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M. Dikić, M. Tesic, Z. Markovic, V. Giga, A. Djordjevic-Dikic, J. Stepanović, B. Beleslin, I. Jovanović et al.

BackgroundThe risk stratification of patients with diabetes mellitus (DM) is a major objective for the clinicians, and it can be achieved by coronary flow velocity reserve (CFVR) or with coronary artery calcium score (CS). CS evaluates underlying coronary atherosclerotic plaque burden and CFVR estimates both presence of coronary artery stenosis and microvascular function. Consequently, CFVR may provide unique risk information beyond the extent of coronary atherosclerosis.AimOur aim is to assess joint prognostic value of CFVR and CS in asymptomatic DM patients.Materials and methodsWe prospectively included 200 asymptomatic patients (45,5 % male, mean age 57,35 ± 11,25), out of which, there were 101 asymptomatic patients with DM and 99 asymptomatic patients without DM, but with one or more conventionally risk factors for coronary artery disease. We analyzed clinical, biochemical, metabolic, inflammatory parameters, CS by Agatston method, transthoracic Doppler echocardiography CFVR of left anterior descending artery and echocardiographic parameters.ResultsTotal CS and CS LAD were significantly higher, while mean CFVR was lower in diabetics compared to the nondiabetics. During 1 year follow-up, 24 patients experienced cardio-vascular events (one cardiovascular death, two strokes, three myocardial infarctions, nine new onsets of unstable angina and nine myocardial revascularizations): 19 patients with DM and five non DM patients, (p = 0,003). Overall event free survival was significantly higher in non DM group, compared to the DM group (94,9 % vs. 81,2 %, p = 0,002 respectively), while the patients with CS ≥200 and CFVR <2 had the worst outcome during 1 year follow up in the whole study population as well as in the DM group. At multivariable analysis CFVR on LAD (HR 12.918, 95 % CI 3.865–43.177, p < 0.001) and total CS (HR 13.393, 95 % CI 1.675–107.119, p = 0.014) were independent prognostic predictors of adverse events in DM group of patients.ConclusionBoth CS and CFVR provide independent and complementary prognostic information in asymptomatic DM patients. When two parameters are analyzed together, the risk stratification ability improves, even when DM patients are analyzed together with non DM patients. As a result, DM patients with CS ≥200 and CFVR <2 had the worst outcome. Consequently, the use of two tests identified subset of patients who can derive the most benefit from the intensive prevention measures.

M. Ostojić, T. Potpara, M. Polovina, Mladen M Ostojić

INTRODUCTION Electrocardiographic (ECG) diagnosis of acute myocardial infarction (AMI) in patients with paced rhythm is difficult. Sgarbossa's criteria represent helpful diagnostic ECG tool. CASE REPORT A 57-year-old female patient with paroxysmal atrial fibrillation and a permanent pacemaker presented in the Emergency Department with prolonged typical chest pain and ECG recording suggestive for AMI. Documented ECG changes correspond to the first Sgarbossa's criterion for AMI in patients with dual pacemakers (ST-segment elevation of 5 mn in the presence of the negative QRS complex). The patient was sent to catheterization lab where coronary angiogram reveled normal findings. ECG changes occurred due to pericardial reaction following two interventions: pacemaker implantation a month before and radiofrequency catheter ablation of AV junction two weeks before presentation in Emergency Department. CONCLUSION This case report points out to the limitations of proposed criteria that aid in the recognition of AMI in patients with underlying paced rhythm and possible cause(s) of transient electrocardiographic abnormalities.

B. Parapid, N. Danchin, A. Menotti, H. Blackburn, H. Adachi, D. Kromhout, D. Jacobs, A. Nissinen et al.

M. Polovina, M. Ostojić, T. Potpara

We compared plasma levels of biomarkers of inflammation (CRP) and oxidation (oxLDL), determined at study inclusion in lone atrial fibrillation (LAF) patients (48.6 ± 11.5 years; 74.0% men) and sinus rhythm controls (49.7 ± 9.3 years; 72.7% men, P > 0.05), and investigated the association of baseline CRP and oxLDL levels with the risk for vascular disease (VD) development (hypertension, cerebrovascular disease, coronary/peripheral artery disease, and pulmonary embolism) during prospective follow-up. Baseline CRP (1.2 [0.7–1.9] mg/L versus 1.1 [0.7–1.6] mg/L) and oxLDL levels (66.3 ± 21.2 U/L versus 57.1 ± 14.6 U/L) were higher in LAF patients (both P < 0.05). Following a median of 36 months, incident VD occurred in 14 (28.0%) LAF patients, all of whom developed arterial hypertension, and in 5 (11.4%) controls (hypertension, n = 4; coronary artery disease, n = 1), P < 0.05. LAF patients developed VD more frequently and at a younger age. Both CRP (HR, 2.54; 95% CI, 1.26–5.12; P = 0.009) and oxLDL (HR, 2.24; 95% CI, 1.14–4.40; P = 0.019) were multivariate predictors of incident hypertension in LAF patients, but not in the controls. Further research should clarify clinical relevance of investigated biomarkers for risk stratification and treatment of LAF patients.

J. Kostic, A. Djordjevic-Dikic, M. Dobric, D. Milašinović, M. Nedeljković, S. Stojkovic, J. Stepanović, M. Tesic et al.

BackgroundNicorandil, as a selective potassium channel opener, has dual action including coronary and peripheral vasodilatation and cardioprotective effect through ischemic preconditioning. Considering those characteristics, nicorandil was suggested to reduce the degree of microvascular dysfunction.MethodsThirty-two patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention (pPCI) were included in the study. Index of microvascular resistance (IMR) was measured in all patients immediatelly after pPCI before the after administration of Nicorandil. ST segment resolution was monitored before intervention and 60 min after terminating the procedure. Echocardiographic evaluation of myocardial function and transthoracic Doppler derived Coronary flow reserve (CFR) of infarct related artery (IRA) was performed during hospitalization and 3 months later.ResultsIMR was significantly lower after administration of Nicorandil (9.9 ± 3.7 vs. 14.1 ± 5.1, p < 0.001). There was significant difference in ST segment elevation before and after primary PCI with administration of Nicorandil (6.9 ± 3.7 mm vs. 1.6 ± 1.6 mm, p < 0.001). Transthoracic Doppler CFR measurement improved after 3 months (2.69 ± 0.38 vs. 2.92 ± 0.54, p = 0.021), as well as WMSI (1.14 ± 0.17 vs. 1.07 ± 0.09, p = 0.004).ConclusionIntracoronary Nicorandil administration after primary PCI significantly decreases IMR, resulting in improved CFR and ventricular function in patients with STEMI undergoing primary PCI.

S. Obradovic, N. Djukanović, Z. Todorović, I. Markovic, D. Zamaklar-Trifunović, D. Protic, M. Ostojić

AIM The aim of this study was to examine whether the termination of long-term clopidogrel therapy results in a proinflammatory state and whether lipid parameters influence the inflammatory response after stopping the drug. METHODS A prospective, multicenter study was conducted among 200 patients with implanted coronary stents who received dual antiplatelet therapy for one year, without ischemic or bleeding events. According to the guidelines, clopidogrel was discontinued after one year. In all patients, the high-sensitivity C-reactive protein (hsCRP), soluble CD40 ligand (sCD40L) and lipid [total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)] levels were measured twice: on the day of cessation of clopidogrel and 45 days after the termination of clopidogrel treatment. RESULTS In men (n=151), the sCD40L serum levels were significantly higher 45 days after the discontinuation of clopidogrel (p=0.007), while the hsCRP levels were not significantly different (p=0.407). Furthermore, when analyzed across the HDL-C quartiles, the hsCRP and sCD40L values were found to be associated with the levels of HDL-C after the discontinuation of clopidogrel in men. In addition, the men in the first HDL-C quartile exhibited the most pronounced increase in the sCD40L levels (p=0.001) and had significantly higher hsCRP levels (p=0.001) compared to the subjects in the other quartiles. Other lipid parameters did not show any associations with the sCD40L or hsCRP levels. CONCLUSIONS The discontinuation of clopidogrel is associated with higher increments in the sCD40L level, and a pronounced proinflammatory response is associated with a lower HDL-C concentration.

D. Trifunovic, S. Stanković, J. Marinković, M. Banovic, Nina Đukanović, O. Vasović, B. Vujisić-Tešić, M. Petrović et al.

Summary Background: Oxidized low density lipoprotein (ox-LDL) and high-sensitive C-reactive protein (hs-CRP) are elevated in diabetes mellitus (DM) and associated with accelerated atherosclerosis. Little is known about their dynamics in the acute phase of ST segment elevation myocardial infarction (STEMI), especially in relation to the presence of DM and pre-diabetes (pre-DM). This study aimed to analyze timedependent changes in ox-LDL and hs-CRP regarding the presence of pre-DM and DM in STEMI patients treated by primary percutaneous coronary intervention (pPCI). Methods: In 103 consecutive patients with the first anterior STEMI ox-LDL and hs-CRP were measured before pPCI, on day 2 and day 7 after pPCI. Results: Patients were classified into: non-diabetics, pre-diabetics and diabetics. In each group the maximal ox-LDL concentration was found on admission, decreased on day 2 and reached the lowest values on day 7 (p<0.001). Diabetics had the highest ox-LDL concentrations compared to pre-diabetics and non-diabetics (on admission: p=0.028, on day 2: p=0.056, on day 7: p=0.004). hs-CRP concentration rose from admission, reached its peak on day 2 and decreased on day 7, in each group (p<0.001). Significant differences in hs-CRP concentrations were found between non-diabetics and pre-diabetics on admission (p=0.018) and day 2 (p=0.026). In a multivariate analysis DM was an independent determinant of high ox-LDL concentrations. Both ox-LDL and hs-CRP significantly correlated with Killip class, left ventricular ejection fraction, NT-proBNP and peak troponin I. Conclusions: In patients with the first STEMI treated by pPCI there were significant differences in ox-LDL and hs-CRP concentrations between non-diabetics, pre-diabetics and diabetics. Ox-LDL and hs-CRP concentrations were related to heart failure parameters. Kratak sadržaj Uvod: Oksidovani lipoprotein niske gustine (ox-LDL) i vi- sokosenzitivni C-reaktivni protein (hs-CRP) povišeni su u dijabetes melitusu (DM) i povezani sa ubrzanom atero- sklerozom. Malo je poznata njihova dinamika u akutnoj fazi infarkta miokarda sa elevacijom ST segmenta (STEMI), na- ročito uzavisnosti od prisustva DM ili predijabetesa (pre-DM). Ova studija je analizirala promenu koncentracija ox-LDL i hs-CRP u akutnoj fazi STEMI u odnosu na prisustvo pre- DM i DM kod bolesnika lečenih primarnom perkutanom koronarnom intervencijom (pPKI). Metode: Kod 103 konsekutivna bolesnika sa prvim pred- njim STEMI, hs-CRP i ox-LDL mereni su pre pPCI, drugog i sedmog dana nakon pPKI. Rezultati: Bolesnici su podeljeni u tri grupe: nedijabetičari, predijabetičari i dijabetičari. U svakoj grupi maksimalna koncentracija ox-LDL bila je na prijemu, smanjivala se drugog dana i postizala najniže vrednosti sedmog dana (p<0,001). Dijabetičari su uvek imali najviše vrednosti ох- LDL u poređenju sa predijabetičarima i nedijabetičarima (na prijemu: p=0,028, drugog dana: p=0,056 i sedmog dana: p=0,004). Koncentracija hs-CRP je u svakoj grupi rasla od prijema, postizala maksimalne vrednosti drugog dana i smanjivala se sedmog dana (p<0,001). Značajna razlika u koncentraciji hs-CRP između nedijabetičara i predijabetičara registrovana je na prijemu (p=0,018) i dru- gog dana (p=0,026). U multivarijantnoj analizi DM je bio nezavisan prediktor visokih koncentracija ox-LDL. I ox-LDL i hs-CRP su značajno korelisali sa Killip klasom, ejekcionom frakcijom leve komore, koncentracijom NT-proBNP i mak- simalnom vrednošču troponina I. Zaključak: Kod bolesnika sa prvim STEMI lečenim pPKI postojale su značajne razlike u koncentraciji ox-LDL i hs- CRP između nedijabetičara, predijabetičara i dijabetičara. Koncentracije ox-LDL i hs-CRP značajno su korelisale sa parametrima srčane insuficijencije.

D. Trifunovic, J. Marinković, B. Beleslin, M. Ostojić

A. Gershlick, C. Westerhout, P. Armstrong, K. Huber, S. Halvorsen, P. Steg, M. Ostojić, P. Goldstein et al.

krvni sudovi, S. I. K. Sudovi, Glavni urednik, M. Ostojić, M. Nedeljković, R. Babic, M. Ilić, L. Davidovic et al.

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