(Circulation. 2000;102:2180.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Coronary Composition and Macrophage Infiltration in Atherectomy Specimens From Patients With Diabetes Mellitus
From the Gill Heart Institute, University of Kentucky, Lexington, Ky (P.R.M.); the Cardiac Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Mass (I.F.P., M.N.L.); the Cardiovascular Institute (V.F., J.T.F.) and the Department of Pathology (J.T.F.), The Mount Sinai School of Medicine, New York, NY; the Department of Internal Medicine, Mount Sinai Medical Center, Miami, Fla (A.M.M.); and the Excelsitas Medical Center, Buenos Aires, Argentina (V.H.B.).
Correspondence to Pedro R. Moreno, MD, 111B-CDD, VA Medical Center, Lexington, Kentucky 40511. E-mail pmoreno{at}pop.uky.edu
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Background—Lipid-rich, inflamed atherosclerotic lesions are associated with plaque rupture and thrombosis, which are the most important causes of death in patients with diabetes mellitus. This study was designed to quantify lipid composition and macrophage infiltration in the coronary lesions of patients with diabetes mellitus.
Methods and Results—A total of 47 coronary atherectomy specimens from patients with diabetes mellitus were examined and compared with 48 atherectomy specimens from patients without diabetes. Plaque composition was characterized by trichrome staining. Macrophage infiltration was characterized by immunostaining. Clinical and demographic data were similar in both groups. The percentage of total area occupied by lipid-rich atheroma was larger in specimens from patients with diabetes (7±2%) than in specimens from patients without diabetes (2±1%; P=0.01), and the percentage of total area occupied by macrophages was larger in specimens from patients with diabetes (22±3%) than in specimens from patients without diabetes (12±1%; P=0.003). The incidence of thrombus was also higher in specimens from patients with diabetes than in specimens from patients without diabetes (62% versus 40%; P=0.04). Plaque composition, macrophage infiltration, and thrombus were similar in lesions from diabetic patients treated with insulin compared with lesions from patients treated with sulfonylureas or diet.
Conclusions—Coronary tissue from patients with diabetes exhibits a larger content of lipid-rich atheroma, macrophage infiltration, and subsequent thrombosis than tissue from patients without diabetes. These differences suggest an increased vulnerability for coronary thrombosis in patients with diabetes mellitus.
Key Words: atherosclerosis • coronary disease • diabetes mellitus • plaque
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Atherosclerosis is the major cause of premature death in patients with either insulin-dependent or non–insulin-dependent diabetes; it accounts for
80% of all deaths and 75% of all
hospitalizations in these patients.1 Diabetic patients
with ischemic heart disease have a poor outcome after
myocardial infarction compared with nondiabetic patients.2
This outcome is even worse in diabetic patients treated with
sulfonylureas.3 Furthermore, diabetic patients have an
increased incidence of restenosis after
percutaneous transluminal coronary angioplasty
compared with nondiabetic patients.4 Plaque composition may play a role in the plaque disruption and thrombosis that leads to acute coronary events.5 6 7 Lesions with a large lipid core and increased macrophage infiltration may have a higher risk for disruption than sclerotic plaques.7 8 9 In addition, macrophage infiltration is also a predictor for restenosis after coronary intervention.10 Despite extensive autopsy studies, histopathologic analyses of lipid composition and macrophage infiltration in coronary lesions from patients with diabetes mellitus are limited. This study was designed to identify differences in plaque composition and macrophage infiltration in coronary lesions from patients with diabetes mellitus.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Definitions and Patient Population
From October 1990 to November 1994, 82 consecutive directional coronary atherectomy (DCA) procedures were performed for symptomatic coronary artery disease in patients with diabetes mellitus at the cardiac catheterization laboratory of Massachusetts General Hospital. Of these procedures, 47 were performed in culprit coronary lesions from patients with acute ischemic events; these patients comprise the study population. Forty-eight specimens from the culprit lesions of patients without diabetes mellitus who were matched to the study population by clinical syndrome comprise the control group. Lesions from patients treated for restenosis, saphenous vein graft disease, stable angina, or congestive heart failure were excluded. Diabetes mellitus was defined as a fasting blood glucose level >140 mg/dL in
2
different values. All diabetic patients were known diabetics
(mean, 8±4 years) at the time of the intervention. There were 13
insulin-dependant and 34 non–insulin-dependant diabetic patients. Of
the 34 non–insulin-dependent diabetics, 14 were treated with
sulfonylureas and 20 were treated with diet. To further evaluate if
plaque composition was different in these 3 groups of diabetic
patients, a subgroup analysis was performed.
Atherectomy Specimens
Multiple pieces of tissue were obtained from each lesion and
immediately immersion-fixed in 10% buffered formalin. Tissue was
routinely processed for paraffin embedding. Sections were serially cut
at 5 µm, mounted on lysine-coated slides, and stained with
hematoxylin and eosin and with the trichrome method.
Morphometry
Total and segmental areas for each of the plaque components were
quantified by planimetry for each specimen. The trichrome connective
tissue stain was used to identify and quantify specimen composition, as
previously reported.11 Briefly, collagen-rich
fibrocellular tissue is composed of tissue with scant cells and densely
stained collagen (Figure 1A
);
hypercellular tissue is composed of a loose connective tissue matrix
containing numerous stellate cells (Figure 1B); lipid-rich
atheromatous gruel is composed of acellular debris with
cholesterol clefts (Figure 1C); and thrombus, which
is defined as fibrin deposition, plaque hemorrhage, or both,
stains red (Figure 1D). Media was recognized by the presence of
internal elastic lamina and more orderly arranged smooth muscle cells
and connective tissue matrix and was excluded. Each specimen area was
outlined at a low magnification (x40) and quantified by manual
planimetry. Total area in square millimeters and the percentage of the
total area are reported.
|
Immunocytochemistry
Human macrophage antibody staining was performed using
5-µm-thick sections that were deparaffinized and rehydrated with
PBS. Macrophages were identified using anti-human
pan-macrophage anti–CD-68 and KP-1 (M814 DAKO) at a
concentration of 7.6 µg/mL. Sections were blocked with normal goat
serum and 3% H2O2 in
water, washed in PBS, and incubated with the primary antibody for 1
hour at 37°C. They were then washed in PBS, and primary antibodies
were detected with a biotin-streptavidin–amplified detection system
(SuperSensitive Kit, Biogenex) that was developed with
diaminobenzidine. Sections were dehydrated, cover-slipped, and
examined. Positive control slides (spleen for KP-1), nonimmune negative
controls, and processing controls were performed. Each stained sample
was outlined manually, and the areas occupied by stained
macrophages were measured. All measurements were performed in a
blind fashion.
Statistical Analysis
Results are expressed as mean±SEM, and P<0.05 was
considered statistically significant. To compare 2 discrete
variables (clinical and demographic data in diabetics versus
nondiabetics), a 2-tailed Fisher test was used, and to compare 3
discrete variables (clinical and demographic data in the 3 diabetic
groups), a 
2 test was performed. A 2-tailed
Student’s t test was used to compare Gaussian samples. To
compare data that are not compatible with a normal frequency
distribution, a 2-tailed Student’s t test was performed
with a logarithmic transformation of each individual value
(morphometric data), and to compare data that are not compatible with a
normal frequency distribution after logarithmic transformation
(thrombus data), a robust test was used to compare medians (Rs1
software 6.0, Brooks Animation).
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Clinical and Demographic Data
The clinical and demographic characteristics of the study and control populations were similar (Table 1
). No significant differences existed
between the 2 groups in age, sex, or clinical syndrome at the time of
atherectomy. The incidence of risk factors for coronary artery
disease was similar as well. The number of vessels containing a >50%
lesion was greater in the diabetic group (Table 1). Three
subgroups of diabetic patients were identified; they were (1) patients
under insulin therapy, (2) patients under oral sulfonylurea therapy,
and (3) patients under diet therapy. The clinical and demographic
characteristics of the patients in these subgroups were similar (Table 2).
|
|
Morphometry Data
Total plaque area was similar in specimens from diabetic and
nondiabetic patients (Table 3). The
percentage of total area occupied by lipid-rich atheroma
was larger in specimens from patients with diabetes than in specimens
from patients without diabetes (P=0.01).
|
The area occupied by thrombus was larger in specimens from patients
with diabetes than in specimens from patients without diabetes
(P=0.03; Table 3
). The incidence of coronary
thrombus was also higher in specimens from patients with diabetes
mellitus (29 of 47) than in specimens from patients without diabetes
(19 of 48; 62% versus 40%, respectively; P=0.04). The
percentage of total area occupied by macrophages is shown in
Figure 2. Macrophage infiltration
was greater in specimens from patients with diabetes than in specimens
from patients without diabetes (22±3% versus 12±1%;
P=0.003). Figure 3 provides an
example of macrophage regions in the atherectomy tissue of
patients with and without diabetes mellitus. The plaque composition of
lesions from patients with diabetes according to therapy is shown in
Table 4. No differences existed in
lipid-rich atheroma, collagen-rich fibrocellular tissue,
hypercellular tissue, or macrophage areas in specimens from
diabetic patients treated with sulfonylureas compared with specimens
from diabetic patients treated with insulin or diet alone. The
incidence of thrombus was 69% in the insulin group (9 of 13), 64% in
the sulfonylurea group (9 of 14), and 55% in the diet-alone group (11
of 20; P=NS).
|
|
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
This study demonstrates a significant increase in lipid pool content and macrophage infiltration in coronary specimens from patients with diabetes mellitus. In addition, coronary thrombosis was found more frequently in the coronary specimens from patients with diabetes mellitus.
The common factor precipitating acute coronary events is thrombosis. Thrombosis occurs in disrupted or eroded plaques. Plaque disruption (fibrous cap rupture) is more frequently seen in men and occurs in plaques with a large lipid core, increased macrophage infiltration, and decreased collagen and smooth muscle cell content.5 6 7 8 9 Plaque erosion (loss of endothelial cells) is more frequently seen in premenopausal women with sudden cardiac death and occurs in plaques with abundant smooth muscle cells, which are usually in clusters.12 13 In this study, the incidence of coronary thrombosis was higher in specimens from patients with diabetes mellitus. This finding is in agreement with those of Silva et al,14 who found an increased incidence of angioscopically documented coronary thrombosis in diabetic patients with unstable angina. It is also in agreement with recent clinical studies showing a significant benefit of aggressive antithrombotic therapy with platelet IIb/IIIa receptor antagonists in diabetic patients undergoing percutaneous revascularization.15
The increased thrombotic predisposition of diabetic tissue may be multifactorial. First, a larger amount of lipid-rich atheroma was found in lesions from patients with diabetes. Previous studies identified the lipid core as the major thrombogenic substrate of the atherosclerotic plaque.16 17 Second, increased areas of macrophage infiltration were found in the lesions from patients with diabetes. Previous studies showed that culprit lesions from patients with acute coronary syndromes have an increased macrophage content when compared with lesions from patients with chronic stable angina.9 The present study included only culprit lesions from patients with either unstable angina or myocardial infarction; thus, the increased macrophage infiltration observed in the diabetic population represents an increase over the increase seen in lesions from patients with acute coronary syndromes. Finally, macrophages colocalize with tissue factor in coronary lesions from patients with unstable angina,11 and tissue factor is considered the primary initiator of thrombogenesis and thrombin generation in vivo.18
The use of sulfonylurea drugs reportedly increases cardiovascular mortality in patients with diabetes mellitus.3 19 20 21 Sulfonylureas may impair ischemic preconditioning and prevent coronary vasodilation in response to ischemia.21 In addition, sulfonylureas may have atherogenic properties.22 In an attempt to identify differences in plaque composition between diabetic patients treated with sulfonylurea agents and those treated with insulin or diet, a subgroup analysis was performed. No significant differences were observed in this analysis, which suggests that sulfonylurea treatment may not be involved in changing the coronary plaque composition of patients with diabetes mellitus. However, this analysis was performed on a small number of lesions in each group, which diminishes its power to identify potential differences. Further studies should be performed to confirm these findings. Finally, atherosclerotic lesions from patients with diabetes mellitus exhibit an increased amount of advanced glycosylation end products.23 Specific receptors for proteins modified by these products have been identified in macrophages, and these receptors may play a role in arterial wall collagen turnover in patients with diabetes.24 However, the role of advanced glycosylation end products in plaque disruption is unclear and remains to be elucidated.
Limitations
Macrophage infiltration could be evaluated by cell
counting and not by quantified planimetry. However, comparisons of
macrophage areas are properly evaluated by quantified
planimetry. In addition, DCA can extract only 33% of the plaque in
primary lesions, so histological analysis may
not reflect total plaque composition.25 Furthermore, DCA
has been almost totally replaced by coronary stenting in
clinical practice. This explains why the sample collection for this
study was performed >6 years ago. Nevertheless, DCA is a unique
technique to obtain human coronary tissue in vivo.
Conclusions
Coronary tissue from patients with diabetes exhibits a
larger content of lipid-rich atheroma, macrophage
infiltration, and subsequent thrombosis than tissue from patients
without diabetes. These differences suggest an increased vulnerability
for plaque disruption and thrombosis in patients with diabetes
mellitus.
|
Acknowledgments |
|---|
This study was supported in part by a research grant to Dr Pedro R. Moreno from the Mario Santo Domingo Foundation in Barranquilla, Colombia and by funds from The Cardiovascular Institute at The Mount Sinai School of Medicine. The authors thank Drs Maximiliano Giraudo, William N. O’Connor, and K. Raman Purushothaman and Ms Veronica Gulle for their expert technical assistance.
Received April 18, 2000; revision received June 9, 2000; accepted June 13, 2000.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Aronson D, Rayfield EJ. Diabetes and obesity. In: Fuster V, Ross R, Topol EJ, eds. Atherosclerosis and Coronary Artery Disease. Philadelphia, Pa: Lippincott-Raven; 1996:327–359.
2.
Aronson D, Rayfield EJ, Chesebro JH. Mechanisms
determining course and outcome of diabetic patients who have had acute
myocardial infarction. Ann Intern Med.. 1997;126:296–306.
3.
Garratt KN, Brady PA, Hassinger NL, et al.
Sulfonylurea drugs increase early mortality in patients with diabetes
mellitus after direct angioplasty for acute myocardial infarction.
J Am Coll Cardiol.. 1999;33:119–124.
4.
Van Belle E, Abolmaali K, Bauters C, et al.
Restenosis, late vessel occlusion. and left
ventricular function six months after balloon angioplasty
in diabetic patients. J Am Coll Cardiol.. 1999;34:476–485.
5.
Falk E, Shah PK, Fuster V. Coronary plaque
disruption. Circulation.. 1995;92:657–671.
6.
Libby P. Molecular bases of the acute coronary
syndromes. Circulation.. 1995;91:2844–2850.
7.
Davies MJ, Richardson PD, Woolf N, et al. Risk of
thrombosis in human atherosclerotic plaques: role of extracellular
lipid, macrophage, and smooth muscle cell content. Br
Heart J.. 1993;69:377–381.
8.
Buja LM, Willerson JT. Role of inflammation in
coronary plaque disruption. Circulation.. 1994;89:503–505.
9.
Moreno PR, Falk E, Palacios IF, et al.
Macrophage infiltration in acute coronary syndromes:
implications for plaque rupture. Circulation.. 1994;90:775–778.
10.
Moreno PR, Bernardi VH, Lopez-Cuellar J, et al.
Macrophage infiltration predicts restenosis after
coronary intervention in patients with unstable angina.
Circulation.. 1996;94:3098–3102.
11.
Moreno PR, Bernardi VH, Lopez-Cuellar J, et al.
Macrophages, tissue factor and smooth muscle cells in unstable
angina: implications for cell-mediated thrombogenicity in acute
coronary syndromes. Circulation.. 1996;94:3090–3097.
12.
Farb A, Burke AP, Tang AL, et al. Coronary
plaque erosion without rupture into a lipid core: a frequent cause of
coronary thrombosis in sudden coronary death.
Circulation.. 1996;93:1354–1363.
13.
Virmani R, Kolodgie FD, Burke AP, et al. Lessons from
sudden coronary death: a comprehensive morphological
classification scheme for atherosclerotic lesions. Arterioscler
Thromb Vasc Biol. 2000;20:1262–1275.
14.
Silva JA, Escobar A, Collins TJ, et al. Unstable
angina: a comparison of angioscopic findings between diabetic and
nondiabetic patients. Circulation.. 1995;92:1731–1736.
15.
Marso SP, Lincoff AM, Ellis SG, et al. Optimizing the
percutaneous interventional outcomes for patients with
diabetes mellitus: results of the EPISTENT (Evaluation of Platelet
IIb/IIIa Inhibitor for Stenting Trial) diabetic substudy.
Circulation.. 1999;100:2477–2484.
16. Fermandez-Ortiz A, Badimón JJ, Falk E, et al. Characterization of relative thrombogenicity of atherosclerotic plaque components: implications for consequences of plaque rupture. J Am Coll Cardiol.. 1994;23:1562–1569.[Abstract]
17.
Toschi V, Gallo R, Lettino M, et al. Tissue factor
modulates the thrombogenicity of human atherosclerotic plaques.
Circulation.. 1997;95:594–599.
18. Nemerson Y. The tissue factor pathway of blood coagulation. Semin Hematol.. 1992;29:170–176.[Medline] [Order article via Infotrieve]
19. Rytter L, Troelsen S, Beck-Nielsen H. Prevalence and mortality of acute myocardial infarction in patients with diabetes. Diabetes Care.. 1985;8:230–234.[Abstract]
20. Meinert CL, Knatterud GL, Prout TE, et al. A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes, II: mortality results. Diabetes. 1970;19(suppl):789–830.
21.
Brady PA, Terzic A. The sulfonylurea controversy: more
questions from the heart. J Am Coll Cardiol.. 1998;31:950–956.
22. Sobenin IA, Maksumova MA, Slavina ES, et al. Sulfonylureas induce cholesterol accumulation in cultured human intimal cells and macrophages. Atherosclerosis.. 1994;105:159–163.[Medline] [Order article via Infotrieve]
23. Nakamura Y, Horii Y, Nishino T, et al. Immunohistochemical localization of advanced glycosylation end products in coronary atheroma and cardiac tissue in diabetes mellitus. Am J Pathol.. 1993;143:1649–1656.[Abstract]
24.
Vlassara H, Brownlee M, Crami A. Novel
macrophage receptor for glucose-modified proteins is distinct
from previously described scavenger receptors. J Exp Med.. 1986;164:1301–1309.
25. Weissman NJ, Palacios IF, Nidorf SM, et al. Three-dimensional intravascular ultrasound assessment of plaque volume after successful atherectomy. Am Heart J.. 1995;130:413–419.[Medline] [Order article via Infotrieve]
This article has been cited by other articles:
 |
|
 |
|
  E. Erdmann and R. Wilcox Pioglitazone and mechanisms of CV protection QJM, December 2, 2009; (2009) hcp168v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. R. Moreno The High-Risk Thin-Cap Fibroatheroma: A New Kid on the Block Circ Cardiovasc Interv, December 1, 2009; 2(6): 500 - 502. [Full Text] [PDF]
|
|
|
|
|
|
J. B. Lindsey, J. A. House, K. F. Kennedy, and S. P. Marso Diabetes Duration Is Associated With Increased Thin-Cap Fibroatheroma Detected by Intravascular Ultrasound With Virtual Histology Circ Cardiovasc Interv, December 1, 2009; 2(6): 543 - 548. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kimura, T. Kakuta, T. Yonetsu, A. Suzuki, Y. Iesaka, H. Fujiwara, and M. Isobe Clinical Significance of Echo Signal Attenuation on Intravascular Ultrasound in Patients With Coronary Artery Disease Circ Cardiovasc Interv, October 1, 2009; 2(5): 444 - 454. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Yang, Y. Park, H. Zhang, X. Gao, E. Wilson, W. Zimmer, L. Abbott, and C. Zhang Role of MCP-1 in tumor necrosis factor-{alpha}-induced endothelial dysfunction in type 2 diabetic mice Am J Physiol Heart Circ Physiol, October 1, 2009; 297(4): H1208 - H1216. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Liu, H. Doi, A. Maehara, G. S. Mintz, J. de Ribamar Costa Jr, K. Sano, G. Weisz, G. D. Dangas, A. J. Lansky, E. M. Kreps, et al. A Volumetric Intravascular Ultrasound Comparison of Early Drug-Eluting Stent Thrombosis Versus Restenosis J. Am. Coll. Cardiol. Intv., May 1, 2009; 2(5): 428 - 434. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. J. Hong, M. H. Jeong, Y. H. Choi, J. S. Ko, M. G. Lee, W. Y. Kang, S. E. Lee, S. H. Kim, K. H. Park, D. S. Sim, et al. Plaque characteristics in culprit lesions and inflammatory status in diabetic acute coronary syndrome patients. J. Am. Coll. Cardiol. Img., March 1, 2009; 2(3): 339 - 349. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. A. Jaffer, C. Vinegoni, M. C. John, E. Aikawa, H. K. Gold, A. V. Finn, V. Ntziachristos, P. Libby, and R. Weissleder Real-Time Catheter Molecular Sensing of Inflammation in Proteolytically Active Atherosclerosis Circulation, October 28, 2008; 118(18): 1802 - 1809. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K Nasu, E Tsuchikane, O Katoh, H Fujita, J-F Surmely, M Ehara, Y Kinoshita, N Tanaka, T Matsubara, Y Asakura, et al. Plaque characterisation by Virtual Histology intravascular ultrasound analysis in patients with type 2 diabetes Heart, April 1, 2008; 94(4): 429 - 433. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Heinonen, P. Leppanen, I. Kholova, H. Lumivuori, S.-K. Hakkinen, F. Bosch, M. Laakso, and S. Yla-Herttuala Increased Atherosclerotic Lesion Calcification in a Novel Mouse Model Combining Insulin Resistance, Hyperglycemia, and Hypercholesterolemia Circ. Res., November 9, 2007; 101(10): 1058 - 1067. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. O. McDonald, R. G. Gerrity, C. Jen, H.-J. Chen, K. Wark, T. N. Wight, A. Chait, and K. D. O'Brien Diabetes and Arterial Extracellular Matrix Changes in a Porcine Model of Atherosclerosis J. Histochem. Cytochem., November 1, 2007; 55(11): 1149 - 1157. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Berry, J.-C. Tardif, and M. G. Bourassa Coronary Heart Disease in Patients With Diabetes: Part II: Recent Advances in Coronary Revascularization J. Am. Coll. Cardiol., February 13, 2007; 49(6): 643 - 656. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Cuccurullo, A. Iezzi, M. L. Fazia, D. De Cesare, A. Di Francesco, R. Muraro, R. Bei, S. Ucchino, F. Spigonardo, F. Chiarelli, et al. Suppression of Rage as a Basis of Simvastatin-Dependent Plaque Stabilization in Type 2 Diabetes Arterioscler Thromb Vasc Biol, December 1, 2006; 26(12): 2716 - 2723. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Otsuka, S. Sugiyama, S. Kojima, H. Maruyoshi, T. Funahashi, K. Matsui, T. Sakamoto, M. Yoshimura, K. Kimura, S. Umemura, et al. Plasma Adiponectin Levels Are Associated With Coronary Lesion Complexity in Men With Coronary Artery Disease J. Am. Coll. Cardiol., September 19, 2006; 48(6): 1155 - 1162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. T. Bloomgarden Third Annual World Congress on the Insulin Resistance Syndrome: Atherothrombotic disease Diabetes Care, August 1, 2006; 29(8): 1973 - 1980. [Full Text] [PDF]
|
|
|
|
|
|
I. J. Goldberg and H. M. Dansky Diabetic Vascular Disease: An Experimental Objective Arterioscler Thromb Vasc Biol, August 1, 2006; 26(8): 1693 - 1701. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ohtani, Y. Ueda, I. Mizote, J. Oyabu, K. Okada, A. Hirayama, and K. Kodama Number of Yellow Plaques Detected in a Coronary Artery Is Associated With Future Risk of Acute Coronary Syndrome: Detection of Vulnerable Patients by Angioscopy J. Am. Coll. Cardiol., June 6, 2006; 47(11): 2194 - 2200. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. R. Vaidyula, A. K. Rao, M. Mozzoli, C. Homko, P. Cheung, and G. Boden Effects of Hyperglycemia and Hyperinsulinemia on Circulating Tissue Factor Procoagulant Activity and Platelet CD40 Ligand Diabetes, January 1, 2006; 55(1): 202 - 208. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M Carter Inflammation, thrombosis and acute coronary syndromes Diabetes and Vascular Disease Research, October 1, 2005; 2(3): 113 - 121. [Abstract] [PDF]
|
|
|
|
 |
|
 R. F. Bonvini, T. Hendiri, and E. Camenzind Inflammatory response post-myocardial infarction and reperfusion: a new therapeutic target? Eur. Heart J. Suppl., October 1, 2005; 7(suppl_I): I27 - I36. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. King III, G. Dangas, J. W. Moses, S. B. King III, G. Dangas, and J. W. Moses Surgery Is Preferred for the Diabetic With Multivessel Disease Circulation, September 6, 2005; 112(10): 1500 - 1515. [Full Text] [PDF]
|
|
|
|
|
|
K. Toutouzas, V. Markou, M. Drakopoulou, I. Mitropoulos, E. Tsiamis, M. Vavuranakis, S. Vaina, and C. Stefanadis Increased Heat Generation From Atherosclerotic Plaques in Patients With Type 2 Diabetes: An increased local inflammatory activation Diabetes Care, July 1, 2005; 28(7): 1656 - 1661. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. T. Bloomgarden Second World Congress on the Insulin Resistance Syndrome: Mediators, pediatric insulin resistance, the polycystic ovary syndrome, and malignancy Diabetes Care, July 1, 2005; 28(7): 1821 - 1830. [Full Text] [PDF]
|
|
|
|
|
|
J. Molnar, S. Yu, N. Mzhavia, C. Pau, I. Chereshnev, and H. M. Dansky Diabetes Induces Endothelial Dysfunction but Does Not Increase Neointimal Formation in High-Fat Diet Fed C57BL/6J Mice Circ. Res., June 10, 2005; 96(11): 1178 - 1184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Iakovou, T. Schmidt, E. Bonizzoni, L. Ge, G. M. Sangiorgi, G. Stankovic, F. Airoldi, A. Chieffo, M. Montorfano, M. Carlino, et al. Incidence, Predictors, and Outcome of Thrombosis After Successful Implantation of Drug-Eluting Stents JAMA, May 4, 2005; 293(17): 2126 - 2130. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Flaherty and C. J. Davidson Diabetes and Coronary Revascularization JAMA, March 23, 2005; 293(12): 1501 - 1508. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. P. Kadoglou, S. S. Daskalopoulou, D. Perrea, and C. D. Liapis Matrix Metalloproteinases and Diabetic Vascular Complications Angiology, March 1, 2005; 56(2): 173 - 189. [Abstract] [PDF]
|
|
|
|
|
|
S. P Marso, J. W Murphy, J. A House, D. M Safley, and W. S Harris Metabolic syndrome-mediated inflammation following elective percutaneous coronary intervention Diabetes and Vascular Disease Research, February 1, 2005; 2(1): 31 - 36. [Abstract] [PDF]
|
|
|
|
|
|
P. R. Moreno and V. Fuster New aspects in the pathogenesis of diabetic atherothrombosis J. Am. Coll. Cardiol., December 21, 2004; 44(12): 2293 - 2300. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-K. Hong, G. S. Mintz, C. W. Lee, Y.-H. Kim, S.-W. Lee, J.-M. Song, K.-H. Han, D.-H. Kang, J.-K. Song, J.-J. Kim, et al. Comparison of Coronary Plaque Rupture Between Stable Angina and Acute Myocardial Infarction: A Three-Vessel Intravascular Ultrasound Study in 235 Patients Circulation, August 24, 2004; 110(8): 928 - 933. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K P Morgan, A Kapur, and K J Beatt Anatomy of coronary disease in diabetic patients: an explanation for poorer outcomes after percutaneous coronary intervention and potential target for intervention Heart, July 1, 2004; 90(7): 732 - 738. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P L Sanchez, J L Morinigo, P Pabon, F Martin, I Piedra, I F Palacios, and C Martin-Luengo Prognostic relations between inflammatory markers and mortality in diabetic patients with non-ST elevation acute coronary syndrome Heart, March 1, 2004; 90(3): 264 - 269. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Roffi and E. J. Topol Percutaneous coronary intervention in diabetic patients with non-ST-segment elevation acute coronary syndromes Eur. Heart J., February 1, 2004; 25(3): 190 - 198. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. E. Sobel, D. J. Taatjes, and D. J. Schneider Intramural Plasminogen Activator Inhibitor Type-1 and Coronary Atherosclerosis Arterioscler Thromb Vasc Biol, November 1, 2003; 23(11): 1979 - 1989. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kobayashi, N. Inoue, Y. Ohashi, M. Terashima, K. Matsui, T. Mori, H. Fujita, K. Awano, K. Kobayashi, H. Azumi, et al. Interaction of Oxidative Stress and Inflammatory Response in Coronary Plaque Instability: Important Role of C-Reactive Protein Arterioscler Thromb Vasc Biol, August 1, 2003; 23(8): 1398 - 1404. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. G. L. Biondi-Zoccai, A. Abbate, G. Liuzzo, and L. M. Biasucci Atherothrombosis, inflammation, and diabetes J. Am. Coll. Cardiol., April 2, 2003; 41(7): 1071 - 1077. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Qu, T. T. Le, S. P. Azen, M. Xiang, N. D. Wong, T. M. Doherty, and R. C. Detrano Value of Coronary Artery Calcium Scanning by Computed Tomography for Predicting Coronary Heart Disease in Diabetic Subjects Diabetes Care, March 1, 2003; 26(3): 905 - 910. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Sambola, J. Osende, J. Hathcock, M. Degen, Y. Nemerson, V. Fuster, J. Crandall, and J. J. Badimon Role of Risk Factors in the Modulation of Tissue Factor Activity and Blood Thrombogenicity Circulation, February 25, 2003; 107(7): 973 - 977. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Detrano Counterpoint: Do People With Diabetes Benefit From Coronary Calcium Scans? Diabetes Care, February 1, 2003; 26(2): 543 - 544. [Full Text] [PDF]
|
|
|
|
|
|
N. Marx, J. Froehlich, L. Siam, J. Ittner, G. Wierse, A. Schmidt, H. Scharnagl, V. Hombach, and W. Koenig Antidiabetic PPAR{gamma}-Activator Rosiglitazone Reduces MMP-9 Serum Levels in Type 2 Diabetic Patients With Coronary Artery Disease Arterioscler Thromb Vasc Biol, February 1, 2003; 23(2): 283 - 288. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Laakso and J. Kuusisto Diabetology for cardiologists Eur. Heart J. Suppl., January 1, 2003; 5(suppl_B): B5 - B13. [Abstract] [PDF]
|
|
|
|
|
|
R. Ferrara, G. Guardigli, and R. Ferrari Myocardial metabolism: the diabetic heart Eur. Heart J. Suppl., January 1, 2003; 5(suppl_B): B15 - B18. [Abstract] [PDF]
|
|
|
|
|
|
R. H. Eckel, M. Wassef, A. Chait, B. Sobel, E. Barrett, G. King, M. Lopes-Virella, J. Reusch, N. Ruderman, G. Steiner, et al. Prevention Conference VI: Diabetes and Cardiovascular Disease: Writing Group II: Pathogenesis of Atherosclerosis in Diabetes Circulation, May 7, 2002; 105 (18): e138 - e143. [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||