Our data show that significant weight loss 2 years after GBS is associated with: 1) markedly improved exercise capacity, 2) a reduction in resting HR and systolic BP and, 3) a marked improvement in HR recovery after exercise. These changes are likely contributed to by a relative enhancement of cardiac vagal tone, with potential contributions from decreased resting sympathetic tone and more rapid sympathetic withdrawal after termination of exercise. The improvements in the physiological parameters are independently related to the amount of weight lost and to decreased insulin resistance. These data support other recent findings suggesting that the sustained weight loss associated with GBS may result in long-term reductions in cardiovascular morbidity and mortality.15, 23, 24
Obesity is associated with increased long-term mortality, mainly from cardiovascular causes. 25
Atherosclerosis and heart failure appear to account in part, for the excess mortality in obese individuals. Improved autonomic tone may lead to reductions in both of these disease processes. Such an improvement in autonomic tone might directly contribute to reductions in cardiovascular events since persistent sympathetic stimulation can cause myocyte hypertrophy, myocyte cell death and cardiac fibrosis.26
Indirectly, reductions in sympathetic tone could attenuate the development of heart disease via BP reductions. The lowering of serum lipids and the resolution of insulin resistance following GBS-induced weight loss would be expected to amplify all of the aforementioned cardioprotective effects.23, 24
There is evidence of increased susceptibility to arrhythmias in obese patients. 27
Esposito et al.
suggested that prolonged cardiac repolarization was associated with obesity because of an altered sympathovagal balance. 28
If this is true, then it is possible that GBS might reduce arrhythmic events in severely obese subjects through autonomic mechanisms. The possibility that GBS could reduce arrhythmic tendencies is important conceptually, because there are reports that extreme weight loss achieved through some dietary methods has been associated with sudden cardiac death. 29
In the latter case, electrolyte or nutritional imbalances were the likely mechanisms of the arrhythmias. It would be important to know that GBS is not associated with risk factors for sudden cardiac death. Longer follow up will be needed in order to define whether the improved autonomic tone seen after GBS translates into a reduction in clinical event rates.
Interestingly, Billakanty et al described 15 patients who developed syncope related to orthostatic hypotension ~ 5 months after bariatric surgery.30
The authors of this report found evidence that these subjects had autonomic insufficiency as a cause for the new neurological symptoms. These data imply that even seemingly beneficial changes in autonomic function can be pathological if they are excessive or occur too rapidly. We are not aware of such symptoms in our patient population.
Previous studies as well as ours have shown substantial decreases in the frequency of metabolic syndrome, hypertension, diabetes and the use of BP lowering or diabetes medications following GBS. 31–33
As well, it has also been shown that weight loss via a hypocaloric diet results in a reduction in sympathetic markers.34
Our findings are in keeping with these earlier studies, but our longer duration of follow up indicates a sustained effect after GBS. It is quite likely that both weight loss and
improved glycemic regulation contribute to the autonomic improvements we found. It is not possible to completely separate the influences of these processes. The multivariable analysis shown in suggests that a lower BMI and a lower HOMA-IR at the time of the 2-year follow up each have independent associations with improvement in HR recovery.
Lifestyle modification usually includes changes in diet and increased exercise. Increases in parasympathetic and decreases in sympathetic nerve activity, and improved HR recovery have been seen after weight loss achieved by dieting in obese individuals. 20, 35, 36
Similarly, it is well known that exercise training is associated with increased resting vagal tone and more rapid HRR after exercise. 37, 38
Unfortunately, very few severely obese patients are able to maintain significant weight loss through lifestyle modification. Among the various surgical procedures practiced today, Roux-en-Y GBS is still the most common. In the Swedish Obesity Study, GBS was associated with significantly more initial weight loss, and more sustained weight loss than gastric banding alone.39
Moreover, patients undergoing gastric banding procedures did not maintain reductions in BP at 10 year follow up. Prior to the present study, it was unclear whether weight loss achieved via Roux-en-Y GBS resulted in autonomic benefits similar to those achieved with diet and exercise. Our findings now extend the autonomic benefits of weight loss to patients undergoing this form of bariatric surgery.
Other factors such as sex hormone levels are significantly affected by adiposity and weight loss.40
Although we do not have measurements of these hormones in the majority of our patients, the anticipated direction of change with marked weight loss would be a relative increase in circulating levels of male vs. female sex hormones. Previous work suggests that males have higher cardiac sympathetic tone whereas females have higher parasympathetic cardiac autonomic tone.41
If changes in sex hormones were a major factor contributing to the observed changes in HR recovery, marked weight loss would likely reduce rather than increase HR recovery when compared to baseline. Seventy seven % of female subjects who provided data on menstrual status at baseline were premenopausal.
Multiple variables changed following GBS. Thus, it is not possible to define a single mechanism responsible for the main outcome of improved HR recovery. Regardless of the exact mechanism(s), our data strongly suggest that bariatric surgery may improve the conditions associated with high cardiovascular mortality in obesity. This would be an extremely important outcome given the very rapid rise in the prevalence of obesity and the increasing use of surgical weight loss procedures. Another issue is that our population was 83% female. In our small percentage of male subjects we saw similar improvements in HR recovery as were seen in the women. Importantly, severe obesity is twice as prevalent in females as in males and women are often underrepresented in cardiovascular studies. It would also be very informative to collect direct measures of parasympathetic and sympathetic activity such as serum catecholamines, microneurography or even heart rate variability. Those measurements are not available from this dataset and in some cases are quite difficult to acquire in severely obese subjects. We also do not have 24 hour Holter monitoring in our subjects. Exercise was not specifically prescribed or monitored in either group. While it is likely that some patients who lost weight did more exercise than those who did not lose weight, we cannot quantitatively assess the effects of exercise on our outcome measures. Follow-up on these patients has not been long enough to study potential changes in clinical arrhythmias or survival. Despite these limitations, weight loss with GBS showed very promising results and further studies of mechanisms and outcomes are clearly warranted.