Cardiovascular Death Hazard Ratio Research Articles

The impact of hemodialysis on mortality risk and cause of death in Staphylococcus aureus endocarditis

BackgroundThe risk of infective endocarditis (IE) is markedly increased in patients receiving chronic hemodialysis compared with the general population, but outcome data are sparse. The present study investigated causes and risk factors of mortality in a hemodialysis-treated end-stage kidney disease- (ESKD) and a non-ESKD population with staphylococcus (S.) aureus endocarditis.MethodsHemodialysis-treated ESKD patients with S. aureus endocarditis were identified from Danish National Registries and Non-ESKD patients from The East Danish Database on Endocarditis. For establishing the cause of death The Danish Registry of Cause of Death was used. Independent risk factors of outcome were identified in multivariable Cox regression models.ResultsOne hundred twenty-one hemodialysis patients and 190 non-ESKD patients with S. aureus endocarditis were included during 1996–2012 and 2002–2012, respectively. The all-cause in-hospital mortality was 22.3% in hemodialysis- and 24.7% in non-ESKD patients. One-year mortality, excluding in-hospital mortality, was 26.4% in hemodialysis patients and 15.2% in non-ESKD patients.The hazard ratio of all-cause mortality in hemodialysis was 2.64 (95% CI 1.70–4.10) at > 70 days after admission compared with non-ESKD. Age (HR 1.03 (95% CI 1.02–1.04)) and diabetes mellitus (HR 2.17 (95% CI 1.54–3.10)) were independent risk factors of all-cause mortality. The hazard ratio of cardiovascular death in hemodialysis was 3.20 (95% CI 1.78–5.77) at > 81 days after admission compared with non-ESKD. Age and diabetes mellitus were independently related to cardiovascular death.ConclusionAll-cause in-hospital mortality rates were similar in hemodialysis and non-ESKD patients with S. aureus endocarditis whereas one-year mortality rates were significantly increased in the hemodialysis population.

Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout

BackgroundCardiovascular risk is increased in patients with gout. We compared cardiovascular outcomes associated with febuxostat, a nonpurine xanthine oxidase inhibitor, with those associated with allopurinol, a purine base analogue xanthine oxidase inhibitor, in patients with gout and cardiovascular disease.MethodsWe conducted a multicenter, double-blind, noninferiority trial involving patients with gout and cardiovascular disease; patients were randomly assigned to receive febuxostat or allopurinol and were stratified according to kidney function. The trial had a prespecified noninferiority margin of 1.3 for the hazard ratio for the primary end point (a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or unstable angina with urgent revascularization).ResultsIn total, 6190 patients underwent randomization, received febuxostat or allopurinol, and were followed for a median of 32 months (maximum, 85 months). The trial regimen was discontinued in 56.6% of patients, and 45.0% discontinued follow-up. In the modified intention-to-treat analysis, a primary end-point event occurred in 335 patients (10.8%) in the febuxostat group and in 321 patients (10.4%) in the allopurinol group (hazard ratio, 1.03; upper limit of the one-sided 98.5% confidence interval [CI], 1.23; P=0.002 for noninferiority). All-cause and cardiovascular mortality were higher in the febuxostat group than in the allopurinol group (hazard ratio for death from any cause, 1.22 [95% CI, 1.01 to 1.47]; hazard ratio for cardiovascular death, 1.34 [95% CI, 1.03 to 1.73]). The results with regard to the primary end point and all-cause and cardiovascular mortality in the analysis of events that occurred while patients were being treated were similar to the results in the modified intention-to-treat analysis.ConclusionsIn patients with gout and major cardiovascular coexisting conditions, febuxostat was noninferior to allopurinol with respect to rates of adverse cardiovascular events. All-cause mortality and cardiovascular mortality were higher with febuxostat than with allopurinol. (Funded by Takeda Development Center Americas; CARES ClinicalTrials.gov number, NCT01101035.)

Prognostic Performance of Heart Rate Recovery on an Exercise Test in a Primary Prevention Population.

BackgroundHeart rate (HR) recovery has been investigated in specific patient cohorts, but there is less information about the role of HR recovery in general populations. We investigated whether HR recovery has long‐term prognostic significance in primary prevention.Methods and ResultsExercise tests performed between 1993 and 2010 on patients aged 30 to 79 years without cardiovascular disease were included. Mortality was determined from Mayo Clinic records and Minnesota Death Index. Total, cardiovascular, and non‐cardiovascular mortality was reported according to HR recovery <13 bpm using Cox regression. 19 551 patients were included, 6756 women (35%), age 51±10 years. There were 1271 deaths over follow‐up of 12±5 years. HR recovery declined after age 60, and was also lower according to diabetes mellitus, hypertension, obesity, current smoking, and poor cardiorespiratory fitness but not sex or β‐blockers. Adjusting for these factors, abnormal HR recovery was a significant predictor of total (hazard ratio [95% confidence interval]=1.56 [1.384–1.77]), cardiovascular (1.95 [1.57–2.42]), and non‐cardiovascular death (1.41 [1.22–1.64]). Hazard ratios for cardiovascular death according to abnormal HR recovery were significant in all age groups (30–59, 60–69, 70–79), in both sexes, in patients with and without hypertension, obesity, and diabetes mellitus, but not in patients taking β‐blockers, current smokers, and patients with normal cardiorespiratory fitness.Conclusions HR recovery is a powerful prognostic factor predicting total, cardiovascular, and non‐cardiovascular death in a primary prevention cohort. It performs consistently well according to sex, age, obesity, hypertension, and diabetes mellitus but shows diminished utility in patients taking β‐blockers, current smokers, and patients with normal cardiorespiratory fitness.

CYP2C19 LOF and GOF-Guided Antiplatelet Therapy in Patients with Acute Coronary Syndrome: A Cost-Effectiveness Analysis.

This study aimed to examine the cost-effectiveness of CYP2C19 loss-of-function and gain-of-function allele guided (LOF/GOF-guided) antiplatelet therapy in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). A life-long decision-analytic model was designed to simulate outcomes of three strategies: universal clopidogrel (75mg daily), universal alternative P2Y12 inhibitor (prasugrel 10mg daily or ticagrelor 90mg twice daily), and LOF/GOF-guided therapy (LOF/GOF allele carriers receiving alternative P2Y12 inhibitor, wild-type patients receiving clopidogrel). Model outcomes included clinical event rates, quality-adjusted life-years (QALYs) gained and direct medical costs from perspective of US healthcare provider. Base-case analysis found nonfatal myocardial infarction (5.62%) and stent thrombosis (1.2%) to be the lowest in universal alternative P2Y12 inhibitor arm, whereas nonfatal stroke (0.72%), cardiovascular death (2.42%), and major bleeding (2.73%) were lowest in LOF/GOF-guided group. LOF/GOF-guided arm gained the highest QALYs (7.5301 QALYs) at lowest life-long cost (USD 76,450). One-way sensitivity analysis showed base-case results were subject to the hazard ratio of cardiovascular death in carriers versus non-carriers of LOF allele and hazard ratio of cardiovascular death in non-carriers of LOF allele versus general patients. In probabilistic sensitivity analysis of 10,000 Monte Carlo simulations, LOF/GOF-guided therapy, universal alternative P2Y12 inhibitor, and universal clopidogrel were the preferred strategy (willingness-to-pay threshold=50,000 USD/QALY) in 99.07%, 0.04%, and 0.89% of time, respectively. Using both CYP2C19 GOF and LOF alleles to select antiplatelet therapy appears to be the preferred antiplatelet strategy over universal clopidogrel and universal alternative P2Y12 inhibitor therapy for ACS patients with PCI.

Independent Prognostic Value of Single and Multiple Non-Specific 12-Lead Electrocardiographic Findings for Long-Term Cardiovascular Outcomes: A Prospective Cohort Study.

AimsThe long-term prognostic effect of non-specific 12-lead electrocardiogram findings is unknown. We aimed to evaluate the cumulative prognostic impact of axial, structural, and repolarization categorical abnormalities on cardiovascular death, independent from traditional risk scoring systems such as the Framingham risk score and the NIPPON DATA80 risk chart.Methods and ResultsA total of 16,816 healthy men and women from two prospective, longitudinal cohort studies were evaluated. 3,794 (22.6%) individuals died during a median follow-up of 15 years (range, 2.0–24 years). Hazard ratios for cardiovascular death, all-cause death, coronary death and stroke death were calculated for the cumulative and independent axial, structural, and repolarization categorical abnormalities adjusted for the Framingham risk score and the NIPPON DATA80 risk chart. Individuals with two or more abnormal categories had a higher risk of cardiovascular death after adjustment for Framingham risk score (men: HR 4.27, 95%CI 3.35–5.45; women: HR 4.83, 95%CI 3.76–6.22) and NIPPON DATA80 risk chart (men: HR 2.39, 95%CI 1.87–3.07; women: HR 2.04, 95%CI 1.58–2.64).ConclusionCumulative findings of axial, structural, and repolarization abnormalities are significant predictors of long-term cardiovascular death in asymptomatic, healthy individuals independent of traditional risk stratification systems.

Adaptive Servo-Ventilation for Central Sleep Apnea in Systolic Heart Failure

BackgroundCentral sleep apnea is associated with poor prognosis and death in patients with heart failure. Adaptive servo-ventilation is a therapy that uses a noninvasive ventilator to treat central sleep apnea by delivering servo-controlled inspiratory pressure support on top of expiratory positive airway pressure. We investigated the effects of adaptive servo-ventilation in patients who had heart failure with reduced ejection fraction and predominantly central sleep apnea.MethodsWe randomly assigned 1325 patients with a left ventricular ejection fraction of 45% or less, an apnea–hypopnea index (AHI) of 15 or more events (occurrences of apnea or hypopnea) per hour, and a predominance of central events to receive guideline-based medical treatment with adaptive servo-ventilation or guideline-based medical treatment alone (control). The primary end point in the time-to-event analysis was the first event of death from any cause, lifesaving cardiovascular intervention (cardiac transplantation, implantation of a ventricular assist device, resuscitation after sudden cardiac arrest, or appropriate lifesaving shock), or unplanned hospitalization for worsening heart failure.ResultsIn the adaptive servo-ventilation group, the mean AHI at 12 months was 6.6 events per hour. The incidence of the primary end point did not differ significantly between the adaptive servo-ventilation group and the control group (54.1% and 50.8%, respectively; hazard ratio, 1.13; 95% confidence interval [CI], 0.97 to 1.31; P=0.10). All-cause mortality and cardiovascular mortality were significantly higher in the adaptive servo-ventilation group than in the control group (hazard ratio for death from any cause, 1.28; 95% CI, 1.06 to 1.55; P=0.01; and hazard ratio for cardiovascular death, 1.34; 95% CI, 1.09 to 1.65; P=0.006).ConclusionsAdaptive servo-ventilation had no significant effect on the primary end point in patients who had heart failure with reduced ejection fraction and predominantly central sleep apnea, but all-cause and cardiovascular mortality were both increased with this therapy. (Funded by ResMed and others; SERVE-HF ClinicalTrials.gov number, NCT00733343.)

Cardiovascular mortality among a cohort of hypertensive and normotensives in Rio de Janeiro - Brazil - 1991-2009.

BackgroundAlthough there is strong evidence of the benefits of antihypertensive treatment, the high prevalence of this important cardiovascular risk factor and its complications, as well as the low control rates of hypertension observed in many studies justify the investigation of these relationships in population studies. The objective was to investigate the ratio of cardiovascular disease mortality between hypertensives (non-treated, controlled and uncontrolled) and non-hypertensives in a cohort of a population sample of adults living in Ilha do Governador, Rio de Janeiro state, Brazil, who were classified in a survey conducted in 1991 and 1992 and whose death certificates were sought 19 years later.MethodsA cohort study was performed on probabilistic linkage between data from an epidemiological study of hypertension performed in Ilha do Governador, in Rio de Janeiro, Brazil (1991 to 1992) and data from the Mortality Information System of Rio de Janeiro (1991 to 2009). The survey aimed to estimate the prevalence of hypertension and other cardiovascular risk factors in 1,270 adults aged 20 years or older selected through a probabilistic sampling of households at three economic levels (low, middle and high income). We performed a probabilistic record linkage of these databases and estimated the risk of cardiovascular death using Kaplan-Meier method to plot survival curves and Cox proportional hazards models comparing hypertensive subjects all together, and by hypertension subgroups: untreated, controlled, and uncontrolled hypertensives with non-hypertensive ones.ResultsA total of 170 deaths occurred, of which 31.2 % attributed to cardiovascular causes. The hazard ratio for cardiovascular death was 6.1 times higher (95 % CI 2.7 – 13.7) in uncontrolled hypertensive patients relative to non-hypertensive patients. The hazard ratios for untreated hypertensive and controlled hypertensive patients were 2.7 times (95 % CI 1.1 – 6.3) and 2.1 times (95 % CI 0.38 – 11.5) higher than for normotensive patients, respectively.ConclusionThe present study demonstrated a higher cardiovascular death risk among hypertensive than among non-hypertensive ones that is not associated uniquely to treatment, because uncontrolled hypertensives demonstrated a greater risk than untreated ones. Although the subgroups of hypertensive individuals were susceptible to changes in their classification over the 19 years of the study, the baseline classification was consistent with a worse prognosis in these individuals.

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Objectives To assess the association between number of births and long-term maternal total and cardiovascular mortality stratified on education. Methods A population-based cohort study. Setting: Medical Birth Registry of Norway. Participants: Mothers with births registered in the Medical Birth Registry of Norway during the period 1967–2009. Mothers with first birth before 1991 were included. The data was organized in maternally linked sibling files. Cox proportional hazard models were used. Main Outcome Measures: Hazard ratios of maternal total and cardiovascular mortality, at 40–69 years, by number of births stratified on education (ten or less years and more than ten years of education). Results We found a J-shaped association between total mortality and cardiovascular mortality with increasing number of births among women with ten or less years of education, while there was no significant association among women with more than ten years of education. Compared to mothers with more than ten years of education and two births, the adjusted hazard ratio of cardiovascular death among those with five or more births and same education was 1.12 (95% confidence intervals (CI) 0.74–1.69). The corresponding hazard ratio among those with ten or less years of education was 3.57 (3.05–4.19). Mothers with only one birth had increased risk of both cardiovascular and total mortality, independent of educational level. Conclusions Our results suggest that the association between increasing number of births and later life cardiovascular mortality is explained by factors associated with educational level and not by adverse physiological changes accumulating over repeated pregnancies. The increased mortality among mothers with only one birth point toward underlying physiological factors associated with subfertility and/or chronic disease. Disclosures F. Halland: None. L. deRoo: None. N. Morken: None. K. Klungsoyr: None. A.J. Wilcox: None. R. Skjaerven: None.

Peripheral artery disease and outcomes after myocardial infarction: An individual-patient meta-analysis of 28,771 patients in CAPRICORN, EPEHESUS, OPTIMAAL and VALIANT

To examine the prevalence of peripheral artery disease (PAD) and the relationship between PAD and cardiovascular (CV) outcomes in subjects with left ventricular systolic dysfunction, heart failure or both after acute myocardial infarction (MI). PAD is associated with poorer prognosis in patients with stable and unstable coronary heart disease but whether PAD is associated with worse outcomes following substantial acute MI is unknown. Univariate and multivariate Cox proportional hazards modelling was used to compare clinical outcomes in an individual-patient meta-analysis of 4 trials (CAPRICORN, EPHESUS, OPTIMAAL and VALIANT). Of the 28,771 patients randomized, 2357 (8.2%) had PAD. These patients were older and had more co-morbidity and were less likely to be prescribed aspirin or a beta-blocker compared to patients without PAD. Over a mean follow-up of 2.7 years, 5121 (17.8%) patients died and 15,055 (52.3%) experienced CV death or hospitalization. PAD was an independent predictor of all individual and composite CV outcomes examined (including heart failure), with the exception of stroke. In patients with PAD (compared to those without PAD), the adjusted hazard ratio (HR) for all-cause mortality was 1.25 (95% CI 1.15-1.37; p<0.001) and the HR for CV death, non-fatal MI, non-fatal stroke or heart failure hospitalization was 1.24 (1.16-1.33; p<0.001). PAD is common and is an independent predictor of worse outcomes in patients already at high risk after MI because of left ventricular systolic dysfunction, heart failure or both. These patients represent an important group for intensive application of secondary preventive therapies.

T6 Thrombocytosis is Associated with Increased Short and Long Term Mortality After Exacerbation of Chronic Obstructive Pulmonary Disease

IntroductionThere is increasing evidence suggesting that platelets play a significant role in inflammation in addition to their established role in thrombosis. Systemic inflammation is linked to poor short and long...

Intermediate Thrombin Activation Is Associated with Reduced Cardiovascular Death Independently of Markers of Lipid Metabolism and Inflammation

Abstract 31Clinical trials showed an increased frequency of cardiovascular death (CVD) in patients receiving direct thrombin inhibitors. Considering the detrimental effect of local coagulation activation during an acute cardiovascular event these observations are deemed unexpected. These observations raise the question whether enhanced thrombin generation may convey protective effects during non-acute disease stages of cardiovascular disease.To address the question whether increased endogenous thrombin generation may convey beneficial effects in regard to cardiovascular disease we evaluated the association of the ETP and prothrombin fragment 1+2 (F1+2) with cardiovascular death (CVD) in a large prospective study (3156 individuals, median follow up ten years, Ludwigshafen RIsk and Cardiovascular Health (LURIC)-study). Furthermore, we explored the association of ETP with markers of inflammation (CRP, SAA), endothelial dysfunction (sICAM-1, sVCAM-1), and inflammatory cell activation (PAFAH).An inverse association between ETP and CVD was observed, with the lowest hazard ratio (HR) in the 3rd ETP quartile. This effect remained significant after adjusting for age, gender, DM, BMI, smoking, hypertension, hsCRP, LDL, HDL and triglycerides and after excluding patients receiving anticoagulants (HR for MOR 0.675, CI 0.531–0.858, P=0.001, and HR for CVD 0.667, CI 0.493–0.903, P=0.009). The nadir of sICAM-1 or sVCAM-1 was observed in the 3rd, for PAFAH in the 4th ETP quartile. When stratifying patients according to F1+2 we observed a similar U-shaped association with CVD (lowest HR in the 2nd quartile: 0.718, CI 0,524–0.983, P=0.039). In contrast, the HR for CVD according to fibrinogen strata increased continuously across the quartiles (highest HR in the 4th quartile: 1.828, CI 1.318–2.536, P<0.001).These results establish that intermediate levels of ETP or PTF1+2 are associated with a reduced HR for CVD and with lower plasma levels of markers of endothelial dysfunction or inflammatory cell activation. Based on these data we propose that low but sustained levels of thrombin generation mediate vasculo-protective effects translating long term into a reduced risk of CVD. These data may provide a rationale for the observed increased frequency of myocardial infarction in clinical studies evaluating direct thrombin inhibitors. Disclosures:No relevant conflicts of interest to declare.

Low DBP may not be an independent risk for cardiovascular death in revascularized coronary artery disease patients

It remains controversial whether extremely low DBP is a risk for cardiovascular events in patients with coronary artery disease (CAD). Coronary revascularization therapy became prevalent in CAD patients. We sought to determine the impact of low DBP on cardiovascular events and to investigate the predicting factors in revascularized CAD patients. We subanalyzed 7180 stable, chronic CAD patients (median follow-up period 3.6 years) of 9877 patients undergoing first coronary artery bypass graft or percutaneous coronary intervention in the registry of the Coronary REvascularization Demonstrating Outcome study in Kyoto (CREDO-Kyoto). Kaplan-Meier analysis revealed that unadjusted cumulative incidence of cardiovascular death was greater in patients with preprocedural DBP of less than 70 mmHg than in those with DBP of at least 70 mmHg, whereas the cumulative incidences of nonfatal myocardial infarction (MI) and of stroke were similar between the two groups. Stepwise logistic regression analysis showed that estimated glomerular filtration ratio (inversely), pulse pressure, left ventricular ejection fraction of less than 0.40, history of heart failure, prior cerebrovascular disease, and prior MI were independent risks for cardiovascular death in patients with DBP of less than 70 mmHg. After adjustments for the independent risks, the cumulative hazard ratio for cardiovascular death did not differ between patients with DBP of less than 70 mmHg and those with DBP of at least 70 mmHg. Renal insufficiency, more advanced vascular damage, and left ventricular systolic dysfunction were significant factors accounting for increased cardiovascular death in revascularized CAD patients with DBP of less than 70 mmHg. It was suggested that after adjustments for these independent risks, low DBP may not be a significant risk for cardiovascular death in revascularized CAD patients.

Association of Pretransplant Serum Phosphorus with Posttransplant Outcomes

Serum phosphorus levels are associated with mortality, cardiovascular disease, and renal function loss in individuals with and without chronic kidney disease. The association of pretransplant serum phosphorus levels with transplant outcomes is not clear. Data of the Scientific Registry of Transplant Recipients (SRTR) up to June 2007 were linked to the database (2001 through 2006) of one of the U.S.-based large dialysis organizations (DaVita). The selected 9384 primary kidney recipients were divided into five groups according to pretransplant serum phosphorus levels (mg/dl): <3.5, 3.5 to <5.5 (reference group), 5.5 to <7.5, 7.5 to <9.5, and ≥9.5. Unadjusted and multivariate adjusted risks for transplant outcomes were compared. Patients were 48 ± 14 years old and included 37% women and 27% African Americans. After multivariate adjustment, all-cause and cardiovascular death hazard ratios were 2.44 (95% confidence interval: 1.28 to 4.65) and 3.63 (1.13 to 11.64), respectively, in recipients in the ≥9.5 group; allograft loss hazard ratios were 1.42 (1.04 to 1.95) and 2.36 (1.33 to 4.17) in recipients with 7.5 to >9.5 and ≥9.5, respectively. No significant association with delayed graft function was found. Pretransplant phosphorus levels 7.5 to <9.5 mg/dl and ≥9.5 mg/dl were associated with increased risk of functional graft failure and increased risk of all-cause and cardiovascular deaths, respectively, when compared with 3.5 to <5.5 mg/dl. Additional studies are needed to examine whether more aggressive control of pretransplant serum phosphorus may improve posttransplant outcomes.

Aboriginal to non-Aboriginal differentials in 2-year outcomes following non-fatal first-ever acute MI persist after adjustment for comorbidity

We investigated the relationship between Aboriginality and 2-year cardiovascular disease outcomes in non-fatal first-ever myocardial infarction during 2000-04, with progressive adjustment of covariates, including comorbidities. Historical cohort study. Person-linked hospital and mortality records were used to identify 28-day survivors of first-ever myocardial infarction in Western Australia during 2000-04 with 15-year lookback. The outcome measures were: (1) cardiovascular disease death; (2) recurrent admission for myocardial infarction; and (3) the composite of (1) and (2). Compared with non-Aboriginal patients, Aboriginals were younger and more likely to live remotely. The proportions having 5-year histories of diabetes and chronic kidney disease were double and triple those of non-Aboriginals. When adjusting for demographic variables alone, the Aboriginal to non-Aboriginal hazard ratios for cardiovascular death or recurrent myocardial infarction were 3.6 (95% CI 2.5-5.3) in men and 4.5 (95% CI 2.8-7.3) in women. After adjustment for comorbidities, including diabetes, chronic kidney disease and heart failure, the hazard ratios decreased 36% and 47% to 2.3 (1.6-3.0) and 2.4 (1.5-4.0) in males and females, respectively. The high prevalence of comorbidities in Aboriginal people, including diabetes, kidney disease, heart failure, and other risk factors contribute substantially to the disparity in post-myocardial infarction outcomes in Aboriginal people, reinforcing the importance of both primary prevention and comprehensive management of chronic conditions in this population. Aboriginality remains a significant independent risk factor for disease recurrence or mortality, even after adjusting for comorbidity, suggesting the need for society-level interventions addressing social disadvantage.

Association of Hemoglobin and Survival in Peritoneal Dialysis Patients

Interventional trials and some observational studies show target hemoglobin >13 g/dl to be associated with higher mortality in erythropoiesis-stimulating agent-treated (ESA-treated) hemodialysis patients; data for peritoneal dialysis (PD) patients are limited. We tested our hypothesis that higher and lower achieved hemoglobin levels are associated with increased mortality in 9269 ESA-treated PD patients from all DaVita dialysis clinics during the time period July 2001 through June 2006 followed through June 2007 using a time-dependent analysis. Lower hemoglobin was associated with significantly higher all-cause mortality in ESA-treated PD patients: with hemoglobin of 11.0 to <12.0 g/dl as reference, the time-dependent adjusted death hazard ratios for hemoglobin levels of 10.0 to <11.0, 9.0 to <10.0, and ≤9.0 g/dl were 1.12 (1.00 to 1.24), 1.30 (1.12 to 1.50), and 1.38 (1.14 to 1.67), respectively. The time-dependent adjusted hazard ratios for cardiovascular death with hemoglobin levels of 10.0 to <11.0, 9.0 to <10.0, and ≤9.0 g/dl were 1.11 (0.93 to 1.32), 1.37 (1.09 to 1.72), and 1.12 (0.79 to 1.57), respectively. The same trend for association of lower hemoglobin level with higher mortality was seen in African-American and non-African American men and women. In contrast, there was no association between higher achieved hemoglobin and all-cause or cardiovascular mortality in ESA-treated PD patients. Lower, but not higher, achieved hemoglobin is associated with higher mortality in ESA-treated PD patients. Randomized controlled trials are needed to examine the target hemoglobin level with lowest mortality in PD patients.

Impacto de la apertura de un nuevo laboratorio de hemodinámica sobre la supervivencia a 30 días y a 2 años en los pacientes con infarto de miocardio

Introduction and objectives To determine the effect of opening an on-site diagnostic catheterization facility on 30-day and 2-year mortality rates in patients with myocardial infarction (MI). Methods The study included 1539 consecutive MI patients aged 25–74 years who were recruited before and after the catheterization laboratory opened in 1998: during 1995–1997 and 1999–2003, respectively. Results The 641 consecutive MI patients recruited in 1995–1997 had worse 30-day mortality than the 898 recruited between 1999–2003 (11.2% versus 6.35%, respectively; P = .001). The number of coronary angiographies and percutaneous coronary interventions carried out was greater in the second period (19.4% versus 3.3%, and 54.8% versus 23.0%, respectively; P < .001). Two-year survival curves were significantly better in the second period for all-cause and cardiovascular death. The adjusted odds ratio for death at 30 days was 0.58 (95% confidence interval [CI] 0.36–0.95) for the second period compared with the first and the adjusted hazard ratio for cardiovascular death at 2 years for patients still alive at 30 days was 0.62 (95%CI 0.39–0.99). After adjustment for the prescription of statins, angiotensin-converting enzyme inhibitors, beta-blockers and antiplatelet drugs at discharge, the effect observed at 2 years was no longer significant. Conclusions Opening a new on-site diagnostic catheterization unit significantly increased the 30-day survival of MI patients. However, the increase in 2-year survival of 30-day survivors observed was largely explained by the implementation of better secondary prevention. Full English text available from: www.revespcardiol.org

Effect of Opening a New Catheterization Laboratory on 30-Day and 2-Year Survival Rates in Myocardial Infarction Patients

Introduction and objectives To determine the effect of opening an on-site diagnostic catheterization facility on 30-day and 2-year mortality rates in patients with myocardial infarction (MI). Methods The study included 1539 consecutive MI patients aged 25–74 years who were recruited before and after the catheterization laboratory opened in 1998: during 1995–1997 and 1999–2003, respectively. Results The 641 consecutive MI patients recruited in 1995–1997 had worse 30-day mortality than the 898 recruited between 1999–2003 (11.2% versus 6.35%, respectively; P = .001). The number of coronary angiographies and percutaneous coronary interventions (PCIs) carried out was greater in the second period (19.4% versus 3.3%, and 54.8% versus 23.0%, respectively; P < .001). Two-year survival curves were significantly better in the second period for all-cause and cardiovascular death. The adjusted odds ratio for death at 30 days was 0.58 (95% confidence interval [CI] 0.36–0.95) for the second period compared with the first and the adjusted hazard ratio for cardiovascular death at 2 years for patients still alive at 30 days was 0.62 (95%CI 0.39–0.99). After adjustment for the prescription of statins, angiotensin-converting enzyme inhibitors, beta-blockers and antiplatelet drugs at discharge, the effect observed at 2 years was no longer significant. Conclusions Opening a new on-site diagnostic catheterization unit significantly increased the 30-day survival of MI patients. However, the increase in 2-year survival of 30-day survivors observed was largely explained by the implementation of better secondary prevention.

Decreased Kidney Function

Chronic kidney disease is an important risk factor for development and progression of atherosclerosis. The objective of the current study was to investigate the contribution of moderate kidney failure to cardiovascular (CV) mortality and morbidity after carotid endarterectomy (CEA). In addition, we investigated which proportion received optimal medical treatment or underwent diagnostic workup of the kidneys prior to CEA. Between 2002 and 2009, 1085 patients undergoing CEA were included in this study. Estimated glomerular filtration rate (eGFR) was assessed at baseline. Moderate kidney failure was defined as an eGFR 30-59 and compared with normal or mildly reduced kidney function (eGFR ≥60). Primary endpoint was CV death, composed of fatal myocardial infarction, fatal stroke, and ruptured abdominal aneurysm. Secondary endpoints were CV morbidity. Moderate kidney failure (eGFR 30-59) was observed in 26.5% (288/1085) of the patients. During a median follow-up of 2.95 years (0.0 to 3.0 years), the adjusted hazard ratio for CV death with an eGFR 30-59 was 2.22 (1.27 to 3.89). Adjusted hazard ratio for MI with an eGFR 30-59 was 1.90 (1.04 to 3.47). No higher risk for stroke and peripheral interventions was observed. Of all patients with an eGFR 30-59, 38.3% (105/274) received angiotensin-converting enzyme inhibitors, 74.5% (204/274) received statins, and 34.4% (99/288) visited a nephrologist. Patients with an eGFR 30-59 have a 2.2-fold increased risk for CV death and 1.9-fold increased risk for myocardial infarction the 3 three years after CEA compared with patients with an eGFR ≥60, independent of other CV risk factors. A minority of these patients receive optimal medical treatment, which might explain the increased risk for progression of chronic kidney disease and CV morbidity and mortality.

Proton-Pump Inhibitors Are Associated With Increased Cardiovascular Risk Independent of Clopidogrel Use

Controversy remains on whether the dual use of clopidogrel and proton-pump inhibitors (PPIs) affects clinical efficacy of clopidogrel. To examine the risk for adverse cardiovascular outcomes related to concomitant use of PPIs and clopidogrel compared with that of PPIs alone in adults hospitalized for myocardial infarction. A nationwide cohort study based on linked administrative registry data. All hospitals in Denmark. All patients discharged after first-time myocardial infarction from 2000 to 2006. The primary outcome was a composite of rehospitalization for myocardial infarction or stroke or cardiovascular death. Patients were examined at several assembly time points, including 7, 14, 21, and 30 days after myocardial infarction. Follow-up was 1 year. Of 56 406 included patients, 9137 (16.2%) were re-hospitalized for myocardial infarction or stroke or experienced cardiovascular death. Of the 24 702 patients (43.8%) who received clopidogrel, 6753 (27.3%) received concomitant PPIs. The hazard ratio for cardiovascular death or rehospitalization for myocardial infarction or stroke for concomitant use of a PPI and clopidogrel among the cohort assembled at day 30 after discharge was 1.29 (95% CI, 1.17 to 1.42). The corresponding ratio for use of a PPI in patients who did not receive clopidogrel was 1.29 (CI, 1.21 to 1.37). No statistically significant interaction occurred between a PPI and clopidogrel (P = 0.72). Unmeasured and residual confounding, time-varying measurement errors of exposure, and biases from survival effects were possible. Proton-pump inhibitors seem to be associated with increased risk for adverse cardiovascular outcomes after discharge, regardless of clopidogrel use for myocardial infarction. Dual PPI and clopidogrel use was not associated with any additional risk for adverse cardiovascular events over that observed for patients prescribed a PPI alone.

Are coronary revascularization and myocardial infarction a homogeneous combined endpoint in hypertension trials? The Losartan Intervention For Endpoint reduction in hypertension study

Construction of prognostically relevant endpoints for clinical trials in hypertension has increasingly included coronary revascularization with myocardial infarction (MI) as manifestations of coronary artery disease. However, whether coronary revascularization and MI predict other cardiovascular events similarly is unknown. We examined risks of cardiovascular death, all-cause death, and stroke following MI or coronary revascularization in hypertensive patients with left ventricular hypertrophy (LVH) enrolled in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE). We studied 9113 patients after excluding those who died within 7 days after MI or underwent coronary revascularization within 24 h after MI. In multivariate Cox regression adjusting for participating countries, time-varying systolic blood pressure, and Framingham risk score, hazard ratios for cardiovascular death, all-cause death, and stroke were, respectively, 4.5 (P<0.0001), 2.9 (P<0.0001), and 1.9 (P=0.003) in 321 patients with MI as first event. In similar models, coronary revascularization as first event (n=202) was not associated with increased risks of cardiovascular death, all-cause death, and stroke (P=0.06-0.86). During follow-up of hypertensive patients with LVH, occurrence of MI but not coronary revascularization as first cardiovascular event significantly increased risk of subsequent cardiovascular death, all-cause death, and stroke. In view of differences in prognostic implications, when the goal is to have a prognostically relevant composite endpoint for trials in hypertensive patients, caution should be used in combining coronary revascularization with MI.