Beta-Blockers and Hypertension: Some Questions and Answers.

INTRODUCTION: International guidelines have removed b-blockers from first-line treatment of hypertension, limiting their use to patients with compelling indications. The position of guidelines stems from the results of studies performed with the 1st and 2nd generation of b-blockers, which concluded that these drugs have lower cardiovascular protection, compared with other antihypertensive agents. AIM: The aim of our mini review is to answer to some questions about the effect of b-blockers on hypertension and cardiovascular protection and if these effects are different from those of other antihypertensive drugs, particularly in young and elderly patients. METHODS: We evaluated the relevant systematic reviews and meta-analyses, which reported the effectiveness of b-blockers on blood pressure and cardiovascular outcomes, compared with placebo/no treatment and with other antihypertensive agents. RESULTS: Beta-blockers, decreased high blood pressure with no significant difference from other common antihypertensive agents. Moreover b-blockers, compared with placebo, lowered the risk of major cardiovascular outcomes, while, compared with other drug classes, the reported results are very heterogeneous. Therefore it is difficult, globally, to find a difference between b-blockers and other drug classes. CONCLUSIONS: Rather than looking for differences in the cardiovascular protective effect between b-blockers and other antihypertensive agents, we have to consider the different pathophysiology of hypertension in young [sympathetic hyperactivity] and elderly patients [arterial stiffness, high aortic systolic pressure]. Considering these aspects, non-vasodilating b-blockers are preferred, as first-line, in young/middle aged hypertensive subjects, while vasodilating b-blockers, are most appropriate, in elderly patients, for the favourable hemodynamic profile.

Do Statins Counteract the Effect of Antidiabetic Drugs? Results of the SCEAD Study.

PURPOSE: Diabetes and dyslipidemia are leading causes of mortality and morbidity. According to international guidelines, statins are the cornerstone of treatment in patients with diabetes and/or dyslipidemia. However, statins and antidiabetic agents have opposite pharmacological effects, because statins, particularly atorvastatin and rosuvastatin, impair glucose homeostasis, increasing the risk of new-onset diabetes, whereas antidiabetic drugs improve glycemic homeostasis. The aim of this study was to investigate the effect of atorvastatin, rosuvastatin, and pitavastatin on glucose homeostasis in patients with type 2 diabetes mellitus (T2DM) and dyslipidemia during stable treatment with hypoglycemic drugs. MATERIALS AND METHODS: The study was conducted as a pilot, prospective, randomized, open label, parallel group with blinded-endpoints (PROBE) study. Of 180 recruited patients with T2DM and dyslipidemia, 131 were randomized to atorvastatin (n=44), rosuvastatin (n=45), and pitavastatin (n=42) and treated for 6 months. RESULTS: Fasting plasma glucose (FPG) marginally decreased in patients assigned to atorvastatin (-3.5 mg/dL, p=0.42) and rosuvastatin (-6.5 mg/dL, p=0.17), while it decreased much more in patients treated with pitavastatin (-19.0 mg/dL, p<0.001). Mean glycated hemoglobin A1c (HbA1c ) values remained unchanged during treatment with atorvastatin (-0.10%, p=0.53) and rosuvastatin (0.20%, p=0.40), but were significantly reduced with pitavastatin (-0.75%, p=0.01). Atorvastatin, rosuvastatin, and pitavastatin significantly lowered (p<0.001) plasma levels of total cholesterol, low-density lipoprotein-cholesterol, and triglycerides, while high-density lipoprotein-cholesterol (HDL-C) levels increased significantly (p=0.04) only in the pitavastatin group. CONCLUSION: The results of the present study suggest that pitavastatin affects FPG and HbA1c less than atorvastatin and rosuvastatin in patients with T2DM and concomitant dyslipidemia. Lipid-lowering efficacies were not significantly different among the three statins, with the exception of HDL-C, which increased significantly with pitavastatin. Although the pharmacological mechanism of pitavastatin on glucose homeostasis in patients with T2DM during stable antidiabetic therapy is not known, it can be assumed that pitavastatin has less drug interaction with hypoglycemic agents or that it increases plasma levels of adiponectin.

[The evaluation of hypertensive patients who are supposedly under control according to office blood pressure measurements with ambulatuar blood pressure monitoring: an observational prospective study in three big cities (AKB3IL study)]. / Ofis ölçümleri ile kan basincinin kontrol altinda oldugu düsünülen hipertansiyonlu hastalarin ambulatuvar kan basinci monitörizasyonu ile degerlendirilmesi: Üç büyük ilde ileriye dönük gözlem çalismasi (AKB3IL çalismasi).

OBJECTIVES: The aim of the study is to evaluate hypertensive patients who are supposedly under control according to office blood pressure measurements with 24 hour ambulatuar blood pressure monitoring for determining their actual controlled hypertension rate. In addition, we investigate the adherence ratio of blood pressure measurements to current guidelines. STUDY DESIGN: Nine hundred-forty hypertensive patients supposedly under control according to office blood pressure measurements were enrolled in the study. Twenty-four hour ambulatuar blood pressure monitoring was performed on all of them. RESULTS: Actual controlled hypertension was determined in 617 (65.6%) patients whereas 323 (34.4%) patients had uncontrolled hypertension. The blood pressure measurements that were over threshold values were seen mostly at night and in the early morning during ambulatuar blood pressure monitoring. Nocturnal and early morning hypertension was determined in most of the patients who were supposedly under control according to office blood pressure measurements. This was especially true in patients with high cardiovascular risk such as diabetes mellitus, chronic kidney failure, and metabolic syndrome. CONCLUSION: Efficacy of antihypertensive therapy during 24 hour and the early morning period is essential for optimal risk modification.

Long pentraxin-3 measured at late phase associated with GRACE risk scores in patients with non-ST elevation acute coronary syndrome and coronary stenting.

OBJECTIVES: We analyzed pentraxin 3 (PTX3) levels and the relation of PTX3 levels with GRACE risk scores in 39 patients with non-ST elevation acute coronary syndrome (ACS) and stabile angina after stenting. STUDY DESIGN: Seventeen patients with ACS and 22 patients with stabile angina who underwent coronary stenting were included in the study. PTX3 levels were measured serially at admission, at the 8th hour and at the 24th hour after stenting. RESULTS: While diabetes and hypertension were more frequent in the stabile angina group, leukocyte counts were significantly higher in the ACS group. PTX3 levels measured at the 8th hour were significantly higher in the ACS group compared to the stabile angina group (p=0.003). Strong correlations were observed between 24th hour PTX3 levels and GRACE scores calculated for risk of death and death/MI at admission (in-hospital/to 6 months), and for risk of death/MI at discharge to 6 months (R=0.571, p=0.01, R=0.564, p=0.01; R=0.558, p=0.02, R=0.512, p=0.03; R=0.653, p=0.004, respectively). CONCLUSION: The serum PTX3 levels may provide important information for the early risk stratification of patients with ACS who underwent coronary stenting.

Left atrial appendage function in mitral stenosis: is it determined by cardiac rhythm?

BACKGROUND AND AIM OF THE STUDY: The left atrial appendage (LAA) is a common source of cardiac thrombus formation associated with systemic embolism in patients with mitral stenosis (MS). Low flow velocities in the LAA are important factors in the development of thrombosis. Whilst oral anticoagulant therapy is used routinely in MS with atrial fibrillation (AF), the characteristics of LAA contractile functions and the protective role of oral anticoagulant treatment in patients with MS in sinus rhythm (SR) are unclear. The study aim was to compare LAA contractile functions in patients with MS who were either in SR or had AF. METHODS: The study population comprised 51 patients with MS, who had undergone both standard transthoracic and transesophageal echocardiography. The patients were allocated to two groups, according to the presence of AF or SR. Ten healthy, gender-matched subjects were included in the study as a control group. RESULTS: Except for age, the characteristics of the groups were similar. In patients with SR and AF, the LAA contractile functions were significantly lower than in controls. While the LAA contractile functions of the SR group were significantly lower than the AF group (LAA emptying/filling velocity: 26 +/- 7/24 +/- 8 versus 19 +/- 5/17 +/- 5 cm/s; p = 0.002 and p = 0.001, respectively, LAA maximum/minimum area: 5.4 +/- 1.2/3.2 +/- 0.9 versus 6.2 +/- 1.1/3.7 +/- 0.8 cm2, p = 0.02 and p =0.02, respectively), no statistically significant differences were observed between patients in SR with mitral valve area (MVA) <1.5 cm2 and patients in AF. Four SR patients (13%) and six AF patients (27%) had LAA thrombus. A strong correlation was observed between the MVA and LAA peak emptying/filling velocity in patients with MS in SR (r = 0.739, p = 0.0001 and r = 0.728, p = 0.0001, respectively). CONCLUSION: The study results showed that LAA contractile function is diminished in patients with moderate-severe MS in SR, and to a similar degree as patients in AF. It was concluded that patients with moderate-severe MS in SR have a higher risk for thromboembolic events than MS patients in AF.

A floating thrombus in sinus of valsalva complicated with cardiogenic shock in a patient with plasminogen activator inhibitor 1 4G/5G polymorphism.

Thrombus in sinus of Valsalva is unusual reason for acute myocardial infarction. We demonstrated a case with floating thrombus in sinus of Valsalva obstructing the right coronary ostium intermittently, and causing cardiogenic shock. The patient was diagnosed with multiplane transesophageal echocardiography and treated successfully with surgical removal of mass. A homozygote polymorphism of plasminogen activator inhibitor (PAI) 1 4G/5G was found. This is the first report demonstrating a patient with PAI 1 polymorphism and thrombus of Valsalva complicated with cardiogenic shock.

Angiotensin receptor neprilysin inhibitor for patients with heart failure and reduced ejection fraction: Real-world experience from Turkey (ARNi-TR).

OBJECTIVE: Heart failure (HF) is a growing public health problem with high morbidity and mortality. Recently, angiotensin receptor neprilysin inhibitor (ARNi) has emerged as a promising treatment for HF with reduced ejection fraction (HFrEF). Here, we shared our experience with the use of ARNi in HFrEF from multiple centers in Turkey. METHODS: The ARNi-TR is a multicenter, noninterventional, retrospective, observational study. Overall, 779 patients with HF from 22 centers in Turkey who were prescribed sacubitril/valsartan were examined. Initial clinical status, biochemical and echocardiographic parameters, and New York Heart Association functional class (NYHA-FC) values were compared with follow-up values after 1 year of ARNi use. In addition, the effect of ARNi on number of annual hospitalizations was investigated, and the patients were divided into 2 groups, depending on whether ARNi was initiated at hospitalization or under outpatient clinic control. RESULTS: N-terminal pro-brain natriuretic peptide (NT-proBNP), left-ventricle ejection fraction (LV-EF), and NYHA-FC values improved significantly in both groups (all parameters, p<0.001) within 1-year follow-up. In both groups, a decrease in hemoglobin A1c (HbA1c) values was observed in ARNi use (p<0.001), and a decrease in daily diuretic doses and hospitalizations owing to HF were observed after ARNi use (all comparisons, p<0.001). Hypotension (16.9%) was the most common side effect in patients using ARN. CONCLUSION: The ARNi-TR study offers comprehensive real-life data for patients using ARNi in Turkey. The use of ARNi has shown significant improvements in FC, NT-proBNP, HbA1c levels, and LV-EF. Likewise, reductions in the number of annual hospitalizations and daily furosemide doses for HF were seen in this study.

Prediction of head-up tilt test result: is it possible?

BACKGROUND: The determination of early, accurate, predictive criteria for a positive result would permit a reduction in the duration of the head-up tilt testing (HUTT). Previous studies propounded that existence of early sympathetic overreactivity (rapid and sustained increase in heart rate) during HUTT predicts positive result. However, the exact value of this variable is unknown. We analyzed the early heart rate (HR) responses to HUTT and evaluated their ability to predict HUTT result. METHODS: Consecutive patients referred to the syncope unit of our center for recurrent unexplained syncope were studied. RESULTS: We studied 189 consecutive patients and 67 (35%) patients had a negative HUTT; 122 (65%) patients had a positive HUTT. The early HR increase was defined as the maximum HR during the first 10 minutes of tilting minus the resting HR before tilting. The receiver-operator curves (ROCs) show the overall performance of the HR changes for predicting the HUTT result. For all variables, area under the ROC curve (AUC) was nearly equivalent to 0.50 and early HR increase was not a predictor of the negative result of HUTT (AUC = 0.546). Also there was no any significant correlation between the magnitude of early HR increase and patient age (r =-0.03, P = 0.76). CONCLUSIONS: The results suggest that the early increase in HR during the first 10 minutes of the HUTT may not be a useful parameter for predicting the test result. Many factors, such as late exaggeration in sympathetic activity during HUTT and age-dependent reduction in baroreflex sensitivity, may attenuate the predictive value of early HR increase.

Non ST-segment elevation myocardial infarction in patient with essential thrombocythemia.

A 68-year-old woman presented with acute chest pain and a greatly increased platelet count. Cardiac catheterization revealed subtotal occlusion and a thrombus-like filling defect in the right coronary artery. The patient was successfully treated with intravenous tirofiban. Essential thrombocythemia was diagnosed based on bone marrow findings, clinical presentation and laboratory analysis. The relationship between intracoronary thrombus and essential thrombocythemia is discussed.

Helicobacter pylori seropositivity in patients with acute coronary syndromes.

The aim of this study was to investigate the seroprevalence of Helicobacter pylori (HP) in patients with coronary atherosclerosis and acute coronary syndromes. We enrolled 152 patients (group I, 73 patients with acute coronary syndrome; group II, 79 patients with chronic stable angina) and 22 control subjects. An enzyme-linked immunosorbent assay for immunoglobulin (Ig) G test for HP diagnosis was used on all enrolled subjects. C-reactive protein (CRP) was also measured in all patients as an inflammatory marker. Seropositivity rates for HP were significantly higher in patients with coronary artery disease than in controls (80.2% versus 54.5%; P < 0.05). Although CRP level was significantly higher in group I than in group II (1.72 +/- 2.89 mg/dl versus 0.53 +/- 0.63 mg/dl, P < 0.0001), HP infection rates were similar between groups (86.3% versus 74.6%, P > 0.05). Infection with HP may influence atherogenesis through low-grade, persistent inflammatory stimulation. However, our data show evidence of increased systemic inflammation in patients with acute coronary syndrome, which was unrelated to an increased HP seropositivity.

A Rare Access Site Complication after Transcatheter Aortic Valve Implantation.

In the majority of patients undergoing transcatheter aortic valve implantation, the transfemoral access is the suggested approach due to its less invasive nature and feasibility in patients with suitable vascular anatomy. The complications of the transfemoral access site are generally vascular; however, we herein present a rare case of colon perforation following the transfemoral procedure owing to prior abdominal surgery. A transfemoral aortic valve was inserted on account of severe aortic stenosis and a high probability of surgical mortality. The patient developed acute abdomen following the procedure. Hemicolectomy was performed because of colonic perforation caused by femoral catheterization. The patient was well at 3 months' follow-up.

Effect of monocyte chemoattractant protein-1 (MCP-1) gene polymorphism in Turkish patients with premature coronary artery disease.

OBJECTIVES: It has been suggested that monocyte chemoattractant protein-1 (MCP-1) is important in the initiation of atherosclerosis and crucial in monocyte recruitment into the subendothelial lesions. Recent studies have demonstrated that MCP-1 -2518 A>G polymorphism is associated with susceptibility to coronary artery disease (CAD). Since there are conflicting reports on the possible association of MCP-1 -2518 A>G polymorphism with CAD, we investigated the role of this polymorphism in Turkish patients with premature CAD. MATERIAL AND METHODS: Genomic DNA was collected from 171 premature CAD patients and 151 healthy individuals. MCP-1 -2518 A>G polymorphism was genotyped using the PCR-RFLP method. RESULTS: There were no differences between genotype distribution and allele frequencies in the premature CAD and control groups (AA: 49.7 %; AG: 40.3 %; GG: 10.0 % in premature CAD groups and AA: 53.7 %; AG: 34.4 %; GG: 11.9 % in controls; p = 0.53). The prevalence of the G allele was 0.302 in patients and 0.291 in controls. CONCLUSIONS: Our data demonstrate that MCP-1 -2518 A>G polymorphism is not associated with premature CAD in Turkish patients. Further studies are needed to elucidate the role of this polymorphism in the pathogenesis of CAD in various populations.

No association of interleukin-6 gene polymorphism (-174 G/C) with premature coronary artery disease in a Turkish cohort.

OBJECTIVES: Interleukin-6 (IL-6) may contribute to the inflammatory response by activating endothelial cells and stimulating the synthesis of fibrinogen. It might thus be important in the pathogenesis of inflammation associated with coronary artery disease (CAD). Several studies suggested that the -174 C allele was associated with an increased prevalence of coronary heart disease. The aim of this study was to investigate further the association of the IL-6 -174 G/C allele status with premature CAD. METHODS: A total of 120 patients and 105 controls were included in the study. The IL-6 -174 G/C polymorphism was genotyped using PCR-restriction fragment length polymorphism. RESULTS: The genotype distribution of the -174 G/C polymorphism was not different in premature CAD patients (GG: 53%; GC: 42.6%; CC: 4.3%) and controls (GG: 54.3%; GC: 39%; CC: 6.7%) (P=0.72). The prevalence of the C allele was 25.6% in patients and 26.1% in controls. By multiple regression analysis, family history, smoking, diabetes, and hypertension were independent risk factors of premature CAD, but not IL-6 genotype. CONCLUSIONS: We conclude that the IL-6 -174 G/C polymorphism is not associated with the risk of premature CAD, and does not contribute to cardiovascular risk stratification.

OPERATOR DEPENDENCY OF THE RADIATION EXPOSURE IN CARDIAC INTERVENTIONS: FEASIBILITY OF ULTRA LOW DOSE LEVELS.

INTRODUCTION: Mean radiation exposure in invasive cardiology varies greatly between different centres and interventionists. The International Commission on Radiological Protection and the EURATOM Council stipulate that, despite reference values, 'All medical exposure for radiodiagnostic purposes shall be kept as low as reasonably achievable' (ALARA). The purpose of this study is to establish the effects of the routine application of ALARA principles and to determine operator and procedure impact on radiation exposure in interventional cardiology. MATERIALS AND METHODS: A total of 240 consecutive cardiac interventional procedures were analysed. Five operators performed the procedures, two of whom were working in accordance with ALARA principles (Group 1 operators) with the remaining three working in a standard manner (Group 2 operators). Radiation exposure levels of these two groups were compared. RESULTS: Total fluoroscopy time and the number of radiographic runs were similar between groups. However, dose area product and cumulative dose were significantly lower in Group 1 when compared with Group 2. Radiation levels of Group 1 were far below even the reference levels in the literature, thus representing an ultra-low-dose radiation exposure in interventional cardiology. CONCLUSION: By use of simple radiation reducing techniques, ultra-low-dose radiation exposure is feasible in interventional cardiology. Achievability of such levels depends greatly on operator awareness, desire, knowledge and experience of radiation protection.

Directly ventricular septal defect closure without using arteriovenous wire loop: Our adult case series using transarterial retrograde approach.

OBJECTIVE: The standard transcatheter ventricular septal defects (VSD) closure procedure is established with arteriovenous (AV) loop and is called as antegrade approach. The directly retrograde transarterial VSD closure without using AV loop might be better option as shortens the procedure time and decreases radiation exposure. METHODS: Our series consist of twelve sequential adult cases with congenital VSDs (seven with perimembranous, four with muscular, one with postoperative residuel VSD). The mean age was 26.9 (Range 18-58), the mean height was 168.75 cm (Range 155-185cm), and the mean body mass index was 23.4 (Range 17.3-28.4). Maximum and minimum defect sizes were 10 and 5 mm and the mean defect size was 6.24 mm. The procedure was performed with left heart catheterization and advancing the delivery sheath over the stiff exchange wire then VSD occlusion from left side. RESULTS: The defects were successfully closed with this technique in eleven patients. In sixth patient, the defect could not be cannulated by the delivery sheath, as the tip of the sheath did not reach the defect and VSD was closed with same sheath by standard transvenous approach using AV loop. We didn't encounter any complication releated to semilunar or atrioventricular valves. Atrioventricular conduction system was not affected by the procedure in any patients. The median procedure and fluoroscopy times were 66 and 16.5 minutes respectively. CONCLUSION: Transarterial retrograde VSD closure without using AV loop simplifies the procedure, decreases the radiation exposure, and shortens the procedure time. The only limitation in adult patients is delivery sheath length.

Percutaneous septal ablation for left mid-ventricular obstructive hypertrophic cardiomyopathy: a case report.

BACKGROUND: Mid-ventricular obstructive hypertrophic cardiomyopathy (MVOHC) is a rare type of cardiomyopathy. The diagnosis is based on the hourglass appearance on the left ventriculogram and the presence of pressure gradient between apical and basal chamber of the ventriculum on the hemodynamic assessment. CASE PRESENTATION: The present case represents successful percutaneous treatment with septal ablation to patient with MVOHC associated with systolic anterior motion of the mitral valve and obstruction at both the mid-ventricular and outflow levels. CONCLUSION: Alcohol septal ablation has been proposed as less invasive alternatives to surgery in patients with MVOHC.

Association of platelet-activating factor acetylhydrolase gene polymorphism with premature coronary artery disease in Turkish patients.

OBJECTIVE: Platelet-activating factor (PAF) is a phospholipid with multiple actions that is involved in inflammatory diseases as well as in atherogenesis. It is inactivated by a plasma enzyme, PAF-acetylhydrolase (PAF-AH). Deficiency of this enzyme in plasma is caused by a missense mutation in the gene (G994T). The aim of this study was to investigate association of this mutation with premature coronary artery disease (CAD). METHODS: One hundred and fifteen unrelated Turkish patients with a diagnosis of premature CAD and 128 unrelated healthy subjects were enrolled in this study. Genotyping was performed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). RESULTS: The prevalence of the G994T mutation in the patients was 2.60 % (heterozygote), and 0 % in the controls. There was no significant difference in allele frequency and genotype distribution among the study groups. CONCLUSION: The G9943T mutation in the plasma PAF acetylhydrolase gene is not associated with premature CAD in Turkish subjects.

The effects of long-term regular exercise on endothelial functions, inflammatory and thrombotic activity in middle-aged, healthy men.

As studying with population carrying no classical cardiovascular risk factors seems to be an advantage in isolating effects of regular exercise on endothelial functions, inflammatory and thrombotic activity; the present study was designed to evaluate the clear effects of long-term regular exercise in middle-aged, healthy men. A total of 32 regularly exercising (three times per week, 12.8 ± 6.8 years) men (Group I, mean age = 53.2 ± 6. 1 yrs) and 32 sex- and age-matched sedentary subjects (Group II, mean age = 51.0 ± 7.7 yrs) were involved in the study. All participants were non-smokers and with no history of hypertension and diabetes. During one day preceding tests, the subjects refrained from training and maintained their normal diet. In all subjects, body mass index (BMI), percentage of body fat (% BF) and maximal oxygen uptake (VO2max) were calculated. Serum uric acid, glucose, HbA1c, lipids, high-sensitive C-reactive protein (hs-CRP), fibrinogen levels, white blood cell (WBC) and platelet count were measured. Resting heart rates and blood pressures were recorded and standard exercise stress test was applied using the modified Bruce protocol. Flow-mediated and nitrate-induced dilatation (FMD and NID) of the brachial artery and carotid intima-media thickness (cIMT) were evaluated as markers of endothelial functions and early atherosclerosis. Mean BMI, % BF, systolic and diastolic blood pressures, WBC and platelet count, HbA1c, total and LDL cholesterol, hs-CRP and fibrinogen levels were similar between the groups. Group I had significantly lower serum glucose, uric acid and triglyceride (p < 0.05, p < 0.005 and p < 0.05, respectively) and higher HDL cholesterol levels (p < 0.0001) than in Group II. FMD values were significantly higher in Group I than in Group II (p < 0.005) while there were no significant differences in NID and cIMT measures between the groups. VO2max and cIMT showed a negative correlation in Group I (r = -0.463, p < 0.0001). Negative correlations also existed between VO2max and fibrinogen levels in both Group I and II (r = -0.355, p < 0.05 and r = -0.436, p < 0.05, respectively). These results are concordant with the concept of favorable effects of regular physical exercise on cardiovascular health based on enhancement of endothelial functions even in subjects who have low cardiovascular risk profile. Key PointsThe present study results suggest that regular exercise is effective on endothelial functions even in subjects who have low risk for cardiovascular disease.Therefore, regular exercise is feasible in improving endothelial functions independently from cardiovascular risk profile.