Renatomaria Bianchi

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.

Impact of gene polymorphisms, platelet reactivity, and the SYNTAX score on 1-year clinical outcomes in patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention: The GEPRESS study

OBJECTIVESnThe aim of this study was to investigate the association between high on-treatment platelet reactivity (HPR) and the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score (SS) for risk prediction of major adverse cardiovascular events (MACE) in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS) undergoing percutaneous coronary intervention (PCI).nnnBACKGROUNDnPlatelet function testing may be used to optimize antiplatelet therapy in high-risk patients, butxa0identification of this category of patients remains challenging.nnnMETHODSnThe GEPRESS (Gene Polymorphism, Platelet Reactivity, and the Syntax Score) study was a prospective, multicenter, observational study enrolling 1,053 patients with NSTEACS undergoing PCI and treated with clopidogrel. The platelet reactivity index (PRI) was measured at 3 time points: before PCI, at hospital discharge, and 1 month after PCI. Genetic variants of clopidogrel metabolism were determined in 750 patients. Patients were stratified by the presence of HPR (PRI >50%) and by tertile of the SS (upper SS tertilexa0≥15). The primary objective of this study was the risk of MACE in the period between 1 month and 1 year.nnnRESULTSnBetween 1 month and 1 year, 1-month HPR was an independent predictor of MACE in patients with an SSxa0≥15, but not in those with an SSxa0<15, displaying a 5-fold increase in event rates (10.4% vs. 2.5%; pxa0< 0.0001). CYP2C19*2 was the only single nucleotide polymorphism associated with HPR, but it was not associated with MACE. Although there was a significant variability in the PRI across the 1-month period, predischarge HPR and SS effectively stratified the risk of subsequent MACE up to 1-year follow-up.nnnCONCLUSIONSnIn clopidogrel-treated patients with NSTEACS undergoing PCI, HPR was independently associated with an increased risk of MACE only in the presence of a high SS.

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

Contrast-induced nephropathy (CIN) is most commonly defined as acute renal failure occurring within 48–72xa0h of exposure to an intravascular radiographic contrast medium that is not attributable to other causes. In the international literature, a 25% increase in serum creatinine levels or an increase in absolute values of 0.5xa0mg/dl from baseline has been suggested to define CIN. The reported incidence of CIN varies widely, ranging from 2 to 50%. This variability results from differences in the presence or absence of risk factors. With a retrospective analysis we evaluated the use of saline hydration plus N-acetyl cysteine (NAC) to prevent CIN in a low-risk population of patients undergoing coronary artery angiography compared with an historic low risk group not treated. From January 2009 to December 2009, 152 consecutive patients who underwent coronary artery angiography with a low osmolarity contrast agent were enrolled in our study, and compared with an historic control group consisting of 172 low-risk patients. Nephrotoxic drugs such as diuretics, ACE-I and ARBs were stopped at least 24xa0h before the procedure. Inclusion criteria to define low-risk population were the absence of: diabetes, age >65xa0years, or baseline creatinine >1.4xa0mg/dl. We have treated group A (152 patients, 47.3%) with a saline hydration (1xa0ml/kg/h) plus N-acetyl cysteine 600xa0mg 12xa0h before and 12xa0h after the procedure; group B (group control of 170 patients, 52.7%) were not treated. The overall incidence of CIN was 7.1% (23 patients). In particular, the incidence of CIN was 2.6% (4 patients) in the group A and 11.2% (19 patients) in the group B (pxa0=xa00.002). In the multivariate analysis, including risk factor such as age, hypertension, hypercholesterolemia, current smoking habit baseline creatinine level, contrast index and hydration, the last variable was the only one inversely correlated independently with the incidence of CIN (pxa0=xa00.001). In conclusion, intravenous hydration with saline and NAC is an effective and low cost tool in preventing CIN in patients undergoing coronary artery angiography, and, according to the current guidelines, should be used in all high-risk patients for CIN. Our results show that even in patients at low risk, hydration with saline 0.9% plus NAC is useful and significantly reduces the incidence of CIN.

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 and Cardiovascular Disease: From a Biochemical Marker to an Attractive Therapeutic Target

BACKGROUNDnDespite recent advances, there is still an unmet need in antithrombotic therapy. New drugs have to overcome old targets, looking for new complementary strategies to counteract thrombus formation and propagation. Since its initial recognition in the 50s, von Willebrand Factor (VWF) has proved to be a contributor in clot formation. The contribution of VWF to platelet adhesion and aggregation is pivotal at high shear rates (i.e. microcirculation and critical artery stenosis), where globular-inactive-VWF elongates in a long chain-active conformation. Particularly, at sites of plaque erosion/disruption the activation of VWF may contribute critically to post-stenotic thrombus formation. In this context, VWF is a potential target of antithrombotic therapies. The plasma concentration of VWF increases in high risk population and predicts cardiovascular (CV) outcome. VWF demonstrates an emerging role in different clinical settings; for example, in valvular heart disease where it has been recently proposed as a new fluido-dynamic marker of disease severity and a predictor of successful correction. Drugs used in daily clinical practice (LMWHs, statins, N-acetylcysteine, glycoprotein IIb/IIIa inhibitors) may have an unselective antagonism on the VWF-pathway. Recently, several tailor-made inhibitors of VWF have been investigated. In animal models and clinical studies monoclonal antibodies, aptamers and nanobodies have been demonstrated to directly interfere with the VWF pathway. These studies proved the powerful antithrombotic property and the acceptable level of safety of this strategy.nnnCONCLUSIONnWe provide an overview of the drugs that a have a role in VWF-antagonism, illustrating how they might become a potential option to overcome current limitations of antithrombotic therapy.

Evidence of right coronary from mid-left anterior descending coronary: a rare case of coronary anomalous origin

A 53-year-old man with a familial history of CAD, a smoker, and with a high LDL cholesterol was referred to our cardiology division for typical angina. Stress ECG and myocardial perfusion scintigraphy were positive for an extended area of ischaemia on the anterior left ventricle wall. We then performed a coronary angiography showing normal left main originating from the left sinus …

Contemporary evidence of coronary atherosclerotic disease and myocardial bridge on left anterior descending artery in a patient with a nonobstructive hypertrophic cardiomyopathy.

To the Editor. We report the case of patient P.R., a 46-year-old man with an echocardiographic diagnosis of nonobstructive hypertrophic cardiomyopathy since 2001. The patient’s major cardiovascular risk factors were a familial history of coronary artery disease and mild hypertension. In the previous 6 months, the patient complained of dyspnea on exertion (NYHA II), tachycardia and typical angina. An exercise stress test and subsequent physical stress echocardiography were completely negative. Due to the worsening of the symptoms at rest, we decided to perform selective coronary angiography. An 80% stenosis was detected in the proximal tract of the left anterior descending artery (LAD), at the level of the origin of the first diagonal branch. Three centimeters distal to this lesion, in the middle segment of the LAD, a clear dynamic (systolic) narrowing of the coronary arterial lumen was detected, suggesting a myocardial bridge (Fig. 1). This finding was confirmed by performing an intravascular ultrasound (IVUS) examination (Fig. 2).

Bioresorbable vascular scaffold versus everolimus-eluting stents or drug eluting balloon for the treatment of coronary in-stent restenosis: 1-Year follow-up of a propensity score matching comparison (the BIORESOLVE-ISR Study)

to compare the 1‐year outcome between bioresorbable vascular scaffold (BVS), everolimus‐eluting stent (EES), and drug‐eluting balloon (DEB) for in‐stent restenosis (ISR) treatment.

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.