ecent research has shown that inflammation plays a key role in coronary artery disease (CAD) and other manifestations of atherosclerosis. Immune cells dominate early atherosclerotic lesions, their effector molecules accelerate progression of the lesions, and activation of inflammation can elicit acute coronary syndromes. This review highlights the role of inflammation in the pathogenesis of atherosclerotic CAD. It will recount the evidence that atherosclerosis, the main cause of CAD, is an inflammatory disease in which immune mechanisms interact with metabolic risk factors to initiate, propagate, and activate lesions in the arterial tree. A decade ago, the treatment of hypercholesterolemia and hypertension was expected to eliminate CAD by the end of the 20th century. Lately, however, that optimistic prediction has needed revision. Cardiovascular diseases are expected to be the main cause of death globally within the next 15 years owing to a rapidly increasing prevalence in developing countries and eastern Europe and the rising incidence of obesity and diabetes in the Western world. 1 Cardiovascular diseases cause 38 percent of all deaths in North America and are the most common cause of death in European men under 65 years of age and the second most common cause in women. These facts force us to revisit cardiovascular disease and consider new strategies for prediction, prevention, and treatment.

/pdf/inflammation-atherosclerosis-and-coronary-artery-disease-23ryhxhuc2.pdf

Inflammation, Atherosclerosis, and Coronary Artery Disease

99mTc
: technetium-99m
201TI
: thallium 201
ABCB1
: ATP-binding cassette sub-family B member 1
ABI
: ankle-brachial index
ACC
: American College of Cardiology
ACCF
: American College of Cardiology Foundation
ACCOMPLISH
: Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension
ACE
: angiotensin converting enzyme
ACIP
: Asymptomatic Cardiac Ischaemia Pilot
ACS
: acute coronary syndrome
ADA
: American Diabetes Association
ADP
: adenosine diphosphate
AHA
: American Heart Association
ARB
: angiotensin II receptor antagonist
ART
: Arterial Revascularization Trial
ASCOT
: Anglo-Scandinavian Cardiac Outcomes Trial
ASSERT
: Asymptomatic atrial fibrillation and Stroke Evaluation in pacemaker patients and the atrial fibrillation Reduction atrial pacing Trial
AV
: atrioventricular
BARI 2D
: Bypass Angioplasty Revascularization Investigation 2 Diabetes
BEAUTIFUL
: Morbidity-Mortality Evaluation of the If Inhibitor Ivabradine in Patients With Coronary Artery Disease and Left Ventricular Dysfunction
BIMA
: bilateral internal mammary artery
BMI
: body mass index
BMS
: bare metal stent
BNP
: B-type natriuretic peptide
BP
: blood pressure
b.p.m.
: beats per minute
CABG
: coronary artery bypass graft
CAD
: coronary artery disease
CAPRIE
: Clopidogrel vs. Aspirin in Patients at Risk of Ischaemic Events
CASS
: Coronary Artery Surgery Study
CCB
: calcium channel blocker
CCS
: Canadian Cardiovascular Society
CFR
: coronary flow reserve
CHARISMA
: Clopidogrel for High Atherothrombotic Risk and Ischaemic Stabilization, Management and Avoidance
CI
: confidence interval
CKD
: chronic kidney disease
CKD-EPI
: Chronic Kidney Disease Epidemiology Collaboration
CMR
: cardiac magnetic resonance
CORONARY
: The CABG Off or On Pump Revascularization Study
COURAGE
: Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation
COX-1
: cyclooxygenase-1
COX-2
: cyclooxygenase-2
CPG
: Committee for Practice Guidelines
CT
: computed tomography
CTA
: computed tomography angiography
CV
: cardiovascular
CVD
: cardiovascular disease
CXR
: chest X-ray
CYP2C19*2
: cytochrome P450 2C19
CYP3A
: cytochrome P3A
CYP3A4
: cytochrome P450 3A4
CYP450
: cytochrome P450
DANAMI
: Danish trial in Acute Myocardial Infarction
DAPT
: dual antiplatelet therapy
DBP
: diastolic blood pressure
DECOPI
: Desobstruction Coronaire en Post-Infarctus
DES
: drug-eluting stents
DHP
: dihydropyridine
DSE
: dobutamine stress echocardiography
EACTS
: European Association for Cardiothoracic Surgery
EECP
: enhanced external counterpulsation
EMA
: European Medicines Agency
EASD
: European Association for the Study of Diabetes
ECG
: electrocardiogram
Echo
: echocardiogram
ED
: erectile dysfunction
EF
: ejection fraction
ESC
: European Society of Cardiology
EXCEL
: Evaluation of XIENCE PRIME or XIENCE V vs. Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization
FAME
: Fractional Flow Reserve vs. Angiography for Multivessel Evaluation
FDA
: Food & Drug Administration (USA)
FFR
: fractional flow reserve
FREEDOM
: Design of the Future Revascularization Evaluation in patients with Diabetes mellitus: Optimal management of Multivessel disease
GFR
: glomerular filtration rate
HbA1c
: glycated haemoglobin
HDL
: high density lipoprotein
HDL-C
: high density lipoprotein cholesterol
HR
: hazard ratio
HRT
: hormone replacement therapy
hs-CRP
: high-sensitivity C-reactive protein
HU
: Hounsfield units
ICA
: invasive coronary angiography
IMA
: internal mammary artery
IONA
: Impact Of Nicorandil in Angina
ISCHEMIA
: International Study of Comparative Health Effectiveness with Medical and Invasive Approaches
IVUS
: intravascular ultrasound
JSAP
: Japanese Stable Angina Pectoris
KATP
: ATP-sensitive potassium channels
LAD
: left anterior descending
LBBB
: left bundle branch block
LIMA
: Left internal mammary artery
LDL
: low density lipoprotein
LDL-C
: low density lipoprotein cholesterol
LM
: left main
LMS
: left main stem
LV
: left ventricular
LVEF
: left ventricular ejection fraction
LVH
: left ventricular hypertrophy
MACE
: major adverse cardiac events
MASS
: Medical, Angioplasty, or Surgery Study
MDRD
: Modification of Diet in Renal Disease
MERLIN
: Metabolic Efficiency with Ranolazine for Less Ischaemia in Non-ST-Elevation Acute Coronary Syndromes
MERLIN-TIMI 36
: Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes: Thrombolysis In Myocardial Infarction
MET
: metabolic equivalents
MI
: myocardial infarction
MICRO-HOPE
: Microalbuminuria, cardiovascular and renal sub-study of the Heart Outcomes Prevention Evaluation study
MPI
: myocardial perfusion imaging
MRI
: magnetic resonance imaging
NO
: nitric oxide
NSAIDs
: non-steroidal anti-inflammatory drugs
NSTE-ACS
: non-ST-elevation acute coronary syndrome
NYHA
: New York Heart Association
OAT
: Occluded Artery Trial
OCT
: optical coherence tomography
OMT
: optimal medical therapy
PAR-1
: protease activated receptor type 1
PCI
: percutaneous coronary intervention
PDE5
: phosphodiesterase type 5
PES
: paclitaxel-eluting stents
PET
: positron emission tomography
PRECOMBAT
: Premier of Randomized Comparison of Bypass Surgery vs. Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease
PTP
: pre-test probability
PUFA
: polyunsaturated fatty acid
PVD
: peripheral vascular disease
QoL
: quality of life
RBBB
: right bundle branch block
REACH
: Reduction of Atherothrombosis for Continued Health
RITA-2
: Second Randomized Intervention Treatment of Angina
ROOBY
: Veterans Affairs Randomized On/Off Bypass
SAPT
: single antiplatelet therapy
SBP
: systolic blood pressure
SCAD
: stable coronary artery disease
SCORE
: Systematic Coronary Risk Evaluation
SCS
: spinal cord stimulation
SES
: sirolimus-eluting stents
SIMA
: single internal mammary artery
SPECT
: single photon emission computed tomography
STICH
: Surgical Treatment for Ischaemic Heart Failure
SWISSI II
: Swiss Interventional Study on Silent Ischaemia Type II
SYNTAX
: SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery
TC
: total cholesterol
TENS
: transcutaneous electrical neural stimulation
TERISA
: Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina
TIME
: Trial of Invasive vs. Medical therapy
TIMI
: Thrombolysis In Myocardial Infarction
TMR
: transmyocardial laser revascularization
TOAT
: The Open Artery Trial
WOEST
: What is the Optimal antiplatElet and anticoagulant therapy in patients with oral anticoagulation and coronary StenTing

Guidelines summarize and evaluate all evidence available, at the time of the writing process, on a particular issue with the aim of assisting physicians in selecting the best management strategies for an individual patient with a given condition, taking into account the impact on outcome, as well …

/pdf/2013-esc-guidelines-on-the-management-of-stable-coronary-2178xukyyy.pdf

2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology.

There has been much effort recently to probe the long-recognized relationship between the pathological processes of infection, inflammation and cancer. For example, epidemiological studies have shown that approximately 15% of human deaths from cancer are associated with chronic viral or bacterial infections. This Review focuses on the molecular mechanisms that connect infection, inflammation and cancer, and it puts forward the hypothesis that activation of nuclear factor-kappaB (NF-kappaB) by the classical, IKK-beta (inhibitor-of-NF-kappaB kinase-beta)-dependent pathway is a crucial mediator of inflammation-induced tumour growth and progression, as well as an important modulator of tumour surveillance and rejection.

NF-kappaB: linking inflammation and immunity to cancer development and progression.

https://www.just.edu.jo/DIC/ClinicGuidlines/Management%20of%20hip%20and%20knee%20Osteoarthritis.pdf

OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines

background Selective cyclooxygenase-2 (COX-2) inhibitors have come under scrutiny because of reports suggesting an increased cardiovascular risk associated with their use. Experimental research suggesting that these drugs may contribute to a prothrombotic state provides support for this concern. methods We reviewed all potentially serious cardiovascular events among 2035 patients with a history of colorectal neoplasia who were enrolled in a trial comparing two doses of celecoxib (200 mg or 400 mg twice daily) with placebo for the prevention of colorectal adenomas. All deaths were categorized as cardiovascular or noncardiovascular, and nonfatal cardiovascular events were categorized in a blinded fashion according to a prespecified scheme. results

https://www.nejm.org/doi/pdf/10.1056/NEJMoa050405

Cardiovascular Risk Associated With Celecoxib in a Clinical Trial for Colorectal Adenoma Prevention

background Selective inhibition of cyclooxygenase-2 (COX-2) may be associated with an increased risk of thrombotic events, but only limited long-term data have been available for analysis. We report on the cardiovascular outcomes associated with the use of the selective COX-2 inhibitor rofecoxib in a long-term, multicenter, randomized, placebo-controlled, double-blind trial designed to determine the effect of three years of treatment with rofecoxib on the risk of recurrent neoplastic polyps of the large bowel in patients with a history of colorectal adenomas. methods A total of 2586 patients with a history of colorectal adenomas underwent randomization: 1287 were assigned to receive 25 mg of rofecoxib daily, and 1299 to receive placebo. All investigator-reported serious adverse events that represented potential thrombotic cardiovascular events were adjudicated in a blinded fashion by an external committee. results A total of 46 patients in the rofecoxib group had a confirmed thrombotic event during 3059 patient-years of follow-up (1.50 events per 100 patient-years), as compared with 26 patients in the placebo group during 3327 patient-years of follow-up (0.78 event per 100 patient-years); the corresponding relative risk was 1.92 (95 percent confidence interval, 1.19 to 3.11; P=0.008). The increased relative risk became apparent after 18 months of treatment; during the first 18 months, the event rates were similar in the two groups. The results primarily reflect a greater number of myocardial infarctions and ischemic cerebrovascular events in the rofecoxib group. There was earlier separation (at approximately five months) between groups in the incidence of nonadjudicated investigator-reported congestive heart failure, pulmonary edema, or cardiac failure (hazard ratio for the comparison of the rofecoxib group with the placebo group, 4.61; 95 percent confidence interval, 1.50 to 18.83). Overall and cardiovascular mortality was similar in the two groups. conclusions Among patients with a history of colorectal adenomas, the use of rofecoxib was associated with an increased cardiovascular risk.

/pdf/cardiovascular-events-associated-with-rofecoxib-in-a-3mevkkcm5s.pdf

Bettina Oxenius

Papers

Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial

Peptic Ulcer and Bleeding Events Associated With Rofecoxib in a 3-Year Colorectal Adenoma Chemoprevention Trial