Review Articles in 2008

The pharmaceutical development of a cardiovascular polypill presents several unique challenges. In this Review, Dr Guglietta and Dr Guerrero highlight important considerations regarding the selection of the type and number of components, the type of pharmaceutical formulation, and approval by regulatory agencies.

Secondary prevention of ischemic heart disease could have a huge impact on the global epidemic of cardiovascular disease. Here Ginés Sanz and Valentin Fuster consider the value of a 'polypill' for secondary prevention, examine the most efficacious combination of agents and explore whether widespread use could improve adherence and improve treatment affordability in low-income countries.

The pericardium, myocardium, coronary arteries and pulmonary arteries are the main cardiac targets for disease in people who are infected with HIV. Mpiko Ntsekhe and Bongani Mayosi discuss the cardiac manifestations of HIV in sub-Saharan Africa, where approximately 70% of the 34 million people worldwide with HIV and AIDS live.

Atrial fibrillation and heart failure share many common risk factors, and are often seen together in an individual patient. Each of these conditions alone can cause the development and worsening of the other. In this article, Morrison et al. discuss the clinical and pathological relationships between these two conditions, review current treatment strategies, and propose areas for future research that will help define the optimal therapeutic approach for patients with concurrent atrial fibrillation and heart failure.

Reduced adiponectin levels have been shown to correlate with increased risk of cardiovascular disease in obese individuals and in patients with diabetes and hyperglycemia. In this Review, Drs Goldstein, Scalia and Ma discuss the various signaling pathways that mediate adiponectin's protective effects in the vasculature and the myocardium.

Thirteen years after his seminal Review on flow-mediated endothelial mechanotransduction, Peter Davies reviews the complex spatiotemporal shear stress characteristics that can predict atherosclerosis susceptibility. He also examines endothelial flow-induced responses—collectively known as mechanotransduction—and the spatially decentralized mechanism of endothelial mechanotransduction.

Mills et al. explore the preclinical and clinical evidence and examine the potential pathways through which air pollution—an important and modifiable determinant of cardiovascular disease—mediates adverse cardiovascular effects. Understanding the mediators and mechanisms will enable the development of strategies to reduce the impact of air pollution on cardiovascular disease.

Aspirin can effectively prevent arterial thrombosis; however, its efficacy is limited as it inhibits the synthesis of only one platelet agonist (thromboxane A₂). Here Raju and colleagues review agents that target ADP-mediated platelet activation. They examine controversies and unresolved issues associated with clopidogrel—the optimum loading dose, duration of treatment and incomplete platelet inhibition—and the new ADP-receptor antagonists prasugrel, AZD6140 and cangrelor, and explore their potential relative to each other and to clopidogrel.

Vascular complications following cancer treatment are relatively common, particularly in patients with advanced stages of cancer. In this Review, Dr Daher and Dr Yeh describe the vascular complications of treatment with 5-fluorouracil, bevacizumab, and several new tyrosine kinase inhibitors, with special emphasis on thrombotic complications and hypertension.

Atrial fibrillation is characterized by structural remodeling of the atrial myocardium—a slow process that comprises morphological changes that affect atrial myocardial architecture and atrial ultrastructure. Here Corradi et al. examine the morphological changes that characterize the fibrillating atrial myocardium at histological and ultrastructural levels, and explore how the pathogenetic mechanisms involved in AF could lead to new treatments.

The existence of diabetic cardiomyopathy has been debated; however, substantial data now demonstrate that diabetes impairs ventricular function independent of other risk factors. Here Lebeche et al. examine the hypothesis that impaired calcium regulation and insulin signaling contribute to the detrimental effect of diabetes on cardiomyocyte function. How these two abnormalities interact to induce cardiac dysfunction is also investigated.

Although optimum treatment for patients with acute ST-segment elevation myocardial infarction has been established through randomized clinical trials, the majority of patients do not receive all the guideline-recommended therapies promptly. In this Review, Keith Fox and Kurt Huber present a European perspective on the disparities between the evidence base and clinical practice in the treatment of ST-segment elevation myocardial infarction and propose that an integrated network of care, aimed at minimizing delays between symptom onset and treatment, is essential to improving outcomes among these patients.

Patients with fulminant myocarditis present with acute-onset, severe heart failure and are often in cardiogenic shock. However, if patients are quickly diagnosed and given aggressive treatment, most will make a full recovery. Gupta et al. highlight the importance of early recognition of fulminant myocarditis and provide a comprehensive review of its epidemiology, pathophysiology, clinical presentation, methods of diagnosis, management, and prognosis.

Tohru Minamino and Issei Komuro examine the research on age-associated vascular pathophysiology at the cellular level, specifically telomere shortening, DNA damage and the replicative ability of cardiovascular cells, particularly stem cells or progenitor cells. They explore vascular senescence in the context of human progeroid syndromes and what the future holds for the treatment of age-associated vascular disease.

Despite the wealth of research into C-reactive protein (CRP), it remains unclear which patient populations would benefit from and should be targeted for high-sensitivity assay CRP testing. In this important Review, Musunuru et al. address the relevance of CRP in a variety of scenarios encountered in clinical practice—from primary prevention of cardiovascular disease, stroke and diabetes mellitus, to secondary prevention of cardiovascular disease.

How should trial-derived evidence be interpreted so that findings can be applied directly in patient care? By understanding study design and statistical methodology, the results of observational studies, prospective randomized trials, and registry studies can be reconciled. Here Brown and coworkers examine different study designs and their impact on the interpretation of data.

SERCA2a is one of the most promising targets for the treatment of heart failure. Kawase and Hajjar examine mounting evidence demonstrating the beneficial effects associated with SERCA2a overexpression, and provide a balanced discussion of the risks associated with SERCA2a as a target for the treatment of cardiovascular disease.

Despite statin therapy, patients with diabetes still face a substantial residual cardiovascular risk. The need for additional therapies is, therefore, sorely needed. Here Staels et al. explore to what extent peroxisome proliferator-activated receptor α agonists, such as fibrates, can improve the lipid profile and associated risk markers.

The immune system is instrumental in the pathogenesis of atherosclerosis. Here, Jacob George examines the growing knowledge of the role of regulatory T cells in atherosclerosis development. This field of research holds great potential for future development of novel therapeutic modalities designed to attenuate atherosclerosis and stabilize vulnerable plaques.

Ventricular tachycardia (VT) is a cause of early, intermediate and late morbidity and mortality in patients who have undergone palliative repair of congenital heart disease. Christopher Snyder provides a concise overview regarding the etiology of ventricular tachycardia in these patients and in-depth information to aid diagnosis, risk assessment and long-term management of postoperative VT in this unique population.