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Biomedical subjects

J N Cohn

Publications and source records attributed to J N Cohn.

At least 55 records · Page 3Linked to original sources
PubMed1999

Racial differences in response to therapy for heart failure: analysis of the vasodilator-heart failure trials. Vasodilator-Heart Failure Trial Study Group.

BACKGROUND: Heart failure in blacks has been associated with a poorer prognosis than in whites. In such diseases as hypertension, blacks show pathophysiological differences and respond differently to some therapies than whites. The aim of this study is to evaluate the clinical characteristics and response to therapy of black compared with white patients with heart failure. METHODS AND RESULTS: In the first Vasodilator-Heart Failure Trial (V-HeFT I), 180 black male patients were compared with 450 white male patients for baseline characteristics, prognosis, and response to therapy. In V-HeFT II, the same comparisons were made for 215 black and 574 white male patients, including an analysis stratified by the presence or absence of a history of hypertension. In both trials, black patients had a lower incidence of coronary artery disease, greater incidence of previous hypertension, and a greater cardiothoracic ratio (P < .05) than white patients. In V-HeFT II, plasma norepinephrine levels were significantly less in blacks; plasma renin activity was less only in blacks with a history of hypertension. Overall mortality or hospitalization for congestive heart failure did not differ between blacks and whites in the placebo group in V-HeFT I. However, the mortality of black patients receiving hydralazine plus isosorbide dinitrate (H-I) was reduced (P = .04) in V-HeFT I, whereas white patients showed no difference from placebo. In V-HeFT II, only white patients showed a mortality reduction from enalapril therapy compared with H-I therapy (P = .02). Whites also showed evidence of greater blood pressure reduction and enhanced regression of cardiac size in response to enalapril. When stratified by history of hypertension in V-HeFT II, only whites with a history of hypertension, who had greater renin levels, showed significant mortality reduction with enalapril compared with H-I therapy. Hospitalization rates did not differ between treatment groups in either study. CONCLUSION: Whites and blacks showed differences in cause, neurohormonal stimulation, and pharmacological response in heart failure. This retrospective analysis suggests angiotensin-converting enzyme inhibitors are particularly effective in whites, and the H-I combination can be equally effective in blacks. Prospective trials involving large numbers of black patients are needed to further clarify their response to therapy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Rationale and design of the Valsartan Heart Failure Trial: a large multinational trial to assess the effects of valsartan, an angiotensin-receptor blocker, on morbidity and mortality in chronic congestive heart failure.

BACKGROUND: To investigate the role of persistent angiotensin activity despite angiotensin-converting enzyme inhibitor therapy in the progression of heart failure, the Valsartan Heart Failure Trial has been designed to investigate the effect of the angiotensin-receptor blocker, valsartan, on morbidity and mortality. METHODS AND RESULTS: Nearly 5,000 patients with New York Heart Association classes II to IV heart failure, while receiving all standard therapy, are being randomized to treatment with valsartan, 160 mg twice daily, or placebo in a worldwide study. Follow-up will be continued until 906 deaths have been recorded. Additional end points will include the need for hospitalization, other major morbid events, quality--of life measurement, changes in neurohormone levels, and changes in left ventricular size and function. Substudies will explore exercise tolerance, arrhythmias, and magnetic resonance imaging. CONCLUSION: This study should help establish the role of angiotensin-receptor blockade in the treatment of heart failure.

Adolescent↗
PubMed1999

Improving outcomes in congestive heart failure: Val-HeFT. Valsartan in Heart Failure Trial.

The aims of the treatment of heart failure are to improve the quality of life and slow the progression of cardiac disease. Improvement of quality of life is best assessed by questionnaire; progression of the disease is assessed by measuring mortality and morbidity. The agenda for the future is to establish intermediate markers for progression of cardiac disease that can be substituted for morbidity and mortality, and thus improve the efficiency and shorten the follow-up of clinical trials. At present, polypharmacy is required to achieve optimal improvements in quality and duration of life. Furthermore, some drugs may favorably affect one end point and adversely affect the other; for example, beta-blockers may exert adverse short-term effects on quality of life but may slow progression of the disease. Certain inotropic drugs may reduce symptoms but shorten life expectancy. Angiotensin-converting enzyme (ACE) inhibitors have exerted favorable effects on both quality of life and mortality, but the magnitude of these benefits has been disappointingly small. Persistent angiotensin-induced vasoconstriction and endocrine effects, despite ACE inhibition, is one possible explanation. The Valsartan in Heart Failure Trial (Val-HeFT) has been designed to test the efficacy and safety of the AT(1) receptor blocker (ARB) valsartan in combination with ACE inhibitors and all other prescribed therapies in patients with heart failure. The study is powered to detect a mortality benefit and should therefore establish the role of ARBs in this patient group. When this trial and other ongoing studies are completed, we will be more able to define the role of ARBs in the treatment of heart failure.

Angiotensin II↗
PubMed1999

Prevention of heart failure.

Heart failure (HF) is a progressive process and the objective of treatment should be to prevent progression. Treatment should begin at the stage of asymptomatic left ventricular dysfunction (LVD), not only to reduce mortality but also to preserve exercise capacity and quality of life. To prevent clinical progression in patients with asymptomatic LVD or HF, left ventricular remodelling and dilatation must be prevented. The SOLVD prevention trial-the only clinical trial on the prevention of HF-showed that ACE inhibition significantly reduced the development of HF, but did not significantly reduce mortality. Plasma norepinephrine is elevated in patients with asymptomatic LVD, is further elevated in patients with overt HF, and is correlated with increased mortality. Inhibition of the sympathetic nervous system by administration of beta-blocking agents is therefore a logical treatment for patients with HF or asymptomatic LVD. Clinical trials have shown that beta-blocking agents increase left ventricular ejection fraction and reduce left ventricular dimensions in patients with HF, indicating regression of left ventricular remodelling. Almost all the patients in these studies were receiving an ACE inhibitor as part of their background medication, therefore the relative efficacy of beta-blocking agents and ACE inhibitors in the regression of remodelling is not known. CARMEN, a double-blind, randomised, parallel group study of carvedilol versus enalapril versus carvedilol + enalapril in 450 patients with mild HF, will provide this information.

Adrenergic beta-Antagonists↗
PubMed1999

Age-related abnormalities in arterial compliance identified by pressure pulse contour analysis: aging and arterial compliance.

The objective of this study was to evaluate age-related changes in pulsatile arterial function. Aging alters arterial pulsatile function and produces consistent changes in the pressure pulse contour. A reduced systemic arterial compliance that can be derived from analysis of the pulse contour is regarded as the best clinical index of impaired pulsatile arterial function and may mark the presence of early vascular damage. We analyzed intra-arterial brachial artery waveforms in 115 healthy normotensive volunteers (83 men, 32 women) and radial artery waveforms obtained with the use of a calibrated tonometer device in 212 healthy volunteers (147 women, 65 men). A computer-based assessment of the diastolic pressure decay and a modified Windkessel model of the circulation were used to quantify changes in arterial waveform morphology in terms of large artery or capacitive compliance, oscillatory or reflective compliance in the small arteries, inertance, and systemic vascular resistance. Large artery compliance and oscillatory compliance correlated negatively with age for both invasive and noninvasive groups (r=-0.50 and r=-0.55; r=-0.37 and r=-0.66; P<0.001 for all). The slopes of the regression lines for the decline in oscillatory compliance with age were significantly steeper than those recorded for large artery compliance estimates. The change in blood pressure with age independently contributed to the decrease in large artery compliance but not oscillatory compliance in both groups. Consistent age-related changes were found in the pressure pulse contour by analysis of waveforms obtained invasively or noninvasively from the upper limb. The change in the oscillatory or reflective compliance estimate was independent of blood pressure change and may represent a better marker than large artery or capacitive compliance of the degenerative aging process in altering pulsatile arterial function.

Adult↗
PubMed1999

Vascular wall function as a risk marker for cardiovascular disease.

Elevated systolic blood pressure (SBP) and wide pulse pressure (PP) are both important risk markers for cardiovascular disease. They are indicative of a vascular abnormality, most likely located at the endothelial-vascular interface, where the balance between vasodilator and vasoconstriction determines vascular tone, structure and change in blood pressure. This abnormality makes vessel walls vulnerable to degeneration. Reducing blood pressure in patients with endothelial-vascular dysfunction has been found to reduce the rates of cardiovascular events. Preliminary data also suggest that drug therapy has successfully improved endothelial dysfunction. Endothelial release of nitric oxide has little effect on the aorta, but affects the elasticity of thinner-walled branch vessels and arterioles beneficially. Nitric oxide is normally released in response to increased blood flow and this process is often impaired by various disease states. Since blood flow can be measured, endothelial function can be assessed. Arterial compliance can be determined clinically by a technique that combines pulse wave recording and computer analysis of diastolic decay. In certain disease states, compliance seems to be reduced more in smaller vessels, a marker of early stage vascular disease. Screening for arterial elasticity with this tool can identify those patients with early stages of arterial wall disease and prevent further damage. However, further research is needed to determine whether the benefit lies in lowering blood pressure or in the actual effect of the drug in restoring the function of the arterial wall.

Arteries↗
PubMed1998

A dose-dependent increase in mortality with vesnarinone among patients with severe heart failure. Vesnarinone Trial Investigators.

BACKGROUND: Vesnarinone, an inotropic drug, was shown in a short-term placebo-controlled trial to improve survival markedly in patients with severe heart failure when given at a dose of 60 mg per day, but there was a trend toward an adverse effect on survival when the dose was 120 mg per day. In a longer-term study, we evaluated the effects of daily doses of 60 mg or 30 mg of vesnarinone, as compared with placebo, on mortality and morbidity. METHODS: We enrolled 3833 patients who had symptoms of New York Heart Association class III or IV heart failure and a left ventricular ejection fraction of 30 percent or less despite optimal treatment. The mean follow-up was 286 days. RESULTS: There were significantly fewer deaths in the placebo group (242 deaths, or 18.9 percent) than in the 60-mg vesnarinone group (292 deaths, or 22.9 percent) and longer survival (P=0.02). The increase in mortality with vesnarinone was attributed to an increase in sudden death, presumed to be due to arrhythmia. The quality of life had improved significantly more in the 60-mg vesnarinone group than in the placebo group at 8 weeks (P<0.001) and 16 weeks (P=0.003) after randomization. Trends in mortality and in measures of the quality of life in the 30-mg vesnarinone group were similar to those in the 60-mg group but not significantly different from those in the placebo group. Agranulocytosis occurred in 1.2 percent of the patients given 60 mg of vesnarinone per day and 0.2 percent of those given 30 mg of vesnarinone. CONCLUSIONS: Vesnarinone is associated with a dose-dependent increase in mortality among patients with severe heart failure, an increase that is probably related to an increase in deaths due to arrhythmia. A short-term benefit in terms of the quality of life raises issues about the appropriate therapeutic goal in treating heart failure.

Aged↗
PubMed1998

Preventing congestive heart failure.

The morbidity, mortality and health care costs associated with congestive heart failure make prevention a more attractive public health strategy than treatment. Aggressive management of etiologic factors, including hypertension, coronary artery disease, valvular disease and excessive alcohol intake, can prevent the left ventricular remodeling and dysfunction that lead to heart failure. Early intervention with angiotensin converting enzyme inhibitors in patients with chronic left ventricular dysfunction can prevent, as well as treat, the syndrome. Several intervention strategies in patients with acute myocardial infarction can slow or prevent the left ventricular remodeling process that antedates congestive heart failure. The primary care physician must be alert to the need for aggressive intervention to reduce the burden of heart failure syndrome on the patient and on society.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

The importance of arterial compliance in cardiovascular drug therapy.

Arterial compliance, defined as a change in dimension in response to a given change in stress, is becoming an increasingly important clinical parameter. Related concepts, such as distensibility, elasticity, and stiffness, and more traditional concepts such as resistance, afterload, and impedance need to be differentiated from compliance, although they are frequently (inappropriately) used interchangably. Many studies cannot differentiate between compliance changes due to a drug's effect on blood pressure and those due to a drug's effect on vessel wall integrity. This differentiation is important because a more physiologic therapy, one that benefits pulsatile and nonpulsatile flow, should be of greater clinical benefit than a therapy that only lowers blood pressure. A number of methods have been used to estimate compliance, but to date there is no generally agreed-on best method. There also are no longitudinal studies that relate abnormal compliance and drug effects to outcome. Nonetheless, patients at risk from a variety of disease states, such as hypertension, diabetes mellitus, and hypercholesterolemia, may benefit from earlier recognition of abnormal compliance. Earlier recognition may lead to interventions that would reduce their risk. This review includes a discussion of compliance and related estimates of blood vessel function and attempts to summarize the data currently available regarding the effects of cardioactive drugs on arterial compliance.

Adrenergic beta-Antagonists↗
PubMed1998

Non-invasive studies of peripheral vascular compliance using a non-occluding photoplethysmographic method.

A non-invasive technique is implemented to measure a peripheral vascular compliance index Cindex, using an infrared photoplethysmographic waveform as an indicator of intravascular volume change and a continuous blood pressure monitor to measure the blood pressure during each heart-beat. The non-linear behaviour of Cindex with pressure and the effect of age on Cindex are studied in 62 males (15-73 years). Repeatability tests and the effect of ice-water exposure of a portion of a limb are studied in 10 and 14 subjects, respectively. For each individual, Cindex measurements are taken at discrete values of local mean arterial pressure (Pmean), and a Cindex against Pmean plot is obtained. There is a statistically significant difference (p < 0.05) in Cindex for the lower values of Pmean (60-100 mmHg) between two age groups formed (15-52 and 58-73 years). The cold-pressor test (CPT) shows a 68% median decrease in Cindex, with an inter-quartile range of 60-77%, in a matter of seconds. The results suggest that Cindex may be a useful noninvasive indicator of peripheral vascular compliance in humans.

Adolescent↗
PubMed1998

Functional impact of an increase in ventricular mass after myocardial damage and its attenuation by converting enzyme inhibition.

BACKGROUND: A increase in left ventricular mass after ventricular damage has been identified as an initial response to injury. However, the functional significance of this response has not been clearly established and is the focus of this study. METHODS AND RESULTS: Twelve mongrel dogs underwent transmyocardial direct current shock to produce transmural left ventricular damage. Six were assigned to converting enzyme inhibitor therapy initiated 24 hours after damage and continued for 4 weeks. The remaining six dogs served as a control group. Left ventricular structure (mass and end diastolic volume) and systolic function (regional and global ejection fraction at rest and during afterload stress) were assessed by magnetic resonance imaging before damage and at the end of the 4-week period. After myocardial damage, left ventricular mass increased from 93.6 +/- 4.0 to 107.5 +/- 3.4 gm in the control group (P < .01) with no change in ventricular volume. Ramipril-treated dogs displayed a reduction in mass (83.2 +/- 2.2 to 74.6 +/- 2.9 gm, P < .05). In the control group, there was greater reduction in global ejection fraction in response to afterload stress at 4 weeks compared with baseline (-16 +/- 4 vs -4 +/- 3%, P = .03). Ejection fraction response to afterload stress was maintained at 4 weeks in the converting enzyme inhibitor-treated group (-5 +/- 3 vs - 1 +/- 4%) and was different at 4 weeks from the control group (-1 +/- 4 vs -16 +/- 4%, P = .004). CONCLUSION: The increase in left ventricular mass noted after direct current shock was associated with the impairment of systolic function during afterload stress. Inhibition of this mass increase results in preservation of function, thus further supporting the concept that attenuation of ventricular remodeling should be a therapeutic goal.

Angiotensin-Converting Enzyme Inhibitors↗