Relación entre el estilo de vida y la salud ósea y cardiovascular en una cohorte de pacientes con síndrome metabólico” "association between lifestyle and bone and cardiovascular health in a cohort of metabolic syndrome patients”

ABSTRACT Background and aim: Current lifestyle is causing a remarkable increase in overweight up to epidemic numbers globally. In Spain, over 60% of the adult population is overweight or obese. According to this trend, an increase of 16% in the number of cases is estimated by 2030 associated with a 58% increase in direct healthcare costs. An association between osteoporosis, cardiovascular disease (CVD) and cardiovascular-related mortality has been reported. The common risk factors involved in bone fragility and CVD could partially explain this association. Bone-related proteins, such as osteocalcin (OC), are of special interest for the study of CVD. OC is a typically bone protein involved in bone mineralization after incorporation into the extracellular matrix. However, studies in vitro and in animal models have shown that its infracarboxylated fraction (ucOC) is released into the bloodstream, regulating insulin secretion and insulin sensitivity by acting directly on pancreatic beta cells and on adipocytes. These findings have assigned a new role to the bone as an endocrine organ with extra-skeletal functions. Visceral obesity in conjunction with other disorders, such as dyslipidaemia, hypertension and fasting hyperglycaemia lead to the metabolic syndrome (MetS), conferring thus a larger risk of developing CVD. Weight loss promoted by a balanced diet along the regular exercise practice can reduce the MetS incidence and type 2 diabetes (T2D) development and the cardiovascular complications and bone disorders they cause. Moreover, it could be associated with the improvement of the bone quality determined by bone microarchitecture measurement and markers involved in both bone and cardiovascular metabolism as is the ucOC. Although the large bibliography between bone and cardiovascular metabolism and the health outcomes they are associated to, the studies carried out so far in MetS patients are not conclusive, and more human studies are necessary to confirm these results. This doctoral thesis aims were: 1. To analyze the evolution of the cardiometabolic profile, CVR and serum ucOC levels at baseline and after six and twelve months of follow-up in a cohort of MetS patients. 2. To analyze the influence of weight loss, Mediterranean diet (MedDiet) adherence and physical activity on MetS parameters, CVR and serum ucOC levels in the study population. 3. To determine bone quality though densitometry and TBS and to analyze its association with ucOC serum levels and cardiovascular risk (CVR) parameters in a sample of women from the cohort and to evaluate the influence that weight loss, diet quality and physical exercise practice can have on bone health in those women. Methods: This one year following-up study included 235 patients with MetS, aged 55-75 years (53,2% women). Anthropometric data, lipid and glucose profile and circulating ucOC levels were measured at baseline and after six and twelve months of following. CVR was determined as a global and unified score of the diagnostic criteria for MetS (CV-ZS). Framingham and REGICOR scores were calculated to correlate to CV-ZS. Physical activity and MedDiet adherence were assessed. Bone mass density (BMD) and microarchitecture bone were determined at baseline and 12 after months in a women subgroup from the cohort and BMD and microarchitecture bone adjusted FRAX score was estimated when this data was available. T student and ANOVA tests were performed to descriptive assessment. Linear regression model was performed in order to analyze the association between circulating ucOC and CVR. A receiver operating curve (ROC) was performed to analyze the utility of ucOC as T2D risk estimator in our study population. Results: After 12 months following-up of the study population our results confirmed that weight loss can improve cardiometabolic health in MetS patients. They improved their lipid and glycemic profile though the obesity reduction. CVR determined by the calculated scores showed a significant decrease in the study population. Weight loss was associated with the diet quality improvement measured by the MedDiet adherence and with the increase of physical practice. Participants that showed higher physical activity showed lower CVR and improved MetS determinants rates as HDL-C, triglycerides levels and the obesity. UcOC levels showed a significant increase on average at 6 months of follow-up, however it decreased at 12 months reaching baseline rates. Women and MetS non T2D population showed the highest levels of ucOC which was correlated negatively with CVR and positively with HDL-C. UcOC serum levels appeared to be a CVR estimator in MetS since patients below the 25 percentile of ucOC levels showed a worse cardiometabolic profile. Moreover ucOC levels was associated with T2D in those patients. Bone health results of the subgroup women we studied showed an improvement of the bone quality though of TBS although they did not increased their BMD score. T2D women showed higher BMD, however they showed lower TBS than women diagnosed with T2D. MedDiet and physical activity showed an association with some of the bone health determinants. Conclusion: The present study confirms that weight loss, MedDiet adherence and physical activity are associated with CVR reduction and MetS determinants improvement and moreover MetS reversion. The measurement of circulating ucOC could be a useful tool to identify increased cardiovascular and T2D risk in MetS patients without T2D. The measurement of circulating ucOC levels could become a strategy to identify MetS patients at high risk in order to establish preventive and therapeutic approaches. In addition, lower serum levels of ucOC could contribute to T2D development. These findings break new ground for new research lines to evaluate the role of ucOC as a biomarker and as a potential therapeutic target, as well as the usefulness of CV-ZS in clinical practice in future longitudinal studies.