Efstathios D. Pagourelias

Safety and efficacy of long-term statin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study: a post-hoc analysis

BACKGROUND Long-term statin treatment reduces the frequency of cardiovascular events, but safety and efficacy in patients with abnormal liver tests is unclear. We assessed whether statin therapy is safe and effective for these patients through post-hoc analysis of the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) study population. METHODS GREACE was a prospective, intention-to-treat study that randomly assigned by a computer-generated randomisation list 1600 patients with coronary heart disease (aged <75 years, with serum concentrations of LDL cholesterol >2·6 mmol/L and triglycerides <4·5 mmol/L) at the Hippokration University Hospital, Thessaloniki, Greece to receive statin or usual care, which could include statins. The primary outcome of our post-hoc analysis was risk reduction for first recurrent cardiovascular event in patients treated with a statin who had moderately abnormal liver tests (defined as serum alanine aminotransferase or aspartate aminotransferase concentrations of less than three times the upper limit of normal) compared with patients with abnormal liver tests who did not receive a statin. This risk reduction was compared with that for patients treated (or not) with statin and normal liver tests. FINDINGS Of 437 patients with moderately abnormal liver tests at baseline, which were possibly associated with non-alcoholic fatty liver disease, 227 who were treated with a statin (mainly atorvastatin 24 mg per day) had substantial improvement in liver tests (p<0·0001) whereas 210 not treated with a statin had further increases of liver enzyme concentrations. Cardiovascular events occurred in 22 (10%) of 227 patients with abnormal liver tests who received statin (3·2 events per 100 patient-years) and 63 (30%) of 210 patients with abnormal liver tests who did not receive statin (10·0 events per 100 patient-years; 68% relative risk reduction, p<0·0001). This cardiovascular disease benefit was greater (p=0·0074) than it was in patients with normal liver tests (90 [14%] events in 653 patients receiving a statin [4·6 per 100 patient-years] vs 117 [23%] in 510 patients not receiving a statin [7·6 per 100 patient-years]; 39% relative risk reduction, p<0·0001). Seven (<1%) of 880 participants who received a statin discontinued statin treatment because of liver-related adverse effects (transaminase concentrations more than three-times the upper limit of normal). INTERPRETATION Statin treatment is safe and can improve liver tests and reduce cardiovascular morbidity in patients with mild-to-moderately abnormal liver tests that are potentially attributable to non-alcoholic fatty liver disease. FUNDING None.

Comparison of Effectiveness of Ranolazine Plus Amiodarone Versus Amiodarone Alone for Conversion of Recent-Onset Atrial Fibrillation

Ranolazine, an antianginal agent with antiarrhythmic properties, prevents atrial fibrillation (AF) in patients with acute coronary syndrome. In experimental models, the combination of ranolazine and amiodarone has marked synergistic effects that potently suppress AF. Currently, the clinical effect of the ranolazine-amiodarone combination for the conversion of AF is unknown. This prospective randomized pilot study compared the safety and efficacy of ranolazine plus amiodarone versus amiodarone alone for the conversion of recent-onset AF. We enrolled 51 consecutive patients with AF (<48-hour duration) eligible for pharmacologic cardioversion. Patients (33 men, 63 ± 8 years of age) were randomized to intravenous amiodarone for 24 hours (group A, n = 26) or to intravenous amiodarone plus oral ranolazine 1,500 mg at time of randomization (group A + R, n = 25). The 2 groups were well balanced with respect to clinical characteristics and left atrial diameter. Conversion within 24 hours (primary end point) was achieved in 22 patients (88%) in group A + R versus 17 patients (65%) in group A (p = 0.056). Time to conversion was shorter in group A + R than in group A (9.8 ± 4.1 vs 14.6 ± 5.3 hours, p = 0.002). According to Cox regression analysis, left atrial diameter and A + R treatment were the only independent predictors of time to conversion (hazard ratio 5.35, 95% confidence interval 2.37 to 12.11, p <0.001; hazard ratio 0.81, 95% confidence interval 0.74 to 0.88, p <0.001, respectively). There were no proarrhythmic events in either group. In conclusion, addition of ranolazine to standard amiodarone therapy is equally safe and appears to be more effective compared to amiodarone alone for conversion of recent-onset AF.

Left Ventricular Outflow Tract Obstruction as a Risk Factor for Sudden Cardiac Death in Hypertrophic Cardiomyopathy

The effect of left ventricular outflow tract obstruction (LVOTO) at rest on the incidence of sudden death (SD) in patients with hypertrophic cardiomyopathy is rather conflicting. The aim of this study was the evaluation of LVOTO at rest as a new potential risk factor for SD in hypertrophic cardiomyopathy. A total of 166 patients (112 men, 51.8 +/- 15.6 years) were studied; 50 patients (30.1%) had peak instantaneous LVOTO gradients of > or = 30 mm Hg at rest. During the follow-up period (median 32.4 months, range 1 to 209), 13 patients either died suddenly, or had cardiac arrest, documented sustained ventricular tachycardia, or implantable cardioverter defibrillator discharge. The cumulative event-free survival rate was 92% in patients with LVOTO, and 92% in patients without obstruction (p = NS). LVOTO at rest was associated with a particularly low positive predictive value for SD (8%), although a high negative predictive value (92%) was recorded. Patients having syncope or presenting with a maximum wall thickness > or =3 cm in echocardiography were more sensitive to SD emergence because they had a 13.07 (95% confidence interval 4.00 to 46.95, p <0.0001) and a 10.07 (95% confidence interval 2.92 to 34.79, p = 0.003) greater relative risk, respectively. In conclusion, our cohort study results do not support LVOTO as an independent risk factor for SD in patients with hypertrophic cardiomyopathy.

Right Atrial and Ventricular Adaptations to Training in Male Caucasian Athletes: An Echocardiographic Study

BACKGROUND The aim of this study was to investigate the systolic and diastolic properties of the right cardiac chambers (the right ventricle and right atrium) among different subsets of athletes to unveil potential variations in right ventricular and right atrial remodeling secondary to different training modes. METHODS A cohort of Caucasian male top-level athletes (n = 108; 80 endurance athletes [EAs], mean age, 31.2 ± 10.4 years; 28 strength-trained athletes [SAs], mean age, 27.4 ± 5.7 years) and untrained controls (n = 26; mean age, 26.6 ± 5.6 years) (P = .327) were prospectively enrolled. Conventional echocardiographic parameters, including transtricuspid inflow, Doppler tissue imaging, and two-dimensionally derived peak systolic longitudinal strain and strain rate indices of the right ventricle and right atrium, were calculated. RESULTS EAs had greater internal right ventricular and right atrial dimensions compared with SAs and controls. There were no significant differences concerning strain between groups (-23.1 ± 3.7% in EAs vs -25.1 ± 3.2% in SAs vs -23.1 ± 3.5% in controls, P = .052), with SAs presenting higher global systolic strain rates (-1.42 ± 0.22 sec(-1) in SAs vs -1.21 ± 0.21 sec(-1) in EAs vs -1.2 ± 0.28 sec(-1) in controls, P = .016), as well as greater right atrial strain rate systolic and diastolic components. Training volume (highly vs moderately trained athletes) did not significantly influence deformation parameters. No significant differences concerning diastolic transtricuspid inflow and Doppler tissue imaging indices were also noted among different athlete groups and controls. CONCLUSIONS Despite the existence of right geometric alterations in athletes participating in different sport disciplines, few meaningful differences in deformation and diastolic function exist.

Statins and cardiovascular outcomes in elderly and younger patients with coronary artery disease: a post hoc analysis of the GREACE study

Introduction The effect of cardiovascular disease (CVD) prevention measures aimed at elderly patients requires further evidence. We investigated the effect of statin treatment (targeted to achieve guideline goals) on CVD outcomes in different age groups to determine whether statins are more beneficial in the elderly. Material and methods The primary endpoint of this post hoc analysis of the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study (n = 1,600 patients with established coronary heart disease (CHD), mean follow-up 3 years) was the absolute and relative CVD event (a composite of death, myocardial infarction, revascularization, unstable angina, heart failure and stroke) risk reduction in age quartiles (each n = 200). Patients on “structured care” with atorvastatin (n = 800) followed up by the university clinic and treated to lipid goal were compared with the corresponding quartiles on “usual care” (n = 800) followed up by specialists or general practitioners of the patients choice outside the hospital. Results In the elderly (mean age 69 ±4 and 70 ±3 years in the “structured” and “usual care”, respectively) the absolute CVD event reduction between “structured” and “usual care” was 16.5% (p < 0.0001), while in the younger patients (mean age 51 ±3 years and 52 ±3 years in the “structured” and “usual care”, respectively) this was 8.5% (p = 0.016); relative risk reduction (RRR) 60% (p < 0.0001) vs. 42% respectively (p = 0.001). The elderly had higher rates of chronic kidney disease and higher uric acid levels, plus an increased prevalence of diabetes, metabolic syndrome and non-alcoholic fatty liver disease. These factors might contribute to the increased CVD risk in older patients. Conclusions All age groups benefited from statin treatment, but the elderly on “structured care” had a greater absolute and relative CVD risk reduction than the younger patients when compared with the corresponding patients assigned to “usual care”. These findings suggest that we should not deprive older patients of CVD prevention treatment and lipid target achievement.

Statin-Induced Increase in HDL-C and Renal Function in Coronary Heart Disease Patients.

Background Little is known about the potential of statin-induced high-density lipoprotein cholesterol (HDL-C) increase to improve renal function in coronary heart disease (CHD) patients. Methods and Results In thispost hocanalysis of the GREek Atorvastatin and Coronary heart disease Evaluation (GREACE) Study we investigated the effect of HDL-C increase after statin treatment on renal function. From a total of 1,600 patients, 880 were on various statins (mainly atorvastatin) and 720 were not. Other secondary prevention therapies were similar in the 2 groups. After a 3 year follow up, the lipid profile was unchanged in the statin untreated group and estimated glomerular filtration rate (eGFR) was reduced by 5.1% compared with baseline (P<0.0001). In contrast, in the statin treated group non-HDL-C was reduced by 43%, HDL-C was increased by 7% and there was a significant increase in eGFR compared with baseline by 9.8% (P<0.0001). In multiple regression analysis, the mean 7% increase in HDL-C in the treated arm during the entire study was associated with a 5.6% increase in eGFR recorded after the 6th week of treatment. The odds ratio of eGFR increase with every 5% statin-induced rise in HDL-C was 1.78 (95% confidence interval 1.19-3.34; P=0.001). Conclusions Statin treatment significantly improved renal function. Statin-induced HDL-C increase significantly and independently contributed to this improvement. This finding supports the concept that improving lipid variables other than low density lipoprotein cholesterol is also beneficial to preserving renal function.

Carbon dioxide balneotherapy and cardiovascular disease

Carbon dioxide (CO2) balneotherapy is a kind of remedy with a wide spectrum of applications which have been used since the Middle Ages. However, its potential use as an adjuvant therapeutic option in patients with cardiovascular disease is not yet fully clarified. We performed a thorough review of MEDLINE Database, EMBASE, ISI WEB of Knowledge, COCHRANE database and sites funded by balneotherapy centers across Europe in order to recognize relevant studies and aggregate evidence supporting the use of CO2 baths in various cardiovascular diseases. The three main effects of CO2 hydrotherapy during whole body or partial immersion, including decline in core temperature, an increase in cutaneous blood flow, and an elevation of the score on thermal sensation, are analyzed on a pathophysiology basis. Additionally, the indications and contra-indications of the method are presented in an evidence-based way, while the need for new methodologically sufficient studies examining the use of CO2 baths in other cardiovascular substrates is discussed.

Chronotropic incompetence and its relation to exercise intolerance in hypertrophic cardiomyopathy.

BACKGROUND Diminished functional capacity is common in hypertrophic cardiomyopathy (HCM), although the underlying mechanisms are complicated. We studied the prevalence of chronotropic incompetence and its relation to exercise intolerance in patients with HCM. METHODS Cardiopulmonary exercise testing was performed in 68 patients with HCM (age 44.8 ± 14.6 years, 45 males). Chronotropic incompetence was defined by chronotropic index (heart rate reserve)/(220-age-resting heart rate) and exercise capacity was assessed by peak oxygen consumption (peak Vo(2)). RESULTS Chronotropic incompetence was present in 50% of the patients and was associated with higher NYHA class, history of atrial fibrillation, higher fibrosis burden on cardiac MRI, and treatment with β-blockers, amiodarone and warfarin. On univariate analysis, male gender, age, NYHA class, maximal wall thickness, left atrial diameter, peak early diastolic myocardial velocity of the lateral mitral annulus, history of atrial fibrillation, presence of left ventricular outflow tract obstruction (LVOTO) at rest, and treatment with beta-blockers were related to peak Vo(2). Peak heart rate during exercise, heart rate reserve, chronotropic index, and peak systolic blood pressure were also related to peak Vo(2). On multivariate analysis male gender, atrial fibrillation, presence of LVOTO and heart rate reserve were independent predictors of exercise capacity (R(2) = 76.7%). A cutoff of 62 bpm for the heart rate reserve showed a negative predictive value of 100% in predicting patients with a peak Vo(2) <80%. CONCLUSIONS Blunted heart rate response to exercise is common in HCM and represents an important determinant of exercise capacity.

Seasonal variation in the occurrence of stroke in Northern Greece: a 10 year study in 8204 patients

Abstract Objective: The effect of seasonal variation on the occurrence of stroke remains controversial. The objective of this study was to determine whether there is a seasonal variation in the occurrence of stroke in Northern Greece. Methods: We recorded the seasonal stroke rates over a 10 year period (from January 1997 to December 2006) in 8204 patients in Northern Greece. The findings were analysed separately for ischemic stroke (IS), intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH) and transient ischemic attack (TIA). Results: In patients with IS, there was a significant seasonal variation (p<0·001), with the peak incidence in spring (8·4% above average) and the lowest rate in summer (10·4% below average). There was no significant seasonal variation in the occurrence of the other stroke subtypes (ICH, SAH and TIA) when they were considered individually. Discussion: The seasonal effect on stroke incidence needs to be defined so as to improve the provision of preventive measures.

Brain natriuretic peptide and the athlete’s heart: a pilot study

Background:  The role of brain natriuretic peptide (BNP) in differentiating the athlete’s heart from maladaptive cardiac hypertrophy is unclear.