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Increased perivascular fat mass contributes to cardiometabolic risk (CMR). High peribrachial adipose tissue (PBAT) associates with insulin resistance independently of established CMR parameters. It is unknown to what extent periaortic adipose tissue (PAAT) may have a similar impact. In 95 participants, precise quantification of total adipose tissue, PBAT, PAAT, visceral adipose tissue (VAT), and liver fat (LF) content was performed by whole-body magnetic resonance imaging. Insulin sensitivity was determined by oral glucose tolerance test and carotid intima–media thickness (cIMT) by high-resolution ultrasound. In univariate analyses, PAAT correlated with PBAT (β = .65, P < .0001). A negative correlation of PAAT (β = −.35, P = .0002) and PBAT (β = −.43, P < .0001) with insulin sensitivity was observed. While in a stepwise forward regression analysis the relationship of PAAT with insulin sensitivity was no longer significant after adjustment for VAT, LF content, and other CMR factors ( P = 0.42), PBAT still correlated with insulin sensitivity ( r2 = .35, P = .01). The association between PAAT and cIMT (β = .49, P < .0001) remained significant after adjustment for these variables ( r2 = .42, P = .0001). Although PAAT and PBAT strongly correlate, PAAT is not associated with insulin resistance, but with cIMT. Therefore, PAAT and PBAT may act differently as possible modulators of insulin resistance and subclinical atherosclerosis.

Aim: The visceral adiposity index (VAI) has been proposed as an estimate of visceral adipose tissue (VAT) mass and as an indicator of VAT dysfunction. Both parameters are associated with cardiometabolic risk, including insulin resistance. In this study, we investigated whether VAI is associated with subclinical atherosclerosis in subjects who were free of cardiovascular disease but were at risk of developing diabetes mellitus.Methods: A total of 731 adults with a median age of 47 years old without diabetes mellitus were included in this cross-sectional study. The anthropometric data, blood pressure, and lipid profiles of 398 women and 333 men were measured. All subjects underwent an oral glucose tolerance test, and carotid intima -media thickness (cIMT) was evaluated by ultrasound. Insulin resistance was estimated using the homeostatic model assessment of insulin resistance (HOMA-IR).Results: VAI and HOMA-IR (beta(st) = 0.44, p < 0.0001), VAI and cIMT (beta(st) = 0.17, p < 0.0001), and HOMA-IR and cIMT (beta(st) = 0.09, p = 0.0127) were correlated with each other. After adjusting for cofounding variables, VAI is still correlated with HOMA-IR (beta(st) = 0.42, p < 0.0001). Furthermore, VAI (beta(st) = 0.07, p = 0.0392) but not HOMA-IR (beta(st )= 0.03, p = 0.37) was correlated with cIMT independently of other established cardiovascular risk factors.Conclusion: The calculation of VAI may provide a better estimation of subclinical atherosclerosis than the calculation of HOMA-IR.

To longitudinally assess the value of cardiac functional and viability imaging as a supplement to MR angiography in patients with atherosclerotic disease.Cardiac MRI was performed in 195 consecutive patients with symptomatic peripheral arterial disease. Of these, 186 patients were followed for 22 +/- 5 months for the presence of cardiac events (cardiac death, acute coronary syndrome and hospitalisation as a result of congestive heart failure).Myocardial viability imaging showed a high prevalence of known (n = 31) and occult myocardial infarctions (MI) (n = 26). Cardiac events occurred more often in patients with reduced ventricular function (ejection fraction (EF) less than 40%, cardiac event in 4/8 patients; EF 40-55%, cardiac event in 10/40 patients; EF greater than 55%, cardiac event in 15/138 patients) as well as in patients with occult MI (8/25 patients) and known MI (11/30 patients). In patients with normal function, the detection of a previous MI was of high relevance to prognosis.Both reduced EF and the presence of MI influence patients' prognoses. Performing cardiac MRI in this patient population may influence further patient management including intensified risk factor intervention.

Monocyte-chemoattractant-protein (MCP)-1 and its receptor CCR2 have been shown to play a pivotal role in vascular inflammation and atherosclerotic plaque formation. However, it is currently unclear whether MCP-1/CCR2 triggered inflammation affects nitric oxide (NO)-bioavailability, hence influencing vascular function, a sign of early atherosclerosis. Therefore, we sought to investigate the association between serum levels of MCP-1 and NO-bioavailability, expressed as flow mediated dilation (FMD) in vivo, and the impact of CCR2 gene variations on FMD. We studied a German population of 242 prediabetic individuals (144 women, 98 men; mean age 45+/-0.8 years) via FMD by high-resolution ultrasound (13MHz). In order to replicate our findings, a second, independent population (n=115; 44 women, 77 men; mean age 48+/-1.0 years) (total=357 individuals) from Italy was studied. Vascular function in the Italian population was studied via intra-arterial application of acetylcholine. MCP-1 serum-levels were assessed by ELISA and CCR2 polymorphisms were determined by sequencing. MCP-1 serum levels showed no association with FMD (p=0.90), whereas the CCR2 promoter polymorphism was associated with elevated FMD (T/T: 5.6+/-0.3%; T/A: 6.7+/-0.4%; A/A: 8.3+/-0.8%; p=0.01) after adjusting for possible confounders. These results were confirmed in the independent Italian population (A/A: 97.1+/-20.3 vs. T/T: 60.5+/-5.6% forearm blood-flow increase; p

Circulating trimethylamine N-Oxide (TMAO) levels predict cardiovascular disease (CVD), possibly by impacting on cholesterol metabolism and oxidative stress. Because hepatic TMAO production is regulated by insulin signalling and it is unclear whether and to what extent circulating TMAO levels associate with CVD risk, independently of insulin resistance and its important determinants fatty liver and visceral obesity, we have now addressed this question in 220 subjects who participated in the Tübingen Lifestyle Intervention Program. Visceral fat mass (r = 0.40, p 20%). We provide novel information that increased serum TMAO levels associate with increased cIMT, independently of established cardiovascular risk markers, including insulin resistance, visceral obesity and fatty liver. Furthermore, the decrease of cIMT during a lifestyle intervention may be related to the decrease of TMAO levels.

Background— Antidiabetic thiazolidinediones (TZDs), like rosiglitazone or pioglitazone, improve endothelial function in patients with type 2 diabetes or metabolic syndrome, but it is currently unknown, whether these beneficial effects of TZDs depend on their metabolic action or may be caused by direct effects on the endothelium. Therefore, the present study examined whether short-term rosiglitazone treatment influences endothelium-dependent vasodilation as well as serum levels of vascular disease biomarkers in healthy, nondiabetic subjects. Methods and Results— Short-term treatment (21 days) of healthy subjects (n=10) did not significantly change blood glucose levels or lipid profile. In contrast, rosiglitazone significantly increased flow-mediated, endothelium-dependent vasodilation already within the first day from 5.3±2.7% at baseline to 7.8±2.6%, further increasing it to 9.4±3.0% at day 21. In addition, the early improvement of endothelium-dependent vasodilation was paralleled by a rapid reduction of serum levels of the biomarkers C-reactive protein (CRP), serum amyloid A (SAA), and sE-selectin. Moreover, after drug withdrawal all markers remained suppressed for the whole follow-up period of 7 days. In contrast, rosiglitazone treatment did not significantly affect tumor necrosis factor (TNF)-α, interleukin (IL)-6, sICAM-1, sVCAM-1, and sCD40L levels. Conclusions— Our study suggests a direct effect of TZD treatment on endothelial function and inflammatory biomarkers of arteriosclerosis, promoting the concept that TZDs, independent of their metabolic action, may exhibit protective effects in the vessel wall.