Concentracions plasmàtiques d'heme oxigenasa-1, inflamació de baix grau i rigidesa arterial en l'obesitat mòrbida amb síndrome d'apnea-hipopnea del son. efecte de la cirurgia bariàtrica

Student thesis: Doctoral thesis


Morbid obesity and obstructive sleep apnea (OSA) are mutually reinforced and share common pathological mechanisms involved in their etiology and comorbidity, such as low-degree inflammation and an increase in oxidative stress and sympathetic activity. These mechanisms have been associated with an increase in arterial stiffness, which occurs in obesity and OSA and involves a higher prevalence of cardiovascular morbidity. Therefore, it would be useful to identify common therapeutic targets in order to develop new treatments directed to decrease low-degree inflammation and arterial stiffness in both pathologies. One of these targets might be the heme oxygenase 1 (HO-1), a new adipokine with beneficial effects on oxidative stress, inflammatory stress, and the cardiovascular system, and which has been scarcely studied in obesity and OSA. Thus, in patients with morbid obesity and OSA without continuous positive airway pressure (CPAP), we assessed the impact of OSA severity on HO-1 plasmatic levels, low-degree inflamation, and arterial stiffness, as well as the effect of bariatric surgery on these. We studied 88 patients, before and 1 year after surgical intervention. Blood pressure, anthropometric parameters, HOMA insulin resistance index, and plasmatic levels of HO-1 (Elisa Kit bioNova científica, s. l. Madrid), TNF-α, IL-6, IL-1β, and adiponectin (Milliplex Catalog, Merk Millipore, Madrid) were studied. In order to measure arterial stiffness, we studied pulse wave velocity (PWV) and the heart-rate adjusted augmentation index (Alx@75) by applanation tonometry (Sphygmocor ® version 7. 0 AtCor Medical, Sidney, Australia). We also conducted a respiratory polysomnography (CE-Series Compumedics, Victoria, Austrialia). Before surgical intervention, higher levels of low-degree inflammation and arterial stiffness were seen at higher OSA severity, but this was not the case for HO-1. Low-degree inflammation was directly related to hypoxemia, whereas arterial stiffness was related to OSA severity indices. The observed differences in arterial stiffness were mainly accounted for antihypertensive therapy and age. Bariatric surgery decreased HO-1 levels, low-degree inflammation and arterial stiffness. Surgery impact on HO-1 and low-degree inflammation was greater in the high severity OSA group, while the improvement over arterial stiffness was greater in patients with moderate OSA. HO-1 decrease was positively related to the decrease in insulin resistance and, in the sever OSA group, it was related to the decrease in PCR plasmatic levels. The improvement in low-degree inflammation was associated to the improvement in anthropometric parameters and hypoxia. The reduction in arterial stiffness was positively related to excess weight loss and inflammation improvement, and this reduction was higher in those patients with lower SAHS severity and higher fat percentage before surgery. Our results show that OSA severity has consequences in the inflammation and arterial stiffness of patients with morbid obesity, and that bariatric surgery alleviates these, as a consequence of the improvement in the indices of the sleep breathing disorder and the anthropometric parameters. They also show that bariatric surgery decreases HO-1 plasmatic levels in patients with morbid obesity and OSA, and that this decrease is related to the improvement in inflammation and insulin resistance, suggesting that the adipokine plays a role in inflammation and metabolism.
Date of Award28 Jun 2016
Original languageCatalan
SupervisorFerran Segura Porta (Tutor), Maria Assumpta Caixas Pedragos (Director) & Maria Mercedes Rigla Cros (Director)

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