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.

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.

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 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.

[Low density lipoprotein apheresis]. / Mazo tankio lipoproteinu afereze.

Increased blood cholesterol concentration is one of the main factors in ischemic heart disease, development of which is determined by atherosclerotic changes in coronary vessels. Diet and treatment with 3-hydroxi-3-metilglutaril coenzyme A (HMG-CoA) reductase inhibitors helps to reduce low density lipoprotein cholesterol (LDL-Ch) blood concentration up to recommended level of 3.0 mmol/l in most patients but in some patients particularly with familial dyslipidemias cholesterol concentration remains increased even after treatment with maximal doses of lipid-regulating agents or their combinations. The most frequently used mechanical methods of cholesterol removal from blood include the procedures of extracorporeal apheresis. Low density lipoprotein (LDL) apheresis not only significantly reduces the blood concentrations of total cholesterol (TCh), and LDL-Ch, lipoprotein (a) (Lp(a) and fibrinogen but also stops the progression of atherosclerosis in coronary vessels.