Long term effect of weight loss on atherosclerosis

Obesity has become a disease reaching pandemic proportions and is a leading cause of increased morbidity and mortality rates worldwide. In addition to behavioral and medical approaches, various types of surgery on the gastrointestinal tract, originally developed to treat severe or morbid obesity (`bariatric surgery`), constitute powerful options to facilitate weight loss in severely obese patients, often normalizing the multiple co morbidities of obesity, reducing or avoiding the need for medications and providing a potentially cost-effective approach to treating the disease. In a recent statement by the International Diabetes Federation on bariatric surgery in obese Type 2 Diabetes patients several research recommendations were pointed out, among others, that `Studies are needed to establish the long term benefits and complications of surgery`. Among others, the Swedish Obese Study is one of the large scale prospective studies on long term outcomes after bariatric surgery. Numerous pivotal findings were obtained from these studies. In the late 90s we started a prospective study in Innsbruck that was focused on metabolic aspects of bariatric surgery. During the last years several such metabolic issues were investigated by our group. The advantage of our study design was the `in detail` determination of body composition, functional and structural atherosclerosis and several metabolic parameters and the patients were examined at baseline and reexamined at 1.5 years and 5 years. Aim of this proposal is to determine the long term (i.e. 10 years) effects of bariatric surgery on atherosclerosis and to recruit a control group of severely obese patients. Besides the expected results on our primary objective structural atherosclerosis, the results of this study will document the status of approximately 250 patients undergoing bariatric surgery and controls. In 2009, medical guidelines for clinical practice for the perioperative nutritional, metabolic, and nonsurgical support of the bariatric surgery patients were published. However, these guidelines are currently only partially implemented in clinical routine, especially the routine follow up schedule that was published. In this long term follow up we will also perform routine analyses of the nutritional and metabolic status of these patients and we will investigate the complications that the patients experienced. These results should in long term change clinical practice by enforcing strict follow up examinations.

Due to funding of the project KLI 348, the Department for Internal Medicine I at the Medical University of Innsbruck was able to extensively investigate the long-term effects of bariatric surgery on several topics relevant for cardiovascular health. A total of 173 patients who were treated with surgical interventions aiming at pronounced and sustained weight loss (i.e. bariatric surgery) was recruited prior to and 10 years after surgery. Clinical and laboratory examinations included detailed anamnesis of changes in body weight, concomitant medication, co-morbidities, adverse events relating to bariatric surgery, subsequent need for re-operation, re-interventions of baseline surgery, draw of blood samples, electrical estimation of body composition, and quality of life. A total of 6 dependent subsequent research projects were initiated using data obtained in the project KLI 348, some of which the most important are to be explained in detail below: - It was found that the thickness of representative blood vessels remained stable within 10 years after bariatric surgery. The thickness of blood vessels (namely the mid-layer (media) and the innermost layer (intima) of the carotid artery (IMT)) is a surrogate marker for the risk to develop cardiovascular disease and / or to die from cardiovascular disease. In the general population, IMT tends to increase with age and in the presence of certain risk factors for cardiovascular disease such as overweight, smoking and sedentary lifestyle. However, the present investigation shows evidence that bariatric surgery was able to maintain IMT and to prevent the natural gain in IMT, which can be interpreted as a reduced risk to develop cardiovascular disease. - It was found that bariatric surgery was capable to protect genetic material. Every time a body cell divides, its genetic material needs to be copied and allocated to both resulting cells. Complex structures, so called telomeres made of genetic material and specific proteins are forming a protective layer, which prevents the genetic material from attrition during cell division which would result in cell death. It is known that telomeres are being shortened with every cell division cycle. The present investigation showed evidence that bariatric surgery resulted in an elongation of telomere length. In the general population, telomere length tends to decrease with age and in the presence of certain risk factors for cardiovascular disease. The protection of telomere length was found to be due to amelioration of metabolic risk factors rather than by weight loss alone. - The liver is the central organ of lipid metabolism in the human body. Liver cells are able to absorb process and produce blood lipids, which may nourish or harm the remaining body. Depending on the meals fat content, the liver has to absorb vast amounts of potentially harmful blood lipids, with low-density lipoproteins (LDL) being the most prominent subtype. The livers ability to absorb LDL mainly depends on the concentration of LDL docking sites on the liver cell surface, which in turn is regulated by a specific protein called proprotein-converstase subtilisin-kexin type-9 (PCSK-9). The concentration of PCSK-9 negatively correlates with the amount of LDL being absorbed by liver cells. The present investigation showed evidence that the concentration of PCSK-9 decreased in parallel to body weight within 10 years after bariatric surgery, increasing the livers ability to absorb LDL particles, which may lead to atherosclerosis and cardiovascular disease.