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Biomedical subjects

Gregg C Fonarow

Publications and source records attributed to Gregg C Fonarow.

At least 73 records · Page 4Linked to original sources
PubMed2004

Early withdrawal of statin therapy in patients with non-ST-segment elevation myocardial infarction: national registry of myocardial infarction.

BACKGROUND: There is increasing interest in the non-lipid-lowering effects of statins and their effect on outcomes in patients with acute coronary syndrome. It has been suggested that withdrawal of statin therapy during an acute coronary syndrome may attenuate any benefits of pretreatment, thereby providing indirect evidence of the importance of their non-lipid-lowering effects. METHODS: This observational study compared the demographic and clinical characteristics and hospital outcomes in patients with non-ST-segment elevation myocardial infarction enrolled in the National Registry of Myocardial Infarction 4. Comparison groups consisted of patients previously receiving statins who also received statins within 24 hours of hospital admission (n = 9,001), patients previously using statins in whom therapy was discontinued (n = 4,870), and patients who did not receive statins at any time before or during hospitalization (n = 54,635). RESULTS: Of 13,871 patients receiving statins before hospital admission, 35.1% had treatment withdrawn during the first 24 hours of hospitalization. These patients had increased hospital morbidity and mortality rates relative to patients in whom therapy was continued, with higher rates of heart failure, ventricular arrhythmias, shock, and death. In multivariate analyses, these patients were at statistically significant increased risk of hospital death compared with those continuing statin therapy and at similar risk compared with those not receiving statins before or during hospitalization. CONCLUSIONS: Withdrawal of statin therapy in the first 24 hours of hospitalization for non-ST-segment elevation myocardial infarction is associated with worse hospital outcomes. In the absence of data from randomized clinical trials, our findings suggest that statin therapy should be continued during hospitalization for myocardial infarction unless strongly contraindicated.

Aged↗
PubMed2004

Role of in-hospital initiation of carvedilol to improve treatment rates and clinical outcomes.

Patients with heart failure face a very high risk of hospitalization and mortality. Despite compelling scientific evidence that beta-blockers reduce hospitalizations and mortality in patients with heart failure, this lifesaving therapy continues to be underused. Studies in a variety of clinical settings have documented that a significant proportion of patients with heart failure are not receiving treatment with this guideline-recommended, evidence-based therapy when physicians are guided by conventional care. A similar treatment gap has been documented for lipid-lowering therapy in patients with coronary artery disease. It has been demonstrated that initiation of lipid-lowering and other cardiovascular protective medications before hospital discharge for atherosclerotic cardiovascular events results in a marked increase in treatment rates, improved long-term patient compliance, and better clinical outcomes. This has led to national guidelines being revised to endorse this approach as the standard of care. Recent studies demonstrate that carvedilol can be safely and effectively initiated in patients with heart failure before hospital discharge and that this improves clinical outcomes. Adopting in-hospital initiation of carvedilol as the standard of care for patients hospitalized with heart failure could dramatically improve treatment rates-thus substantially reducing the risk of future hospitalizations and prolonging life in the many patients with heart failure hospitalized each year.

Adrenergic beta-Antagonists↗
PubMed2004

Reverse epidemiology of conventional cardiovascular risk factors in patients with chronic heart failure.

Traditional risk factors of a poor clinical outcome and mortality in the general population, including body mass index (BMI), serum cholesterol, and blood pressure (BP), are also found to relate to outcome in patients with chronic heart failure (CHF), but in an opposite direction. Obesity, hypercholesterolemia, and high values of BP have been demonstrated to be associated with greater survival among CHF patients. These findings are in contrast to the well-known associations of over-nutrition, hypercholesterolemia, and hypertension with a poor outcome in the general population. The association between traditional cardiovascular risk factors and an adverse clinical outcome in CHF patients is referred to as "reverse epidemiology." The mechanisms for this inverse association in CHF is not clear. There are other populations with a similar risk factor reversal phenomenon, including patients with end-stage renal disease receiving dialysis, those with advanced malignancies, and individuals with advanced age. Several possible causes are hypothesized: the time discrepancy of the competing risk factors may play a role; the presence of the "malnutrition-inflammation complex syndrome" in CHF patients may explain the existence of reverse epidemiology; and a decreased level of lipoprotein molecules may distort their endotoxin-scavenging role, predisposing CHF patients with a low serum cholesterol level to inflammatory consequences of endotoxemia. It is possible that new goals for such traditional risk factors as BMI, serum cholesterol, and BP should be developed for CHF. Reverse epidemiology of conventional cardiovascular risk factors is observed in CHF and may have a bearing on the management of these patients; thus, it deserves further investigation.

Body Mass Index↗
PubMed2004

Interleukin-6 (IL-6) expression and natural killer (NK) cell dysfunction and anergy in heart failure.

Immune dysfunction has been postulated to play a role in the pathophysiology of chronic heart failure. We examined the relation between interleukin-6 (IL-6) production and natural killer (NK) cell dysfunction in patients with chronic heart failure. Sera and peripheral blood mononuclear cells (PBMCs) were collected from 82 patients with advanced heart failure. Levels of circulating NK cells and T cells were determined by flow cytometry. NK cell function was measured by standard cytotoxicity assays. IL-6 in supernatants of PBMC cultured in vitro was quantitated by an enzyme-linked immunosorbent assay. The levels of circulating NK cells were lower in patients with heart failure than in normal controls (p = 0.0037). NK cells from patients with heart failure also exhibited impaired cytolytic functions in the absence of stimuli and in response to IL-2 and IL-12 (p <0.0001 for all conditions). PBMCs from patients with heart failure produced higher levels of IL-6 in response to a T-cell stimulus than did PBMCs from healthy controls (p = 0.0012). The level of IL-6 produced by unstimulated PBMCs in patients with heart failure correlated with NK cell cytolytic impairment (p = 0.0012). These results demonstrated that PBMCs are a source of IL-6 in patients with heart failure. Production of IL-6 by PBMCs correlated with NK cell anergy to other cytokines that use signal transduction pathways that may be regulated by IL-6. These results support a model of cytokine-induced anergy in conditions that result in high systemic levels of IL-6.

Adult↗
PubMed2004

The oxidation hypothesis of atherogenesis: the role of oxidized phospholipids and HDL.

For more than two decades, there has been continuing evidence of lipid oxidation playing a central role in atherogenesis. The oxidation hypothesis of atherogenesis has evolved to focus on specific proinflammatory oxidized phospholipids that result from the oxidation of LDL phospholipids containing arachidonic acid and that are recognized by the innate immune system in animals and humans. These oxidized phospholipids are largely generated by potent oxidants produced by the lipoxygenase and myeloperoxidase pathways. The failure of antioxidant vitamins to influence clinical outcomes may have many explanations, including the inability of vitamin E to prevent the formation of these oxidized phospholipids and other lipid oxidation products of the myeloperoxidase pathway. Preliminary data suggest that the oxidation hypothesis of atherogenesis and the reverse cholesterol transport hypothesis of atherogenesis may have a common biological basis. The levels of specific oxidized lipids in plasma and lipoproteins, the levels of antibodies to these lipids, and the inflammatory/anti-inflammatory properties of HDL may be useful markers of susceptibility to atherogenesis. Apolipoprotein A-I (apoA-I) and apoA-I mimetic peptides may both promote a reduction in oxidized lipids and enhance reverse cholesterol transport and therefore may have therapeutic potential.

Animals↗
PubMed2004

Cost-effectiveness of screening with B-type natriuretic peptide to identify patients with reduced left ventricular ejection fraction.

OBJECTIVES: This study was designed to evaluate the cost-effectiveness of screening patients with a B-type natriuretic peptide (BNP) blood test to identify those with depressed left ventricular systolic function. BACKGROUND: Asymptomatic patients with depressed ejection fraction (EF) may have less progression to heart failure if they can be identified and treated. METHODS: We used a decision model to estimate economic and health outcomes for different screening strategies using BNP and echocardiography to detect left ventricular EF <40% for men and women age 60 years. We used published data from community cohorts (gender-specific BNP test characteristics, prevalence of depressed EF) and randomized trials (benefit from treatment). RESULTS: Screening 1,000 asymptomatic patients with BNP followed by echocardiography in those with an abnormal test increased the lifetime cost of care (176,000 US dollars for men, 101,000 US dollars for women) and improved outcome (7.9 quality-adjusted life years [QALYs] for men, 1.3 QALYs for women), resulting in a cost per QALY of 22,300 US dollars for men and 77,700 US dollars for women. For populations with a prevalence of depressed EF of at least 1%, screening with BNP followed by echocardiography increased outcome at a cost < 50,000 US dollars per QALY gained. Screening would not be attractive if a diagnosis of left ventricular dysfunction led to significant decreases in quality of life or income. CONCLUSIONS: Screening populations with a 1% prevalence of reduced EF (men at age 60 years) with BNP followed by echocardiography should provide a health benefit at a cost that is comparable to or less than other accepted health interventions.

Aged↗
PubMed2004

Managing the patient with diabetes mellitus and heart failure: issues and considerations.

Heart failure affects nearly 5 million Americans and is associated with high morbidity and mortality rates. It is now recognized that activation of multiple neurohormonal systems is intrinsic in the pathophysiology of heart failure. Patients with diabetes mellitus are at high risk for heart failure, and some of the complications of diabetes (e.g., insulin resistance) contribute to the development and progression of heart failure, partly because of their effects on neurohormonal systems. Pharmacologic intervention directed toward these systems (i.e., angiotensin-converting enzyme [ACE] inhibition, use of aldosterone antagonists, and beta-adrenergic blockade) has been shown to decrease the morbidity and mortality associated with heart failure. Despite this knowledge, ACE inhibitors, aldosterone antagonists, and beta-blockers are grossly underused, and deaths and hospitalizations due to heart failure have steadily increased. Guidelines for the management of heart failure recommend the use of ACE inhibitors and beta-blockers in patients with mild, moderate, or severe disease. Aldosterone antagonists are recommended in severe heart failure, and recent data also support their use in mild to moderate heart failure. Concerns about the increased incidence of hypoglycemia, worsening dyslipidemia, and decreased insulin sensitivity with beta-blocker use may be preventing physicians from prescribing these agents for patients with diabetes with heart failure. Although evidence from earlier clinical trials justifies some of these concerns, newer vasodilating beta-blockers (e.g., carvedilol) have been shown to have a neutral or positive effect on dyslipidemia and insulin resistance. beta-Blockade in conjunction with ACE inhibition should be standard therapy for all patients with diabetes who have heart failure. Furthermore, early in-hospital initiation of neurohormonal intervention can provide earlier benefit to these patients.

Adrenergic beta-Antagonists↗
PubMed2004

Statin therapy is associated with improved survival in ischemic and non-ischemic heart failure.

OBJECTIVES: This study aimed to investigate the impact of hydroxymethylglutaryl coenzyme A reductase inhibitor (statin) therapy in patients with advanced heart failure (HF). BACKGROUND: Although statins are known to reduce mortality in coronary artery disease (CAD), the impact of statin therapy in patients with HF has not been well studied. Both the potential risks and benefits of statins in HF have been described. METHODS: We studied a cohort of 551 patients with systolic HF (left ventricular ejection fraction [EF] <or=40%) referred to a single university center for clinical management and/or transplant evaluation. Survival without the necessity of urgent heart transplantation was determined. RESULTS: The patients' mean age was 52 +/- 13 years; mean EF was 25 +/- 7%. Forty-five percent of the cohort had CAD, and 45% were receiving statin therapy, including 73% and 22% of CAD and non-CAD patients with HF, respectively. Patients receiving statins were significantly older and more likely to be male, with higher rates of hypertension, diabetes, and smoking. The EF and cholesterol levels were similar between treated and non-treated patients. Statin use was associated with improved survival without the necessity of urgent transplantation in both non-ischemic and ischemic HF patients (91% vs. 72%, p < 0.001 and 81% vs. 63%, p < 0.001 at one-year follow-up, respectively). After risk adjustment for age, gender, CAD, cholesterol, diabetes, medications, hemoglobin, creatinine, and New York Heart Association functional class, statin therapy remained an independent predictor of improved survival (hazard ratio 0.41 95% confidence interval 0.18 to 0.94). CONCLUSIONS: Statin therapy is associated with improved survival in patients with ischemic and non-ischemic HF. Randomized trials are needed for confirmation of a therapeutic benefit.

Cohort Studies↗
PubMed2004

Overview of acutely decompensated congestive heart failure (ADHF): a report from the ADHERE registry.

Acute decompensated heart failure (ADHF) has emerged as a major public health problem, and HF has become the leading cause of hospitalization in persons over 65 years of age. It is estimated that there are 6.5 million hospital days attributed to ADHF each year. Patients hospitalized with ADHF face a substantial risk of readmission, as high as 50% by 6 months after discharge. Despite the large number of patients hospitalized and this substantial risk, data on these patients have been limited and there has been little effort to improve the quality of care for patients hospitalized with ADHF. The Acute Decompensated Heart Failure National Registry (ADHERE) was designed to bridge this gap in knowledge and care by prospectively studying the characteristics, management, and outcomes of a broad spectrum of patients hospitalized with ADHF. Participating community and university hospitals identified patients with a primary or secondary discharge diagnosis of HF and collected medical history, management, treatments, and health outcomes via secure Web browser technology. As of October 2004, more than 160,000 patients from 281 hospitals have been enrolled. These patients differ substantially from those typically enrolled in randomized clinical trials. Initial data from the ADHERE registry have provided important insights into the clinical characteristics, patterns of care, and outcomes of patients with ADHF. ADHERE has documented significant delays in diagnosis and initiation of ADHF therapies as well as a substantial under-use of evidenced-based, guideline-recommended chronic HF therapies at hospital discharge. As such, there are substantial opportunities to improve the quality of care for ADHF patients in the nation's hospitals.

Acute Disease↗
PubMed2004

Quality of care and outcomes in acute decompensated heart failure: The ADHERE Registry.

Despite 1 million or more annual hospitalizations, the management of acute decompensated heart failure remains largely empiric. Data are lacking regarding patient characteristics, usual comorbidities, commonly used treatment strategies, clinical outcomes, and adherence to recently published quality indicators. The Acute Decompensated Heart Failure National Registry (ADHERE(R)) has been established to capture data regarding the presentation, management, and expected outcomes of acute decompensated heart failure. The size of the registry and its web-based platform allow for evaluation of compliance with quality indicators, assessment of mortality risk, and correlation of parenteral treatment strategies with clinical outcomes. More than 100,000 patient episodes have been recorded in the registry. These patient data have been reviewed and reveal important findings regarding acute decompensated heart failure and potential opportunities to improve the quality of care.

Acute Disease↗
PubMed2004

Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF): rationale and design.

Heart failure (HF) affects >5 million patients in the United States, and its prevalence is increasing every year. Despite the compelling scientific evidence that angiotensin-converting enzyme inhibitors and beta-blockers reduce hospitalizations and mortality rates in patients with HF, these lifesaving therapies continue to be underused. Several studies in a variety of clinical settings have documented that a significant proportion of eligible patients with HF are not receiving treatment with these guideline-recommended, evidence-based therapies. In patients hospitalized with HF, who are at particularly high risk for re-hospitalization and death, the initiation of beta-blockers is often delayed because of concern that early initiation of these agents may exacerbate HF. Recent studies suggest that beta-blockers can be safely and effectively initiated in patients with HF before hospital discharge and that clinical outcomes are improved. The Initiation Management Predischarge Process for Assessment of Carvedilol Therapy for Heart Failure (IMPACT-HF) trial demonstrated that pre-discharge initiation of carvedilol was associated with a higher rate of beta-blocker use after hospital discharge, with no increase in hospital length of stay. In addition, there was no increase in the risk of worsening of HF. Studies of hospital-based management systems that rely on early (pre-discharge) initiation of evidence-based therapies for patients with cardiovascular disease have also found increases in post-discharge use of therapy and a reduction in the rates of mortality and hospitalization. On the basis of these pivotal studies, the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) program is designed to improve medical care and education of hospitalized patients with HF and accelerate the initiation of evidence-based HF guideline recommended therapies by administering them before hospital discharge. A registry component, planned as the most comprehensive database of the hospitalized HF population focusing on admission to discharge and 60- to 90-day follow-up, is designed to evaluate the demographic, pathophysiologic, clinical, treatment, and outcome characteristics of patients hospitalized with HF. The ultimate aim of this program is to improve the standard of HF care in the hospital and outpatient settings and increase the use of evidence-based therapeutic strategies to save lives.

Adrenergic beta-Antagonists↗
PubMed2004

Approach to the management of diabetic patients with heart failure: role of thiazolidinediones.

Diabetes mellitus is a chronic, progressive disease that results in microvascular and macrovascular complications. Patients with diabetes are at high risk for developing heart failure, and the prevalence of diabetes in patients with heart failure ranges from 24% to 44%, with an estimated 1 to 2 million individuals in the United States having both diabetes and heart failure. Patients with diabetes and heart failure are at increased risk for mortality. Primary treatment goals in diabetes include restoration and maintenance of normoglycemia, avoidance of diabetic complications, and prevention of cardiovascular events. The range of therapeutic options for glycemic control has been extended with the introduction of thiazolidinediones (TZDs) used as monotherapy or in combination with other oral antidiabetic medications or insulin. TZDs decrease plasma insulin levels, improve endothelial function, decrease vascular inflammation, and decrease C-reactive protein levels, effects that are potentially beneficial in patients with heart failure. Weight gain and peripheral edema are recognized side effects of these drugs, particularly when used in combination with insulin. Although health care providers should be aware of the potential risk of worsened heart failure when TZDs are used in patients with diabetes and heart failure, these agents may be considered for use in patients with New York Heart Association class I and II heart failure when appropriate monitoring can be provided. Prospective clinical trials are currently under way to further define the cardiovascular safety and efficacy of TZDs in diabetic patients with heart failure.

Diabetes Complications↗