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The aim of the study was to determine whether epicardial adipose tissue thickness (EAT), a new cardiometabolic risk factor, is associated with essential hypertension. The sample included 127 asymptomatic patients with one or more cardiovascular risk factors consecutively referred for cardiac computed tomography angiography. Data were collected retrospectively and compared between hypertensive (n=39) and normotensive (n=88) patients. The hypertensive patients had a significantly higher mean EAT thickness than the normotensive group (2.81±1.6 mm vs 2.07±1.43 mm; P=.011) and a significantly elevated mean coronary artery calcium score (316.8±512.6 vs 108.73±215; P=.0257). The odds ratio for a patient with tissue thickness ≥2.4 mm having hypertension was 1.396 (95% confidence interval, 1.033–1.922). Factors independently associated with hypertension were body mass index, low‐density lipoprotein, and age. A model score was developed using the logistic regression coefficients for calculation of individual risk. Hypertensive patients have significantly higher than normal EAT thickness. Epicardial adipose tissue thickness may serve as a risk indicator for hypertension and cardiovascular morbidity.

In their recently published article, Lazeri and coworkers aimed at assessing the relation between uric acid, measured on Intensive Cardiac Care Unit admission, and mortality at short term follow-up in 466 consecutive ST elevation myocardial infarction (STEMI) patients submitted to percutaneous coronary intervention (PCI), as well as its relation with inflammatory markers [1]. They showed that higher uric acid (UA) were detectable in the 21.5%. In-hospital mortality was higher in patients with elevated UA (OR 3.9). At backward stepwise regression analysis UA resulted as an independent predictor for in-hospital mortality (OR 1.82). They concluded that uric acid holds a prognostic role for in-hospitalmortality in the acute phase of STEMI patients submitted to PCI. Uric acid (UA) is the main end product of metabolism of purines, which in turn are derived mostly from diet, de novo biosynthesis, and breakdown of nucleic acids [2]. Large epidemiologic studies have demonstrated that hyperuricemia is associated with an increased incidence of coronary heart disease (CHD) and increased mortality in those with CHD [3-6]. In the National Health and Nutrition Examination Survey I Epidemiologic Follow-up study, increased serum uric acid levels measured at baseline were independently associated with an increase in cardiovascular mortality; after adjusting for other risk factors, each 1 mg/dL rise in serum UA was associated with significant increases in cardiovascular and CHD mortality in men (hazard ratio 1.09 and 1.17) and women (hazard ratio 1.26 and 1.30) [3]. Proposed

We strongly believe that relying solely upon ameliorating myocardial ischemia by coronary revascularization may be an inadequate clinical strategy for the prevention of sudden cardiac death (SCD) in dialysis and chronic obstructive pulmonary disease (COPD) patients. More importantly when predicting SCD risk in patients with coronary artery disease one should assess not only left ventricular ejection fraction but also the other clinical parameters such as renal replacement therapy and COPD.

Cellular cardiomyoplasty is an investigational technique that may have the potential to reduce myocardial infarct size and improve cardiac function in patients with ischemic heart disease. However, experience with this approach is still limited to a few small trials, some which were not blinded or had other design problems. Although there is no sufficient evidence to believe that granulocyte colony-stimulating factor (G-CSF) may be a useful treatment in patients with ST segment elevation myocardial infarction (STEMI) who undergo primary percutaneous coronary intervention, further large-scale clinical studies are needed to examine the exact role of G-CSF in the management of those patients.

The importance of antiplatelet therapy has been appreciated more after the introduction of stent implantations into clinical practice. Use of coated stents has lowered the late restenosis rates to less than 10%, however, this technical achievement has brought together the need for longer and more intense antiplatelet therapies. Although dual antiplatelet therapy has become standard after stent implantations and been imported into practice guidelines, certain problems persist regarding the duration of therapy, ongoing stent thrombosis under dual antiplatelet therapy and whether triple antiplatelet therapy or its alternatives might provide additional benefit in these patients. In this paper, we discussed different aspects of dual and triple antiplatelet therapy in patients undergoing percutaneous coronary intervention.

Young patients with myocardial infarction usually have multiple risk factors for coronary heart disease (CHD). In some studies, for example, as many as 90 to 97% had one or more traditional risk factors for atherosclerosis. Although CHD is an uncommon entity in young patients, it constitutes an important problem for both the patient and the physician because of the devastating effect of this disease. More importantly, these patients have different risk factor profiles, clinical presentations, and prognoses than older patients.

Reduced rates of restenosis with drug-eluting stent (DES) may make left main coronary artery (LMCA) stenting more feasible in the future and there is increasing evidence of improved outcomes with PCI using DES compared to bare metal stents in LMCA disease. Some recent studies such as DES-DIABETES, SIRTAX, and ISAR-DIABETES have suggested that sirolimus-eluting stents (SES) may be associated with better outcomes in diabetic patients compared with paclitaxel-eluting stents (PES). It is unknown whether the use of SES instead of PES, or new generation stents such as everolimus-eluting stents, would be associated with better outcomes in patients with LMCA disease undergoing percutaneous coronary intervention (PCI). We strongly believe that further long-term follow-up results of those trials, as well as the results of other ongoing trials on this topic (e.g., FREEDOM, PRE-COMBAT) will elucidate the place of PCI in the management of LMCA disease.

Direct stenting, without predilation, reduces procedural time, radiation exposure, and costs. In patients with ST segment elevation myocardial infarction (STEMI), direct stenting may also reduce embolization of plaque constituents, lowering the incidence of the no-reflow phenomenon, thereby increasing myocardial perfusion and salvage. Compared with balloon angioplasty, stents achieve better immediate angiographic results because of the larger arterial lumen, less restenosis and re-occlusion, and fewer subsequent major ischemic events. Primary stenting has become the preferred strategy for primary percutaneous coronary intervention in patients with STEMI if it is technically possible.

The diagnosis of cardiac syndrome X (CSX) is often a diagnosis of exclusion and hence requires a systematic and comprehensive assessment of each patient to rule out more common causes of chest discomfort. The definitive technique for the diagnosis of CSX is not currently available. Many patients with chest pain and normal coronary angiograms have neither metabolic nor hemodynamic evidence of myocardial ischemia. Causes of nonischemic chest pain such as esophageal dysfunction, pulmonary hypertension, and mitral valve prolapse, should also be considered and pursued. Although chronic inflammation induced by Helicobacter pylori infection might play a part in the pathophysiology of CSX, one can conclude that nonischemic chest pain resulting from gastrointestinal disease such as esophagitis, gastritis cannot be completely excluded in the patients with CSX. We believe future large scale prospective cohort studies will be needed to solve that dilemma.

The prevalence of the metabolic syndrome (MS) is high among obese children and adolescents and increases with the severity of the obesity, and with central adiposity in particular. In addition, adverse biochemical markers of cardiovascular risk are already present in this population. The metabolic syndrome is an important risk factor for subsequent development of type 2 diabetes and/or cardiovascular diseases. Therefore, the key clinical implication of a diagnosis of MS is identification of a patient needing aggressive lifestyle modification focused on weight reduction and increased physical activity. In contrast to the data from adults, long-term cardiovascular risk in children and adolescents with the MS has not been clearly determined.

Stent strut fracture (SSF) may be an important complication after drug-eluting stent (DES) implantation particularly in patients undergoing sirolimus-eluting stent (SES) implantation. The occurrence of SSF at 6 to 9 months after the SES implantation, which was relatively common, resulted in a higher rate of focal in-stent restenosis. Although this angiographic unfavorable outcome did not lead to an increased risk of adverse cardiac events in the current study, we believe that large-scale prospective studies are needed to elucidate the exact pathophysiology and clinical sequela of the stent strut fracture, including bare metal stents.

We have read with great enthusiasm the recently published article byKitta and coworkers entitled ‘Low adiponectin levels predict late in-stent restenosis after bare-metal stenting in native coronary arteries’ [1]. That study included 148 consecutive patients who had elective percutaneous coronary intervention (PCI) with bare-metal stents in de novo lesions of native coronary arteries for symptomatic coronary artery disease (CAD). Adiponectin levels were measured 3 days or less before PCI. In the current study, angiographic in-stent restenosis (ISR) was found in 49 (33%) patients during 6 months of the follow-up. Adiponectin levels were lower in patients with ISR than those without ISR. Adiponectin levels were inversely correlated with late luminal loss of the stented lesions. Using multivariate logistic regression analysis, low adiponectin levels served as a predictor of ISR that was independent of angiographic and procedural variables, and clinical factors known to be associated with ISR (odds ratio 7.9). Furthermore, low adiponectin levels also independently predicted target lesion revascularization (TLR) during follow-up (odds ratio 3.7). They conclude that low adiponectin levels have a predictive value for late ISR after PCI with bare-metal stents in native coronary arteries. Adiponectin, also referred to as adipocyte complement related protein-30, Adipo-Q, and adipose tissue most abundant gene transcript-1, is an adipose-specific plasma protein that has drawn substantial attention recently in the research of obesity andmetabolic syndrome [2]. Increasing attention has been paid to the direct vascular effects of adiponectin. Decreased plasma adiponectin levels are observed in patients with diabetes, metabolic syndrome, and coronary artery disease, and this may play a key role in the development of insulin resistance. Although the mechanisms underlying anti-inflammatory properties of adiponectin are not well understood, adiponectin's anti-inflammatory and antiatherogenic properties may be related, in part, to its ability to stimulate production ofNO from vascular endothelium [3–6]. The potential impact of low plasma adiponectin on cardiovascular system cannot be overemphasized.Ouchi et al. found that the plasma adiponectin levels were lower in CAD patients than normal controls [7]. Huang and coworkers reported that the plasma adiponectin levels were inversely related to the numbers of CAD risk factors in overweight or obese adults [8]. In addition, several studies using adiponectin knockout mice have demonstrated the potential effects of adiponectin directly on the vascular wall in favor of adiponectin as a cardiovascular protective adipocytokine [9,10]. Increasing evidence from both in vitro and in vivo studies suggests that adiponectin modulation is important in the development of atherosclerosis. It was reported that adiponectin fromplasma accumulated in the injured artery and suppressed the endothelial inflammatory response and vascular smooth muscle cell proliferation, as well as macrophage-to foam cell transformation [11]. Adiponectin suppresses the proliferation and migration of smooth muscle cells induced by platelet-derived growth factor in smooth muscle cells [12]. Increasing adiponectin levels using an adenoviral vector attenuates neointimal proliferation in mechanically balloon injured arteries in adiponectin deficient mice [13]. Plasma C reactive protein (CRP) levels are negatively correlated with plasma adiponectin levels in male patients with CAD, and CRP messenger ribonucleic acid is expressed in human adipose tissue. Of interest, a significant inverse correlation is observed between CRP and adiponectin messenger ribonucleic acid levels in human adipose tissues [14]. Recent studies report an inverse correlation between plasma adiponectin and IL-6 concentrations [15]. Thus, adiponectin may indirectly inhibit CRP and IL-6 expression through its ability to inhibit production of TNF-alfa [16]. International Journal of Cardiology 137 (2009) 54–85 www.elsevier.com/locate/ijcard

[1] Gianni M, Dentali F, Grandi AM, et al. Apical ballooning syndrome or takotsubo cardiomyopathy: a systematic review.EurHeart J 2006;27:1523–9. [2] Bybee KA, Prasad A, Barsness GW, et al. Clinical characteristics and thrombolysis inmyocardial infarction frame counts inwomenwith transient left ventricular apical ballooning syndrome. Am J Cardiol 2004;94:343–6. [3] Kurisu S, Sato H, Kawagoe T, et al. Tako-tsubo like left ventricular dysfunction with ST segment elevation: a novel cardiac syndrome mimicking acute myocardial infarction. Am Heart J 2003;143:448–55. [4] Desmet WJR, Adriaenssens BFM, Dens JAY. Apical ballooning of the left ventricle: first series in white patients. Heart 2003;89:1027–31. [5] Tomcsanyi J, Marosi A, Arabadzisz K, et al. Tako-tsubo syndrome associated with sexual intercourse. Int J Cardiol 2007;121:e27–8. [6] Bybee KA, Kara T, Prasad A, et al. Systematic review: transient left ventricular apical ballooning: a syndrome that mimics ST-segment elevation myocardial infarction. Ann Intern Med 2004;41:858–65.

Given that the majority of hypertensives require more than one drug to control blood pressure, the pleitropic effects (especially anti-inflammatory effects) and favourable metabolic profile of nebivolol could make it an alternative drug regimen for hypertensives requiring beta-blocker treatment. Although standard beta-blockers seem to have a hard time at present, we are convinced that perhaps the new generation beta-blockers such as nebivolol might yet 'rescue' the reputation of beta blockers in the near-future.

Celik, Turgay/0000-0001-8418-0130 WOS: 000262978900017 PubMed: 17692950 Stent strut fracture (SSF) after drug-eluting stent (DES) implantation may be an important complication after DES implantation particularly in patients undergoing sirolimus eluting stent implantation. Since SSF is a highly relevant adverse event which can result in in-stent restenosis and thrombosis, we belive that DES with flexible stent platform or biodegradable DES may be needed to prevent this potential catastrophic complication. (C) 2007 Elsevier Ireland Ltd. All rights reserved.

No clear and generally accepted definition of clopidogrel resistance has been achieved up to now. We believe that the new point-of-care assays of platelet function may help the clinicians to overcome to define clopidogrel resistance especially in patients undergoing percutaneous coronary intervention in whom the level of inhibition of platelets is clinically essential.

Once the diagnosis of Takotsubo cardiomyopathy has been made, treatment should be based upon the patient's overall clinical condition. Up to now, there has been no controlled data to guide the optimal medical regimen, but it is reasonable to treat these patients with standard medications for left ventricular systolic dysfunction during acute phase. This includes aspirin, beta-blockers, ACE-inhibitors, and diuretics as necessary for volume overload. Since this type of cardiomyopathy is a transient disorder, the appropriate duration of therapy is not known. Although the current study demonstrates that the use of beta-blockers, aspirin, ACE inhibitors and calcium channel blockers does not seem to be indicated for chronic treatment of Takotsubo cardiomyopathy, we strongly believe that we need to achieve the data which will be obtained from large scale prospective studies in the near future to assess the clinical significance of chronic medical treatment.

Given the results of the BARI and ARTS I trials and a meta-analysis, coronary artery bypass surgery has been preferred to percutaneous coronary intervention in diabetics with multivessel coronary artery disease requiring hypoglycemic treatment and in whom internal mammary artery grafts can be used. This approach was strongly recommended in a 2002 ACC/AHA Task Force on the management of patients with acute coronary syndrome. But, these recommendations were made before the availability of drug-eluting stents. We strongly believe that the ongoing, multi-centre FREEDOM, CARDia and SYNTAX trials will elucidate the optimal revascularization strategy for diabetic patients with multivessel disease in the near future.

Recent researches have shown that active inflammation is considered a crucial step in the pathogenesis of acute coronary syndromes. C-reactive protein has long been utilized as a nonspecific clinical marker of inflammation, with the advent of high-sensitivity assays, has emerged as one of the most powerful independent predictors of cardiovascular disease. However, it is not clear whether C-reactive protein is only an excellent indicator or a perfect trigger in acute coronary syndromes. In this paper, we discussed the role of C-reactive protein in the pathogenesis of acute coronary syndromes.

In the recently published article, Wang and coworkers have tried to evaluate the prevalance of circulating C. pneumoniae DNA and its relationship with the severity and extent of coronary artery disease (CAD) [1]. In the current study, the presence of circulating C. pneumoniae DNA was determined by real-time PCR assay. They found that the prevalance of circulating C. pneumoniae DNA was significantly associated with multi-vessel disease. The odds ratio was 5.1 after adjustment for conventional risk factors. Finally, they drew the conclusion that presence of circulating C. pneumoniae DNA was associated with advanced CAD, suggesting C. pneumoniae infection as a contributing factor to the prog

Although hyperglycemia during acute myocardial infarction (AMI) is associated with worse short and long-term cardiovascular outcomes, whether control of glycemia is sufficient to reduce morbidity and mortality is not proven at the present time. On the other hand, the target glucose levels in patients with AMI have yet to be defined. We believe that future major outcome studies will clearly define optimal glucose concentrations in patients with AMI.

The data obtained from retrospective studies have indicated that patients with chronic heart failure (CHF) on statin treatment have good cardiovascular outcomes, in both ischemic and nonischemic dilated cardiomyopathy. There is an ongoing debate about whether the effects of statins on ubiquinone and cholesterol levels might have a negative impact in patients with CHF. We believe that 3 large scale ongoing randomized clinical trials (the GISSI-HF, CORONA and UNIVERSE) will come to end the debate over the safety and efficacy of statin treatment in patients with CHF.

Park and coworkers have evaluated the angiographic pattern of in-stent restenosis (ISR) and their subsequent clinical outcomes in the patients previously treated with sirolimuseluting stent (SES) or paclitaxel-eluting stent (PES) in a wellprepared clinical study [1]. They showed that diffuse ISR pattern was more common in PES implantation mainly because of higher incidence of diffuse intrastent ISR, whereas focal ISR was more common in SES implantation mainly because of higher incidence of focal margin ISR. However their subsequent target lesion revascularization rate was not different among both types of drug-eluting stent (DES) types in the current study. Sirolimus and paclitaxel are completely different drugs with distinct mechanism of action to prevent ISR. Sirolimus is a macrocylic triene antibiotic that has immunosupressive and antiproliferative properties, whereas paclitaxel is an antiproliferative agent which intereferes with the function of microtubules responsible for proper chromosome segragation during cell division [2]. Considering their charecteristics, sirolimus is regarded as a cytostatic drug and paclitaxel is regarded as cytotoxic. How can be explained the different angiographic ISR patterns after placement of sirolimus or paclitaxel-eluting stent? Some essential differences between SES and PES may help us to understand the different efficacy and safety profile of both DES types. Since sirolimus has a large therapeutic

In the recently published original article, Nienhuis and coworkers have througly examined the prognostic importance of elevated cardiac enyzmes after elective percutaneous coronary intervention (PCI). In that prospective observational study, they found that increase of troponin T after elective PCI had stronger prognostic implication when compared to increased creatine kinase (CK) [1]. Variable degrees of myocardial injury can be observed during PCI, as reflected by rises in cardiac enzymes such as CK and troponins [2–5]. Cardiac troponins aremore sensitive and more specific than CK for diagnosing minor myocardial damage [6]. Several reports have demonstrated that an increase in troponin T can be encountered in a proportion of patients ranging from b10% to 50% [7]. The adverse prognostic significance of myocardial biomarkers of injury after PCI is well known [3,8–10]. But, the degree of cardiac injury is modest making it unlikely that prognosis is closely related to the extent of injury in most cases. Elevations in myocardial biomarkers of injury might reflect the extent of coronary artery disease , embolic events, stent expansion, or the lack of collateral blood flow to area at the risk in patients undergoing PCI [11]. However the baseline troponin levels as a covariant have usually not included in most PCI outcome trials even though it has been measured and included in the analysis of the data like as the current study. Miller and coworkers have assessed the timing and magnitude of post-PCI troponin T levels and their relationships to outcomes in patients with or without pre-PCI baseline troponin T elevations [11]. They showed that long-term prognosis was most often related to baseline pre-PCI troponin value and not the biomarker res

In their well designed longitudinal study, Yue et al. attempted to explore the relationship between ECG and biochemichal markers in patients with coronary artery disease (CAD) [1]. They found a significant association between ECG parameters reflecting abnormal repolarization and elevated levels of C-reactive protein (CRP) and fibrinogen. Also, abnormal heart rate variability was associated with increased concentrations of soluble E-selectin. However they found no association between ECG markers and parameters reflecting increased procoagulation states. Electrocardiographic abnormalities in asymptomatic patients are often indicative of ischemic myocardium resulting from a compromised coronary circulation [2,3]. But, these ECG findings alone are not sufficiently predictive in patients with CAD. On the other hand, the concurrent presence of microalbuminuria may enhance the predictive value of STand T wave abnormalities. This was obtained from the data of the population-based The Prevention of REnal and Vascular ENdstage Disease (PREVEND) study [4]. In that study, the patients with both ST–T changes and microalbuminuria compared to those with ST–T changes alone had marked increases in the incidence of all-cause mortality (7.2 vs. 1.1%) and cardiovascularmortality (2.7 vs. 0.5%).Microalbuminuria had a greater impact on the risk of all-cause mortality than classical risk factors such as hypertension, hypercholesterolemia, smoking, obesity and diabetes mellitus. How microalbuminuria increases cardiovascular mortality is not well understood. As far as we know, microalbuminuria in nondiabetics appears to be the signal from the kidney that the vascular tree (especially the endothelium) is not function

In the light of current data obtained from prospective outcome studies, we believe that it is premature to support the use of homocysteine-lowering vitamins including folic acid in patients with established coronary artery disease in order to improve cardiovascular outcomes. We think that future large-scale epidemiological trials with very long-term follow-up periods will probably solve this dilemma.

Despite growing recognition of the frequent presentation of cardio-renal syndrome, its underlying pathophysiology is not well understood, and no consensus as to its appropriate management has been achieved. On the other hand, there is growing evidence that the presence of anemia can worsen cardiac function and symtomps in patients with congestive heart failure (CHF) and that correction of anemia may beneficial. We believe that the treatment modalities, especially eryhtropoietin, to correct anemia will be an important part of our therapeutic armemanterium in the battle against CHF.

In their recently published large population-based case control study, Rejnmark and coworkers have demonstrated that current use of small, accumulated amounts of vitamin K antagonists (VKA) was associated with increased fracture risk. However, they found that risk of fracture was not increased in patients who had used a large accumulated dose. They proposed that risk of fracture was increased due to circumstances related to initiation therapy rather than due to a direct pharmacological effect of VKA [1]. As far as every clinician knows, warfarin decreases the tendency of blood to clot by inhibiting the vitamin Kdependent gamma-carboxylation of clotting factors, namely II, VII, IX and X [2]. Interestingly, warfarin inhibits the gamma-carboyxlation of osteocalcin; non-carboxylated osteocalcin cannot bind calcium effectively [3]. Moreover, vitamin K might directly reduce bone resorption by the mechanisms of decreased prostaglandin E2 synthesis and osteoclast-like cell formation [4,5]. Those data have led the clinicians to suspect that warfarin may adversely affect bone metabolism. Some important clinical findings have supported this hypothesis. First, mean serum vitamin K concentrations in patients with fractures have been found to be lower than in normals [6,7]. Second, it was shown that the percentage of non-carboyxlated osteocalcin in elderly women was higher than in young women [8]. Third, another study clearly demonstrated that the risk of hip fracture in women with high serum levels of non-carboyxlated osteocalcin were higher than in women with low levels [9]. Lastly, vitamin K therapy has been shown to reduce urinary excretions of hydroxyproline which is a marker of bone

In the carefully designed placebo-controlled study, Tveit and coworkers showed that treatment with angiotensin II type 1 receptor blocker (ARB) candesartan for 3–6 weeks before after electrical cardioversion and 6 months after electrical cardioversion had no effect on the recurrence rate of atrial fibrillation (AF) in patients with persistent AF [1]. To the best of our knowledge, ARBs have been shown to be effective in the prevention of AF despite the fact that this essential benefit appears to be limited to patients with systolic left ventricular (LV) dysfunction or LV hypertrophy associated with hypertension [2]. Our group has recently showed that telmisartan significantly lowered P-wave dispersion values, indicative of nonhomogenous conduction in the left atrium and AF frequency in patients with hypertension after 6-month treatment [3]. Three mechanisms have been suggested to explain antiarrhythmic actions of ARBs in AF. First, improved LV-hemodynamics and reduced atrial stretch. Second, suppressed angiotensin-II induced fibrosis and third, direct modulation of ion-channel function [4]. Three randomized studies have demonstrated that therapy with angiotensin converting enzyme (ACE) inhibitors or ARBs combined with amiodarone may reduce the recurrence rate of AF after electrical cardioversion as compared to amiodarone alone [5–7]. Also, it has been found that candesartan prevented shortening of the atrial effective refractory period during rapid atrial pacing in dogs [8]. However, Tveit et al. found no beneficial effect on the recurrence rate of AF in patients treated

Modulation of myocardial free fatty acid metabolism is the key target for metabolic interventions in patients with coronary artery disease (CAD) with diabetes mellitus (DM). Because of its beneficial effects on heart metabolism at rest and on myocardial ischemia and left ventricular function, trimetazidine should be always combined with classical anti-ischemic treatment in patients with DM with CAD. We believe that, the new metabolic agents including L-carnitine, dichloroacetate, perhexiline and etomoxir will be added into our arsenal for the battle against CAD especially in patients with DM in the near future.

In the current study, DeltaQT dispersion (DeltaQTD) was found to be a new predictor of neurologic change which may be potentially useful in prediction of functional recovery in patients with acute cerebrovascular accident treated with thrombolytic treatment. We believe that DeltaQTD might be a new prognostic determiner in patients with acute cerebrovascular accident undergoing thrombolytic treatment. But it is too early to talk about the prognostic significance in patients with acute cerebrovascular accident not undergoing thrombolytic treatment.

Cyclooxygenase-2 (COX-2) inhibitors dilemna in cardiovascular medicine has not been resolved yet. The cardiovascular safety of selective COX-2 inhibitors other than rofecoxib is uncertain. Given the ongoing controversy surrounding the use of COX-2 inhibitors, futher clinical studies with different types of drugs are required to establish safety and therapeutic benefit in patients with coronary artery disease.

We have read with great enthusiasm the study published in the recent issue of the Journal, Ge and coworkers [1]. In that study, they analyzed serial changes of serum matrix metalloproteinases (MMPs), namely MMP-2 (Gelatinase A) and MMP-9 (Gelatinase B) and tissue inhibitor of MMP-1 (TIMP-1) levels on the 1st, 3rd and 7th day after stent implantation in patients with stable angina undergoing successful coronary stenting. They found that, only increased serum MMP-9 levels was associated with increased risk of in-stent restenosis (ISR) after stent implantation in 6-month control angiographies. It has been demonstrated that MMPs play a significant role in the pathogenesis of restenosis orchestrating extracellular matrix (ECM) degradation and the release of matrix-degrading MMPs, including MMP-2 and MMP-9, which enhance neointimal remodeling after plain angioplasty [2,3]. Remodeling after ECM after vascular injury facilitates migration and proliferation of vascular smooth muscle cells (VSMCs), and MMPs play an essential role in this [4]. TIMPs inhibit migration of VSMCs and also stabilize the ECM [5]. Among TIMPs, TIMP-3 has been shown to be particularly suitable as potential inhibitor of ISR in animal coronary stenting models [5]. However, one has to question if the migration of VSMCs is absolutely necessary to form a restenotic plaque because intimal VSMCs are already present in the original plaque. When a TIMP is given before and after balloon injury for up to 14 days, the number of VSMCs was greatly reduced, but not completely obliterated [3]. From that standpoint of view, we consider that although MMPs, including gelatinase B play a key role in the pathogenesis of ISR in which multiple