Updates in Small Interfering RNA for the Treatment of Dyslipidemias.

PURPOSE OF REVIEW: Atherosclerotic cardiovascular disease (ASCVD) is still the leading cause of death worldwide. Despite excellent pharmacological approaches, clinical registries consistently show that many people with dyslipidemia do not achieve optimal management, and many of them are treated with low-intensity lipid-lowering therapies. Beyond the well-known association between low-density lipoprotein cholesterol (LDL-C) and cardiovascular prevention, the atherogenicity of lipoprotein(a) and the impact of triglyceride (TG)-rich lipoproteins cannot be overlooked. Within this landscape, the use of RNA-based therapies can help the treatment of difficult to target lipid disorders. RECENT FINDINGS: The safety and efficacy of LDL-C lowering with the siRNA inclisiran has been documented in the open-label ORION-3 trial, with a follow-up of 4 years. While the outcome trial is pending, a pooled analysis of ORION-9, ORION-10, and ORION-11 has shown the potential of inclisiran to reduce composite major adverse cardiovascular events. Concerning lipoprotein(a), data of OCEAN(a)-DOSE trial with olpasiran show a dose-dependent drop in lipoprotein(a) levels with an optimal pharmacodynamic profile when administered every 12 weeks. Concerning TG lowering, although ARO-APOC3 and ARO-ANG3 are effective to lower apolipoprotein(apo)C-III and angiopoietin-like 3 (ANGPTL3) levels, these drugs are still in their infancy. In the era moving toward a personalized risk management, the use of siRNA represents a blossoming armamentarium to tackle dyslipidaemias for ASCVD risk reduction.

Vitamin D replacement ameliorates serum lipoprotein functions, adipokine profile and subclinical atherosclerosis in pre-menopausal women.

BACKGROUND AND AIMS: Low vitamin D (vitD) has been linked to increased cardiovascular (CV) risk, but the effects of vitD supplementation are not clarified. We evaluated the impact of vitD normalization on HDL cholesterol efflux capacity (CEC), which inversely correlates with CV risk, the proatherogenic serum cholesterol loading capacity (CLC), adipokine profile and subclinical atherosclerosis. METHODS AND RESULTS: Healthy premenopausal women with vitD deficiency (n = 31) underwent supplementation. Subclinical atherosclerosis was evaluated by flow-mediated dilation (FMD), pulse wave velocity (PWV) and augmentation index (AIx), measured with standard techniques. HDL CEC and serum CLC were measured by a radioisotopic and fluorimetric assay, respectively. Malondialdehyde (MDA) in HDL was quantified by the TBARS assay. Pre-ß HDL was assessed by 2D-electrophoresis. Serum adipokines were measured by ELISA. VitD replacement restored normal levels of serum 25-hydroxyvitamin D (25OHD) and significantly improved FMD (+4%; p < 0.001), PWV (-4.1%: p < 0.001) and AIx (-16.1%; p < 0.001). Total CEC was significantly improved (+19.5%; p = 0.003), with a specific increase in the ABCA1-mediated CEC (+70.8%; p < 0.001). HDL-MDA slightly but significantly decreased (-9.6%; p = 0.027), while no difference was detected in pre-ß HDL. No change was observed in aqueous diffusion nor in the ABCG1-mediated CEC. Serum CLC was significantly reduced (-13.3%; p = 0.026). Levels of adiponectin were increased (+50.6%; p < 0.0001) and resistin levels were decreased (-24.3%; p < 0.0001). After vitD replacement, an inverse relationship was found linking the ABCA1-mediated CEC with pre-ß HDL (r2 = 0.346; p < 0.001) and resistin (r2 = 0.220; p = 0.009). CONCLUSION: Our data support vitD supplementation for CV risk prevention.

Lipid lowering drug therapy in patients with coronary heart disease from 24 European countries--Findings from the EUROASPIRE IV survey.

OBJECTIVE: Since dyslipidaemia is one of the most important risk factors for coronary heart disease (CHD), lowering of LDL-cholesterol (LDL-C) causes significant reduction in morbidity and mortality, particularly in patients with established CHD. The aim of this survey was to assess how statins were prescribed in CHD patients at discharge after a coronary event from hospitals throughout Europe and how the intake of these drugs was reported by the patients when they were seen more than one year later in relationship with their achieved LDL-C levels. METHODS: 6648 CHD patients' data from centres in 24 European countries were gathered using standardized methods. Lipid measurements were performed in one central laboratory. Patients were divided in three groups: high-intensity statin therapy, moderate or low intensity statin therapy and no statin therapy at all. RESULTS: 90.4% CHD patients were on statin therapy at the time of discharge from the hospital which decreased to 86% one year later. Only 37.6% of these patients were prescribed a high-intensity statin at discharge which even decreased to 32.7% later. In only 6 countries (all of them high-income countries) the number of patients on a high-intensity statin therapy increased substantially after the hospital discharge. It is worrying that statin therapy was discontinued in 11.6% and that only 19.3% of all CHD patients achieved target values of LDL-C < 1.8 mmol/L at the time of interview. CONCLUSIONS: Too many CHD patients with dyslipidaemia are still inadequately treated and most of these patients on statin therapy are not achieving the treatment targets. Therapeutic control of LDL-C is clearly related to the intensity of lipid lowering drug regimen after the CHD event indicating that a considerable potential still exists throughout Europe to reduce CHD mortality and morbidity rates through more efficient LDL-C lowering.

Evaluation of cardiac autonomic functions in patients with systemic lupus erythematosus.

BACKGROUND: Cardiovascular involvement is one of the leading causes of death among patients with systemic lupus erythematosus (SLE). In this study, we aimed to investigate cardiac autonomic functions in SLE patients. METHODS: We enrolled 36 patients (25 female; mean age 34.2 ± 10.2 years) with SLE and 32 healthy subjects (23 female; mean age 35.0 ± 10.3 years). All participants underwent 24-h Holter recording. Heart rate recovery (HRR) indices were calculated by subtracting first, second, and third-minute heart rates from maximal heart rate. All patients underwent heart rate variability (HRV), heart rate turbulence (HRT) and QT dispersion analysis. The mean SLE duration was 8.4 ± 4.0 years. RESULTS: According to the baseline demographic characteristics, both groups were similar with regard to age, gender, body mass index and left ventricular ejection fraction. Mean HRR1 (32.6 ± 10.9 vs. 42.5 ± 6.5, p = 0.038), HRR2 (51.0 ± 16.9 vs. 61.0 ± 10.8, p = 0.01) and HRR3 (52.8 ± 17.5 vs. 65.8 ± 9.8, p < 0.001) values were significantly higher in control group. When HRV was considered, SDNN, SDANN, RMSSD, PNN50 and high frequency (HF) component were significantly decreased in patients with SLE compared with healthy controls, but low frequency (LF) component and LF/HF were significantly higher in SLE patients. In addition, HRT onset and HRT slope values were significantly less negative in SLE patients. QT dispersion was significantly greater in SLE patients than healthy subjects (81.3 ± 15.8 vs. 53.2 ± 13.1, p < 0.001). CONCLUSION: Our study results suggest that cardiac autonomic functions are impaired in SLE patients despite the absence of overt cardiac involvement and symptoms. Further studies are needed to elucidate the prognostic significance and clinical implications of impaired autonomic functions in patients with SLE.

The association between serum uric acid level and coronary artery disease.

OBJECTIVE: This study was designed to determine the relationship between serum uric acid level and the presence and severity of coronary artery disease (CAD). METHODS: A total of 1012 patients who underwent coronary angiography were included in this study. All patients were assessed for the presence of cardiovascular risk factors and ongoing medications. Serum uric acid and creatinine level, as well as a fasting lipid profile and fasting blood glucose, were measured in all patients before the procedure. The severity of CAD was assessed by the Gensini score. RESULTS: Of 1012 patients (mean age, 59.4 +/- 10.24 years), 680 were men (mean age, 58.7 +/- 10.5 years) and 332 were women (mean age, 61.0 +/- 9.51 years). Of the study patients, 703 (69%) were hypertensive, 292 (28.9%) were diabetic (DM), 304 (30%) had a smoking history, 306 (30%) had low high-density lipoprotein cholesterol levels and 350 (34%) had hypertriglyceridaemia. CAD was present in 689 (68%) patients who were assessed by coronary angiography. One-, two- and three-vessel disease was detected in 32.6%, 32.5% and 34.9% of the patients respectively; left main coronary artery lesion was detected in 15% of the patients. A statistically significant difference in the mean uric acid concentrations was found between the patients with or without CAD [380 +/- 121 micromol/l (6.39 +/- 2.04 mg/dl) vs. 323.5 +/- 83.2 micromol/l (5.44 +/- 1.40 mg/dl) p < 0.001]. Based on logistic regression analysis, the increased serum uric acid level was found to be associated with the presence of CAD in both men and women (p < 0.001). The increased serum uric acid level was also found to be associated with the severity of CAD in both men and women based on multivariate linear regression analysis (p < 0.001). CONCLUSION: In conclusion, serum uric acid level was found to be associated with the presence and severity of CAD.

Advanced age is associated with endothelial dysfunction in healthy elderly subjects.

BACKGROUND: Aging is associated with an increased risk for atherosclerosis in which endothelial dysfunction is an early marker. OBJECTIVE: The purpose of this study was to determine if endothelial function is altered with increasing age in healthy subjects. METHOD: The study population consisted of 30 elderly and 36 younger subjects free from major cardiovascular risk factors. Transthoracic echocardiography was performed for each subject to rule out structural heart disease. Endothelial function was evaluated by flow-mediated dilation (FMD) of the brachial artery via ultrasound. RESULTS: Baseline characteristics of the elderly and the younger group were similar, except for age (mean age: 71.3 +/- 5.8 vs. 26.5 +/- 7.2). Transthoracic echocardiography was normal in all subjects. FMD of the elderly group was significantly lower than the younger group (7.9 +/- 3.1 in the elderly, 10.8 +/- 1.9 in the younger group, p < 0.001). A negative relationship was found between FMD and age (r = -0.528, p < 0.001). CONCLUSION: It can be concluded that endothelial function detected by FMD declines with increasing age in healthy human subjects. Advanced age is a predictor of impaired endothelial function.

Determining the relationship between metabolic syndrome score and angiographic severity of coronary artery disease.

BACKGROUND: Cardiovascular disease is leading cause of mortality and morbidity in developed and developing countries. Metabolic syndrome (MS) is a risk factor for coronary artery disease (CAD). The effect of MS on angiographic severity of CAD is not well defined. The aim of this study was to examine the effect of MS on angiographic severity of CAD by using Gensini score. METHODS: The total number of 1003 patients who underwent elective coronary angiography in catheter laboratory were included in the study. MS score based on National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) criteria which ranged between zero and five were calculated for each subject. Gensini scores were determined by examining coronary angiograms of the patients. RESULTS: The study population consisted of 634 (63%) male, and 369 (37%) female subjects. The mean age was 59 +/- 11. MS based on NCEP ATP III was present in 246 (25%) patients. CAD was present in 691 patients (69%). The median of Gensini score was five (0-192) in the total sample, 18 (1-192) in the patients with CAD and 25 (0-192) in the patients with MS. A positive correlation was found between MS score and Gensini score (r = 0.402, p < 0.001). CONCLUSIONS: In this study, it was determined that as the severity of MS increases, the angiographic severity of CAD increases as well. Besides, the most important factor on Gensini score was diabetes mellitus in male and hypertension in female subjects.

Effects of hazelnut-enriched diet on plasma cholesterol and lipoprotein profiles in hypercholesterolemic adult men.

OBJECTIVE: Frequent consumption of nuts is associated with favorable plasma lipid profiles and reduced risk of coronary heart disease (CHD). This study was conducted to investigate the effects of hazelnut-enriched diet on plasma cholesterol and lipoprotein profiles in hypercholesterolemic adult men compared with baseline and control diet, and also to measure the anthropometric parameters, habitual physical activities, nutrient intake and endothelial function. SUBJECTS AND DESIGN: Fifteen hypercholesterolemic men aged 48+/-8 years were recruited voluntarily. A well-controlled, 2-period (P1 and P2) study design with a total of 8-week was implemented. In the P1, subjects consumed a control diet (low-fat, low-cholesterol and high-carbohydrate). During the P2, the control diet was supplemented with MUFA-rich hazelnut (40 g/day), which provided 11.6% of total energy content. Anthropometric parameters and habitual physical activities were recorded. Plasma total and HDL cholesterol, TAG, ApoA-1, Apo B, total homocysteine and glucose concentrations were measured. All parameters and measurements were obtained at baseline and end of each 4-week diet period. RESULTS: Body weights of subjects remained stable throughout the study. Compared with baseline, the hazelnut-enriched diet decreased (P<0.05) the concentrations of VLDL cholesterol, triacylglycerol, apolipoprotein B by 29.5, 31.8, and 9.2%, respectively, while increasing HDL cholesterol concentrations by 12.6%. Total/HDL cholesterol and LDL/HDL cholesterol ratios favorably decreased (P<0.05). Although insignificant there was a decreasing trend for the rest of parameters, particularly in total (5.2%) and LDL cholesterol (3.3%) in subjects consuming a hazelnut-enriched diet compared to that of the baseline. No changes were found in fasting levels of glucose, Apo A-1 and homocysteine between the control and hazelnut-enriched diets. CONCLUSIONS: This study demonstrated that a high-fat and high-MUFA-rich hazelnut diet was superior to a low-fat control diet because of favorable changes in plasma lipid profiles of hypercholesterolemic adult men and, thereby positively affecting the CHD risk profile. SPONSORSHIP: Funding provided by a grant from the Hazelnut Promotion Group, Giresun, Turkey.

Development and in vitro/in vivo evaluations of bioadhesive buccal tablets for nicotine replacement therapy.

Buccal bioadhesive tablet formulations of nicotine hydrogen tartrate (NHT) for nicotine replacement therapy (NRT) were developed using chitosan and carbomer at different ratios. Magnesium hydroxide was incorporated into the formulations as pH increasing agent. In vitro release and bioadhesion properties of the tablets were investigated. Release of NHT from the tablets was increased with the increasing amount of chitosan in formulations whilst the bioadhesion of the tablet was decreased. In vivo studies were carried out in healthy, non-smoker volunteers in comparison to a commercially available transdermal patch. Plasma nicotine and cotinine levels were determined using gas chromatography-mass spectrophotometry. No significant difference was found between the maximum plasma nicotine concentrations (Cmax) obtained with the buccal tablet and the transdermal patch (p > 0.05). Time to reach the Cmax was 2.9 +/- 0.2 h and 11.5 +/- 1.3 h, and AUC0-24 values were 59.3 +/- 5.1 ng x h x mL(-1) (0-12 h) and 204.1 +/- 31.2 ng x h x mL(-1) for buccal tablet and transdermal patch, respectively.

Sub-optimal drug treatment of diabetes and cardiovascular risk in diabetic patients in Turkey. A countrywide survey.

OBJECTIVES: The present study is a snapshot of how diabetic patients are treated for diabetes and coexisting cardiovascular risk factors in Turkey. We also addressed the question of what percentage of these patients are treated appropriately according to the current guidelines. Next step will be to determine which pharmacological treatment strategies affect mortality and morbidity in these patients and whether there are regional differences in these outcomes. METHODS: To get a representative picture, Turkey was splitted into four parts with different ethnic and socioeconomic features then centers were randomized within each of these parts. Number of the centers in a region were calculated according to the population of that region. 305 physicians in 11 cities participated in data collection during a period of 3 months. Consecutive 2226 diabetic patients patients who were above 55 years of age were included. Detailed information was obtained about the demographic features and the cardiovascular risk factor and diabetes status of the patients together with relevant drug treatment. Laboratory analyses were done locally and recorded if performed during the last 3 months. RESULTS: Most patients were treated with oral antidiabetic monotherapy regardless of diabetes duration, metabolic control and complication and cardiovascular risk factor status. There was a trend among physicians except for endocrinologists to underprescribe insulin. Monotherapy also was the main mode of treatment for hypertension. Angiotensin converting enzyme inhibitors were generally not used as first line treatment contrary to the recommendations and angiotensin converting enzyme inhibitors and angiotensin receptor blockers are not prescribed for renoprotection in microalbuminuric patients. Statins, fibrates, metformin and aspirin were largely underused. CONCLUSION: The present study indicates that diabetic patients are undertreated in Turkey. Therefore every effort should be spent to implement current guidelines in diabetic patients in order to prevent macro and microvascular complications of diabetes.

QT dispersion and cardiac involvement in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the dispersion of repolarization variables in patients with rheumatoid arthritis (RA). METHODS: Electrocardiography (ECG) and Doppler echocardiography were performed on 40 patients with RA, which were divided into two groups according to the duration of disease and in 48 healthy controls. RESULTS: All patients had significantly longer QT dispersion (QTd) and corrected QT dispersion (QTc-d) values (p<0.05). The mean values of diastolic function variables were significantly different in all patients compared to healthy controls (p<0.05). There were no statistically significant differences between patient groups in terms of diastolic function variables except IVRT. However, QTd and QTc-d were significantly longer in patients with disease duration over 5 years (p<0.05). CONCLUSION: We conclude that repolarization heterogeneity and diastolic dysfunction are commonly seen in RA, and QTd is significantly longer in those patients with a disease duration over 5 years compared to those with new onset RA.

The effects of chronic carvedilol therapy on QT dispersion in patients with congestive heart failure.

BACKGROUND: Carvedilol therapy reduces mortality from sudden cardiac death and progressive pump failure in congestive heart failure (CHF). However, the effect(s) of carvedilol on ventricular repolarization characteristics is unclear. AIM: The aim of the study was to investigate the effects of chronic carvedilol therapy on ventricular repolarization characteristics as assessed by QT dispersion (QTd) in patients with CHF. METHOD: Nineteen patients (age 53+/-12 years; 16 male, three female) with CHF (eight ischemic, 11 non-ischemic dilated cardiomyopathy) were prospectively included in the study. Carvedilol was administered in addition to standard therapy for CHF at a dose of 3.125 mg bid and uptitrated biweekly to the maximum tolerated dose. From standard 12-lead electrocardiograms the maximum and minimum QT intervals (QTmax, QTmin), QTd, corrected QT intervals (QTcmax, QTcmin) and corrected QTd (QTcd) values were calculated at baseline, after the 2nd and the 16th month of carvedilol therapy. RESULTS: A significant reduction was noted in the QTd and QTcd values with carvedilol therapy after the 16th month (QTd: 81+/-22 ms vs. 40+/-4.3 ms P<0.001; QTcd: 91+/-25 ms vs. 51+/-7 ms P<0.001), but not after the 2nd month (P>0.05). The resting heart rate was also significantly reduced after a 16-month course of carvedilol therapy (78+/-13 bpm vs. 66+/-15 bpm, P<0.05). Carvedilol therapy did not alter QTmax and QTcmax intervals (P>0.05), however, QT min and QTcmin significantly increased with carvedilol at the 16th month (P<0.001 and P<0.01, respectively). CONCLUSION: Long-term carvedilol therapy was associated with a reduction in QTd, an effect that might contribute to the favorable effects of carvedilol in reducing sudden cardiac death in CHF.

Effects of hormone replacement therapy on heart rate variability in postmenopausal women.

BACKGROUND: Hormone replacement therapy (HRT) is associated with reduced cardiovascular risk, but the underlying mechanism(s) are not fully understood. This study investigated the effects of a 6-month course of HRT on cardiac autonomic function parameters assessed by heart rate variability (HRV) in postmenopausal women. METHODS: Forty-six healthy postmenopausal women (age 48 +/- 5, range 40-60) with normal baseline electrocardiogram and negative exercise testing were enrolled. HRT, which was either 0.625 mg/day conjugated equine estrogen (CEE) plus 2.5 mg/day medroxyprogesterone acetate or 0.625 mg/day CEE alone were administered depending on hysterectomy status. Power spectral analysis of HRV was performed to calculate the low frequency component in absolute (LF) and normalized units (LF nu), high frequency component in absolute (HF), and normalized units (HF nu), and the LF/HF ratio. The standard deviation of RR intervals (SDNN) was calculated from the time series of RR intervals. RESULTS: A 6-month course of HRT did not significantly alter resting heart rate (P > 0.05). The LF/HF ratio and LF nu significantly decreased after HRT (P = 0.022 and P = 0.032), whereas a significant increase was noted in the HF component of HRV (P = 0.043), indicating an improvement in cardiac autonomic function. The SDNN value, which was 28.8 +/- 11.8 ms before HRT significantly increased to 35.4 +/- 16.7 ms after 6 months (P = 0.011). CONCLUSION: Our results indicate that a 6-month course of HRT may significantly improve cardiac autonomic function parameters, a finding that could at least partly explain the potential cardioprotective effect(s) of HRT.

What is the optimal evaluation time of the QT dispersion after acute myocardial infarction for the risk stratification?

The sequential changes of the corrected QT dispersion (QTcD) were studied in 136 patients 1 day to 30 days after a transmural acute myocardial infarction (AMI) to investigate the optimal measurement time of QT dispersion for risk stratification. The study group included 136 patients (89 men; mean age, 57+/-10 years) with transmural AMI who were treated with thrombolytics (Tr+ group, n = 73) or not (Tr- group, n = 63) and 65 healthy controls (43 men; mean age, 56+/-7 years). Fourteen patients in whom ventricular tachycardia (VT), ventricular fibrillation (VF), or sudden cardiac death developed during the 30-day period were also evaluated as major cardiac arrhythmia (MCA) group. ECGs were obtained for each patient on days 1, 3, 5, 10, 15, and 30 after AMI. QTc dispersion in patients with AMI (for every period of QTcD after MI) was significantly more prolonged than in normal controls (49.3+/-16.3 ms) (p<0.001). QTcD was significantly greater in patients without thrombolytics than in patients with thrombolytics for every period (days 1, 3, 5, 10, 15, and 30) of QTcD after MI (p<0.001). The mean of QTcD was significantly greater in patients with MCA than in patients without MCA group for every period (days 1, 3, 5, 10, 15, and 30) of QTcD after MI (p < 0.05). Maximal QTcD was seen on day 10 (p < 0.05 1st vs day 10 for each group) after myocardial infarction, and then reached a plateau for an each group. The ideal time to measure the QTD for risk stratification is at least 10 days after AMI.

The diagnostic value of 12-lead electrocardiogram in predicting infarct-related artery and right ventricular involvement in acute inferior myocardial infarction.

BACKGROUND: The aim of the present study was to investigate the predictive value of presentation and 24-hour electrocardiograms in defining the infarct-related artery (IRA), its lesion segment, and the right ventricular involvement in acute inferior myocardial infarction (MI). METHODS: One hundred forty-nine patients with acute inferior MI were included. Infarct-related artery, its lesion segment, and the validity of new ECG criteria for the diagnosis of right ventricular MI (RVMI) were investigated by means of criteria obtained from admission and 24- hour ECGs. RESULTS: The presence of ST-segment elevation in lead III > lead II criterion (Criterion 1) and ST-segment depression in lead I > lead aVL criterion (Criterion 2) from admission ECG defined the right coronary artery (RCA) as IRA with a sensitivity of 64% and a specificity of 100%. These two criteria also defined the proximal or mid lesions in RCA as culprit lesions (sensitivity of 99%, specificity of 96%). Absence of these two criteria indicated Cx as IRA with a sensitivity of 50% and a specificity of 97%. The depth of Q wave in lead III > lead II criterion (Criterion 3) had no value for discrimination of IRA, but the width of Q wave in lead III > lead II criterion (Criterion 4) supported the RCA to be IRA with a sensitivity of 60% and a specificity of 61% (Criteria 3 and 4 were obtained from 24-hour ECGs). The finding of Criterion 1 plus Criterion 5 (ST elevation in V(1) but no ST elevation in V2) on admission ECG had a sensitivity of 63% and a specificity of 99% in the diagnosis of RVMI. CONCLUSION: We concluded that 12-lead ECG is a cheap, easy, and readily obtainable diagnostic approach in discrimination of IRA and its culprit lesion segment. However, despite high specificity, due to moderate degree sensitivity, its value for the diagnosis of RVMI is questionable.

A retrospective review of 228 episodes of infective endocarditis where rheumatic valvular disease is still common.

Two hundred and twenty-eight episodes of infective endocarditis in adult patients (mean age 36 years) were reviewed retrospectively. There were 183 episodes (80%) of native valve, 15 (7%) early prosthetic valve and 30 (13%) late prosthetic valve endocarditis. The most common predisposing factor was rheumatic valvular disease (65%). None of the patients were intravenous drug users. According to the Duke criteria, the number of definite, probable and rejected episodes were 121 (53%), 94 (41%) and 13 (6%), respectively. Additional minor criteria increased the number of definite endocarditis to 82%. The Duke criteria are not primarily intended to influence treatment decisions but are helpful in standardising research activities. The choice of the level of sensitivity or specificity of the criteria may be adjusted according to the aim of the study and prevalence of disease in a particular area. More sensitive criteria may be valuable in those countries where the prevalence of rheumatic valvular disease is still high.

Echocardiographic evaluation of left and right ventricular diastolic function in patients with chronic obstructive pulmonary disease.

The aim of this study was to investigate the effects of chronic obstructive pulmonary disease (COPD) on left ventricular and right ventricular diastolic and systolic functions. Forty-eight patients with severe COPD were studied. Patients were divided into 2 subgroups according to pulmonary artery pressures: 25 patients with pulmonary hypertension (group 1) and 23 patients with normal pulmonary artery pressure (group 2). As a control group, 59 normal subjects were studied (group 3). Patients in group 1 had higher tricuspid peak A velocity, lower tricuspid E velocity, longer isovolumetric relaxation time, higher mitral A wave, lower mitral E wave, and slower color propagation velocity than groups 2 and 3. There was no significant difference between left ventricular diastolic filling parameters between groups 2 and 3. Patients with COPD and pulmonary hypertension have left and right ventricular diastolic dysfunction. However, patients with COPD and normal pulmonary artery pressure have normal left and right ventricular diastolic function.

Detection of Chlamydia pneumoniae and Helicobacter pylori DNA in human atherosclerotic plaques by PCR.

Chlamydia pneumoniae and Helicobacter pylori can cause persistent infections of the respiratory and gastrointestinal tract, respectively. It has been suggested that persistent infection of arteries with these bacteria can contribute to the development of atherosclerosis. The aims of this study were to determine the presence of C. pneumoniae and H. pylori DNA in atherosclerotic plaque samples by PCR and to evaluate the correlation between clinical status and DNA positivity of these bacteria. Eighty-five consecutive patients (mean age, 59 +/- 10; 75 male, 10 female) undergoing coronary artery bypass grafting, carotid endarterectomy, and surgery of the abdominal aorta for atherosclerotic obstructive lesions were included in the study. Forty-six endarterectomy specimens from the atherosclerotic lesions and 39 specimens from healthy regions of the ascending aorta, which were accepted as the control group, were excised. The presence of microorganism DNA in endarterectomy specimens was assessed by PCR. C. pneumoniae DNA was found in 12 (26%) of 46 endarterectomy specimens and none of the healthy vascular-wall specimens (P < 0.001), while H. pylori DNA was found in 17 (37%) of 46 endarterectomy specimens and none of the controls (P < 0.001). Either C. pneumoniae or H. pylori DNA was positive in 23 (50%) of 46 patients and none of the controls (P < 0. 001). Six of the atherosclerotic lesions showed coexistence of both of the microorganism DNAs. The presence of C. pneumoniae and H. pylori DNA in a considerable number of atherosclerotic plaques but their absence in healthy vascular wall supports the idea that they may have a role in the development of atherosclerosis, especially in countries where infection is prevalent and where conventional risk factors fail to explain the high prevalence of atherosclerotic vascular disease.

T wave alternans can decrease after coronary revascularization.

Clinical observations and animal experiments indicate that T wave alternans (TWA) is associated with an increased propensity for ventricular fibrillation, and thus it may be considered as a noninvasive marker of life-threatening ventricular arrhythmias. There is substantial evidence indicating that TWA is an intrinsic property of ischemic myocardium. This study was performed to determine the role of percutaneous transluminal coronary angioplasty (PTCA)-induced myocardial ischemia in the development of TWA and the effects of revascularization. The authors recorded bipolar X, Y, and Z leads of 111 consecutive patients (mean age: 56 years) undergoing PTCA before, during, and 24 hours after the procedure. T wave alternans signal was calculated in 97 patients (43 left anterior descending, 26 right coronary artery, and 28 circumflex or major obtuse margin branch) by fast Fourier transformation technique after signal processing. Twenty-four hours after the procedure, the mean and peak X, Y, and Z values for TWA had all been significantly reduced from baseline and during balloon inflation (p<0.01). The findings point out that induced ischemia could be a trigger for T wave alternans, and successful revascularization can reduce alternans.