 20 years and every year 5% of them develop hepatocellular carcinoma (HCC). Current epidemiologic models suggest that the incidence of HCC and of the mortality associated with chronic HCV infection will continue to increase through 2015, a finding consisting with the perception of liver specialists today.

http://www.em-consulte.com/article/248381

The risk of nonsteroidal anti-inflammatory drugs

In conclusion, the use of NSAIDs was associated with a small, nonsignificant overall coronary risk that was more apparent for non-ST-segment elevation ACS. This risk was stronger when NSAIDs were used at high doses or in patients with previous ischemic heart disease.

http://www.ajconline.org/article/S0002-9149(09)02836-7/fulltext

HRT use reduces risk of colon cancer, research shows
A study of more than 800 women showed those who took hormone replacement therapy had half the risk of colon cancer compared with women who never used HRT. The report in the American Journal of Gastroenterology found the longer a woman was on HRT, the lower the risk for colon cancer.

http://www.reuters.com/article/idUSTRE6385AQ20100409

Healthy eating tied to lower risk of Alzheimer's
Researchers studied the eating habits of more than 2,000 people 65 and older and found that the risk of Alzheimer's disease was 38% lower in those whose diets consisted of fish, fruits, nuts, poultry and leafy vegetables and were low in red meat and butter. "We know that these foods are definitely helpful for other conditions and diseases, and now we have this hint that they may be helpful for brain diseases," one of the researchers said. The study was published in the Archives of Neurology.

http://healthday.com/Article.asp?AID=638000

The dangers of long-acting beta-agonists
This study reports that long-acting β-agonists increase the risk for asthma-related intubations and deaths, even when used in a controlled fashion with concomitant inhaled corticosteroids.

http://www.amjmed.com/article/S0002-9343(09)01110-3/fulltext

Review: Being overweight increases stroke risk

A review in the journal Stroke of studies that included almost 2.3 million people found that being overweight increases the risk of ischemic stroke by 22%, while being obese increases the risk 64%. Researchers said being overweight and obese independently affected stroke risk, possibly because fat cells can secrete substances that contribute to inflammation, artery hardening or blood clotting

http://www.reuters.com/article/idUSTRE63426Z20100405

Diabetics face higher risk of death from cancer
A review of 15 studies showed people with Type 2 diabetes who are diagnosed with cancer had a 50% higher chance of dying in the month after surgery than nondiabetic cancer patients. The risk was particularly true for those diagnosed with colorectal or esophageal cancers, the study in Diabetes Care found.

http://www.healthday.com/Article.asp?AID=637488

Treating Nonalcoholic Fatty Liver: Pioglitazone or Vitamin E?

Vitamin E is superior to placebo in treating nonalcoholic steatohepatitis, according to a New England Journal of Medicine study. Pioglitazone, although showing some efficacy, did not achieve statistically significant results.

Researchers, pursuing earlier findings that thiazolidinediones and antioxidants can lead to improvements in fatty liver, randomized some 250 nondiabetic patients with nonalcoholic steatohepatitis to 2 years' treatment with either pioglitazone, vitamin E, or placebo. Improved histologic findings were the study's primary outcome.

Liver biopsies showed that vitamin E recipients had a higher rate of improvement than those on placebo (43% vs. 19%). The improvement among pioglitazone recipients versus placebo did not reach statistical significance (34% vs. 19%). Both treatments reduced alanine and aspartate aminotransferase levels significantly from baseline values.

http://content.nejm.org/cgi/content/full/NEJMoa0907929

NIH Panel Says There's No Evidence That Anything Prevents Alzheimer Disease

"There is currently no evidence of even moderate scientific quality supporting the association of any modifiable factor ... with reduced risk of Alzheimer's disease," a panel convened by theNational Institutes of Health concluded on Wednesday. Evidence for measures to prevent cognitive decline is "similarly limited," the panel said.

The factors in question include intake of dietary supplements, use of prescription and nonprescription drugs, diet, physical activity, and social engagement.

The panel added that despite the limited evidence regarding cognitive decline, some of the measures "are not necessarily harmful and may confer other benefits."

http://www.nih.gov/news/health/apr2010/od-28.htm

Vitamin B Therapy Adversely Affects Progression of Diabetic Nephropathy

B vitamins given to lower homocysteinemia — and thereby to reduce renal and vascular complications of diabetes — don't have the desired effect, according to a JAMA study.

Researchers randomized nearly 250 patients with diabetic nephropathy to either high-dose B vitamins or placebo. The study's primary outcome measure was the change in glomerular filtration rate (GFR) between baseline and study's end.

After a mean follow-up of 32 months, GFRs declined more, on average, in the treatment group than in the control group (16.5 vs. 10.7 mL/min). A composite outcome of myocardial infarction, stroke, revascularization, and all-cause mortality also favored controls. The need for dialysis did not differ between groups. Homocysteine values, however, were significantly lower in the treatment group.

Pointing to earlier studies showing no treatment benefit, the authors conclude that "it would be prudent to discourage the use of high-dose B vitamins as a homocysteine-lowering strategy."

Tumor Necrosis Factor Antagonists May Improve Cardiovascular Outcomes in Inflammatory Disorders

New findings increase hope that these anti-TNF agents will reduce risk in psoriasis patients.

Accuracy of X-Rays for Detecting Hip and Pelvis Fractures

Both false-positives and false-negatives are not uncommon

X-ray imaging of the hip and pelvis can miss acute fractures. In a retrospective study to determine the accuracy of radiography, Duke University researchers identified 92 consecutive patients (mean age, 71) who received hip or pelvis x-rays in the emergency department and then underwent hip or pelvis magnetic resonance imaging (MRI) within 1 day. Falls and motor vehicle trauma were the usual indications for radiography. Key findings were as follows:

· In 13 patients with normal x-rays, MRI revealed 6 fractures of the hip and 17 fractures of the pelvis.

· In 11 of 26 patients whose x-rays suggested fractures, MRI showed no fractures.

· In 7 of the 15 patients whose MRIs confirmed fractures found on x-rays, MRI also identified second fractures that x-ray imaging missed.

Liraglutide(Victoza) Outperforms Sitagliptin(Januvia) for Meformin-Resistant Diabetes

In metformin-resistant diabetes, incretin-based treatment with liraglutide outperforms sitagliptin, at least in the short term, according to a Lancet study designed by liraglutide's manufacturer.

Researchers randomized some 650 patients whose diabetes was not adequately controlled with metformin alone to one of three added daily regimens for 26 weeks: 1.2 or 1.8 mg of subcutaneous liraglutide, or 100 mg of oral sitagliptin. (Liraglutide is a glucagon-like peptide-1 receptor agonist, and sitagliptin is a dipeptidyl peptidase-4 inhibitor.)

By the 26-week mark, the reduction in glycated hemoglobin values — the primary endpoint — was greater among liraglutide users (mean reductions of 1.50% for the 1.8-mg dose, and 1.24% for the 1.2-mg dose) than among sitagliptin users (0.90%). Nausea was more common among liraglutide users.

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60307-8/fulltext

Effect of Nateglinide(Starlix) on the Incidence of Diabetes and Cardiovascular Events

Conclusions Among persons with impaired glucose tolerance andestablished cardiovascular disease or cardiovascular risk factors,assignment to nateglinide for 5 years did not reduce the incidenceof diabetes or the coprimary composite cardiovascular outcomes.

http://content.nejm.org/cgi/content/short/362/16/1463?query=TOC

Effect of Valsartan(Diovan) on the Incidence of Diabetes and Cardiovascular Events

Conclusions Among patients with impaired glucose tolerance andcardiovascular disease or risk factors, the use of valsartanfor 5 years, along with lifestyle modification, led to a relativereduction of 14% in the incidence of diabetes but did not reducethe rate of cardiovascular events

http://content.nejm.org/cgi/content/short/362/16/1477?query=TOC

Inflammatory markers track with obesity starting very early in life

Levels of inflammatory markers begin increasing among children carrying excess weight within the first several years of life, according to a study published in the April 2010 issue of Pediatrics.
In the cross-sectional study, researchers assessed associations between obesity and multiple inflammatory markers among children aged 1 to 17 years participating in the National Health and Nutrition Examination Survey.

High Intake of Added Sugars Linked to Dyslipidemia Among U.S. Adults

High intake of added sugars is associated with increased risk for low HDL cholesterol and high triglycerides, according to a JAMA report.

Researchers studied some 6000 adults participating in the National Health and Nutrition Examination Survey (NHANES). Consumption of added sugars (e.g., high-fructose corn syrup and other caloric sweeteners used in prepared foods) was calculated from 24-hour dietary recalls.

In adjusted analyses, the odds of having low HDL cholesterol and high triglycerides rose significantly with increasing intake of added sugars. For example, compared with adults who got less than 5% of their total energy intake from added sugars, those getting 17.5%–25% of their energy from added sugars were about twice as likely to have low HDL levels.

The researchers found no consistent association between added sugars and LDL cholesterol.

A prudentupper limit of intake is half of the discretionary calorie allowance,which for most American women is no more than 100 calories perday and for most American men is no more than 150 calories perday from added sugars.

http://circ.ahajournals.org/cgi/content/abstract/120/11/1011

Tamoxifen vs. Raloxifene in Preventing Breast Cancer

Tamoxifen appears to be superior to raloxifene in primary prevention of invasive breast cancer, but it comes at the cost of higher toxicity, according to follow-up data from the STAR study published in Cancer Prevention Research.

The STAR investigators randomized nearly 20,000 postmenopausal women at increased risk for breast cancer (5-year predicted risk of at least 1.66% based on the Gail model) to either daily tamoxifen or raloxifene for 5 years. After a median of 81 months' follow-up, women in the raloxifene group were at greater risk for invasive breast cancer, compared with the tamoxifen group (relative risk, 1.24). There was no significant difference in noninvasive breast cancer rates or in overall mortality rates, but the raloxifene group had lower rates of invasive uterine cancer, thromboembolic events, and cataracts.

The authors say that their results "help to clarify that both raloxifene and tamoxifen are good preventive choices for higher-risk postmenopausal women, depending largely on a woman'spersonal risk factors for breast cancer."

http://cancerpreventionresearch.aacrjournals.org/content/early/2010/04/14/1940-6207.CAPR-10-0076.full.pdf+htm

Revisiting Colchicine for Acute Gout

Low-dose colchicine was reasonably effective and nontoxic.

Dietary Glycemic Load and Index and Risk of Coronary Heart Disease in a Large Italian Cohort

Conclusion In this Italian cohort, high dietary GL andcarbohydrate intake from high-GI foods increase the overallrisk of CHD in women but not men.

http://archinte.ama-assn.org/cgi/content/abstract/170/7/640?ct

Primary Prevention of Cardiovascular Events with Aspirin

No benefit was observed in a group at high risk for vascular disease.

Greater Intake of Fruits and Vegetables Offers 'Very Weak' Reduction in Cancer Risk

Increased consumption of fruits and vegetables is associated with a "very weak," albeit statistically significant, reduction in overall cancer risk, according to an observational study in the Journal of theNational Cancer Institute.

Nearly 480,000 European adults completed food-frequency and lifestyle questionnaires and were followed for roughly 9 years. During that time, 6% were diagnosed with cancer. After adjustment for smoking, alcohol intake, and other confounders, an increase in intake of 200 g/day (roughly 2 servings) of fruits and vegetables was associated with a 4% reduction in overall cancer risk.

An editorialist says the study "strongly confirms" that previous case-control studies were "overly optimistic" and that any link between fruit and vegetable intake and cancer risk "is weak at best." He adds, however, that efforts to increase fruit and vegetable consumption are "still worthwhile," given their beneficial effects on cardiovascular disease.

Antibiotics to "Treat" Patients with Mildly Elevated Prostate-Specific Antigen Levels?

A drop in PSA after antibiotic therapy did not indicate lower risk for prostate cancer.

Some clinicians prescribe antibiotics for patients with mildly elevated prostate-specific antigen (PSA) levels. The rationale is that asymptomatic prostatitis raises PSA levels and that a drop in PSA after antibiotic therapy provides reassurance that cancer is unlikely to develop. Urologists in Brazil conducted a randomized trial to examine this premise.

The researchers enrolled 98 asymptomatic men (age range, 50–75) with PSA levels between 2.5 and 10.0 ng/dL and normal digital rectal examinations who were considered to have asymptomatic prostatitis (they had defined increases in white cell counts in post–prostatic-massage urine or urethral secretions). Each man received a 4-week course of either ciprofloxacin or placebo; PSA levels were then remeasured, and 12-core biopsies were performed.

The antibiotic and placebo groups did not differ significantly in the proportion of men with posttreatment decreases in PSA levels (53% and 59%); in both groups, about 30% of men with posttreatment decreases in PSA levels exhibited prostate cancer on biopsy. In fact, the proportion with cancer was as high among men whose PSA levels decreased as among men whose PSA levels increased.

Excess Weight Raises Risk for Liver Disease

And heavy drinking adds synergistically to the risk.

Earlier research suggests that excessive weight raises risks for developing liver disease and for dying from it. However, the interaction between excessive weight and alcohol consumption in causing liver disease is less clear. The results of two recent studies shed new light on these associations.

Scottish investigators analyzed prospective data from 9600 men (mean age at study entry, 47), who were followed for a median 29 years. After adjustment for multiple variables, death from liver disease was associated significantly with increasing body-mass index (BMI) and with increasing alcohol consumption. Furthermore, a synergistic interaction between BMI and alcohol consumption was observed: Compared with underweight or normal-weight nondrinking men, men who drank 15 units of alcohol weekly had progressively higher death rates from liver disease as their weight increased (relative rates, 3.2 for underweight or normal-weight men, 7.0 for overweight men, and 18.9 for obese men).

Other U.K. researchers analyzed prospective data from 1.2 million women (mean age, 56) with mean follow-up of 6 years. Increasing BMI was associated with increasing risk for cirrhosis: For women who drank <70 g of alcohol weekly (about 0.4 drinks daily), absolute risk for cirrhosis per 1000 women was 0.8 for those with normal BMIs and 1.0 for those who were obese; for women who drank >150 g of alcohol weekly, corresponding risks were 2.7 and 5.0.

Does Absence of Coronary Artery Calcification Exclude Obstructive Coronary Artery Disease?

In symptomatic patients, overall sensitivity of a CAC score of 0 for predicting absence of obstructive CAD was only 45%.

Gottlieb I et al. J Am Coll Cardiol 2010 Feb 16; 55:627

Fragility in Aged Skin — It's Not the Fibroblasts

Local factors make skin fibroblasts behave differently in older people.

The skin of elderly patients is thin, partly because it contains less collagen. The production of collagen by fibroblasts is regulated by transforming growth factor-β (TGF-β) and connective tissue growth factor (CTGF). Chronologically aged skin produces less type 1 procollagen, and this loss of collagen causes increased skin fragility, impaired wound healing, and, alas, facial wrinkles.

A research group has now showed that, in contrast to their status in young fibroblasts, TGF-β, CTGF, and type I procollagen were all downregulated in fibroblasts from aged human skin. However, when both aged-derived and youth-derived fibroblasts were cultured, the expression levels of TGF-β, CTGF, and type I procollagen did not differ. Apparently, local factors made skin fibroblasts behave differently in the fibroblasts of older people — for example, in the realm of skin tension. TGF-β stimulated CTGF and type I procollagen synthesis in fibroblasts, although both TGF-β and CTGF operate by complex, independent, context-dependent distinct mechanisms.

http://www.ncbi.nlm.nih.gov/pubmed/19641518?dopt=Abstract

Dutasteride Gives Mixed Results in Preventing Prostate Cancer

Dutasteride lowers the incidence of prostate cancer, but not high-grade tumors, according to a New England Journal of Medicine study.

In a double-blind study designed by dutasteride's manufacturer, some 6700 high-risk men underwent randomization to either daily dutasteride or placebo. At entry, subjects were 50 to 75 years old, had PSA levels between 2.5 and 10 ng/mL, and had had a negative biopsy.

During 4 years' follow-up, the incidence of biopsy-detected cancer was lower in the treatment group than in controls (20% vs. 25%). The number of high-grade tumors, however, was significantly higher in the treatment group during the last 2 years of follow-up.

An editorialist concludes that the 5-alpha-reductase inhibitors like dutasteride "do not prevent ... but merely temporarily shrink tumors that have a low potential for being lethal." He adds that, because the drugs suppress PSA levels, "men may have a false sense of security," thus delaying diagnosis.

Conclusions Over the course of the 4-year study period, dutasteridereduced the risk of incident prostate cancer detected on biopsyand improved the outcomes related to benign prostatic hyperplasia.

http://content.nejm.org/cgi/content/short/362/13/1192