Periodontitis, Dental Procedures, and Young-Onset Cryptogenic Stroke.

Periodontitis is associated with an increased risk of ischemic stroke, and the risk may be particularly high among young people with unexplained stroke etiology. Thus, we investigated in a case-control study whether periodontitis or recent invasive dental treatments are associated with young-onset cryptogenic ischemic stroke (CIS). We enrolled participants from a multicenter case-control SECRETO study including adults aged 18 to 49 y presenting with an imaging-positive first-ever CIS and stroke-free age- and sex-matched controls. Thorough clinical and radiographic oral examination was performed. Furthermore, we measured serum lipopolysaccharide (LPS) and lipotechoic acid (LTA) levels. Multivariate conditional regression models were adjusted for stroke risk factors, regular dentist visits, and patent foramen ovale (PFO) status. We enrolled 146 case-control pairs (median age 41.9 y; 58.2% males). Periodontitis was diagnosed in 27.5% of CIS patients and 20.1% of controls (P < 0.001). In the fully adjusted models, CIS was associated with high periodontal inflammation burden (odds ratio [OR], 95% confidence interval) with an OR of 10.48 (3.18-34.5) and severe periodontitis with an OR of 7.48 (1.24-44.9). Stroke severity increased with the severity of periodontitis, having an OR of 6.43 (1.87-23.0) in stage III to IV, grade C. Invasive dental treatments performed within 3 mo prestroke were associated with CIS, with an OR of 2.54 (1.01-6.39). Association between CIS and invasive dental treatments was especially strong among those with PFO showing an OR of 6.26 (1.72-40.2). LPS/LTA did not differ between CIS patients and controls but displayed an increasing trend with periodontitis severity. Periodontitis and recent invasive dental procedures were associated with CIS after controlling for multiple confounders. However, the role of bacteremia as a mediator of this risk was not confirmed.

Elevated Glucose Oxidation, Reduced Insulin Secretion, and a Fatty Heart May Be Protective Adaptions in Ischemic CAD.

BACKGROUND: Insulin resistance, ß-cell dysfunction, and ectopic fat deposition have been implicated in the pathogenesis of coronary artery disease (CAD) and type 2 diabetes, which is common in CAD patients. We investigated whether CAD is an independent predictor of these metabolic abnormalities and whether this interaction is influenced by superimposed myocardial ischemia. METHODS AND RESULTS: We studied CAD patients with (n = 8) and without (n = 14) myocardial ischemia and eight non-CAD controls. Insulin sensitivity and secretion and substrate oxidation were measured during fasting and oral glucose tolerance testing. We used magnetic resonance imaging/spectroscopy, positron emission and computerized tomography to characterize CAD, cardiac function, pericardial and abdominal adipose tissue, and myocardial, liver, and pancreatic triglyceride contents. Ischemic CAD was characterized by elevated oxidative glucose metabolism and a proportional decline in ß-cell insulin secretion and reduction in lipid oxidation. Cardiac function was preserved in CAD groups, whereas cardiac fat depots were elevated in ischemic CAD compared to non-CAD subjects. Liver and pancreatic fat contents were similar in all groups and related with surrounding adipose masses or systemic insulin sensitivity. CONCLUSIONS: In ischemic CAD patients, glucose oxidation is enhanced and correlates inversely with insulin secretion. This can be seen as a mechanism to prevent glucose lowering because glucose is required in oxygen-deprived tissues. On the other hand, the accumulation of cardiac triglycerides may be a physiological adaptation to the limited fatty acid oxidative capacity. Our results underscore the urgent need of clinical trials that define the optimal/safest glycemic range in situations of myocardial ischemia.

Similar patterns of myocardial metabolism and perfusion in patients with type 2 diabetes and heart disease of ischaemic and non-ischaemic origin.

AIMS/HYPOTHESIS: Type 2 diabetes and insulin resistance are often associated with the co-occurrence of coronary atherosclerosis and cardiac dysfunction. The aim of this study was to define the independent relationships between left ventricular dysfunction or ischaemia and patterns of myocardial perfusion and metabolism in type 2 diabetes. METHODS: Twenty-four type 2 diabetic patients--12 with coronary artery disease (CAD) and preserved left ventricular function and 12 with non-ischaemic heart failure (HF)--were enrolled in a cross-sectional study. Positron emission tomography (PET) was used to assess myocardial blood flow (MBF) at rest, after pharmacological stress and under euglycaemic hyperinsulinaemia. Insulin-mediated myocardial glucose disposal was determined with 2-deoxy-2-[(18)F]fluoroglucose PET. RESULTS: There was no difference in myocardial glucose uptake (MGU) between the healthy myocardium of CAD patients and the dysfunctional myocardium of HF patients. MGU was strongly influenced by levels of systemic insulin resistance in both groups (CAD, r = 0.85, p = 0.005; HF, r = 0.77, p = 0.01). In HF patients, there was an inverse association between MGU and the coronary flow reserve (r = -0.434, p = 0.0115). A similar relationship was observed in non-ischaemic segments of CAD patients. Hyperinsulinaemia increased MBF to a similar extent in the non-ischaemic myocardial of CAD and HF patients. CONCLUSIONS/INTERPRETATION: In type 2 diabetes, similar metabolic and perfusion patterns can be detected in the non-ischaemic regions of CAD patients with normal cardiac function and in the dysfunctional non-ischaemic myocardium of HF patients. This suggests that insulin resistance, rather than diagnosis of ischaemia or left ventricular dysfunction, affects the metabolism and perfusion features of patients with type 2 diabetes.

Analytic system matrix resolution modeling in PET: an application to Rb-82 cardiac imaging.

This work explores application of a novel resolution modeling technique based on analytic physical models which individually models the various resolution degrading effects in PET (positron range, photon non-collinearity, inter-crystal scattering and inter-crystal penetration) followed by their combination and incorporation within the image reconstruction task. In addition to phantom studies, the proposed technique was particularly applied to and studied in the task of clinical Rb-82 myocardial perfusion imaging, which presently suffers from poor statistics and resolution properties in the reconstructed images. Overall, the approach is able to produce considerable enhancements in image quality. The reconstructed FWHM for a Discovery RX PET/CT scanner was seen to improve from 5.1 mm to 7.7 mm across the field-of-view (FoV) to approximately 3.5 mm nearly uniformly across the FoV. Furthermore, extended-source phantom studies indicated clearly improved images in terms of contrast versus noise performance. Using Monte Carlo simulations of clinical Rb-82 imaging, the resolution modeling technique was seen to significantly outperform standard reconstructions qualitatively, and also quantitatively in terms of contrast versus noise (contrast between the myocardium and other organs, as well as between myocardial defects and the left ventricle).

Present and future of clinical cardiovascular PET imaging in Europe--a position statement by the European Council of Nuclear Cardiology (ECNC).

This position statement was prepared by the European Council of Nuclear Cardiology and summarises the current and future potential of PET as a clinical cardiovascular diagnostic imaging tool. The first section describes how methodological developments have positively influenced the transition of PET from a research tool towards a clinical diagnostic test. In the second section, evidence in support of its superior diagnostic accuracy, its value to guide decision making and to predict outcome and its cost effectiveness is summarised. The third section finally outlines new PET-based approaches and concepts, which will likely influence clinical cardiovascular medicine in the future. The notion that integration of cardiac PET into healthcare systems and disease management algorithms will advance quality of care is increasingly supported by the literature highlighted in this statement.

Non-invasive estimation of hepatic blood perfusion from H2 15O PET images using tissue-derived arterial and portal input functions.

PURPOSE: The liver is perfused through the portal vein and the hepatic artery. When its perfusion is assessed using positron emission tomography (PET) and (15)O-labeled water (H(2) (15)O), calculations require a dual blood input function (DIF), i.e., arterial and portal blood activity curves. The former can be generally obtained invasively, but blood withdrawal from the portal vein is not feasible in humans. The aim of the present study was to develop a new technique to estimate quantitative liver perfusion from H(2) (15)O PET images with a completely non-invasive approach. METHODS: We studied normal pigs (n=14) in which arterial and portal blood tracer concentrations and Doppler ultrasonography flow rates were determined invasively to serve as reference measurements. Our technique consisted of using model DIF to create tissue model function and the latter method to simultaneously fit multiple liver time-activity curves from images. The parameters obtained reproduced the DIF. Simulation studies were performed to examine the magnitude of potential biases in the flow values and to optimize the extraction of multiple tissue curves from the image. RESULTS: The simulation showed that the error associated with assumed parameters was <10%, and the optimal number of tissue curves was between 10 and 20. The estimated DIFs were well reproduced against the measured ones. In addition, the calculated liver perfusion values were not different between the methods and showed a tight correlation (r=0.90). CONCLUSION: In conclusion, our results demonstrate that DIF can be estimated directly from tissue curves obtained through H(2) (15)O PET imaging. This suggests the possibility to enable completely non-invasive technique to assess liver perfusion in patho-physiological studies.

Effects of exhaustive stretch-shortening cycle exercise on muscle blood flow during exercise.

AIM: The influence of exhaustive stretch-shortening cycle exercise (SSC) on skeletal muscle blood flow (BF) during exercise is currently unknown. METHODS: Quadriceps femoris (QF) BF was measured in eight healthy men using positron emission tomography before and 3 days after exhaustive SSC exercise. The SSC protocol consisted of maximal and submaximal drop jumps with one leg. Needle biopsies of the vastus lateralis muscles were taken immediately and 2 days after SSC for muscle endothelial nitric oxide synthase (eNOS) and interleukin-1-beta (IL-1beta) mRNA level determinations. RESULTS: All subjects reported subjective muscle soreness after SSC (P < 0.001), which was well in line with a decrease in maximal isometric contraction force (MVC) and increase in serum creatine kinase activity (CK) (P = 0.018). After SSC muscle BF was 25% higher in entire QF (P = 0.043) and in its deep and superficial muscle regions, whereas oxygen uptake remained unchanged (P = 0.893). Muscle biopsies revealed increased IL-1beta (30 min: 152 +/- 75%, P = 0.012 and 2 days: 108 +/- 203%, P = 0.036) but decreased or unchanged eNOS (30 min; -21 +/- 57%, P = 0.050 and 2 days: +101 +/- 204%, P = 0.779) mRNA levels after SSC. CONCLUSION: It was concluded that fatiguing SSC exercise induces increased muscle BF during exercise, which is likely to be associated with pro-inflammatory processes in the exercised muscle.

Non-esterified fatty acids impair insulin-mediated glucose uptake and disposition in the liver.

AIMS/HYPOTHESIS: We investigated the effect of elevated circulating NEFA on insulin-mediated hepatic glucose uptake (HGU) and whole-body glucose disposal (M) in eight healthy male subjects. METHODS: Studies were performed using positron emission tomography (PET) and [(18)F]-2-fluoro-2-deoxyglucose ([(18)F]FDG) during euglycaemic hyperinsulinaemia (0-120 min) and an Intralipid/heparin infusion (IL/Hep; -90-120 min). On a different day, similar measurements were taken during euglycaemic hyperinsulinaemia and saline infusion (SAL). Graphical and compartmental analyses were used to model liver data. RESULTS: Circulating NEFA increased approximately three-fold during IL/Hep, and declined by 81+/-7% in the SAL study ( p