Aleksandras Laucevičius

EUROASPIRE IV : a European Society of Cardiology survey on the lifestyle, risk factor and therapeutic management of coronary patients from 24 European countries

Aims To determine whether the Joint European Societies guidelines on cardiovascular prevention are being followed in everyday clinical practice of secondary prevention and to describe the lifestyle, risk factor and therapeutic management of coronary patients across Europe. Methods and results EUROASPIRE IV was a cross-sectional study undertaken at 78 centres from 24 European countries. Patients <80 years with coronary disease who had coronary artery bypass graft, percutaneous coronary intervention or an acute coronary syndrome were identified from hospital records and interviewed and examined ≥ 6 months later. A total of 16,426 medical records were reviewed and 7998 patients (24.4% females) interviewed. At interview, 16.0% of patients smoked cigarettes, and 48.6% of those smoking at the time of the event were persistent smokers. Little or no physical activity was reported by 59.9%; 37.6% were obese (BMI ≥ 30 kg/m2) and 58.2% centrally obese (waist circumference ≥ 102 cm in men or ≥88 cm in women); 42.7% had blood pressure ≥ 140/90 mmHg (≥140/80 in people with diabetes); 80.5% had low-density lipoprotein cholesterol ≥ 1.8 mmol/l and 26.8% reported having diabetes. Cardioprotective medication was: anti-platelets 93.8%; beta-blockers 82.6%; angiotensin-converting enzyme inhibitors/angiotensin receptor blockers 75.1%; and statins 85.7%. Of the patients 50.7% were advised to participate in a cardiac rehabilitation programme and 81.3% of those advised attended at least one-half of the sessions. Conclusion A large majority of coronary patients do not achieve the guideline standards for secondary prevention with high prevalences of persistent smoking, unhealthy diets, physical inactivity and consequently most patients are overweight or obese with a high prevalence of diabetes. Risk factor control is inadequate despite high reported use of medications and there are large variations in secondary prevention practice between centres. Less than one-half of the coronary patients access cardiac prevention and rehabilitation programmes. All coronary and vascular patients require a modern preventive cardiology programme, appropriately adapted to medical and cultural settings in each country, to achieve healthier lifestyles, better risk factor control and adherence with cardioprotective medications.

Identifying circulating microRNAs as biomarkers of cardiovascular disease: a systematic review

The aim of the present study is to identify microRNAs (miRs) with high potential to be used as biomarkers in plasma and/or serum to clinically diagnose, or provide accurate prognosis for survival in, patients with atherosclerosis, coronary artery disease, and acute coronary syndrome (ACS). A systematic search of published original research yielded a total of 72 studies. After review of the risk of bias of the published studies, according to Cochrane Collaboration and the QUADUAS Group standards, 19 studies were selected. Overall 52 different miRs were reported. In particular, miR-133a/b (5 studies), miR-208a/b (6 studies), and miR-499 (7 studies) were well studied and found to be significant diagnostic and/or prognostic markers across different cardiovascular disease progression stages. miR-1 and miR-145b are potential biomarkers of ACS; miR-1 with higher sensitivity for all acute myocardial infarction (AMI), and miR-145 for STEMI and worse outcome of AMI. But when miRs were studied across different ACS study populations, patients had varying degrees of coronary stenosis, which was identified as an important confounder that limited the ability to quantitatively pool the study results. The identified miRs were found to regulate endothelial function and angiogenesis (miR-1, miR-133), vascular smooth muscle cell differentiation (miR-133, miR-145), communication between vascular smooth muscle and endothelial cell to stabilize plaques (miR-145), apoptosis (miR-1, miR-133, miR-499), cardiac myocyte differentiation (miR-1, miR-133, miR-145, miR-208, miR-499), and to repress cardiac hypertrophy (miR-133). Their role in these processes may be explained by regulation of shared RNA targets such as cyclin-dependent kinase inhibitor 1A (or p21), ETS proto-oncogene 1, fascin actin-bundling protein 1, hyperpolarization-activated cyclic nucleotide-gated potassium channel 4, insulin-like growth factor 1 receptor LIM and SH3 protein 1, purine nucleoside phosphorylase, and transgelin 2. These mechanistic data further support the clinical relevance of the identified miRs. miR-1, miR-133a/b, miR-145, miR-208a/b, and miR-499(a) in plasma and/or serum show some potential for diagnosis of cardiovascular disease. However, biased selection of miRs in most studies and unexplained contrasting results are major limitations of current miR research. Inconsistencies need to be addressed in order to definitively identify clinically useful miRs. Therefore, this paper presents important aspects to improve future miR research, including unbiased selection of miRs, standardization/normalization of reference miRs, adjustment for patient comorbidities and medication, and robust protocols of data-sharing plans that could prevent selective publication and selective reporting of miR research outcomes.

The impact of systemic sclerosis on arterial wall stiffness parameters and endothelial function

Systemic sclerosis (SSc) is characterized by thickening and fibrosis of skin and internal organs that is associated with vascular damage. SSc may lead to arterial dysfunction and premature aging of the arteries. However, its relationship with parameters of arterial wall dysfunction has not been fully explored. To determine if carotid–radial pulse wave velocity (PWV), aortic augmentation index (AIx) and endothelial function are altered in SSc patients, 17 consecutive patients with SSc and 34 age- and gender-matched controls were included in our study. PWV and AIx were assessed non-invasively by applanation tonometry. The endothelium-dependent flow-mediated dilatation (FMD) test in a brachial artery was performed by the ultrasound system. The blood investigations included serum lipid profile, glucose, and high-sensitivity CRP (hsCRP) measurements. As compared to controls, SSc patients had significantly higher medians of the AIx (p = 0.002) and the PWV (p = 0.04) and the median of the FMD was significantly lower (p = 0.001). Stepwise linear regression including comorbid factors showed that SSc was a significant independent predictor of all arterial wall parameters measures. SSc patients have increased AIx and PWV and lower FMD as compared to control subjects. The relationship between SSc and measures of arterial wall parameters still remains unclear. Though replication of the results presented here is required, we conclude that SSc has a great impact on large and conduit arteries damage.

Arterial wall dysfunction in systemic lupus erythematosus

Carotid-radial pulse wave velocity (PWV), aortic augmentation index (AIx) and endothelium-dependent flow-mediated dilatation (FMD) have been repeatedly showed to be related to premature atherosclerosis and cardiovascular diseases in different settings of population. The increased arterial stiffness and endothelium dysfunction may add to premature aging of the arteries in systemic lupus erythematosus (SLE) patients. Still data about arterial stiffness and endothelium function in inflammatory rheumatic diseases are not well described. The aim of this study was to determine the PWV, its derivate marker AIx and FMD and factors possibly influencing them in young SLE women without significant organ damage. Thirty women between 23 and 55 years with an established SLE diagnosis and 66 healthy women were consequently included in the study and both groups were comparable according to age, body mass index (BMI), serum lipid profile and creatinine. PWV was determined by measuring carotid-radial pulse wave transit time with the help of applanation tonometry and AIx, its derivate marker, was calculated as a difference between two waveform peaks expressed as a percentage of the pulse pressure. The FMD was performed by obtaining the repeated scans of the brachial artery at rest and during reactive hyperemia. In SLE women, PWV and AIx were significantly higher and FMD was not different from controls. In linear multiple stepwise regression analysis if patients and controls were both considered, PWV was weakly related to mean blood pressure (MBP), AIx was mostly predicted by age and MBP and FMD was predicted by the diameter of blood vessel, BMI, high density lipoproteins. If the sole SLE setting was analyzed, PWV was not related to any of the pending parameters, AIx turned out to be related to organ damage measured by Systemic Lupus International collaborative Clinics (SLICC) index and age, and FMD obtained strong and significant relation with vessel diameter, and BMI, and disease duration. Regardless of the small number of study group patients, we can state that controlling for MBP and taking measures towards organ damage prevention can partially slow down the process of early atherosclerosis in SLE patients.

Extracorporeal shockwave myocardial revascularization improves clinical symptoms and left ventricular function in patients with refractory angina.

BackgroundMedical therapy for refractory angina is limited and the prognosis is poor. Experimental data suggest that the use of extracorporeal shockwave myocardial revascularization (ESMR) can contribute to angiogenesis and improve symptoms of angina and left ventricular (LV) function. The objective of this study was to examine the effects of ESMR on clinical symptoms as well as LV function as assessed by cardiac MRI in patients with refractory angina. MethodsPatients with Canadian Cardiovascular Society (CCS) class III–IV angina despite medical therapy and ischemia documented on thallium or echo-dobutamine were eligible for the study. ESMR therapy was applied with a commercially available cardiac shockwave generator system under echocardiographic guidance. LV function was assessed before and 6 months after therapy by cardiac MRI. ResultsTwenty patients (four women, 16 men; mean age 64 years, range 45–83) were included in the study. The CCS class after treatment improved in all patients (16 patients angina pectoris CCS from III to II and four patients from IV to III). The use of sublingual nitroglycerin was significantly reduced as well. There was a significant improvement in LV ejection fraction as assessed by blinded MRI following therapy in the overall population (51 vs. 59%, P<0.05). ConclusionThis study demonstrates the potential efficacy of ESMR for the treatment of refractory angina pectoris. The patients showed both a significant clinical response as well as improved LV ejection fraction on serial MRI imaging. Larger studies are needed to adequately define the clinical utility of this novel therapy.

Value of scar imaging and inotropic reserve combination for the prediction of segmental and global left ventricular functional recovery after revascularisation

BackgroundThis study sought to prospectively and directly compare three cardiovascular magnetic resonance (CMR) viability parameters: inotropic reserve (IR) during low-dose dobutamine (LDD) administration, late gadolinium enhancement transmurality (LGE) and thickness of the non-contrast-enhanced myocardial rim surrounding the scar (RIM). These parameters were examined to evaluate their value as predictors of segmental left ventricular (LV) functional recovery in patients with LV systolic dysfunction undergoing surgical or percutaneous revascularisation. The second goal of the study was to determine the optimal LDD-CMR- and LGE-CMR-based predictor of significant (≥ 5%) LVEF improvement 6 months after revascularisation.MethodsIn 46 patients with chronic coronary artery disease (CAD) (63 ± 10 years of age, LVEF 35 ± 8%), wall motion and the above mentioned CMR parameters were evaluated before revascularisation. Wall motion and LGE were repeatedly assessed 6 months after revascularisation. Logistic regression analysis models were created using 333 dysfunctional segments at rest.ResultsAn LGE threshold value of 50% (LGE50) and a RIM threshold value of 4 mm (RIM4) produced the best sensitivities and specificities for predicting segmental recovery. IR was superior to LGE50 for predicting segmental recovery. When the areas under the ROC curves is compared, the combined viability prediction model (LGE50 + IR) was significantly superior to IR alone in all analysed sets of segments, except the segments with an LGE from 26% to 75% (p = 0.08). The RIM4 model was not superior to the LGE50 model. A myocardial segment was considered viable if it had no LGE or had any LGE and produced IR during LDD stimulation. ROC analysis demonstrated that ≥ 50% of viable segments from all dysfunctional and revascularised segments in a patient predict significant improvement in LVEF with a 69% sensitivity and 70% specificity (AUC 0.7, p = 0.05). The cut-off of ≥ 3 viable segments was a less useful predictor of significant global LV recovery.ConclusionsLDD-CMR is superior to LGE-CMR as a predictor of segmental recovery. The advantage is greatest in the segments with an LGE from 26% to 75%. The RIM cut-off value of 4 mm had no superiority over the LGE cut-off value of 50% in predicting the segmental recovery. Patients with ≥ 50% of viable segments from all dysfunctional and revascularised had a tendency to improve LVEF by ≥ 5% after revascularisation.

Hypertension and Cardiac Arrhythmias

Arterial hypertension is a widespread disease and one of important yet under-recognized and under-treated causes of atrial and ventricular arrhythmias. Hypertrophy of cardiac muscle in hypertensive patients is characterized not only by increased myocardial mass, but also by proliferation of fibrous tissue and decreased intercellular coupling, that lead to inhomogeneity of electrical properties and propensity to various arrhythmias. Many trials show the importance of treating hypertension in order to restore normal myocardial function and decrease the number of premature beats, runs of ventricular tachycardia, and attacks of atrial fibrillation. To date, the most convincing data are collected regarding the importance of blockade of renin-angiotensin-aldosterone system (RAAS) in order to avoid arrhythmias in arterial hypertension. Other antihypertensive drug classes (eg beta-blockers, calcium antagonists) are also useful, and investigational compounds that aim at regression of hypertrophy are under search. Polymorphism of genes coding the function of RAAS, pathways of synthesis and degradation of proteins and other cardiac and extracardiac systems involved in regulation of blood pressure, are recognized as promising targets for research.

Randomized evaluation of a novel, fixed-dose combination of perindopril 3.5 mg/amlodipine 2.5 mg as a first-step treatment in hypertension.

Objective: To evaluate perindopril 3.5 mg/amlodipine 2.5 mg once daily, a novel fixed-dose combination adapted for first-step treatment in patients with hypertension. This fixed dose had to be equivalent to amlodipine 5 mg in terms of blood pressure efficacy, but with an expected better tolerability profile. We selected two drugs with complementary modes of action, with doses chosen so that each drug would contribute similarly to the overall blood pressure-lowering effect Methods: An international, randomized, double-blind, placebo-controlled study with six equal parallel treatment arms and an 8-week randomized treatment period, whose design, clinical significance and non-inferiority criteria were in accordance with European guidelines. Results: In all, 1581 patients with mild-to-moderate uncomplicated hypertension (mean age 51.7 years) were randomized and 94.7% completed the study. The combination was statistically and clinically superior to placebo (between-group differences: SBP: −7.22 mmHg, DBP: −4.12 mmHg, P < 0.001 for both). Rates of response and normalization of blood pressure were greater with the combination (P < 0.001 for both) and numerical differences relative to placebo were apparent at 2 weeks. The combination was superior to either component given singly (P < 0.001 for both drugs, for SBP and DBP), and was non-inferior to both component drugs given singly at their lowest clinically-approved doses. The components of the combination had similar effects on SBP (perindopril 3.5 mg: −16.3 mmHg; amlodipine 2.5 mg: −16.0 mmHg). Adverse events relating to peripheral oedema were less frequent with the combination than with amlodipine 5 mg. Conclusions: The observed blood pressure-lowering efficacy, rapidity of onset of effect and favourable safety profile of the combination perindopril 3.5 mg/amlodipine 2.5 mg indicate its potential suitability for use as first-step treatment in hypertension.

Lithuanian High Cardiovascular Risk (LitHiR) primary prevention programme - rationale and design

Lithuanian High Cardiovascular Risk (LitHiR) primary prevention programme - rationale and design Objectives: According to the latest WHO data, coronary heart disease deaths in Lithuania reached 38.3% of total deaths. Based on the unfavourable situation with cardiovascular morbidity and mortality in Lithuania the Lithuanian High Cardiovascular Risk (LitHiR) programme aimed at estimation and aggressive managing of cardiovascular risk factors. This paper describes the Lithuanian High Cardiovascular Risk programme protocol. Design and methods: In 2006 the Lithuanian High Cardiovascular Risk programme was started. LitHiR programme recruited men - at the age of 40-54 years and women - 50-64 years without overt cardiovascular disease. The two-level approach - primary health care institutions (PHCI) and specialized cardiovascular prevention units (CVPU) - was applied. The subjects selected were tested for cardiovascular risk and those with high cardiovascular risk were sent to secondary (CVPU) level, for other the plan of preventive measures of risk factor reduction was created. In years 2006-2010 overall 266,391 persons (36.9% from all target population) were examined. Among them 164,657 subjects (61.8%) were tested for the first time, 68,832 (25.8%) were tested repeatedly one time, 32,848 subjects (12.3%) were tested repeatedly for two and more times. Conclusions: The programme aimed at estimation and managing of cardiovascular risk factors striving to reduce acute cardiovascular event related morbidity and mortality, to slow down the progression of sub-clinical atherosclerosis into overt cardiovascular disease, to increase the number of newly identified cases of diabetes, metabolic syndrome and latent course of atherosclerosis related diseases, to decrease hospitalizations for treatment of arterial hypertension and coronary heart disease.

Impact of renal sympathetic denervation on cardiac sympathetic nerve activity evaluated by cardiac MIBG imaging.

AIMS The objective of the present study was to investigate an effect of renal artery sympathetic denervation (RASD) on patients with resistant hypertension and RASD effect on cardiac sympathetic nerve activity. It is known that an abnormally activated sympathetic tone is associated with progression of heart failure (HF). METHODS AND RESULTS We investigated 16 patients with resistant arterial hypertension (mean age 54.88±7.89 years, mean 24-hr ambulatory blood pressure [BP] systolic 161.07±20.12 mmHg, diastolic 97.6±16.25 mmHg, using 6.44±0.96 antihypertensive drugs), who underwent bilateral RASD. Echocardiography, 24-hr ambulatory BP and 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy were performed before and six months after RASD. There were no significant changes in 24-hr ambulatory systolic and diastolic BP before RASD and six months after it: systolic BP before RASD was 161.07±20.12 mmHg and 144.93±17.27 mmHg after (p=0.050); diastolic BP before RASD was 97.6±16.25 mmHg and 89.87±12.33 mmHg after (p=0.182). We observed a significant change in cardiac sympathetic nerve activity assessed by 123I-MIBG scintigraphy, as an increase of late heart-to-mediastinum (H/M) ratio, varying from 2.21±0.47 to 2.35±0.52 m/s (p=0.02). CONCLUSIONS Selective RASD significantly reduces cardiac sympathetic overdrive assessed by 123I-MIBG scintigraphy. Presumably, this positively affects HF progression in patients with resistant arterial hypertension.