Circulation. 2009;120:1843-1844
doi: 10.1161/CIRCULATIONAHA.109.192659
(Circulation. 2009;120:1843-1844.)
© 2009 American Heart Association, Inc.
Clinical Summaries
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Anthropometry, Body Fat, and Venous Thromboembolism: A Danish Follow-Up Study
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The distribution of body fat predicts the risk of coronary heart
disease, and central obesity consistently has been shown to
be a risk factor for coronary heart disease, whereas peripheral
obesity (measured as high hip circumference) appears to protect
against coronary heart disease. The importance of fat distribution
with regard to the risk of venous thromboembolism (VTE), ie,
deep venous thrombosis and pulmonary embolism, has not been
evaluated. In a 10-year follow-up study of 56 014 middle-aged
men and women, which included 641 verified incident events of
VTE, we evaluated the risk of VTE according to different measurements
of fat distribution in the body. Our results show that all measurements
of obesity are positively associated with VTE in both sexes.
We also showed that a higher hip circumference in normal-weight
persons was associated with a higher risk for VTE, which is
in contrast to studies on coronary heart disease. We found statistically
significant positive associations between idiopathic (unprovoked)
VTE and all measurements of obesity. The associations between
VTE and the anthropometric measurements persisted after adjustment
for hypertension, diabetes mellitus, or hypercholesterolemia,
which shows that the effect of obesity was not mediated solely
by these factors. See p
1850.
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Cardiac Resynchronization Induces Major Structural and Functional Reverse Remodeling in Patients With New York Heart Association Class I/II Heart Failure
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Cardiac resynchronization therapy (CRT) has proved efficacious
in New York Heart Association (NYHA) class III/IV heart failure
(HF). This key echocardiographic study assessed the impact of
CRT on structural and functional reverse remodeling in patients
with NYHA class I/II HF. The REsynchronization reVErses Remodeling
in Systolic left vEntricular dysfunction (REVERSE) trial was
a large, prospective, double-blind, controlled trial of CRT
in patients with NYHA class I/II HF, a QRS
120 ms, left ventricular
(LV) end-diastolic dimension
55 mm, and LV ejection fraction
40% who were randomly assigned to active therapy (CRT-on; n=419)
or control (CRT-off; n=191). Doppler echocardiograms were recorded
at baseline, before hospital discharge, and at 6 and 12 months.
The present study showed that CRT in patients with NYHA class
I/II HF who were already receiving optimal therapy with a β-blocker
(95%), angiotensin-converting enzyme inhibitor, or angiotensin
receptor blocker (97%) resulted in LV reverse remodeling with
favorable changes in LV volume, shape, and ejection fraction
similar to those that occurred in patients in NYHA class III/IV;
however, there were no accompanying changes in LV diastolic
function, LV mass, or severity of mitral regurgitation. There
was 3-fold greater LV reverse remodeling in patients with a
nonischemic origin of HF than in those with an ischemic origin.
Our findings have potentially important clinical implications
in that CRT may delay or interrupt the natural disease progression
of HF in these patients. This and ongoing studies may define
an important therapeutic role for CRT in patients with NYHA
class I/II, as well as class III/IV HF, especially those cases
with a nonischemic cause. See p
1858.
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Three-Year Outcomes After Sirolimus-Eluting Stent Implantation for Unprotected Left Main Coronary Artery Disease: Insights From the j-Cypher Registry
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Despite the growing popularity of stenting unprotected left
main coronary arteries with drug-eluting stents, long-term outcomes
have not been assessed adequately. This large multicenter registry
in Japan (the j-Cypher registry) compared the 3-year clinical
outcomes of 582 patients undergoing percutaneous coronary intervention
for unprotected left main coronary artery (ULMCA) lesions with
those of 12 242 patients undergoing percutaneous coronary intervention
for non-ULMCA lesions only. The influence of lesion location
and bifurcation stenting strategy on clinical outcomes was also
assessed in 476 patients whose ULMCA lesions were treated exclusively
with sirolimus-eluting stents. The main findings of this study
are as follows: (1) Percutaneous coronary intervention for ULMCA
lesions was associated with a higher late mortality rate than
for lesions located elsewhere, but this finding was mainly related
to factors other than the left main being the treatment site;
(2) sirolimus-eluting stent implantation in ostial/shaft left
main lesions was associated with a better 3-year target-lesion
revascularization rate than in distal bifurcation lesions; and
(3) patients with ULMCA plus 3-vessel disease had poor long-term
outcome in terms of coronary revascularization, stent thrombosis,
and cardiac death. Therefore, although ULMCA stenting with a
sirolimus-eluting stent is an attractive option, clinical outcomes
are less satisfactory in patients who need bifurcation 2-stent
treatment or who have extensive coronary artery disease outside
the ULMCA. Consideration of the individual patient’s risk
stratification is important when selecting coronary revascularization
strategies in patients with ULMCA disease. See p
1866.
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Volumetric Intravascular Ultrasound Analysis of Paclitaxel-Eluting and Bare Metal Stents in Acute Myocardial Infarction: The Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction Intravascular Ultrasound Substudy
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In the prospective, multicenter Harmonizing Outcomes With Revascularization
and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial,
patients with ST-segment elevation myocardial infarction within
12 hours of symptom onset were randomized 3:1 to TAXUS EXPRESS
paclitaxel-eluting stents or EXPRESS bare metal stents. The
intravascular ultrasound substudy enrolled 464 patients with
baseline and 13-month follow-up imaging at 36 centers. Paclitaxel-eluting
compared with bare metal stents significantly reduced percent
net volume obstruction (6.5% [first and third quartiles, 2.2%
and 10.8% ] versus 15.6% [first and third quartiles, 7.2% and
28.8];
P<0.0001) but also resulted in more late-acquired
stent malapposition (29.6% versus 7.9%;
P=0.0005) resulting
from positive vessel remodeling. Plaque and/or thrombus protrusion
through stent struts was initially present in 70.4% of paclitaxel-eluting
stents and 64.8% of bare metal stents; all resolved during follow-up.
New aneurysm formation, stent fracture, and subclinical thrombus
were uncommon, although seen only in paclitaxel-eluting stents.
The present data demonstrate a reduction in neointimal hyperplasia
and restenosis in ST-segment elevation myocardial infarction
patients treated with paclitaxel-eluting stents compared with
bare metal stents. Long-term follow-up is required to establish
whether the increased frequency of late-acquired stent malapposition
with paclitaxel-eluting stents has clinical significance. See
p
1875.
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Glycome and Transcriptome Regulation of Vasculogenesis
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Promotion of neovasculature holds the potential for ameliorating
coronary artery disease. The TOPCARE-AMI (Transplantation Of
Progenitor Cells And Regeneration Enhancement in Acute Myocardial
Infarction) trial indicated that circulating endothelial progenitor
cells could improve left ventricular ejection fraction in patients
after myocardial infarction. Recent studies have demonstrated
that embryonic stem cells can differentiate into functional
endothelial cells through vasculogenesis, which results in functional
improvement that arises from increased neovascularization. The
harnessing of vasculogenesis has the potential to revolutionize
regenerative medicine but is contingent on a means to regulate
cellular differentiation. In the present study, we demonstrate
that the glyco-microenvironment of the stem cell, specifically
the sulfated heparan sulfate glycosaminoglycans, plays a critical
role in facilitating vasculogenesis. We confirmed these findings
in vivo in larval zebrafish, in which desulfation of heparan
sulfate glycosaminoglycans resulted in impaired vascular development.
The phenotype is rescued with exogenous sulfated heparan sulfate
glycosaminoglycans. Finally, we identified several downstream
pathways that may mediate the regulation of vasculogenesis by
heparan sulfate glycosaminoglycans, including a novel FOXO3A/5-IGF2
signaling pathway. This study reveals the exciting potential
of harnessing defined cellular glyco-microenvironments for directed
differentiation of precursor cells into endothelial cells, leading
to neovascularization. See p
1883.
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Hyperhomocysteinemia Promotes Inflammatory Monocyte Generation and Accelerates Atherosclerosis in Transgenic Cystathionine β-Synthase–Deficient Mice
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Hyperhomocysteinemia (HHcy) is an independent risk factor for
cardiovascular diseases. In this study, we established novel
disease models with severe HHcy and hypercholesterolemia in
which the mouse cystathionine β-synthase (CBS) and apolipoprotein
E (apoE) genes are deficient and an inducible human CBS or disease-relevant
mutant CBS (S466L) transgene is introduced to circumvent the
neonatal lethality of CBS deficiency (
Tg-hCBS apoE–-/–- Cbs–-/–- or
Tg-S466L Cbs–-/–- mice).
First, we demonstrated that severe HHcy accelerated atherosclerosis
and inflammatory monocyte/macrophage accumulation in the lesion
and increased plasma tumor necrosis factor-
and monocyte chemoattractant
protein-1 levels in
Tg-hCBS apoE–-/–- Cbs–-/–- mice fed a high-fat diet. Thus, systemic inflammation possibly
mediated the enhanced Ly-6C monocyte/macrophage accumulation
in the lesion. We also found that severe HHcy induced Ly-6C
hi and Ly-6C
mid inflammatory monocyte subset expansion in the peripheral
blood, spleen, and bone marrow in
Tg-hCBS apoE–-/–- Cbs–-/–- and
Tg-S466L Cbs mice independently of
hyperlipidemia. Furthermore, we discovered that
L-homocysteine,
but not
L-cysteine, promoted Ly-6C
hi monocyte subset survival
and Ly-6C
mid subset differentiation in cultured primary mouse
splenocytes. Finally, we reported that Hcy-induced Ly-6C
mid subset differentiation was abolished by superoxide dismutase/catalase
or the NAD(P)H oxidase inhibitor apocynin. Taken together, these
results show that HHcy selectively promoted Ly-6C monocyte subset
differentiation and enhanced their accumulations in the lesion,
contributing to accelerated atherosclerosis in HHcy. Thus, the
present study provides important insights into HHcy-related
cardiovascular disease. See p
1893.
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 -H2AX Foci as a Biomarker for Patient X-Ray Exposure in Pediatric Cardiac Catheterization: Are We Underestimating Radiation Risks?
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Interventional cardiologists should be aware that x-ray doses
to patients can be high, especially in cases of complex procedures
involving extensive use of fluoroscopy and multiple cine runs.
With respect to the x-ray–induced oncogenic risk, children
undergoing a catheterization procedure, eg, for treatment of
congenital heart disease, require special attention in view
of their higher radiosensitivity and the fraction of the body
irradiated. For some patients, cardiac catheterization procedures
need to be repeated several times, leading to significant cumulative
effective doses and cancer risks. In the present study, a biomarker
approach (analysis of
-H2AX foci in lymphocytes) was used to
assess DNA damage induced by interventional x-rays in a pediatric
patient group. These patient data point to a low-dose hypersensitivity,
resulting in risk estimates seriously higher than those obtained
from the linear-no-threshold hypothesis, generally used in radiation
protection until now. Present data emphasize the importance
of all measures, technical and procedural, for reducing and
optimizing patient x-ray exposure. This applies also to the
hybrid approach, which combines surgery and interventional techniques.
The direct link between x-ray exposure and effects in patients
observed in the present work should trigger the radiological
awareness of interventional cardiologists. See p
1903.
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High Levels of Acetylated Low-Density Lipoprotein Uptake and Low Tyrosine Kinase With Immunoglobulin and Epidermal Growth Factor Homology Domains-2 (Tie2) Promoter Activity Distinguish Sinusoids From Other Vessel Types in Murine Bone Marrow
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Changes in the bone marrow microvasculature have been demonstrated
to result from the presence of certain forms of leukemia in
the bone marrow. Increases in the number of vascular cross sections
within a given section of the bone marrow have been the primary
method of demonstrating increases in marrow vascular density.
Furthermore, antiangiogenic treatments have been used to treat
hematologic malignancies such as multiple myeloma. However,
understanding the biology of this extravascular tissue is imperative
to developing better targeted therapy. Here, a mouse model is
used to demonstrate that the arteriolar and venous vasculatures
are physiologically different. Expression of the receptor Tie2
(tyrosine kinase with immunoglobulin and EGF homology domains)
was seen predominantly in the arteriolar vessels. Furthermore,
endocytosis of the functional endothelial marker acetylated
low-density lipoprotein was more pronounced in the marrow sinusoids
and veins but not the arterioles. These results suggest that
the bone marrow vasculature is functionally heterogeneous. Recognizing
this heterogeneity, studies should be undertaken to determine
what types of vessels increase in disease states such as multiple
myeloma. Understanding this heterogeneity and how disease affects
specific types of blood vessels could allow the development
of better targeted therapy to treat marrow disorders. See p
1910.
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