Abstract-Atherosclerotic cardiovascular disease results in Ͼ19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of

Atherosclerotic cardiovascular disease results in >19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of opportunity in the field of cardiovascular medicine. This consensus document concludes the following. (1) Rupture-prone plaques are not the only vulnerable plaques. All types of atherosclerotic plaques with high likelihood of thrombotic complications and rapid progression should be considered as vulnerable plaques. We propose a classification for clinical as well as pathological evaluation of vulnerable plaques. (2) Vulnerable plaques are not the only culprit factors for the development of acute coronary syndromes, myocardial infarction, and sudden cardiac death. Vulnerable blood (prone to thrombosis) and vulnerable myocardium (prone to fatal arrhythmia) play an important role in the outcome. Therefore, the term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future. (3) A quantitative method for cumulative risk assessment of vulnerable patients needs to be developed that may include variables based on plaque, blood, and myocardial vulnerability. In Part I of this consensus document, we cover the new definition of vulnerable plaque and its relationship with vulnerable patients. Part II of this consensus document will focus on vulnerable blood and vulnerable myocardium and provide an outline of overall risk assessment of vulnerable patients. Parts I and II are meant to provide a general consensus and overviews the new field of vulnerable patient. Recently developed assays (eg, C-reactive protein), imaging techniques (eg, CT and MRI), noninvasive electrophysiological tests (for vulnerable myocardium), and emerging catheters (to localize and characterize vulnerable plaque) in combination with future genomic and proteomic techniques will guide us in the search for vulnerable patients. It will also lead to the development and deployment of new therapies and ultimately to reduce the incidence of acute coronary syndromes and sudden cardiac death. We encourage healthcare policy makers to promote translational research for screening and treatment of vulnerable patients.

Background-A method is needed to identify nonstenotic, lipid-rich coronary plaques that are likely to cause acute coronary events. Near-infrared (NIR) spectroscopy can provide information on the chemical composition of tissue. We tested the hypothesis that NIR spectroscopy can identify plaque composition and features associated with plaque vulnerability in human aortic atherosclerotic plaques obtained at the time of autopsy. Methods and Results-A total of 199 samples from 5 human aortic specimens were analyzed by NIR spectroscopy.Features of plaque vulnerability were defined by histology as presence of lipid pool, thin fibrous cap (Ͻ65 m by ocular micrometry), and inflammatory cell infiltration. An InfraAlyzer 500 spectrophotometer was used. Spectral absorbance values were obtained as log (1/R) data from 1100 to 2200 nm at 10-nm intervals. Principal component regression was used for analysis. An algorithm was constructed with 50% of the samples used as a reference set; blinded predictions of plaque composition were then performed on the remaining samples. NIR spectroscopy sensitivity and specificity for histological features of plaque vulnerability were 90% and 93% for lipid pool, 77% and 93% for thin cap, and 84% and 89% for inflammatory cells, respectively. Conclusions-NIR

Previous studies in our laboratory have implicated adipose tissue as a potential site for local angiotensin II (ANG II) synthesis. However, functions of ANG II in adipose tissue and the impact of ANG II on body weight regulation are not well defined. To study the effect of ANG II on body weight, a chronic ANG II infusion model was used. In study 1, a low dose of ANG II (175 ng ⋅ kg−1 ⋅ min−1) was infused into rats for 14 days. Plasma ANG II levels were not elevated after 14 days of infusion. ANG II-infused rats did not gain weight over the 14-day protocol and exhibited a lower body weight than controls on day 8. Food intake was not altered, but water intake was increased in ANG II-infused rats. Blood pressure gradually increased to significantly elevated levels by day 14. Thermal infrared imaging demonstrated an increase in abdominal surface temperature. Measurement of organ mass demonstrated site-specific reductions in white adipose tissue mass after ANG II infusion. In study 2, the dose-response relationship for ANG II infusion (200, 350, and 500 ng ⋅ kg−1 ⋅ min−1) was determined. Body weight (decrease), blood pressure (increase), white adipose mass (decrease), plasma ANG II levels (increase), and plasma leptin levels (decrease) were altered in a dose-related manner after ANG II infusion. In study 3, the effect of ANG II infusion (350 ng ⋅ kg−1 ⋅ min−1) was examined in rats treated with the vasodilator hydralazine. Hydralazine treatment normalized blood pressure in ANG II-infused rats. The effect of ANG II to decrease body weight was augmented in hydralazine-treated rats. These results demonstrate that low levels of ANG II infusion regulate body weight through mechanisms related to increased peripheral metabolism and independent of elevations in blood pressure.

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A near-IR imaging system and parallel vector supercomputer are used with a fiber-optic probe to produce chemical maps of the intimal surface of living arteries. Spectrometric information collected at hundreds of near-IR wavelengths is assembled into color pictures of the lipoprotein and apolipoprotein composition of atheromas using a vectorized 3-D cellular automaton-based algorithm that operates in parallel. The nonparametric mathematics developed to identify and quantify the constituents of each voxel in the artery wall avoid the matrix factorizations that generate excess error in other pattern recognition methods and permit analysis in a wavelength space of over 1000 dimensions using fewer than 100 calibration samples. A surface feature resolution of 5.5 microns and depth resolution of 6.5 microns are achieved with the system. Data from the fiber optics confirm the injury hypothesis of lesion formation and the differing roles of HDL and LDL in cholesterol transport. In clinical studies, approximately 1/2 of human arterial lesions appear fibrous and contain little or no lipid. As such, these lesions would not be expected to regress in response to cholesterol-lowering agents such as lovastatin. Identification of lesion types in vivo will enhance the efficacy of treatment programs.

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