Amy Hsu

Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials

INTRODUCTION Oxidised LDL is thought to play an important part in the pathogenesis of atherosclerosis. Observational studies have associated alpha tocopherol (vitamin E), beta carotene, or both, with reductions in cardiovascular events, but not clinical trials. We did a meta-analysis to assess the effect of these compounds on long-term cardiovascular mortality and morbidity. METHODS We analysed seven randomised trials of vitamin E treatment and, separately, eight of beta carotene treatment; all trials included 1000 or more patients. The dose range for vitamin E was 50-800 IU, and for beta carotene was 15-50 mg. Follow-up ranged from 1.4 to 12.0 years. FINDINGS The vitamin E trials involved a total of 81788 patients and the beta carotene trials 138113 in the all-cause mortality analyses. Vitamin E did not provide benefit in mortality compared with control treatment (11.3 vs 11.1%, odds ratio 1.02 [95% CI 0.98-1.06] p=0.42) or significantly decrease risk of cardiovascular death (6.0 vs 6.0%, p=0.86) or cerebrovascular accident (3.6 vs 3.5%, p=0.31). Beta carotene led to a small but significant increase in all-cause mortality (7.4 vs 7.0%, 1.07 [1.02-1.11] p=0.003) and with a slight increase in cardiovascular death (3.4 vs 3.1%, 1.1 [1.03-1.17] p=0.003). No significant heterogeneity was noted for any analysis. INTERPRETATION The lack of a salutary effect was seen consistently for various doses of vitamins in diverse populations. Our results, combined with the lack of mechanistic data for efficacy of vitamin E, do not support the routine use of vitamin E.

Intravascular Ultrasound-Derived Measures of Coronary Atherosclerotic Plaque Burden and Clinical Outcome

OBJECTIVES The aim of this study was to investigate the relationship between intravascular ultrasound (IVUS)-derived measures of atherosclerosis and cardiovascular outcomes. BACKGROUND IVUS has been used in clinical trials to evaluate the effect of medical therapies on coronary atheroma progression. METHODS Coronary plaque progression was evaluated in 4,137 patients in 6 clinical trials that used serial IVUS. The relationship between baseline and change in percent atheroma volume (PAV) and total atheroma volume with incident major adverse cardiovascular events (MACE) was investigated. RESULTS PAV increased by 0.3% (p < 0.001), and 19.9% of subjects experienced MACE (0.9% death, 1.8% myocardial infarction, 18.9% coronary revascularization). Greater baseline PAVs were observed in patients who experienced myocardial infarctions (42.2 +/- 9.6% vs. 38.6 +/- 9.1%, p = 0.001), coronary revascularization (41.2 +/- 9.3% vs. 38.1 +/- 9.0%, p < 0.001), or MACE (41.3 +/- 9.2% vs. 38.0 +/- 9.0%, p < 0.001). Each standard deviation increase in PAV was associated with a 1.32-fold (95% confidence interval: 1.22 to 1.42; p < 0.001) greater likelihood of experiencing a MACE. During follow-up (21.1 +/- 3.7 months), greater increases in PAV, but not total atheroma volume, were observed in subjects who experienced MACE compared with those who did not (0.95 +/- 0.19% vs. 0.46 +/- 0.16%, p < 0.001). Each standard deviation increase in PAV was associated with a 1.20-fold (95% confidence interval: 1.10 to 1.31; p < 0.001) greater risk for MACE. Multivariate analysis revealed that factors associated with MACE included baseline PAV (p < 0.0001), change in PAV (p = 0.002), smoking (p = 0.0002) and hypertension (p = 0.01). CONCLUSIONS A direct relationship was observed between the burden of coronary atherosclerosis, its progression, and adverse cardiovascular events. The relationship between disease progression and outcomes largely reflected the need for coronary revascularization. These data support the use of atherosclerosis imaging with IVUS in the evaluation of novel antiatherosclerotic therapies.

Hospital Characteristics Associated With Feeding Tube Placement in Nursing Home Residents With Advanced Cognitive Impairment

CONTEXT Tube-feeding is of questionable benefit for nursing home residents with advanced dementia. Approximately two-thirds of US nursing home residents who are tube fed had their feeding tube inserted during an acute care hospitalization. OBJECTIVE To identify US hospital characteristics associated with higher rates of feeding tube insertion in nursing home residents with advanced cognitive impairment. DESIGN, SETTING, AND PATIENTS The sample included nursing home residents aged 66 years or older with advanced cognitive impairment admitted to acute care hospitals between 2000 and 2007. Rate of feeding tube placement was based on a 20% sample of all Medicare Claims files and was assessed in hospitals with at least 30 such admissions during the 8-year period. A multivariable model with the unit of the analysis being the hospital admission identified hospital-level factors independently associated with feeding tube insertion rates, including bed size, ownership, urban location, and medical school affiliation. Measures of each hospitals care practices for all patients with serious chronic illnesses were evaluated, including intensive care unit (ICU) use in the last 6 months of life, the use of hospice services, and the ratio of specialist to primary care physicians. Patient-level characteristics were also considered. MAIN OUTCOME MEASURE Endoscopic or surgical insertion of a gastrostomy tube during a hospitalization. RESULTS In 2797 acute care hospitals with 280,869 admissions among 163,022 nursing home residents with advanced cognitive impairment, the rate of feeding tube insertion varied from 0 to 38.9 per 100 hospitalizations (mean [SD], 6.5 [5.3]; median [interquartile range], 5.3 [2.6-9.3]). The mean rate of feeding tube insertions per 100 admissions was 7.9 in 2000, decreasing to 6.2 in 2007. Higher insertion rates were associated with the following hospital features: for-profit ownership vs government owned (8.5 vs 5.5 insertions per 100 hospitalizations; adjusted odds ratio [AOR], 1.33; 95% confidence interval [CI], 1.21-1.46), larger size (>310 beds vs <101 beds: 8.0 vs 4.3 insertions per 100 hospitalizations; AOR, 1.48; 95% CI, 1.35-1.63), and greater ICU use in the last 6 months of life (highest vs lowest decile: 10.1 vs 2.9 insertions per 100 hospitalizations; AOR, 2.60; 95% CI, 2.20-3.06). These differences persisted after controlling for patient characteristics. Specialist to primary care ratio and hospice use were weakly or not associated with feeding tube placement. CONCLUSION Among nursing home residents with advanced cognitive impairment admitted to acute care hospitals, for-profit ownership, larger hospital size, and greater ICU use was associated with increased rates of feeding tube insertion, even after adjusting for patient-level characteristics.

Impact of Blood Transfusion on Short- and Long-Term Mortality in Patients With ST-Segment Elevation Myocardial Infarction

OBJECTIVES We sought to examine the short- and long-term outcomes of blood transfusion in patients presenting with ST-segment elevation myocardial infarction (STEMI). BACKGROUND The short- and long-term consequences of blood transfusion in anemic patients with recent STEMI remain controversial. METHODS We evaluated 30-day, 6-month, and 1-year all-cause mortality among 4,131 STEMI patients enrolled in the GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) IIb trial. Patients were categorized according to whether they received a blood transfusion during hospitalization. Cox proportional hazards survival models with transfusion as a time-dependent covariate were conducted for the whole and for the propensity-matched groups. Additionally, a series of sensitivity analyses assessed the magnitude of hidden bias that would need to be present to explain the associations actually observed. RESULTS Death at 30 days (13.7% vs. 5.5%), 6 months (19.7% vs. 6.9%), and 1 year (21.8% vs. 8.7%) was significantly higher for transfused patients than for nontransfused patients, respectively. After adjusting for over 25 baseline characteristics, nadir hemoglobin, and propensity score for transfusion, and using transfusion as a time-dependent covariate, transfusion remained significantly associated with increased risk of mortality at 30 days (hazard ratio [HR]: 3.89, 95% confidence interval [CI]: 2.66 to 5.68, p < 0.001), 6 months (HR: 3.63, 95% CI: 2.67 to 4.95, p < 0.001), and 1 year (HR: 3.03, 95% CI: 2.25 to 4.08, p < 0.001). Similar results were observed in the propensity-matched patients. CONCLUSIONS Blood transfusion is associated with increased short- and long-term mortality in the setting of STEMI.

β-Blockers and Cardiovascular Events in Patients With and Without Myocardial Infarction Post Hoc Analysis From the CHARISMA Trial

Background—The long-term efficacy of &bgr;-blockers in patients with and without myocardial infarction (MI) is controversial. Methods and Results—This is post hoc analysis from the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial of 4772 patients with prior MI, 7804 patients with known atherothrombosis, and 2101 patients with risk factors alone but without heart failure. Primary outcome was a composite of nonfatal MI, stroke, or cardiovascular mortality. The cohorts were divided into 2 groups based on baseline &bgr;-blocker use. In the propensity score–matched prior MI cohort, after 28 months of follow-up, &bgr;-blocker use was associated with a 31% lower risk of the primary outcome (70 [7.1%] versus 100 [10.2%]; hazards ratio, 0.69; 95% confidence interval, 0.50–0.94; P=0.021), driven by a lower risk of recurrent MI (33 [3.4%] versus 48 [4.9%]; hazards ratio, 0.62; 95% confidence interval, 0.39–1.00; P=0.049) with no difference in mortality (52 [5.3%] versus 66 [6.7%]; P=0.20). In the known atherothrombotic disease and the risk factors alone cohorts, &bgr;-blocker use was not associated with lower ischemic outcomes, whereas a trend toward a higher risk of stroke (3.5% versus 1.5%; hazards ratio, 2.13; 95% confidence interval, 0.92–4.92; P=0.079) was observed in the risk factors alone cohort. This higher stroke risk was significant in the regression model adjusted to the propensity score (hazards ratio, 2.69; 95% confidence interval, 1.33–5.44; P=0.006) and in the multivariable models. Conclusions—&bgr;-blocker use in patients with prior MI but no heart failure was associated with a lower composite cardiovascular outcome driven by lower risk of recurrent MI with no difference in mortality. However, &bgr;-blocker use was not associated with lower cardiovascular events in those without MI, with a suggestion of inferior outcome with regard to stroke risk. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00050817.

Effect of aliskiren on progression of coronary disease in patients with prehypertension: The AQUARIUS randomized clinical trial

IMPORTANCE Blood pressure reduction and renin-angiotensin-aldosterone system inhibition are targets for treatment of atherosclerosis. The effect of renin inhibition on coronary disease progression has not been investigated. OBJECTIVE To determine the effects of renin inhibition with aliskiren on progression of coronary atherosclerosis. DESIGN, SETTING, AND PARTICIPANTS A double-blind, randomized, multicenter trial (Aliskiren Quantitative Atherosclerosis Regression Intravascular Ultrasound Study) comparing aliskiren with placebo in 613 participants with coronary artery disease, systolic blood pressure between 125 and 139 mm Hg (prehypertension range), and 2 additional cardiovascular risk factors conducted at 103 academic and community hospitals in Europe, Australia, and North and South America (enrollment from March 2009 to February 2011; end of follow-up: January 31, 2013). INTERVENTIONS Participants underwent coronary intravascular ultrasound (IVUS) imaging and were randomized to receive 300 mg of aliskiren (n = 305) or placebo (n = 308) taken orally daily for 104 weeks. Disease progression was measured by repeat IVUS examination after at least 72 weeks of treatment. MAIN OUTCOMES AND MEASURES The primary efficacy parameter was the change in percent atheroma volume (PAV) from baseline to study completion. Secondary efficacy parameters included the change in normalized total atheroma volume (TAV) and the percentage of participants with atheroma regression. Safety and tolerability were also assessed. RESULTS Evaluable imaging data were available at baseline and follow-up for 458 participants (74.7%). The primary IVUS efficacy parameter, PAV, did not differ between participants treated with aliskiren (-0.33%; 95% CI, -0.68% to 0.02%) and placebo (0.11%; 95% CI, -0.24% to 0.45%) (between-group difference, -0.43% [95% CI, -0.92% to 0.05%]; P = .08). The secondary IVUS efficacy parameter, TAV, did not differ between participants treated with aliskiren (-4.1 mm3; 95% CI, -6.27 to -1.94 mm3) and placebo (-2.1 mm3; 95% CI, -4.21 to 0.07 mm3) (between-group difference, -2.04 mm3 [95% CI, -5.03 to 0.95 mm3]; P = .18). There were no significant differences in the proportion of participants who demonstrated regression of PAV (56.9% vs 48.9%; P = .08) and TAV (64.4% vs 57.5%; P = .13) in the aliskiren and placebo groups, respectively. CONCLUSIONS AND RELEVANCE Among participants with prehypertension and coronary artery disease, the use of aliskiren compared with placebo did not result in improvement or slowing of progression of coronary atherosclerosis. These findings do not support the use of aliskiren for regression or prevention of progression of coronary atherosclerosis. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00853827.

Long-term outcomes and clinical predictors for pacemaker-requiring bradyarrhythmias after cardiac transplantation: Analysis of the UNOS/OPTN cardiac transplant database

BACKGROUND Pacemaker-requiring bradyarrhythmias after cardiac transplantation are common, and rarely can lead to sudden cardiac death. Prior outcomes studies have been limited to single-center data. OBJECTIVE This study sought to define the long-term outcomes and clinical predictors for pacemaker-requiring bradyarrhythmias in the cardiac transplant population. METHODS This study used multivariable analysis of the United Network for Organ Sharing/Organ Procurement and Transplantation Network (UNOS/OPTN) database of sequential U.S. cardiac transplant recipients from 1997 to 2007 stratified by postoperative bradyarrhythmias requiring a pacemaker. The primary end point was all-cause mortality. RESULTS Among 35,987 cardiac transplant recipients (age 46.1 ± 18.3 years, 76% male, 22% bicaval technique) with a follow-up of 6.3 ± 4.7 years, pacemaker-requiring bradyarrhythmias occurred in 3,940 patients (10.9%). Pacemaker recipients demonstrated improved survival (median 8.0 years vs. 5.2 years, P < .001), decreased 5-year mortality (13.8% vs. 17.7%, P < .001), and overall crude mortality (42.9% vs. 45.9%, P < .001). Multivariable propensity-score-adjusted analysis demonstrated improved survival among pacemaker recipients (adjusted hazard ratio 0.84, 95% confidence interval [CI] 0.80 to 0.88, P < .001) after adjustment for donor/recipient age, UNOS listing status, donor heart ischemic time, surgical technique, graft rejection, and other common comorbidities. The bicaval surgical technique was strongly protective against a postoperative pacemaker requirement (odds ratio [OR] 0.33, 95% CI 0.29 to 0.36, P < .001) in multivariable analysis. Among the other variables studied, only increasing donor age (OR 1.04, 95% CI 1.00 to 1.09, P < .001) and recipient age (OR 1.09, 95% CI 1.0 to 1.12, P < .001) were associated with a permanent pacemaker requirement. CONCLUSION Cardiac transplant recipients with pacemaker-requiring bradyarrhythmias have an excellent long-term prognosis. Increased mortality in the nonpacemaker group merits further investigation. Biatrial surgical technique and increasing donor/recipient age are associated with postoperative pacemaker requirement.

Peripheral vascular disease and one-year mortality following percutaneous coronary revascularization

The association between peripheral vascular disease and outcomes after percutaneous coronary intervention was examined in the Do Tirofiban and Reopro Give Similar Efficacy Outcome Trial (TARGET). After adjustments in a multivariate model, a history of peripheral vascular disease was found to be associated with a two- to threefold increase in mortality at 1 year after coronary stent placement.

High-Sensitivity C-Reactive Protein in Acute Heart Failure: Insights From the ASCEND-HF Trial

BACKGROUND Inflammation is associated with progression of chronic heart failure (HF). Few data exist on high-sensitivity C-reactive protein (hsCRP) levels and their importance in acute HF. METHODS AND RESULTS In this biomarker substudy of the ASCEND-HF trial, we measured hsCRP levels at admission (n = 794), 48-72 hours (n = 677), and 30 days (n = 581) and evaluated their association with outcomes. Levels of hsCRP were considerably elevated at admission (median 12.6 mg/L, interquartile range [IQR] 5.23-30.5) and 48-72 hours (median 11.0 mg/L, IQR 4.87-29.9) and declined only at 30 days (median 4.7 mg/L, IQR 1.83-13.1). Admission hsCRP was not associated with dyspnea improvement at 6 hours (74.1%) and 24 hours (86.2%), in-hospital death or worsening HF (n = 37; 4.7%), 30-day mortality or HF readmission (death: n = 25 [3.2%]; combined death and HF readmission: n = 95 [12.0%]), or 180-day mortality (n = 96; 12.1%). Hospital stay (median 5 days, IQR 3-7) was longer among patients with higher admission hsCRP levels (0.57 days per log2-hsCRP in adjusted models; 95% confidence interval [CI] 0.33-0.81; P < .001). Levels of hsCRP at 48-72 hours did not predict 30-day mortality or HF readmission and were only marginally associated with 180-day mortality. However, higher hsCRP at 30 days among survivors was associated with higher 180-day mortality in models including admission hsCRP (adjusted hazard ratio [HR] per log2-hsCRP: 1.23; 95% CI 1.04-1.45; P = .016). Patients with an hsCRP increase at day 30, defined as >10% increase over baseline value, had higher 180-day mortality risk compared with those with unchanged or decreased 30-day hsCRP (HR 2.29, 95% CI 1.16-4.52; P = .017). CONCLUSIONS Levels of hsCRP are elevated among patients with acute HF. Increasing levels at 30 days after discharge are associated with higher 180-day mortality.

The association between early ventricular arrhythmias, renin-angiotensin-aldosterone system antagonism, and mortality in patients with ST-segment-elevation myocardial infarction: Insights from global use of strategies to open coronary arteries (GUSTO) V

BACKGROUND The long-term prognostic significance of early (<48 hours) ventricular fibrillation (VF) or sustained ventricular tachycardia (VT) in patients with an acute myocardial infarction remains controversial. Emerging data suggest that some of the benefit of renin-angiotensin-aldosterone system (RAAS) antagonism may be derived from a reduction in the incidence of these arrhythmias in the setting of acute myocardial infarction. METHODS We assessed the relationship between early VF/VT (defined as within 48 hours after admission) and mortality in 16,588 patients from global use of strategies to open coronary arteries (GUSTO) V trial. Furthermore, we examined the relationship between baseline use of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB), early VF/VT, and mortality. RESULTS Early VF or VT occurred in 732 (4.4%) patients. Compared to patients without VF/VT, those experiencing early VF or VT had a significant increase in 30-day mortality (22% vs 5%, P < .001). Baseline use of an ACEI/ARB was associated with a decreased incidence of early VF/VT (odds ratio 0.65, 0.47-0.89, P = .008). A lower 30-day mortality was seen in patients with early VF/VT on baseline ACEI/ARB compared with patients with early VF/VT not receiving an ACEI/ARB at baseline (17.7% vs 24.2%, respectively, P = .04). The association between baseline RAAS antagonism and mortality persisted after adjustment for multiple confounders. CONCLUSIONS In patients presenting with acute myocardial infarction, early VF/VT identifies those at increased risk for 30-day mortality. Baseline use of RAAS antagonists is associated with a reduced incidence of malignant arrhythmias. Identifying how this association impacts short-term mortality in this patient population requires further prospective evaluation.