Abstract W P386: Matrix Metalloproteinase Levels May Mediate Ischemic Stroke Incidence and Recovery in Stroke Patients with Metabolic Syndrome

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Ashley B Petrone ◽  
Taura L Barr ◽  
Kelly Devlin ◽  
Sara B Fournier ◽  
Evan D Devallance ◽  
...  

Intro: The metabolic syndrome (MetS) is highly prevalent in the US characterized by a combination of risk factors that can lead to cardiovascular disease (CVD). While the association between CVD, inflammation, and stroke risk has been characterized, the immune mechanisms underlying increased risk of stroke in MetS is unclear. While stroke risk is higher among MetS, MetS individuals tend to have better stroke recovery than controls. The immune response may mediate these paradoxical observations in stroke. In particular, matrix metalloproteinases (MMP) enzymes play a role in stroke incidence and recovery. Similar to MetS, MMPs have a dual role in stroke, as they are harmful immediately after stroke, but play a vital role in brain repair and recovery following stroke. We hypothesize that elevated levels of MMPs in MetS may account for the paradoxical increased stroke risk, yet better recovery seen in stroke patients with MetS. Methods: MMP protein concentrations were obtained from fasting venous samples and quantified using a Multi-Analyte Profiling Kit (Millipore) on the Luminex®. Each subject was assigned a metabolic risk score (MRS) based on sex, age, SBP, treatment for hypertension, smoking and diabetes status, HDL, and total cholesterol. B-mode ultrasound images of the right common carotid artery were obtained to measure intima-medial thickness (cIMT). Spearman correlations were used to measure the relationship between MRS, cIMT, and MMP levels. Results: In n=68 subjects (60% female) with a mean age of 48+14 yrs, MRS of 25+12, and cIMT of 0.57+0.12 mm. MRS was significantly correlated with cIMT (r=0.39, p< .001). Further, cIMT was positively correlated with MMP1 (r=0.025, p=0.04), MMP7 (r=0.5, p=0.01), and MMP9 (r=0.31, p=0.01). Conclusion: Plasma concentrations of MMP1, 7, and 9 were significantly correlated with cIMT, indicating that increased severity of MetS is associated with increased inflammation. Elevated MMP protein levels may account for the increased stroke risk, yet better recovery seen in stroke patients with MetS.

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Raymond C Seet ◽  
Yi Zhang ◽  
Eelco F Wijdicks ◽  
Alejandro A Rabinstein

Background: The influence of high body mass index (BMI) in acute stroke patients treated with intravenous thrombolysis has not been extensively studied. Previous studies have observed an “obesity paradox” among stroke patients, where better outcomes were observed among overweight and obese patients. The purpose of this study is to determine the influence of obesity and risk components of metabolic syndrome to stroke recovery in patients undergoing intravenous recombinant tissue plasminogen activator (rtPA) treatment. Methods: Patients with acute ischemic stroke who received intravenous rtPA within three-hour from symptom onset at St. Marys Hospital, Mayo Clinic, Rochester, between April 2006 and January 2011, were included in this study. Information on vascular risk factors, stroke severity, and baseline hemodynamic and laboratory indices, were collected. Study outcomes, consisting symptomatic intracerebral hemorrhage (sICH) and poor functional recovery (modified Rankin scale >2), were compared between obese (body mass index, BMI >30 kg/m 2 ), overweight (BMI 25-30 kg/m 2 ) and normal weight (BMI <25 kg/m 2 ) patients. The association between BMI, risk components of the metabolic syndrome and dose of rtPA per kg body weight to stroke outcomes were assessed in a multivariable model. Results: A total of 158 patients (mean age, 75 years; baseline NIHSS, 11), frequency-matched by age and baseline stroke severity, were included in this study. No differences in the frequency of SICH and poor functional recovery were observed among obese, overweight and normal weight patients, before and after adjusting for their baseline characteristics. A linear trend towards worse stroke recovery was observed in patients with a greater number of metabolic risk components (p-trend=0.043). By contrast, there were no significant associations between the number of risk components of metabolic syndrome with respect to sICH. Using stepwise regression analyses, age, baseline stroke severity and the number of risk components of the metabolic syndrome accounted for 52% variation in functional recovery following rtPA treatment. Conclusions: Acute stroke outcomes do not differ between obese and overweight patients. The presence of metabolic risk factors contributes significantly to functional outcomes following rtPA treatment. These results suggest that decreasing the prevalence of metabolic syndrome in the community could reduce the societal burden of stroke-related disability.


2007 ◽  
Vol 30 (4) ◽  
pp. 95
Author(s):  
Valerie Taylor ◽  
Glenda M. MacQueen

Bipolar disorder and major depression are life-shortening illnesses. Unnatural causes such as suicide and accidents account for only a portion of this premature mortality1 Research is beginning to identify that mood disordered patients have a higher incidence of metabolic syndrome, an illness characterized by dyslipidemia, impaired glucose tolerance, hypertension and obesity.2 Metabolic syndrome is associated with an increased risk for a variety of physical illnesses. Hypothesis: Never treated patients with mood disorders have preexisting elevations in the prevalence of the component variables of metabolic syndrome. Central obesity will be especially elevated, predicting increased premature mortality. Methods: We assessed never treated patients with mood disorders for metabolic syndrome and its component variables. Patients were assessed at baseline and followed up at 6-month intervals. All psychiatric pharmacotherapy was documented. Body mass index (BMI) was also obtained and the percentage of deaths attributable to overweight and obesity was calculated using the population attributable risk (PAR). [PAR= ∑[P (RR-1)/RR] Results: Prior to the initiation of treatment, patients did not differ from population norms with respect to metabolic syndrome or BMI. At 2-year follow-up, BMI had increased for unipolar patients 2.02 points and 1.92 points for bipolar patients. (p < .001) This increase in BMI predicted an increase in mortality of 19.4%. Conclusion: An increase in visceral obesity is often the first component of metabolic syndrome to appear and may indicate the initiation of this disease process prematurely in this group. The increase in BMI places patients with mood disorders at risk for premature mortality and indicates a need for early intervention. References 1.Osby U, Brandt L, Correia N, Ekbom A & Sparen P. Excess mortability in bipolar and Unipolar disorder rin Sweden. Archives of General Psychiatry, 2001;58: 844-850 2.Toalson P, Saeeduddin A, Hardy T & Kabinoff G. The metabolic syndrome in patients with severe mental illness. Journal of Clinical Psychiatry, 2004; 6(4): 152-158


2019 ◽  
Vol 17 (6) ◽  
pp. 595-603 ◽  
Author(s):  
Sezcan Mumusoglu ◽  
Bulent Okan Yildiz

The metabolic syndrome (MetS) comprises individual components including central obesity, insulin resistance, dyslipidaemia and hypertension and it is associated with an increased risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). The menopause per se increases the incidence of MetS in aging women. The effect(s) of menopause on individual components of MetS include: i) increasing central obesity with changes in the fat tissue distribution, ii) potential increase in insulin resistance, iii) changes in serum lipid concentrations, which seem to be associated with increasing weight rather than menopause itself, and, iv) an association between menopause and hypertension, although available data are inconclusive. With regard to the consequences of MetS during menopause, there is no consistent data supporting a causal relationship between menopause and CVD. However, concomitant MetS during menopause appears to increase the risk of CVD. Furthermore, despite the data supporting the association between early menopause and increased risk of T2DM, the association between natural menopause itself and risk of T2DM is not evident. However, the presence and the severity of MetS appears to be associated with an increased risk of T2DM. Although the mechanism is not clear, surgical menopause is strongly linked with a higher incidence of MetS. Interestingly, women with polycystic ovary syndrome (PCOS) have an increased risk of MetS during their reproductive years; however, with menopausal transition, the risk of MetS becomes similar to that of non-PCOS women.


2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
S Cuschieri

Abstract Background A relationship between depression and metabolic syndrome has been reported. Considering the diabesity rates effecting the small state of Malta it was considered appropriate to explore for links between these diseases, their metabolic determinants with depression. Methods A national health examination survey was conducted. A validated questionnaire note down (1) self-reported depression (2) anti-depressive medication (3) PHQ-9 depression symptoms score (&gt;5 positive for depression). Participants with the presence of one or more of these variables were labelled as having depression. Body mass index (BMI), waist circumference (WC) and blood pressure (BP) were measured. Blood testing for fasting blood glucose (FBG) and lipid profile were performed. The biochemical (FBG, Lipid profiles) and anthropometric profiles (BMI, WC, BP) of the depression population were compared to those without this disease. Univariant and multivariant binary logistic regression models were performed. Results The depression population (17.2% of the total population) had significantly higher median LDL, triglyceride (TG) and total cholesterol (TC) levels when compared to those without the disease (p = &lt;0.01). On univariant modelling each variable (LDL OR:1.15 p = 0.01; TG OR:1.16 p = 0.01; TC OR:1.64 p = &lt;0.01) showed a positive association with having depression even after adjusting for confounding factors (sex, age, education, smoking, alcohol habits). On multivariant modelling only an increase in TC was associated with increased risk of having depression (OR: 1.36 CI95%: 1.05-1.76 p = 0.02) after adjusting for confounders. Conclusions The various components of the metabolic syndrome appeared not to be associated with a diagnosis of depression. Only high cholesterol level exhibited a metabolic link with depression. Although further research is merited, it is suggested that physicians incorporate a depression screening tool as part of their consultation when examining high-risk patients. Key messages A metabolic syndrome profile is not linked with depression. A high cholesterol level is linked with depression, making these individuals susceptible to potential cardiovascular disease.


2021 ◽  
Vol 10 (8) ◽  
pp. 1567
Author(s):  
Katarzyna Konończuk ◽  
Eryk Latoch ◽  
Beata Żelazowska-Rutkowska ◽  
Maryna Krawczuk-Rybak ◽  
Katarzyna Muszyńska-Rosłan

Childhood cancer survivors are highly exposed to the development of side effects after many years of cessation of anticancer treatment, including altered lipid metabolism that may result in an increased risk of overweight and metabolic syndrome. Adipocyte (A-FABP) and epidermal (E-FABP) fatty acid-binding proteins are expressed in adipocytes and are assumed to play an important role in the development of lipid disturbances leading to the onset of metabolic syndrome. The aim of this study was to investigate the association between serum A-FABP and E-FABP levels, overweight, and components of the metabolic syndrome in acute lymphoblastic leukemia survivors. Sixty-two acute lymphoblastic leukemia (ALL) survivors (34 females) were included in the study. The mean age at the time of the study was 12.41 ± 4.98 years (range 4.71–23.43). Serum levels of A-FABP and E-FABP were analyzed using a commercially available ELISA kit. The ALL survivors presented statistically higher A-FABP levels in comparison with the healthy controls (25.57 ± 14.46 vs. 15.13 ± 7.61 ng/mL, p < 0.001). The subjects with body mass index (BMI) above the normal range (18 overweight, 10 obese) had a greater level of A-FABP compared to the ALL group with normal BMI (32.02 ± 17.10 vs. 20.33 ± 9.24 ng/mL, p = 0.006). Of all participants, 53.23% had at least one risk factor of metabolic syndrome; in this group, only the A-FABP level showed a statistically significant difference compared to the healthy control group (30.63 ± 15.91 vs. 15.13 ± 7.61 ng/mL, p < 0.001). The subjects with two or more metabolic risk factors (16.13%) presented higher levels of both A-FABP (33.62 ± 17.16 vs. 15.13 ± 7.61 ng/mL, p = 0.001) and E-FABP (13.37 ± 3.62 vs. 10.12 ± 3.21 ng/mL, p = 0.021) compared to the controls. Univariable regression models showed significant associations between BMI and systolic blood pressure with the A-FABP level (coeff. 1.02 and 13.74, respectively; p < 0.05). In contrast, the E-FABP level was only affected by BMI (coeff. 0.48; p < 0.01). The findings reported herein suggest that the increased levels of A-FABP and E-FABP may be involved in the pathogenesis of overweight and the onset of metabolic syndrome in acute lymphoblastic leukemia. However, further longitudinal, prospective studies of fatty acid-binding proteins and their potential role in the pathogenesis of obesity and metabolic syndrome in ALL survivors remain to be performed.


2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Joel G. Anderson ◽  
Ann Gill Taylor

The metabolic syndrome, affecting a substantial and increasing percentage of the worldwide population, is comprised of a cluster of symptoms associated with increased risk of type 2 diabetes, cardiovascular disease, and other chronic conditions. Mind-body modalities based on Eastern philosophy, such as yoga, tai chi, qigong, and meditation, have become increasingly popular worldwide. These complementary therapies have many reported benefits for improving symptoms and physiological measures associated with the metabolic syndrome. However, clinical trial data concerning the effectiveness of these practices on the syndrome as a whole have not been evaluated using a systematic and synthesizing approach. A systematic review was conducted to critically evaluate the data from clinical trials examining the efficacy of mind-body therapies as supportive care modalities for management of the metabolic syndrome. Three clinical trials addressing the use of mind-body therapies for management of the metabolic syndrome were identified. Findings from the studies reviewed support the potential clinical effectiveness of mind-body practices in improving indices of the metabolic syndrome.


2010 ◽  
Vol 69 (2) ◽  
pp. 211-220 ◽  
Author(s):  
J. Bernadette Moore

Non-alcoholic fatty liver disease (NAFLD) is now the most common liver disease in both adults and children worldwide. As a disease spectrum, NAFLD may progress from simple steatosis to steatohepatitis, advanced fibrosis and cirrhosis. An estimated 20–35% of the general population has steatosis, 10% of whom will develop the more progressive non-alcoholic steatohepatitis associated with markedly increased risk of cardiovascular- and liver-related mortality. Development of NAFLD is strongly linked to components of the metabolic syndrome including obesity, insulin resistance, dyslipidaemia and type 2 diabetes. The recognition that NAFLD is an independent risk factor for CVD is a major public health concern. There is a great need for a sensitive non-invasive test for the early detection and assessment of the stage of NAFLD that could also be used to monitor response to treatment. The cellular and molecular aetiology of NAFLD is multi-factorial; genetic polymorphisms influencing NAFLD have been identified and nutrition is a modifiable environmental factor influencing NAFLD progression. Weight loss through diet and exercise is the primary recommendation in the clinical management of NAFLD. The application of systems biology to the identification of NAFLD biomarkers and factors involved in NAFLD progression is an area of promising research.


2010 ◽  
Vol 162 (5) ◽  
pp. 919-923 ◽  
Author(s):  
Anna C Phillips ◽  
Douglas Carroll ◽  
Catharine R Gale ◽  
Janet M Lord ◽  
Wiebke Arlt ◽  
...  

ObjectivesThe aim of these analyses was to examine the association of cortisol, DHEAS and the cortisol:DHEAS ratio with the metabolic syndrome (MetS) and its components.DesignThe analyses were cross-sectional.MethodsParticipants were 4255 Vietnam era US army veterans. From military service files, telephone interviews and a medical examination, occupational, socio-demographic and health data were collected. MetS was ascertained from data on body mass index; fasting blood glucose or a diagnosis of diabetes; blood pressure or a diagnosis of hypertension; high-density lipoprotein cholesterol; and triglyceride levels. Contemporary morning fasted cortisol and DHEAS concentrations were determined. The outcomes were MetS and its components. Analysis was by logistic regression, first adjusting for age and then additionally for an array of candidate confounders.ResultsCortisol, although not in the fully adjusted analysis, and DHEAS were both related to MetS. Whereas high cortisol concentrations were associated with an increased risk of MetS, high DHEAS concentrations appeared protective. By far, the strongest associations with MetS were observed for the cortisol:DHEAS ratio; the higher the ratio, the greater the risk of having MetS. The ratio was also significantly related to four of the five MetS components.ConclusionsThe cortisol:DHEAS ratio is positively associated with MetS. Prospective analyses are needed to help untangle direction of causality, but this study suggests that the cortisol:DHEAS ratio is worthy of further study in this and other health contexts.


2013 ◽  
Vol 98 (12) ◽  
pp. 4899-4907 ◽  
Author(s):  
Kyung Hee Park ◽  
Lesya Zaichenko ◽  
Mary Brinkoetter ◽  
Bindiya Thakkar ◽  
Ayse Sahin-Efe ◽  
...  

Context: Irisin, a recently identified hormone, has been proposed to regulate energy homeostasis and obesity in mice. Whether irisin levels are associated with risk of the metabolic syndrome (MetS), cardiometabolic variables, and cardiovascular disease (CVD) risk in humans remains unknown. Objective: Our objective was to assess the associations between baseline serum irisin levels and MetS, cardiometabolic variables, and CVD risk. Design, Setting, and Subjects: We conducted a comparative cross-sectional evaluation of baseline circulating levels of the novel hormone irisin and the established adipokine adiponectin with MetS, cardiometabolic variables, and CVD risk in a sample of 151 subjects. Results: Baseline irisin levels were significantly higher in subjects with MetS than in subjects without MetS. Irisin was associated negatively with adiponectin (r = −0.4, P &lt; .001) and positively with body mass index (r = 0.22, P = .008), systolic (r = 0.17, P = .04) and diastolic (r = 0.27, P = .001) blood pressure, fasting glucose (r = 0.25, P = .002), triglycerides (r = 0.25, P = .003), and homeostasis model assessment for insulin resistance (r = 0.33, P &lt; .001). After adjustment for potential confounders, including body mass index, subjects in the highest tertile of irisin levels were more likely to have MetS (odds ratio [OR] = 9.44, 95% confidence interval [CI] = 2.66–33.44), elevated fasting blood glucose (OR = 5.80, 95% CI = 1.72–19.60), high triglycerides (OR = 3.89, 95% CI = 1.16–13.03), and low high-density lipoprotein cholesterol (OR = 3.30, 95% CI = 1.18–9.20). Irisin was independently associated with homeostasis model assessment for insulin resistance and general Framingham risk profile in multiple linear regression analyses after adjustment for confounders. Adiponectin demonstrated the expected associations with outcomes. Conclusions: Irisin is associated with increased risk of MetS, cardiometabolic variables, and CVD in humans, indicating either increased secretion by adipose/muscle tissue and/or a compensatory increase of irisin to overcome an underlying irisin resistance in these subjects.


2018 ◽  
Vol 96 (1) ◽  
pp. 97-102 ◽  
Author(s):  
Hanin Aburasayn ◽  
Rami Al Batran ◽  
Keshav Gopal ◽  
Malak Almutairi ◽  
Amina Eshreif ◽  
...  

The percentage of women who are obese at the time of conception or during pregnancy is increasing, with animal and human studies demonstrating that offspring born to obese dams or mothers are at increased risk for obesity and the metabolic syndrome. Our goal was to confirm in an experimental model of metabolic syndrome in the dam, whether the offspring would be at increased risk of obesity. Conversely, we observed that male offspring born to dams with metabolic syndrome had no alterations in their body mass profiles, whereas female offspring born to dams with metabolic syndrome were heavier at weaning, but exhibited no perturbations in energy metabolism. Moreover, they gained weight at a reduced rate versus female offspring born to healthy dams, and thus weighed less at study completion. Hence, our findings suggest that factors other than increased adiposity and insulin resistance during pregnancy are responsible for the increased risk of obesity in children born to obese mothers.


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