Objectives The goal of this study was to identify histomorphologic characteristics of atherosclerotic plaques and to determine the amenability of some of these components to be used as markers for invasive and noninvasive imaging. Background Rupture of the atherosclerotic plaques is responsible for the majority of acute coronary events, and the culprit lesions demonstrate distinct histopathologic features. It has been tacitly believed that plaque rupture (PR) is associated with angiographically minimally occlusive lesions. Methods We obtained 295 coronary atherosclerotic plaques, including stable (fibroatheroma [FA]; n = 105), vulnerable (thin-cap fibroatheroma [TCFA]; n = 88), and disrupted plaques (plaque rupture [PR]; n = 102) from the hearts of 181 men and 32 women who had died suddenly. The hierarchical importance of fibrous cap thickness, percent luminal stenosis, macrophage area, necrotic core area, and calcified plaque area was evaluated by using recursive partitioning analysis. Because clinical assessment of fibrous cap thickness is not possible by noninvasive imaging, it was excluded from the second set of partitioning analysis. Results Thickness of the fibrous cap emerged as the best discriminator of plaque type; the cap thickness measured <55 μm in ruptured plaques, and all FA were associated with >84-μm cap thickness. Although the majority of TCFA were found in the 54- to 84-μm thickness group, those with <54-μm thickness were more likely to show <74% luminal stenosis (area under the curve: FA, 1.0; TCFA, 0.89; PR, 0.90). After exclusion of cap thickness, analysis of the plaque characteristics revealed macrophage infiltration and necrotic core to be the 2 best discriminators of plaque types (area under the curve: FA, 0.82; TCFA, 0.58; PR, 0.72). More than 75% cross-section area stenosis was seen in 70% of PR and 40% of TCFA; only 5% PR and 10% TCFA were <50% narrowed. Conclusions This postmortem study defines histomorphologic characteristics of vulnerable plaques, which may help develop imaging strategies for identification of such plaques in patients at a high risk of sustaining acute coronary events.

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Background: Many volatile organic compounds are present in exhaled breath and may represent by-products of endogenous biological processes. Ethanol is produced via alcoholic fermentation of glucose by gut bacteria and yeast, while acetone derives from oxidations of free fatty acids, influenced by glucose metabolism. We hypothesized that the integrated analysis of breath ethanol and acetone would provide a good approximation of the blood glucose profile during a glucose load.Methods: We collected simultaneous exhaled breath gas, ambient air, and serum glucose and insulin samples from 10 healthy volunteers at baseline and during an oral glucose tolerance test (OGTT) (ingestion of 75 g of glucose followed by 120 min of sampling). Gas samples were analyzed by gas chromatography/mass spectrometry.Results: Mean glucose values displayed a typical OGTT pattern (rapid increase, peak values at 30-60 min, and gradual return to near baseline by 120 min). Breath ethanol displayed a similar pattern early in the test, with peak values at 30 min; this was followed by a fast return to basal levels by 60 min. Breath acetone decreased progressively below basal levels, with lowest readings obtained at 120 min. A multiple regression analysis of glucose, ethanol, and acetone was used to estimate glucose profiles that correlated with measured glucose values with an average individual correlation coefficient of 0.70, and not lower than 0.41 in any subject.Conclusion: The integrated analysis of multiple exhaled gases may serve as a marker of blood glucose levels. Further studies are needed to assess the usefulness of this method in different populations.

The mechanism responsible for diminished exercise performance in cystic fibrosis (CF) is not clear. We hypothesized that reduced muscle size, rather than an intrinsic muscle defect, was the primary factor in such diminished exercise performance. Twenty-two subjects with CF (14 females and eight males, aged 6.5 to 17.7 yr, with FEV(1) of 46% to 111% predicted) participated in a study of this hypothesis, and were compared with healthy children tested in the same laboratory. Muscle size was estimated from midthigh muscle cross-sectional area (CSA) obtained by magnetic resonance imaging, and fitness was determined by progressive cycle ergometer exercise testing with breath-by-breath measurements of gas exchange. Peak oxygen consumption (V O(2)) was reduced in CF subjects (956 +/- 81 [mean +/- SEM] ml/min, as compared with 1,473 +/- 54 ml/min in controls; p < 0.00001). Surprisingly, CF subjects had a lower peak V O(2) per CSA (mean for CF subjects 70 +/- 3% predicted, p < 0.0001) than did controls, whereas muscle CSA in CF subjects was not significantly smaller than in controls. The scaling parameters of peak V O(2) and muscle CSA did not differ significantly between healthy controls (0.80 +/- 0.16) and CF subjects (1.03 +/- 0.12). Indexes of aerobic function that are less effort-dependent than peak V O(2) were also lower in the CF subjects (e.g., the slope of V O(2) versus work rate [WR] (DeltaV O(2)/DeltaWR) was 68 +/- 2% predicted; p < 0.005). The study data did not support the initial hypothesis, and suggest a muscle-related abnormality in oxygen metabolism in patients with CF.