Circulation. 2008;117:1121-1123
doi: 10.1161/CIRCULATIONAHA.107.189180
(Circulation. 2008;117:1121-1123.)
© 2008 American Heart Association, Inc.
Clinical Summaries
 |
Dietary Fish and  -3 Fatty Acid Consumption and Heart Rate Variability in US Adults
|
|---|
Consumption of fish and
-3 fatty acid reduces risk of cardiac
death, but mechanisms are not well established. Heart rate variability
(HRV) predicts cardiac death and reflects specific electrophysiological
pathways and influences. To elucidate electrophysiological influences
and support effects on clinical risk, we evaluated the associations
between habitual consumption of fish and marine
-3 fatty acids
and HRV, assessed by both 12-lead ECG (n=4263) and 24-hour Holter
monitoring (n=1152), in a population-based cohort of older US
adults. After multivariable adjustment, consumption of tuna
or other broiled/baked fish was associated with specific HRV
components, including indices suggestive of greater vagal predominance
and moderated baroreceptor responses (eg, higher root mean square
successive differences of normal-to-normal intervals, higher
normalized high-frequency power, and lower low-frequency/high-frequency
ratio) and less erratic sinoatrial node firing (eg, lower Poincaré
ratio and higher short-term fractal scaling exponent). Findings
were similar for estimated dietary consumption of marine
-3
fatty acids. For the magnitudes of the observed differences
in HRV comparing the highest with the lowest category of fish
intake, the differences in relative risk of coronary heart disease
death during 10.8 years of follow-up ranged from 1.1% lower
risk for the difference in standard deviation of normal-to-normal
intervals to 5.9% and 8.4% lower risk for the differences in
the Poincaré ratio and short-term fractal scaling exponent,
respectively. Thus, habitual consumption of tuna/other fish
and marine
-3 fatty acid are associated with specific and clinically
relevant differences in HRV in older adults, including indices
of more favorable vagal activity, baroreceptor responses, and
sinoatrial node function. Cellular mechanisms and implications
for clinical risk deserve further investigation. See p
1130.
|
Association of Leukocyte Telomere Length With Circulating Biomarkers of the Renin-Angiotensin-Aldosterone System: The Framingham Heart Study
|
|---|
Leukocyte telomere length (LTL) reflects the cumulative burden
of oxidative stress and inflammation experienced over a life
course. Activation of the renin-angiotensin-aldosterone system
is associated with increased oxidative stress and inflammation.
We tested the hypothesis that LTL may be related to circulating
biomarkers of the renin-angiotensin-aldosterone system by examining
the cross-sectional relations of LTL and circulating renin and
aldosterone concentrations in 1203 Framingham Heart Study participants.
In multivariable analyses adjusting for confounders, LTL was
inversely related to renin and the renin-to-aldosterone ratio
but directly related to aldosterone. Relations of LTL to renin-angiotensin-aldosterone
system biomarkers and to the renin-to-aldosterone ratio were
stronger in those with hypertension. Participants with hypertension
who were in the top tertile of the renin-to-aldosterone ratio
had an LTL that was 182 base pairs shorter relative to those
in the lowest tertile. These observations raise the hypothesis
that the renin-to-aldosterone ratio may be a biomarker of the
cumulative exposure to oxidative stress and inflammation, especially
in people with high blood pressure. Additional investigations
are warranted to confirm our observations. See p
1138.
|
Rural Interhospital Transfer of ST-Elevation Myocardial Infarction Patients for Percutaneous Coronary Revascularization: The Stat Heart Program
|
|---|
When a door-to-balloon time of
90 minutes can be achieved, primary
percutaneous coronary intervention (PPCI) is preferred over
intravenous fibrinolytic therapy as a reperfusion strategy for
ST-elevation myocardial infarction (STEMI). Unfortunately, only
25% of US hospitals have PPCI-capable facilities. Interhospital
transfer of STEMI patients from non–PCI-capable (STEMI-referral)
to PPCI-capable (STEMI-accepting) facilities has been suggested
as a strategy (transfer PCI) to enhance the generalizability
of PPCI. In rural US communities, unexpected impediments to
interhospital transport may contribute to reperfusion delays,
necessitating alternative "backup" treatment strategies (ie,
full-dose intravenous fibrinolysis). We established a regional
transfer PCI STEMI consortium (Stat Heart) in rural central
Illinois consisting of 6 STEMI-referral hospitals, which were
within 28 to 88 miles of our 2 STEMI-accepting facilities. We
used a 4-step, guideline-based STEMI protocol that empowered
the STEMI-referral emergency department physician to initiate
treatment and to expedite interhospital transfer for primary
or rescue PCI, if needed, after fibrinolysis. Among the first
230 Stat Heart patients, the median door-to-balloon time among
those receiving PPCI was 117 minutes. Unexpected interhospital
transport delays (usually resulting from inclement weather)
required the use of intravenous fibrinolysis in 19 patients
(8.3%; 9 requiring rescue PCI) with achievement of a median
door-to-needle time of 27 minutes. In Stat Heart, we observed
that universal reperfusion strategies for all STEMI patients
at all times are not always feasible (ie, "one size does not
fit all") and demonstrated that interhospital transfer for timely
primary and rescue PCI can be achieved safely in rural US communities
when incorporated within coordinated healthcare networks. See
p
1145.
|
Activatable Magnetic Resonance Imaging Agent Reports Myeloperoxidase Activity in Healing Infarcts and Noninvasively Detects the Antiinflammatory Effects of Atorvastatin on Ischemia-Reperfusion Injury
|
|---|
Myeloperoxidase is a signature enzyme of inflammatory cells
(neutrophils, monocytes, and macrophages) and can serve as a
surrogate marker for the extent of tissue inflammation in myocardial
infarction. Here, we present a novel approach to noninvasive
imaging of myeloperoxidase activity locally in the myocardium.
Using an "activatable" paramagnetic myeloperoxidase substrate
with magnetic resonance imaging, the approach could be used
to identify patients at risk for adverse remodeling after myocardial
infarction and may guide novel therapeutic strategies to prevent
heart failure. Because neutrophils and/or monocytes/macrophages
play key roles in inflammation and tissue repair, the imaging
agent also could be used to assess atherosclerosis, myocarditis,
or transplant rejection. See p
1153.
|
Endothelial Cilia Are Fluid Shear Sensors That Regulate Calcium Signaling and Nitric Oxide Production Through Polycystin-1
|
|---|
Patients with polycystic kidney disease exhibit an enhanced
propensity for hypertension. Studies have revealed that mutations
which result in abnormal ciliary proteins such as polaris and
polycystin-1 lead to the development of polycystic kidney disease
in mice. These findings suggest an association between ciliary
function and the development of hypertension. Kidney cells that
exhibit abnormal ciliary proteins fail to sense fluid shear
stress. Within endothelial cells, this hemodynamic fluid flow
can regulate blood pressure by altering calcium signaling and
nitric oxide production. Here, we show that embryonic mouse
aortic endothelial cells possess primary cilia, specialized
organelles that sense and convert fluid shear stresses into
changes in intracellular calcium and nitric oxide production.
Polaris and polycystin-1 were shown to mediate these effects.
In addition, prolonged activation of cilia by high shear stress
would induce proteolytic cleavage of polycystin-1, thereby desensitizing
endothelial cells to these mechanical stimuli. Overall, these
findings suggest that dysfunction of endothelial cilia could
interfere with normal shear-induced regulatory mechanisms that
may contribute to abnormal vascular control in polycystic kidney
disease patients and hence may lead to hypertension. Furthermore,
hypertensive patients who exhibit ciliary desensitization resulting
from continuous exposure to high levels of fluid shear might
be unable to respond normally to small but damaging daily fluctuations
in blood pressure. This might increase the likelihood of localized
blood vessel injury, aneurysm, hemorrhage, edema, atherosclerosis,
vascular ectasia, dissection, and other abnormalities. Greater
insight into this novel mechanism of endothelial flow sensing
by cilia may lead to advanced understanding of focal cardiovascular
diseases and development of novel forms of "ciliary therapy"
in the future. See p
1161.
|
Cardioprotection by N-Acetylglucosamine Linkage to Cellular Proteins
|
|---|
Despite decades of intensive effort, our understanding of the
mechanisms of myocardial cell injury and survival remains limited.
In this report, we take a unique approach to the problem and
illustrate a potentially new paradigm of ischemic cardiobiology.
The present study identifies one of the first enzymatically
reversible posttranslational modifications, other than phosphorylation,
to figure prominently in myocardial ischemia/reperfusion injury
in vivo. Previous data suggest that the posttranslational modification
O-linked β-
N-acetylglucosamine (
O-GlcNAc) may act as an
intracellular metabolic or stress sensor, linking glucose metabolism
to cellular function. Considering this, we hypothesized that
augmentation of
O-GlcNAc levels represents an endogenously recruitable
mechanism of cardioprotection. From a mechanistic vantage point,
O-GlcNAc levels waned synchronously with events related to mitochondrial
permeability transition pore formation. Proteomic analysis identified
several potential targets of
O-GlcNAc modification, including
a putative mitochondrial permeability transition pore member,
voltage-dependent anion channel. Thus,
O-GlcNAc signaling represents
a unique endogenously recruitable mechanism of cardioprotection
in vivo that may involve direct modification of mitochondrial
proteins critical for survival (eg, voltage-dependent anion
channel). Identification of all of the potential targets of
O-GlcNAc modification in the heart, particularly in the human
myocardium, and the question of whether augmentation of
O-GlcNAc
levels during ischemic preconditioning is necessary for the
infarct-sparing effects of preconditioning will be the focus
of future studies. See p
1172.
|
Effect of the Italian Smoking Ban on Population Rates of Acute Coronary Events
|
|---|
The adverse health effects of environmental tobacco smoke are
well established; they include lung cancer and respiratory and
cardiovascular diseases. Coronary artery disease has been clearly
associated with exposure to passive smoking, and the physiopathological
mechanisms of this association are well understood. In several
countries around the world, laws banning smoking in public places
have been implemented to protect people’s health, but
the evidence of their beneficial health effects has remained
limited. The aim of this study was to evaluate the effect of
the national comprehensive smoking ban on population rates of
acute coronary events in Rome, the largest Italian city. Both
out-of-hospital cardiac deaths and hospitalizations were considered.
During the first year of implementation of the law, fewer coronary
events than in previous years were observed in subjects 35 to
64 years old (an 11.2% decrease) and in subjects 65 to 74 years
old (a 7.9% decrease). No evidence was found of a reduction
in acute coronary events in the population over 74 years of
age, possibly because their exposure levels were less influenced.
Subjects of low socioeconomic position had the greatest reduction
in acute coronary events after the smoking ban. These data strengthen
preliminary findings from the United States and Europe and show
that smoking bans are simple and effective interventions for
improving public health. Because coronary heart disease is the
leading cause of death, even a small proportional reduction
could have tremendous public health implications. See p
1183.
|
The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) Trial: First Randomized Placebo-Controlled Study of Myoblast Transplantation
|
|---|
The recognition that heart failure is caused largely by the
irreversible loss of a substantial number of cardiomyocytes
has led to the concept that implantation of contractile cells
in postinfarction myocardium could improve left ventricular
function. Preclinical studies showing that skeletal myoblasts
met this objective have paved the way for early-phase clinical
trials, which were not able to establish the efficacy of the
procedure. The Myoblast Autologous Grafting in Ischemic Cardiomyopathy
(MAGIC) trial is the first to address this issue. Using the
rigorous standards of randomized, controlled, double-blind studies,
it enrolled 97 patients with severe left ventricular dysfunction
scheduled for bypass surgery and allocated them to receive in-scar
injections of a placebo medium or autologous myoblasts. After
6 months, neither global nor regional function improved in treated
patients beyond that seen in the placebo group. However, the
highest dose of myoblasts was associated with a significant
antiremodeling effect. Recordings of internal defibrillators
showed that the 6-month incidence of ventricular arrhythmias
did not differ significantly among groups despite a trend toward
a greater number of early postoperative events after myoblast
grafting. These results lead to 3 main conclusions: (1) Implanted
myoblasts may exert some therapeutic benefits, possibly through
paracrine signaling; (2) it remains uncertain whether these
effects have an impact on patient outcomes; and (3) to move
the field from proof of concept to active therapy requires the
optimization of the best cells matching the target clinical
setting (acute infarction or heart failure), their method of
delivery, and strategies enabling the enhancement of graft survival
and its functional integration. See p
1189.
|
Aortic Valvuloplasty in Pediatric Patients Substantially Postpones the Need for Aortic Valve Surgery: A Single-Center Experience of 188 Patients After up to 17.5 Years of Follow-Up
|
|---|
Aortic valvuloplasty (AoVP) of congenital aortic valve stenosis
is an established procedure regarded as a valid alternative
for surgical management. However, its long-term efficacy in
preventing or postponing aortic valve surgery remains uncertain
for the individual patient. Therefore, the aim of this study
was to examine the long-term results of AoVP in pediatric patients
and its efficacy in preventing or postponing aortic valve surgery.
This study reviewed up to 17.5 years of follow-up data of all
188 patients who received AoVP at the Deutsches Herzzentrum
München in Munich, Germany. The patients were divided into
those <1 month of age (group <1 month; n=68) and those
1 month of age (group
1 month; n=120) at the time of AoVP. After
the first and second AoVP, moderate and severe aortic regurgitation
developed in 29% and 14%, respectively, of the patients in group
<1 month and in 19% and 29%, respectively, of the patients
in group
1 month. Survival after 10 years free from aortic valve
surgery was 59% (95% confidence interval, 45 to 73) in group
<1 month and 70% (95% confidence interval, 59 to 81) in group
1 month. This study shows that the long-term results of AoVP
of congenital aortic valve stenosis in pediatric patients and
its efficacy in preventing or postponing aortic valve surgery
are very good. About two thirds of the patients are free from
aortic valve surgery 10 years after AoVP. See p
1201.
|
A Quantitative Trait Locus (LSq-1) on Mouse Chromosome 7 Is Linked to the Absence of Tissue Loss After Surgical Hindlimb Ischemia
|
|---|
When occlusions are present in the large arteries to the lower
extremity, the result is the most common form of peripheral
arterial disease (PAD). PAD, a major healthcare problem, has
2 major clinical presentations: intermittent claudication and
critical limb ischemia. Despite the significant overlap in risk
factors leading to the development of both clinical presentations,
patients with critical limb ischemia frequently have ongoing
or imminent tissue loss and thus have a higher rate of amputation
and mortality. Patients with intermittent claudication rarely
develop tissue loss. Therefore, we hypothesized that underlying
genetic differences may influence the clinical outcomes in PAD.
In the present study, we used a preclinical model of PAD and
identified a chromosomal region in mice, termed LSq-1, that,
when present, was associated with absence of tissue loss. This
is the first identification of such a quantitative trait locus
in PAD. This study can serve as a valuable foundation for future
studies to identify specific gene(s) involved in PAD in patients.
We describe how these results can be used to rapidly identify
human orthologs of the mouse genes. Such information has the
potential to advance our understanding of the pathophysiology
of PAD, as well as new treatment options. See p
1207.
Related Articles:
-
Aortic Valvuloplasty in Pediatric Patients Substantially Postpones the Need for Aortic Valve Surgery: A Single-Center Experience of 188 Patients After up to 17.5 Years of Follow-Up
- Sohrab Fratz, Hans Peter Gildein, Gunter Balling, Walter Sebening, Thomas Genz, Andreas Eicken, and John Hess
Circulation 2008 117: 1201-1206.
[Abstract]
[Full Text]
-
Endothelial Cilia Are Fluid Shear Sensors That Regulate Calcium Signaling and Nitric Oxide Production Through Polycystin-1
- Surya M. Nauli, Yoshifumi Kawanabe, John J. Kaminski, William J. Pearce, Donald E. Ingber, and Jing Zhou
Circulation 2008 117: 1161-1171.
[Abstract]
[Full Text]
-
Rural Interhospital Transfer of ST-Elevation Myocardial Infarction Patients for Percutaneous Coronary Revascularization: The Stat Heart Program
- Frank V. Aguirre, Joji J. Varghese, Michael P. Kelley, Wilfred Lam, Charles L. Lucore, John B. Gill, Lisa Page, Leah Turner, Conrad Davis, and Frank L. Mikell
Circulation 2008 117: 1145-1152.
[Abstract]
[Full Text]
-
Effect of the Italian Smoking Ban on Population Rates of Acute Coronary Events
- Giulia Cesaroni, Francesco Forastiere, Nera Agabiti, Pasquale Valente, Piergiorgio Zuccaro, and Carlo A. Perucci
Circulation 2008 117: 1183-1188.
[Abstract]
[Full Text]
-
Cardioprotection by N-Acetylglucosamine Linkage to Cellular Proteins
- Steven P. Jones, Natasha E. Zachara, Gladys A. Ngoh, Bradford G. Hill, Yasushi Teshima, Aruni Bhatnagar, Gerald W. Hart, and Eduardo Marbán
Circulation 2008 117: 1172-1182.
[Abstract]
[Full Text]
-
Association of Leukocyte Telomere Length With Circulating Biomarkers of the Renin-Angiotensin-Aldosterone System: The Framingham Heart Study
- Ramachandran S. Vasan, Serkalem Demissie, Masayuki Kimura, L. Adrienne Cupples, Nader Rifai, Charles White, Thomas J. Wang, Jeffrey P. Gardner, Xiaogian Cao, Emelia J. Benjamin, Daniel Levy, and Abraham Aviv
Circulation 2008 117: 1138-1144.
[Abstract]
[Full Text]
-
Dietary Fish and -3 Fatty Acid Consumption and Heart Rate Variability in US Adults
- Dariush Mozaffarian, Phyllis K. Stein, Ronald J. Prineas, and David S. Siscovick
Circulation 2008 117: 1130-1137.
[Abstract]
[Full Text]
-
The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) Trial: First Randomized Placebo-Controlled Study of Myoblast Transplantation
- Philippe Menasché, Ottavio Alfieri, Stefan Janssens, William McKenna, Hermann Reichenspurner, Ludovic Trinquart, Jean-Thomas Vilquin, Jean-Pierre Marolleau, Barbara Seymour, Jérôme Larghero, Stephen Lake, Gilles Chatellier, Scott Solomon, Michel Desnos, and Albert A. Hagège
Circulation 2008 117: 1189-1200.
[Abstract]
[Full Text]
-
A Quantitative Trait Locus (LSq-1) on Mouse Chromosome 7 Is Linked to the Absence of Tissue Loss After Surgical Hindlimb Ischemia
- Ayotunde O. Dokun, Sehoon Keum, Surovi Hazarika, Yongjun Li, Gregory M. Lamonte, Ferrin Wheeler, Douglas A. Marchuk, and Brian H. Annex
Circulation 2008 117: 1207-1215.
[Abstract]
[Full Text]
-
Activatable Magnetic Resonance Imaging Agent Reports Myeloperoxidase Activity in Healing Infarcts and Noninvasively Detects the Antiinflammatory Effects of Atorvastatin on Ischemia-Reperfusion Injury
- Matthias Nahrendorf, David Sosnovik, John W. Chen, Peter Panizzi, Jose-Luiz Figueiredo, Elena Aikawa, Peter Libby, Filip K. Swirski, and Ralph Weissleder
Circulation 2008 117: 1153-1160.
[Abstract]
[Full Text]
Top
Dietary Fish and {omega}-3...
Association of Leukocyte...