21: DETERMINANTS OF VASCULAR INFLAMMATION BY 18-FLUORODEOXYGLUCOSE PET/MRI: FINDINGS FROM THE PSORIASIS, ATHEROSCLEROSIS AND CARDIOMETABOLIC DISEASE INITIATIVE

2016 ◽  
Vol 64 (3) ◽  
pp. 815.2-816
Author(s):  
MT Kabbany ◽  
AA Joshi ◽  
M Ahlman ◽  
J Rodante ◽  
JB Lerman ◽  
...  

Purpose of StudyPsoriasis (PSO), a chronic inflammatory disease associated with increased CV risk, provides a clinical human model to study inflammatory atherogenesis. We aimed to assess the major determinants of vascular inflammation (VI) measured by 18FDG PET-MRI in a well-phenotyped PSO cohort.Methods Used124 consecutive patients with PSO underwent 18FDG PET-MRI scans. We used target-to-background ratio to quantify VI 120 minutes post FDG injection. Homeostatic model assessment of insulin resistance (HOMA-IR) was measured, along with cholesterol efflux capacity (CEC) and HDL particle concentration by NMR (Liposcience) fasting.Summary of ResultsOur cohort was middle aged (mean 49±13.3 years) with mild to moderate PSO, and low CV risk (median Framingham Risk Score (FRS) 2, IQR 2–6). PSO was associated with increased VI (β=0.27, p<0.005), compared to healthy controls. VI was associated with HOMA-IR (β=0.26, p<0.001), CEC (β=−0.12, p=0.04) and HDL particle concentration (β=−0.19, p=0.003) beyond traditional CV risk factors (age, gender, FRS and BMI). Among these, HOMA-IR provided maximum incremental value in predicting VI beyond traditional risk factors (χ2=39.36, p<0.001).ConclusionsVI by FDG PET MRI is associated with traditional CV risk factors and cardiometabolic parameters. Insulin resistance and CEC were most strongly associated with VI by 18FDG PET-MRI beyond traditional CV risk factors and BMI in PSO suggesting that cardiometabolic disease increases CV risk in PSO.Abstract 21 Figure 1

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Balaji Natarajan ◽  
Taufiq Salahuddin ◽  
Jenny Dave ◽  
Martin Playford ◽  
Julia Doveikis ◽  
...  

Introduction: Psoriasis (PSO), an inflammatory skin disease is associated with increased cardiovascular disease (CVD) risk. We have previously shown the presence of insulin resistance (IR) in psoriasis, however how this relates to subclinical vascular disease is unknown. Here, our aim was to determine whether IR relates to vascular inflammation (VI) measured by 18 FDG PET-CT in a well-phenotyped psoriasis cohort (NCT 01778569). Hypothesis: We assessed the hypothesis that an increase in IR is associated with greater VI. Methods: We performed 18 FDG PET-CT scans on 86 consecutive patients with psoriasis (Siemens Biograph). Target-to-background ratio (TBR) was used as the VI measure. Fasting plasma samples were collected and homeostatic model assessment of IR (HOMA-IR) was used to stratify the study group into normal (n=41) vs high (n=45) HOMA-IR groups using an accepted cut-off value (3.0). Lipid profile and lipoprotein characteristics were also obtained using NMR spectroscopy (Liposcience, USA). Results: Our study cohort was middle aged with mild to moderate PSO (Table 1). There was increased VI by TBR in this sample (mean 1.8±0.3) as compared to published values for CAD (mean 1.6±0.3). The high HOMA-IR group had greater skin involvement by psoriasis, an increased incidence of CVD risk factors and an atherogenic lipid profile on NMR spectroscopy when compared to the normal HOMA-IR group. There was greater VI in the high HOMA-IR group (Mean±SD: 1.91±0.3 vs 1.69±0.2, p<0.001) which was robust to multivariate adjustment for age, gender, CVD risk factors and BMI (beta 0.38, p <0.01). Finally, on likelihood ratio testing, we observed an incremental effect when HOMA-IR was added to a fully adjusted model with BMI as a covariate (chi 2 5.65, p = 0.02). Conclusion: Psoriasis increases VI by 18 FDG PET-CT, which is strongly related to the presence of IR beyond traditional CVD risk factors and BMI. This suggests that inflammatory IR may have direct impact on the development of vascular inflammation.


Author(s):  
Jana Jurkovičová ◽  
Katarína Hirošová ◽  
Diana Vondrová ◽  
Martin Samohýl ◽  
Zuzana Štefániková ◽  
...  

The prevalence of cardiometabolic risk factors has increased in Slovakian adolescents as a result of serious lifestyle changes. This cross-sectional study aimed to assess the prevalence of insulin resistance (IR) and the associations with cardiometabolic and selected lifestyle risk factors in a sample of Slovak adolescents. In total, 2629 adolescents (45.8% males) aged between 14 and 18 years were examined in the study. Anthropometric parameters, blood pressure (BP), and resting heart rate were measured; fasting venous blood samples were analyzed; and homeostasis model assessment (HOMA)-insulin resistance (IR) was calculated. For statistical data processing, the methods of descriptive and analytical statistics for normal and skewed distribution of variables were used. The mean HOMA-IR was 2.45 ± 1.91, without a significant sex differences. IR (cut-off point for HOMA-IR = 3.16) was detected in 18.6% of adolescents (19.8% males, 17.6% females). IR was strongly associated with overweight/obesity (especially central) and with almost all monitored cardiometabolic factors, except for total cholesterol (TC) and systolic BP in females. The multivariate model selected variables such as low level of physical fitness, insufficient physical activity, breakfast skipping, a small number of daily meals, frequent consumption of sweetened beverages, and low educational level of fathers as significant risk factors of IR in adolescents. Recognizing the main lifestyle risk factors and early IR identification is important in terms of the performance of preventive strategies. Weight reduction, regular physical activity, and healthy eating habits can improve insulin sensitivity and decrease the incidence of metabolic syndrome, type 2 diabetes, and cardiovascular disease (CVD).


Author(s):  
Nijole Kazukauskiene ◽  
Aurelija Podlipskyte ◽  
Giedrius Varoneckas ◽  
Narseta Mickuviene

Background: Individuals with insulin resistance (IR) have a high risk of diabetes or metabolic syndrome, and they are more likely to have depression. Furthermore, IR by itself is a major cardiovascular risk factor in healthy persons. Thus, we aimed to investigate IR in association with thyroid function, psychoemotional state, and cardiovascular risk factors among 45–84-year-old citizens of Palanga. Methods: A randomized epidemiological study was performed with 850 subjects. All participants were evaluated for sociodemographic, clinical, and cardiovascular risk factors and biochemical analysis. IR was evaluated by the homeostasis model assessment of IR (HOMA-IR). Results: All study participants were stratified into groups without IR (HOMA-IR ≤ 2.7) and with IR (HOMA-IR > 2.7). The analysis of parameters between the two study groups showed some statistically significant relationships between IR and cardiovascular risk factors. The predictable accuracy was presented using receiver performance characteristic curves for HOMA-IR scores in women and men separately. If the HOMA-IR score is higher than 3.45, individuals are significantly more likely to have type 2 diabetes mellitus (T2DM). Conclusions: An increase of fasting glucose and more frequent incidence of metabolic syndrome, diabetes, and cardiovascular diseases in subjects with IR are associated with the prevalence of cardiovascular risk factors. There was no significant association between thyroid function and HOMA-IR. HOMA-IR cut-offs could predict the presence of T2DM.


Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Youssef A Elnabawi ◽  
Amit K Dey ◽  
Agastya D Belur ◽  
Aditya Goyal ◽  
Jacob W Groenendyk ◽  
...  

Introduction: Serum uric acid (sUA), a known inflammosome-inducer, is associated with prospective risk of coronary artery disease in a dose-dependent fashion. Psoriasis (PSO), a chronic inflammatory disease associated with elevated burden of systemic inflammation and subclinical coronary artery disease, provides a reliable human model to study how sUA may relate to non-calcified coronary plaque burden (NCB) measured by computed coronary tomography angiography (CCTA). Hypothesis: We hypothesized that sUA would directly associate with NCB beyond traditional cardiovascular (CV) risk factors. Methods: 103 consecutive PSO patients and 47 healthy volunteers (HV) underwent CCTA (320 detector row, Toshiba) for coronary plaque burden quantification using QAngio (Medis). PSO severity was assessed by Psoriasis Area Severity Score (PASI) and divided into severe PSO (PASI>10) and mild-moderate PSO (PASI<10). All patients had fasting blood draws for the measurement of sUA at a certified clinical lab. Results: PSO patients were older than HV and had a higher CV risk by Framingham risk score (FRS) (Table 1). We observed a significant trend towards increase in sUA among severe PSO, mild-moderate PSO, and HV groups (mean 6.4, 5.9, 5.4 respectively, p=0.02 for trend). A positive association was observed between sUA and NCB, which was stronger in severe PSO after adjustment for traditional CV risk, alcohol, statins, and systemic/biologic PSO treatment (Severe PSO: β=0.27, p<0.001; Mild-moderate PSO: β=0.18, p=0.03), not significant in HV (β=0.18, p=0.12). Conclusions: sUA is independently associated with NCB in states of chronic inflammation such as PSO, and as such, may potentially serve as a biomarker for subclinical coronary atherosclerosis. However, larger prospective studies of CV outcomes in chronic inflammatory diseases are needed to confirm these results.


2009 ◽  
Vol 160 (1) ◽  
pp. 45-52 ◽  
Author(s):  
Lucia Pacifico ◽  
Vito Cantisani ◽  
Caterina Anania ◽  
Elisabetta Bonaiuto ◽  
Francesco Martino ◽  
...  

ObjectiveThe association between hyperuricemia, metabolic syndrome (MS), and atherosclerotic vascular disease has been reported in adults, but very little is known about this association in children. The aims of our study were to ascertain the correlates of uric acid (UA) in a sample of obese children, and to investigate whether UA is associated with carotid intima-media thickness (IMT) independently from classical risk factors including MS.MethodsWe analyzed carotid IMT along with serum triglycerides, total and high-density lipoprotein cholesterol, glucose, insulin, insulin resistance index (as homeostasis model assessment of insulin resistance), alanine aminotransferase, γ-glutamyltransferase, creatinine, and UA in 120 obese children and 50 healthy control children.ResultsUA concentrations were significantly higher in obese children compared with controls; moreover, they correlated with the most established cardiovascular risk factors. In the group of obese children, after adjustment for age, sex, pubertal stage, and creatinine, an independent association between UA levels and the presence of MS syndrome was observed (unstandardized coefficient, 0.044 (95% confidence intervals (CI) 0.015–0.072); P<0.01). Carotid IMT significantly increased in the fourth quartile of UA compared with that in the first, second, and third quartile (0.49 (0.46–0.53), 0.53 (0.49–0.56), and 0.55 (0.52–0.59) vs 0.61 (95% CI, 0.58–0.64); P<0.01). When multivariate analysis was performed after adjusting for age, gender, pubertal stage, creatinine, and MS (considered as a single clinical entity), or the individual components of MS simultaneously included, the association between UA and carotid IMT was significant (P<0.01).ConclusionsIn obese children and adolescents, increased UA levels are associated with carotid atherosclerosis.


2004 ◽  
pp. 715-718 ◽  
Author(s):  
KM Choi ◽  
J Lee ◽  
KW Lee ◽  
JA Seo ◽  
JH Oh ◽  
...  

OBJECTIVE: Ghrelin is a recently discovered peptide, which is produced primarily in the stomach. This orexigenic peptide participates not only in the induction of mealtime hunger but also in long-term body weight regulation and energy homeostasis. Adiponectin is a protein secreted by adipocytes, and has been proposed to mediate obesity-related insulin resistance. Moreover, concentrations of adiponectin are reduced in individuals with obesity, insulin resistance and cardiovascular disease. However, human data are sparse about the direct relationship between adiponectin, ghrelin and cardiovascular risk factors including insulin resistance. DESIGN: Three hundred and thirty-eight elderly Korean women (mean age+/-s.d., 72.3+/-5.5 years) were included in the present study. METHODS: Plasma ghrelin and adiponectin levels were measured by RIA. Anthropometric measurements were taken and a 75 g oral glucose tolerance test performed. Fasting insulin and lipid profile were measured and insulin resistance was determined using the homeostasis model assessment insulin resistance index (HOMA-R) and the quantitative insulin sensitivity check index. RESULTS: Plasma adiponectin levels were negatively correlated with central obesity indices such as waist circumference (r=-0.27, P<0.001) and waist-to-hip ratio (WHR) (r=-0.32, P<0.001), and with insulin resistance indices such as fasting insulin (r=-0.17, P=0.004) and HOMA-R (r=-0.13, P=0.035). Plasma ghrelin levels were negatively correlated with WHR (r=-0.12, P=0.03), but plasma adiponectin and ghrelin levels were not correlated (r=0.03, P=0.66). Multiple regression analysis showed that adiponectin was associated with WHR, fasting insulin and fasting glucose levels. When ghrelin was used as a dependent variable, only WHR remained in the final fitted model. CONCLUSION: Fasting plasma adiponectin and ghrelin levels were found to be associated with central obesity or insulin resistance. However, plasma adiponectin and ghrelin concentrations were not associated with each other in elderly Korean women.


Author(s):  
Malgorzata Malczewska-Malec ◽  
Iwona Wybranska ◽  
Iwona Leszczynska-Golabek ◽  
Lukasz Partyka ◽  
Jadwiga Hartwich ◽  
...  

AbstractThis study analyzes the relationship between risk factors related to overweight/obesity, insulin resistance, lipid tolerance, hypertension, endothelial function and genetic polymorphisms associated with: i) appetite regulation (leptin, melanocortin-3-receptor (MCR-3), dopamine receptor 2 (D2R)); ii) adipocyte differentiation and insulin sensitivity (peroxisome proliferator-activated receptor-γThe 122 members of 40 obese Caucasian families from southern Poland participated in the study. The genotypes were analyzed by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) or by direct sequencing. Phenotypes related to obesity (body mass index (BMI), fat/lean body mass composition, waist-to-hip ratio (WHR)), fasting lipids, glucose, leptin and insulin, as well as insulin during oral glucose tolerance test (OGTT) (4 points within 2 hours) and during oral lipid tolerance test (OLTT) (5 points within 8 hours) were assessed. The insulin sensitivity indexes: homeostasis model assessment of insulin resistance, whole body insulin sensitivity index, hepatic insulin sensitivity and early secretory response to an oral glucose load (HOMA-IR, ISI-COMP, ISI-HOMA and DELTA) were calculated.The single gene mutations such as CWe conclude that the polymorphisms we investigated were weakly correlated with obesity but significantly modified the risk factors of the metabolic syndrome.


2005 ◽  
Vol 33 (3) ◽  
pp. 284-294 ◽  
Author(s):  
G Derosa ◽  
AV Gaddi ◽  
L Ciccarelli ◽  
E Fogari ◽  
M Ghelfi ◽  
...  

We evaluated the effect of glimepiride plus metformin and rosiglitazone plus metformin on glucose, and on cardiovascular risk parameters such as lipoprotein(a) (Lp[a]) and homocysteine (HCT) in patients with type 2 diabetes and metabolic syndrome. Ninety-nine patients in the multicentre, randomized, double-blind study took metformin (1500 mg/day) plus glimepiride (2 mg/day) or rosiglitazone (4 mg/day) for 12 months. Changes in body mass index, glycosylated haemoglobin (HbA1c), Lp(a) and HCT were primary efficacy variables. Fasting plasma glucose (FPG), post-prandial plasma glucose (PPG) and homeostasis model assessment index were also used to assess efficacy. On average, HbA1c decreased by 9.1% and 8.1%, FPG decreased by 7.3% and 10.9%, and PPG decreased by 7.6% and 10.5%, respectively, in the glimepiride and rosiglitazone groups after 12 months. Patients receiving rosiglitazone experienced more rapid improvement in glycaemic control than those on glimepiride, and showed a significant improvement in insulin resistance-related parameters. There was a statistically significant decrease in basal homocysteinaemia in glimepiride-treated patients (−27.3%), but not in rosiglitazone-treated patients. Rosiglitazone plus metformin significantly improved long-term control of insulin resistance-related parameters compared with glimepiride plus metformin, although glimepiride treatment was associated with a slight improvement in cholesterolaemia, not observed in the rosiglitazone-treated patients, and with significant improvements in non-traditional risk factors for cardiovascular disease, such as basal homocysteinaemia and plasma Lp(a) levels.


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