The incremental value of myocardial viability, evaluated by 18F-fluorodeoxyglucose positron emission tomography, and cardiovascular magnetic resonance for mortality prediction in patients with previous myocardial infarction and symptomatic heart failure.

OBJECTIVES: To find the imaging mortality predictors in patients with previous myocardial infarction (MI), symptomatic heart failure (HF), and reduced left ventricle (LV) ejection fraction (EF). METHODS: for the study 39 patients were selected prospectively with prior MI, symptomatic HF, and LVEF ≤40%. All patients underwent transthoracic echocardiography (TTE), single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI), 18F-FDG positron emission tomography (FDG PET). 31 patients underwent cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE). Patients were divided into two groups: 1 group - cardiac death; 2 group - no cardiac death. Myocardial scars were assessed on a 5-point-scale. Follow-up data was obtained. RESULTS: Imaging features disclosed significant difference (p < 0.05) of defect score (CMR and SPECT-PET), LV end-diastolic diameter (EDD) (TTE), LVEDD index (CMR), LV global longitudinal strain (CMR) and LV global circumferential strain (CMR) between the groups. Predictors of cardiac death were: LVEDD index (TTE) and LV global longitudinal strain. The cut-off values to predict cardiac death were: defect score (CMR) 25 (AUC, 79.5%; OR 1.8, 95% CI 1.2-2.7), SPECT-PET defect score 22 (AUC, 73.9%; OR 0.5, 95% CI 0.3-0.7), LVEDD (TTE) 58 mm (AUC, 88.4%; OR 23.6, 95% CI 2.6-217.7), LVEDDi 30 mm/m2 (TTE) (AUC, 73.6%; OR 22.0, 95% CI 1.9-251.5), LVEDDi 33.6 mm/m2 (CMR) (AUC, 73.6%; OR 22.0, 95% CI 1.9-251.5), LV global longitudinal strain -13.4 (AUC, 87.8%; OR 2.1, 95% CI 1.2-3.7) and LV global circumferential strain -16.3 (AUC, 76.1%; OR 1.9, 95% CI 1.2-3.0). CONCLUSIONS: Imaging features, such as defect score (CMR) >25, SPECT-PET defect score >22, LVEDD (TTE) >58 mm, LVEDDi (TTE) >30 mm/m2, LVEDDi (CMR) >33.6 mm/m2, LV global longitudinal strain -13.4 and LV global circumferential strain -16.3, may increase sensitivity and specificity of FDG PET and LGE CMR predicting of late mortality.

Value of myocardial deformation parameters for detecting significant coronary artery disease.

Introduction: The study aimed to evaluate the diagnostic value of global and regional myocardial deformation parameters derived from two-dimensional speckle-tracking echocardiography to detect functionally significant coronary artery stenosis. Methods: Dobutamine stress echocardiography and cardiac magnetic resonance myocardial perfusion imaging (CMR-MPI) were performed on 145 patients with a moderate and high probability of coronary artery disease (CAD) and LVEF≥55%. Significant CAD was defined as>50% stenosis of the left main stem,>70% stenosis in a major coronary vessel, or in the presence of intermediate stenosis (50-69%) validated as hemodynamically significant by CMRMPI. Patients were divided in two groups: non-pathological (48.3%) vs pathological (51.7%), according to CAG and CMR-MPI results. Afterwards, off-line speckle-tracking analysis was performed to analyse myocardial deformation parameters. Results: There were no differences in myocardial deformation parameters at rest between groups, except global longitudinal strain (GLS) and global radial strain (GRS) were significantly lower in the CAD (+) group: -21.3±2.2 vs.-16.3±2.3 (P<0.001) and 39.7±23.2 vs. 24.5±15.8 (P<0.001). GLS and regional longitudinal strain rate (SR) had the highest diagnostic value at high dobutamine dose with AUC of 0.902 and 0.878, respectively. At early recovery, GLS was also found to be the best myocardial deformation parameter with a sensitivity of 78%, specificity 67%, AUC 0.824. Conclusion: Global and regional myocardial deformation parameters are highly sensitive and specific in detecting functionally significant CAD. The combination of deformation parameters and WMA provides an incremental diagnostic value for patients with a moderate and high probability of CAD, especially the combination with regional longitudinal SR.

Blood direct PCR: impact of CYP2C19 and CYP4F2 variants for bleeding prediction in ST-elevation myocardial infarction patients with ticagrelor.

Aims: The goals of this study were to develop a new technique that could pave the way for a quicker determination of CYP4F2 rs3093135 and CYP2C19 rs4244285 variants directly from a patient's blood and to attempt to apply this technique in clinical practice. Patients & methods: The study included 144 consecutive patients admitted with ST elevation myocardial infarction. A blood-direct PCR and real-time PCR were used to detect variants of interest. Results & conclusion: Patients with bleeding events had the CYP2C19 GG (*1*1) variant more frequently than patients without bleeding events. The CYP4F2 TT variant was more frequently detected in patients with bleeding events 3 months after hospitalization.

Ticagrelor is one of the main antiplatelet drugs used for prevention of coronary blood clots after interventional procedures in patients with acute coronary syndromes. It has previously been shown that gene variants of CYP2C19 and CYP4F2 may affect antiplatelet therapy. This paper reports a novel instrument and the results of genetic tests obtained using this instrument. Our instrument can detect variants of the genes associated with ticagrelor antiplatelet therapy in only 40 min. These findings might facilitate individualized treatment with ticagrelor of patients with ST-elevation myocardial infarction.

Importance of Thyroid Hormone level and Genetic Variations in Deiodinases for Patients after Acute Myocardial Infarction: A Longitudinal Observational Study.

This study aimed to examine the influence of thyroid hormone (TH) levels and genetic polymorphisms of deiodinases on long-term outcomes after acute myocardial infarction (AMI). In total, 290 patients who have experienced AMI were evaluated for demographic, clinical characteristics, risk factors, TH and NT-pro-BNP. Polymorphisms of TH related genes were included deiodinase 1 (DIO1) (rs11206244-C/T, rs12095080-A/G, rs2235544-A/C), deiodinase 2 (DIO2) (rs225015-G/A, rs225014-T/C) and deiodinase 3 (DIO3) (rs945006-T/G). Both all-cause and cardiac mortality was considered key outcomes. Cox regression model showed that NT-pro-BNP (HR = 2.11; 95% CI = 1.18- 3.78; p = 0.012), the first quartile of fT3, and DIO1 gene rs12095080 were independent predictors of cardiac-related mortality (HR = 1.74; 95% CI = 1.04-2.91; p = 0.034). The DIO1 gene rs12095080 AG genotype (OR = 3.97; 95% CI = 1.45-10.89; p = 0.005) increased the risk for cardiac mortality. Lower fT3 levels and the DIO1 gene rs12095080 are both associated with cardiac-related mortality after AMI.

The association of matrix metalloproteinases polymorphisms and interleukins in advanced age-related macular degeneration.

PURPOSE: To assess the impact of matrix metalloproteinase (MMP)1-1607 1G/2G (rs1799750), MMP7-181 A/G (rs11568818) single-nucleotide polymorphism and systemic cytokins interleukin-1 beta (IL-1ß), IL-6 levels on the development of exudative age-related macular degeneration (eAMD) Methodology: The study group comprised 282 patients with eAMD, and the control group enrolled 379 randomly selected persons. The genotyping of MMP1-1607 (rs1799750) and MMP7-181 (rs11568818) was performed by using the polymerase chain reaction-based restriction fragment length polymorphism method. To determine IL-1ß and IL-6 serum levels, the immunoenzymatic method with monoclonal antibodies coated plates was performed. RESULTS: MMP1 rs1799750 1G/2G genotype was more frequently found in the development of eAMD. It was associated with a 4.3-fold increased risk for eAMD under the codominant model and a 4.9-fold increased risk for eAMD under the overdominant model. The effect was more pronounced at the age of less than 65 years. IL-1ß concentration was significantly higher for MMP1 rs1799750 1G/1G genotype and MMP7 rs11568818 A/G genotype in eAMD patients compared with control group subjects. CONCLUSIONS: MMP1 rs1799750 1G/2G genotype was found to play a significant role in the development of eAMD at the age of less than 65 years. IL-1ß concentration was significantly higher in eAMD patients for MMP1 rs1799750 1G/1G genotype and MMP7 rs11568818 A/G genotype compared with control group subjects.

Association of the genetic and traditional risk factors of ischaemic heart disease with STEMI and NSTEMI development.

INTRODUCTION: To evaluate the influence of traditional risk factors of ischaemic heart disease and genetic factors to predict different types of acute coronary syndromes. MATERIALS AND METHODS: Five hundred and twenty-three patients with acute coronary syndromes (393 with ST elevation myocardial infarction (STEMI) and 130 with non-ST elevation myocardial infarction (NSTEMI)) comprised the study group. The control group consisted of 645 subjects free from symptoms of ischaemic heart disease and stroke. Genetic polymorphisms of MMP-2 (-735) C/T, MMP-2 (-1306) C/T, MMP-3 (-1171) 5A/6A, MMP-9 (-1562) C/T and ACE I/D were evaluated using polymerase chain reaction. RESULTS: Patients with acute coronary syndromes more often had ID or II genotype than DD genotype of ACE ( P = 0.04) and 5A5A or 5A6A genotype than 6A6A genotype of MMP-3 ( P = 0.02) in comparison to the control group. The genotypes of other matrix metalloproteinase genes did not differ between the groups. 5A5A and 5A6A genotypes of MMP-3 (odds ratio (OR) 1.5; P = 0.021), II and ID genotypes of ACE (OR 1.7; P = 0.006) along with traditional ischaemic heart disease risk factors such as smoking (OR 4.9; P = 0.001), hypertension (OR 2.0; P = 0.001), diabetes mellitus (OR 2.9; P = 0.001) and dyslipidaemia (OR 2.1; P = 0.001) increased the risk of STEMI. However, the polymorphism of MMP-3 5A/6A and ACE I/D was not associated with the occurrence of NSTEMI. CONCLUSIONS: Genetic polymorphisms of MMP-3 5A/6A and ACE I/D along with conventional ischaemic heart disease risk factors increase the risk of the occurrence of STEMI, while having no influence on the pathogenesis of NSTEMI.

Primary percutaneous coronary intervention in octogenarians.

BACKGROUND: Limited data are available on the outcome of primary percutaneous coronary intervention (PCI) in octogenarian patients, as the elderly are under-represented in randomized trials. This study aims to provide insights on clinical characteristics, management and outcome of the elderly and very elderly presenting with STEMI. METHODS: 2225 STEMI patients ≥70years old (mean age 76.8±5.1years and 53.8% men) were admitted into the network of the ISACS-TC registry. Of these patients, 72.8% were ≥70 to 79years old (elderly) and 27.2% were ≥80years old (very-elderly). The primary end-point was 30-day mortality. RESULTS: Thirty-day mortality rates were 13.4% in the elderly and 23.9% in the very-elderly. Primary PCI decreased the unadjusted risk of death both in the elderly (OR: 0.32, 95% CI: 0.24-0.43) and very-elderly patients (OR: 0.45, 95% CI 0.30-0.68), without significant difference between groups. In the very-elderly hypertension and Killip class ≥2 were the only independent factors associated with mortality; whereas in the elderly female gender, prior stroke, chronic kidney disease and Killip class ≥2 were all factors independently associated with mortality. Factors associated with the lack of use of reperfusion were female gender and atypical chest pain in the very-elderly and in the elderly; in the elderly, however, there were some more factors, namely: history of diabetes, current smoking, prior stroke, Killip class ≥2 and history chronic kidney disease. CONCLUSIONS: Age is relevant in the prognosis of STEMI, but its importance should not be considered secondary to other major clinical factors. Primary PCI appears to have beneficial effects in the octogenarian STEMI patients.

Invasive versus conservative strategy in acute coronary syndromes: The paradox in women's outcomes.

BACKGROUND: We explored benefits and risks of an early invasive compared with a conservative strategy in women versus men after non-ST elevation acute coronary syndromes (NSTE-ACS) using the ISACS-TC database. METHODS: From October 2010 to May 2014, 4145 patients were diagnosed as having a NSTE-ACS. We excluded 258 patients managed with coronary bypass surgery. Of the remaining 3887 patients, 1737 underwent PCI (26% women). The primary endpoint was the composite of 30-day mortality and severe left ventricular dysfunction defined as an ejection fraction <40% at discharge. RESULTS: Women were older and more likely to exhibit more risk factors and Killip Class ≥2 at admission as compared with men. In patients who underwent PCI, peri-procedural myocardial injury was not different among sexes (3.1% vs. 3.2%). Women undergoing PCI experienced higher rates of the composite endpoint (8.9% vs. 4.9%, p=0.002) and 30-day mortality (4.4% vs. 2.0%, p=0.008) compared with men, whereas those who managed with only routine medical therapy (RMT) did not show any sex difference in outcomes. In multivariable analysis, female sex was associated with favorable outcomes (adjusted HR for the composite endpoint: 0.72, 95% CI: 0.58-0.91) in patients managed with RMT, but not in those undergoing PCI (adjusted HR: 0.96, 95% CI: 0.61-1.52). CONCLUSIONS: We observed a more favorable outcome in women than men when patients were managed with RMT. Women and men undergoing PCI have similar outcomes. These data suggest caution in extrapolating the results from men to women in an overall population of patients in the context of different therapeutic strategies.

Factors associated with use of percutaneous coronary intervention among elderly patients presenting with ST segment elevation acute myocardial infarction (STEMI): Results from the ISACS-TC registry.

BACKGROUND: A substantial proportion of elderly with ST segment elevation myocardial infarction (STEMI) do not undergo percutaneous coronary intervention (PCI). We sought to investigate factors associated with the decision not to perform coronary angiography at admission in these patients. METHODS: We evaluated 1315 STEMI patients aged ≥75years old enrolled in the International Survey of Acute Coronary Syndromes in Transitional Countries (ISACS TC) registry between October 2010 and February 2015. They were compared with 6667 patients aged <75years old enrolled in the registry in the same time frame. RESULTS: Elderly patients were less likely to undertake invasive coronary evaluation compared with younger patients (62.1% vs. 78.9; p<0.001%). In the older group there were a lower proportion of patients presenting <12h after symptom onset (66.5% vs.76.9%, p<0.001), and a higher prevalence of comorbidities. Few elderly were treated with current recommended evidence based treatments (aspirin, clopidogrel, heparins, beta-blocker, statins, and ACE-inhibitors). Logistic analysis adjusted for age and sex showed that older age was associated with underuse of coronary angiography (OR 0.46, 95% CI: 0.41-0.53, p<0.001). Clinical factors that were associated with underuse of angiography in patients over 75 were: female sex (OR: 0.77), presence of comorbidities (OR: 0.91), anemia (OR: 0.44) and late hospital admission (OR: 0.89). CONCLUSIONS: In the ISACS-TC, more than one third of the elderly with STEMI did not undergo coronary angiography at admission. Sex, comorbidities, and late hospital admission were independent factors associated with the underuse of PCI in these patients.

Early and late diastolic strain rate vs global longitudinal strain at rest and during dobutamine stress for the assessment of significant coronary artery stenosis in patients with a moderate and high probability of coronary artery disease.

BACKGROUND: The aim of this prospective study was to assess the usefulness of global longitudinal strain (GLS), regional diastolic and systolic strain, strain rate (SR) parameters at rest and during dobutamine stress echocardiography for detecting significant coronary artery stenosis in patients with a moderate or high probability of coronary artery disease (CAD). METHODS: Dobutamine stress echocardiography and adenosine magnetic resonance imaging (AMRI) were performed on 127 patients with a moderate and high probability of CAD and left ventricle ejection fraction ≥55%. CAD was defined as ≥70% diameter stenosis on coronary angiography validated as hemodynamically significant by AMRI. Patients were grouped according to coronary angiography and AMRI results: CAD (-) n=67 (52.8%) vs CAD (+) n=60 (47.2%). RESULTS: There were no significant differences of clinical characteristics, conventional echocardiography, and deformation parameters between the two groups at rest except that GLS was higher in the CAD (-) group (-21.5±2.4% vs -16.2±2.1%, P=.00). GLS at high dobutamine doses had the highest area under the ROC curve (AUC) (AUC 0.955, sensitivity 94%, specificity 92%). Radial late diastolic SR at low doses performed best out of all diastolic parameters with an AUC of 0.789, sensitivity 76.7%, specificity 91.7%. Other deformation parameters including visual assessment were inferior. CONCLUSIONS: Global longitudinal strain is highly sensitive and specific in detecting hemodynamically significant coronary artery stenosis in moderate- to high-risk patients without known CAD. This is the first study showing that GLS is more sensitive and specific compared with early and late diastolic SR parameters or visual assessment in detecting CAD.

N-carboxymethyllysine as a biomarker for coronary artery disease and age-related macular degeneration.

BACKGROUND AND OBJECTIVE: An association between coronary artery disease (CAD) and age-related macular degeneration (ARMD) has long been postulated, but exact mechanisms remain unclear. The global prevalence of CAD and ARMD increases and early biomarkers for early diagnosis of these diseases are necessary. The aim of this study was to investigate the plasma level of oxidative stress biomarker CML in patients with and without angiographic findings of atherosclerosis in the coronary arteries (CADath+ and CADath-, respectively) and to assess if there was an association of CAD with ARMD. MATERIALS AND METHODS: The study enrolled 233 subjects. Based on cardiologic and ophthalmologic examinations, the patients were divided into four subgroups: CADath+ARMD+, CADath+ARMD-, CADath-ARMD+, and CADath-ARMD-. The enzyme-linked immunosorbent assay was used for the measurement of plasma CML levels. Serum lipid levels were determined by an automatic analyzer using conventional enzymatic methods. RESULTS: CADath+ patients had higher CML concentration compared to CADath- subjects (1.04±0.6 vs. 0.83±0.4ng/mL, P<0.001). The highest mean CML level (1.12±0.7ng/mL) was found in CADath+ARMD+ patients. The mean plasma CML concentration was higher in subjects with any of the analyzed diseases compared to CADath-ARMD- subjects. A significant positive association of CADath+ (OR=2.50, 95% CI 1.60-3.90, P=0.0001), ARMD (OR=2.08, 95% CI 1.40-3.11, P=0.0001) and both analyzed diseases (OR=4.67, 95% CI 2.29-9.53, P=0.0001) with an increased level of plasma CML in a logistic regression model adjusting by age was identified. CONCLUSIONS: The level of CML, an oxidative stress biomarker, reflects the presence of atherosclerosis in coronary arteries and shows a possible link between ARMD and CADath+ via oxidative status.

Comparison of Early Versus Delayed Oral ß Blockers in Acute Coronary Syndromes and Effect on Outcomes.

The aim of this study was to determine if earlier administration of oral ß â€‹blocker therapy in patients with acute coronary syndromes (ACSs) is associated with an increased short-term survival rate and improved left ventricular (LV) function. We studied 11,581 patients enrolled in the International Survey of Acute Coronary Syndromes in Transitional Countries registry from January 2010 to June 2014. Of these patients, 6,117 were excluded as they received intravenous ß blockers or remained free of any ß â€‹blocker treatment during hospital stay, 23 as timing of oral ß â€‹blocker administration was unknown, and 182 patients because they died before oral ß blockers could be given. The final study population comprised 5,259 patients. The primary outcome was the incidence of in-hospital mortality. The secondary outcome was the incidence of severe LV dysfunction defined as an ejection fraction <40% at hospital discharge. Oral ß blockers were administered soon (≤24 hours) after hospital admission in 1,377 patients and later (>24 hours) during hospital stay in the remaining 3,882 patients. Early ß â€‹blocker therapy was significantly associated with reduced in-hospital mortality (odds ratio 0.41, 95% CI 0.21 to 0.80) and reduced incidence of severe LV dysfunction (odds ratio 0.57, 95% CI 0.42 to 0.78). Significant mortality benefits with early ß â€‹blocker therapy disappeared when patients with Killip class III/IV were included as dummy variables. The results were confirmed by propensity score-matched analyses. In conclusion, in patients with ACSs, earlier administration of oral ß â€‹blocker therapy should be a priority with a greater probability of improving LV function and in-hospital survival rate. Patients presenting with acute pulmonary edema or cardiogenic shock should be excluded from this early treatment regimen.

Reperfusion therapy for ST-elevation acute myocardial infarction in Eastern Europe: the ISACS-TC registry.

AIMS: Widespread availability of tertiary hospitals with catheterization facilities, although vigorously promoted, has yet to become a reality in many countries with economy in transition. We sought to evaluate the clinical profile and mortality of patients who were hospitalized with a diagnosis of ST-segment elevation myocardial infarction (STEMI) and either received reperfusion therapy or remained without reperfusion in Eastern Europe. METHODS AND RESULTS: Data were obtained from the International Survey of Acute Coronary Syndromes in Transitional Countries (ISACS-TC; NCT01218776) on STEMI patients admitted to 57 hospitals in Eastern European countries from January 2010 to February 2015. The primary endpoint was 30-day mortality. Of 7982 patients, 65 (0.8%) had a documented contraindication to reperfusion, 5973 (75.5%) received fibrinolysis ( n = 1032) or underwent primary percutaneous coronary intervention (p-PCI; n = 4941), and 1944 patients (24.6%) did not receive any reperfusion therapy. The overall unadjusted 30-day mortality rate was 7.9%. Thirty-day mortality rates were higher in non-reperfusion patients (16.0 vs. 5.0% in the p-PCI group and 7.4% in fibrinolysis group). The strongest factors associated with not attempting reperfusion therapy among these patients were female sex (OR 1.29 CI 1.07-1.56), age (OR 1.02; CI 1.01-1.03), prior MI (OR 1.79; CI 1.38-2.32), prior cerebrovascular events (OR 1.87; CI 1.30-2.68), chronic kidney disease (OR 1.76; CI 1.22-2.53), Killip class >1 (OR 1.31; CI 1.06-1.62), and time to admission >12 h (OR 15.9; CI 13.1-19.3). CONCLUSIONS: A substantial number of patients are still not offered any reperfusion therapy in many Eastern European countries with economy in transition, and this was associated with increased 30-day mortality. Time from symptoms onset to admission >12 h was the highest ranking among factors related to lack of reperfusion therapy. Quality improvement efforts should focus on minimizing delay to hospital admission among STEMI patients.

Role of MMP-2 (-1306 C/T) Polymorphism in Age-Related Macular Degeneration.

PURPOSE: To determine if the frequency of the MMP-2 (-1306 C/T) genotype has an influence on the development of early age-related macular degeneration (AMD). METHODOLOGY: The study enrolled 387 patients with early AMD and a random sample of 682 healthy persons (control group). The genotyping of MMP-2 (-1306 C/T) was carried out using the real-time polymerase chain reaction method. RESULTS: The analysis of the MMP-2 (-1306 C/T) gene polymorphism did not reveal any differences in the genotype distribution between the patients with AMD and the control subjects. When the study population was divided into age groups, the C/C genotype was more prevalent in the AMD patients aged <65 years than those aged ≥65 years (65.19% versus 53.88%, p = 0.0294), and the C/T genotype was more frequent in the AMD patients aged ≥65 years when compared with the AMD patients aged <65 years (40.78% versus 26.52%, p = 0.0037). Moreover, in the female group younger than 65 years, the frequency of the C/C genotype was greater in the AMD group than the control group (75% versus 58.91%, p = 0.0232). CONCLUSIONS: This study showed a significantly greater prevalence of the C/C and C/T genotypes in the patients with AMD younger than 65 years and those aged ≥65 years, respectively. Moreover, the AMD women aged <65 years were the carriers of the C/C genotype significantly more frequently than their control counterparts.

Effect of clinical factors and gene polymorphism of CYP2C19*2, *17 and CYP4F2*3 on early stent thrombosis.

AIM: To determine the main clinical and genetic factors having impact on early coronary stent thrombosis. MATERIALS & METHODS: Genotyping of CYP2C19*2, *17 and CYP4F2*3 in patients with (n = 31) and without stent thrombosis (n = 456) was performed. Clinical and genetic data were analyzed by binary logistic regression. RESULTS: Smoking (OR: 0.317; 95% CI: 0.131-0.767), high-density lipoprotein level in mmol/l (OR: 0.142; 95% CI: 0.040-0.506), CYP2C19*2*2 versus *1*1 and *1*2 genotype (OR: 11.625; 95% CI: 3.498-38.633), CYP4F2 AA versus GA and GG genotype (OR: 3.532; 95% CI: 1.153-10.822) were associated with early stent thrombosis. CONCLUSION: For the first time we have identified a clinically important polymorphism (CYP4F2 G1347A) that was independently associated with early stent thrombosis. Original submitted 18 August 2014; Revision submitted 10 November 2014.

The Role of Matrix Metalloproteinases Polymorphisms in Age-Related Macular Degeneration.

BACKGROUND: Matrix metalloproteinases (MMP) are responsible for the degradation of extracellular matrix components and play an important role in the physiological and pathological remodeling of tissues. PURPOSE: To assess the impact of MMP-2 Rs2285053 (C->T), MMP-3 Rs3025039 (5A->6A), and MMP-9 Rs3918242 (C->T) single nucleotide polymorphism on the development of early age-related macular degeneration (AMD). METHODS: The study group comprised 148 patients with AMD, and the control group enrolled 526 randomly selected persons. The genotyping of MMP-3 Rs3025039, MMP-2 Rs2285053, and MMP-9 Rs3918242 was performed by using the real-time PCR method. RESULTS: The frequency of the MMP-2 (-735) C/T and MMP-3 (-1171) 5A/6A genotypes did not differ significantly between the patients with AMD and the control group, while the MMP-9 (-1562) C/C genotype was more frequently detected in patients with AMD than the control group (73.7% vs. 64.6%, p=0.048). Logistic regression analysis showed that the MMP-9 (-1562) C/C genotype increased the likelihood of developing early AMD (OR=1.51, 95% CI: 1.01-2.21; p=0.046). After the subdivision into the groups by age, a significant difference only in the frequency of the MMP-9 (-1562) C/C genotype was found comparing the AMD patients and the control group younger than 65 years (79.7% vs. 66.4%, p=0.039). CONCLUSIONS: Only MMP-9 Rs3918242 (C->T) single nucleotide polymorphism was found to play a significant role in the development of AMD, and the effect was more pronounced at the age of less than 65 years.

Prevalence of high-risk profile in middle-aged subjects with arterial hypertension: a nationwide survey.

Hypertension is the most common non-communicable disease and the leading cause of cardiovascular disease in the world. It presents an important public health challenge in both economically developed and developing countries. In 2006, the Lithuanian High Cardiovascular Risk programme was launched. The programme recruited men aged 40-54 and women aged 50-64 without overt cardiovascular disease. We analysed a group of 23,204 subjects included in the programme at the primary level. Arterial hypertension was present in 57.6% of the subjects: 63.2% in the females and 49.2% in the males. In the hypertensive middle-aged subjects, grade 1 hypertension was present in 53.1%, grade 2 in 22.4%, and grade 3 in merely 5.9% of the subjects. The prevalence of a minimum of three concomitant risk factors among the hypertensive patients was 78.0%, compared with 52.1% in the patients without hypertension (p < 0.001). Blood pressure goals were attained in 20.8% of the hypertensive women and in 14.4% of the hypertensive men. In Lithuania, a high prevalence of hypertension was characteristic of middle-aged subjects. Although the blood pressure elevation had not reached high levels, the presence of at least three risk factors concomitant to hypertension was more expressed in them compared with the non-hypertensive subjects.

The role of clinical parameters and of CYP2C19 G681 and CYP4F2 G1347A polymorphisms on platelet reactivity during dual antiplatelet therapy.

Dual antiplatelet therapy with aspirin and clopidogrel is used to lower the risk of arterial thrombosis. However, this strategy is not always successful owing to high interindividual variability in response to antiplatelet therapy. To evaluate an impact of CYP2C19 G681A and CYP4F2 G1347A polymorphisms and clinical factors on dual antiplatelet effect of clopidogrel and aspirin. Totally 89 patients who continued dual aspirin and clopidogrel antiplatelet therapy for at least of 14 days were included into the further study. Test for platelet aggregation was performed according to the classical Born method. Genotyping of CYP2C19*2 and CYP2C19*3 and CYP4F2*3 was done by using commercial probes from Applied Biosystems (UK). Patient age, weight and body weight index did not correlate significantly with platelet aggregation level both induced by ADP and epinephrine (P > 0.05). Serum concentration of creatinine, diabetes, angiotensin II receptor blockers, B-blockers, statin or omeprazole use had no significant effect on platelet aggregation. The users of angiotensin-converting enzyme inhibitors had lower platelet aggregation levels with epinephrine vs. nonusers: 28.80 ±â€Š13.25 vs. 51.15 ±â€Š23.50, P < 0.03, respectively. Platelet aggregation with ADP was higher in CYP2C19*1*2 genotype carriers than in CYP2C19*1*1 carriers (P = 0.01). Platelet aggregation with epinephrine was higher in CYP4F2 GA genotype carriers than in GG (P = 0.04) or AA (P = 0.01) carriers. Our study confirms that CYP2C19 G681A genotype has an impact on antiplatelet effect of clopidogrel. The novelty is that the platelet aggregation after induction with epinephrine is influenced by CYP4F2 G1347A genotype.

Association of major cardiovascular risk factors with the development of acute coronary syndrome in Lithuania.

Cardiovascular (CV) disease remains the leading cause of death in Lithuania. Timely recognition of CV risk factors and intervention to reduce these risk factors is of absolute importance to prevent coronary heart disease and reduce its burden on society. This study aimed to compare the prevalence of major CV risk factors in general population and acute coronary syndrome (ACS) patients and to determine their association with the development of ACS. Five hundred and twenty-three ACS patients and 645 age- and gender-matched control subjects were enrolled in the study. Smoking, dyslipidaemia, diabetes, and hypertension, but not overweight or obesity, were significantly more prevalent in the ACS patients, compared with control group. The prevalence of smoking, overweight or obesity, and dyslipidaemia were significantly higher in younger patients. Hypertension was highly prevalent in all age subgroups. More than a half of all patients aged <45 years had three or four CV risk factors. Smoking [odds ratio (OR), 7.03, P < 0.0001], hypertension (OR, 1.82; P = 0.001), dyslipidaemia (OR, 1.99; P < 0.0001), and diabetes (OR, 2.30; P < 0.001) were significantly associated with ACS. Significant association of traditional CV risk factors, such as smoking, dyslipidaemia, hypertension, and diabetes with ACS, and high prevalence of these risk factors, especially in younger individuals, calls for attention, and implementation of prevention programmes to reduce the burden of CV morbidity and mortality in Lithuania.

Left ventricular remodelling after acute myocardial infarction: impact of clinical, echocardiographic parameters and polymorphism of angiotensinogen gene.

INTRODUCTION: The development of left ventricular remodelling after acute myocardial infarction is a predictor of heart failure and mortality. The purpose of the present study was to assess whether the polymorphism of angiotensinogen (AGT) gene with threonine (T) instead of methionine (M) at amino acid 235 in exon 2 (M235T) had effects on cardiac remodelling after acute myocardial infarction. METHODS: One hundred and forty-one patients (mean age 56.4±11.1 years) with a first acute myocardial infarction were enrolled. Within 24-72 hours of the onset of the symptoms and at a four month period two-dimensional echocardiography was performed. Remodelling was defined as a 20% increase from the baseline in left ventricular end-diastolic volume. The genotypes of the study group were compared with the reference group (n=1010) genotypes. AGT M235T polymorphism was determined using polymerase chain reaction amplification. RESULTS: At follow-up, 49 patients (34.7%) were classified as having left ventricular remodelling. Anterior localization of the infarct (p=0.008), leucocyte count at admission (p=0.040), global left ventricular longitudinal strain (p=0.021) and MM genotype of AGT (p=0.024) were independent predictors of ventricular remodelling after myocardial infarction. CONCLUSIONS: Anterior wall infarction, increased leucocyte count, decreased longitudinal strain of left ventricular and polymorphism of AGT M235T may predict remodelling after myocardial infarction.