Survival And Ventricular Enlargement Research Articles

Abstract 286: Prognostic Value of Blood Urea Nitrogen / Creatinine Ratio in Patients Post Myocardial Infarction: Experience From the Survival and Ventricular Enlargement Trial

Introduction: Renal function assessed by serum creatinine-based estimated glomerular filtration rate (eGFR), is an established prognostic marker in the general population and following an acute myocardial infarction. Elevation of the blood urea nitrogen / creatinine ratio (BUN/CR) indicates appropriate renal response to systemic hypoperfusion and suggests acute cardio-renal alteration. We aimed to determine the prognostic value of the BUN/CR for adverse cardiovascular (CV) events and mortality in patients with acute myocardial infarction and left ventricular dysfunction. Methods: We used data from the Survival and Ventricular Enlargement (SAVE) trial that randomized 2231 patients 3 to 16 days following an acute myocardial infarction with left ventricular ejection fraction of ≤ 40% to captopril or placebo. Patients with a creatinine level >2.5 mg/dl were not included in the trial. Patients were categorized according to quartiles of BUN/CR, or as high BUN/CR (if ≥ 20) versus low. Cox proportional hazard regression models were used to evaluate the association of BUN/CR with mortality and adverse CV events. Results: There were 461 patients with high BUN/CR (≥ 20). They were older, more likely to be women, have a lower body mass index, higher eGFR, a prior myocardial infarction and a lower left ventricular ejection fraction at baseline. In univariable analysis, an elevated BUN/CR was associated with an increased risk of heart failure but not with other clinical endpoints (death, CV death, or a composite of death, MI or heart failure). In multivariable models that included age, gender, eGFR, diabetes, Killip class, hypertension, assignment to captopril arm, and left ventricular ejection fraction, a high BUN/CR was not predictive of any endpoint (p>0.5). Conclusion: Although an elevated BUN/CR may represent systemic hypoperfusion, it does not appear to be an independent prognostic marker for adverse CV events and mortality in patients with acute myocardial infarction and left ventricular dysfunction.

Thromboembolism and Antithrombotic Therapy in Patients With Heart Failure in Sinus Rhythm

Heart failure (HF) represents a major and growing public health problem because of its prevalence, incidence, morbidity, mortality, and economic costs. The prevalence of HF is 2% to 3% of the general population.1 Five million Americans are affected, with >550 000 cases diagnosed each year.2 The mortality rate from severe HF remains >60% within 5 years of diagnosis, and 50% of hospitalized patients with HF require readmission within 6 months of discharge. In the US estimated costs amount to > $35 billion per year.3 Although several therapies (eg, β-blockers, angiotensin-converting enzyme [ACE] inhibitors, and cardiac resynchronization therapy) have been proven effective in improving HF outcomes, many unanswered questions about optimal treatment remain. One area of ongoing uncertainty is the appropriate role for antithrombotic therapy in patients with HF. Observational data suggest that patients with HF have an increased venous thromboembolism (VTE) risk (deep venous thromboembolism [DVT], pulmonary embolism [PE], peripheral arterial thromboembolism, and stroke).4 These epidemiological findings are supported by multiple mechanisms that can contribute to a hypercoagulable state in patients with HF. Despite this increased risk of VTE, the role of antithrombotic therapy remains unclear. In this article, we provide an overview of epidemiology, pathophysiology, clinical trial data, and therapeutic recommendations for prevention of thromboembolism in HF. We searched PubMed for articles published between 1958 and 2010 using the following search terms: epidemiology of heart failure , thromboembolism and heart failure , thrombogenesis and heart failure , anticoagulation in heart failure , antiplatelet agent and heart failure , aspirin and heart failure , bleeding risk and anticoagulation , and aspirin and angiotensin-converting enzyme inhibitors . We also studied abstracts from national and international cardiovascular meetings to identify unpublished studies using the key words anticoagulation and dilated cardiomyopathy . Data from published observational studies and secondary …

Risk of All-Cause Mortality, Recurrent Myocardial Infarction, and Heart Failure Hospitalization Associated With Smoking Status Following Myocardial Infarction With Left Ventricular Dysfunction

Patients with left ventricular (LV) systolic dysfunction after myocardial infarction (MI) are at particularly high risk for recurrent adverse outcomes. The magnitude of the decrease in risk associated with smoking cessation after MI has not been well described in patients with LV dysfunction after MI. We aimed to quantify the risk decrease associated with smoking cessation in subjects with LV dysfunction after MI. The Survival and Ventricular Enlargement (SAVE) trial randomized 2,231 subjects with LV dysfunction 3 to 16 days after MI. Smoking status was assessed at randomization and at regular intervals during a median follow-up of 42 months. Propensity score-adjusted Cox proportional hazard models were used to quantify the decrease in risk of all-cause mortality, death or recurrent MI, and death or heart failure (HF) hospitalization associated with smoking cessation. In baseline smokers who survived to 6 months without interval events, smoking cessation at 6-month follow-up was associated with a significantly lower adjusted risk of all-cause mortality (hazard ratio [HR] 0.57, 95% confidence interval [CI] 0.31 to 0.91), death or recurrent MI (HR 0.68, 95% CI 0.47 to 0.99), and death or HF hospitalization (HR 0.65, 95% CI 0.46 to 0.92). In conclusion, in patients with LV dysfunction after MI, smoking cessation is associated with a 40% lower hazard of all-cause mortality and a 30% lower hazard of death or recurrent MI or death or HF hospitalization. These findings indicate that smoking cessation is beneficial after high-risk MI and highlight the importance of smoking cessation as a therapeutic target in patients with LV dysfunction after MI.

Monocytes: Protagonists of Infarct Inflammation and Repair After Myocardial Infarction

Myocardial infarction (MI) is the most frequent cause of heart failure, which is an incapacitating disease with high prevalence and broad socioeconomic impact. In 2008 in the United States, 5.7 million people suffered from heart failure, and more than 287 000 people died.1 Timely revascularization of ischemic myocardium reduces acute infarct mortality, and current standard therapy with β blockers and angiotensin-converting enzyme (ACE) inhibitors curbs development of post-MI heart failure. For example, ACE inhibitor treatment reduced mortality from 25% to 20% in the Survival and Ventricular Enlargement (SAVE) trial.2 Although this is a major advance, long-term mortality remains high. The combination of reduced acute infarct mortality due to efficient acute care and insufficient options to treat infarct survivors chronically has contributed to an increased heart failure prevalence (Figure 1).3 Figure 1. Disease statistics. A, Deaths per 100 000 population for coronary heart disease in men, ages 35 to 74 years, United States, 1970 to 2005. B, Deaths due to heart failure, United States, 1970 to 2005. C, Hospitalizations per 100 000 population for heart failure, age ≥65 years, United States, 1971 to 2006. Adapted from National Heart, Lung, and Blood Institute Fact Book 2008.3 The need to understand and treat heart failure better has motivated clinicians and basic scientists to explore new therapeutic strategies to repair the failing heart, for instance, with stem cells.4,5 Augmentation of intrinsic wound healing that occurs during the first 1 to 2 weeks after MI is a prospective approach with the potential to prevent heart failure. During this period, the infarct is highly active biologically.6–8 Delicate granulation tissue undergoes rapid turnover of cells and of structural components such as the extracellular matrix. Preexisting collagen is digested and new matrix is laid down. During these extensive changes of tissue …

Surgical Management of Ischemic Mitral Regurgitation

Case presentation: A 62-year-old man visited his cardiologist describing a 6-month history of increasing fatigue and shortness of breath on exertion. His medical history included an inferoposterior myocardial infarction (MI) 3 years previously that was treated with drug-eluting stents to his left circumflex and right coronary arteries. The result of physical examination was remarkable for crackles audible throughout the lower half of both lung fields, an elevated jugular venous pulse to the angle of the jaw, and a grade 3/6 holosystolic murmur loudest at the apex with radiation to the left axilla. An echocardiogram revealed a left ventricular ejection fraction (LVEF) of 15% to 20%, severe mitral regurgitation (MR), and a left ventricular end systolic dimension of 70 mm. The patient underwent a repeat cardiac angiogram that revealed patent stents in the circumflex and right coronary arteries and no other significant stenoses. The decision was made to surgically correct the patient’s MR with a mitral valve operation. He was brought to the operating room, where he was given general anesthesia, and a transesophageal echocardiogram was performed. Examination of the mitral valve revealed poor leaflet coaptation with a degree of leaflet tethering that resulted in severe MR. Inasmuch as the valve leaflets appeared structurally normal, a mitral valve repair procedure using a complete rigid annuloplasty ring was performed. A postoperative echocardiogram revealed trace MR, and the patient experienced no postoperative complications. This patient is a typical example of a growing problem in our aging population, namely, ischemic mitral regurgitation (IMR). IMR clearly has a negative impact on survival in patients with coronary artery disease, even in patients with mild to moderate MR; greater degrees of MR portend an even worse prognosis.1 With almost a fifth of patients who experience an MI followed by the development of IMR,2,3 and over …

Quality Improvement

Outcomes research examines the effects of healthcare interventions and policies on health outcomes for individual patients and populations in routine practice, as opposed to the idealized setting of clinical trials. A national survey from 1998 to 2000 that evaluated the extent to which patients received established processes of care for 30 medical conditions illustrated the importance of outcomes research.1 Among adults living in 12 metropolitan areas in the United States, only half of patients received proven elements of preventive care, treatments for acute illness, and chronic disease management for which they were eligible. For cardiovascular conditions, the use of proven therapies varied widely from 68% to 25% of patients who received recommended care for coronary artery disease and atrial fibrillation, respectively.1 Despite these gaps between ideal and actual care, patient outcomes have improved in many fields. For instance, the age-adjusted mortality from cardiovascular disease in the United States fell by >40% from 1980 to 2000 as a result of improvements in risk factor modification and uptake of evidence-based treatments for coronary artery disease, myocardial infarction, and heart failure.2,3 Nevertheless, many Americans do not receive the ideal recommended care (either at all or in a timely fashion), whereas others receive too much or the wrong care.4,5 In the field of cardiovascular diseases, substantial opportunities for improvement remain. Outcomes research has generated a foundation of knowledge about what constitutes ideal care and what gaps exist between ideal and actual care, but we have less understanding about how to deliver this ideal care to every patient every day. The potential for basic science breakthroughs to reach and improve the health of individual patients and populations may be substantially delayed or may not be realized if science is not efficiently translated to action. Moreover, in many cases, increased delivery of …

Ecological Studies and Cardiovascular Outcomes Research

Is it better to have a heart attack in the United States or Canada? Ecological studies are epidemiological evaluations in which the unit of analysis is populations, or groups of people, rather than individuals.1 They can answer important questions such as the question posed above that cannot easily be answered using any other form of study design. Ecological studies are conducted by researchers in a variety of disciplines, including outcomes researchers, to study potential causal associations between 1 or more exposure and outcome variables. They are frequently used where alternative study designs are not possible (eg, randomized control trials), such as when investigating the effect of geographical and temporal factors on disease incidence or the effect of a government policy change on health outcomes. In this overview, we provide an introduction to the use of ecological studies in cardiovascular outcomes research, drawing on published examples from our group and others. It is important for clinicians to be aware of both the potential strengths and weaknesses of this type of study design. Because ecological studies are ubiquitous in the medical literature, it is not possible to review all published cardiovascular ecological studies in a systematic manner. Individual-level variables are properties of each person whereas ecological variables are properties of groups, organizations, or places.1,2 All ecological studies are potentially prone to the so-called “ecological fallacy,” which is a term for the biases that may occur when the association that exists between variables at an aggregate level may not represent the true association that exists at an individual level.3 On the other hand, the ecological fallacy may be offset by avoidance of the “individualistic fallacy” whereby one assumes that individual patients are unaffected by the neighborhood in which they live or the setting in which they are treated.4 Complete …

Left Ventricular End‐Diastolic Pressure and Risk of Subsequent Heart Failure in Patients Following an Acute Myocardial Infarction

Left ventricular end-diastolic pressure (LVEDP) is an important measure of ventricular performance and may identify patients at increased risk for developing late clinical symptoms of heart failure (HF). The primary outcome in this analysis of 744 patients from the Survival and Ventricular Enlargement (SAVE) trial was the development of death or HF over a mean time of 36 months. The mean LVEDP for all patients was 23+/-9 mm Hg, and 75% of participants (n=558) had an LVEDP >15 mm Hg. Patients with an LVEDP >30 mm Hg (n=187) had the highest risk of death or HF (unadjusted hazard ratio, 1.40; 95% confidence interval [CI], 1.00-1.97) when compared with the other 2 cohorts combined (n=603). After adjustment for other known predictors of cardiac risk, LVEDP no longer remained significant (adjusted hazard ratio, 1.12; 95% CI, 0.77-1.65). Elevated LVEDP is common following myocardial infarction; however, it is not an independent predictor of subsequent HF risk. The variability in LVEDP is not fully explained by infarct size and atherosclerotic burden.

Uncertainty on the Use of Aldosterone Antagonists for Primary Therapy for Sudden Cardiac Death in the Setting of Implanted Devices

In the early development of therapy for acute myocardial infarction, it was thought that once the necrotic process had been completed (usually within 24 hours of coronary artery occlusion), additional therapies could not affect outcome. However, after completion of the necrotic process, the myocardial infarction may thin and stretch (involving lengthwise slippage of myocytes), a phenomenon referred to as myocardial infarct expansion. This process causes local left ventricular cavity dilatation followed by gradual global left ventricular dilatation and lengthwise (eccentric) hypertrophy of the noninfarcted tissue. Apoptosis (programmed cell death) and some attempt of the myocardium to regenerate, especially at the infarct border zone, may also contribute to this remodeling process of the ventricle. If the left ventricle remodels in such a way that it becomes very dilated, then the prognosis is poor, and heart failure is more likely to occur.1 These later processes of myocardial infarct expansion and left ventricular remodeling became the target of therapies such as angiotensin-converting enzyme (ACE) inhibition that could be initiated after 24 hours of coronary occlusion. ACE inhibition, angiotensin receptor blockade, and long-term β-blockade have become standard pharmacological approaches for postinfarction left ventricular dysfunction and heart failure. Response by Pitt and Pitt p 2989 Ventricular arrhythmias can occur in both the acute and chronic phases of acute myocardial infarction and can lead to sudden cardiac death (SCD). Reentrant arrhythmias may arise at the border zone of infarcts, causing monomorphic ventricular tachycardia that may occur years after the index infarction. Recurrent myocardial ischemia resulting in an unstable substrate may contribute to polymorphic ventricular tachycardia or ventricular fibrillation. Agents such as β-blockers that are anti-ischemic may reduce sudden death by quieting this unstable substrate. In the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II, implantable defibrillators were shown to reduce mortality in post–myocardial infarction patients with …

Prevention of cardiovascular events in end-stage renal disease: Results of a randomized trial of fosinopril and implications for future studies

Cardiovascular events (CVEs) are the leading cause of death in chronic hemodialysis patients. Results of trials in non-end-stage renal disease (ESRD) patients cannot be extrapolated to patients with ESRD. It is critical to test cardiovascular therapies in these high-risk patients who are usually excluded from major cardiovascular trials. The study objective was to evaluate the effect of fosinopril on CVEs in patients with ESRD. Eligible patients were randomized to fosinopril 5 mg titrated to 20 mg daily (n=196) or placebo (n=201) plus conventional therapy for 24 months. The primary end point was combined fatal and nonfatal first major CVEs (cardiovascular death, resuscitated death, nonfatal stroke, heart failure, myocardial infarction, or revascularization). No significant benefit for fosinopril was observed in the intent to treat analysis (n=397) after adjusting for independent predictors of CVEs (RR=0.93, 95% confidence interval (CI) 0.68-1.26, P=0.35). The per protocol secondary supportive analysis (n=380) found a trend towards benefit for fosinopril (adjusted RR=0.79 (95% CI 0.59-1.1, P=0.099)). In the patients who were hypertensive at baseline, systolic and diastolic blood pressures were significantly decreased in the fosinopril as compared to the placebo group. After adjustment for risk factors, trends were observed suggesting fosinopril may be associated with a lower risk of CVEs. These trends may have become statistically significant had the sample size been larger, and these findings warrant further study.

Increase in Creatinine and Cardiovascular Risk in Patients with Systolic Dysfunction after Myocardial Infarction

Baseline renal function is a potent independent risk factor for adverse events after acute myocardial infarction (MI). Worsening renal function (WRF) has been shown to influence outcomes in the heart failure population, but its impact on cardiovascular risk in the post-MI period has not been well defined. For assessment of the prognostic importance of WRF, 2231 patients who had left ventricular dysfunction and were enrolled in the Survival and Ventricular Enlargement (SAVE) trial were studied. Patients were randomly assigned between 3 and 16 d (average 11 d) after acute MI to receive captopril or placebo; those with a serum creatinine of >2.5 mg/dl were excluded from SAVE. WRF was defined as an increase in creatinine of >0.3 mg/dl measured from baseline to 2 wk after randomization. The predictive value of WRF on cardiovascular morbidity and mortality was examined during 42 mo of follow-up. Paired serum creatinine measurements at baseline and 2 wk were available in 1854 patients. WRF occurred in 223 (12.0%) patients and was a stronger predictor of death (hazard ratio [HR] 1.46; 95% confidence interval [CI] 1.05 to 2.02) than baseline creatinine (HR 1.31; 95% CI 1.01 to 1.70). WRF also showed an increased risk for cardiovascular death (HR 1.62; 95% CI 1.14 to 2.30) and the composite end point (HR 1.32; 95% CI 1.03 to 1.70). When stratified by treatment, 104 (5.7%) and 116 (6.4%) patients with WRF in the placebo and captopril groups had no significant association between treatment group and WRF (P = 0.38). The risk for death associated with WRF was HR 1.63 (95% CI 1.05 to 2.52) in the placebo group compared with HR 1.33 (95% CI 0.81 to 2.21) in the captopril group (P = 0.49 for interaction). WRF as early as 2 wk after MI was not uncommon (12.0%) and was associated with increased mortality in patients without renal dysfunction at baseline. Patients who received captopril did not demonstrate more WRF than patients who received placebo. Monitoring serum creatinine in patients during the first few weeks after MI may help to identify those who are at highest risk and guide effective long-term therapeutic choices.

Section 3: Prevention of Ventricular Remodeling, Cardiac Dysfunction, and Heart Failure

Section 3: Prevention of Ventricular Remodeling, Cardiac Dysfunction, and Heart Failure

Risk Assessment in Patients with Depressed Left Ventricular Function After Myocardial Infarction Using the Myocardial Performance Index–Survival and Ventricular Enlargement (SAVE) Experience

Myocardial performance index (MPI) is a noninvasive, quantitative Doppler measure of global cardiac function, integrating systolic and diastolic functions. The prognostic significance of MPI is less clear for cardiovascular (CV) events after myocardial infarction (MI) among individuals at high risk with depressed left ventricular (LV) systolic function. We analyzed echocardiograms from 512 patients with depressed LV function after MI enrolled in the Survival and Ventricular Enlargement (SAVE) echocardiographic substudy. Baseline MPI measures were obtainable in 226 patients. The cohort was separated by median MPI (0.50). MPI was related to baseline clinical and echocardiographic characteristics, ventricular remodeling, and subsequent CV events, including recurrent MI, heart failure, CV death, and a composite of all CV end points. An MPI of 0.5 or more was associated with larger infarct size and reduced LV systolic function at baseline; other baseline characteristics between the groups were similar. A total of 64 (28.3%) patients experienced CV events. Baseline MPI did not influence ventricular remodeling and did not modify the relationship between ventricular dilatation and CV events. After covariate adjustment, an MPI of 0.50 or higher remained an independent predictor for adverse CV events (hazard ratio [HR], 2.00, 95% confidence interval 1.17-3.43). An MPI of 0.50 or greater is an independent predictor for CV events after MI in patients with known LV dysfunction.

The Transition From Hypertrophy to Failure

Hypertensive heart disease is a major contributor to cardiovascular morbidity and mortality, especially in African Americans, in whom LV hypertrophy is 2 to 3-fold more common in the general population as compared with whites.1 In the classic paradigm of hypertensive heart disease, concentric hypertrophy (a nondilated, thick-walled left ventricle typically with a normal left ventricular ejection fraction [LVEF]) is a common precursor to LV failure (an increased LV volume with reduced LVEF).2 Although molecular triggers of this transition from concentric hypertrophy to failure have been the subject of intense investigation, there are no previous large, longitudinal cohort studies in humans demonstrating that this progression occurs frequently. The transition from concentric LV hypertrophy to failure has been well demonstrated in animal models including the spontaneously hypertensive rat,3 or after aortic banding4 or transgenic manipulation,5 and also in humans with aortic stenosis6 or familial hypertrophic cardiomyopathy.7 Whether this paradigm faithfully represents the natural history of hypertensive heart disease is not yet known (Figure). An alternative paradigm is that the LV response to elevated blood pressure is either hypertrophy or failure, with transition between the 2 uncommon in the absence of an interval cardiac injury. Potential pathways in progression of hypertensive heart disease. Hypertension can lead to concentric left ventricular hypertrophy (LVH), characterized by nondilated, thick-walled left ventricle (arrow, top left). After “transition to failure,” the LV is dilated with reduced LVEF. Coronary artery disease often via MI is a common contributor to this transition (first horizontal arrow). Whether concentric LVH commonly leads to low EF in absence of an interval MI or significant coronary artery disease is uncertain (second horizontal arrow). If LVH is not common precursor to LV …

Ischemic Mitral Regurgitation and Its Related Risk After Myocardial Infarction

In this issue of Circulation , Bursi et al1 report that ischemic mitral regurgitation is a more common finding after myocardial infarction (MI) than was previously thought and is an independent predictor of heart failure and death among 30-day infarct survivors. Seldom is mitral regurgitation actively investigated, and investigation is often only prompted by clinical examination. The data Bursi et al report support findings from the 1970s, which suggested that clinical examination is not sensitive in the detection and assessment of mitral regurgitation.2 The authors conclude that Doppler echocardiographic assessment of mitral regurgitation should be actively sought and included in post-MI risk stratification. See p 295 Early invasive studies demonstrated an association between mitral regurgitation and increased 1-year mortality. Tcheng et al3 reported a mitral regurgitation prevalence of 17% in 255 patients. One-year mortality rates showed a graded association with the degree of mitral regurgitation: 11%, 22%, and 52% in patients with no regurgitation, angiographic grade 1 to 2 regurgitation, and grade 3 to 4 regurgitation, respectively. When clinical confounders were adjusted for by multivariate analysis, only grade 3 to 4 mitral regurgitation carried a significantly increased 1-year mortality risk. A similarly designed study reported a post-MI mitral regurgitation prevalence of 13% and showed that mitral regurgitation predicted cause-specific cardiovascular mortality.4 The larger SAVE (Survival and Ventricular Enlargement)5 study of 727 patients reported that even mild (grade 1 to 2) ischemic mitral regurgitation was an independent predictor of cause-specific post-MI cardiovascular mortality. Echocardiographic studies of ischemic mitral regurgitation also have confirmed the prognostic significance of even mild mitral regurgitation.6,7 One-year mortality rates of 4.8%, 12.4%, and 24% were observed among 417 patients assessed within 48 hours of MI with absent, mild, and moderate to severe mitral regurgitation, respectively. Multivariate analysis revealed that even mild …

Issue Highlights

HomeCirculationVol. 110, No. 24Issue Highlights Free AccessIn BriefPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessIn BriefPDF/EPUBIssue Highlights Originally published14 Dec 2004https://doi.org/10.1161/circ.110.24.3617Circulation. 2004;110:3617CHRONIC KIDNEY DISEASE, CARDIOVASCULAR RISK, AND RESPONSE TO ANGIOTENSIN-CONVERTING ENZYME INHIBITION AFTER MYOCARDIAL INFARCTION: THE SURVIVAL AND VENTRICULAR ENLARGEMENT (SAVE) STUDY, by Tokmakova et al.It is well known that kidney disease portends increased cardiovascular mortality. This increased risk is likely to be largely due to hypertension, dyslipidemia, and anemia associated with kidney disease, but unknown factors contributing to plaque rupture also may play a role. ACE inhibitors have been shown to reduce the risk of myocardial infarction and death in patients with chronic kidney disease but often are not prescribed because of concerns about deterioration in kidney function. The SAVE investigators report, from their randomized study of captopril versus placebo in 2000 patients with ejection fractions <40% after acute myocardial infarction, that heightened cardiovascular risk occurred at a threshold of an estimated glomerular filtration rate (GFR) of 60 mL · min−1 · 1.73 m−2. Captopril tended to have a larger relative treatment effect and a greater absolute benefit in reducing the risk of cardiovascular events, including myocardial infarction, in patients with lower GFRs. Only 9 patients with GFRs <60 mL · min−1 · 1.73 m−2 needed to be treated for 31/2 years to reduce 1 cardiovascular event. See p 3667.IMPAIRED l-ARGININE TRANSPORT AND ENDOTHELIAL FUNCTION IN HYPERTENSIVE AND GENETICALLY PREDISPOSED NORMOTENSIVE SUBJECTS, by Schlaich et al.Prior studies have demonstrated dysfunction of the vascular endothelium in patients with hypertension, but the underlying mechanisms remain incompletely defined. In this regard, experimental studies have implicated impaired transport of l-arginine into endothelial cells, leading to an intracellular deficiency of the substrate for synthesis of nitric oxide. In this issue of Circulation, Schlaich and colleagues demonstrate impaired uptake of l-arginine in the forearm and into isolated blood monocytes in patients with hypertension. Interestingly, the results were similar in normotensive individuals with a family history of hypertension. The mechanisms accounting for impaired l-arginine transport were not determined in this human study and will require further study; however, these findings provide further evidence that loss of endothelium-derived nitric oxide precedes the development of hypertension and thus may contribute to the underlying pathogenesis of the disease in some individuals. See p 3680.GENOME-WIDE SCAN FOR JAPANESE FAMILIAL INTRACRANIAL ANEURYSMS: LINKAGE TO SEVERAL CHROMOSOMAL REGIONS, by Yamada et al.According to the American Stroke Association (http://www.americanheart.org/presenter.jhtml?identifier=3018827) it is estimated that about 3 to 5 million people in the United States have cerebral aneurysms, the vast majority of which are asymptomatic. However, bleeding occurs in approximately 0.5% to 3% of intracranial aneurysms, leading to major morbidity and mortality. Family history of aneurysm is known to be a risk factor, with first-degree relatives having a 4-fold increased risk of intracranial aneurysms. In this issue of Circulation, Yamada, Utsunomiya, and colleagues describe 29 Japanese intracranial aneurysm families with at least 3 affected relatives. They performed a genome-wide linkage scan and found several areas of suggestive linkage on chromosomes 17 and 19 and the X chromosome. The investigators examined polymorphisms in 4 potential, attractive candidate genes but found no evidence of association. The study describes attractive regions for further investigation of genetic susceptibility for intracranial aneurysms but underscores the difficulty in pinpointing the genetic determinants of complex diseases. See p 3727.Visit www.circ.ahajournals.org:Images In Cardiovascular MedicineEsophageal Migration During Left Atrial Catheter Ablation for Atrial Fibrillation. See p e528.Cardiac Sarcoidosis in a Patient With Hypertrophic Cardiomyopathy Demonstrated by Magnetic Resonance Imaging and Single Photon Emission Computed Tomography Dual-Isotope Scintigraphy. See p e529.CorrespondenceLetter Regarding Article by Ridker et al, “Should C-Reactive Protein Be Added to Metabolic Syndrome and to Assessment of Global Cardiovascular Risk?” See p e532.Download figureDownload PowerPoint Previous Back to top Next FiguresReferencesRelatedDetails December 14, 2004Vol 110, Issue 24 Advertisement Article InformationMetrics https://doi.org/10.1161/circ.110.24.3617 Originally publishedDecember 14, 2004 PDF download Advertisement

Chronic Kidney Disease, Cardiovascular Risk, and Response to Angiotensin-Converting Enzyme Inhibition After Myocardial Infarction

Persons with end-stage renal disease and those with lesser degrees of chronic kidney disease (CKD) have an increased risk of death after myocardial infarction (MI) that is not fully explained by associated comorbidities. Future cardiovascular event rates and the relative response to therapy in persons with mild to moderate CKD are not well characterized. We calculated the estimated glomerular filtration rate (eGFR) using the 4-variable Modification of Diet in Renal Disease method in 2183 Survival And Ventricular Enlargement (SAVE) trial subjects. SAVE randomized post-MI subjects (3 to 16 days after MI) with left ventricular ejection fraction < or =40% and serum creatinine <2.5 mg/dL to captopril or placebo. Cox proportional hazards models were used to evaluate the relative hazard rates for death and cardiovascular events associated with reduced eGFR. Subjects with reduced eGFR were older and had more extensive comorbidities. The multivariable adjusted risk ratio for total mortality associated with reduced eGFR from 60 to 74, 45 to 59, and <45 mL x min(-1) x 1.73 m(-2) (compared with eGFR > or =75 mL x min(-1) x 1.73 m(-2)) was 1.11 (0.86 to 1.42), 1.24 (0.96 to 1.60) and 1.81 (1.32 to 2.48), respectively (P for trend =0.001). Similar adjusted trends were present for CV mortality (P=0.001), recurrent MI (P=0.017), and the combined CV mortality and morbidity outcome (P=0.002). The absolute benefit of captopril tended to be greater in subjects with CKD: 12.4 versus 5.5 CV events prevented per 100 subjects with (n=719) and without (n=1464) CKD, respectively. CKD was associated with a heightened risk for all major CV events after MI, particularly among subjects with an estimated glomerular filtration rate <45 mL x min(-1) x 1.73 m(-2). Randomization to captopril resulted in a reduction of CV events irrespective of baseline kidney function.

Antecedent hypertension and the effect of captopril on the risk of adverse cardiovascular outcomes after acute myocardial infarction with left ventricular systolic dysfunction: Insights from the Survival and Ventricular Enlargement trial

Background Hypertension is a well-established risk factor for myocardial infarction (MI), but its prognostic importance in survivors of an acute MI is less clear. Methods We used Cox proportional hazards models to examine the risk of any major cardiovascular event (cardiovascular death, heart failure, recurrent MI, or stroke)—combined or individual components—and all-cause death and evaluate the efficacy of captopril in 906 patients with hypertension and 1325 patients without hypertension in the Survival and Ventricular Enlargement (SAVE) clinical trial. All patients had survived an acute MI with resultant left ventricular (LV) systolic dysfunction, but without overt heart failure, and were randomized within 3 to 16 days after the index MI to receive either captopril or placebo. The mean (± SD) follow-up period was 42 ± 10 months. Results After adjustment for known risk factors, medication use at enrollment, and baseline systolic blood pressure, patients with hypertension had a significant increase in the risk of experiencing a combined cardiovascular event (47.7% vs 31.3%; hazard ratio [HR], 1.49; 95% CI, 1.28–1.74), cardiovascular death (23.4% vs 15.9%; HR, 1.40; 95% CI, 1.12–1.74), heart failure (27.7% vs 15.5%; HR, 1.64; 95% CI, 1.34–2.02), and all-cause death (27.4 vs 19.3%; HR, 1.25; 95% CI, 1.02–1.53), and a similar but statistically non-significant increase in the risk of non-fatal or fatal recurrent MI (17.4% vs 10.9%; HR, 1.27; 95% CI, 0.98–1.65), and non-fatal or fatal stroke (5.0% vs 3.6%; HR, 1.31; 95% CI, 0.81–2.09). Captopril resulted in similar benefits for both patients with and patients without hypertension. The number of combined cardiovascular events prevented for every 100 patients treated with captopril was 7.0 (95% CI, 0.5–13.5) in patients with hypertension and 7.5 (95% CI, 2.6–12.5) in patients without hypertension. Conclusions In survivors of an acute MI with LV systolic dysfunction, antecedent hypertension was associated with a greater risk of subsequent adverse cardiovascular events, not directly explained by elevated blood pressure levels. Captopril use was beneficial in both patients with and patients without hypertenson.

Alcohol consumption and prognosis in patients with left ventricular systolic dysfunction after a myocardial infarction

ObjectivesWe assessed the influence of alcohol intake on the development of symptomatic heart failure (HF) in patients with left ventricular (LV) dysfunction after a myocardial infarction (MI). BackgroundIn contrast to protection from coronary heart disease, alcohol consumption has been linked to cardiodepressant effects and has been considered contraindicated in patients with HF. MethodsThe Survival And Ventricular Enlargement (SAVE) trial randomized 2,231 patients with a LV ejection fraction (EF) <40% following MI to an angiotensin-converting enzyme inhibitor or placebo. Patients were classified as nondrinkers, light-to-moderate drinkers (1 to 10 drinks/week), or heavy drinkers (>10 drinks/week) based on alcohol consumption reported at baseline. The primary outcome was hospitalization for HF or need for an open-label angiotensin-converting enzyme inhibitor. Analyses were repeated using alcohol consumption reported three months after MI. ResultsNondrinkers were older and had more comorbidities than light-to-moderate and heavy drinkers. In univariate analyses, baseline light-to-moderate alcohol intake was associated with a lower incidence of HF compared with nondrinkers (hazard ratio [HR] 0.71; 95% confidence interval [CI] 0.57 to 0.87), whereas heavy drinking was not (HR 0.91; 95% CI 0.67 to 1.23). After adjustment for baseline differences, light-to-moderate baseline alcohol consumption no longer significantly influenced the development of HF (light-to-moderate drinkers HR 0.93; 95% CI 0.75 to 1.17; heavy drinkers HR 1.25; 95% CI 0.91 to 1.72). Alcohol consumption reported three months after the MI similarly did not modify the risk of adverse outcome. ConclusionsIn patients with LV dysfunction after an MI, light-to-moderate alcohol intake either at baseline or following MI did not alter the risk for the development of HF requiring hospitalization or an open-label angiotensin-converting enzyme inhibitor.

Current medical treatment for the exacerbation of chronic heart failure resulting in hospitalization

Am Heart J 2003;145:S3-17.