Agata Bielecka-Dabrowa

Takotsubo cardiomyopathy — The current state of knowledge

Takotsubo cardiomyopathy is defined as acute chest pain during stressful incidents which is associated with ST-segment abnormalities and/or increased serum troponin levels. There is also regressive systolic dysfunction which is usually localized in the apical and medial left ventricles but there are no significant coronary artery lesions. The ventricular asynergy is also described in the right ventricle but is less common. Almost all the patients are women. The onset of this disease is typically triggered by an acute emotional or stress event or by an accumulation of trivial and repetitive stresses. The etiology of this syndrome remains unclear. Myocardial ischemia and reperfusion due to microvascular spasm, aborted myocardial infarction and related no-reflow phenomenon have been proposed as inducers of Takotsubo cardiomyopathy. The temporal relationship between the stressful event and the triggering of the clinical syndrome as well as the report of elevated catecholamine plasma levels during the acute phase suggest a possible involvement of the sympathetic nervous system. A smaller left ventricular size and hormonal disturbances in women may also play a role.

The mechanisms of atrial fibrillation in hyperthyroidism

Atrial fibrillation (AF) is a complex condition with several possible contributing factors. The rapid and irregular heartbeat produced by AF increases the risk of blood clot formation inside the heart. These clots may eventually become dislodged, causing embolism, stroke and other disorders. AF occurs in up to 15% of patients with hyperthyroidism compared to 4% of people in the general population and is more common in men and in patients with triiodothyronine (T3) toxicosis. The incidence of AF increases with advancing age. Also, subclinical hyperthyroidism is a risk factor associated with a 3-fold increase in development of AF. Thyrotoxicosis exerts marked influences on electrical impulse generation (chronotropic effect) and conduction (dromotropic effect). Several potential mechanisms could be invoked for the effect of thyroid hormones on AF risk, including elevation of left atrial pressure secondary to increased left ventricular mass and impaired ventricular relaxation, ischemia resulting from increased resting heart rate, and increased atrial eopic activity. Reentry has been postulated as one of the main mechanisms leading to AF. AF is more likely if effective refractory periods are short and conduction is slow. Hyperthyroidism is associated with shortening of action potential duration which may also contribute to AF.

HSP 70 and atherosclerosis – protector or activator?

Background: Atherosclerosis and its complications represent the leading cause of morbidity and mortality. Heat shock protein 70 (HSP70) protects cellular elements from injury by reducing oxidation, inflammation and apoptosis and by refolding damaged proteins. HSP70 improves viability of stressed vascular smooth muscle cells, possibly via its chaperone functions. It has been proposed that the response mounted against bacterial HSPs results in an autoimmune reaction, which has the potential to cause complement-mediated endothelial injury, and hence accelerate atherogenesis. Objective: to examine the roles of HSPs in atherosclerosis. Methods: A literature review. Results/Conclusions: The role of HSPs in atherosclerosis is controversial. HSP60 probably acts as an autoantigen, and may trigger both cell- and antibody-mediated immune responses, while HSP70 is likely to be involved in cytoprotection. The significance of this inverse relation between HSP70 and atherosclerosis has not yet been elucidated. Whether HSPs will become therapeutic targets remains to be established.

An update on biomarkers of heart failure in hypertensive patients.

Biomarkers should have high sensitivity, specificity, reproducibility, be cost-effective, and provide incremental predictive or diagnostic utility over standard risk factors or tests. Despite numerous studies investigating biomarkers in heart failure (HF), there are only a few that predict HF in hypertensive patients. This article summarizes data from numerous studies concerning possible biomarkers of HF in hypertensive patients such as: serum uric acid (SUA), interleukins, monocyte chemoattractant protein one (MCP-1), cardiotrophin-1 (CT-1), carboxy-terminal propeptide of procollagen type I (PICP), type I collagen telopeptide (CITP) and N-terminal propeptide of type III procollagen (PIIINP), metalloproteinases (MMPs), B-type natriuretic peptide (BNP) and its derivatives, glycoprotein CA125 and cystatin C. Early detection of patients of increased risk of hypertensive heart disease may result in early implementation of effective preventive strategies. Therefore, there is need to identify newer biomarkers, if they can improve risk prediction, identifying patients, in which earlier or more aggressive intervention will improve clinical outcomes.

The Rise and Fall of Hypertension: Lessons Learned from Eastern Europe

Hypertension is a progressive cardiovascular syndrome that arises from many differing, but interrelated, etiologies. Hypertension is the most prevalent cardiovascular disorder, affecting 20% to 50% of the adult population in developed countries. Arterial hypertension is a major risk factor for cardiovascular diseases and death. Epidemiologic data have shown that control of hypertension is achieved in only a small percentage of hypertensive patients. Findings from the World Health Organization project Monitoring Trends and Determinants in Cardiovascular Diseases (MONICA) showed a remarkably high prevalence (about 65%) of hypertension in Eastern Europeans. There is virtually no difference however, between the success rate in controlling hypertension when comparing Eastern and Western European populations. Diagnosing hypertension depends on both population awareness of the dangers of hypertension and medical interventions aimed at the detecting elevated blood pressure, even in asymptomatic patients. Medical compliance with guidelines for the treatment of hypertension is variable throughout Eastern Europe. Prevalence of hypertension increases with age, and the management of hypertension in elderly is a significant problem. The treatment of hypertension demands a comprehensive approach to the patient with regard to cardiovascular risk and individualization of hypertensive therapy.

The effects of statins on blood pressure in normotensive or hypertensive subjects — A meta-analysis of randomized controlled trials

OBJECTIVE The aim of this meta-analysis was to investigate whether statin therapy is associated with blood pressure (BP)-lowering in patients with or without hypertension. BACKGROUND The beneficial effects of statins on the cardiovascular system may in part be related to effects beyond lipid-lowering. It has been suggested that statins may reduce BP; however the available data are still ambiguous and often conflicting. METHODS Data from Scopus, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials for the years 1966-January 2012 were searched for studies that investigated the effect of statins on BP in normotensive or in hypertensive subjects. We included all randomized controlled clinical trials that investigated this effect. Changes in systolic and diastolic BP were the key outcomes of interest. RESULTS The final analysis included 18 trials and 5628 subjects (4692 normotensive and 936 hypertensive patients) randomized to receive either statins or placebo. The weighted mean difference of systolic (∆SBP) and diastolic blood pressure (∆DBP) in normotensive patients for the 11 statin trials included were 0.03 (95% CI: -0.95-1.02; p = 0.95) and -0.28 (95% CI: -0.80-0.24; p = 0.29), respectively. For hypertensive patients treated with statins (8 trials) the weighted mean difference of ∆SBP and ∆DBP were 1.45 (95% CI: -0.49-3.39; p = 0.14) and -1.32 (95% CI: -3.93-1.28; p = 0.32) respectively. CONCLUSIONS Despite previous suggestions statin therapy in normotensive or hypertensive patients does not lead to significant reductions in systolic or diastolic BP.

The meaning of hypokalemia in heart failure

Maintenance of normal potassium (K(+)) homeostasis has become an increasingly important limiting factor in the therapy of heart failure (HF). With the application of loop diuretics and digoxin, hypokalemia has become a frequent and feared side effect of treatment. Low serum K(+) in HF may be also a marker of increased neurohormonal activity and disease progression. To gain the maximum benefit from treatment, we need to individualize drug use and carefully monitor electrolytes. Symptomatic HF patients (New York Heart Association class III-IV) should be prescribed the lowest dose of diuretic necessary to maintain euvolemia. Mild hypokalemia may be corrected by the use of aldosterone receptor antagonists such as spironolactone or eplerenone. However, a more severe hypokalemia should preferably be corrected using K(+) supplement. Serum K levels should be frequently checked and maintained between 4.0 and 5.5 mEq/l (mmol/l).

Current place of beta-blockers in the treatment of hypertension.

Hypertension represents the most common cardiovascular risk factor, affecting more than 25% of the adult population in developed societies. Although beta-blockers have been previously shown to effectively reduce blood pressure and have been used for hypertension treatment for over 40 years, their effect on cardiovascular morbidity and mortality in hypertensive patients remains controversial and their use in uncomplicated hypertension is currently still under debate. According to the previous recommendations beta-blockers should not be preferred as first-line therapy in hypertension patients. This review summarizes the current knowledge on application of beta-blockers in patients with hypertension and discusses the most recent guidelines of the European Society of Hypertension (2009) on beta-blockers applications.

Heart failure biomarkers in patients with dilated cardiomyopathy

BACKGROUND We set out to evaluate the utility of selected heart failure (HF) biomarkers in patients with dilated cardiomyopathy (DCM). METHODS In a prospective, randomized study, 68 DCM patients with left ventricular ejection fraction (LVEF) ≤ 40% treated optimally were included. They were observed for 5 years. Initial and control tests included full clinical examination, measurement of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and IL-10, syndecan-4, cystatin C (CysC) and N-terminal pro-brain natriuretic peptide (NT-proBNP), echocardiographic examination, and the assessment of exercise capacity in 6-minute walk test (6MWT). RESULTS Finally, after 5-year follow-up we analyzed the data of 45 DCM patients. Concentration of syndecan-4 correlated negatively with LVEF (R=-0.36, p=0.02) and positively with LV systolic (R=0.57, p<0.001) and diastolic diameters (R=0.64, p<0.001). A positive correlation between CysC and right ventricular diastolic diameter (R=0.38, p=0.01), and negative correlations between CysC and glomerular filtration rate (R=-0.49, p<0.001), LVEF (R=-0.4, p=0.02), and 6 MWT (R=-0.46, p<0.001) were noted. Patients who had an increase in LVEF during 5 years were characterized by lower levels of CysC (p=0.01) and NT-proBNP (p<0.001). CysC≤95mg/l and NT-proBNP≤32pg/ml were the best predictors of LVEF increase in DCM patients. Multivariate regression analysis showed that 6 MWT was the only independent predictor of HF re-hospitalization (OR 0.989; p<0.001), and NT-proBNP and LV diastolic diameter were the only risk factors of increased mortality (OR 1.001; p=0.007 and OR 2.960; p=0.025, respectively) in DCM patients. CONCLUSIONS CysC correlates negatively with both kidney function and exercise capacity. Syndecan-4 may be a useful biomarker for predicting adverse LV remodeling in DCM patients.

The Multi-Biomarker Approach for Heart Failure in Patients with Hypertension

We assessed the predictive ability of selected biomarkers using N-terminal pro-brain natriuretic peptide (NT-proBNP) as the benchmark and tried to establish a multi-biomarker approach to heart failure (HF) in hypertensive patients. In 120 hypertensive patients with or without overt heart failure, the incremental predictive value of the following biomarkers was investigated: Collagen III N-terminal propeptide (PIIINP), cystatin C (CysC), lipocalin-2/NGAL, syndecan-4, tumor necrosis factor-α (TNF-α), interleukin 1 receptor type I (IL1R1), galectin-3, cardiotrophin-1 (CT-1), transforming growth factor β (TGF-β) and N-terminal pro-brain natriuretic peptide (NT-proBNP). The highest discriminative value for HF was observed for NT-proBNP (area under the receiver operating characteristic curve (AUC) = 0.873) and TGF-β (AUC = 0.878). On the basis of ROC curve analysis we found that CT-1 > 152 pg/mL, TGF-β < 7.7 ng/mL, syndecan > 2.3 ng/mL, NT-proBNP > 332.5 pg/mL, CysC > 1 mg/L and NGAL > 39.9 ng/mL were significant predictors of overt HF. There was only a small improvement in predictive ability of the multi-biomarker panel including the four biomarkers with the best performance in the detection of HF—NT-proBNP, TGF-β, CT-1, CysC—compared to the panel with NT-proBNP, TGF-β and CT-1 only. Biomarkers with different pathophysiological backgrounds (NT-proBNP, TGF-β, CT-1, CysC) give additive prognostic value for incident HF in hypertensive patients compared to NT-proBNP alone.