Effect of implementing the 5As of obesity management framework on provider-patient interactions in primary care.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Obesity counselling in primary care is positively associated with self-reported behaviour change in patients with obesity. Obesity counselling is rare, and when it does occur, it is often of low quality because of poor training and/or competency of providers' obesity management, lack of time and economical disincentives, and negative attitude towards obesity and obesity management. 5As frameworks are routinely used for behaviour-change counselling and addiction management (e.g. smoking cessation), but few studies have examined its efficacy for weight management. WHAT THIS STUDY ADDS: This study presents pilot data from the implementation and evaluation of an obesity management tool (5As of Obesity Management developed by the Canadian Obesity Network) in a primary care setting. Results show that the tool facilitates weight management in primary care by promoting physician-patient communications, medical assessments for obesity and plans for follow-up care. Obesity remains poorly managed in primary care. The 5As of Obesity Management is a theory-driven, evidence-based minimal intervention designed to facilitate obesity counselling and management by primary care practitioners. This project tested the impact of implementing this tool in primary care clinics. Electronic self-administered surveys were completed by pre-screened obese subjects at the end of their appointments in four primary care clinics (over 25 healthcare providers [HCPs]). These measurements were performed before (baseline, n = 51) and 1 month after implementing the 5As of Obesity Management (post-intervention, n = 51). Intervention consisted of one online training session (90 min) and distribution of the 5As toolkit to HCPs of participating clinics. Subjects completing the survey before and after the intervention were comparable in terms of age, sex, body mass index, comorbidities, satisfaction and self-reported health status (P > 0.2). Implementing the 5As of Obesity Management resulted in a twofold increase in the initiation of obesity management (19 vs. 39%, P = 0.03), and caused a statistically significant increase in the perceived follow-up/coordination efforts (self-reported Patient Assessment of Chronic Illness Care components, 45 ± 22 vs. 67 ± 12 points, P = 0.002), as well as two components of the 5As framework: Assess (50 ± 29 vs. 66 ± 15 points, P = 0.03) and Assist (54 ± 26 vs. 72 ± 13 points, P = 0.01). Our results suggest that using the 5As of Obesity Management facilitates weight management in primary care by promoting physician-patient communications, medical assessments for obesity and plans for follow-up care.

Effect of prenatal hypoxia in transgenic mouse models of preeclampsia and fetal growth restriction.

Mice lacking endothelial nitric oxide synthase (eNOS(-)(/-)) or catechol-O-methyl transferase (COMT(-/-)) exhibit a preeclampsia-like phenotype and fetal growth restriction. We hypothesized that a hypoxic insult would result in a more severe phenotype. Pregnant eNOS(-/-), COMT(-/-) and control (C57BL/6J) mice were randomized to hypoxic (10.5% O(2)) or normal conditions (20.9% O(2)) from gestational day 10.5 to 18.5. Hypoxia increased the blood pressure in all genotypes and proteinuria in C57BL/6J and eNOS(-/-) mice. Fetal survival was significantly reduced following hypoxia, particularly in eNOS(-/-) mice. Birth weight was decreased in both C57BL/6J and COMT(-/-) mice. Placentas from COMT(-/-) mice demonstrated increased peroxynitrite. Despite similar hypoxia-induced effects on maternal blood pressure and proteinuria, eNOS(-/-) embryos have a decreased tolerance to hypoxia. Compared to C57BL/6J, COMT(-/-) mice exhibited less severe changes in proteinuria and fetal growth when exposed to prenatal hypoxia. This relative resistance to prenatal hypoxia was associated with a significant increase in placental levels of peroxynitrite.

Efficacy and safety of long-term low-calorie diet in severely obese patients non-eligible for surgery.

The aim of this study was to describe the long-term efficacy and safety of low-calorie diets (LCDs; providing 900 kcal day(-1) ) in obese patients who have failed to achieve adequate weight loss with standard medical management and are non-eligible for surgical therapeutic options. Charts from a regional hospital-based outpatient bariatric programme were reviewed. Eight patients (75% male, age 60.1 ± 7.8 years) with severe obesity (body mass index 57.1 ± 8.8 kg m(-2) ) and undergoing long-term LCD (33 ± 10 months) were identified. Variables of interest included anthropometric, cardiovascular risk and nutritional parameters, thyroid, renal and liver function, changes in medications, side effects and adverse events. Average weight loss was 44 ± 15 kg (27 ± 13% of initial weight) at 24 months. Long-term management with LCD resulted in substantial and sustained improvements in glucose homeostasis, blood pressure and lipid profile. LCD was well tolerated with minor self-limited side effects. Over the follow-up period, two subjects underwent coronary revascularization and one patient underwent knee replacement surgery - all recovered without complications. These findings suggest that in selected obese patients (non-eligible for surgery), long-term management with LCD may provide an alternative option for substantial and sustainable weight loss with significant improvements in metabolic and cardiovascular health.

Increased plasma levels of total homocysteine but not asymmetric dimethylarginine in Hispanic subjects with ischemic stroke FREC-VI sub-study.

BACKGROUND AND PURPOSE: Despite sharing some metabolic and pathological mechanisms, the reported association between total homocysteine (tHcy), asymmetric dimethylarginine (ADMA) and stroke remains controversial, particularly in Hispanic populations from developing countries in which genetic, socioeconomic, and nutritional factors are different to those described in developed countries. Our objectives were to determine the relationships of these factors to stroke and to each other independent of other cardiovascular risk factors, and to explore potential sex differences. METHODS: This national (Colombia) multicenter case-control study included 238 cases and 238 controls to evaluate traditional and emerging risk factors for ischemic stroke including tHcy and ADMA plasma levels. RESULTS: The median plasma levels of tHcy were 8.48 µM for controls and 10.01 µM for cases (P<0.0001). Plasma levels of tHcy between 12 and 50µM were considered moderate hyperhomocysteinemia (HtHcy). There were no differences in plasma ADMA concentration between groups (P=0.40). Plasma levels of ADMA and creatinine were not correlated (P=0.47). After adjusting for confounding factors, the presence of HtHcy was strongly associated with stroke (OR 8.97; P<0.0001). The adjusted association between HtHcy and stroke in men (OR 9.98) was comparable to that in women (OR 8.98) (P=0.41). CONCLUSIONS: In this Hispanic population, with relatively normal renal function, plasma levels of tHcy but not ADMA were associated with stroke independent of other cardiovascular risk factors.

The effect of hypoxia-induced intrauterine growth restriction on renal artery function.

The risk of developing cardiovascular diseases is known to begin before birth and the impact of the intrauterine environment on subsequent adult health is currently being investigated from many quarters. Following our studies demonstrating the impact of hypoxia in utero and consequent intrauterine growth restriction (IUGR) on the rat cardiovascular system, we hypothesized that changes extend throughout the vasculature and alter function of the renal artery. In addition, we hypothesized that hypoxia induces renal senescence as a potential mediator of altered vascular function. We demonstrated that IUGR females had decreased responses to the adrenergic agonist phenylephrine (PE; pEC50 6.50 ± 0.05 control v. 6.17 ± 0.09 IUGR, P < 0.05) and the endothelium-dependent vasodilator methylcholine (MCh; E max 89.8 ± 7.0% control v. 41.0 ± 6.5% IUGR, P < 0.001). In IUGR females, this was characterised by increased basal nitric oxide (NO) modulation of vasoconstriction (PE pEC50 6.17 ± 0.09 IUGR v. 6.42 ± 0.08 in the presence of the NO synthase inhibitor N-nitro-l-arginine methyl ester hydrochloride (l-NAME; P < 0.01) but decreased activated NO modulation (no change in MCh responses in the presence of l-NAME), respectively. In contrast, IUGR males had no changes in PE or MCh responses but demonstrated increased basal NO (PE pEC50 6.29 ± 0.06 IUGR v. 6.42 ± 0.12 plus l-NAME, P < 0.01) and activated NO (E max 37.8 ± 9.4% control v. -0.8 ± 13.0% plus l-NAME, P < 0.05) modulation. No significant changes were found in gross kidney morphology, proteinuria or markers of cellular senescence in either sex. In summary, renal vascular function was altered by hypoxia in utero in a sex-dependent manner but was unlikely to be mediated by premature renal senescence.

Effects of hypoxia-induced intrauterine growth restriction on cardiac siderosis and oxidative stress.

We have previously shown that adult rat offspring born intrauterine growth restricted (IUGR) as a result of a prenatal hypoxic insult exhibit several cardiovascular characteristics that are compatible with common manifestations of chronic iron toxicity. As hypoxia is one of the major regulators of iron absorption and metabolism, we hypothesized that hypoxia-induced IUGR offspring will have long-term changes in their ability to regulate iron metabolism leading to myocardial iron deposition and induction of myocardial oxidative stress. Pregnant Sprague Dawley rats were randomized to control (n = 8) or maternal hypoxia (11.5% oxygen; n = 8) during the last 6 days of pregnancy. At birth, litters were reduced to eight pups (four male and four female). At 4 or 12 months of age, offspring were euthanatized and samples (blood and myocardium) were collected. In only the male offspring, IUGR and aging were associated with an increase in myocardial markers of oxidative stress such as oxidized/reduced glutathione ratio and malondialdehyde. Aged male IUGR offspring also exhibited interstitial myocardial remodeling characterized by myocyte loss and disrupted extracellular matrix.Contrary to our hypothesis, however, neither IUGR nor aging were associated with changes in any systemic or local markers of iron metabolism. Our results suggest that hypoxic insults leading to IUGR produce long-term effects on the levels of oxidative stress and connective tissue distribution in the myocardium of male but not female offspring.

Effect of gestational diabetes on maternal artery function.

Endothelial dysfunction has been observed systemically in women with gestational diabetes (GDM). Important cardiovascular adaptations occur during pregnancy, including enhanced endothelium-dependent vasodilation in systemic and uterine arteries, which are necessary to ensure the health of both mother and fetus. The effects of GDM, however, on uterine artery function and the possible mechanisms that mediate endothelial dysfunction remain unknown. The aim of this study was to utilize a mouse model of GDM to investigate (a) effects on uteroplacental flow, (b) endothelial function of uterine and mesenteric arteries, and (c) possible mechanisms of any dysfunction observed. Pregnant mice heterozygous for a leptin receptor mutation (Lepr(db) (/+); He) spontaneously develop GDM and were compared to wild-type (WT) mice at day 18.5 of gestation. Uterine artery flow was assessed using ultrasound biomicroscopy. Uterine and mesenteric artery function was assessed using wire myography. Arterial superoxide production was measured using oxidative fluorescence microphotography. In vivo uteroplacental perfusion was impaired in mice with GDM, indicated by a significant increase in uterine artery resistance index. Maximal endothelium-dependent relaxation to methacholine was significantly impaired in mesenteric arteries from mice with GDM, while sensitivity was significantly reduced in uterine arteries. Both uterine and mesenteric arteries from mice with GDM exhibited a greater dependence on nitric oxide and increased superoxide production compared with those from mice with a healthy pregnancy. A significant source of superoxide in GDM mice was uncoupled nitric oxide synthase. These changes may contribute to the development of some of the fetal and maternal complication associated with GDM.

Flow-mediated vasodilation is impaired in adult rat offspring exposed to prenatal hypoxia.

There is now a demonstrated association between low birth weight and increased mortality later in life. Changes in fetal development may program the cardiovascular system and lead to an increased risk of cardiovascular diseases later in life. In addition, aging is a risk factor for vascular endothelial-dependent dysfunction. However, the impact of being born intrauterine growth restricted (IUGR) on the normal aging mechanisms of vascular dysfunction is not clear. We hypothesized that IUGR would cause changes in vascular function that would affect the mechanisms of flow-induced vasodilation later in life in an age- or sex-dependent manner. To create an IUGR model, pregnant Sprague-Dawley rats were placed in a hypoxic (11.5% O2) or control (room air, 21% O2) environment from days 15 to 21 of pregnancy. Both male and female offspring were investigated at 4 or 12 mo of age. Vascular function was assessed in small mesenteric arteries using flow-induced vasodilation, a physiological stimuli of vasodilation, in a pressure myograph. Flow-induced vasodilation was unaffected at a young age, but was significantly reduced in aging IUGR compared with aging controls (P < 0.05). Underlying vasodilator mechanisms were altered such that nitric oxide-mediated vasodilation was abolished in both young adult and aging IUGR males and females and in aging control females (P > 0.05). Endothelium-derived hyperpolarizing factor-mediated vasodilation was maintained in all groups (P < 0.01). A change in the mechanisms of vasodilation occurring at an earlier age in IUGR offspring may predispose them to develop cardiovascular diseases as an aging adult.

Mechanisms of endothelium-dependent vasodilation in male and female, young and aged offspring born growth restricted.

Numerous epidemiological studies have shown that cardiovascular dysfunction in adult life may be programmed by compromised growth in utero. Aging is a risk factor for vascular endothelial-dependent dysfunction. After birth, the impact of intrauterine growth restriction (IUGR) on normal aging mechanisms of vascular dysfunction is not known. We hypothesized that IUGR would cause changes in vascular function that would affect the mechanisms of endothelium-dependent vasodilation later in life in an age- or sex-dependent manner. To create an IUGR model, pregnant Sprague-Dawley rats were placed in a hypoxic (12% O(2)) or control (room air, 21% O(2)) environment from days 15 to 21 of the pregnancy, and both male and female offspring were investigated at 4 or 12 mo of age. Endothelial function was assessed in small mesenteric arteries using methacholine (MCh)-induced vasodilation in a wire myograph system. The involvement of nitric oxide (NO), prostaglandins, and endothelium-derived hyperpolarizing factor (EDHF) was assessed using the inhibitors N(omega)-nitro-l-arginine methyl ester hydrochloride, meclofenamate, or a combination of apamin and TRAM-34 (SK(Ca) and IK(Ca) blockers), respectively. EDHF-induced vasodilation was further investigated by using inhibitors of P450 epoxygenases [N-methylsulfonyl-6-(2-propargyloxyphenyl) hexanamide] and gap junctions (18alpha-glycyrrhetinic acid). NO-mediated vasodilation was significantly reduced in aged controls and both young and aged IUGR females. EDHF-mediated vasodilation was maintained in all groups; however, an additional involvement of gap junctions was found in females exposed to hypoxia in utero, which may represent a compensatory mechanism. A change in the mechanisms of vasodilation occurring at an earlier age in IUGR offspring may predispose them to adult cardiovascular diseases.