bluuebunny/crossref_metadata_2025 huggingface dataset:
Restenosis Rates in Diabetic Patients
Authors: Van Belle Eric , Bauters Christophe , Hubert Edouard , Bodart Jean-Christophe , Abolmaali Kaveh , Meurice Thibaud , McFadden Eugène P. , Lablanche Jean-Marc , Bertrand Michel E.
Published: June 2012

Background
Diabetes is a major risk factor for restenosis after coronary balloon angioplasty. Recent studies have shown that coronary stenting significantly reduces restenosis compared with balloon angioplasty alone. However, limited information is available on the effect of coronary stenting in diabetic patients.

Methods and Results
We designed this study to analyze the effect of diabetes on restenosis in patients treated with either balloon angioplasty or coronary stenting who were enrolled in a 6-month angiographic follow-up program. Three hundred consecutive patients, 19% of whom were diabetics, who underwent coronary stent implantation during a single-vessel procedure on native coronary vessels and who had 6-month angiographic follow-up constituted the study group (stent group). Three hundred consecutive patients who underwent 6-month angiographic follow-up after single-vessel conventional balloon angioplasty served as control patients (balloon group). Preprocedural, postprocedural, and follow-up angiograms were analyzed with quantitative angiography. In the balloon group, the restenosis rate was almost twofold higher in diabetic than in nondiabetic patients (63% versus 36%;
P
=.0002) owing to both a greater late loss (0.79±0.70 versus 0.41±0.61 mm, respectively;
P
<.0001) and a higher rate of late vessel occlusion (14% versus 3%, respectively;
P
<.001). In the stent group, restenosis rates were similar in diabetics and nondiabetics (25% versus 27%, respectively). Furthermore, in the stent group, late loss (0.77±0.65 versus 0.79±0.57 mm, respectively) and the rate of late vessel occlusion (2% versus 1%, respectively) did not differ significantly between diabetic and nondiabetic patients.

Conclusions
Although diabetics have increased rates of restenosis and late vessel occlusion after simple balloon angioplasty, they have the same improved outcome with coronary stenting that has been documented in nondiabetic patients.
Ethnic Origin and Serum Levels of 1α,25-Dihydroxyvitamin D
3
Are Independent Predictors of Coronary Calcium Mass Measured by Electron-Beam Computed Tomography
Authors: Doherty Terence M. , Tang Weiyi , Dascalos Steven , Watson Karol E. , Demer Linda L. , Shavelle Robert M. , Detrano Robert C.
Published: June 2012

Background
Blacks have been found to have lower amounts of coronary calcium as well as higher levels of the osteoregulatory steroid 1,25-dihydroxyvitamin D
3
[1,25(OH)
2
D
3
] than whites. We sought to determine if racial differences in coronary calcium mass could be explained by differences in serum levels of 1,25(OH)
2
D
3
.

Methods and Results
We evaluated standard coronary risk factors, quantified coronary calcium mass with electron-beam computed tomography (EBCT), and measured serum 1,25(OH)
2
D
3
with radioimmunoassay in 283 high-risk subjects (51 [18%] black, 232 [82%] white). Black subjects had lower masses of coronary calcium than whites (14 versus 47 mg;
P
=.003). Serum 1,25(OH)
2
D
3
levels were slightly higher in blacks (41 versus 38 pg/mL;
P
=.05). Log 1,25(OH)
2
D
3
levels were inversely proportional to log-transformed calcium mass (
r
=−.19;
P
=.001) in both races. Multivariate linear regression demonstrated that both black race (
P
=.02) and 1,25(OH)
2
D
3
levels (
P
=.007) contributed inversely and independently to coronary calcium mass. However, an interaction term of race×1,25(OH)
2
D
3
did not significantly contribute to coronary calcium mass, indicating that other undetermined factors in addition to 1,25(OH)
2
D
3
are responsible for ethnic differences in coronary calcium mass.

Conclusions
Both black race and serum levels of 1,25(OH)
2
D
3
are independent negative determinants of coronary calcium mass. Nevertheless, diminished amounts of coronary calcium in blacks are not accounted for by higher 1,25(OH)
2
D
3
levels.
Effect of Ca
2+
on GP IIb-IIIa Interactions With Integrilin
Authors: Phillips David R. , Teng Willie , Arfsten Ann , Nannizzi-Alaimo Lisa , White Melanie M. , Longhurst Celia , Shattil Sanford J. , Randolph Anne , Jakubowski Joseph A. , Jennings Lisa K. , Scarborough Robert M.
Published: June 2012

Background
Integrilin (eptifibatide), a potent inhibitor of the fibrinogen binding function of GP IIb-IIIa, has been shown to reduce the thrombotic complications of angioplasty and of acute coronary syndromes. The present study was designed to determine whether the reduced Ca
2+
concentrations in plasma anticoagulated with citrate affect Integrilin binding to GP IIb-IIIa and the ex vivo pharmacodynamic measurements for this drug.

Methods and Results
Lower concentrations of Integrilin were found to inhibit platelet aggregation in plasma anticoagulated with citrate (for ADP, mean±SD IC
50
=140±40 nmol/L, n=6; Ca
2+
=40 to 50 μmol/L) than with PPACK (IC
50
=570±70 nmol/L,
P
<.0001, n=6; Ca
2+
≈1 mmol/L). Chelation of Ca
2+
with EDTA or citrate caused a similar degree of enhancement in the inhibitory activity of Integrilin. Measurements of D3 LIBS epitope expression showed that the enhanced inhibitory activity was caused by enhanced GP IIb-IIIa occupancy by Integrilin. Citrate anticoagulation decreased the amounts of Integrilin required to inhibit the binding of PAC1, a monoclonal antibody that mimics the GP IIb-IIIa binding activity of fibrinogen. Reduced Ca
2+
also increased Integrilin inhibition of the binding of biotinylated fibrinogen to purified, immobilized GP IIb-IIIa.

Conclusions
These data suggest that citrate anticoagulation removes Ca
2+
from GP IIb-IIIa and enhances the apparent inhibitory activity of Integrilin. This finding indicates that the inhibitory activity of Integrilin is overestimated in blood samples collected with citrate, suggesting that it may be possible to achieve greater antithrombotic efficacy beyond that observed in clinical trials to date with Integrilin.
Enalapril Does Not Enhance Exercise Capacity in Patients After Fontan Procedure
Authors: Kouatli Amjad A. , Garcia Jorge A. , Zellers Thomas M. , Weinstein Ellen M. , Mahony Lynn
Published: June 2012

Background
Angiotensin-converting enzyme inhibitors improve exercise capacity in adults with congestive heart failure by decreasing systemic vascular resistance and improving ventricular diastolic function.
P
atients who have undergone the Fontan procedure have decreased cardiac output, increased systemic vascular resistance, abnormal diastolic function, and decreased exercise capacity compared with normal people.

Methods and Results
To test the hypothesis that afterload reduction therapy alters hemodynamic variables and augments exercise capacity in patients after a Fontan procedure, we compared the results of graded exercise with maximal effort from 18 subjects (14.5±6.2 years of age, 4 to 19 years after Fontan procedure) in a randomized, double-blind, placebo-controlled crossover trial using enalapril (0.2 to 0.3 mg · kg
−1
· d
−1
, maximum 15 mg). Each treatment was administered for 10 weeks. Diastolic filling patterns at rest were assessed by Doppler determination of the systemic atrioventricular valve flow velocity at the conclusion of each therapy. No difference was detected in resting heart rate, blood pressure, or cardiac index. Diastolic filling patterns were also similar. Exercise duration was not different (6.4±2.6 [enalapril] versus 6.7±2.6 minutes [placebo]). The mean percent increase in cardiac index from rest to maximum exercise was slightly but significantly decreased in subjects after 10 weeks of enalapril therapy (102±34% [enalapril] versus 125±34% [placebo];
P
<.02). At maximal exercise, cardiac index (3.5±0.9 [enalapril] versus 3.8±0.9 L · min
−1
· m
2
[placebo]), oxygen consumption (18.3±9 [enalapril] versus 20.5±7 mL · min
−1
· kg
−1
[placebo]), minute ventilation (57.5±17 [enalapril] versus 55.4±19 L/min [placebo]), and total work (247±181 [enalapril] versus 261±197 W [placebo]) were not different.

Conclusions
We conclude that enalapril administration for 10 weeks does not alter abnormal systemic vascular resistance, resting cardiac index, diastolic function, or exercise capacity in patients who have undergone a Fontan procedure.
Effect of Cardiac Surgery Patient Characteristics on Patient Outcomes From 1981 Through 1995
Authors: Warner Christi D. , Weintraub William S. , Craver Joseph M. , Jones Ellis L. , Gott John Parker , Guyton Robert A.
Published: June 2012

Background
Previous studies have demonstrated increased risk in patients undergoing coronary artery bypass surgery (CABG), but the effect of this increasing risk on outcomes has not been well documented. The purposes of this study were (1) to evaluate patients who had CABG from 1993 to 1995 (group III) and compare them with patients from 1981 through 1987 (group I) and 1988 through 1992 (group II) to determine if the trend toward higher-risk patients continued and (2) to evaluate what effect risk had on in-hospital outcomes.

Methods and Results
Data were collected prospectively on patients undergoing CABG. Patients from the three time periods were compared by use of univariate and multivariate statistics. Risk models for mortality were developed by use of logistic regression. Significant changes were noted in the three time periods, with risk increasing over time. Increased risk was associated with increased mortality in group II, but mortality declined in group III despite the continued increase in patient risk. Group II had an increase in complications, with little change in group III. The actual mortality rate was lower than predicted in group III.

Conclusions
Patients undergoing CABG are increasingly high risk. In-hospital mortality rates declined during the period from 1993 through 1995 and were lower than predicted despite the increase in risk. This decreased mortality rate may reflect greater experience in providing care to high-risk patients and improved myocardial protection and surgical and anesthetic techniques. Although continued analysis of patient risk and benefit is needed, researchers must be cognizant of the rapid changes in technology and knowledge and should correlate changes in the process of care with outcomes.
Apolipoprotein(a) Attenuates Endogenous Fibrinolysis in the Rabbit Jugular Vein Thrombosis Model In Vivo
Authors: Biemond Bart J. , Friederich Philip W. , Koschinsky Marlys L. , Levi Marcel , Sangrar Waheed , Xia Jiazhi , Büller Harry R. , Cate Jan W. ten
Published: June 2012

Background
In many case-control as well as epidemiological studies, increased lipoprotein(a) [Lp(a)] levels are considered to constitute an independent risk factor for premature coronary artery and cerebrovascular disease. Lp(a) resembles an LDL particle with an additional linked protein [apolipoprotein(a), apo(a)], whose molecular structure has been demonstrated to be homologous to the fibrinolytic proenzyme plasminogen. Because of the high similarity between plasminogen and apo(a), apo(a) may potentially interfere in the fibrinolytic system by competing with plasminogen for fibrin binding sites. In vitro studies have demonstrated that Lp(a) indeed competes with plasminogen binding to fibrin and inhibits tissue plasminogen activator (TPA)-mediated activation of plasminogen. No direct in vivo studies to test this hypothesis have been performed.

Methods and Results
To test this hypothesis, we studied the effect of a recombinant form of apo(a) on endogenous and TPA-mediated thrombolysis in an in vivo model of experimental venous thrombosis. Thrombi containing either 16 μg r-apo(a), 8 μg r-apo(a), or vehicle (HEPES-buffered saline, control) were formed in the jugular veins of a rabbit and showed significantly reduced endogenous thrombolysis after 60 minutes in a dose-dependent fashion, ID 2.7±0.9% and 4.6±1.8%, respectively, versus 7.4±1.6% of that of the control. High concentrations of incorporated apo(a) significantly reduced TPA-induced thrombolysis (12.2±2.5% versus 22.2±2.6% in the control thrombi), but no effect of lower concentrations of incorporated r-apo(a) was demonstrated on the exogenous TPA-induced thrombolysis.

Conclusions
The present study demonstrates the attenuation of endogenous fibrinolysis by apo(a) in an in vivo model of experimental venous thrombosis, lending support to the proposed mechanism of impaired fibrinolysis by which Lp(a) may contribute to atherothrombotic disorders.
Effects of Atrial Dilatation on Refractory Period and Vulnerability to Atrial Fibrillation in the Isolated Langendorff-Perfused Rabbit Heart
Authors: Ravelli Flavia , Allessie Maurits
Published: June 2012

Background
Atrial fibrillation (AF) is frequently observed under conditions that are associated with atrial dilatation. The aim of this study was to investigate the effects of atrial dilatation on the substrate of AF.

Methods and Results
In 15 Langendorff-perfused rabbit hearts, the interatrial septum was perforated, and after occlusion of the caval and pulmonary veins, biatrial pressure was increased by raising the level of an outflow cannula in the pulmonary artery. Right and left atrial effective refractory periods (AERPs), monophasic action potentials (MAPs), and inducibility of AF by single premature stimuli were measured as a function of atrial pressure. Increasing the atrial pressure from 0.5±0.7 to 16.2±2.2 cm H
2
O resulted in a progressive shortening of the right AERP from 82.2±9.8 to 48.0±5.1 ms. In the left atrium, an increase in pressure up to 7.4±0.3 cm H
2
O had no effect on the AERP. At higher pressures, however, the left AERP also shortened, from 67.5±7.5 to 49.3±2.0 ms. The duration of MAPs also decreased by an increase in atrial pressure, showing a high correlation with the shortening in AERP (
r
=.94,
P
<.01). All these changes were completely reversible within 3 minutes after release of the atrial stretch. Dilatation of the atria was a major determinant for the vulnerability to AF. The inducibility of AF increased from 0% at low pressures to 100% when the atrial pressure was >10 cm H
2
O. Release of the atrial wall stress resulted in prompt cardioversion of AF. The increased vulnerability for AF was highly correlated with the shortening in AERP (logistic regression
r
=.97). No correlation was found with the spatial dispersion between right and left AERPs.

Conclusions
Increased atrial pressure in the isolated rabbit heart resulted in a significant increase in vulnerability to AF that was closely correlated to shortening of the AERP. These changes were completely reversible within 3 minutes after release of the atrial stretch, resulting in prompt termination of AF.
Heterozygous Lipoprotein Lipase Deficiency
Authors: Nordestgaard Børge G. , Abildgaard Susanne , Wittrup Hans H. , Steffensen Rolf , Jensen Gorm , Tybjærg-Hansen Anne
Published: June 2012

Background
Patients with mutations on both alleles of the lipoprotein lipase gene resulting in complete lipoprotein lipase deficiency exhibit the chylomicronemia syndrome with severe hypertriglyceridemia and increased risk of pancreatitis and possibly of ischemic heart disease. This study examined frequency, lipid levels, and risk of ischemic heart disease for heterozygous carriers of lipoprotein lipase mutations known to cause the chylomicronemia syndrome in the homozygous state.

Methods and Results
Two mutations were screened for in 9259 individuals in a general population sample and in 948 patients with verified ischemic heart disease. The percent frequencies of heterozygous individuals with the Gly
188
→Glu and Ile
194
→Thr substitutions in the general population were 0.06% (95% CI, 0.04% to 0.23%) and 0% (95% CI, 0.00% to 0.12%), respectively. The Gly
188
→Glu substitution was associated with an increase in plasma triglycerides of 0.8±0.3 mmol/L (mean±SEM) and a decrease in plasma HDL cholesterol, apo A-I, and glucose levels of 0.45±0.07 mmol/L, 17±6 mg/dL, and 1.1±0.2 mmol/L, respectively. On multiple logistic regression analysis allowing for age, sex, plasma cholesterol, plasma lipoprotein (a), hypertension, diabetes mellitus, smoking, and body mass index, both plasma triglycerides and HDL cholesterol levels were independent predictors of ischemic heart disease. Finally, the Gly
188
→Glu substitution was more common among patients with verified ischemic heart disease (percent frequency of heterozygous individuals, 0.32%) than among individuals from the general population (odds ratio, 4.9; 95% CI, 1.2 to 19.6). The effects of the Gly
188
→Glu substitution were more pronounced than those of the common Asn
291
→Ser substitution.

Conclusions
Heterozygous lipoprotein lipase deficiency due to the Gly
188
→Glu substitution appears to increase plasma triglycerides and reduce HDL levels and may thereby predispose carriers to ischemic heart disease.
Attenuation of Unfavorable Remodeling by Exercise Training in Postinfarction Patients With Left Ventricular Dysfunction
Authors: Giannuzzi Pantaleo , Temporelli Pier Luigi , Corrà Ugo , Gattone Marinella , Giordano Amerigo , Tavazzi Luigi , Group for the ELVD Study
Published: June 2012

Background
Exercise is currently recommended for patients after myocardial infarction; however, the effects of regular exercise on the remodeling process remain to be defined. The aim of this multicenter, randomized study was to investigate whether a long-term physical training program influences left ventricular size and function in postinfarction patients with systolic dysfunction.

Methods and Results
Consecutive patients with <40% ejection fraction after a first Q-wave myocardial infarction were randomly assigned to a 6-month exercise training program (n=39) or control group (n=38). After 6 months, a significant increase in work capacity was observed only in the training group (from 4.462±1.095 to 5.752±1.749 kilopond-meters [Kp-m],
P
<.01), not in the control group (from 4.375±1.143 to 4.388±1.199 Kp-m), whereas left ventricular volumes had increased in the control group (end-diastolic volume, from 94±26 to 99±27 mL/m
2
,
P
<.01; end-systolic volume, from 62±20 to 67±23 mL/m
2
,
P
<.01) but not in the training group (end-diastolic volume, from 93±28 to 92±28 mL/m
2
,
P
=NS; end-systolic volume, from 61±22 to 57±23 mL/m
2
,
P
=NS). Conversely, ejection fraction had improved in the training group (from 34±5% to 38±8%,
P
<.01) but not in the control group (from 34±5% to 33±7%,
P
=NS).

Conclusions
In postinfarction patients with systolic dysfunction, long-term exercise training may attenuate the unfavorable remodeling response and even improve ventricular function over time.
Integrated Mechanism for Functional Mitral Regurgitation
Authors: He Shengqiu , Fontaine Arnold A. , Schwammenthal Ehud , Yoganathan Ajit P. , Levine Robert A.
Published: June 2012

Background
Functional mitral regurgitation in patients with ischemic or dilated ventricles has been related to competing factors: altered tension on the leaflets due to displacement of their papillary muscle and annular attachments, which restricts leaflet closure, versus global ventricular dysfunction with reduced transmitral pressure to close the leaflets. In vivo, however, geometric changes accompany dysfunction, making it difficult to study these factors independently. Functional mitral regurgitation also paradoxically decreases in midsystole, despite peak transmitral driving pressure, suggesting a change in the force balance acting to create a regurgitant orifice, with rising transmitral pressure counteracting forces that restrict leaflet closure. In vivo, this mechanism cannot be tested independently of annular contraction that could also reduce midsystolic regurgitation.

Methods and Results
An in vitro model was developed that allows independent variation of papillary muscle position, annular size, and transmitral pressure, with direct regurgitant flow rate measurement, to test the hypothesis that functional mitral regurgitation reflects an altered balance of forces acting on the leaflets. Hemodynamic and echocardiographic measurements of excised porcine valves were made under physiological pressures and flows. Apical and posterolateral papillary muscle displacement caused decreased leaflet mobility and apical leaflet tethering or tenting with regurgitation, as seen clinically. It reproduced the clinically observed midsystolic decrease in regurgitant flow and orifice area as transmitral pressure increased. Tethering delayed valve closure, increased the early systolic regurgitant volume before complete coaptation, and decreased the duration of coaptation. Annular dilatation increased regurgitation for any papillary muscle position, creating clinically important regurgitation; conversely, increased transmitral pressure decreased regurgitant orifice area for any geometric configuration.

Conclusions
The clinically observed tented-leaflet configuration and dynamic regurgitant orifice area variation can be reproduced in vitro by altering the three-dimensional relationship of the annular and papillary muscle attachments of the valve so as to increase leaflet tension. Increased transmitral pressure acting to close the leaflets decreases the regurgitant orifice area. These results are consistent with a mechanism in which an altered balance of tethering versus coapting forces acting on the leaflets creates the regurgitant orifice.
Sodium Restriction Shifts Circadian Rhythm of Blood Pressure From Nondipper to Dipper in Essential Hypertension
Authors: Uzu Takashi , Ishikawa Kazuhiko , Fujii Takashi , Nakamura Satoko , Inenaga Takashi , Kimura Genjiro
Published: June 2012

Background
Sodium restriction has been widely used for treatment of hypertension and renal diseases. Whether sodium restriction can transform the circadian rhythm of blood pressure from nondipper to dipper is examined.

Methods and Results
Patients (n=42) with essential hypertension were maintained on a high-sodium diet (12 to 15 g of NaCl per day) and a low-sodium diet (1 to 3 g/d) for 1 week each. On the last day of each diet, blood pressures were measured noninvasively every hour for 24 hours with an automatic oscillometric device. Twenty-one patients were classified as non–sodium sensitive whereas 21 were classified as sodium sensitive on the basis of a ≥10% change in 24-hour mean arterial pressure caused by sodium restriction. Nocturnal blood pressure fall was significant in the non–sodium sensitive subjects but not in sodium-sensitive subjects. There was a significant interaction between sodium restriction and nocturnal fall in blood pressure only in the sodium-sensitive subjects, indicating that the degree of the nocturnal fall was affected by sodium restriction. Furthermore, changes in the nocturnal fall induced by sodium restriction had a positive relationship with sodium sensitivity (
r
=.38,
P
<.02) and a negative relationship with the nocturnal fall before sodium restriction (
r
=−.75,
P
<.0001).

Conclusions
These findings show the difference in nocturnal fall in blood pressure between the non–sodium sensitive and sodium-sensitive types of essential hypertension. The diminished nocturnal fall, recognized in the sodium-sensitive type, is restored by sodium restriction, indicating that the circadian rhythm of blood pressure shifted from a nondipper to a dipper pattern. On the other hand, the nocturnal fall is not affected by sodium restriction in the non–sodium sensitive type, and the circadian rhythm remains of the dipper variety.
Enhanced Endothelin-Mediated Coronary Vasoconstriction and Attenuated Basal Nitric Oxide Activity in Experimental Hypercholesterolemia
Authors: Mathew Verghese , Cannan Charles R. , Miller Virginia M. , Barber Dustan A. , Hasdai David , Schwartz Robert S. , Holmes David R. , Lerman Amir
Published: June 2012

Background
Experimental hypercholesterolemia is associated with coronary vasomotor dysfunction. This study was designed to test the hypothesis that experimental hypercholesterolemia is characterized by altered coronary vasomotor responses to endothelin and inhibition of the endogenous NO pathway.

Methods and Results
Endothelin-1 (ET-1) at 5 ng · kg
−1
· min
−1
or
N
G
-monomethyl-
l
-arginine (L-NMMA), a competitive inhibitor of nitric oxide synthase (NOS), at 50 μg · kg
−1
· min
−1
was infused into the left anterior descending coronary artery in pigs before and after 10 weeks of cholesterol diet. There was a significant increase in serum cholesterol. At 10 weeks, ET-1 resulted in an accentuated decrease in coronary blood flow (CBF) and coronary artery diameter (CAD) compared with baseline (−88±6% versus −45±9%,
P
<.05, and −77±14% versus −18±8%,
P
<.05, respectively) and an increase in coronary vascular resistance (CVR) (242±18% versus 110±17%,
P
<.05); ET receptor density and binding affinity in epicardial coronary arteries were unchanged. The effect of L-NMMA on CBF, CAD, and CVR was attenuated at 10 weeks (−7±8% versus −48±4%, −2±3% versus −17±5%, and 16±10% versus 125±32%; each
P
<.05). Immunohistochemistry staining for constitutive NOS revealed a decrease in immunoreactivity in the coronary arteries of hypercholesterolemic pigs.

Conclusions
The present study demonstrates an enhanced coronary vasoconstrictive response to pathophysiological doses of endothelin and an attenuated response to the inhibition of endogenous NO activity, suggesting an alteration in coronary vascular reactivity in experimental hypercholesterolemia.
Prevention of the Angiographic Progression of Coronary and Vein-Graft Atherosclerosis by Gemfibrozil After Coronary Bypass Surgery in Men With Low Levels of HDL Cholesterol
Authors: Frick M. Heikki , Syvänne Mikko , Nieminen Markku S. , Kauma Heikki , Majahalme Silja , Virtanen Vesa , Kesäniemi Y. Antero , Pasternack Amos , Taskinen Marja-Riitta
Published: June 2012

Background
Studies have shown that treatment of hyperlipidemia, especially lowering of plasma LDL levels, retards the progression of coronary atherosclerosis and prevents clinical cardiovascular events. No such studies have focused on subjects with low levels of HDL cholesterol.

Methods and Results
We randomly assigned 395 post–coronary bypass men, who had an HDL cholesterol concentration ≤1.1 mmol/L and LDL cholesterol ≤4.5 mmol/L, to receive gemfibrozil 1200 mg/d or placebo. Coronary angiography was performed at baseline and after, on average, 32 months of therapy. Changes in coronary dimensions were assessed by computer-assisted analysis. Average on-trial serum triglyceride concentrations were 1.69±0.68 and 1.02±0.37, total cholesterol 5.48±0.68 and 4.83±0.63, LDL cholesterol 3.84±0.59 and 3.39±0.56, and HDL cholesterol 0.88±0.15 and 0.98±0.17 mmol/L in the placebo and gemfibrozil groups, respectively (mean±SD, each
P
<.001). The change in per-patient means of average diameters of native coronary segments was –0.04±0.11 mm in the placebo group and –0.01±0.10 mm in the gemfibrozil group (
P
=.009). The equivalent changes in minimum luminal diameters of stenoses were –0.09±0.18 and –0.04±0.15 mm, respectively (
P
=.002). A similar, albeit nonsignificant, trend toward treatment benefit was found in the predefined primary study end point, segments unaffected by grafts and those distal to graft insertions. In aortocoronary bypass grafts, 23 subjects (14%) assigned to placebo had new lesions in the follow-up angiogram, compared with 4 subjects (2%) assigned to gemfibrozil (
P
<.001).

Conclusions
Gemfibrozil therapy retarded the progression of coronary atherosclerosis and the formation of bypass-graft lesions after coronary bypass surgery in men with low HDL cholesterol as their main lipid abnormality.
Chlamydia Pneumoniae
, Cytomegalovirus, and Herpes Simplex Virus in Atherosclerosis of the Carotid Artery
Authors: Chiu B. , Viira E. , Tucker W. , Fong I.W.
Published: June 2012

Background
Chlamydia pneumoniae
and the herpes viruses cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV-1) have been associated with human atherosclerosis in seroepidemiological and separate histopathological studies. We investigated the concurrent presence of these microorganisms in patients undergoing carotid endarterectomy.

Methods and Results
Endarterectomy specimens from 76 patients with carotid artery stenosis were stained for
C pneumoniae
, CMV, and HSV-1 particles with specific IgG monoclonal antibodies by the avidin-biotin-peroxidase method. IgG antibodies to CMV and
C pneumoniae
were also measured in the serum. These were correlated with plaque morphology and the presence of the microorganisms in the atherosclerotic plaques.
C pneumoniae
was detected in 54 (71%) (95% confidence interval [CI], 59.5% to 80.9%), CMV was detected in 27 (35.5%) (CI, 24.9% to 47.3%), and HSV-1 was detected in 8 (10.5%) (CI, 4.7% to 19.7%) versus none of 20 (0%) control normal carotid artery and aortic tissue (autopsy) specimens (CI, 0% to 16.8%) (
P
<.001 for CMV and
C pneumoniae
). At least one microorganism was detected in 59 of the specimens (77.6%) (CI, 66.6% to 86.4%), with a single microorganism present only in 35 (46%), two microorganisms present in 18 (23.7%) (CI, 14.7% to 34.8%), and all three present in 6 (7.9%) (CI, 3.0% to 16.4%). Atherosclerotic plaques with thrombosis were more likely to have
C pneumoniae
(80.4%) or CMV (57.8%) than were plaques without thrombosis (56.7% and 16.7%, respectively;
P
=.04 and .007). There was no correlation between the presence of CMV and
C pneumoniae
in the atherosclerotic vessels and serum antibody titers.

Conclusions C pneumoniae
and CMV are commonly detected in atherosclerotic plaques of the carotid arteries, but their presence cannot be predicted by measuring serum antibodies. The presence of these microorganisms may predispose to a greater risk of thrombosis in the plaques, but further studies are needed to confirm this observation.
Normalization of Acquired QT Prolongation in Humans by Intravenous Potassium
Authors: Choy Anna Maria , Lang Chim C. , Chomsky Don M. , Rayos Glenn H. , Wilson John R. , Roden Dan M.
Published: June 2012

Background
QT interval prolongation and dispersion have been implicated in serious arrhythmias in congestive heart failure (CHF) and the congenital and drug-induced long-QT syndromes (LQTS). In a subset of the congenital LQTS, infusion of potassium can correct QT abnormalities, consistent with in vitro increases in outward currents such as
I
Kr
or
I
K1
when extracellular potassium concentration ([K
+
]
o
) is increased. Furthermore, increasing [K
+
]
o
decreases the potency of
I
Kr
-blocking drugs in vitro. The purpose of this study was to test the hypothesis that increasing [K
+
]
o
corrects QT abnormalities in CHF and in subjects treated with quinidine.

Methods and Results
KCl (maximum, 40 mEq) was infused into (1) 12 healthy subjects treated with quinidine sulfate (5 doses of 300 mg/5 h) or placebo and (2) 8 CHF patients and age-matched normal control subjects. Mean [K
+
] increased from 4 to 4.2 mEq/L to 4.7 to 5.2 mEq/L. Potassium infusion significantly reversed QTU
c
prolongation, especially in the precordial leads (quinidine, 590±79 to 479±35 [±SD] ms
1/2
,
P
<.001; CHF, 521±110 to 431±47 ms
1/2
,
P
<.05). There was no effect in either control group. Similarly, potassium decreased QTU
c
dispersion (quinidine, 210±62 to 130±75 ms
1/2
,
P
<.01; CHF, 132±68 to 84±35 ms
1/2
,
P
=.07) and was without effect in the control subjects. QT morphological abnormalities, including U waves and bifid T waves, were reversed by potassium.

Conclusions
Potentially arrhythmogenic QT abnormalities during quinidine treatment and in CHF can be nearly normalized by modest elevation of serum potassium.
Randomized, Double-blind Comparison of Hirulog Versus Heparin in Patients Receiving Streptokinase and Aspirin for Acute Myocardial Infarction (HERO)
Authors: White H. D. , Aylward P. E. , Frey M. J. , Adgey A. A. J. , Nair R. , Hillis W. S. , Shalev Y. , Brown M. A. , French J. K. , Collins R. , Maraganore J. , Adelman B.
Published: June 2012

Background
Thrombolytic therapy improves survival after myocardial infarction through reperfusion of the infarct-related artery. Thrombin generated during thrombolytic administration may reduce the efficacy of thrombolysis. A direct thrombin inhibitor may improve early patency rates.

Methods and Results
Four hundred twelve patients presenting within 12 hours with ST-segment elevation were given aspirin and streptokinase and randomized in a double-blind manner to receive up to 60 hours of either heparin (5000 U bolus followed by 1000 to 1200 U/h), low-dose hirulog (0.125 mg/kg bolus followed by 0.25 mg · kg
−1
· h
−1
for 12 hours then 0.125 mg · kg
−1
· h
−1
), or high-dose hirulog (0.25 mg/kg bolus followed by 0.5 mg · kg
−1
· h
−1
for 12 hours then 0.25 mg · kg
−1
· h
−1
). The primary outcome was Thrombolysis In Myocardial Infarction trial (TIMI) grade 3 flow of the infarct-related artery at 90 to 120 minutes. TIMI 3 flow was 35% (95% CI, 28% to 44%) with heparin, 46% (95% CI, 38% to 55%) with low-dose hirulog, and 48% (95% CI, 40% to 57%) with high-dose hirulog (heparin versus hirulog,
P
=.023; heparin versus high-dose hirulog,
P
=.03). At 48 hours, reocclusion had occurred in 7% of heparin, 5% of low-dose hirulog, and 1% of high-dose hirulog patients (
P
=NS). By 35 days, death, cardiogenic shock, or reinfarction had occurred in 25 heparin (17.9%), 19 low-dose hirulog (14%), and 17 high-dose hirulog patients (12.5%) (
P
=NS). Two strokes occurred with heparin, none with low-dose hirulog, and two with high-dose hirulog. Major bleeding (40% from the groin site) occurred in 28% of heparin, 14% of low-dose hirulog, and 19% of high-dose hirulog patients (heparin versus low-dose hirulog,
P
<.01).

Conclusions
Hirulog was more effective than heparin in producing early patency in patients treated with aspirin and streptokinase without increasing the risk of major bleeding. Direct thrombin inhibition may improve clinical outcome.
Flow-Mediated Dilation in 9- to 11-Year-Old Children
Authors: Leeson C.P.M. , Whincup P.H. , Cook D.G. , Donald A.E. , Papacosta O. , Lucas A. , Deanfield J.E.
Published: June 2012

Background
Early life factors, particularly size at birth, may influence later risk of cardiovascular disease, but a mechanism for this influence has not been established. We have examined the relation between birth weight and endothelial function (a key event in atherosclerosis) in a population-based study of children, taking into account classic cardiovascular risk factors in childhood.

Methods and Results
We studied 333 British children aged 9 to 11 years in whom information on birth weight, maternal factors, and risk factors (including blood pressure, lipid fractions, preload and postload glucose levels, smoking exposure, and socioeconomic status) was available. A noninvasive ultrasound technique was used to assess the ability of the brachial artery to dilate in response to increased blood flow (induced by forearm cuff occlusion and release), an endothelium-dependent response. Birth weight showed a significant, graded, positive association with flow-mediated dilation (0.027 mm/kg; 95% CI, 0.003 to 0.051 mm/kg;
P
=.02). Childhood cardiovascular risk factors (blood pressure, total and LDL cholesterol, and salivary cotinine level) showed no relation with flow-mediated dilation, but HDL cholesterol level was inversely related (−0.067 mm/mmol; 95% CI, −0.021 to −0.113 mm/mmol;
P
=.005). The relation between birth weight and flow-mediated dilation was not affected by adjustment for childhood body build, parity, cardiovascular risk factors, social class, or ethnicity.

Conclusions
Low birth weight is associated with impaired endothelial function in childhood, a key early event in atherogenesis. Growth in utero may be associated with long-term changes in vascular function that are manifest by the first decade of life and that may influence the long-term risk of cardiovascular disease.
Simultaneous Overexpression of Two Stress Proteins in Rat Cardiomyocytes and Myogenic Cells Confers Protection Against Ischemia-Induced Injury
Authors: Lau Sandy , Patnaik Nandita , Sayen M. Richard , Mestril Ruben
Published: June 2012

Background
Mitochondria are known to be a major target during ischemic cardiac injury. Previous studies have shown that in rodent myogenic cells and in the hearts of transgenic mice in which the heat shock or stress protein 70 is increased, there is a marked tolerance to ischemia/reperfusion injury. Two other heat shock proteins (HSP60 and HSP10) are known to form, within the mitochondria, a chaperonin complex that is important for mitochondrial protein folding and function. We were then interested in investigating whether increased expression of these two stress proteins is able to protect myogenic cells against ischemia/reperfusion injury.

Methods and Results
We generated recombinant adenoviral vectors containing HSP60, HSP10, or a combination of the two genes. These adenoviral constructs overexpress significant amounts of these stress proteins in both rat neonatal cardiomyocytes and the myogenic H9 c2 cell line. Cells infected with an adenoviral construct overexpressing both HSP60 and HSP10 were found to be protected against simulated ischemia, whereas cells infected with adenoviral constructs overexpressing only HSP60 or HSP10 alone were not rendered tolerant to simulated ischemic injury.

Conclusions
These results suggest that the simultaneous expression of these two proteins that form a chaperonin complex in the mitochondria plays an important role in the survival of myogenic cells after ischemia/reperfusion injury.
Role of the Purkinje System in Spontaneous Ventricular Tachycardia During Acute Ischemia in a Canine Model
Authors: Arnar David O. , Bullinga John R. , Martins James B.
Published: June 2012

Background
A role for the Purkinje system in the development of spontaneous ventricular tachycardia (VT) during acute ischemia has been suspected but not proved. We used a three-dimensional activation mapping system incorporating Purkinje signals to characterize the mechanism and site of origin of spontaneous VT occurring in the first 30 minutes after coronary artery occlusion in a dog model.

Methods and Results
The left anterior descending coronary artery was occluded in 48 dogs after instrumentation of the risk zone with 21 multipolar plunge needles, each recording 6 bipolar electrograms through the myocardial wall. VT of Purkinje origin was defined as a focal endocardial VT with a Purkinje potential identified before muscle potential on the electrode recording the earliest activity. Purkinje potentials were identified on an average of 10 of the 21 plunge needles. During atrial pacing at cycle lengths of 300 to 700 ms, a total of 25 VTs were observed from 18 of the 48 dogs (37.5%). Of the VTs, 15 (60.0%) were of focal Purkinje origin, 1 (4.0%) of focal endocardial origin, 2 (8.0%) of focal midmyocardial origin, and 2 (8.0%) of focal epicardial origin; 3 (12.0%) had a reentrant mechanism, whereas in 2 (8.0%), the mechanism could not be defined. The mean cycle length of all VTs was 265±17 ms (mean±SEM, n=25). Of the 25 VTs, 19 originated from an ischemic area as defined by significant decreases in voltages of muscle electrograms at the time of occurrence of the VT, 4 originated from an ischemic border zone, and the origin of 2 could not be determined.

Conclusions
In this model, VT with a focal mechanism is commonly seen in the early ischemic period. Sixty percent of the VTs were of focal Purkinje origin as characterized by three-dimensional activation mapping. The results of this study indicate that Purkinje tissue may play an important role in the development of early ischemic VT.
A New Treatment for Severe Pulmonary Embolism
Authors: Koning René , Cribier Alain , Gerber Lowell , Eltchaninoff Hélène , Tron Christophe , Gupta Vivek , Soyer Robert , Letac Brice
Published: June 2012

Background
The rheolytic thrombectomy catheter has been specially designed to remove intravascular thrombus from coronary and peripheral arteries. It demonstrates a practical application of Bernoulli’s principle relating to a low-pressure zone in the region of a high-velocity jet. In this device, this effect is created by direct high-pressure saline jets located at the tip. Thrombus is drawn into this region and, because of the large pressure difference, undergoes mechanical thrombolysis due to the powerful mixing forces. The resulting microparticles are aspirated through the same catheter and removed from the body.

Methods and Results
We report the use of this device in two patients presenting with severe pulmonary embolism and contraindications to thrombolytic therapy. The two procedures were successfully performed with an excellent immediate angiographic result at the site of the rheolytic thrombectomy. In both cases, the clinical improvement was maintained at follow-up with the same good angiographic result and a decrease to a normal level of the systolic pulmonary pressure.

Conclusions
This preliminary results suggest that this easy technical method may be useful in the treatment of life-threatening pulmonary embolism in patients with absolute contraindications to thrombolytic therapy. A larger cohort of patients is necessary to determine whether this treatment should be proposed as an alternative to the use of fibrinolytics in selected patients.
Apolipoprotein(a) Induces Monocyte Chemotactic Activity in Human Vascular Endothelial Cells
Authors: Poon Michael , Zhang Xiaoxia , Dunsky Kevin G. , Taubman Mark B. , Harpel Peter C.
Published: June 2012

Background
Elevated levels of lipoprotein(a) [Lp(a)] are associated with premature atherosclerosis; however, the mechanisms are not known. Recruitment of monocytes to the blood vessel wall is an early event in atherogenesis.

Methods and Results
This study has found that unoxidized Lp(a) induced human umbilical vein endothelial cells (HUVECs) to secrete monocyte chemotactic activity (MCA), whereas LDL under the same conditions did not. In the absence of HUVECs, Lp(a) had no direct MCA. Endotoxin was shown not to be responsible for the induction of MCA. Actinomycin D and cycloheximide inhibited the HUVEC response to Lp(a), indicating that protein and RNA synthesis were required. The apolipoprotein(a) [apo(a)] portion of Lp(a) was identified as the structural component of Lp(a) responsible for inducing MCA. Lp(a) and apo(a) also stimulated human coronary artery endothelial cells to produce MCA. Granulocyte-monocyte colony–stimulating factor (GM-CSF) antigen was not detected in the Lp(a)-conditioned medium, nor was monocyte chemoattractant protein-1 mRNA induced in HUVECs by Lp(a).

Conclusions
These findings suggest that Lp(a) may be involved in the recruitment of monocytes to the vessel wall and provide a novel mechanism for the participation of Lp(a) in the atherogenic process.
Fasting Triglycerides, High-Density Lipoprotein, and Risk of Myocardial Infarction
Authors: Gaziano J. Michael , Hennekens Charles H. , O’Donnell Christopher J. , Breslow Jan L. , Buring Julie E.
Published: June 2012

Background
Recent data suggest that triglyceride-rich lipoproteins may play a role in atherogenesis. However, whether triglycerides, as a marker for these lipoproteins, represent an independent risk factor for coronary heart disease remains unclear, despite extensive research. Several methodological issues have limited the interpretability of the existing data.

Methods and Results
We examined the interrelationships of fasting triglycerides, other lipid parameters, and nonlipid risk factors with risk of myocardial infarction among 340 cases and an equal number of age-, sex-, and community-matched control subjects. Cases were men or women of <76 years of age with no prior history of coronary disease who were discharged from one of six Boston area hospitals with the diagnosis of a confirmed myocardial infarction. In crude analyses, we observed a significant association of elevated fasting triglycerides with risk of myocardial infarction (relative risk [RR] in the highest compared with the lowest quartile=6.8; 95% confidence interval [CI]=3.8 to 12.1;
P
for trend <.001). Results were not materially altered after control for nonlipid coronary risk factors. As expected, the relationship was attenuated after adjustment for HDL but remained statistically significant (RR in the highest quartile=2.7; 95% confidence interval [CI]=1.4 to 5.5;
P
for trend=.016). Furthermore, the ratio of triglycerides to HDL was a strong predictor of myocardial infarction (RR in the highest compared with the lowest quartile=16.0; 95% CI=7.7 to 33.1;
P
for trend <.001).

Conclusions
Our data indicate that fasting triglycerides, as a marker for triglyceride-rich lipoproteins, may provide valuable information about the atherogenic potential of the lipoprotein profile, particularly when considered in context of HDL levels.
Randomized, Double-Blind, Placebo-Controlled Study of Supplemental Vitamin E on Attenuation of the Development of Nitrate Tolerance
Authors: Watanabe Hideki , Kakihana Masaaki , Ohtsuka Sadanori , Sugishita Yasuro
Published: June 2012

Background
The attenuation of intracellular production of cGMP has been known to be a mechanism of nitrate tolerance. A recent in vitro study showed an increase in superoxide levels and a reduced activation of guanylate cyclase in tolerant vessels. We investigated the preventive effect of an antioxidant, vitamin E, on the development of nitrate tolerance.

Methods and Results
In this double-blind, placebo-controlled study, 24 normal volunteers and 24 patients with ischemic heart disease (IHD patients) were randomized to receive either vitamin E (200 mg TID vitamin E group) or placebo (placebo group). Vasodilator response to nitroglycerin was assessed with forearm plethysmography by measurement of the change in the forearm blood flow before and 5 minutes after sublingual administration of 0.3 mg nitroglycerin, and at the same time, blood samples were taken from veins to measure the platelet cGMP level. Measurements of the forearm blood flow and blood sampling were obtained serially at baseline (day 0), 3 days after vitamin E or placebo alone was taken (day 3), and 3 days after application of a 10-mg/24-h nitroglycerin tape concomitantly with oral vitamin E or placebo (day 6). The responses of forearm blood flow (%FBF) and cGMP (%cGMP) after sublingual nitroglycerin on day 0 (%FBF: normal volunteers, 32±12 versus 31±11; IHD patients, 35±15 versus 34±15; %cGMP: normal volunteers, 38±10 versus 35±11; IHD patients, 37±11 versus 38±12, vitamin E group versus placebo group) and day 3 (%FBF: normal volunteers, 33±9 versus 32±12; IHD patients, 35±12 versus 33±13; %cGMP: normal volunteers, 38±10 versus 37±11; IHD patients, 36±14 versus 37±10, vitamin E group versus placebo group) were not different between the two groups. On day 6, %FBF and %cGMP in the placebo group were significantly lower compared with day 0, and there were significant differences in them between the two groups (%FBF: normal volunteers, 30±12 versus 17±9,
P
<.01; IHD patients, 28±14 versus 17±8,
P
<.01; %cGMP: normal volunteers, 35±11 versus 8±5,
P
<.01; IHD patients, 38±10 versus 12±4,
P
<.01, vitamin E group versus placebo group).

Conclusions
These results indicate that the combination therapy with vitamin E is potentially a useful method to prevent the development of nitrate tolerance.