HHAL MEDICAL NEWS DECEMBER2011
Aliskiren Trial Halted Because of Adverse Events
The antihypertensive drug aliskiren (Tekturna in the U.S., Rasilez in the
European Union) should no longer be coadministered with angiotensin-converting–enzyme (ACE) inhibitors or angiotensin-receptor
blockers (ARBs), the manufacturer announced Tuesday following the early termination of the ALTITUDE trial. Patients taking
these combinations should be switched to another antihypertensive regimen.
In
the study, patients with type 2 diabetes and impaired renal function were given aliskiren or placebo in addition to an ACE
inhibitor or ARB. A data monitoring group opted to stop the trial after the aliskiren group
had a higher-than-expected incidence of nonfatal stroke, renal complications, hyperkalemia, and hypotension after 18 to 24
months.
Manufacturer news release (Free)
Study: More fat comes back when dieters regain weight
Dieters who regain weight barely recover the lean mass they
lost and usually end up regaining higher fat mass, a study in the American Journal of Clinical Nutrition showed. Researchers
studied 78 nonactive postmenopausal women and found that 84% put on more than the benchmark of 4.4 pounds. Most regained four
times as much fat as muscle after a 12-month follow-up. WebMD
What the right diet can do -- and how much
-- in heart disease
Medicated secondary prevention patients show evident, though small, responses to both the Mediterranean and the Therapeutic Lifestyle Changes diets. The data show improved markers of redox homeostasis
and metabolic effects, potentially related to atheroprotection. The American Journal of Cardiology
Fish lowers heart disease risk in women, study finds
Danish researchers found that young women who eat fish with high omega-3 fatty acids are significantly less likely
to develop cardiovascular diseases. The study in Hypertension involving 49,000 pregnant women between 1996 and 2008 showed
that those who never ate fish had 50% more heart problems than women who frequently ate fish, and were 90% more likely to
develop cardiovascular illnesses than women who ate fish weekly. HealthDay News
Being overweight increases obesity risk factors
Low levels of education, parental obesity and an unhealthy
diet can cause already overweight individuals to gain more weight, experts reported in PLoS ONE. Researcher Paul Williams
said environmental factors that have less effect on lean people may have more significant effects on their overweight counterparts. New Kerala (India)/Asian News International
Coagulation self-management
Our analysis showed that self-monitoring and self-management of oral coagulation
is a safe option for suitable patients of all ages. Patients should also be offered the option to self-manage their
disease with suitable health care support as backup. (Free registration required.) The Lancet
Monitoring at 3-Month Intervals Might Be
Feasible for Some Warfarin Patients
Monthly
testing might be unnecessary for some stable patients.
Schulman S et
al. Ann Intern Med 2011
Nov 15; 155:653
Antiplatelet Therapy for Atrial Fibrillation: One Drug or Two?
In an ACTIVE substudy, the net clinical benefit of adding clopidogrel to aspirin in patients who were
not candidates for warfarin was small and statistically nonsignificant.
In the ACTIVE W trial, warfarin was clearly superior to dual antiplatelet therapy (DAT: aspirin plus
clopidogrel) for the prevention of ischemic events in patients with atrial fibrillation In the ACTIVE A trial involving patients
who were unsuitable for warfarin therapy, the advantages of DAT over aspirin alone were ambiguous To quantify the net clinical
benefit of DAT in the ACTIVE A population, t he ACTIVE investigators assigned weights to ischemic and hemorrhagic events by
hazard ratio (HR) for death and by a composite measure of risk for death or disability.
Compared with ischemic stroke, the HR for death after hemorrhagic stroke was three times higher, and the HR
for death after subdural hemorrhage was 40% lower. The composite of death and disability was also more frequent after hemorrhagic
stroke than after ischemic stroke or subdural hemorrhage. The net clinical benefit of adding clopidogrel to aspirin, expressed
as ischemic stroke equivalents prevented per 100 patient years, was 0.57 when calculated by HR for death and 0.67 when calculated
by the composite of death and or disability. Estimated net clinical benefit (using the death or disability model) was highest
in patients with previous stroke or transient ischemic attack and in those with CHADS2 scores 3 (2.08 and 1.03 ischemic
stroke equivalents prevented per 100 patient years, respectively). However, the confidence intervals for all of these estimates
crossed zero.
Connolly SJ et al. Ann
Intern Med 2011 Nov 1; 155:579
Medline abstract
Antihypertensive Therapy with
Chlorthalidone Increases Longevity, Long-Term Follow-Up Finds
In patients with isolated systolic hypertension, active treatment increases longevity
free from cardiovascular death — on average by 1 day for each month of treatment — according to aJAMA study.
Researchers
examined long-term survival data from the SHEP trial, in which patients received either chlorthalidone- or placebo-based stepped
care for isolated systolic hypertension. The intervention lasted 4.5 years, after which all participants were advised to go
on active therapy.
At long-term follow-up some 22 years later, active therapy
conferred a gain in life expectancy free from cardiovascular death of roughly 6 months.
The authors say the results send "a strong message that may result in increased patient adherence
to drug therapy and decrease the degree of therapeutic inertia by health care providers."
http://jama.ama-assn.org/content/306/23/2588.short
Vitamin D deficiency and bone loss
Low 25 hydroxyvitamin (OH) D levels are associated with increased parathyroid hormone levels leading to progressive
bone loss. Our data suggest that a 25(OH)D threshold of 50 nmol/L is sufficient for parathyroid hormone suppression and prevention
of secondary hyperparathyroidism in persons with normal renal function. 25(OH)D levels greater than 75 nmol/L do not seem
to be associated with additional change in parathyroid hormone levels. The American
Journal of Medicine
Longevity Proteins Linked To Anxiety
http://www.medicalnewstoday.com/printerfriendlynews.php?newsid=238969
Oxytocin Makes You Feel More Extroverted
http://www.medicalnewstoday.com/printerfriendlynews.php?newsid=238967
Bone
Fractures Can Be Predicted By Dental X-Rays
http://www.medicalnewstoday.com/printerfriendlynews.php?newsid=238777
Breast Cancer And Heart Disease May Have Common Roots
http://www.medicalnewstoday.com/printerfriendlynews.php?newsid=239532
Starch Intake May Influence Risk For Breast Cancer Recurrence
Intermittent, Low-Carbohydrate
Diets More Successful Than Standard Dieting, Present Possible Intervention For Breast Cancer Prevention
http://www.medicalnewstoday.com/printerfriendlynews.php?newsid=238904
http://www.medicalnewstoday.com/printerfriendlynews.php?newsid=238903
40%
Of Cancers Avoidable, UK Research
http://www.medicalnewstoday.com/printerfriendlynews.php?newsid=238793
Vitamin D Lowers Fracture Risk, but Its Effects on Cancer and CVD Aren't Clear
Two reviews on vitamin D appearing in the Annals
of Internal Medicine point to its role in lowering fracture risk, but
say little is known about its effect on cardiovascular disease and cancer.
One
review, undertaken to help the U.S. Preventive Services Task Force draft recommendations, concludes that vitamin D, combined
with calcium supplements, reduces fracture risk in older adults. The effect is greater among institutionalized adults than
among those living in the community or among postmenopausal women. The reviewers point to conflicting findings on whether
vitamin D might decrease (or even increase) the risk for cancer and thus could draw no conclusions.
The other review points to research linking hypovitaminosis D with cardiovascular disease, but says
that several confounders may be at work in the association. The review concludes that "no clear evidence indicates that
vitamin D supplementation has a role to play in the prevention of cardiovascular disease."
Annals
of Internal Medicine review
for USPSTF
Link Between Low Vitamin
D Levels And Higher Degrees Of Insulin Resistance
http://www.medicalnewstoday.com/printerfriendlynews.php?newsid=238683
Likely Cause Of Essential Tremor Discovered
http://www.medicalnewstoday.com/printerfriendlynews.php?newsid=238787
Listening To Music Lights Up The Whole Brain
http://www.medicalnewstoday.com/printerfriendlynews.php?newsid=238670
Follow-Up: Interview About CPAP's Effects on Metabolic Syndrome
Use of a continuous positive airway pressure (CPAP) device in people with
obstructive sleep apnea may improve some components of metabolic syndrome, particularly hypertension, according to an industry-supported
study in the New England Journal of Medicine.
Researchers in India randomized 90 people with at least moderately severe sleep apnea to 3 months of
either CPAP or sham CPAP (sham treatment used a mask with escape holes and a flow restrictor). Following a 1-month washout,
patients switched treatments. More than 80% had metabolic syndrome before treatment.
More
patients receiving CPAP therapy, versus sham therapy, experienced a reversal of metabolic syndrome (13% vs. 1%). CPAP was
also associated with greater reductions in blood pressure (differences between treatments: systolic: -3.9 mm Hg; diastolic:
-2.5 mm Hg), glycated hemoglobin, cholesterol, BMI, and abdominal fat.
The
authors write: "These results suggest a significant clinical benefit that will lead to a reduction in cardiovascular
risk."
NEJM article
Niacin in Patients with Low HDL Cholesterol Levels Receiving Intensive Statin Therapy
The AIM-HIGH Investigators
N Engl J Med
2011; 365:2255-2267December 15, 2011
BACKGROUND
In patients with established cardiovascular disease, residual cardiovascular
risk persists despite the achievement of target low-density lipoprotein (LDL) cholesterol levels with statin therapy. It is
unclear whether extended-release niacin added to simvastatin to raise low levels of high-density lipoprotein (HDL) cholesterol
is superior to simvastatin alone in reducing such residual risk.
CONCLUSIONS
Among patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of less than
70 mg per deciliter (1.81 mmol per liter), there was no incremental clinical benefit from the addition of niacin to statin
therapy during a 36-month follow-up period, despite significant improvements in HDL cholesterol
and triglyceride levels. (Funded by the National Heart, Lung, and Blood Institute and Abbott Laboratories; AIM-HIGH ClinicalTrials.gov
number, NCT00120289.)
http://www.nejm.org/doi/full/10.1056/NEJMoa1107579?query=TOC
Sodium Excretion of >7 g or <3 g Daily Is Associated with
Elevated Cardiovascular Morbidity
By comparison,
higher potassium excretion was associated with lower stroke risk.
The WHO recommends
daily sodium intake of less than 2 g, based on relatively short trials in which the effect of sodium intake on blood pressure
was assessed. In this study, researchers analyzed data for 28,880 patients in two international clinical trials of an angiotensin-receptor
blocker; most patients (mean age, 67; 70% men) had histories of myocardial infarction, stroke, hypertension, or diabetes.
People with congestive heart failure (CHF), decreased renal function, or uncontrolled hypertension were excluded. Mean daily
sodium excretion (a surrogate for sodium intake) was 4.77 g, and daily potassium excretion was 2.19 g.
At
5 years, a composite outcome of cardiovascular mortality, myocardial infarction, stroke, and hospitalization for CHF occurred
in 4729 patients. Patients with urinary sodium excretion of 4 to 6 g daily had the lowest risk for the composite outcome.
Risk was higher by 21%, 16%, 15%, and 49% for patients with daily excretion of <2 g, 2–3 g, 7–8 g, and >8
g, respectively. Compared with patients who had daily potassium excretion of <1.5 g, risk for stroke was 32% lower in those
with excretion of >3 g. These analyses were adjusted for numerous clinical and demographic factors.
Comment: This J-shaped relation between sodium intake and cardiovascular outcomes conflicts with current recommendations to
limit daily sodium intake to 2 g. However, an editorialist is unconvinced and believes that randomized trials are needed to
account for confounding caused by preexisting disease and risk factors. The small number of patients with low sodium intake
— 3% of the total sample had urinary excretion <2 g daily — also tempers the results. Consuming a diet high
in natural foods and low in processed foods would result in a lower sodium–potassium ratio –– which could
be more important than the actual intake level
O'Donnell MJ et
al. JAMA 2011 Nov
23/30; 306:2229
Whelton PK. JAMA 2011 Nov 23/30; 306:2262
Medline abstract
Medline abstract
Rectal Cancer Incidence Rose After Radiation Therapy for Prostate
Cancer
Excess 10-year risk
was roughly one case per 100 men.
A
U.S. study demonstrated an increased risk for rectal cancer following external-beam radiation therapy for prostate cancer.Now,
Israeli researchers have analyzed data from their national cancer registry to address this issue.
Of
nearly 30,000 men with prostate cancer diagnosed between 1982 and 2005, 2163 received radiation therapy (either external-beam
or brachytherapy), and 26 of these men received subsequent diagnoses of rectal cancer. Compared with the age-adjusted incidence
of rectal cancer in the entire Israeli male population, the incidence was significantly higher in the radiation-therapy group
(standardized incidence ratio, 1.8). This increase would correspond roughly to one additional case per 100 men during 10 years
of follow-up. In contrast, patients who underwent radical prostatectomy did not have excess risk for rectal cancer.
Margel D et al. Ann Surg 2011
Dec 254:947
High blood glucose levels up colorectal cancer risk in older women
Postmenopausal women with the highest blood glucose levels
were nearly twice as likely to develop colorectal cancer over 12 years than those who had the lowest levels, a study showed.
Researchers examined 4,500 women ages 50 to 70 and found that 35 patients in the "high" group -- not quite high
enough to be diabetic -- developed colorectal cancer by the end of the study period, compared with only 18 in the "low"
group. The findings appear in the British Journal of Cancer. U.S. News & World Report/HealthDay
News (11/30),MyHealthNewsDaily.com
No Evidence of Adverse Outcomes from Long-Term
Statin Therapy
Vascular
benefits persist, without elevated risk for nonvascular morbidity or cancer.
No
Evidence of Adverse Outcomes from Long-Term Statin Therapy
Vascular benefits
persist, without elevated risk for nonvascular morbidity or cancer.
In randomized trials of statin therapy, lowering LDL cholesterol levels by 40 mg/dL during 5 years
cut vascular mortality and morbidity by about 25% without affecting nonvascular morbidity or mortality. But observational
studies over longer periods have suggested associations between lower LDL cholesterol levels and elevated rates of nonvascular
morbidity and mortality –– and elevated risks for some kinds of cancer.
In
the British Heart Protection Study, 20,000 patients at elevated vascular risk were randomized to receive daily simvastatin
(40 mg) or placebo. At 5 years, simvastatin recipients had a 23% relative reduction in major vascular events and a 14% relative
reduction in overall mortality; the differences between groups widened over time. The authors now report outcomes after an
average 5.7 years of post-trial follow-up, during which statin use and lipid levels were similar in both groups.
Patients in the simvastatin group had 14% fewer first major vascular events in the first post-trial
year, but no significant differences were noted between groups thereafter. In addition, no significant post-trial differences
were observed between groups in vascular or nonvascular mortality or in cancer incidence.
Heart Protection Study Collaborative Group. Lancet 2011 Dec 10; 378:2013
Nonalcoholic Fatty Liver Disease Isn't
Associated with Excess Mortality
The same
was true for nonalcoholic steatohepatitis.
Nonalcoholic fatty liver disease (NAFLD) is associated with
cirrhosis, liver cancer, and several cardiovascular (CV) risk factors such as diabetes and obesity. Prior studies, however,
have not established a clear association between NAFLD and early mortality, and most of these studies were based on highly
selected patient populations (e.g., those with biopsy-proven NAFLD). To assess this association, researchers conducted a prospective
cohort study based on data from the Third National Health and Nutrition Examination Survey (1988–1994), which involved
more than 11,000 adults (age range, 20–74) who underwent baseline hepatic ultrasonography.
NAFLD
was defined as "the presence of moderate to severe hepatic steatosis with normal liver enzyme levels." Nonalcoholic
steatohepatitis (NASH) was defined as "the presence of moderate to severe hepatic steatosis with increased levels of
liver enzymes," without evidence of hepatitis B or C infection or iron overload. The prevalence of NAFLD was 16%, the
prevalence of NASH was 3%, and median follow-up was 14.5 years. Neither NAFLD nor NASH was associated with elevated all-cause
mortality or death from CV disease, cancer, or liver disease. These outcomes were noted both in analyses that were adjusted
for CV risk factors and in those that were not.
Comment: In this large prospective study, NAFLD
and NASH were not associated with elevated risk for all-cause mortality or death from CV disease, cancer, or liver disease.
However, these results should be interpreted with some caution, in part because the authors had to create their own ultrasound-
and laboratory-based definitions. Although ultrasonography accurately detects hepatic steatosis, ultrasound-detected hepatic
steatosis combined with elevated liver enzymes has limited sensitivity and specificity for NASH. The authors call for further
studies with large samples and more-refined diagnostic methods to determine the effects of NASH on mortality.
Lazo M et al. BMJ 2011
Nov 18; 343:d6891
Statins After Stroke or TIA: More Evidence of Benefits
A substudy of the SPARCL trial indicates that patients with stroke or transient ischemic attack benefit
from statin therapy regardless of baseline diabetes.
Callahan A et
al. Arch Neurol 2011
Oct 68:1245
.
Statins Don't Lower Risk for Infections
A meta-analysis
of 11 randomized trials showed no benefit.
van
den Hoek HL et al. BMJ 2011
Nov 29; 343:d7281
Bone Health in Women Who Discontinue Menopausal
Hormone Therapy
Bone mineral density
fell and fracture risk rose after HT cessation.
Karim
R et al. Menopause 2011
Nov 18:1172
Poststroke Blood Pressure Affects Risk
for Recurrent Stroke
Risk was elevated
with low and high systolic BP.
Risk for a first ischemic
stroke is generally proportional to the level of systolic blood pressure (BP), but optimal poststroke BP for prevention of
recurrent stroke is less clear. To examine this issue, researchers conducted a post hoc analysis of data from a previously
published secondary prevention study that involved about 20,000 patients (mean age, 66; two thirds men) with recent noncardioembolic
ischemic stroke
The original study addressed the role of various antiplatelet regimens, and BP
was managed by investigators at their discretion. Patients were assessed several times during a mean follow-up of 2.5 years,
during which the risk for recurrent stroke was about 8%. Compared with patients who had low-normal systolic BP (120–129
mm Hg), risk for recurrent stroke was elevated in patients whose mean systolic BP during the study was very low (<120 mm
Hg; 29% relative increase), high (140–149 mm Hg; 23% increase), or very high ( 150 mm Hg; 108% increase); risk with high-normal
systolic BP (130–139 mm Hg) was similar to that with low-normal BP. These analyses were adjusted for clinical and demographic
factors.
Ovbiagele B et al. JAMA 2011 Nov 16; 306:2137
Medline abstract
The association of acetaminophen and asthma prevalence and severity.
Positive associations exist between acetaminophen use and asthma in children.
McBride
JT. Pediatrics 2011
Dec 128:1181
Abstract
The epidemiologic association
between acetaminophen use and asthma prevalence and severity in children and adults is well established. A variety of observations
suggest that acetaminophen use has contributed to the recent increase in asthma prevalence in children: (1) the strength of
the association; (2) the consistency of the association across age, geography, and culture; (3) the dose-response relationship;
(4) the timing of increased acetaminophen use and the asthma epidemic; (5) the relationship between per-capita sales of acetaminophen
and asthma prevalence across countries; (6) the results of a double-blind trial of ibuprofen and acetaminophen for treatment
of fever in asthmatic children; and (7) the biologically plausible mechanism of glutathione depletion in airway mucosa. Until
future studies document the safety of this drug, children with asthma or at risk for asthma
should avoid the use of acetaminophen.
Could Iron-Fortified Formula Be Bad for Development?
Children given iron-fortified formula
as infants scored lower on cognitive and visual-motor tests at age 10 years.
Lozoff B et al. Arch Pediatr
Adolesc Med 2011 Nov 7;
Christian P. Arch Pediatr Adolesc Med 2011
Nov 7;
http://pediatrics.jwatch.org/cgi/content/full/2011/1207/1?q=topic_nutrition
Intermittent Budesonide in Preschool Children
with Recurrent Wheezing
As-needed inhaled
corticosteroids were as effective as daily inhaled steroids for certain children.
Whole-Body Vibration: No Benefit for BMD
Daily use
of devices for 1 year did not improve bone-mineral density.
Slatkovska
L et al. Ann Intern Med 2011
Nov 15; 155:668
Using Hemoglobin A1c vs Diabetes as a High-Risk Equivalent |
Conclusions In
both women and men with diabetes at baseline, we observed significant
improvements in predictive ability of CVD
risk using models incorporating HbA1c levels compared with classification of diabetes as a cardiovascular risk equivalent.
http://archinte.ama-assn.org/cgi/content/abstract/archinternmed.2011.351v1?ct
Improved Fitness Linked to Reduced
Mortality in Men, Regardless of BMI
Men who maintain or improve
their cardiorespiratory fitness have lower mortality risks than those who become less fit — regardless of changes in
BMI — a Circulation study finds.
Some 14,000 men underwent clinical exams at baseline (mean age, 44) and again roughly 6 years later.
Cardiorespiratory fitness was measured in metabolic equivalents (METs) during both exams, and mortality was assessed until
11 years after the last examination.
Among the
findings:
· Maintaining or improving cardiorespiratory
fitness between the two exams conferred lower mortality risk, even after controlling for BMI changes.
·
For each 1-MET increase in fitness, the risks for all-cause and CVD mortality dropped by 15% and 19%,
respectively.
· BMI changes did not independently
predict mortality.
The authors
conclude: "The long-term effect of fitness change, primarily resulting from increasing physical activity, is likely to
be at least as important as weight loss for reducing premature mortality."
Circulation article
Walking affects weight but not muscle strength, study finds
Women who walked more than 10,000 steps per day weighed less and had lower
body fat readings but did not have greater muscle strength or agility compared with those who logged fewer steps, according
to Canadian researchers. The study in the journal Menopause did not measure the intensity of walking, and the research team
is planning future studies to test whether higher-impact walking affects outcomes. Reuters
Physical Activity and Cognition
in Women With Vascular Conditions
Conclusion: Regular physical activity, including walking, was associated with better preservation of cognitive
function in older women with vascular disease or risk factors.
http://archinte.ama-assn.org/cgi/content/abstract/171/14/1244?ct
Activity Energy Expenditure and Incident Cognitive Impairment in Older Adults
Conclusions : These findings indicate that greater AEE may be
protective against cognitive impairment in a dose-response manner. The significance of overall activity
in contrast to vigorous or light activity should be determined.
http://archinte.ama-assn.org/cgi/content/abstract/171/14/1251?ct
Exercise Referral Schemes Have Marginal
Benefits for Sedentary Patients
Patients exercised more, but body-mass
index, blood pressure, and lipid levels remained unchanged.
Pavey
TG et al. BMJ 2011
Nov 6; 343:d6462
Williams NH. BMJ 2011 Nov 6; 343:d6615
Medline abstract
