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Biomedical subjects

Jay N Cohn

Publications and source records attributed to Jay N Cohn.

At least 37 records · Page 2Linked to original sources
PubMed2005

Anemia and change in hemoglobin over time related to mortality and morbidity in patients with chronic heart failure: results from Val-HeFT.

BACKGROUND: Anemia is known to be a prognostic marker for patients with heart failure. However, little is known about the prognostic value of changes in hemoglobin (Hgb) over time or about the causes of anemia. METHODS AND RESULTS: Retrospective analysis of Valsartan Heart Failure Trial data indicated that the quartile of patients with the biggest average decrease in Hgb over 12 months (from 14.2 to 12.6 g/dL) had significantly (P< or =0.01) increased risk of subsequent hospitalization (hazard ratio [HR], 1.47), morbid events (HR, 1.41), and death (HR, 1.6) compared with the quartile that exhibited little change in Hgb over 12 months (from 13.7 to 13.8 g/dL). Increasing Hgb was significantly associated with lower mortality in patients with (HR, 0.78) and without (HR, 0.79) anemia at baseline. Anemia at baseline and the changes in Hgb were independently associated with serum albumin, blood pressure, glomerular filtration rate, B-type natriuretic peptide, and C-reactive protein. Lack of anemia at baseline and increases in Hgb over 12 months were not associated with smaller left ventricular diameters or higher ejection fractions. CONCLUSIONS: Changes in Hgb over 12 months were inversely associated with subsequent risk of mortality and morbidity, independently of the effects of baseline anemia and other important predictors. Several factors were independently related to anemia at baseline and changes in Hgb, suggesting multiple causes of anemia in patients with heart failure. These findings raise important questions about the optimal level of Hgb in patients with moderate to severe heart failure and how to achieve them.

Aged↗
PubMed2005

Arterial elasticity as part of a comprehensive assessment of cardiovascular risk and drug treatment.

Early cardiovascular disease can be identified in asymptomatic individuals by noninvasive evaluation of functional and structural abnormalities of the vasculature and heart. These abnomalities are usually a consequence of endothelial dysfunction. A panel of 10 tests, including small and large artery elasticity, has been used as the basis for a screening system that provides a score of 0 to 20 as a guide to the severity of disease. Using that Rasmussen score allows for stratification of patients into low, intermediate, or high risk for progression to cardiovascular morbid events. This comprehensive screening can be performed efficiently in a single room with a single technician. The sensitivity and specificity of this screening system in predicting future cardiovascular events, its superiority to traditional risk factor assessment, and its potential to track the response to therapeutic interventions must be validated in long-term follow-up studies.

Arteries↗
PubMed2005

Valsartan reduces the incidence of atrial fibrillation in patients with heart failure: results from the Valsartan Heart Failure Trial (Val-HeFT).

BACKGROUND: Atrial fibrillation (AF) in heart failure (HF) is generally considered a negative prognostic factor. Recent studies indicate that the incidence of AF might be decreased by renin angiotensin aldosterone system inhibitors. The identification of a treatment to prevent its occurrence is likely to improve patients outcome. The aims of these subanalyses of Val-HeFT were to assess (a) the effects of valsartan in the prevention of AF, (b) the independent predictors of this event, and (c) the prognostic role of AF occurrence. METHODS AND RESULTS: The occurrence of AF was evaluated based on adverse event reports in the patients with HF enrolled in Val-HeFT. Patients were randomized to valsartan or placebo on top of their prescribed treatments for HF. During the mean 23 months of follow-up, AF was reported in 287/4395 patients (6.53%) in sinus rhythm at baseline, of whom 113/2205 (5.12%) were allocated to valsartan and 174/2190 (7.95%) to placebo (P = .0002). Multivariable analysis showed that brain natriuretic peptide (BNP) levels at baseline above the median value (HR 2.28, 95% CI 1.75-2.98), age over 70 years (HR 1.51, 95% CI 1.17-1.95), male sex (HR 1.53, 95% CI 1.07-2.18), and the valsartan treatment (HR 0.63, 95% CI 0.49-0.81) were independently associated with AF occurrence. Cox multivariable regression analysis showed that occurrence of AF was independently associated with a worse prognosis, with the adjusted hazard risks for all-cause mortality and combined mortality/morbidity of 1.40 (95% CI 1.16-1.58) and 1.38 (95% CI 1.12-1.70), respectively. CONCLUSIONS: The results of the present study demonstrate that (a) adding valsartan to prescribed therapy for HF significantly reduces the incidence of AF by 37%; (b) BNP level and advanced age were the strongest independent predictors for AF occurrence; and (c) AF occurrence further worsens the outcome in patients with HF.

Aged↗
PubMed2005

Effect of valsartan on quality of life when added to usual therapy for heart failure: results from the Valsartan Heart Failure Trial.

BACKGROUND: The effect on quality of life (QOL) of valsartan administered in addition to prescribed background heart failure therapy was assessed as a secondary endpoint in the Valsartan Heart Failure Trial (Val-HeFT). METHODS AND RESULTS: QOL was assessed in 3010 patients receiving either valsartan (160 mg twice daily) or placebo in addition to prescribed background therapy (beta-blockers or angiotensin-converting enzyme inhibitors), using the Minnesota Living with Heart Failure (MLWHF) questionnaire. Treatment differences were compared at intervals to 36 months after randomization and at endpoint (last observation) using analysis of covariance and repeated measures mixed-effects, and at endpoint using a Mantel-Haenszel chi-squared test. Scores lower than baseline were indicative of improved QOL. Valsartan had a significant beneficial effect on the least-square mean change in overall MLWHF score from baseline to study endpoint (+/- standard error) (average followup 23.0 months) compared with placebo (0.19 +/- 0.47 versus 1.94 +/- 0.48; P = .005 respectively). The placebo group was characterized by a deterioration in QOL as the trial progressed. More patients on valsartan reported a clinically meaningful improvement in MLWHF score (a decrease of > or =5 points) than on placebo (34.0% versus 30.2%). CONCLUSION: Valsartan compared to placebo added to prescribed therapy slows progressive worsening of QOL in patients with heart failure.

Adrenergic beta-Antagonists↗
PubMed2005

Clinical and analytical considerations in the study of health status in device trials for heart failure.

BACKGROUND: Measures of health status (including symptoms, functional status, or quality of life) assess patients' experiences of their disease, and may therefore be used to quantify the benefits and risks of treatment. The aim of this article is to provide recommendations to regulatory agencies and research sponsors regarding the use of health status measures in medical device trials. METHODS AND RESULTS: A workshop jointly planned by the Heart Failure Society of America and the US Food and Drug Administration was convened in October 2003 in Washington, DC. A Working Group to address health status measures initiated its collaboration at the workshop and continued its efforts throughout the next year. The Working Group recommended assessment of health status in all studies of heart failure therapy. Standardized instruments known to be valid, reliable, responsive to changes, and available in the languages of target populations should be used. Minimizing bias may be accomplished by using blinded, independent evaluators; collecting multiple health status measures; using valid statistical methods; and creating a health status resource bank. CONCLUSION: Assessment of health status should be part of any device trial and should occur regardless of whether the device is intended as destination or bridging therapy. Health status endpoints should be chosen, collected, and analyzed with the same level of scientific rigor as traditional clinical endpoints. Regulatory agencies should require use of analytic methods that handle the complexity of health status data in addition to usual protocol protections.

Clinical Trials as Topic↗
PubMed2005

Expanding the definition and classification of hypertension.

Cardiovascular abnormalities are frequently the cause, as well as the effect, of elevated blood pressure. As such, early cardiovascular disease (CVD) may be established before identifiable blood pressure thresholds are crossed. To identify individuals at risk for CVD at an earlier point in the disease process, as well as to avoid labeling persons as hypertensive who are at low risk for CVD, the Hypertension Writing Group proposes incorporating the presence or absence of cardiovascular risk factors, early disease markers, and target organ damage into the definition and classification scheme of hypertension. To describe both the complexity and progressive nature of hypertension, the following definition is proposed: "Hypertension is a progressive cardiovascular syndrome arising from complex and interrelated etiologies. Early markers of the syndrome are often present before blood pressure elevation is observed; therefore, hypertension cannot be classified solely by discrete blood pressure thresholds. Progression is strongly associated with functional and structural cardiac and vascular abnormalities that damage the heart, kidneys, brain, vasculature, and other organs and lead to premature morbidity and death." Classification of hypertension must involve assessing global cardiovascular risk to situate an individual's risk for CVD and events along a continuum. As knowledge of early CVD continues to evolve, the approach to classifying individuals along that continuum can be expected to evolve accordingly. The four categories currently used to classify hypertension are normal, prehypertension, and stages 1 and 2 hypertension. The population identified with prehypertension includes a subgroup with early CVD. We believe it would be preferable to classify all individuals as either normal or hypertensive, based on their cardiovascular evaluation, using the four categories of normal and stages 1, 2, and 3 hypertension.

Antihypertensive Agents↗
PubMed2005

A-HeFT: old dog, new endothelial tricks.

In conclusion, reduced nitric oxide bioactivity contributes to cardiac and vascular remodeling. Nitricoxide-enhancing therapy can slow cardiac andvascular remodeling. African-Americans with heart failure exhibit nitric oxide deficiency and a dramatic benefit from nitric-oxide-enhancing therapy. The potential benefit of this therapy in other groups with heart failure and in other vascular remodeling disease processes requires further study.

Black or African American↗
PubMed2004

Combination of isosorbide dinitrate and hydralazine in blacks with heart failure.

BACKGROUND: We examined whether a fixed dose of both isosorbide dinitrate and hydralazine provides additional benefit in blacks with advanced heart failure, a subgroup previously noted to have a favorable response to this therapy. METHODS: A total of 1050 black patients who had New York Heart Association class III or IV heart failure with dilated ventricles were randomly assigned to receive a fixed dose of isosorbide dinitrate plus hydralazine or placebo in addition to standard therapy for heart failure. The primary end point was a composite score made up of weighted values for death from any cause, a first hospitalization for heart failure, and change in the quality of life. RESULTS: The study was terminated early owing to a significantly higher mortality rate in the placebo group than in the group given isosorbide dinitrate plus hydralazine (10.2 percent vs. 6.2 percent, P=0.02). The mean primary composite score was significantly better in the group given isosorbide dinitrate plus hydralazine than in the placebo group (-0.1+/-1.9 vs. -0.5+/-2.0, P=0.01; range of possible values, -6 to +2), as were its individual components (43 percent reduction in the rate of death from any cause [hazard ratio, 0.57; P=0.01] 33 percent relative reduction in the rate of first hospitalization for heart failure [16.4 percent vs. 22.4 percent, P=0.001], and an improvement in the quality of life [change in score, -5.6+/-20.6 vs. -2.7+/-21.2, with lower scores indicating better quality of life; P=0.02; range of possible values, 0 to 105]). CONCLUSIONS: The addition of a fixed dose of isosorbide dinitrate plus hydralazine to standard therapy for heart failure including neurohormonal blockers is efficacious and increases survival among black patients with advanced heart failure.

Adult↗
PubMed2004

Severity of left ventricular remodeling defines outcomes and response to therapy in heart failure: Valsartan heart failure trial (Val-HeFT) echocardiographic data.

OBJECTIVES: The objective of this study was to test the hypothesis that the severity of left ventricular remodeling predicts the response to treatment and outcomes in chronic heart failure. BACKGROUND: Reversal of remodeling should produce the most favorable outcome in patients with the most severe remodeling. METHODS: In 5010 heart failure patients on background therapy and randomized to valsartan and placebo, serial recordings of left ventricular internal diastolic diameter (LVIDd) and ejection fraction (EF) were read at sites that had to meet qualifying standards before participating. Baseline LVIDd and EF were pooled across treatments and retrospectively grouped by quartiles Q1 to Q4, representing best to worst. Kaplan-Meier survival curves were obtained by the log-rank test. Q1 was compared with Q4 for mortality and combined mortality and morbidity (M + M) from Cox regression risk ratios (RRs). Valsartan versus placebo changes from baseline in LVIDd and EF were analyzed by quartiles from analysis of covariance. Valsartan and placebo were compared by RRs for M + M. RESULTS: Survival rates were greater in the better quartiles for LVIDd and EF (p < 0.00001). The RR for Q1 versus Q4 in events approached 0.5 for both LVIDd and EF (p < 0.0001). An LVIDd decrease and EF increase were quartile-dependent and greater with valsartan than placebo at virtually all time points. The RR for M + M outcomes favored valsartan in the worse quartiles. CONCLUSIONS: Stratification by baseline severity of remodeling showed that patients with worse LVIDd and EF are at highest risk for an event, yet appear to gain the most anti-remodeling effect and clinical benefit with valsartan treatment.

Antihypertensive Agents↗
PubMed2004

Usefulness of B-type natriuretic peptide assay in the assessment of symptomatic state in hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) has a diverse clinical spectrum that often includes progressive heart failure symptoms and disability. Assessment of symptom severity may be highly subjective, encumbered by the heterogeneous clinical presentation. Plasma B-type natriuretic peptide (BNP) has been used widely as an objective marker for heart failure severity and outcome, predominantly in coronary heart disease with ventricular dilatation and systolic dysfunction. METHODS AND RESULTS: We prospectively assessed plasma BNP as a quantitative clinical marker of heart failure severity in 107 consecutive HCM patients. BNP showed a statistically significant relationship to magnitude of functional limitation, assessed by New York Heart Association (NYHA) functional class: I, 136+/-159 pg/mL; II, 338+/-439 pg/mL; and III/IV, 481+/-334 pg/mL (P<0.001). Multivariable analysis showed that BNP was independently related to NYHA class as well as age and left ventricular wall thickness (each with a value of P=0.0001). BNP > or =200 pg/mL was the most reliable predictor of heart failure symptoms, with positive and negative predictive values of 63% and 79%, respectively. BNP power in distinguishing patients with or without heart failure symptoms was less than that for differentiating between no (or only mild) and severe symptoms (area under receiver operating characteristic curve=0.75 and 0.83, respectively). CONCLUSIONS: Plasma BNP is independently related to the presence and magnitude of heart failure symptoms in patients with HCM. As a clinical marker for heart failure, BNP is limited by considerable overlap in values between categories of heart failure severity as well as confounding variables of left ventricular wall thickness and age.

Adult↗
PubMed2004

Morbidity, mortality, physiologic and functional parameters in elderly and non-elderly patients in the Valsartan Heart Failure Trial (Val-HeFT).

BACKGROUND: The Valsartan Heart Failure Trial (Val-HeFT) demonstrated the favorable effects of the addition of valsartan to prescribed heart failure (HF) therapy on HF hospitalization, and functional and physiological parameters. As the prevalence of HF morbidity and mortality are increased in the elderly, the effect of valsartan in the elderly is of clinical significance. METHODS: In this post-hoc analysis, morbidity, mortality, left ventricular (LV) size and function, brain natriuretic peptide (BNP), aldosterone, norepinephrine (NE), quality of life, and treatment effect with valsartan were examined by subgroups of 2350 elderly (>or= 65 years) and 2660 non-elderly (< 65 years) patients enrolled in Val-HeFT. RESULTS: While the overall incidence of morbidity and mortality was higher in the elderly, valsartan produced beneficial effects in reducing risk of morbidity in the elderly by 11.8% (P = .07), and the non-elderly by 14.6% (P = .09). Valsartan had no effect on mortality compared to placebo in the non-elderly, 15.2% vs 15.0% (P = .87), and elderly, 25.1% vs 24.0%, (P = .64). Valsartan had statistically significant beneficial effects in both the elderly and non-elderly on LV size and function, BNP, aldosterone and quality of life. Beneficial effects on NE were also observed with valsartan in both subgroups with statistically significant reductions produced in the non-elderly. CONCLUSIONS: Val-HeFT demonstrated that elderly patients present with more advanced HF as evidenced by higher morbidity and mortality along with greater neurohormonal activation. In Val-HeFT, valsartan produced a consistent beneficial effect on morbidity, LV function and size, quality of life, and neurohormonal levels in both the elderly and non-elderly.

Adult↗
PubMed2004

Clinical experience with perindopril in African-American hypertensive patients: a large United States community trial.

BACKGROUND: The prevalence of hypertension is greater in African Americans, and management of this condition presents challenges for practicing physicians. METHODS: The effectiveness and safety of perindopril was evaluated in hypertensive African-American patients (n = 1412) and hypertensive white patients (n = 7745) who had participated in a large United States community trial. Patients received perindopril 4 mg once daily for 6 weeks. Based on physicians' clinical judgment at week 6, the dose was either maintained or increased to 8 mg for an additional 6 weeks. RESULTS: Reduction of blood pressure (BP) was significant with perindopril monotherapy (4 to 8 mg once daily) in African Americans and whites (P <.001). The magnitude of BP reduction was significantly more in whites (P <.001). Up-titration of perindopril achieved additional BP reduction in both ethnic groups (P <.001). Control of BP (<140/90 mm Hg) in elderly (>65 years of age) and diabetic African-Americans subgroups was achieved in 32.1% and 31.6%, respectively. Perindopril was safe and well tolerated. CONCLUSIONS: Perindopril monotherapy is effective and is a viable initial therapeutic option as an antihypertensive agent in African-American individuals with hypertension.

Aged↗
PubMed2004

Determinants of radial artery pulse wave analysis in asymptomatic individuals.

BACKGROUND: Noninvasive techniques to evaluate arterial stiffness include noninvasive radial artery pulse contour analysis. Diastolic pulse contour analysis provides a separate assessment of large (C1) and small artery (C2) elasticity. Analysis of the systolic pulse contour identifies two pressure peaks (P1 and P2) that relate to incident and reflected waves. This study aimed to compare indices from systolic and diastolic pulse contour analysis from the radial pressure waveform and to correlate these indices with traditional risk factors in asymptomatic individuals screened for cardiovascular disease. METHODS: In 298 consecutive subjects (206 male and 92 female healthy subjects with a mean age of 50 +/- 12 years), noninvasive radial artery pressure waveforms were acquired with a piezoelectric transducer and analyzed for 1) diastolic indices of C1 and C2 from the CR-2000 CVProfiler, and 2) systolic indices of augmentation as defined by augmentation pressure (AP), augmentation index (AIx), and systolic reflective index (SRI = P2/P1). These indices were then correlated to each other as well as to individual traditional risk factors and the Framingham Risk Score. RESULTS: Diastolic indices were significantly and inversely correlated to systolic indices with C2 showing a stronger inverse association than C1. C2 and Alx were significantly correlated with height, weight, and body mass index in men but not in women. All indices correlated better to blood pressure in women than men. In women, only systolic indices were significantly correlated to HDL cholesterol and only diastolic indices were significantly correlated to LDL cholesterol. All indices were significantly correlated to the Framingham Risk Score, which was stronger in women then men, but when adjusted for age only diastolic indices remained significant in women. CONCLUSIONS: Diastolic and systolic indices of pulse contour analysis correlate differently with traditional risk factors in men and women.

Adult↗