Ioannis Karalis

Effect of increasing doses of Rosuvastatin and Atorvastatin on apolipoproteins, enzymes and lipid transfer proteins involved in lipoprotein metabolism and inflammatory parameters.

Abstract This paper contains detailed results of a sub-population of the prospective randomized RADAR (Rosuvastatin and Atorvastatin in different Dosages And Reverse cholesterol transport) study. Objective: Statin treatment results in substantially decreased incidence of cardiovascular events but the exact pathophysiological mechanism of their beneficial effect is yet unclear. We aimed to examine the effects of up-titrated doses of two widely used statins (atorvastatin (ATOR) and rosuvastatin (ROSU)) on parameters involved in lipoprotein metabolism, in patients with low high density lipoprotein cholesterol values (HDL-C). Research design and methods: In this RADAR substudy, 80 patients, aged 40–80 years, with known cardiovascular disease and low HDL-C (<1.0 mmol/l), were randomized to receive, after an initial 6 week dietary run-in phase, either ATOR 20 mg (n = 41) or ROSU 10 mg (n = 39). The doses were up-titrated (in 6 week intervals) to 80 mg of ATOR or 40 mg of ROSU at 12 weeks. Serum lipoproteins and lipoprotein metabolism parameters were measured at baseline and at 6 and 18 weeks of follow up. Results: Both statins significantly reduced total cholesterol (TChol) and non-HDL-C values with ROSU being more effective for the doses studied (p < 0.05). No statistically significant effect on HDL-C was observed for either statin. Apolipoproteins (apo) B, CI, CIII, AV and E were significantly reduced in both groups (p < 0.05), while the ratio of HDL particles containing both apoAI and apoAII (LpAI-AII) over HDL containing apoAI alone (LpAI) was changed for both statins with the decrease of LpAI being more prominent in the ATOR group (p = 0.028). Cholesterol ester transfer protein (CETP) mass and activity, phospholipid transfer protein (PLTP) activity and lipoprotein-associated phospholipase A2 (Lp-PLA2) mass and activity were all significantly reduced in both treatment groups over the follow-up period (p < 0.001). ATOR displayed a more prominent decrease of PLTP activity compared to ROSU (p = 0.043), while ROSU displayed a more prominent decrease of Lp-PLA2 activity compared to ATOR (p = 0.04). Both statins effectively reduced, in a dose-dependent way, high sensitivity C-reactive protein values over time, while no effect on the levels of circulating inter cellular adhesion molecule 1 (cICAM-1) was observed. Conclusions: The effects of statin treatment extend further and beyond a mere TChol and LDL cholesterol reduction, as demonstrated by the aforementioned alterations of lipoproteins, enzymes and lipid transfer proteins involved in lipoprotein metabolism and pro-atherogenic and inflammatory molecules. ROSU and ATOR displayed a similar pattern of effect on lipid metabolism with discrete differences in the magnitude of this effect in certain variables. Despite the limitations of small population size and lack of clinical end points, reported data provide an insight for the possible pathophysiological mechanisms implicated in the effect of increasing dosages of different statin treatments.

Late acquired stent malapposition: why, when and how to handle?

Stent malapposition (SM), also referred to as incomplete stent apposition, is defined by the separation of at least one stent strut from the intimal surface of the arterial wall with evidence of blood behind the strut, without involvement of side branches.1 SM can be quantified by measuring the number of malapposed struts, the arc subtended by the malapposed struts, the distance between the malapposed struts and the vessel wall, and the area, length and volume of the gap between the stent and the vessel wall.w1 This phenomenon, commonly identified by intravascular ultrasound (IVUS) imaging studies, may be detected early, at the time of stent implantation (and classified as acute) or later, at follow-up (therefore classified as late). Late stent malapposition can be further classified, in terms of pathogenesis, into two broad categories: late persistent SM, when an inadequately apposed stent (during the initial intervention) remains incompletely apposed at follow-up; and the late acquired stent malapposition (LASM) when it is documented despite the appropriate apposition of the stent during the index procedure. The different types of stent malapposition are graphically explained in figure 1A,B. It is evident that differentiating between the two different forms of late SM requires intravascular imaging both at stent implantation and at follow-up.2 Figure 1 Various types of stent malapposition. Reproduced with permission from Hur et al. 2 LASM represents a well recognised problem in interventional cardiology that became more prominent in the era of drug eluting stents (DES) (reported incidence 10–25% compared to about 4–6% after bare metal stent (BMS) implantation, in native coronary arteries).3 ,4 w2 w3 Its clinical significance, that will …

Journey Through Cholesteryl Ester Transfer Protein Inhibition From Bench to Bedside

High-density lipoprotein (HDL) possesses antiatherogenic properties that include reverse cholesterol transport (RCT), maintenance of endothelial function, and protection against thrombosis.1,2 The concentration of HDL is largely determined by the cholesteryl ester transfer protein (CETP) that decreases the ratio of HDL-cholesterol (HDL-C) over low-density lipoprotein-cholesterol (LDL-C). In this review, we will discuss the rationale and effectiveness of using HDL as a therapeutic target, by reducing CETP activity, as a means of cardiovascular morbidity reduction. ### Metabolism and Pathophysiology HDL has been proposed to have several antiatherogenic properties that include the ability to mediate cholesterol efflux from macrophages, antioxidant capacity, anti-inflammatory properties, nitric oxide–promoting activity,1,2 and the ability to transport proteins with their own intrinsic biological activities.3 The steps describing the removal of excess cholesterol from macrophages to ultimate disposition in the feces are collectively known as RCT and are schematically summarized in Figure.4 Small nascent HDL particles composed of phospholipids and apolipoproteins (apo) are synthesized mainly in the liver and the intestine. These particles obtain additional apolipoproteins, free and esterified cholesterol, and excess phospholipids from chylomicrons and very LDL (VLDL) during their lipolytic conversion into triglyceride-depleted remnants. Free cholesterol is also acquired from peripheral tissues. HDL-associated apolipoproteins, including apoAI, play a central role in this process, serving as a signal transduction protein to mobilize cholesteryl esters (CEs) from intracellular pools. Of similar importance are ATP-binding cassette transporters A1 and ATP-binding cassette transporters G1 proteins expressed on the macrophage cell surface that mediate the transfer of cellular unesterified cholesterol to nascent discoidal and maturating globular HDL.5 The accepted cholesterol in HDL is subsequently transformed into CE by lecithin cholesterol acyl transferase, an enzyme that is also activated primarily by apoAI. Subsequently, HDL can transport its CE back to the liver via interaction with the scavenger receptor …

ST-segment elevation associated with allergic reaction to echocardiographic contrast agent administration

We report a case of an allergic reaction after the administration of an echocardiographic contrast agent which resulted in ST-segment elevation. Hypersensitivity and allergic reactions are known causes of acute cardiovascular events. However, only limited reports are available which suggest the exact mechanism of the occurrence of angina or myocardial infarction during severe allergic reactions. In our case, through invasive imaging (coronary angiography and IVUS) we have shown for the first time a transient coronary spasm in the absence of intra-coronary thrombus and only minimal neointimal hyperplasia.

Guide extension catheter stepwise advancement facilitated by repeated distal balloon anchoring

Coronary stent delivery can be extremely challenging in tortuous and calcified lesions especially when radial approach is chosen. Guide extension catheter is a useful tool for overcoming the inherent difficulties arising by the use of radial access in complex percutaneous interventions. We describe a technique for guide extension catheter system advancement by presenting two cases. This was performed stepwise by repeated distal balloon anchoring in the coronary artery of interest.

A systematic review on the safety of Prostar XL versus ProGlide after TAVR and EVAR.

BACKGROUND Endovascular aortic aneurysm repair (EVAR) and transfemoral transcatheter aortic valve replacement (TAVR) are widely spreading minimally invasive procedures performed mainly through the femoral artery. Prostar XL and ProGlide vascular closure devices are used in clinical practice for the hemostasis in these procedures and they have been shown to be safe and effective. PURPOSE The aim of our systematic review is to compare the safety of these two devices for percutaneous closure of large arteriotomies in patients undergoing TAVR and EVAR. METHODS We searched PubMed, EMBASE, Google Scholar and the Cochrane Central Register of Controlled Trials for all randomized and observational published studies that compared Prostar XL vs. ProGlide. Relative risk was calculated by random-effects model. Review Manager 5.1 was used for statistical analysis. RESULTS A total number of 2909 patients were included in our analysis. The rate of overall vascular complications did not differ between Prostar XL and ProGlide {RR 1.35 (0.80-2.29), p=0.27}. In contrary, the risk ratio of all bleeding complications with Prostar XL compared to ProGlide was 1.82 (1.47-2.24, p<0.001) and for major and life-threatening bleeding complications was 2.48 (1.65-3.73, p<0001, suggesting a lower bleeding risk with ProGlide). No statistical difference was found between groups for end-stage acute kidney injury (AKI), with a risk ratio of 2.14 (0.81-5.66), p=0.05. Finally, there were no differences in in-hospital and 30-days mortality rate between the two groups (1.41, 0.56-3.54, p=0.46 and 1.43, 0.55-3.73, p=0.47, respectively). CONCLUSIONS Prostar XL is associated with greater risk of any bleeding as well as life threatening bleeding compared to the ProGlide device. However, no significant differences were observed in the rate of overall vascular complications, end stage AKI and in-hospital and 30-days mortality.

Proximal Left Anterior Descending Artery Acute Occlusion With an Unusual Electrocardiographic Pattern: Not Everything Is ST Elevation

Early detection of electrocardiogram (ECG) abnormalities indicative of acute coronary artery occlusion is crucially important to identify candidates for emergency revascularization. In most cases, ST elevation is the finding that enables diagnosis to be established. However, in some situations, ST elevation corresponding to the territory affected by coronary artery occlusion may not be present, resulting in a delay in reperfusion treatment and larger infarcted areas. We present 2 cases of acute occlusion of the left anterior descending artery with an uncommon but characteristic ECG pattern. The first patient was 61-year-old man with no relevant history of cardiac events, who was attended at home by the emergency services for acute chest pain. In the first ECG performed, approximately 30 minutes after onset of pain, marked ST-segment depression of up to 3 mm was observed after the J point, with steep Q and T waves in the precordial leads V2-V5, 0.5 mm ST elevation in leads aVL and aVR, and ST-segment depression of 1 mm in the inferior leads (Figure 1A). The patient was referred to the catheterization laboratory, where total occlusion of the left anterior descending artery (Figure 1B) was observed with no collateral filling. The lesion was treated by angioplasty and placement of a drug-eluting stent. During the same procedure, 2 lesions with 70% occlusion of the circumflex artery and the right coronary artery were treated by angioplasty and stent placement (Figure 1C). The ECG recorded after the procedure (Figure 1D) showed electrical abnormalities characteristic of the outcome of an anterior infarction, with QS complexes in V1-V2, rS in lead V3, persistent ST elevation, and a negative T wave. The second patient was a 65-year-old man with no relevant history, who was attended for sudden chest pain. The first ECG once again showed ST-segment depression of up to 3 mm after the J point, with minimal Q wave, loss of R wave progression, and prominent T waves in the precordial leads (particularly in leads V2-V3) (Figure 2A). In this case, there was ST elevation in lead aVR of up to 1.5 mm, Q wave in lead aVL, and ST-segment depression in the inferior leads, which reached 2 mm in lead II. Emergency

Emerging drugs for coronary artery disease. From past achievements and current needs to clinical promises

Introduction: Coronary artery disease (CAD) is one of the major causes of morbidity and mortality worldwide, exerting a huge economic burden. Although drug treatment in the past decades has made large advances, significant residual risk remains. However, in the coming years, there are still a lot of great advances and major breakthroughs expected. Areas covered: New treatments are expected to provide higher efficacy with favorable safety profiles. In this review article, we provide an almost complete overview of the recent and emerging drug therapies of CAD. This includes: drugs for the treatment of atherogenic dyslipidemia, drugs that stabilize atherosclerotic plaques and halt their progression guided by novel anti-inflammatory concepts in atherosclerosis treatment, anti-anginal treatments, renin-angiotensin-aldosterone system inhibitors, antiplatelet and anticoagulant drugs. Expert opinion: Efforts have been made to improve the clinical effectiveness and safety of established treatment strategies and target new frontiers through developing novel treatment strategies that tackle different mechanisms of action. Better understanding of the different molecular and cellular mechanisms underlying CAD has resulted in more innovations and achievements in CAD drug therapy, and still a lot more is anticipated in the coming years.

Microcatheters: A valuable tool in the presence of a challenging coronary anatomy in the setting of acute coronary interventions. Case report and mini review ☆

Popularity of microcatheters (MCs) is growing among interventional cardiologists, especially when complex coronary anatomy is involved. However, MCs are still considered by many as a niche tool and their value in common clinical practice and in the setting of acute coronary interventions has not been fully appreciated. This case report highlights the decisive role of MC use in the successful completion of a primary percutaneous coronary intervention. Characteristics and indications of the most commonly used MC are briefly discussed.

Impact of age on transcatheter aortic valve implantation outcomes: a comparison of patients aged ≤ 80 years versus patients > 80 years

Objective To investigate the procedural outcomes and the long-term survival of patients undergoing transcatheter aortic valve implantation (TAVI) and compare study results of patients ≤ 80 years and patients > 80 years old. Methods A total of 240 patients treated with TAVI were divided into two groups according to age ≤ 80 years (n = 105; 43.8%) and > 80 years (n = 135; 56.2%). The baseline characteristics and the procedural outcomes were compared between these two groups of patients. Results With the exception of peripheral artery disease and hypercholesterolemia, which were more frequently observed in the older age group, baseline characteristics were comparable between groups. Complication rates did not differ significantly between patients ≤ 80 years and patients > 80 years. There were no differences in 30-day mortality rates between patients aged ≤ 80 years and patients > 80 years old (9.5% vs. 7.4%, respectively; P = 0.557). After a median follow-up of 28 months (interquartile range: 16–42 months), 50 (47.6%) patients aged ≤ 80 years died compared to 57 (42%) deaths in the group of patients > 80 years old (P = 0.404). Conclusion The results of the present single center study showed that age did not significantly impact the outcomes of TAVI.