Reviews & Analysis

No worldwide consensus exists regarding the best way to manage patients with asymptomatic carotid artery stenosis (CAS). In this thought-provoking article, Professor A. Ross Naylor presents his argument against the use of a 'one size fits all' approach involving the costly widespread use of surgical or percutaneous interventions, a high percentage of which are unnecessary. Instead, he recommends that the medical community should increase efforts to identify those at particularly high risk for stroke, who are the only patients likely to really benefit from these interventions

In the second part of their Review on restenosis after PCI, Jukema and colleagues focus on the technological advances that have fueled revolutionary changes for optimizing outcomes of coronary stenting and the prevention and treatment of in-stent restenosis.

Indisputable evidence that coronary artery calcium score predicts cardiovascular events in asymptomatic individuals exists, even in patients with low to normal LDL cholesterol and elevated C-reactive protein. Conversely, not all studies demonstrate a predictive role for biochemical markers.

Antithrombotic therapy during percutaneous coronary intervention for ST-segment elevation myocardial infarction has evolved substantially over the past 15 years. With the results of the ATOLL trial, enoxaparin should now be considered a therapeutic alternative to unfractionated heparin in the treatment of such patients. Comparative studies of enoxaparin and bivalirudin, using standardized bleeding definitions, are warranted.

Ectopic foci in pulmonary veins can trigger episodes of atrial fibrillation, but how these foci arise remains unclear. Dr Mark Shen and colleagues review the role of the autonomous nervous system in the induction and maintenance of atrial arrhythmias, and discuss neural modulation as a treatment strategy for patients with atrial fibrillation.

The true prognostic implication of carotid intima–media thickness (CIMT) remains a major question for clinicians and the preventive cardiology community. The merits of using CIMT for assessing asymptomatic individuals at risk for developing cardiovascular disease are discussed, together with the potential issues arising from an analysis of CIMT measurement in the Framingham Offspring Study cohort.

Metabolomics is emerging as a powerful tool for the investigation of the molecular mechanisms of cardiovascular disease, including atherosclerosis, ischemia, myocardial infarction, and heart failure. In this Review, the authors discuss advances in the use of NMR spectroscopy and mass spectrometry, particularly in field of lipidomics, and in the search for novel biomarkers of cardiac disease.

Antiplatelet agents effectively reduce the incidence of ischemic events associated with plaque rupture but can cause adverse effects, most notably hemorrhage. Drs Kalyanasundaram and Lincoff address key adverse effects that are associated with antiplatelet agents and discuss potential interactions between these drugs and other medications.

Restenosis of atherosclerotic lesions after initial treatment with angioplasty and stenting occurs in around 15% of patients. Although this condition is complex and the causative mechanisms have not yet been fully identified, they are thought to include inflammation, proliferation, and matrix remodeling with some patients being more 'predisposed' to developing restenosis than others. In this Review, Jukema and colleagues evaluate the available evidence on the pathophysiology of restenosis and provide an overview of the various risk factors for this disease.

The appropriateness of percutaneous coronary intervention in the US has been examined from a large database of more than 500,000 procedures. The findings are surprising and, given their potential to be applied to quality-improvement initiatives, peer-review, and possibly reimbursement decisions, the proper interpretation of these results is essential.

Drs. Chaitman and Laddu review the various approved and experimental pharmacological approaches to treating angina in the context of data from clinical trials, and discuss ongoing and future studies. They also compare the merits of optimal medical therapy with prompt or delayed revascularization by percutaneous coronary intervention or CABG surgery as antianginal strategies.

The field of biological cardiac pacing, which aims to improve upon, supplement and, eventually, to replace electronic pacing has come a long way since its inception more than a decade ago. Broadly, research has been focused on gene and cell therapy. In this Review, Rosen and colleagues highlight milestones achieved through the construction of a 'roadmap' in biological pacing, and discuss the barriers that remain to be overcome before clinical trials of biological pacing can be begun.

The final report from the HORIZONS-AMI trial in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction shows that the early benefits of bivalirudin and paclitaxel-eluting stents are sustained at 3 years. Bivalirudin, thrombus aspiration, and drug-eluting stents might be the new standard of care for primary percutaneous coronary intervention.

Drs Arnold, Cohen, and Magnuson review the published cost-effectiveness analyses of oral antiplatelet therapies for various clinical settings. This information is of increasing importance, given the enormous health-care expenditure worldwide, the advent of novel oral antiplatelet drugs, and the availability in many countries of generic clopidogrel, which is cheaper than the branded version and likely to improve its cost-effectiveness compared with alternative medications.

Evidence is increasing that genetic variation between patients underlies the considerable variability in their response to antiplatelet agents, and, therefore, in clinical outcomes. Drs Ahmad, Voora, and Becker review the genetic loci that seem to have a role in determining platelet response; genes that are involved in the absorption, metabolic activation, and biological activity of aspirin and clopidogrel. Finally, they discuss, in the context of ongoing clinical trials, the merits and potential dangers of using commercial genetic testing and pharmacogenetics to personalize antiplatelet therapy to individual patients.

White-coat hypertension is characterized by an elevation in clinic blood pressure but normal home or ambulatory blood-pressure values, whereas patients with masked hypertension have normal clinic blood pressure and elevated ambulatory or home blood-pressure. In this article, Prof. Mancia and colleagues assess prevalence, diagnosis, and clinical management of white-coat and masked hypertension.

According to a meta-analysis of five clinical trials, high-dose statin therapy is associated with increased risk of new-onset diabetes mellitus. When treating patients with excessive levels of non-HDL cholesterols despite moderate-dose statin therapy, should we prescribe a strategy known to be efficacious, but associated with safety concerns, or should we prescribe combination therapy that has no proven effects on outcomes?

Patients with atrial fibrillation are at substantial risk of thromboembolism and acute ischemic stroke. Professor Gregory Lip gives his perspective on the role of using the antiplatelet agent aspirin for stroke prevention in these patients, compared with warfarin and novel anticoagulant drugs, supported by data from randomized, clinical trials and guideline recommendations.

This Review outlines the main ethical and legal issues surrounding informed consent for the insertion, removal, and deactivation of implantable cardioverter-defibrillators (ICDs). The authors also provide an overview of current guidelines for communication with and involvement of patients and next of kin throughout the decision-making process.

Pulmonary arterial hypertension (PAH) is a rare, but devastating, disease characterized by progressive obliteration of the pulmonary microvasculature. Over the past decade, an increasing number of therapies targeting the prostacyclin, endothelin, and nitric oxide pathways have been shown to improve the symptoms of PAH and even slow disease progression. O'Callaghan and colleagues review the pharmacological agents currently available for the treatment of PAH and discuss potential novel therapeutic targets in this disease.