Mario Crisci

Inflammation and Cardiovascular Disease: From Pathogenesis to Therapeutic Target

Atherosclerosis represents the most common pathological substrate of coronary heart disease (CHD), and the characterization of the disease as a chronic low-grade inflammatory condition is now largely accepted. A number of mediators of inflammation have been widely studied, both as surrogate biomarkers and as causal agents, in the pathophysiological network of atherogenesis and plaque vulnerability. The epidemiological observation that biomarkers of inflammation are associated with clinical cardiovascular risk supports the theory that targeted anti-inflammatory treatment appears to be a promising strategy in reducing residual cardiovascular risk on the background of traditional medical therapy. A large number of randomized controlled trials have shown that drugs commonly used in cardiovascular disease (CVD), such as statins, may be effective in the primary and secondary prevention of cardiovascular events through an anti-inflammatory effect. Moreover, several anti-inflammatory drugs are being tested for their potential to reduce residual cardiovascular risk on the background of validated medical therapy for atherosclerotic disease. In this paper, we review relevant evidence with regard to the relationship between inflammation and CVD, from pathogenesis to therapeutic strategies.

The Role of von Willebrand Factor in Vascular Inflammation: From Pathogenesis to Targeted Therapy

Beyond its role in hemostasis, von Willebrand factor (VWF) is an emerging mediator of vascular inflammation. Recent studies highlight the involvement of VWF and its regulator, ADAMTS13, in mechanisms that underlie vascular inflammation and immunothrombosis, like leukocyte rolling, adhesion, and extravasation; vascular permeability; ischemia/reperfusion injury; complements activation; and NETosis. The VWF/ADAMTS13 axis is implicated in the pathogenesis of atherosclerosis, promoting plaque formation and inflammation through macrophage and neutrophil recruitment in inflamed lesions. Moreover, VWF and ADAMTS13 have been recently proposed as prognostic biomarkers in cardiovascular, metabolic, and inflammatory diseases, such as diabetes, stroke, myocardial infarction, and sepsis. All these features make VWF an attractive therapeutic target in thromboinflammation. Several lines of research have recently investigated “tailor-made” inhibitors of VWF. Results from animal models and clinical studies support the potent anti-inflammatory and antithrombotic effect of VWF antagonism, providing reassuring data on its safety profile. This review describes the role of VWF in vascular inflammation “from bench to bedside” and provides an updated overview of the drugs that can directly interfere with the VWF/ADAMTS13 axis.

Von Willebrand Factor as a Novel Player in Valvular Heart Disease: From Bench to Valve Replacement

von Willebrand Factor (vWF) is a well-known mediator of hemostasis and vascular inflammation. Its dynamic modulation in the bloodstream, according to hemodynamic conditions, makes it an appealing biomarker in patients with valvular heart disease (VHD). Recent studies highlight the close connection between vWF and VHD, with possible implications in the pathogenesis of VHD, promoting valve aging and calcification or favoring the development of infective endocarditis. Moreover, vWF has been recently proposed as a new diagnostic and prognostic tool in patients with valve stenosis or regurgitation, showing a strict correlation with severity of valve disease, outcome, and bleeding (Heyde syndrome). A novel role for vWF is also emerging in patients undergoing percutaneous or surgical valve repair/replacement to select and stratify patients, evaluate periprocedural bleeding risk, and detect procedural complications. We also report our single-center experience, suggesting, for the first time, possible clinical implications for vWF in percutaneous mitral valve repair (MitraClip). This review summarizes recent advances in the role of vWF in VHD with an updated overview going from bench to operating room.

Radial Versus Femoral Access for Coronary Angiography

In a retrospective observational study published in this issue of Angiology, Jin et al analyzed 1392 women from a consecutive cohort undergoing percutaneous coronary intervention (PCI). There was less post-PCI bleeding, fewer major cardiac adverse events, shorter length of stay, and lower hospital costs for the transradial (TR) interventional approach compared to the transfemoral (TF) route. The adoption of TR route as the first approach in patients undergoing PCI is supported by data from several institutions including our own. Two large randomized trials “Radial Versus Femoral Access for Coronary Angiography and Intervention in patients with acute coronary syndromes” and “Minimizing Adverse hemorrhagic event by Transradial access and systemic Implementation of AngioX program” have clearly demonstrated the advantages of radial access compared to the femoral approach in a reduction of major adverse cardiac events and major bleeding. This approach has been also extensively investigated in high-risk setting of patients, such as the elderly patients or women. A recent meta-analysis of 777 841 elderly patients concluded that the TR approach is associated with a reduced risk of stroke, lower rate of vascular complications overall, and mortality benefit in fragile patients with a higher rate of crossover but acceptably low. Conversely, still unclear is the role of TR approach in women, who seem to be more prone to adverse events, often underreported in clinical studies. The main complication related to TR procedures in this setting is due to the smaller diameter of the radial artery, compared to males, and a major rate of vasospasm, the most common cause of radial procedure failure. The Study of Access Site for Enhancement for PCI for women trial demonstrated that the TR approach in women undergoing PCI did not significantly reduce bleeding or vascular complications and access site crossover was observed more often in patients assigned to radial access than the TF. Moreover, a substudy comparing the quality of life or functional status measured after radial versus femoral approach for cardiac catheterization did not observe any difference according to site access. Despite this finding, patient preference for the same access strategy for repeat procedures was significantly greater among patients assigned to the TR compared to the TF approach. More promising results come from The Matrix Access Trial, the largest randomized trial that compared radial and femoral access in acute coronary syndrome. This study clearly demonstrated that the radial approach reduced net clinical events through a reduction in major bleeding and all-cause mortality. In the subgroup analysis, the results of the trial were also confirmed in female patients with a 28% reduction of risk of allcause mortality, myocardial infarction, stroke, or Bleeding Academic Research Consortium 3 or 5 bleeding (odds ratio: 0.72; confidence interval: 0.56-0.93; P 1⁄4 .012). Interestingly, the data in favor of TR access in women were even better compared to the male subgroup (0.89; 0.76-1.05; P 1⁄4 .16). The economic aspects should not to be underestimated. The study by Jin et al showed an important reduction in costs and length of hospital stay. Another study demonstrated that the TR approach was associated with a cost saving exceeding US

Use and efficacy of saline hydration and N-acetyl cysteine to prevent contrast-induced nephropathy in low-risk populations undergoing coronary artery angiography.

800/patient compared to the TF approach. However, the present study is the first that investigated the costs and length of hospital stay in women patients showing a significant reduction when the TR access was used. Finally, in agreement with the big trials, this study confirmed the better profile of the TR approach compared to the TF route and suggested that radial access should become the default access for female patients undergoing PCI.