Christos Varounis

Lipoprotein-Associated Phospholipase A2 Bound on High-Density Lipoprotein Is Associated With Lower Risk for Cardiac Death in Stable Coronary Artery Disease Patients : A 3-Year Follow-Up

OBJECTIVES The aim of this study was to examine the prognostic value of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) associated with high-density lipoprotein (HDL) (HDL-Lp-PLA(2)) in patients with stable coronary artery disease (CAD). BACKGROUND Lp-PLA(2) is a novel risk factor for cardiovascular disease. It has been postulated that the role of Lp-PLA(2) in atherosclerosis may depend on the type of lipoprotein with which it is associated. METHODS Total plasma Lp-PLA(2) and HDL-Lp-PLA(2) mass and activity, lipids, and C-reactive protein were measured in 524 consecutive patients with stable CAD who were followed for a median of 34 months. The primary endpoint was cardiac death, and the secondary endpoint was hospitalization for acute coronary syndromes, myocardial revascularization, arrhythmic event, or stroke. RESULTS Follow-up data were obtained from 477 patients. One hundred twenty-three patients (25.8%) presented with cardiovascular events (24 cardiac deaths, 47 acute coronary syndromes, 28 revascularizations, 22 arrhythmic events, and 2 strokes). Total plasma Lp-PLA(2) mass and activity were predictors of cardiac death (hazard ratio [HR]: 1.013; 95% confidence interval [CI]: 1.005 to 1.021; p = 0.002; and HR: 1.040; 95% CI: 1.005 to 1.076; p = 0.025, respectively) after adjustment for traditional risk factors for CAD. In contrast, HDL-Lp-PLA(2) mass and activity were associated with lower risk for cardiac death (HR: 0.972; 95% CI: 0.952 to 0.993; p = 0.010; and HR: 0.689; 95% CI: 0.496 to 0.957; p = 0.026, respectively) after adjustment for traditional risk factors for CAD. CONCLUSIONS Total plasma Lp-PLA(2) is a predictor of cardiac death, while HDL-Lp-PLA(2) is associated with lower risk for cardiac death in patients with stable CAD, independently of other traditional cardiovascular risk factors.

Osteopontin as a novel prognostic marker in stable ischaemic heart disease: a 3‐year follow‐up study

Eur J Clin Invest 2010; 40 (4): 288–293

Functional Electrical Stimulation is More Effective in Severe Symptomatic Heart Failure Patients and Improves Their Adherence to Rehabilitation Programs

BACKGROUND Functional electrical stimulation (FES) improves exercise capacity and quality of life in chronic heart failure (CHF) patients. However, there is no evidence regarding the effectiveness of this treatment modality according to the severity of CHF. This study compares the effectiveness of FES on exercise capacity, endothelial function, neurohormonal status, and emotional stress in New York Heart Association (NYHA) III-IV versus NYHA II patients. METHODS AND RESULTS Eighteen NYHA II and 13 age- and sex-matched NYHA III-IV patients with stable CHF (left ventricular ejection fraction <35%) underwent a 6-week FES training program. Questionnaires addressing quality of life (Kansas City Cardiomyopathy Questionnaire, functional and overall), and emotional stress (Zung self-rating depression scale, Beck Depression Inventory), as well as plasma B-type natriuretic peptide (BNP), 6-minute walking distance test (6MWT), and endothelial function (flow-mediated dilatation [FMD]) were assessed at baseline and after completion of training protocol. 6MWT and plasma BNP improved significantly in 2 patient groups (both P < .001) after training program. The improvement of BNP was statistically greater in NYHA III-IV patients posttreatment than in those with NYHA II class (F=315.342, P < .001). Similarly, the improvement of 6MWT was statistically greater in NYHA III-IV group than in NYHA II patients (F=79.818, P < .001). Finally, an FES-induced greater improvement of FMD (F=9.517, P=.004) and emotional stress scores was observed in NYHA III-IV patients in comparison to NYHA II patients. There was a higher proportion of NYHA III-IV patients adhering to the FES training program for additional 3 months compared with the NYHA II group of patients (76.9% vs. 55.6%, P < .001). CONCLUSION FES might exert a greater beneficial effect on clinical and neurohormonal status of NYHA III-IV patients in comparison to NYHA II patients. This effect may have important clinical relevance leading to increased adherence of severe CHF patients to exercise rehabilitation programs.

Mortality after catheter ablation for atrial fibrillation compared with antiarrhythmic drug therapy. A meta-analysis of randomized trials

INTRODUCTION Nonrandomized studies suggest a survival benefit for patients with atrial fibrillation (AF) undergoing catheter ablation compared with antiarrhythmic drug (AAD) therapy. Data from randomized trials are lacking. We performed a meta-analysis on mortality in randomized controlled trials comparing AF ablation with AADs. METHODS Pubmed, the Cochrane Central Register of Controlled Trials, and abstracts of major conferences were searched for randomized trials comparing AF catheter ablation with AADs. Eight trials with a total of 930 patients were analyzed. Trial quality was assessed by a modified Jadad scale. Follow-up was 1 year in most trials. We assessed fixed effect risk differences (RDs) with the Mantel-Haenzel method, heterogeneity with I(2) statistic, and publication bias with Beggs funnel plot and with Eggers test. RESULTS A total of 7 deaths were reported: 3 in the ablation and 4 in the AAD arm. There was no difference in mortality between AF ablation and AAD therapy. The RD of mortality in all trials between patients randomized to ablation and those randomized to AADs was -0.003 (95% CI -0.018 to 0.013, P = .74) without evidence for heterogeneity (I(2) = 0%, P = .907). No potential publication bias was found. There was also no difference in rates of stroke or transient ischemic attack between ablation and antiarrhythmic therapy for AF (RD = 0.004, 95% CI -0.010 to 0.018, P = .54). CONCLUSION This meta-analysis of randomized controlled trials showed similar survival of patients undergoing catheter ablation for AF compared with patients treated with AADs after 12 months of follow-up. There was also no difference in the rates of stroke or transient ischemic attack. These findings can be probably explained by the low-risk young populations who were included in the trials and the relatively short 12-month follow-up.

Relationship between plasma osteopontin and oxidative stress in patients with coronary artery disease

Background: It is known that oxidative stress plays an important role in the pathogenesis of atherosclerosis and that an association exists between osteopontin (OPN) and atherosclerosis. Objectives: It was proposed that malondialdehyde (MDA), a biomarker of lipid peroxidation and oxidative stress, would be related to plasma OPN levels in patients with coronary artery disease (CAD). Methods/results: Plasma OPN and MDA levels were measured in 71 patients (60 males and 11 females; mean age 61.7 ± 10 years). Fifty-eight patients had significant CAD (group I) and 13 patients were free of CAD as defined angiographically (group II). Plasma OPN was measured by enzyme-linked immunosorbent assay (ELISA), while MDA was determined spectrophotometrically. Multivariate regression analysis revealed that ln-transformed OPN levels were independently associated with MDA after adjustment for age, hypertension and diabetes mellitus (R2 = 0.278, p = 0.0004 and β regression coefficient = 0.252 [standard error = 0.0958], p = 0.011). OPN and MDA levels were higher in patients with diabetes (73.6 ± 36.2 ng/ml versus 56.1 ± 30.9 ng/ml, p = 0.02 and 2.5 ± 0.5 μM versus 2.0 ± 0.5 μM, p = 0.002, respectively). Conclusions: The association between OPN and MDA levels in patients with CAD suggests an interaction between OPN and oxidative stress. This interaction may play a role in the pathogenesis of atherosclerosis.

Prognostic value of high sensitivity troponin T in patients with acutely decompensated heart failure and non-detectable conventional troponin T levels

BACKGROUND High-sensitivity troponin Τ (hs-TnΤ) allows the detection of very minor myocardial injury and has emerged as a novel prognostic marker in patients with cardiovascular disease. The aim of the present study was to determine the prognostic utility of hs-TnΤ levels in patients admitted to hospital for acutely decompensated heart failure (ADHF) and non-detectable conventional TnΤ levels. METHODS We prospectively enrolled 113 consecutive ADHF patients [77 (68%) men], mean age: 72.7±11.3 years, presented at admission with normal (<0.03 ng/ml) conventional (4th generation) TnΤ levels. Hs-TnΤ levels were measured by relevant commercially available kits and patients were monitored for major adverse events during a median follow-up period of 174 days (94-728 days). RESULTS In the univariate Cox proportional hazard analysis, hs-TnΤ was significantly related to death (HR=1.002 with 95%: confidence interval (CI) 1.001-1.003, P=0.001). In multivariate analysis, it remained a significant predictor of death after adjustment for age, gender, ejection fraction and creatinine levels (HR=1.003 with 95%: CI 1.001-1.005, P=0.008). CONCLUSION hs-TnΤ seems to identify high risk patients hospitalized for ADHF, independently of other classical prognostic biomarkers. Further studies are necessary to confirm the utility of this novel biomarker in risk stratification and management of patients with ADHF.

Mild depression versus C-reactive protein as a predictor of cardiovascular death: a three year follow-up of patients with stable coronary artery disease.

Abstract Objective: Depression is common in patients with coronary artery disease (CAD) and is associated with higher risk of cardiovascular adverse events. We aimed to explore the prognostic role of mild depression on cardiovascular mortality and compare its prognostic value with C-reactive protein (CRP) levels in patients with stable CAD. Research design and methods: We initially recruited 523 consecutive patients with stable CAD. Glucose, lipids and CRP levels were measured and an echocardiographic study was performed. In addition, depressive symptomatology was assessed with the Zung Depression Rating Scale (ZDRS, range 20–80). Patients on antidepressant treatment or with ZDRS score ≥60 were excluded. Patients were followed up at 6 month intervals (median 33 months, interquartile range 24–40 months) by telephone interview. Results: Follow-up data were obtained from 485 patients (92.7%). Nineteen patients with baseline CRP levels >10 mg/L and eight with non-cardiovascular death were excluded from analysis. Of the remaining 458 patients 113 (24.7%) presented cardiac events. Of them 21 died (4.6%), 42 developed acute coronary syndrome (9.2%), 27 (5.9%) had a revascularization procedure due clinical deterioration, two had a stroke (0.44%) and 21 (4.6%) an arrhythmic event. Multivariate Cox regression analysis showed that ZDRS score was independent predictor of cardiovascular death (hazard ratio [HR]: 1.104 with 95% confidence interval [CI]: 1.039–1.172, p = 0.001) after adjustment for conventional risk factors and CRP. The Wald test statistic of CRP was 2.59, whereas the Wald test statistic of ZDRS score was 3.23, indicating better predictability of ZDRS score. ZDRS score was also independent predictor of both cardiovascular death and arrhythmic event (HR: 1.102 with 95% CI: 1.051–1.156, p < 0.001) after adjustment for conventional risk factors and CRP levels. The main limitations of our study were the evaluation of depression at one point in time and the assessment of inflammatory burden by measuring only CRP levels. Conclusions: Mild depression is associated with increased cardiovascular mortality and is a better predictor than CRP levels in patients with stable CAD.

Attainment of optional low-density lipoprotein cholesterol goal of less than 70 mg/dl and impact on prognosis of very high risk stable coronary patients: a 3-year follow-up

Objectives: We aimed to investigate the proportion of very high-risk patients with coronary heart disease (CHD) who achieve the optional low-density lipoprotein cholesterol (LDL-C) target of < 70 mg/dl (1.8 mmol/liter), the factors that influence the success rate and the impact on their prognosis. Research design and methods: We enrolled 1337 consecutive patients with stable CHD. Fasting lipids were determined and all cardiovascular events were recorded during a median follow-up of 33 months. Results: The majority (86.5%) of patients were taking lipid-lowering medication (95.5% statins), but only 50.6% had LDL-C levels of < 100 mg/dl (2.6 mmol/liter). In total, 941 (70.4%) patients were considered very high risk and only 15.1% of them had LDL-C levels of < 70 mg/dl. Τhe use of intensive lipid-lowering medication was associated with 12-fold (95% CI 6.98 – 20.76; p < 0.001) higher possibility in achieving LDL-C levels of < 70 mg/dl. Attainment of LDL-C levels of < 70 mg/dl by patients at very high risk were independent predictors of all cardiovascular events (HR = 0.34, 95% CI 0.17 – 0.70; p = 0.003). Conclusions: The vast majority of very high-risk patients do not achieve the optional LDL-C goal; this is mainly due to the suboptimal uptitration of statin dose and is translated into loss of clinical benefits.

The impact of smoking on long-term outcome of patients with premature (≤35 years) ST-segment elevation acute myocardial infarction

BACKGROUND There are few data regarding the long-term prognosis of young survivors of acute myocardial infarction (AMI). We explored the long-term outcome in individuals who had sustained a premature ST-segment elevation AMI. METHODS We recruited 257 consecutive patients who had survived their first AMI ≤35years of age. Patients were followed up for up to 18years. Clinical end points included all major adverse coronary events (MACE): cardiac death, readmission for acute coronary syndrome, arrhythmias, or coronary revascularization due to clinical deterioration. RESULTS The most prevalent risk factor at presentation was smoking (93.7%). Follow-up data were obtained from 237 patients (32.2±3.7years old). The median follow-up period was 9.1years. During follow-up, 139 (58.6%) patients reported continuation of smoking. Ninety-one (38.4%) patients had recurrent MACE (13 deaths, 59 acute coronary syndromes, 2 arrhythmias, and 17 revascularizations). Multivariable Cox regression analysis showed that persistence of smoking, left ventricular ejection fraction (LVEF), and reperfusion therapy (fibrinolysis or primary coronary angioplasty) were independent predictors of MACE after adjustment for conventional risk factors. Continuation of smoking remained an independent predictor for MACE after additional adjustments for LVEF (hazard ratio 2.154, 95% CI 1.313-3.535, P=.002) or reperfusion treatment (hazard ratio 2.327, 95% CI 1.423-3.804, P=.001). Harrell c statistic showed that the model with persistent smoking had the best discriminatory power compared with models with LVEF or reperfusion treatment. CONCLUSIONS In the era of statins and reperfusion treatment, continuation of smoking is the strongest independent long-term predictor for recurrent MACE in young survivors of premature AMI.

Circadian pattern of symptoms onset in patients ≤35 years presenting with ST-segment elevation acute myocardial infarction

BACKGROUND There are scarce data regarding the circadian pattern of symptoms onset in young patients presenting with acute myocardial infarction (AMI). We explored whether young patients with ST-segment elevation AMI exhibit a circadian variation in symptoms onset. METHODS We recruited prospectively 256 consecutive patients who had survived their first ST-segment elevation AMI ≤35 years of age. Patients were categorized into 4 groups by 6-h intervals over 24 h. RESULTS In 49 patients (19.1%) the clinical presentation of AMI was atypical. The symptoms onset was as follows: 00:01 to 06:00, 19.1%, 06:01 to 12:00, 32.4%; 12:01 to 18:00, 28.1%; and 18:01 to 24:00, 20.3%. There was a significant association between the time of day and the likelihood of symptoms onset (Rayleigh test, p<0.001). Between 00:01 and 06:00 the incidence of AMI onset was lower than expected and between 06:01 and 12:00 was higher (p=0.034 and p=0.011, respectively), whereas in the other 6-h period groups no difference was found between expected and observed AMI incidence (p=0.280 and p=0.131). No significant differences were found regarding clinical characteristics, i.e. traditional risk factors, reperfusion treatment of AMI, ejection fraction of left ventricle, time interval from pain onset to hospital arrival, dietary habits and physical activity, among the 6-h period groups. CONCLUSIONS ST-segment elevation AMI in individuals ≤35 years of age follows a circadian pattern with a morning peak. This information might be useful for the prompt diagnosis and treatment of AMI in very young patients which occurs rarely and frequently with atypical clinical presentation.