Influenza infection exerts prominent inflammatory and thrombotic effects on the atherosclerotic plaques of apolipoprotein E-deficient mice.

BACKGROUND: The role of infection in the development and complications of atherosclerosis has been the focus of much attention. We reported previously that influenza vaccination was associated with reduced risk of recurrent myocardial infarction. Here, we report the effect of influenza A virus on the apolipoprotein E-deficient (apoE(-/-)) mouse, an animal model of atherosclerosis. METHODS AND RESULTS: Twenty-four apoE(-/-) mice >24 months old were injected with 1 LD(50) (lethal dose 50) of influenza A virus. Ten wild-type C57BL/6 infected mice and 11 noninfected age-matched apoE(-/-) mice served as controls. Multiple aortic sections were studied histologically 3, 5, and 10 days later. The infected mice showed markedly increased intimal cellularity compared with the noninfected apoE(-/-) mice. No aortic abnormalities were seen in infected wild-type mice. Ten infected apoE(-/-) mice had a significant subendothelial infiltrate composed of a heterogeneous group of cells that stained positively for smooth muscle cell actin, F4/80 (macrophages), and CD3 (T lymphocytes). One case of subocclusive platelet and fibrin-rich thrombus was seen. CONCLUSIONS: This study shows that influenza infection promotes inflammation, smooth muscle cell proliferation, and fibrin deposition in atherosclerotic plaques.

Near-infrared spectroscopic characterization of human advanced atherosclerotic plaques.

UNLABELLED: OBJECTIVES; Living human carotid atherosclerotic plaques were examined in vitro by near-infrared (NIR) spectroscopy to determine the spectral features of plaque vulnerability. BACKGROUND: Plaque disruption, a major cause of heart attacks and strokes, cannot generally be predicted, but is thought to depend mainly on plaque composition. Near-infrared spectroscopy has been used to detect components in tissues noninvasively. METHODS: Using an NIR spectrometer fitted with a fiberoptic probe, living human carotid atherosclerotic plaques (from 25 patients) were examined ex vivo for plaque vulnerability. The plaques were cut into smaller sections according to their gross pathologic features, and NIR measurements were done at 20 degrees C, usually within 10 min. RESULTS: According to the American Heart Association's recommended classification scheme, the lesions were classified into three groups: the first group comprised of vulnerable type V/VI lesions; the second group, stable type I/II lesions; and the third (intermediate) group, mainly type III/IV lesions. Cluster analysis of the specimens' NIR spectra identified three major composition groups in each of the three NIR spectral regions: 2,200 to 2,330 nm, 1,620 to 1,820 nm and 1,130 to 1,260 nm. Calculation of the lipid/protein ratios in each group at two NIR regions (2,200 to 2,330 nm) revealed ratios of 1.49 +/- 1.20, 2.12 +/- 1.00 and 3.37 +/- 0.88 for type I/II, type III/IV and advanced type V/VI lesions, respectively (p < 0.03). At 1,620 to 1,820 nm, the respective ratios for these histologic groups were 0.57 +/- 0.21, 1.54 +/- 0.46 and 2.40 +/- 0.44 (p < 0.00003). CONCLUSIONS: The good ex vivo discrimination of histologically vulnerable and stable plaques in this study suggests that NIR spectroscopy has the potential to identify vulnerable atherosclerotic plaques in vivo.

Is it time to prescribe statins to patients with calcified aortic stenosis?

Aortic stenosis (AS) is a common disease especially in the older population. It is associated with high mortality and morbidity. Recent data suggest that coronary artery disease and AS share common risk factors. Retrospective studies suggest that statins might slow the progression of AS but there are no randomized clinical trial data available. It would seem that statins can be considered for medical treatment of AS; however, this needs to be investigated in future randomized clinical trials.

Hypothermia is a bedside predictor of imminent death in patients with congestive heart failure.

BACKGROUND: Most studies on predictors of mortality for patients with congestive heart failure (CHF) have described predictors that are either difficult to measure in routine practice or are only modestly sensitive and specific. Having observed 3 patients whose body temperature decreased shortly before death, we hypothesized that hypothermia may predict inhospital mortality. METHODS: The medical records of 291 patients with a primary discharge diagnosis of CHF were selected from 423 admissions to Memorial Hermann Hospital, Houston, Tex, 1998, after excluding patients with comorbidities that confound body temperature, deaths for causes other than progressive pump failure, and readmissions except the last. Three groups were defined on the basis of admission body temperature (T adm): hypothermia groups T adm (95.5 degrees F-96.5 degrees F) and T adm < 95.5 degrees F, and reference group T adm > or = 96.6 degrees F. Several other known CHF risk factors were studied for confounding, and adjusted hazard ratios were calculated using Cox regression. RESULTS: Of the 291 patients (mean age 73 years, 47% men), 17 (6%) had hypothermia on admission. Mean hospital stay was 5 days. Of the 17 (6%) patients who died of pump failure, 5 had been hypothermic on admission. Hypothermia was significantly associated with survival, and after adjusting for New York Heart Association functional class, hazard ratio for T adm < 95.5 degrees F was 4.46 (95% confidence interval 1.38-14.3) (P trend = .0283). CONCLUSIONS: Hypothermia predicted inhospital death in these patients with CHF. If confirmed by future studies, this finding could prove useful, because temperature can be measured continuously, rapidly, and inexpensively, in or out of the hospital.

Finding vulnerable atherosclerotic plaques: is it worth the effort?

Techniques to identify and treat vulnerable plaques are the focus of enormous research. Some have questioned the benefit of locating individual vulnerable plaque in a multifocal disease. On autopsy, it is found that most deaths are caused by thrombotic occlusion of a single plaque; simultaneous occurrence of 2 occlusive thrombi is rare, but a second vulnerable plaque is common, particularly in acute myocardial infarction (MI). Angiographic progression is poorly predicted by risk factors, and angiographic progression is a weak predictor of MI or death. Intravascular ultrasonography (intravascular ultrasound [IVUS]) studies find plaque rupture in most MI patients and in approximately half with unstable angina, but in only a minority of patients with stable angina. IVUS identifies a second vulnerable plaque in many patients with unstable angina, and in most MI patients. Angioscopy reveals a very low incidence of a second vulnerable plaque compared with angiography and IVUS, but identifies additional yellow plaques in many patients with stable angina and in most patients with unstable angina or MI. Using thermography catheters and a temperature cutoff of 0.1 degrees C, approximately half the patients with stable angina have >1 hot lesion; however, if the cutoff is 0.2 degrees C, only approximately 15% have a second hot lesion. New imaging techniques may detect additional characteristics of plaques and new predictive models may assess the risk of vulnerable plaques and patients. This approach enables physicians to "buy time" by application of local therapies until systemic therapies stabilize plaques. This may also reduce the risk in subjects in whom systemic therapies do not work.

pH Heterogeneity of human and rabbit atherosclerotic plaques; a new insight into detection of vulnerable plaque.

BACKGROUND: Atherosclerotic plaques are heterogeneous with respect to inflammation, calcification, vascularity, oxygen, and temperature. We hypothesized that they also vary in pH and measured pH in living human carotid endarterectomized atherosclerotic plaques (CEA), Watanabe heritable hyperlipidemic (WHHL) rabbit aortas and human umbilical arteries (HUA). METHODS AND RESULTS: We measured pH of CEA of 48 patients, nine WHHL rabbit aortas and 11 HUA specimens (as controls) using a glass type microelectrode mounted on a micromanipulator in a 37 degrees C incubator. We also used single emission and also dual emission fluorescence ratio imaging microscopy employing pH-sensitive probes to confirm pH heterogeneity. Mean pH measured at 415 points of CEA was 7.55+/-0.32; at 275 points of WHHL rabbit aortas it was 7.40+/-0.43; and in 233 points of HUA it was 7.24+/-0.1. In CEA, pH of yellow (lipid-rich) areas was significantly lower than pH in calcified areas (7.15+/-0.01 vs. 7.73+/-0.01, P<0.0001). The coefficients of variation (heterogeneity) of pH in CEA, WHHL rabbit aortas, and HUA were 0.038+/-0.010, 0.039+/-0.007, and 0.009+/-0.003, respectively (P=0.0001). Fluorescence microscopic imaging confirmed pH heterogeneity in both humans and rabbits but not in HUA. In a variance components analysis 82% of the heterogeneity was due to the within-plaque variation and 2% was attributable to between-plaque variation. CONCLUSIONS: Our findings support the hypothesis of pH heterogeneity in plaques, and suggest a possible role for detecting low pH in the detection of plaque vulnerability. The source of pH heterogeneity particularly acidic pH, its impact on the stability of plaques and its potential clinical utility in locating vulnerable plaques remain to be evaluated.

Plaque blush, branch location, and calcification are angiographic predictors of progression of mild to moderate coronary stenoses.

BACKGROUND: Angiographic predictors of plaque progression are weak and few: length, irregular surface, turbulence, low shear, and (in some studies) eccentricity and calcification. Having noted plaques that briefly retained dye after angiography, we interpreted these as plaques with a fissured surface or neovascularization and hypothesized that progression would be predicted by "plaque blush." METHODS: Plaques (<50% diameter stenosis) in 68 pairs of angiograms, 5.6 +/- 4.8 months apart, were reviewed by 2 blinded observers. The presence of plaque blush, calcification, clot (mobile defect), eccentricity, and a branch point location were compared between progressing (> or =20% stenosis increase) and nonprogressing plaques. RESULTS: Sixteen lesions in 15 patients progressed from 29% +/- 13% to 68% +/- 14% over a period of 8.1 +/- 7.9 months. Patients with and without progression were similar in sex, age, congestive heart disease risk factors, medications, interval between angiograms, clinical presentation, and initial stenosis severity. By logistic regression, plaque blush (BL) (P =.002), calcification (CA) (P =.024), and a branch (BR) point location (P =.001) predicted plaque progression. The odds ratio for plaque progression (ORp) was calculated as ORp = e(2.5 x BL + 1.8 x CA + 2.6 x BR). Using an ORp of 1/3, the model has 81% sensitivity and 77% specificity. A second analysis in which each progressive lesion was compared with proximal and distal lesions and with one in a different coronary artery yielded similar results. CONCLUSIONS: In mild to moderate coronary stenoses, studied retrospectively, plaque blush (a new sign) and a branch point location were strong predictors of plaque progression, whereas calcification was a weak predictor of progression.

Thermal detection of vulnerable plaque.

In 1996, we showed that inflamed atherosclerotic plaques give off more heat and that vulnerable plaques may be detected by measuring their temperature. Plaque temperature is correlated directly with inflammatory cell density and inversely with the distance of the cell clusters from the luminal surface. It is inversely related to the density of the smooth muscle cells. We found no significant association between temperature heterogeneity and presence of Chlamydia pneumoniae in plaque or the gross color of human atherosclerotic carotid plaques. We also found pH heterogeneity in plaques from human carotid artery and aortas of Watanabe atherosclerotic rabbits and apolipoprotein E-deficient mice. Areas with lower pH had higher temperature, and areas with a large lipid core showed lower pH with higher temperature, whereas calcified regions had lower temperature and higher pH. We also developed a thermography basket catheter and showed in vivo temperature heterogeneity in atherosclerotic lesions of atherosclerotic dogs and Watanabe rabbits. Thermal heterogeneity was later documented in human atherosclerotic coronary arteries. Temperature difference between atherosclerotic plaque and healthy vessel wall is related to clinical instability. It is correlated with systemic markers of inflammation and is a strong predictor of adverse cardiac events after percutaneous interventions. Thermography is the first in a series of novel "functional" imaging methods and is moving to clinical trials. It may be useful for a variety of clinical and research purposes, such as detection of vulnerable plaques and risk stratification of vulnerable patients.

Houston biosecurity: building a national model.

On September 11, 2001, Al Qaeda terrorists committed an atrocity when they used domestic jetliners to crash into buildings in New York City and Washington, DC, killing thousands of people. In October 2001, another act of savagery occurred, this time using anthrax, not airplanes, to take innocent lives. Each incident demonstrates the vulnerability of an open society, and Americans are left to wonder how such acts can be prevented. Two years later, Al Qaeda operatives are reportedly regrouping, recruiting, and changing their tactics to distribute money and messages to operatives around the world. Many experts believe that terrorist attacks are inevitable. Every city is vulnerable to an attack, and none are fully prepared to handle the residual impact of a biological or chemical attack. A survey conducted by the Cable News Network (CNN) in January 2002, studied 30 major US cities, ranking them based on 6 statistical indices of vulnerability. Thirteen cities were deemed better prepared than Houston, 10 were in a similar state of preparedness, and only 6 were less prepared than Houston. We will discuss the protective measures that have been put in place in Houston, and future steps to take. Other cities can model Houston's experience to develop similar plans nation-wide.

Cardiomyopathy in association with selenium deficiency: a case report.

A 46-year-old man developed "dilated cardiomyopathy" probably caused by selenium deficiency while on total parenteral nutrition (TPN). This development emphasizes the role of considering selenium deficiency as a reversible cause of unexplained cardiomyopathy in impaired nutritional state.

Tissue pH determination for the detection of metabolically active, inflamed vulnerable plaques using near-infrared spectroscopy: an in-vitro feasibility study.

Detection of vulnerable plaques as the underlying cause of myocardial infarction is at the center of attention in cardiology. We have previously shown that infiltration of inflammatory cells in atherosclerotic plaques renders these plaques relatively hot and acidic, with substantial plaque temperature and pH variation. The objective of this investigation was to determine whether near-infrared diffuse reflectance spectroscopy (NIRS) could be used to non-destructively measure the tissue pH in atherosclerotic plaques. NIRS and tissue pH electrode measurements were taken on freshly excised carotid plaques maintained under physiological conditions. The coefficient of determination between NIRS and the pH microelectrode measurement was 0.75 using 17 different areas. The estimated accuracy of the NIRS measurement was 0.09 pH units. These results demonstrate the feasibility of using NIRS tissue pH in freshly excised atherosclerotic plaques in light of marked pH heterogeneity and warrants future in-vivo investigations on pH measurement of atherosclerotic plaques.

Influenza and atherosclerosis: vaccination for cardiovascular disease prevention.

In both animal and human studies, strong prothrombotic and pro-inflammatory effects have been observed after influenza infection. Influenza is an important trigger for acute coronary syndromes, and it has been shown that in the US it may cause up to 90,000 deaths per year simply by triggering fatal myocardial infarctions. Multiple case-control and cohort studies have shown that the influenza vaccine has a marked protective effect against cardiovascular events, decreasing the incidence of these events by 20 - 70% in the settings of primary and secondary prevention. Although influenza vaccination is an extremely cost-effective method of cardiovascular protection and is recommended for all patients with cardiac diseases, it is largely underused in these patients. Therefore, increased efforts should be directed towards educating physicians and patients about the benefits of influenza vaccination in patients with coronary heart disease.