Intraperitoneal bilirubin administration decreases infarct area in a rat coronary

ischemia/reperfusion model.

Ben-Amotz R1, Bonagura J1, Velayutham M2, Hamlin R1, Burns P3, Adin C1.

1
Department of Veterinary Clinical Sciences, The Ohio State University
Columbus, OH, USA.

2
Department of Anesthesiology, Center for Biomedical EPR Spectroscopy and
Imaging, Davis Heart and Lung Research Institute, The Ohio State University
Columbus, OH, USA.

3
Sciences Cliniques, Universit de Montral Montral, QC, Canada.

Abstract

Bilirubin was previously considered a toxin byproduct of heme catabolism. However, a

mounting body of evidence suggests that at physiological doses, bilirubin is a powerful
antioxidant and anti-atherosclerotic agent. Recent clinical studies have shown that human beings
with genetically-induced hyperbilirubinemia (Gilbert Syndrome) are protected against coronary
heart disease. The purpose of this study was to investigate whether administration of exogenous
bilirubin to normal rats would convey similar protective effects in an experimental model of
coronary ischemia. We hypothesized that intraperitoneal bilirubin administration 1 h before
injury would decrease infarct area and preserve left ventricular (LV) systolic function when
compared to non-treated rats. Coronary ischemia was induced by temporary (30 min) ligation of
the left anterior descending coronary artery in control or bilirubin treated rats, followed by a 1-h
period of reperfusion. LV function was estimated by measurements of fractional shortening (FS)
and fractional area shortening using echocardiography. LV function decreased in both
experimental groups after ischemia and reperfusion, although in bilirubin-treated rats FS was less
depressed during the period of ischemia (18.8 vs. 25.8%, p = 0.034). Infarct size was
significantly reduced in the bilirubin treated group compared to the non-treated group (13.34 vs.
25.5%, p = 0.0067). Based on the results of this study, bilirubin supplementation appears to
provide significant decrease in infarct size although protective effects on LV function were noted
only during the period of ischemia. This result also suggests that lipid soluble antioxidant
bilirubin prevents the oxidation of cardiolipin and decreases the infarct size in the heart during
ischemia.

KEYWORDS: antioxidant, bilirubin, cardiac ischemia, fractional shortening,

infarct area, ischemia reperfusion injury, myocardial infarction
Terminalia arjuna in Chronic Stable Angina:
Systematic Review and Meta-Analysis.
Kaur N1, Shafiq N1, Negi H1, Pandey A1, Reddy S2, Kaur H3, Chadha N4, Malhotra S1.

1
Department of Pharmacology, Postgraduate Institute of Medical Education & Research,
Chandigarh 160012, India.

2
Department of Cardiology, Postgraduate Institute of Medical Education & Research,
Chandigarh 160012, India.

3
ICMR Advanced Centre for Evidence-Based Child Health, Advanced Paediatrics Centre,
Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India.

4
Dr. Tulsidas Library, Postgraduate Institute of Medical Education & Research,
Chandigarh 160012, India.

Abstract

Background. Terminalia arjuna is a popular Indian medicinal plant with its bark been used for
over centuries as cardiotonic. The bark has been found to contain several bioactive compounds
including saponins and flavonoids. A number of experimental and clinical studies have been
conducted to explore therapeutic potential of Terminalia arjuna in cardiovascular ailments
specially in patients of coronary heart disease. A number of narrative reviews have been done but
no systematic review has been conducted to date. Objective. To systematically review and
conduct a meta-analysis on the available literature evaluating the efficacy of Terminalia arjuna
in patients of chronic stable angina. Study selection. We included randomised, pseudo-
randomized and before-after comparative studies which compared Terminalia
arjuna/commercial preparation of Terminalia arjuna with current standard/ conventional
treatment regimens in patients with chronic stable angina. Findings. Studies were found to be of
poor methodological design. We found no significant difference in the Terminalia arjuna group
as compared to control arm in the outcomes for which we were able to pool data and undertake
meta-analysis. Conclusions. Currently, the evidence is insufficient to draw any definite
conclusions in favour of or against Terminalia arjuna in patients of chronic stable angina.
Further, well-controlled multicentric clinical trials need to be conducted in large number of
patients to explore the therapeutic potential of Terminalia arjuna if any.
Current Roles and Future Applications of Cardiac CT: Risk Stratification of Coronary
Artery Disease.

Yoon YE1, Lim TH2.

1
Department of Cardiology, Cardiovascular Center, Seoul National University
Bundang Hospital, Seongnam 463-707, Korea.

2
Department of Radiology and Research Institute of Radiology, University of
Ulsan College of Medicine, Asan Medical Center, Seoul 138-736, Korea.

Abstract

Cardiac computed tomography (CT) has emerged as a noninvasive modality for the assessment
of coronary artery disease (CAD), and has been rapidly integrated into clinical cares. CT has
changed the traditional risk stratification based on clinical risk to image-based identification of
patient risk. Cardiac CT, including coronary artery calcium score and coronary CT angiography,
can provide prognostic information and is expected to improve risk stratification of CAD.
Currently used conventional cardiac CT, provides accurate anatomic information but not
functional significance of CAD, and it may not be sufficient to guide treatments such as
revascularization. Recently, myocardial CT perfusion imaging, intracoronary luminal attenuation
gradient, and CT-derived computed fractional flow reserve were developed to combine
anatomical and functional data. Although at present, the diagnostic and prognostic value of these
novel technologies needs to be evaluated further, it is expected that all-in-one cardiac CT can
guide treatment and improve patient outcomes in the near future.

KEYWORDS:
Cardiac computed tomography, Prognosis, Risk stratification

Prevalence of unsuspected glucose intolerance in coronary artery disease (CAD)

patients: Importance of HbA1c.

Somani BL1, Arora MM2, Datta SK3, Negi R4, Gupta A5.

Abstract
BACKGROUND: The mortality and morbidity rates are two to fourfold higher among
Coronary Artery Disease (CAD) patients with type 2 diabetes mellitus (DM).
American Diabetes Association (ADA) and World Health Organization (WHO) define
different criteria for the diagnosis of glucose intolerance. This study compares the
available diagnostic criteria for DM in Indian men and their importance in CAD
patients.

METHODS: This cross-sectional study was done on 794 male volunteers; 483
individuals from general population and 311 patients undergoing angiography for
evaluation of CAD. Individuals with previous clinical history of diabetes mellitus
were excluded.

RESULTS: More than 90% of diabetics by ADA criteria could be diagnosed by

Fasting plasma glucose (FPG) and HbA1c criteria while FPG and pg2h plasma
glucose (WHO criteria) could detect only 74%. Impaired Fasting Glucose (IFG) or
Impaired Glucose Tolerance (IGT) was present in 36.7% of individuals diagnosed to
be diabetic based on HbA1c; more in CAD +ve group (53.8%) than in general
population (23.6%). ROC analysis suggests >121 mg/dl of FPG or >6.2% of HbA1c
as optimum cut-off for the diagnosis of DM. FPG and HbA1c criteria have higher
Relative Risk for presence of coronary artery occlusion and HOMA-IR.

CONCLUSION: Inclusion of HbA1c in the criteria for diagnosis of DM (ADA criteria)

can detect large number of cases with persistent hyperglycemia in the non-
diagnostic range of DM (IFG or IGT) among general population and CAD patients.
This has special relevance to epidemiological studies as the diagnosis of DM can be
made on single fasting blood sample.

KEYWORDS: American Diabetes Association (ADA) criteria, Coronary artery

disease (CAD), Diabetes mellitus (DM), HbA1c, World Health Organization (WHO)
criteria

Multifactor dimensionality reduction analysis of the correlation of chinese medicine

syndrome evolvement and cardiovascular events in patients with stable coronary
heart disease.

Jiao Y1, Li SW, Shang QH, Fu CG, Gao ZY, Xu H, Shi DZ, Chen KJ.

Abstract
OBJECTIVE: To analyze the correlation of Chinese medicine syndrome evolvement
and cardiovascular events in patients with stable coronary heart disease (CHD).

METHODS: This prospective cohort study investigated and collected the clinical
information of patients with stable CHD and observed the syndrome type at the
baseline and 6-month at follow-up, as well as the cardiovascular events during the
6-month and 12-month follow-up. The patients were divided into the event group
and the non-event group. The interaction and the impact of syndrome evolvement
on cardiovascular events were examined through multifactor dimensionality
reduction (MDR) analysis and the results were verified by Chi-square test.

RESULTS: Totally 1,333 of 1,503 stable CHD patients enrolled met the inclusion
criteria of MDR analysis. Among them, 959 (71.9%) cases were males and 374
(28.1%) cases were females. Thirty seven cases had cardiovascular events during 6
to 12 months after the study began. The results of the MDR analysis and
verification using Chi-square test showed that the development of cardiovascular
events was positively correlated with interaction between blood stasis and toxic
syndrome at the baseline, blood stasis at the baseline and qi deficiency at the 6-
month follow-up, toxic syndrome at the baseline and qi deficiency at the 6-month
follow-up, toxic syndrome at the base line and blood stasis at the 6-month follow-
up, qi deficiency and blood stasis at the 6-month follow-up (P <0.05 for all).

CONCLUSIONS: Blood stasis, toxic syndrome and qi deficiency are important

factors of stable CHD. There are positive correlation between cardiovascular events
and syndrome evolution from blood stasis to qi deficiency, from toxic syndrome to
qi deficiency and from toxic syndrome to blood stasis, indicating the pathogenesis
of toxin consuming qi, toxin leading to blood-stasis in stable CHD patients prone to
recurrent cardiovascular events.

Comparative evaluation of efficacy, safety and haemostatic parameters of

enoxaparin and fondaparinux in unstable coronary artery disease.

Shah S1, Khajuria V2, Tandon VR3, Gillani ZH4, Lal M5.

Abstract Aim: To compare the safety and efficacy of Enoxaparin (EX) and
Fondaparinux (FD) in patients with Unstable Coronary Artery Disease (UCAD).
Materials and Methods: A prospective, open label, randomized comparative study
was designed to study the comparative efficacy and safety of EX and FD in UCAD
patients. Recovery, recurrence, major and minor bleeding and biochemical
investigations were evaluated and compared among two arms. Results: The
baseline demographic characteristics were similar in both groups, with mean age of
56.05 and 56.05 years in EX and FD group respectively. Recovery was equal in two
arms. Recurrent MI or angina was seen numerically more in EX group, but it did not
statistically vary from that in the FD group. Incidence of haemorrhage was similar in
both groups at 9 days, but at 30 days, EX showed a higher incidence (p<0.05).
Deaths were prevented in both the treatment arms. Bleeding parameters such as
BT, CT and platelet count were not altered in both groups. Conclusion: FD appeared
to be better than EX in efficacy, as was indicated by a numerically more decrease in
recurrence of angina or MI. FD regimen group also had better safety profile, as there
was no incidence of haemorrhage at 30 days Therefore, we conclude that FD is an
attractive option than EX in UCAD patients.

KEYWORDS: Anticoagulants, Enoxaparin, Fondaparinux, Low molecular weight

heparin

Association of lower extremity arterial calcification with amputation and mortality in

patients with symptomatic peripheral artery disease.

Huang CL1, Wu IH2, Wu YW3, Hwang JJ4, Wang SS5, Chen WJ6, Lee WJ7, Yang WS8.

Author information

Abstract
OBJECTIVE: The clinical implication of the coronary artery calcium score (CS) is
well demonstrated. However, little is known about the association between lower
extremity arterial calcification and clinical outcomes.

METHODS AND RESULTS: Eighty-two patients with symptomatic peripheral artery

disease (age 61.012.4 years) were followed for 2111 months. CSs, ranging from
the common iliac artery bifurcation to the ankle area, were analyzed through
noncontrast multidetector computed tomography images retrospectively. The
primary endpoints of this study were amputation and mortality. Old age, diabetes,
hyperlipidemia, and end-stage renal disease were associated with higher CSs.
Patients with more advanced Fontaine stages also tended to have significantly
higher CSs (p=0.03). During the follow-up period (2111 months), 29 (35%)
patients underwent amputation, and 24 (29%) patients died. Among the patients
who underwent amputation, there were no significant differences in CSs between
the amputated legs and the non-amputated legs. In the Cox proportional hazard
model with CS divided into quartiles, patients with CS in the highest quartile had a
2.88-fold (95% confidence interval [CI] 1.18-12.72, p=0.03) and a 5.16-fold (95% CI
1.13-21.61, p=0.04) higher risk for amputation and all-cause mortality,
respectively, than those with CS in the lowest quartile. These predictive effects
remained after conventional risk factor adjustment.

CONCLUSION: Lower extremity arterial CSs are associated with disease severity
and outcomes, including amputation and all-cause mortality, in patients with
symptomatic peripheral artery disease. However, the independent predictive value
needs further investigation in large scale, prospective studies.

Percutaneous coronary intervention in treatment of multivessel coronary artery

disease in patients with non-ST-segment elevation acute coronary syndrome.

Gsior P1, Desperak P1, Gierlaszyska K2, Hawranek M2, Gierlotka M2, Gsior M2,
Poloski L2.

Abstract

Among patients with non-ST-elevated acute coronary syndromes (NSTE-ACS) the estimated
percentage of single vessel coronary artery disease (SV-CAD) observed during coronarography
is about 20-40%, while multivessel coronary artery disease (MV-CAD) is found in about 40-
60%. Further treatment in patients with both SV CAD and MV CAD is usually culprit vessel
percutaneous coronary intervention (CV-PCI). Nevertheless, in the group of patients with MV-
CAD there is still a problematic decision whether the non-infarct related arteries (non-IRA)
should be treated with PCI. According to the European Society of Cardiology (ESC) guidelines
on myocardial revascularization this decision should be based on the overall clinical and
angiographic status of the patient; simultaneously they suggest performing ad hoc CV-PCI. The
decision of performing intervention in the rest of the narrowed coronary arteries should be made
after consultation with the heart team or according to the protocols adopted in the specific clinic.
Furthermore, there is a question of whether the procedure should be performed immediately after
culprit vessel revascularization or it should be postponed until the patient is stabilized. Due to the
lack of specific recommendations we decided to perform an analysis of existing studies which
compared culprit versus multivessel revascularization in patients with MV-CAD and non-ST-
elevated acute coronary syndromes.

KEYWORDS:
multivessel coronary artery disease, non-ST-elevated acute coronary syndrome, percutaneous
coronary intervention

Pathogenesis of coronary artery disease: focus on genetic risk factors and

identification of genetic variants.

Sayols-Baixeras S, Llus-Ganella C, Lucas G, Elosua R.

Abstract

Coronary artery disease (CAD) is the leading cause of death and disability worldwide, and its
prevalence is expected to increase in the coming years. CAD events are caused by the interplay
of genetic and environmental factors, the effects of which are mainly mediated through
cardiovascular risk factors. The techniques used to study the genetic basis of these diseases have
evolved from linkage studies to candidate gene studies and genome-wide association studies.
Linkage studies have been able to identify genetic variants associated with monogenic diseases,
whereas genome-wide association studies have been more successful in determining genetic
variants associated with complex diseases. Currently, genome-wide association studies have
identified approximately 40 loci that explain 6% of the heritability of CAD. The application of
this knowledge to clinical practice is challenging, but can be achieved using various strategies,
such as genetic variants to identify new therapeutic targets, personal genetic information to
improve disease risk prediction, and pharmacogenomics. The main aim of this narrative review is
to provide a general overview of our current understanding of the genetics of coronary artery
disease and its potential clinical utility.

KEYWORDS:
coronary artery disease, genetic risk factors, genetic variants, pathogenesis

Depression treatment in patients with

coronary artery disease: a systematic review.
Ramamurthy G, Trejo E, Faraone SV.

Abstract

Objective: Depression has been linked to adverse coronary artery disease outcomes. Whether
depression treatment improves or worsens coronary artery disease prognosis is unclear. This 25-
year systematic review examines medical outcomes, and, secondarily, mood outcomes of
depression treatment among patients with coronary artery disease. Data Sources: We
systematically reviewed the past 25 years (January 1, 1986-December 31, 2011) of prospective
trials reporting on the medical outcomes of depression treatment among patients with established
coronary artery disease using keywords and MESH terms from OVID MEDLINE. Search 1
combined depression AND coronary artery disease AND antidepressants. Search 2 combined
depression AND coronary artery disease AND psychotherapy. Search 3 combined depression
AND revascularization AND antidepressants OR psychotherapy. Study Selection: English-
language longitudinal randomized controlled trials, with at least 50 depressed coronary artery
disease patients, reporting the impact of psychotherapy and/or antidepressants on cardiac and
mood outcomes were included. Data Extraction: Data extracted included author name, year
published, number of participants, enrollment criteria, depression definition/measures
(standardized interviews, rating scales), power analyses, description of control arms and
interventions (psychotherapy and/or medications), randomization, blinding, follow-up duration,
follow-up loss, depression scores, and medical outcomes Results: The review yielded 10 trials.
Antidepressant and/or psychotherapy did not significantly influence coronary artery disease
outcomes in the overall population, but most studies were underpowered. There was a trend
toward worse coronary artery disease outcomes after treatment with bupropion. Conclusions:
After an acute coronary syndrome, depression often spontaneously remitted without treatment.
Post-acute coronary syndrome persistence of depression predicted adverse coronary artery
disease outcomes. Antidepressant and/or psychotherapy, particularly as part of the Coronary
Psychosocial Evaluation Studies intervention, may improve prognosis in persistent depression
among post-acute coronary syndrome patients. Noradrenergic antidepressants should be
prescribed cautiously in patients with coronary artery disease.