Prognostic Significance of Plasma Norepinephrine in Patients With Asymptomatic Left Ventricular Dysfunction

Benedict, Claude R.; Shelton, Brent J.; Johnstone, David E.; Francis, Gary S.; Greenberg, Barry; Konstam, Marvin A.; Probstfield, Jeffrey L.; Yusuf, Salim

doi:10.1161/01.cir.94.4.690

Cited by 324 publications

(185 citation statements)

References 27 publications

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“…This has been shown, for example, in patients with congestive heart failure, in which indirect and direct markers of systemic and regional sympathetic drive (venous plasma norepinephrine, heart rate variability, heart rate spectral power, cardiac and renal norepinephrine spillover) have been documented to bear a close and direct relationship with cardiovascular mortality, disease progression and arrhythmic events, including sudden death (46)(47)(48)(49)(50)(51). Similar conclusions have been drawn by assessing the prognostic values of plasma norepinephrine or heart rate variability in the post-stroke phase following an acute myocardial infarction or in patients with vasospastic angina (52)(53)(54)(55). Finally, dysfunction in sympathetic cardiovascular control has also been shown to have prognostic value in non-cardiovascular diseases such as diabetes mellitus and renal failure (56,57), thereby documenting the clinical relevance of the neuroadrenergic overdrive in a broad spectrum of pathological states.…”

Section: Sympathetic Activation Cardiovascular Risk and Organ Damagementioning

confidence: 70%

Sympathetic Overdrive and Cardiovascular Risk in the Metabolic Syndrome

Grassı

2006

Hypertens Res

121

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Section: Sympathetic Activation Cardiovascular Risk and Organ Damagementioning

confidence: 70%

Sympathetic Overdrive and Cardiovascular Risk in the Metabolic Syndrome

Grassı

2006

Hypertens Res

121

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“…High catecholamine levels can damage cardiac myocytes (15,16) and have been associated with cardiac events and mortality in a variety of clinical and population-based samples (17)(18)(19)(20)(21)(22). Thus, altered autonomic tone may contribute to adverse cardiac outcomes in patients with depression.…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

Depressive Symptoms and 24-Hour Urinary Norepinephrine Excretion Levels in Patients With Coronary Disease: Findings From the Heart and Soul Study

Otte¹,

Neylan²,

Pipkin³

et al. 2005

AJP

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Objective-Depressive symptoms are associated with an increased risk of cardiac events in patients with heart disease. Elevated catecholamine levels may contribute to this association, but whether depressive symptoms are associated with catecholamine levels in patients with heart disease is unknown. Method-The authors examined the association between depressive symptoms (defined by a PatientHealth Questionnaire score ≥10) and 24-hour urinary norepinephrine, epinephrine, and dopamine excretion levels in 598 subjects with coronary disease.Results-A total of 106 participants (18%) had depressive symptoms. Participants with depressive symptoms had greater mean norepinephrine excretion levels than those without depressive symptoms (65 μg/day versus 59 μg/day, with adjustment for age, sex, body mass index, smoking, urinary creatinine levels, comorbid illnesses, medication use, and cardiac function). In logistic regression analyses, participants with depressive symptoms were more likely than those without depressive symptoms to have norepinephrine excretion levels in the highest quartile and above the normal range. Depressive symptoms were not associated with dopamine or epinephrine excretion levels.Conclusions-In patients with coronary disease, depressive symptoms are associated with elevated norepinephrine excretion levels. Future longitudinal studies are needed to determine whether elevations in norepinephrine contribute to adverse cardiac outcomes in patients with depressive symptoms.Coronary disease and major depression are the two leading causes of disability worldwide (1). Depressive symptoms occur in about 20% of patients with coronary disease (2,3) and are associated with an increased risk of future cardiac events and mortality (4-7). However, the mechanisms linking depressive symptoms with subsequent cardiac events are unknown (8).Enhanced activity of the sympathetic nervous system with increased concentrations of catecholamines has been proposed as one possible mechanism by which depressive symptoms may increase morbidity and mortality (7-9). This hypothesis is based on evidence suggesting that depressed patients without heart disease have elevated catecholamine levels (10-12). Previous studies have also found alterations of the sympathetic nervous system in depressed NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript patients with coronary heart disease, including increased heart rate (13) and decreased heart rate variability (14). High catecholamine levels can damage cardiac myocytes (15,16) and have been associated with cardiac events and mortality in a variety of clinical and population-based samples (17)(18)(19)(20)(21)(22). Thus, altered autonomic tone may contribute to adverse cardiac outcomes in patients with depression.The Heart and Soul Study is an ongoing prospective cohort study of psychosocial factors and health outcomes in patients with coronary disease (3). We examined the association of depressive symptoms with 24-hour levels of uri-nary norepinephrine, epinephr...

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“…6 Left ventricular dysfunction and reduced tissue perfusion trigger increased neurohormonal activation, including renin release and adrenergic drive, as compensatory responses to support heart rate and myocardial contractility. 6,22 In an enzymatic cascade, renin cleaves angiotensinogen to release angiotensin I, which is then converted, primarily by ACE, into angiotensin II, the main end product and effector of the RAS. Angiotensin II is a powerful vasoconstrictor that affects SNS activation, blood pressure control, and natriuresis, among other biologic functions.…”

Section: Pathogenesis Of Heart Failure: Overviewmentioning

confidence: 99%

“…6 Increased neurohormonal activation has been shown to be a significant predictor of cardiovascular mortality in patients with asymptomatic LV dysfunction. 22 …”

Section: Pathogenesis Of Heart Failure: Overviewmentioning

confidence: 99%

Rationale for the use of angiotensin ii receptor blockers in patients with left ventricular dysfunction (part I of II)

Levine

2005

Clin Cardiol

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Summary: Almost 5 million individuals in the United States are diagnosed with chronic heart failure (HF), and the prevalence is increasing. Angiotensin-converting enzyme (ACE) inhibitors and beta blockers, neurohormonal antagonists that block the renin-angiotensin system (RAS) and the sympathetic nervous system, respectively, have been shown in clinical trials to reduce morbidity and mortality in patients with HF, and these therapies are now integral components of standard HF treatment. Yet, morbidity and mortality rates in HF remain unacceptably high, and the limitations of current standard therapies are becoming increasingly apparent. About 10% of patients with HF are unable to tolerate ACE inhibitors, often because of cough. In addition, ACE inhibition may not completely block the RAS because angiotensin II, the main end product of the RAS, can be generated via non-ACE enzymatic pathways. Angiotensin II receptor blockers (ARBs) may exert more complete RAS blockade than ACE inhibitors by interfering with the binding of angiotensin II at the receptor level, regardless of the enzymatic pathway of production. They are also better tolerated than ACE inhibitors and have been shown to improve symptoms and function in clinical trials in patients with HF. These factors provide a strong rationale for the study of the clinical effects of ARBs in patients with HF.

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Prognostic Significance of Plasma Norepinephrine in Patients With Asymptomatic Left Ventricular Dysfunction

Cited by 324 publications

References 27 publications

Sympathetic Overdrive and Cardiovascular Risk in the Metabolic Syndrome

Sympathetic Overdrive and Cardiovascular Risk in the Metabolic Syndrome

Depressive Symptoms and 24-Hour Urinary Norepinephrine Excretion Levels in Patients With Coronary Disease: Findings From the Heart and Soul Study

Rationale for the use of angiotensin ii receptor blockers in patients with left ventricular dysfunction (part I of II)

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