Arya M. Sharma, MD

Yesterday, on the first day of the 1st Caribbean Obesity Forum, I presented various talks on obesity - its economic implications, its assessment and the need for firmly anchoring obesity treatment in primary care.

Interestingly, several family doctors in the audience raised the interesting issue that here on Barbados (as probably on other islands) many patients are actually quite happy with their weights.

One family physician noted in his presentation the case of an overweight woman, who presented in his practice with diabetes. A few weeks after starting her on metformin, she came back considerably distressed about the fact, that she had now lost a few kilos. He noted that despite explaining out that her diabetes was now under control and her blood pressure had improved, she remained unconvinced about the benefits of being on this treatment. To her, losing weight equated directly with being unhealthy and ‘less sexy’ to her husband.

This topic came up several times during the day, where the issue of how to address obesity related health problems in a culture, where excess weight is considered both physically attractive and a sign of good health - never mind that the Caribbean (as pointed out by other speakers) now has some of the highest diabetes rates in world - I have heard Jamaica referred to as the world capital of foot amputations.

The notion of obesity as a sign of good health of course is not that surprising - especially in countries where malnutrition, infectious diseases, gut parasites, and other ‘wasting’ conditions, are endemic. Being skinny is a sure sign of sickness and weight loss is most alarming.

One discussant reminded me of the African practice of fattening rooms, where brides-to-be would be sequestered and overfed in order to be their ‘best weight’ on their wedding day - the exact opposite of Western societies, where brides wanting to lose weight provide healthy profits for the weight-loss industry.

Obviously, in such a setting, the very idea that excess weight may adversely affect pregnancy outcomes, is clearly a hard sell - as noted by the colleague speaking on the issue of epigenetic programming in utero.

In the discussions, I did point out that while we certainly did not have an issue with women not wanting to lose weight (in fact our challenge is perhaps the opposite - convincing many women that the few extra pounds they would so desperately like to shave off their butts and thighs may actually protect them from diabetes and other health problems), we do have a problem with men trivialising or denying the problem.

These learnings are nevertheless important to me, especially when practicing in a country like Canada, where we see patients with a wide range of ethnic and cultural backgrounds.

As clinicians, let us be aware that when some of our patients appear unconcerned about their weight-realated health problems, they may not simply be unmotivated to consider obesity treatments - they (and their family and friends) may actively oppose and resist them.

AMS
Bridgetown, Barbados

As regular readers will be well aware, our recent publications on the Edmonton Obesity Staging System clearly show that BMI alone is a rather poor measure of mortality risk associated with excess weight.

Thus, according to our analyses of the NHANES population, 20-30% of obese individuals (Stage 0/1) had virtually no increased mortality risk even over the almost 20 year observation period, compared to Stage 2/3 individuals, who had substantially increased risk. Conversely, even in the ‘overweight’ category (BMI 25-30), almost 50% of individuals had a mortality risk as high of that of obese Stage 2/3 individuals.

This means that indications for obesity treatment based on BMI alone will overtreat a substantial number of obese individuals, who may have little benefit in terms of mortality, and miss an even greater number of individuals, who may well benefit from such treatments.

These observations are directly relevant to yesterday’s post on the findings of the SOS study.

As readers will recall, not only was there no relationship between BMI levels and cardiovascular outcomes in the SOS population but the overall cardiovascular risk of these participants - despite the majority being ’severely’ obese - was surprisingly low. In fact, the annual risk for experiencing an adverse cardiovascular outcome for SOS participants was well under 1% per year!

This risk level is highly reminiscent of the overall risk of Stage 0 obese individuals in our NHANES analyses.

Thus, it is readily apparent why it took almost 15 years to demonstrate any cardiovascular benefit of bariatric surgery in the SOS study - clearly this was a very ‘low-risk’ obese population.

Contrast this to the almost 3% annual cardiovascular event rate for the participants in the SCOUT trial, which, by definition, consisted exclusively of Stage 2/3 individuals. In this population, it took less than 3.5 years of even very modest weight-loss (3 to 10 kg) to significantly reduce cardiovascular outcomes.

But did surgery prove more beneficial in higher-risk participants in the SOS trial? It certainly did!

In fact, the only predictor of greater benefit of having bariatric surgery in the SOS paper proved to be having an elevated plasma insulin level - a rather crude marker of insulin resistance. It is fair to assume that these participants were in fact those with higher obesity Stages (elevated fasting insulin levels alone, would already suggest at least Stage 1 obesity).

The importance of this difference is reflected in the numbers-needed-to-treat (NNT): as low as 21 in participants with baseline plasma insulin concentrations above the median (>17.0 mU/L) and as high as 173 in individuals below or at the median (≤17.0 mU/L) insulin concentration.

This essentially means that you would need to operate only 21 patients with Stage 1+ obesity to ’save’ one life (over 15 years) but 173 Stage 0 patients for the same benefit. It does not take a financial genius to figure out that from a ‘cost-per-life-saved’ perspective, operating on Stage 1+ patients is a ‘no-brainer’ whereas operating on Stage 0 patients would (and should) probably raise some eyebrows (especially in a publicly funded healthcare system).

Thus, as we have argued before (and argued by Livingstone in an editorial accompanying the SOS paper in JAMA), it is high time we fully appreciate the “inadequacy of BMI as an indication for bariatric surgery” and begin adopting more sophisticated criteria (such as those of the Edmonton Obesity Staging System) to ensure that this treatment is available to those who are likely to benefit the most.

AMS
London, UK

Padwal RS, Pajewski NM, Allison DB, & Sharma AM (2011). Using the Edmonton obesity staging system to predict mortality in a population-representative cohort of people with overweight and obesity. CMAJ : Canadian Medical Association journal = journal de l’Association medicale canadienne, 183 (14) PMID: 21844111

Livingston EH (2012). Inadequacy of BMI as an indicator for bariatric surgery. JAMA : the journal of the American Medical Association, 307 (1), 88-9 PMID: 22215170

Earlier this week, I posted on an analysis of the SCOUT trial, in which we found a clear and significant ‘dose-response’ relationship between moderate weight loss (3-10 Kg) and reduced cardiovascular outcomes (including death) in the over 10,000 high-risk participants in this trial.

So far, the only data showing a reduction in overall mortality with weight loss comes from studies looking at the effects of bariatric surgery, such as the ongoing Swedish Obese Subjects (SOS) study, which just published its latest findings in the Journal of the American Medical Association (JAMA).

In this paper, Lars Sjöström and colleagues from the University of Gothenburg, Sweden, specifically examine the relationship between bariatric surgery, weight loss, and cardiovascular events in the SOS study.

Some readers may recall that the SOS study is an ongoing, nonrandomized, prospective, controlled study conducted at 25 public surgical departments and 480 primary health care centers in Sweden of 2010 obese participants who underwent bariatric surgery and 2037 contemporaneously matched obese controls who received usual care. Inclusion criteria were age 37 to 60 years and a body mass index of at least 34 in men and at least 38 in women. Surgery patients underwent gastric bypass (13.2%), banding (18.7%), or vertical banded gastroplasty (68.1%), and controls received usual care in the Swedish primary health care system.

In the present analysis, bariatric surgery was associated with an almost 50% reduction in the number of cardiovascular deaths (28 events among 2010 patients in the surgery group vs 49 events among 2037 patients in the control group) over the almost 15 years of follow-up. Similarly, there was an almost 35% reduction in the number of total first time (fatal or non-fatal) cardiovascular events (myocardial infarction or stroke, whichever came first) in the surgery group (199 vs. 234 events).

Notably, however, the investigators found no significant relationship between cardiovascular outcomes and baseline BMI or the magnitude of weight loss. This is in contrast to the SCOUT study, where we found a clear ‘dose-response’ relationship between the amount of weight lost and the reduction in cardiovascular outcomes.

Several factors may explain this lack of ‘dose-response’ relationship in the SOS study.

For one, the SOS population, despite being far more obese than the participants in the SCOUT trial, were at a much lower risk for cardiovascular complications. Thus, the annualised event rate per 1000 participants in the SCOUT trial population was more than four times that of the SOS trial (30 vs. 7). Thus, the SOS study, despite its size, duration, and heavier BMI of participants, may simply be underpowered to demonstrate a ‘dose-response’ relationship between the magnitude of weight loss and reduction in cardiovascular outcomes.

Another explanation for the lack of ‘dose response’ in the SOS vs. SCOUT trial could be related to the overall magnitude of weight loss. Thus, while average weight loss in the SCOUT trial was just under 5%, the average weight loss in SOS was about 20%. if, as many suspect, a moderate 5-10% weight loss is all it takes to significantly reduce cardiovascular risk, the average weight loss of 20% in SOS would obscure any ‘dose-response’ relationship, as all participants in SOS, so to say, were already on the highest effective ‘dose’ of weight loss.

Thus, by no means is it clear from the SOS study that losing 20% of your body weight through bariatric surgery is any better than losing just 5% of your body weight as far as cardiovascular outcomes are concerned (this is not denying any other potential benefits of bariatric surgery on diabetes, cancer, arthritis, sleep apnea, or quality of life).

Thus, in light of the recent SCOUT findings, the superiority of bariatric surgery to medical obesity treatment in reducing cardiovascular outcomes would indeed need to be demonstrated in a ‘head-to-head’ trial  - a study that is unlikely to be done anytime soon.

interestingly, the lack of relationship between baseline BMI and cardiovascular outcomes and the remarkably low overall incidence of cardiovascular complications in the SOS patients raises a number of other important issues regarding indications for surgery - a topic that I will save for tomorrow’s post.

AMS
Berlin, Germany

Sjöström L, Peltonen M, Jacobson P, Sjöström CD, Karason K, Wedel H, Ahlin S, Anveden Å, Bengtsson C, Bergmark G, Bouchard C, Carlsson B, Dahlgren S, Karlsson J, Lindroos AK, Lönroth H, Narbro K, Näslund I, Olbers T, Svensson PA, & Carlsson LM (2012). Bariatric surgery and long-term cardiovascular events. JAMA : the journal of the American Medical Association, 307 (1), 56-65 PMID: 22215166

Faithful readers will recall previous posts on the results of the SCOUT trial, in which we studied 10,744 overweight or obese subjects (≥55 years) with pre-existing cardiovascular disease and/or type 2 diabetes mellitus, who received the anti-obesity drug sibutramine plus weight management during a 6-week lead-in Period, before randomisation to continue on sibutramine (N=4906) or to receive placebo (N=4898) plus ongoing lifestyle management for another 4-5 years.

In SCOUT, participants randomised to sibutramine had an 11% higher risk of experiencing a non-fatal cardiovascular outcome (non-fatal myocardial infarction, non-fatal stroke, or resuscitated cardiac arrest) compared to the placebo group. This finding, led to the voluntary withdrawal of sibutramine in most countries (including the US and Canada).

However, as discussed before, one of the critical design features of the SCOUT trial, was that participants had to continue on medication irrespective of whether or not they actually lost weight. This is obviously very different from how an anti-obesity drug would be used in clinical practice, where no patient would likely continue taking a drug that was clearly not effective.

Thus, while the original paper, published in the New England Journal of Medicine, presented the intention-to-treat analysis, which simply compared the two treatment arms, irrespective of whether individuals lost weight or not, we have now published an analysis in Obesity, Diabetes, and Metabolism that looks at the cardiovascular outcomes in relationship to the actual weight loss during the 6-week lead-in period and over the first 12 months of the trial.

While average weight loss in the 6-week lead-in period was -2.54 kg, post-randomisation 12-month weight loss was significantly greater in the sibutramine-treated participants (-4.18 kg) compared to placebo (-1.87 kg). There was of course a considerable spread in changes in body weight both during the lead-in period and within each treatment arm post-randomisation with some participants losing little (or even gaining some) weight with others losing considerable weight (well into the 10-15% range).

The analysis clearly shows that the degree of weight loss during both the lead-in Period and through month 12 was associated with a progressive reduction in risk for the total population of experiencing ‘hard’ outcomes like having a stroke, a heart attack, or dying of other causes over the 5-year assessment.

To my knowledge, this is the first demonstration of a reduction in ‘hard’ cardiovascular outcomes with intentional (non-surgical) weight loss (3-10 kg).

Although more events occurred in the randomised sibutramine group, on average, a modest weight loss of approximately 3kg achieved in the Lead-in Period appeared to offset this increased event rate.

Thus, this analysis demonstrates that even moderate weight loss over short-term (6 weeks) and longer-term (6-12 months) periods is associated with reduction in subsequent cardiovascular mortality for the following 4-5 years even in those with pre-existing cardiovascular disease.

There are some limitations in the interpretation of these findings in that they represent a post-hoc analysis and the participants all had at least mild, moderate, or severe cardiovascular disease (EOSS 2-3). Thus, we still do not know whether or not losing weight reduces risk in obese individuals without pre-existing heart disease (EOSS 0-1).

Despite these caveats, this study certainly represents a ‘historical’ milestone in being the first to show that even modest intentional weight loss can reduce cardiovascular outcomes in a high-risk population.

Not a bad way to start off the new year.

AMS
Berlin, Germany

Caterson ID, Finer N, Coutinho W, Van Gaal LF, Maggioni AP, Torp-Pedersen C, Sharma AM, Legler UF, Shepherd GM, Rode RA, Perdok RJ, Renz CL, James WP, & on the behalf of the SCOUT Investigators (2011). Maintained Intentional Weight Loss Reduces Cardiovascular Outcomes: Results from the Sibutramine Cardiovascular Outcomes (SCOUT) Trial. Diabetes, obesity & metabolism PMID: 22192338

One of the brochures that was freely distributed at the recent Journées annuelles de santé publique (Québec) meeting I spoke at yesterday in Montreal, is a pamphlet produced by the Québec Public Health Agency (with funding from the Public Health Agency of Canada) on the potential risks of dieting.

The pamphlet notes that:

• 1 woman out of 2 in Quebec wants to lose weight
• 45% of children aged 9 in Quebec aren’t happy with their figure
• Half of Quebec women try dieting more than twice a year
• Losing weight does not mean you are healthier (quite the statement coming from a public health agency)
• Many women mistakenly believe losing weight will improve their self-esteem, make them more attractive and make them sexier.

The pamphlet actually warns that:

“Always being on a diet might make you gain weight. The more you are preoccupied with your weight, the more you are at risk of suffering from depression and stress. Day-to-day activities like meals, getting dressed and playing sports can be transformed into major sources of anxiety.”

The pamphlet is also very clear about why most commercial diets don’t work:

Diets don’t take into account the reasons why you are gaining weight:

• Heredity, disease, medication, age, etc.
• Eating habits, physical activity, being obsessed with one’s own weight, etc.
• Perfectionism, low self-esteem, anxiety, stress, etc.
• Standards of beauty, the environment, the type of work we do, etc.

Finally, it offers the following points to consider when thinking about losing weight:

Weight-loss pace: Does my plan focus on losing more than 1-2 pounds per week?

Methods used: Does my plan focus on what food I eat, physical activity and changing my habits?

Is health professional support available?

Food intervention: Do you vary the meals you make, experiment with different flavours, colours and ingredients? Eating right is good for your health but it can also be fun and delicious!

Physical activity: Does my plan have an element of physical activity, the kind I enjoy?

Efficiency: Has the approach I am taking been scientifically verified, and is it efficient over the long term?

Danger: Is my plan safe, meaning is it devoid of danger and secondary effects?

Advertising: Are the ads related to my plan realistic?

What it costs: Can I realistically evaluate the total cost of my plan?

The brochure is available both in French and English.

Not sure that warning about the ‘dangers of weight loss’ is standard practice with other public health agencies - I certainly haven’t seen similar warning signs in other jurisdictions.

Obviously, the Agency is by no means implying that excess weight or obesity cannot be a health problem - it is simply warning about the possibility that ’self-guided’ non-evidence-based approaches, especially those often promoted by the commercial weight-loss industry, may in the end do more harm than good.

When weight loss is indeed medically indicated - treatment should perhaps be best left to ‘qualified‘ health professionals.

AMS
Toronto, Ontario

p.s. Hat tip to Chantal Bayard of the ASPQ for bringing these brochures to my attention