Обзор американских кардиологических журналов за неделю (ссылки)

[Chevychelov]

Drugmaker Pulls Plug on Oral Anticoagulant

By Peggy Peck, Executive Editor, Reviewed by
September 29, 2011

Review

Astellas Pharma has announced it is shutting down global development of darexaban maleate, a direct factor Xa inhibitor, after an acute coronary syndrome study revealed a higher bleeding risk associated with the drug.

The company said the ACS results reported at the European Society of Cardiology meeting last month in Paris, coupled with its inability to find a development partner for darexaban made further development impractical.

In the ACS study there was a significant dose-dependent increase in major bleeding and clinically relevant nonmajor bleeding at six months among patients treated with darexaban.

But darexaban is not the first direct factor Xa inhibitor to demonstrate safety concerns when used to treat ACS patients -- apixaban failed in phase III for that patient population. And a third factor Xa inhibitor, rivaroxaban (Xarelto), is currently being evaluated for ACS.

Earlier this year, Astellas abandoned plans to seek approval from the Japanese regulatory agency to market the drug for use after surgery.
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Featured Commentary

Issue No. 6, 2011
CETP inhibition in perspective

The sixth in a series of regular Commentaries highlighting topical issues relevant to EAS activities
Cholesteryl ester transfer protein (CETP) inhibition has been a ‘hot topic’ in recent news. At the European Society of Cardiology (ESC) Congress in Paris 27-31 August, two trials with dalcetrapib were presented –dal-PLAQUE and dal-VESSEL. Results and implications from these trials are discussed here.
Dal-PLAQUE
The findings from this small trial, presented as a poster at the ESC Paris, were subsequently published in The Lancet.1 Dal PLAQUE was designed to investigate the effects of dalcetrapib treatment on structural and inflammatory markers of plaque burden, using innovative multimodality imaging techniques.

In this phase IIb, double-blind trial 130 patients (mean age 63 years, 82% male and mean HDL cholesterol 1.2 mmol/L or 46 mg/dL at baseline) with coronary heart disease (CHD) or CHD risk equivalents and treated to a LDL cholesterol level of <2.6 mmol/L (mean 1.9 mmol/L or 74 mg/dL) were randomly allocated to treatment with dalcetrapib 600 mg/day or placebo for 24 months. The primary endpoints were indices of plaque burden from the carotid and abdominal aorta (total vessel area, wall area, wall thickness and normalised wall index) at 24 months measured using magnetic resonance imaging (MRI). Plaque inflammation was also assessed at 6 months using 18F fluoro-deoxyglucose uptake measured by positron emission tomography/computed tomography (FDG-PET/CT).

Treatment with dalcetrapib increased plasma levels of HDL cholesterol levels by 31%, consistent with previous phase II data.2

Dalcetrapib treatment was associated with reduction in structural markers of plaque burden at 24 months, as indicated by:
Significant reduction in total vessel area (absolute change from baseline corrected for placebo, -4.01 mm2, 90%CI -7.23 to -0.80, p=0.041)
A trend for reduction in average wall area (-2.20 mm2, 90%CI -4.54 to 0.13, p=0.12).
The dalcetrapib placebo-corrected changes in total vessel area, average wall area and normalised wall index were either below the pre-specified ‘no harm’ boundary, or the change was numerically lower in the dalcetrapib group than the placebo group.

FDG-PET/CT results showed no evidence of increased vascular inflammation with dalcetrapib at 6 months. The target to background ratio (TBR) for the most diseased segment decreased over 6 months in the dalcetrapib group but did not change in the placebo group (average absolute change 0.19, 90% CI -0.29 to -0.09, p=0.001 versus -0.043, 90% CI -0.14 to 0.06, p=0.51). Exploratory analyses showed that the change in HDL cholesterol level appeared to be inversely correlated with the change in TBR for the most diseased segment at 6 months. A 4.3% reduction in arterial inflammation was observed with each increase in HDL cholesterol tertile (p=0.04).

Dalcetrapib treatment was not associated with any increase in blood pressure. There were 15 adjudicated cardiovascular events (13 on dalcetrapib vs. 2 on placebo).

It is acknowledged that the study was exploratory and therefore no correction was made for multiple statistical analyses. Additionally, patients were only randomised if they had a sufficient PET signal at baseline. Despite these methodological limitations, the data support the hypothesis that HDL cholesterol raising associated with dalcetrapib treatment might reduce inflammation in turn leading to favourable changes in structural vascular changes.

[Chevychelov]

OBESITY: Stepped Approach to Weight Loss Works

By Todd Neale, Senior Staff Writer, October 02, 2011

Action Points
Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.


Explain that stepping up the intensity of a weight-loss intervention only for those patients who fail to reach their goal may be a viable alternative to standard lifestyle approaches.

Point out that this study used a stepped-care approach in which the intensity is increased only if the participant fails to reach a pre-specified goal.
Review

ORLANDO -- Stepping up the intensity of a weight-loss intervention only for those patients who fail to reach their goal may be a viable alternative to standard lifestyle approaches, a randomized trial showed.

There was no significant difference in the percentage of patients who achieved a 10% reduction in weight after 18 months between the stepped-care group and the standard group (26% versus 32%, P>0.05), according to John Jakicic, PhD, of the University of Pittsburgh.

The average percent weight loss was also similar in the two groups (5.8% versus 6.8%, P>0.05), Jakicic reported at the Obesity Society meeting here.

"So the stepped-care approach may present an effective alternative to standard behavioral weight loss interventions," he said.

He added that 30% to 40% of the patients in the stepped-care group remained at one of the first two steps, which involved monthly group meetings, weekly mailed lessons, and mailed feedback on a self-monitoring diary (for both steps), and one phone call per month (for the second step only).

Although behavioral interventions involving lifestyle changes have been shown to be effective at getting patients to lose weight, the intensity of such approaches generally remains the same regardless of whether the participants are responding.

A stepped approach, in which the intensity is increased only if the participant fails to reach a pre-specified goal, has been proposed as an alternative, but the strategy had not been compared with a standard behavioral weight loss intervention in a randomized trial, according to Jakicic.

He and his colleagues designed the Step Up study, which randomized 364 overweight and obese individuals to a stepped-care or standard intervention. The mean age of the participants was 42.2 and the mean body mass index was 33 kg/m2 (ranging from 25 to 39.9 kg/m2). Most of the participants were female (82.7%).

Those in both groups were prescribed dietary goals, with the aim of reducing calories and fat intake, and physical activity targets progressing to 300 minutes of moderate-to-vigorous intensity exercise per week.

The standard behavioral weight loss program involved group sessions weekly for the first six months, twice a month for the next six months, and monthly sessions for the final six months. The program remained consistent for all participants regardless of weight loss achieved.

In the stepped-care group, however, participants were scheduled to attend one group session per month throughout the study and to receive weekly mailed lessons, as well as mailed feedback on their diaries. Those who failed to achieve various weight loss goals -- 5% at three months, 7% at six months, and 10% at nine months and every three months thereafter -- received more frequent contact.

The intensified steps included up to two phone calls per month, up to two individual sessions to discuss weight loss per month, and the provision of meal replacements.

Although participants in both groups lost weight, the absolute loss was significantly greater in the standard group for the first six months (22 pounds versus 17.6 pounds, P<0.05), as was the percent weight loss (9.2% versus 7.6%, P<0.01). At each time point beyond six months, however, there was no significant difference between the two groups for either measure.

Jakicic said that there was more work to be done to evaluate a stepped-care intervention for weight loss, including looking at:
Whether any of the steps were more effective than others
Who responded to the approach
Different approaches for stepping up care
The effect of diet and physical activity behaviors

In addition, he and his colleagues will conduct a cost-effectiveness analysis and examine whether the weight loss thresholds for stepping up care need to be adjusted.

[Chevychelov]

Collateral Blood Supply May Cut Death Risk in CAD

By Todd Neale, Senior Staff Writer,
October 02, 2011

Action Points
Explain that patients who have coronary artery disease (CAD) and strong coronary collateral circulation appear to have improved survival.


Point out that the risk reduction was more pronounced in studies in which most patients underwent percutaneous coronary intervention, and those in which the collateral circulation was assessed using intracoronary pressure measurements versus visual inspection.
Review

Patients who have coronary artery disease (CAD) and strong coronary collateral circulation appear to have improved survival, a meta-analysis showed.

For patients with stable or acute CAD, a high degree of collateralization was associated with a 36% reduction in the risk of dying during follow up for as long as 10 years (RR 0.64, 95% CI 0.45 to 0.91), according to Christian Seiler, MD, of the University Hospital Bern in Switzerland, and colleagues.

The risk reduction was more pronounced in two types of studies: those in which most patients underwent percutaneous coronary intervention (PCI) versus those with no PCI (RR 0.42 versus 0.70), and those in which the collateral circulation was assessed using intracoronary pressure measurements versus visual inspection (RR 0.38 versus 0.71), the researchers reported online in the European Heart Journal.

Coronary collateral circulation is found in individuals with and without coronary artery disease. If one of the epicardial arteries becomes blocked, the collateral arteries can enlarge to provide an alternative source of blood to the heart.

"The coronary collaterals may represent a useful prognostic marker," they wrote. "Patients with a low collateralization have an increased mortality risk and may be monitored more closely."

They added that diagnostic angiography remains important to define the coronary anatomy and the degree of collateralization, which is best accomplished by measuring the intracoronary pressure; an alternative is to use an intracoronary ECG.

The researchers stated that for patients with an MI, increased collateralization has been associated with the following:
Smaller infarct size
Preserved cardiac function after an acute infarction
Reduced post-infarct ventricular dilatation
Reduced post-infarct aneurysm formation


But the relationship between increased collateralization and mortality is less clear.

Seiler and colleagues performed a meta-analysis of 12 studies that included 6,529 patients with stable or acute CAD and reported the degree of coronary collateralization and mortality statistics.

The lower mortality risk with a high degree of collateralization was consistent in patients with stable disease (RR 0.59, 95% CI 0.39 to 0.89), those with subacute MI (RR 0.53, 95% CI 0.15 to 1.92), and those with acute MI (RR 0.63, 95% CI 0.29 to 1.39). The differences among the relative risks were not statistically significant (P=0.149).

The researchers noted that the lack of statistical significance for the relationship in the MI groups was mostly due to limited power from a small sample size.

Although a causal relationship between better collateralization and mortality could not be established, the authors speculated on some possible underlying mechanisms.

Collateral circulation has been shown to reduce QT interval prolongation resulting from acute myocardial ischemia, which puts patients at risk for fatal arrhythmias, they wrote.

In addition, they noted that reductions in infarct size and post-infarct ventricular dilatation and preservation of cardiac function likely have mortality benefits.

"The results of this study highlight the importance of finding means to induce collateral growth," Seiler and colleagues wrote, adding that experimental studies have shown that promoting growth is feasible.

"We further need larger-scale interventional studies which test whether the therapeutic promotion of collaterals translates into improved clinical outcomes," they wrote.

They acknowledged that the analysis was limited in that all of the included studies were observational and most were small and retrospective.

The study was supported by the Swiss National Science Foundation.

The authors reported that they had no conflicts of interest.
Primary source: European Heart Journal
Source reference:
Meier P, et al "The impact of the coronary collateral circulation on mortality: A meta-analysis" Eur Heart J 2011.

[Chevychelov]

OBESITY: Mother, Baby Risk Factors Predict Child's Obesity

By Todd Neale, Senior Staff Writer,
October 03, 2011

Action Points
Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.


Note that at age 7, children with four maternal and infant risk factors had a substantially greater risk of obesity than other children.
Review
ORLANDO -- Targeting four modifiable maternal and infant risk factors may make a large impact on reducing childhood obesity, researchers found.

The four factors were maternal smoking during pregnancy, gestational weight gain, breastfeeding duration, and infant sleep duration, according to Matthew Gillman, MD, of Harvard Medical School in Boston.

At age 7, children with adverse levels of all four risk factors had a substantially greater risk of obesity than those with healthy levels of all four (28% versus 4%). Gillman reported those findings at the Obesity Society meeting here.


"These four factors, which are potentially modifiable, explain a large proportion of obesity in childhood, and the implication is that, if we can mount interventions to change these things, we can go a long way toward preventing childhood obesity," Gillman said.

Several pre- and postnatal risk factors for childhood obesity have been identified, Gillman said, but there have been few studies that have examined the predictive value of combinations of risk factors.

To explore the issue, he and his colleagues turned to Project Viva, a longitudinal cohort study in Massachusetts looking at the health of women and their children.

The current analysis included 948 mother-child pairs who provided information both at baseline and when the child was 7-years-old.

The researchers chose to examine four factors -- all dichotomized for adverse and healthy conditions -- for their relationship with childhood obesity:
Maternal smoking during pregnancy (yes/no)
Gestational weight gain (excessive/not excessive)
Breastfeeding duration (less than 12 months/at least 12 months)
Infant sleep duration (less than 12 hours a day/at least 12 hours a day)


During pregnancy, 9% of the mothers smoked and 58% gained excessive weight. Most of the infants (71%) were breastfed for less than one year and 31% slept less than 12 hours a day.

All four of the risk factors were individually associated with an increased likelihood of obesity when the child was 7 (ORs 1.55 to 2.01), although the relationship reached statistical significance for infant sleep duration only (OR 2.01, 95% CI 1.24 to 3.25).

Overall, 6.9% of the children had adverse levels of none of the risk factors, 36.1% had one risk factor, 40.8% had two, 14.5% had three, and 1.9% had all four.

The overall rate of obesity at age 7 was 10.8%, ranging from a low of 4% for children with healthy levels of all four risk factors to a high of 28% for adverse levels of all four risk factors.

Similar trends were seen for body mass index (BMI) z-score, which ranged from 0.07 to 0.79, and percent body fat, which ranged from 23.2% to 26.5%.

The model was adjusted for maternal BMI and education, child race/ethnicity, and household income. Further adjustment for sugary drink intake, fast food intake, TV screen time, and physical activity did not have substantial effect on the findings.

The researchers calculated that if the population shifted from having two to four of these adverse risk factors to zero or one, 55% of the cases of childhood obesity would be avoided.

Gillman said that some studies of interventions to modify these factors have been performed and some are ongoing.

Infant sleep is modifiable, at least on a population level, by adjusting how parents put their babies to sleep, he said. An example would be teaching parents to rock their babies until they are almost asleep, putting them in their cribs, and allowing them to put themselves to sleep, rather than rocking them until they fall sleep.

More work needs to be done on reducing smoking during pregnancy, Gillman said. Most mothers will stop smoking when they know they are pregnant, but there is room for interventions for smoking cessation at or before the time of conception.

Support interventions using lactation consultants have been shown to be effective for increasing the initiation and duration of breastfeeding.

Although there is not one strategy proven to reduce gestational weight gain, many trials are ongoing, and Gillman said that he expects to see some consensus about effective approaches develop in the coming years.

[Chevychelov]

ECG 'Noise' Predicts Death After MI

By Chris Kaiser, Cardiology Editor,
October 03, 2011

Action Points
Explain that three computational biomarkers analyzing data from long-term Holter monitoring identifies individuals with non-ST-segment elevation acute coronary syndromes (NSTEMI ACS) at risk for cardiovascular death.


Note that these biomarkers rely on data already being collected and appear to independently add to traditional predictors.
Review
Certain ECG signals that were once considered "noise" are associated with a higher risk of death following a non-ST-segment elevation acute coronary syndrome (NSTEMI ACS), according to computational ECG analysis of the MERLIN-TIMI36 trial.

Each of three computational biomarkers derived from long-term Holter ECG signals were strongly associated with cardiovascular death, Zeeshan Syed, PhD, from the University of Michigan in Ann Arbor, and colleagues reported.

After adjusting for TIMI risk score, ejection fraction, and other ECG-based metrics, the computationally-generated biomarkers were still independently associated with cardiovascular death, according to the study published online in Science Translational Medicine.


"The main point of our study is that we are able to make better use of data that we're already collecting," Syed told MedPage Today.

"There's prognostic information buried in the noise, and it's almost invisible because of the sheer volume of the data," Syed said. "The sophisticated computational techniques allow us to home in on truly abnormal ECG signals. These patients with unstable hearts are at a greater risk of dying. Identifying them would allow physicians to initiate more aggressive treatment."

Researchers noted that current metrics such as echocardiography and left ventricular ejection fraction (LVEF) don't always correctly stratify ACS patients into high and low risk. The three computational biomarkers, when added to existing predictors, improved classification by 7% to 13%, they wrote.

About 2.5% of patients die within 90 days following an NSTEMI ACS. The rate increases to about 6% within a year.

The use of echo and a conservative threshold of less than 40% LVEF identifies 31.7% of these deaths, according to the study.

Although the majority of the patients identified by echo are at high risk, we are still missing more than two-thirds of these patients who will die," Syed said.

To better help identify these patients, Syed and colleagues used data mining and machine learning techniques to retrospectively search through 24-hour continuous ECGs from 4,557 heart attack patients enrolled in the MERLIN-TIMI36 trial.

They found that the ECG signals from many of the patients who later suffered cardiovascular death contained similar errant patterns that until now were dismissed as noise or simply undetectable.

The three computational biomarkers are:
Morphologic variability, which assesses myocardial instability by quantifying low-amplitude probabilistic variability in the shape of the ECG waveform over long periods of time
Symbolic mismatch, which quantifies the degree to which long-term ECG signals of individual patients are anomalous relative to those of other patients with a similar clinical history
Heart rate motif, which integrates the frequency with which high- or low-risk heart rate patterns reflecting autonomic function appear in a patient's ECG over long time periods.


In the unadjusted analysis, morphologic variability was the strongest predictor of death (HR 3.31, 95% CI 2.49 to 4.40, P<0.001), followed by symbolic mismatch (HR 2.36, 95% CI 1.73 to 3.22, P<0.001) and heart rate motif (HR 2.21, 95% CI 1.65 to 2.97, P<0.001).

Even after adjusting for traditional risk stratifying techniques, the computational biomarkers were still independently associated with dying compared with the other techniques and as well as compared with each other.

But Syed is not ready to do away with conventional risk stratifying techniques.

"Just as disease is multifactorial, we need to continue to apply multiple risk stratifying approaches including functional and electrical activity," Syed told MedPage Today.

One potential area where these biomarkers might help is in identifying candidates for implantable cardioverter defibrillators, he said.

But there is a spectrum of treatments, including drugs, stents, and devices, which are initiated based on assessment from traditional metrics. The hope of Syed and colleagues is that the computational biomarkers will help "to better stratify patients and define where they should fall within the spectrum of treatment."

Syed said he wants to test these biomarkers prospectively on patients in the hospital, and also on asymptomatic people at an increased risk for heart disease.

The study was limited because about 2,000 patients in the MERLIN-TIMI36 trial did not have continuous ECG data available.

In addition, some of the conventional risk metrics could not be assessed in the patient data, which reduced the size of the multivariate model.

Also, these findings are not generalizable to other populations, such as those with STEMI or heart failure, for example.

[Chevychelov]

OBESITY: Weight Counseling by PCPs Found Lacking

By Todd Neale, Senior Staff Writer,
October 04, 2011

Action Points
Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.


Note that this study of primary care visits documents that despite increases in the prevalence of obesity in the population, there were significant declines in the percentage of adult primary care visits with counseling for weight reduction, diet, and exercise.
Review
ORLANDO -- Even as rates of overweight and obesity rise, primary care physicians appear to be cutting back on weight counseling for their adult patients, researchers found.

From 1995 to 2008 -- when rates of overweight and obesity are estimated to have increased from 52% to 63% -- the percentage of primary care visits that included weight counseling dropped from 7.8% to 6.2% (OR 0.62, P<0.001), according to Chris Sciamanna, MD, MPH, of Penn State College of Medicine in Hershey, Pa.

The reduction was consistent in patients recognized by the physician to have hypertension, diabetes, or obesity, he reported at the Obesity Society meeting here.


During the same time period, there was not a drop-off in the percentage of visits that included tobacco counseling, which Sciamanna said indicates that one of the possible explanations for the reduction in weight counseling is a perception that it does not work.

To back that up, he pointed to a 2003 survey of primary care physicians that found that the treatment of obesity was rated as significantly less effective than therapies for nine out of 10 other chronic conditions.

"I think some of the problem is that we really don't know what works in primary care," Sciamanna said, adding that physicians need effective tools, including websites and programs, to guide the treatment of obese patients.

"Doctors really need to know what to say ... because these things are complicated and we're not trained to counsel," he said. "Unless you're going to change the way doctors are educated, we really need to know what exactly to say and what exactly to do."

In 2003, the U.S. Preventive Services Task Force recommended screening all adult patients for obesity and offering intensive counseling and behavioral interventions to promote weight loss for those who were obese.

The federal government has also set a Healthy People 2020 goal of increasing the proportion of obese-adult office visits that include counseling and education related to losing weight and living a healthy lifestyle.

But despite the guidance, previous studies have shown counseling rates to be low, Sciamanna said. To see if there's been an increase in recent years, he and his colleagues looked at data from the National Ambulatory Medical Care Survey, comparing 15,753 adult patients treated in 1995 to 1996 to 16,766 patients treated in 2007 and 2008.

The analysis was restricted to office-based visits to family physicians, general practitioners, and general internists.

As part of the study, physicians checked off services provided at each visit and what conditions each patient had.

After adjustment for patient and provider characteristics, the percentage of visits that included weight counseling fell by a relative 38% from the earlier to the later time period (OR 0.62, 95% CI 0.50 to 0.77), even for obese patients (from 39.9% to 29.9%).

There were similar trends for diet and exercise counseling as well.

Sciamanna noted some limitations of the analysis, including the uncertainty of the actual body mass index of the patients and the unclear definition of weight counseling as selected by the physicians.

In addition, he said, it is assumed that physicians under-reported the rate of obesity -- about 11% for both time periods.

[Chevychelov]

OBESITY: When Kids Are Young Moms Exercise Less

By Todd Neale, Senior Staff Writer,
October 04, 2011

Action Points
Note that these studies were published as abstracts and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.


Note that these studies indicate that having young children present in the home significantly reduced the physical activity level of parents.
Review
ORLANDO -- Mothers of young children get less exercise than women who do not have children at home, researchers found.

Women with a dependent child younger than 6 participated in an average of 6.38 minutes less moderate-to-vigorous intensity physical activity each day (P<0.05), according to Kristi Adamo, PhD, of the Children's Hospital of Eastern Ontario Research Institute.

That works out to about 45 minutes less exercise per week, she reported at the Obesity Society meeting here.

"I think, at least clinically, that's pretty important," Adamo said, noting that the Canadian national guidelines call for at least 150 minutes of moderate-to-vigorous physical activity per week for adults.


"Future research should continue to focus on strategies to encourage women with young children to establish or re-engage in a physically active lifestyle," she added.

Having dependent children at home has been proposed as a contributing factor to the low physical activity levels observed around the world, although results of previous studies have been mixed regarding the impact of children's age, the number of children, and the sex of the parent, according to Adamo.

To explore the issue, she and her colleagues turned to the Canadian Health Measures Survey for 2007 to 2009. Their analysis included 2,315 men and women ages 20 to 65 who agreed to wear an accelerometer to assess physical activity levels. Only those who wore the device for at least 10 hours a day for at least four days were included.

Overall, 47% of women and 42% of men had a dependent child at home.

When children of all ages were grouped together, having a child at home or having more than one child at home was not associated with the level of physical activity in either men or women.

However, when a child at home was younger than 6, women got significantly less exercise than women with no children at home in a univariate analysis.

The significant difference held up in a model that adjusted for parental age, marital status, household income, hours worked per week, and body mass index.

Women with a child younger than 6 were also significantly less likely to meet the Canadian national recommendation for moderate-to-vigorous physical activity (OR 0.50).

In a univariate analysis, men with a child ages 6 to 11 participated in significantly less physical activity compared with those with no children at home (P<0.05). After adjustment for potential confounders, however, the difference no longer reached statistical significance.

As a possible explanation for the apparently stronger influence of children on the level of physical activity in women compared with men, Adamo said that mothers are typically the primary caregivers when children are young and, in many cultures, the expectations placed on mothers are different from those placed on fathers.

She noted some limitations of the study, including the cross-sectional design, the low response rate and accelerometry compliance in the national survey, and the limited number of variables that could be included in the models.

The findings appear to gain some support from another analysis presented at the meeting by Brooke Tompkins, MA, of the University of North Carolina at Chapel Hill.

She and her colleagues looked at the association between having children in the home and adherence to a standard behavioral weight loss intervention. The study included 127 participants in the control arm of the Step Up study. The intervention included periodic group sessions, a reduction in the intake of calories and fat, and a progression to 300 minutes of moderate-to-vigorous physical activity per week.

Most of the participants (83.5%) were female.

Through six months, the average percentage of weight lost was greater in the participants who did not have children at home after adjustment for gender, race, and marital status (12.32% versus 9.87%, P=0.03).

Those with children attended significantly fewer group sessions, submitted fewer self-monitoring diaries, recorded fewer days of diet, and reported fewer days of exercise (P<0.05 for all).

"If you're expected to come to a weight loss intervention in person, then it might not be feasible for parents," Tompkins said. "So we need to look for other interventions, maybe something online, that are just a little bit easier for parents to do."

[Chevychelov]

OBESITY: Three Questions May Peg Type 2 Diabetes Risk

By Todd Neale, Senior Staff Writer,
October 05, 2011

Action Points
Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.


Explain that a study found that being age 55 or older, having a body mass index (BMI) greater than 30, and having a family history of diabetes predicted a higher risk of developing type 2 diabetes over five years, compared with those who were under 55 with a BMI less than 25 and no family history of diabetes.


Note that although the three-item tool was simpler than the seven-item instrument advocated by the American Diabetes Association, the two instruments were not directly compared in this study.
Review

ORLANDO -- A simple, three-item instrument may be enough to accurately identify those individuals who are at high risk for type 2 diabetes in the next five years, researchers found.

Individuals who were 55 or older, were obese -- with a body mass index (BMI) greater than 30 -- and had a family history of diabetes had a 19.9% risk of developing type 2 diabetes over five years of follow-up, according to Harold Bays, MD, of the Louisville Metabolic and Atherosclerosis Research Center in Kentucky.

Younger individuals with a BMI less than 25 and no family history of the disease, however, had an almost negligible five-year risk (0.3%), Bays reported at the Obesity Society meeting here.

The three-item screener might have advantages over more established tools that use seven or more variables because it might be a less cumbersome way for patients to identify undiagnosed diabetes and start treatment, he said.

The simplified tool emphasizes that weight loss is an option that patients can use to reduce their risk of type 2 diabetes, Bays said.

"I think that's a crucial message to be sent to patients," he said. "It's something that they can proactively address in order to reduce their risk of a serious disease."

There are several algorithms available to estimate the risk of developing type 2 diabetes, including the American Diabetes Association's (ADA's) Diabetes Risk Test, which includes seven variables -- age, race, family history of diabetes, obesity, physical activity, hypertension, and gestational diabetes.

To look at whether it would be feasible to simplify that score with just three variables -- age, family history, and obesity -- Bays and his colleagues turned to the Study to Help Improve Early Evaluation and Management of Risk Factors Leading to Diabetes (SHIELD), a five-year population-based survey.

A baseline survey was sent in 2004 to 22,001 adults in the U.S, with annual follow-up questionnaires sent through 2009.

From the respondents who were free from diabetes at baseline and provided information at the five-year follow-up, the researchers identified high-risk and low-risk groups according to age, family history, and obesity.

Overall, there were 290 high-risk individuals who were 55 or older, were obese, and had a family history of diabetes, and 408 low-risk individuals who were younger than 55, with a BMI less than 25 and no family history of diabetes.

Through five years of follow-up, 19.9% of the high-risk individuals reported developing type 2 diabetes, compared with only 0.3% of the low-risk individuals (P<0.0001).

In an interview, Peter Katzmarzyk, PhD, of the Pennington Biomedical Research Center in Baton Rouge, commented that the simplified algorithm "would certainly expedite the identification of higher-risk patients for type 2 diabetes."

However, the evidence is still preliminary, he said, and future studies should compare the discriminatory ability of the full ADA algorithm with the three-item tool and also test the proposed instrument in a more diverse patient population, as more than 90% of the participants in SHIELD were white.

"But I do think it's a very good first step," Katzmarzyk said.

Bays noted that if a clinician is not currently doing any assessment for type 2 diabetes risk, then whether the simplified tool is inferior or superior to the full algorithm is irrelevant. Those using the full model should probably keep using it, he said, but those who are not using anything might be motivated to start using the simpler option.

Bays and colleagues noted that the analysis was limited in that the diagnosis of diabetes and other conditions was self-reported, and because household panels like SHIELD tend to under-represent very wealthy and very poor populations and do not include military personnel or institutionalized individuals.

[Chevychelov]

Parsing Rivaroxaban Data Raises Efficacy Questions

By Chris Kaiser, Cardiology Editor,
Reviewed by
October 05, 2011

Review

Whether rivaroxaban (Xarelto) is noninferior to warfarin for preventing strokes in patients with atrial fibrillation could depend on how you read the data, two physicians charge.

In the ROCKET-AF trial, the overall rate of stroke and blood clots per 100 patient-years was 2.12 in the once-daily 20 mg rivaroxaban arm compared with 2.42 in the warfarin arm, which reached significance for noninferiority but not for superiority.

The trial showed similar positive data for the per-protocol analysis: rivaroxaban was superior to warfarin with a stroke/blood clot rate of 1.71 per 100 patient-years versus 2.16, again being significant for noninferiority but not for superiority.

However, an analysis of the data by an FDA reviewer "identified important issues affecting interpretation of these results," Thomas R. Fleming, PhD, and Scott S. Emerson, MD, PhD, from the University of Washington in Seattle, wrote in a Perspective piece in the Oct. 6 issue of the New England Journal of Medicine.

Fleming and Emerson noted the importance of the "constancy assumption" in noninferiority trials and how ROCKET-AF might have violated this.

For example, they wrote, patients in the trial were at a higher risk than those who participated in the reference trial.

Other concerns about nonconstancy include the 5% of patients lost to follow-up and the lower-than-average number of patients in the therapeutic range for those on warfarin (55%).

The writers suggested that the "noninferiority margin might need to be modified" because of nonconstancy problems.

Fleming and Emerson also stressed the need for per-randomization analyses in noninferiority trials.

"The importance of per-randomization analyses is very apparent in ROCKET-AF," they wrote, because the on-treatment analysis followed observation at two days after randomization treatment stopped. They said that this time frame is "likely to miss events related to inadequate coagulation during the transition to alternative treatment."

In fact, those in the rivaroxaban arm had higher rates of stroke and blood clots compared with the warfarin arm between two and seven days after stopping treatment with the direct oral factor Xa inhibitor.

Superiority was not established in the per-randomization analysis (RR 0.88, 95% CI 0.78 to 1.03) and a "positive trend seen in the per-protocol analysis of myocardial infarctions was similarly attenuated."

They also noted that a rise in mortality after stopping rivaroxaban treatment "further complicates the noninferiority assessment in ROCKET-AF."

The two commenters compared ROCKET-AF to the RE-LY trial, which compared different doses of twice-daily dabigatran (Pradaxa) in patients with atrial fibrillation with warfarin.

Not only did more patients on warfarin in the RE-LY trial (66%) have a higher average time in therapeutic range compared with ROCKET-AF, but the per-randomization relative risk of stroke or blood clot for those on dabigatran was 0.66 (95% CI 0.53 to 0.82).

"The results robustly support the superiority of dabigatran over warfarin" and Fleming and Emerson asked whether rivaroxaban should now be required to show noninferiority to the direct oral thrombin inhibitor dabigatran.

"The RE-LY results and uncertainty about the validity of the constancy assumption in ROCKET-AF raise concerns that rivaroxaban could be inferior to either dabigatran or warfarin, particularly when the latter is 'used skillfully,'" they wrote.

The FDA analysis also questioned the once-daily dosing of rivaroxaban, saying it wasn't "supported by the available pharmacokinetic and pharmacodynamic data."

All of these problems with ROCKET-AF "could lead to an unproven treatment displacing an effective treatment on the basis of overzealous promotion of more convenient once-daily dosing," they said.

Despite the negative analysis by one of the FDA reviewers, the panel as a whole recommended approval of rivaroxaban. The FDA is expected to make a ruling by Nov. 5.

[Chevychelov]

OBESITY: Teens Clueless About Fast Food Content

By Todd Neale, Senior Staff Writer,
October 05, 2011

Action Points
Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.


Explain that the vast majority of adolescents underestimate the calorie content of meals purchased at fast food restaurants.


Point out that a greater actual calorie count was associated exponentially with a greater underestimate on the part of the participants.
Review
ORLANDO -- The vast majority of adolescents underestimate the number of calories contained in the meals they purchase at fast food restaurants, researchers found.

Of those ages 11 to 20 surveyed outside of fast food chains in four U.S. cities, 80% underestimated the actual calorie content, and 30% misjudged the amount by at least 500 calories, Jason Block, MD, of Harvard Medical School in Boston, reported at the Obesity Society meeting here.

Only 14% of the participants noticed any nutritional information in the restaurant, and fewer still -- 3% -- saw and used the information when ordering.


The findings, Block said, raise concerns that even when calorie information is available on the menus of restaurant chains with at least 20 locations nationwide, as mandated by the Affordable Care Act, people might not use it.

That concern is supported by a similar study conducted in New York City, which found that although most teens noticed the calorie information on menus after such a policy was adopted, only 9% said they considered the information when choosing their food.

As part of the baseline phase of a study to evaluate the new federal regulation, Block and his colleagues surveyed adolescents at fast food restaurants in Boston, Springfield, Mass., Providence, R.I., and Hartford, Conn.

In each city, the researchers visited 10 restaurants three times each, for a total of 120 visits during the study. The chains included McDonald's, Burger King, Subway, Dunkin' Donuts, and Wendy's.

Overall, 36% of the 547 individuals approached agreed to participate in the study. Their mean age was 16 and they were ethnically diverse -- 16% white, 36% black, 28% Hispanic, 6% Asian, and 14% other or multiracial. Based on self-reported height and weight, 26% were overweight or obese, which Block acknowledged seemed low.

The researchers collected the participants' receipts to calculate the calorie content of their meal and administered a short survey on the awareness and use of nutritional information in the restaurant, as well as on the estimated calorie content of the food purchased.

The average actual calorie content of the meals was 746, with 28% of the participants purchasing 1,000 calories or more.

The average estimated calorie content, however, was only 464. The underestimation was consistent across restaurant chains.

A greater actual calorie count was associated exponentially with a greater underestimate on the part of the participants. Those who consumed 1,000 calories, for example, underestimated their meal by an average of 350 calories. For those who consumed 1,500 calories, the estimate was short by 700 calories.

The researchers also asked the participants to estimate how many calories are needed each day to maintain a healthy diet. According to lenient standards, 68% of them were accurate (1,000 to 3,000 calories), 23% underestimated, and 9% overestimated.

Those who underestimated the daily requirement underestimated their meal content by 28% compared with those who were accurate.

On the flip side, those who overestimated the daily requirement overestimated the calorie count by 39%.

These findings, Block said, support the use of an anchoring statement on menus, which, according to federal law, will tell customers that the recommended daily intake is 2,000 calories.

The study "suggests that perhaps this might be a promising, helpful thing for people to put into context the calorie content of meals," Block said.

He noted some limitations of the analysis, including the low response rate and the inability to measure the actual consumption of food. The researchers also were not able to randomly select participants or to sample customers at the drive-thru window.

[Chevychelov]

OBESITY: Sleep Apnea Cut With Weight-Loss Program

By Todd Neale, Senior Staff Writer,
October 06, 2011

Action Points
Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.


Explain that patients with obesity and type 2 diabetes participating in a sleep substudy lost significantly more weight with an intensive lifestyle intervention program than those in the control group and also significantly reduced their apnea-hypopnea index.


Note that improved apnea-hypopnea index tracked with the amount of weight lost but still remained significantly improved for the lifestyle intervention group compared with controls at four years despite gaining back about half the weight lost in the first year.
Review

ORLANDO -- An intensive lifestyle intervention to get obese patients with type 2 diabetes to lose weight had long-lasting effects on obstructive sleep apnea as well, according to results from an ancillary study to the Look AHEAD trial.

Through four years, patients undergoing the intensive intervention maintained about a four-point reduction in apnea-hypopnea index, compared with a sustained four-point increase in the control group, according to Gary Foster, PhD, of Temple University in Philadelphia.

Patients with the most severe obstructive sleep apnea at baseline had the largest gains through four years (P<0.0001), he reported at the Obesity Society meeting here.

Foster noted, however, that with a mean apnea-hypopnea index of 20.5 -- indicating moderate obstructive sleep apnea -- at baseline among the patients, the reductions seen over the course of the study would not, on average, be enough to replace other treatments.

"I don't want to give you the impression that this is an alternative treatment to [continuous positive airway pressure]," he said. "It's probably a complementary treatment."

The findings came from Sleep AHEAD, an ancillary study of the Look AHEAD trial, which compared an intensive lifestyle intervention with diabetes support and education for weight loss in obese patients with type 2 diabetes.

The sleep study was designed to evaluate whether weight loss would be associated with improvements in sleep-disordered breathing, which had been demonstrated in observational studies and smaller randomized trials.

Participants in Look AHEAD were screened with a questionnaire designed to identify patients at increased risk for obstructive sleep apnea. The researchers excluded patients currently being treated for the condition or who had undergone surgery for it, but included those with untreated obstructive sleep apnea.

All 305 patients selected for the sleep study underwent overnight polysomnograms at home. Those with an apnea-hypopnea index of less than 5 were considered free from obstructive sleep apnea. Scores of 5 to less than 15 were considered mild, 15 to less than 30 moderate, and 30 or more severe.

The mean score was 20.5. Only 13.4% of the patients did not have obstructive sleep apnea. Another 33.5%, 30.5%, and 22.6% had mild, moderate, and severe symptoms, respectively.

After one year, patients undergoing the intensive lifestyle intervention lost an average of 24 pounds, whereas those in the control group had no weight loss (P<0.0001).

At the same time, patients in the intervention group had about a six-point reduction in apnea-hypopnea index, compared with a four-point increase in the controls (P<0.0001).

Through four years, patients in the intervention group gained back about half of the weight that was lost, although they sustained a four-point reduction in apnea-hypopnea index. The controls sustained a four-point increase in the index.

At four years, a greater percentage of patients in the intervention group improved their obstructive sleep apnea category from baseline (about 40% versus 15%) and had a remission of apnea symptoms (20% versus 3%).

Although the change in apnea-hypopnea index was significantly related to the weight change, there was still a significant reduction in symptoms even after the change in weight was accounted for (P=0.001).

That indicates that the intervention had an effect on obstructive sleep apnea that was separate from the weight loss, Foster said.

"The likely hero, I think, is fitness," he said, noting that another study has shown that even in the absence of weight loss, changes in fitness can drive changes in apnea-hypopnea index.

[Chevychelov]

OBESITY: CVD Risk Cut With Rejected Weight-Loss Drug

By Todd Neale, Senior Staff Writer,
October 06, 2011

Action Points
Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.


Note that this study demonstrates that weight loss with combination naltrexone/bupropion was associated with improved 10-year risk for overall CV disease, CHD, MI, and CHF as measured by published risk equations.


Point out that confirmation that reduced CV risk is actually associated with improved outcomes will require a prospective trial.
Review
ORLANDO -- It appears that the investigational weight-loss combination of naltrexone standard release and bupropion standard release (Contrave) reduces the predicted 10-year risk of cardiovascular events, an analysis of four phase III trials showed.

Using an average of six major risk prediction models, one year of treatment with the combination in low-risk overweight and obese patients reduced the absolute 10-year risk of cardiovascular events by 0.17%, compared with a reduction of 0.05% with placebo (P<0.05), according to Robert Chilton, DO, of the University of Texas Health Science Center at San Antonio.

Significant reductions were also seen with the combination in the predicted 10-year risk of coronary heart disease, MI, and congestive heart failure relative to placebo (P<0.01 for all), he reported at the Obesity Society meeting here.


The findings, he said, provide confidence that the drug combination will show a benefit in an upcoming cardiovascular outcomes trial.

Naltrexone/bupropion has been shown in randomized trials to be effective in getting overweight and obese patients to lose weight compared with placebo.

The FDA, however, went against the recommendations of one of its advisory committees and did not approve the combination because of concerns about increases in blood pressure in patients taking the active treatment.

The agency told the maker of the drug, Orexigen, that it would need to conduct a cardiovascular outcomes trial to ease doubts about safety before the drug could be approved.

Initially, Orexigen was hesitant to conduct such a trial and said it would no longer seek approval for the combination in the U.S., saying the requested trial "is unprecedented and would generate significantly more information than is necessary or feasible."

The company continued meeting with the FDA, however, and said in a Sept. 20 statement that the design requirements for a cardiovascular outcomes trial "are reasonable and feasible and provide the certainty required to reinitiate development of Contrave."

The proposed trial would enroll a population of overweight and obese individuals with an estimated annual risk of major cardiovascular events of 1 to 1.5%.

According to Orexigen, the FDA said that the drug could be approved if an interim analysis of the trial excludes any unacceptable cardiovascular risk.

"Both FDA and Orexigen estimate that such a study would require approximately 87 total events by the interim analysis to enable resubmission of the New Drug Application for approval," according to a statement from the company. "Orexigen estimates that the entire study would require fewer than 10,000 patients and less than two years from study start to the interim analysis."

The trial is expected to start in the first half of 2012.

According to Chilton, he and his colleagues planned to look at the effect of treatment with naltrexone/bupropion on the predicted 10-year risk of cardiovascular events even before the company submitted data to the FDA for consideration.

The analysis reported at the meeting pooled data on 3,363 patients who participated in the phase III Contrave Obesity Research program, which included four randomized, placebo-controlled trials lasting 56 weeks. Patients on active treatment received 32 mg naltrexone SR/360 mg bupropion SR.

The researchers estimated the change in 10-year risk of cardiovascular events after one year of treatment using six established risk prediction tools -- the Framingham, Fremantle, QRisk2, Reynolds, SCORE, and U.K. Prospective Diabetes Study scores.

The patient population had a low cardiovascular risk at baseline. The mean age was about 46, the mean body mass index was 36 kg/m2, and 12 to 13% had type 2 diabetes.

Averaging the six risk scores together, the predicted 10-year cardiovascular risk at baseline was 5.8% in the drug group and 5.6% in the placebo group.

As seen previously, there was significantly greater weight loss in the active treatment group after one year (7% versus 2.3%, P<0.001).

Using all six of the risk scores, the predicted 10-year risk of cardiovascular disease events dropped to a greater extent with active treatment than with placebo after one year in the overall population, as well as in patients with type 2 diabetes and those without the disease.

There was no significant effect on the predicted risk of ischemic heart disease, cardiovascular mortality, or stroke.

Chilton said that the findings suggest that a cardiovascular outcomes trial will show that the drug combination is safe.

"In a year, we do show risk benefits for cardiovascular reduction in events, so the drug would be something worthwhile," he said, adding that he would prefer having his patients lose weight without drugs.

"Weight loss is very important. If you can do it without the drug, that'd be better yet, but if you need a crutch for a short time this is not a bad option and these are drugs [naltrexone and bupropion] that are both well known," he said. "But I think long term you still need to make a new plan in life and change your entire lifestyle."

Although he did not address the naltrexone/bupropion combination specifically, Jonathan Purnell, MD, an endocrinologist at Oregon Health & Science University in Portland, said that the recent rejections of three investigational weight-loss drugs -- including topiramate/phentermine (Qnexa) and lorcaserin (Lorqess) -- is "very discouraging."

"We lack tools to effectively help people maintain weight loss, even if we have the time and the resources to talk about lifestyle, and we know that lifestyle alone has a very modest impact on sustained weight loss," said Purnell, a spokesman for the Obesity Society.

"Lacking very effective tools -- and a lot of the studies show that these drugs are effective -- is very frustrating for both us as clinicians as well as patients."

[Chevychelov]

FDA Okays Combo Pill for Diabetes, Cholesterol
The FDA has approved a fixed-dose combination tablet that combines the diabetes drug sitagliptin with simvastatin, under the brand name Juvisync.
[Ссылки доступны только зарегистрированным пользователям ]

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Higher HDL Lowers Cardiovascular Risk in Type 2 Diabetes

By Charles Bankhead, Staff Writer,
October 07, 2011

Today Action Points
Explain that a study found that patients with type 2 diabetes who had higher baseline HDL levels or increased HDL from baseline by whatever means had a lower risk of hospitalization for cardiovascular disease than those with lower HDL levels.


Note that while an observational study cannot prove causality, type 2 diabetics whose HDL decreased by ≥6.5 mg/dL showed a significantly increased risk of hospitalization for cardiovascular disease.
Review
Higher HDL levels in patients with type 2 diabetes significantly reduced the odds of hospitalization related to cardiovascular disease, data from a large cohort study showed.

Every 5 mg/dL increase in baseline HDL was associated with a 6% reduction in the CVD hospitalization risk. During a mean follow-up of 55.8 months, each 5 mg/dL increase in HDL was associated with a 4% lower risk.

A categorical analysis centered on a baseline HDL showed that a ≥6.5 mg/dL decrease was associated with an 11% increase in CVD risk, whereas a ≥6.5 mg/dL increase reduced the CVD hazard by 8%, as compared with individuals who remained within 6.4 mg/dL of baseline values.


"Our results add to the growing body of evidence that increasing the HDL cholesterol levels might be an important strategy for CVD risk reduction," Gregory A. Nichols, PhD, of Kaiser Permanente Center for Health Research in Portland, Ore., and co-authors wrote in an article published online in the American Journal of Cardiology.

"The prevention of HDL cholesterol decreases could be equally important," they said.

Patients with type 2 diabetes have a substantially elevated risk of CVD, with estimates ranging as high as 87% greater compared with nondiabetic adults. Reduction of LDL cholesterol remains the focus of lipid management to reduce CVD risk.

However, clinical trials of intensive LDL-lowering with statin drugs have shown that at least 10% of patients have major CVD events, the authors noted in their introduction.

Glycemic control remains the focus of diabetes management, although intensive hypoglycemic treatment has failed to reduce CVD risk in type 2 diabetics, they continued. The findings suggest that treatment targets other than LDL and hemoglobin A1c deserve consideration.

HDL cholesterol offers one potential target for CVD risk reduction in patients with type 2 diabetes. About half of diabetic patients have low HDL levels, an observation that has generated speculation that raising HDL levels might substantially reduce CVD risk in that patient population.

Clinical studies have yet to produce clear evidence that increasing HDL levels will reduce CVD risk in type 2 diabetes, possibly because of the lack of safe and effective agents, the authors continued.

Attempts to use drugs to raise HDL have generally been unsuccessful. Several trials of HDL-raising drugs have been stopped because of an increase in cardiovascular events and mortality including ILLUMINATE and AIM-HIGH.

The search continues, however, for a safe HDL-raising drug. Researchers reported at this year's European Society of Cardiology meeting positive results for such a drug in the phase IIb dal-VESSEL trial, and the DEFINE trial, reported at last year's American Heart Association meeting, showed good results for anacetrapib in terms of safety and efficacy.

In addition, the FDA on Oct. 7 approved Juvisync (sitagliptin and simvastatin), the first combination drug to treat type 2 diabetes and high cholesterol in one tablet.

In an effort to inform on the association between HDL level and CVD risk in type 2 diabetes, Nichols and colleagues performed a retrospective cohort study of 30,067 members of the Kaiser Permanente Northwest and Georgia regions. All patients had type 2 diabetes and had at least two HDL cholesterol measurements during 2001 to 2006.

Investigators analyzed clinical data on the patients through 2009 to determine whether change in HDL cholesterol influenced subsequent risk of CVD-related hospitalization. They examined HDL cholesterol continuously and by three categories: HDL increase ≥6.5 mg/dL from baseline, decrease ≥6.5 mg/dL, and no increase or decrease >6.4 mg/dL.

During follow-up, 61% of the patients had HDL levels that remained within 6.4 mg/dL of baseline values, 21.6% had ≥6.5 mg/dL increases in HDL, and 17% had ≥6.5 mg/dL decreases.

The authors found that 3,023 (10.1%) patients had CVD-related hospitalizations during the follow-up period. After multivariate adjustment, they found that every 5 mg/dL greater baseline HDL level was associated with a statistically significant 6% reduction in the hazard for CVD hospitalization (P<0.0001), and each 5 mg/dL increase from baseline was associated with a 4% reduction in CVD risk (P<0.003).

The categorical analysis showed that every 6.5 mg/dL increase in HDL during follow-up was associated with an 8% reduction in CVD risk, which did not achieve statistical significance (P=0.077). However, each 6.5% or greater decrease in HDL was associated with a significant 11% increase in the CVD hospitalization hazard (P=0.047).

Acknowledging the study's limitations, the authors wrote that an observational study cannot prove causality. They also noted that they could not determine the reasons for changes in HDL levels or whether the changes were maintained throughout the follow-up period.

In addition, 24% of patients with type 2 diabetes could not be included in the study because they did not have two HDL measurements.

"Despite these limitations, we have concluded that the changes in HDL cholesterol are associated with changes in the risk of CVD hospitalizations," the authors wrote in conclusion. "Additional study is needed to understand the role of improving HDL cholesterol in a multifactorial prevention strategy."

[Chevychelov]

OBESITY: No-Cal Drinks Yield Bigger Weight Loss

By Todd Neale, Senior Staff Writer,

Action Points
Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.


Point out that in this study, obese patients who replaced caloric beverages with water or diet beverages were more likely than controls to achieve a clinically meaningful weight loss at six months.
Review

ORLANDO -- Replacing calorie-laden beverages with water or diet drinks may be effective at shedding weight and improving other cardiometabolic parameters in the short term, a randomized trial showed.

In the three-arm trial, there were no significant between-group differences in the percentage of weight lost over six months, but participants in the combined substitution groups were significantly more likely to lose at least 5% of their body weight (OR 2.1, P<0.05) than those who were told only to make healthy dietary choices (the control group), according to Deborah Tate, PhD, of the University of North Carolina's Gillings School of Global Public Health in Chapel Hill.

Participants in the substitution groups were told to replace at least two caloric drinks a day with either water or diet beverages.

Those in the water group had significantly greater improvements in systolic blood pressure and fasting glucose compared with the controls (P<0.05 for both), Tate reported at the Obesity Society meeting here.

"Replacing caloric beverages with noncaloric alternatives, without intensive monitoring of other diet and physical activity, resulted in small but significant weight changes that may be substantial if applied at a population level," Tate said.

Data from the National Health and Nutrition Examination Survey (NHANES) have shown that about 60% of adults report drinking sugar-sweetened beverages, and that adults consume an average of 300 calories per day from such drinks.

To see whether substituting noncaloric alternatives for caloric drinks could make a difference in weight loss, Tate and colleagues conducted the CHOICE (Choose Healthy Options Consciously Everyday) study.

Participants were overweight or obese (body mass index 25 to less than 50 kg/m2) and ages 18 to 65 (mean 42). To enter the study, they had to report consuming at least 280 calories per day from caloric beverages at baseline, not counting unsweetened milk.

The researchers randomized 315 people -- 105 in the control group, 104 in the diet beverage group, and 106 in the water group.

All three groups attended a monthly group session. The control group received information on making healthy dietary and lifestyle choices, but no guidance was given regarding drinks.

The focus of the sessions in the two substitution groups was on replacing at least 200 calories per day from drinks as a means to lose weight. The participants received handouts covering the information that was being discussed in the sessions with the control group. The researchers provided monthly supplies of either bottled water or diet beverages of the participants' choosing.

Through six months, participants in the diet beverage group cut an average of 218 drink calories per day, those in the water group cut an average of 148, and those in the control group cut an average of 86. The differences between the substitution groups and the control group were both significant (P<0.05).

Food intake decreased slightly in all three groups.

Looking at the substitution groups individually, only the participants in the diet beverage group were more likely to lose 5% or more of their body weight (OR 2.3, P<0.05). That is likely the result of better adherence to drink replacement compared with the water group, Tate said.

Blood pressure, fasting glucose, and hydration improved in both substitution groups, although the only significant differences versus the control group were in the water group -- for systolic blood pressure and fasting glucose.

Tate acknowledged that the study was limited by the predominantly female patient population (85%), the use of self-reported measures of diet, and the short duration.

[Chevychelov]

OBESITY: Girls Happy With Their Bodies Don't Binge Eat

By Todd Neale, Senior Staff Writer,
October 07, 2011

Action Points
Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.


Explain that among overweight adolescent girls, those who are more satisfied with their bodies appear to be less likely to develop binge eating disorder.


Note that girls who were satisfied with their bodies gained significantly less body mass than their less-satisfied peers.
Review
ORLANDO -- Among overweight adolescent girls, those who are more satisfied with their bodies appear to be less likely to develop binge eating disorder, researchers found.

Through 11 years of follow-up, girls who said they were pretty much, a lot, or totally satisfied with their bodies had 61% lower odds of meeting criteria for the eating disorder compared with those who were only a little or not at all satisfied (OR 0.39, 95% CI 0.24 to 0.64), according to Kendrin Sonneville, ScD, RD, of Children's Hospital Boston.

They also gained significantly less body mass (0.1 kg/m2 less per year), Sonneville reported at the Obesity Society meeting here.


"This study builds on the existing literature that recognizes body dissatisfaction as a risk factor for negative outcomes during adolescence," she said. "Body satisfaction may be a salient target for both obesity and eating disorder prevention."

Dissatisfaction with one's body -- which is common and even normative in adolescent girls, according to Sonneville -- has been associated with various adverse outcomes, including disordered eating, low self-esteem, and depressive symptoms. Rates of dissatisfaction are particularly high among girls who are overweight or obese.

Body satisfaction, on the other hand, has been associated with fewer unhealthy weight control behaviors and higher levels of physical activity. It also has been tied to less weight gain among overweight and obese adolescent girls, who, nevertheless, are more likely to report binge eating.

To explore the relationship between body satisfaction and binge eating disorder, Sonneville and her colleagues examined data from the Growing Up Today Study (GUTS), an ongoing study of the offspring of women in the Nurses Health Study II. All GUTS participants were 9 to 15 years old when the study began in 1996.

The current analysis included 1,559 girls from the 1996 to 2007 waves of GUTS who were overweight or obese at baseline. Their mean age was 11.8 and the mean BMI was 23.7 kg/m2.

Body satisfaction was assessed using a single question: "In the past year, how happy have you been with the way your body looks?"

Answers ranged from not at all to totally. The 57.2% answering pretty much, a lot, or totally were considered to be satisfied with their bodies.

Binge eating disorder was defined as at least weekly binges that involved eating an amount of food that the girl would be embarrassed about if someone saw her eating it, accompanied by a feeling of being out of control. Overall, 1.7% of girls had the disorder at baseline and were excluded from further analysis.

During the 11-year follow-up, the mean BMI change was 5.1 kg/m2.

About one in every 10 girls (9.5%) met criteria for binge eating disorder at least once during follow-up.

After adjustment for age, BMI, TV viewing, and maternal overweight or obesity, girls who were satisfied with their bodies gained less weight and were less likely to develop binge eating disorder during follow-up compared with their less satisfied peers.

The level of satisfaction seemed to matter, as the attenuation of the BMI increase and the reduction in the odds of developing binge eating disorder were greater as satisfaction increased (P<0.05 for both trends).

For example, girls who were a lot or totally satisfied with their bodies gained 0.13 fewer BMI units than those who were not at all satisfied, and were 85% less likely to develop binge eating disorder (OR 0.15, 95% CI 0.06 to 0.37).

Sonneville acknowledged some limitations, including the use of self-reported data, the measurement of body satisfaction using a single question, and the lack of racial/ethnic diversity in the sample (94% of participants were white).