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Leptin predicts short-term major adverse cardiac events in patients with coronary artery disease.
Puurunen, VP, Kiviniemi, A, Lepojärvi, S, Piira, OP, Hedberg, P, Junttila, J, Ukkola, O, Huikuri, H
Annals of medicine. 2017;(5):448-454
Abstract
INTRODUCTION Leptin is an adipose tissue-derived hormone associated with cardiovascular risk factors. We examined whether leptin predicts major adverse cardiac events (MACE) in coronary artery disease (CAD) patients. METHODS Fasting plasma leptin levels were measured in 1327 male and 619 female CAD patients. The patients were followed up for two years. The primary endpoint (MACE) was the composite of a hospitalisation for congestive heart failure (CHF) or a cardiac death. The secondary endpoint was the composite of an acute coronary syndrome (ACS) or a stroke. RESULTS In regression analysis including established risk variables, high leptin levels were associated with a significantly increased risk of MACE (HR 3.37; 95%CI 1.64-6.90; p = 0.001) and ACS or stroke (HR 1.95; 95%CI 1.29-2.96; p = 0.002). Adding leptin to the risk model for MACE increased the C-index from 0.78 (95%CI 0.71-0.85) to 0.81 (0.74-0.88) and improved classification (NRI 0.36; 95%CI 0.13-0.60; p = 0.002) and discrimination of the patients (IDI 0.016; 95%CI 0.001-0.030; p = 0.031). CONCLUSIONS High plasma leptin levels predict short-term occurrence of CHF or cardiac death and ACS or stroke in patients with CAD independently of established risk factors. The possible harmful effects of leptin should be thoroughly investigated. Key messages Leptin is a peptide hormone secreted mainly by adipose tissue. It has been associated with several cardiovascular risk factors. High leptin levels predict the short-term occurrence of congestive heart failure or cardiac death and ACS or stroke in patients with CAD independently of established risk factors. The possible detrimental effects of leptin on the cardiovascular system should be thoroughly investigated.
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Flecainide therapy suppresses exercise-induced ventricular arrhythmias in patients with CASQ2-associated catecholaminergic polymorphic ventricular tachycardia.
Khoury, A, Marai, I, Suleiman, M, Blich, M, Lorber, A, Gepstein, L, Boulos, M
Heart rhythm. 2013;(11):1671-5
Abstract
BACKGROUND Calsequestrin-associated catecholaminergic polymorphic ventricular tachycardia (CPVT2) can cause sudden death in young individuals in response to stress. Beta-blockers are the mainstay medical treatment for patients with CPVT2. However, they do not prevent syncope and sudden death in all patients. Flecainide was reported to reduce exercise-induced ventricular arrhythmias (EIVA) in patients with ryanodine receptor-associated CPVT. The role of flecainide in CPVT2 is not known. OBJECTIVE To summarize our experience in combining flecainide and beta-blockers in high-risk patients with CPVT2. METHODS All patients with CPVT2 (10 patients) who have high-risk features (syncope, EIVA, or appropriate implantable cardioverter-defibrillator [ICD] shocks) despite beta-blockers with or without calcium channel blockers were treated with a combination of flecainide and beta-blockers. Exercise test was done before and after beginning treatment with flecainide. RESULTS All patients had EIVA and 4 had appropriate ICD shocks before flecainide treatment. EIVA-included frequent ventricular premature beats and or ventricular tachycardia during the exercise test while on high dose of beta-blockers with or without calcium channel blockers before treatment with flecainide. After combination therapy with flecainide and beta-blockers, EIVA were suppressed completely in all patients. During follow-up of 15.5 ± 10.4 months (range 2-29 months), 8 patients were free of symptoms and free of arrhythmias. Two patients had 1 VT storm episode with recurrent ICD shocks despite repeated normal stress test. CONCLUSIONS Flecainide can completely prevent ventricular arrhythmia during exercise and partially prevent recurrent ICD shocks in high-risk patients with CPVT2.
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Serum 25(OH)D is a 2-year predictor of all-cause mortality, cardiac death and sudden cardiac death in chest pain patients from Northern Argentina.
Naesgaard, PA, León De La Fuente, RA, Nilsen, ST, Woie, L, Aarsland, T, Brede, C, Staines, H, Nilsen, DW
PloS one. 2012;(9):e43228
Abstract
BACKGROUND Several studies have shown an association between vitamin D deficiency and cardiovascular risk. Vitamin D status is assessed by determination of 25-hydroxyvitamin D [25(OH)D] in serum. METHODS We assessed the prognostic utility of 25(OH)D in 982 chest-pain patients with suspected acute coronary syndrome (ACS) from Salta, Northern Argentina. 2-year follow-up data including all-cause mortality, cardiac death and sudden cardiac death were analyzed in quartiles of 25(OH)D, applying univariate and multivariate analysis. RESULTS There were statistically significant changes in seasonal 25(OH)D levels. At follow-up, 119 patients had died. The mean 25(OH)D levels were significantly lower among patients dying than in long-term survivors, both in the total population and in patients with a troponin T (TnT) release (n = 388). When comparing 25(OH)D in the highest quartile to the lowest quartile in a multivariable Cox regression model for all-cause mortality, the hazard ratio (HR) for cardiac death and sudden cardiac death in the total population was 0.37 (95% CI, 0.19-0.73), p = 0.004, 0.23 (95% CI, 0.08-0.67), p = 0.007, and 0.32 (95% CI, 0.11-0.94), p = 0.038, respectively. In patients with TnT release, the respective HR was 0.24 (95% CI, 0.10-0.54), p = 0.001, 0.18 (95% CI, 0.05-0.60), p = 0.006 and 0.25 (95% CI, 0.07-0.89), p = 0.033. 25(OH)D had no prognostic value in patients with no TnT release. CONCLUSION Vitamin D was shown to be a useful biomarker for prediction of mortality when obtained at admission in chest pain patients with suspected ACS. TRIAL REGISTRATION ClinicalTrials.gov NCT01377402.
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Atorvastatin therapy may reduce the incidence of sudden cardiac death in patients with advanced chronic heart failure.
Vrtovec, B, Okrajsek, R, Golicnik, A, Ferjan, M, Starc, V, Schlegel, TT, Radovancevic, B
Journal of cardiac failure. 2008;(2):140-4
Abstract
BACKGROUND In retrospective studies, statin therapy has been related to decreased incidence of sudden cardiac death (SCD) in heart failure. We sought to prospectively investigate a relation between atorvastatin therapy and SCD in patients with advanced chronic heart failure. METHODS AND RESULTS We enrolled 110 patients with heart failure with a left ventricular ejection fraction less than 30% and cholesterol level greater than 150 mg/dL. Fifty-five patients were randomized to atorvastatin (10 mg/day) (statin group); the remaining 55 patients received no statins (controls). Patients were followed for 1 year. At baseline, the two groups did not differ in age, sex, left ventricular ejection fraction, cholesterol, B-type natriuretic peptide, heart rate variability, or QT variability. During follow-up, 29 patients died (26%) and 2 patients (2%) underwent heart transplantation. Of the 29 deaths, 13 were attributed to pump failure, 15 were attributed to SCD, and 1 was attributed to noncardiac causes. All-cause mortality was lower in the statin group (9/55, 16%) than in controls (20/55, 36%) (P = .017). The same was true of the SCD rate (3/55 [5%] vs. 12/55 [22%], P = .012), but not of the pump failure (5/55 [9%] vs. 8/55 [15%], P = .38). SCD-free survival was 2.3-times higher in the statin group than in controls (P = .01). CONCLUSIONS Atorvastatin therapy seems to be associated with decreased incidence of SCD in patients with advanced chronic heart failure. Larger studies are ongoing to confirm this hypothesis.
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[Reduction of cardiovascular risk in primary prophylaxy of coronary heart disease].
Sobenin, IA, Prianishnikov, VV, Kunnova, LM, Radinovich, EA, Orekhov, AN
Klinicheskaia meditsina. 2005;(4):52-5
Abstract
The purpose of the study was to evaluate the effects of Allicor, an Allium sativum (garlic) preparation with prolonged activity, on 10-year prognostic risk of coronary heart disease (CHD), acute myocardial infarction (MI) and sudden death in patients with elevated and high risk of CHD. 79 patients with elevated and high risk of CHD were included in a double blind randomized placebo-controlled study. They underwent multifactor evaluation of cardiovascular risk by algorithms based on the results of Framingham and Munster studies. Prolonged (12 months) administration of Allicor significantly reduced the multifactor risk, which was demonstrated by a 13.2% (p = 0.005) reduction of prognostic 10-year risk of CHD in men, and a 7.1% (p = 0.040) reduction of the same parameter in women. Prognostic 10-year risk of MI and sudden death in men was reduced by 26.1% (p = 0.025) and did not change significantly in women. In men the main factor of cardiovascular risk reduction was the decrease of cholesterol and low-density lipoprotein concentration by 23.5 +/- 6.6 mg/dl (p = 0.004), and in women - the increase of high-density lipoprotein level by 2.8 +/- 1.5 mg/dl (p = 0.040). The results of the study demonstrate that prolonged Allicor therapy can be applied to the large category of patients who are in need of atherosclerosis prevention.
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Neuroprotection becomes reality: changing times for cerebral resuscitation.
Damian, MS
Advances in experimental medicine and biology. 2004;:143-50
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Impact of sodium-hydrogen exchange inhibition by cariporide on death or myocardial infarction in high-risk CABG surgery patients: results of the CABG surgery cohort of the GUARDIAN study.
Boyce, SW, Bartels, C, Bolli, R, Chaitman, B, Chen, JC, Chi, E, Jessel, A, Kereiakes, D, Knight, J, Thulin, L, et al
The Journal of thoracic and cardiovascular surgery. 2003;(2):420-7
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Abstract
OBJECTIVES To evaluate the effects of cariporide on all-cause mortality or myocardial infarction at 36 days in patients at risk of myocardial necrosis after coronary artery bypass graft surgery. METHODS In the coronary artery bypass graft cohort of the GUARD During Ischemia Against Necrosis trial, patients > or =18 years who required urgent coronary artery bypass graft, repeat coronary artery bypass graft, or had a history of unstable angina and > or =2 risk factors (age >65 years, female gender, diabetes mellitus, ejection fraction <35%, or left main or 3-vessel disease) were randomized to placebo (n = 743) or cariporide 20 mg (n = 736), 80 mg (n = 705), or 120 mg (n = 734). A 1-hour intravenous infusion was initiated shortly before surgery and administered every 8 hours for 2 to 7 days. Patients were followed up for 6 months. A nonparametric covariance analysis was used to calculate the primary efficacy endpoint. RESULTS Baseline characteristics were similar between treatment groups. The cariporide 20- and 80-mg groups had event rates similar to placebo. The endpoint of all-cause mortality or myocardial infarction at day 36 was significant with cariporide 120 mg versus placebo (event rate 12.2% vs 16.2%; P =.027). The risk reduction was evident on postoperative day 1 (3.3% vs 6.5%; P =.005) and was maintained at 6 months (event rate 15.0% vs 18.6%; P =.033). Cariporide was well tolerated, and most adverse events were mild and transient in this high-risk population. CONCLUSIONS Clinical benefit with cariporide 120 mg was observed early after treatment initiation and continued for 6 months postsurgery, suggesting that sodium-hydrogen exchange inhibition with cariporide is cardioprotective in patients undergoing high-risk coronary artery bypass graft surgery.
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Short QT Syndrome: a familial cause of sudden death.
Gaita, F, Giustetto, C, Bianchi, F, Wolpert, C, Schimpf, R, Riccardi, R, Grossi, S, Richiardi, E, Borggrefe, M
Circulation. 2003;(8):965-70
Abstract
BACKGROUND A prolonged QT interval is associated with a risk for life-threatening events. However, little is known about prognostic implications of the reverse-a short QT interval. Several members of 2 different families were referred for syncope, palpitations, and resuscitated cardiac arrest in the presence of a positive family history for sudden cardiac death. Autopsy did not reveal any structural heart disease. All patients had a constantly and uniformly short QT interval at ECG. METHODS AND RESULTS Six patients from both families were submitted to extensive noninvasive and invasive work-up, including serial resting ECGs, echocardiogram, cardiac MRI, exercise testing, Holter ECG, and signal-averaged ECG. Four of 6 patients underwent electrophysiological evaluation including programmed ventricular stimulation. In all subjects, a structural heart disease was excluded. At baseline ECG, all patients exhibited a QT interval CONCLUSIONS The short QT syndrome is characterized by familial sudden death, short refractory periods, and inducible ventricular fibrillation. It is important to recognize this ECG pattern because it is related to a high risk of sudden death in young, otherwise healthy subjects.
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Prospective study of C-reactive protein, homocysteine, and plasma lipid levels as predictors of sudden cardiac death.
Albert, CM, Ma, J, Rifai, N, Stampfer, MJ, Ridker, PM
Circulation. 2002;(22):2595-9
Abstract
BACKGROUND Sudden cardiac death (SCD) is an important cause of mortality even among apparently healthy populations. However, our ability to identify those at risk for SCD in the general population is poor, and more specific markers are needed. METHODS AND RESULTS To compare and contrast the relative importance of C-reactive protein (CRP), homocysteine, and lipids as long-term predictors of SCD, we performed a prospective, nested, case-control analysis involving 97 cases of SCD among apparently healthy men enrolled in the Physician's Health Study. Of these plasma markers measured, only baseline CRP levels were significantly associated with the risk of SCD over the ensuing 17 years of follow-up (P for trend=0.001). The increase in risk associated with CRP levels was primarily seen among men in the highest quartile, who were at a 2.78-fold increased risk of SCD (95% CI 1.35 to 5.72) compared with men in the lowest quartile. These results were not significantly altered in analyses that (in addition to the matching variables of age and smoking status) controlled for lipid parameters, homocysteine, and multiple cardiac risk factors (relative risk for highest versus lowest quartile 2.65, 95% CI 0.79 to 8.83; P for trend=0.03). In contrast to the positive relationship observed for CRP, neither homocysteine nor lipid levels were significantly associated with risk of SCD. CONCLUSIONS These prospective data suggest that CRP levels may be useful in identifying apparently healthy men who are at an increased long-term risk of SCD.
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Elevated plasma free fatty acid concentrations do not modify cardiac repolarization in patients treated by electrolyte-glucose-insulin infusion.
Nappo, F, Loreto, M, Giugliano, G, Grella, E, Esposito, K, Lettieri, B, Giugliano, D
Journal of endocrinological investigation. 2002;(7):RC19-22
Abstract
Fat emulsion infusion is routinely used as a source of calories and essential fatty acids for critically ill patients who may be at risk for acquired ventricular repolarization alterations due either to drugs or electrolyte disturbances. The aim of this study was to evaluate whether acute elevations of plasma free fatty acid concentrations influence the corrected Q-T interval (Q-Tc), Q-Tc dispersion and sympathetic nervous system activity in patients requiring parenteral nutrition. Thirty hospitalized patients (mean +/- SD: 62 +/- 17 yr of age) requiring total parenteral nutrition received an infusion of 10% (500 ml) triacylglycerol emulsion as a source of calories (450 Kcal); on another occasion, and in random order, the same patients received an infusion of 20% (500 ml) triacylglycerol emulsion (900 Kcal). The infusion lasted 8 h and was preceded by a sc injection of heparin (5,000 U). Infusions of both 10% and 20% triacylglycerol emulsion increased plasma free fatty acid (p<0.00 1) and triacylglycerol (p<0.01) concentrations, and was associated with no significant change in mean BP, heart rate, and plasma catecholamines. At baseline, Q-Tc and Q-Tc dispersion were within the normal range (<440 milliseconds for QTc and <40 ms for QTc-d) and did not show any significant change at any time during infusion of triacylglycerol emulsion at both concentrations. In the setting of a balanced parenteral nutrition, acute elevation of plasma free fatty acid concentrations in critically ill patients do not modify ventricular repolarization.