Incidence and Predictors of Hyperkalemia in Patients With Heart Failure: An Analysis of the CHARM Program Akshay S. Desai, Karl Swedberg, John J. V. McMurray, Christopher B. Granger, Salim Yusuf, ...James B. Young, Mark E. Dunlap, Scott D. Solomon, James W. Hainer, Bertil Olofsson, Eric L. Michelson, Marc A. Pfeffer We examined the incidence and predictors of hyperkalemia in a broad population of patients with symptomatic heart failure enrolled in the CHARM (Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity) Program. Independent of assignment to candesartan or placebo, the risk of hyperkalemia increased with advanced age, male gender, baseline hyperkalemia, renal failure, diabetes, and background use of angiotensin-converting enzyme inhibitors or spironolactone. Candesartan increased the observed rate of hyperkalemia in these subgroups but was associated with a consistent reduction in the risk of cardiovascular death or heart failure hospitalization. Although renin-angiotensin-aldosterone antagonists improve clinical outcomes in heart failure patients, careful surveillance of serum potassium and creatinine is essential.
Objectives We evaluated the effect of angiotensin-converting enzyme (ACE) inhibitor ramipril on the incidence of atrial fibrillation (AF) in patients enrolled in the Heart Outcomes Prevention ...Evaluation trial. Background Atrial fibrillation is the most common arrhythmia affecting the general population and is associated with increased morbidity and mortality. Retrospective secondary analyses of some of the large trials of ACE inhibitors have suggested that ACE inhibitors may prevent AF. Methods We evaluated the occurrence of AF by reviewing the electrocardiogram tracings at entry, at 2 years, and at the end of the study, as well as hospitalizations among 8335 high-risk participants from the Heart Outcomes Prevention Evaluation study, ≥55 years, without known heart failure or left ventricular (LV) systolic dysfunction and followed for a median period of 4.5 years. We compared the impact of ramipril and matched placebo on occurrence of AF. The results were compared to similar trials. Results Over the 4.5 years follow-up, the incidence of new AF was low (2.1%, 177/8335), and ramipril did not significantly reduce the rate of new AF compared with placebo (86/4291 2.0% vs 91/4044 2.2%) with an odds ratio of 0.92 (95% confidence interval, 0.68-1.24; P = .57). These results added to the previous ACE inhibitor trials (excluding trials in patients with LV dysfunction) showed no significant reduction in new AF among patients treated with these agents (1088/20,930 5.0% vs 1343/22,878 5.9%; relative risk, 0.92; 95% confidence interval, 0.80-1.05). Conclusion Although the incidence of AF was low, treatment with ramipril in this population without known LV systolic dysfunction did not significantly reduce this dysrrhythmia.
Red Cell Distribution Width as a Novel Prognostic Marker in Heart Failure: Data From the CHARM Program and the Duke Databank G. Michael Felker, Larry A. Allen, Stuart J. Pocock, Linda K. Shaw, John ...J. V. McMurray, Marc A. Pfeffer, Karl Swedberg, Duolao Wang, Salim Yusuf, Eric L. Michelson, Christopher B. Granger, for the CHARM Investigators Among 36 routine laboratory measures in the CHARM (Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity) program, higher red cell distribution width showed the greatest association with cardiovascular death and heart failure hospitalization (adjusted hazard ratio 1.17 per 1 SD increase, p < 0.001). Only age and cardiomegaly showed better independent association with outcome. This finding was replicated in the Duke Databank, in which red cell distribution width continued to be strongly associated with mortality (adjusted hazard ratio 1.29 per 1 SD, p < 0.001). Understanding how and why this marker is associated with outcome may provide novel insights into heart failure pathophysiology.
Background The OASIS-5 (Organization to Assess Strategies in Ischemic Syndromes-5) trial demonstrated that fondaparinux was noninferior to enoxaparin while reducing the risk of bleeding by 50%. The ...objectives of our study were to assess the effects of fondaparinux compared to enoxaparin in patients stratified by their Global Registry of Acute Coronary Events (GRACE) score and to examine the ability of the GRACE score to predict bleeding in patients with acute coronary syndromes (ACS). Methods We analyzed efficacy and safety according to the GRACE admission risk score. Results The impact of fondaparinux versus enoxaparin on the primary outcome of death, myocardial infarction, and refractory ischemia at 180 days was similar in the low-, intermediate-, and high-risk groups: 7.0% versus 7.7% (hazard ratio HR 0.90, 95% confidence interval CI 0.75-1.08), 10.2% versus 11.3% (HR 0.89, 95% CI 0.77-1.03), and 20.1% versus 21.1% (HR 0.95, 95% CI 0.85-1.06). Major bleeding rates were higher with increasing GRACE risk scores: 2.2%, 3.2%, and 4.1% in the low, intermediate, and high-risk groups. Six-month mortality was 2.2%, 4.2%, and 12.3% in the 3 groups. The risk of major bleeding was substantially lower with fondaparinux in all groups: 1.6% versus 2.9% (HR 0.55, 95% CI 0.39-0.77), 2.2% versus 4.1% (HR 0.53, 95% CI 0.40-0.70), 2.8% versus 5.5% (HR 0.50, 95% CI 0.38-0.64). Conclusion The GRACE score predicted both bleeding and mortality in patients with ACS. The efficacy and safety of fondaparinux were consistent in all risk groups supporting its use in a broad range of ACS patients.
Efficacy and Safety of Fondaparinux Versus Enoxaparin in Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention: Results From the OASIS-5 Trial Shamir R. Mehta, ...Christopher B. Granger, John W. Eikelboom, Jean-Pierre Bassand, Lars Wallentin, David P. Faxon, Ron J. G. Peters, Andrzej Budaj, Rizwan Afzal, Susan Chrolavicius, Keith A. A. Fox, Salim Yusuf We report a prospectively planned analysis of 6,238 patients with acute coronary syndrome who underwent early percutaneous coronary intervention in the OASIS-5 (Fifth Organization to Assess Strategies in Ischemic Syndromes) randomized trial. Fondaparinux compared with enoxaparin reduced major bleeding by more than 50% (2.4% vs. 5.1%, hazard ratio HR 0.46, p < 0.00001), with similar rates of ischemic events, resulting in superior net clinical benefit (death, myocardial infarction, stroke, major bleeding: 8.2% vs. 10.4%, HR 0.78, p = 0.004). Catheter thrombus occurred in <1% in both groups, but was prevented by use of standard unfractionated heparin at the time of percutaneous coronary intervention without compromising the benefits of upstream fondaparinux.
Revascularization for Unprotected Left Main Stem Coronary Artery Stenosis: Stenting or Surgery David P. Taggart, Sanjay Kaul, William E. Boden, T. Bruce Ferguson, Jr, Robert Guyton, Michael Mack, ...Paul Sergeant, Richard J. Shemin, Peter K. Smith, Salim Yusuf This manuscript reviews current data regarding outcomes with surgery and stents for unprotected left main stem stenosis and concludes that coronary artery bypass grafting remains the preferred revascularization treatment for good surgical candidates.
Reply Kaul, Sanjay, MD, FACC; Boden, William E., MD, FACC; Ferguson, T. Bruce, MD, FACC ...
Journal of the American College of Cardiology,
2008, Letnik:
52, Številka:
7
Journal Article
Abstract Background Microflora-dependent trimethylamine-N-oxide (TMAO) formation, which results from intake of choline and L-carnitine-rich food, shows promise as a predictor of cardiovascular ...disease (CVD) risk, but these associations have not been examined in ethnically diverse populations. In a multiethnic population-based study of adults in Canada, we assessed the stability of TMAO and L-carnitine in stored serum samples and their association with intimal medial thickness, prevalent risk factors, and clinical events. Methods In a randomly sampled cross-sectional study of 1286 Canadians, fasting serum samples were collected and stored. In 292 consecutive individuals (99 CVD cases and 193 unmatched control subjects), L-carnitine and TMAO concentrations were assessed using validated analytical approaches. Results The mean (± SD) TMAO level was 1.998 ± 3.13 μM and L-carnitine was 42.29 ± 11.35 μM. The relative levels of the samples did not appreciably change after 3 freeze-thaw cycles (coefficient of variation, 5.6% and 4.7%, respectively). No significant association between L-carnitine levels and prevalent CVD was found, with adjustment for covariates (odds ratio, 1.57; 95% confidence interval, 0.58-4.26; P trend = 0.65), for highest vs lowest quintile group. TMAO levels showed a significant, graded association with prevalent CVD (odds ratio, 3.17; 95% confidence interval, 1.05-9.51; P trend = 0.02). After further adjustment for diabetes status, meat, fish, and cholesterol intake, the association remained significant. No significant association between carotid intimal medial thickness and L-carnitine ( P = 0.64) or TMAO ( P = 0.18) was found. Conclusions Serum TMAO and L-carnitine analysis on stored samples is reliable. Our findings support an association between TMAO with prevalent CVD in a multiethnic population. This finding requires replication in larger studies in which dietary intake and stored serum samples exist.
Combined Metabolomic and Proteomic Analysis of Human Atrial Fibrillation Manuel Mayr, Shamil Yusuf, Graeme Weir, Yuen-Li Chung, Ursula Mayr, Xiaoke Yin, Christophe Ladroue, Basetti Madhu, Neil ...Roberts, Ayesha De Souza, Salim Fredericks, Marion Stubbs, John R. Griffiths, Marjan Jahangiri, Qingbo Xu, A. John Camm A combined metabolomic and proteomic analysis of human atrial tissues from matched cohorts in sinus rhythm, from those who developed atrial fibrillation (AF) post-operatively, and from patients in persistent AF revealed a discordant regulation of energy substrates preceding the onset of arrhythmia and a compensatory increase in ketone bodies in persistent AF.
Objectives This study sought to determine the prevalence of lipid and lipoprotein abnormalities and their association with the risk of a first acute myocardial infarction (AMI) among Asians. ...Background Patterns of lipid abnormalities among Asians and their relative impact on cardiovascular risk have not been well characterized. Methods In a case-control study, 65 centers in Asia recruited 5,731 cases of a first AMI and 6,459 control subjects. Plasma levels of lipids and apolipoproteins in the different Asian subgroups (South Asians, Chinese, Southeast Asians, and Japanese) were determined and correlated with the risk of AMI. Results Among both cases and controls, mean low-density lipoprotein cholesterol (LDL-C) levels were about 10 mg/dl lower in Asians compared with non-Asians. A greater proportion of Asian cases and controls had LDL-C ≤100 mg/dl (25.5% and 32.3% in Asians vs. 19.4% and 25.3% in non-Asians, respectively). High-density lipoprotein cholesterol (HDL-C) levels were slightly lower among Asians compared with non-Asians. There was a preponderance of people with low HDL-C among South Asians (South Asia vs. rest of Asia: cases 82.3% vs. 57.4%; controls 81% vs. 51.6%; p < 0.0001 for both comparisons). However, despite these differences in absolute levels, the risk of AMI associated with increases in LDL-C and decreases in HDL-C was similar for Asians and non-Asians. Among South Asians, changes in apolipoprotein (Apo)A1 predicted risk better than HDL-C. ApoB/ApoA1 showed the strongest association with the risk of AMI. Conclusions The preserved association of LDL-C with risk of AMI among Asians, despite the lower baseline levels, suggests the need to rethink treatment thresholds and targets in this population. The low HDL-C level among South Asians requires further study and targeted intervention.
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