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The hypothalamic-pituitary-adrenal (HPA) axis, like the sympathetic nervous system and the renin-angiotensin-aldosterone (RAA) system, sustains life in stressful situations by increasing vascular tone and ensuring fuel availability. It also modulates inflammation and tissue repair processes. Untoward cardiovascular effects of chronic sympathetic and RAA activation are well recognized, illustrating that the short-term benefit of the physiologic stress response can be detrimental in the long term. Similarly, chronic tissue exposure to glucocorticoids may lead to metabolic and vascular changes that accelerate vascular senescence. Specific situations associated with chronic activation of the HPA axis-such as major depression, inflammatory disease and perhaps the metabolic syndrome-may derive some of their associated cardiovascular risk from untoward glucocorticoid effects. Since there are no definitive clinical studies directly addressing the relationship between the HPA axis and cardiovascular disease, we present indirect evidence from two types of studies: (1) studies that examine the cardiovascular effects of exogenous glucocorticoids, and (2) studies demonstrating that endogenous glucocorticoid activity varies between individuals. The effects of physiologic increases in endogenous glucocorticoid activity may not always mirror the effects of supraphysiologic glucocorticoids. Nevertheless, the known effects of exogenous glucocorticoids provide important insights into the putative effects of endogenous glucocorticoids.

Context: Glucocorticoids are known to acutely increase blood pressure, suppress inflammation, and precipitate insulin resistance. However, the short-term effects of glucocorticoids on other cardiovascular risk factors remain incompletely characterized.Objective: Our objective was to determine the effects of a short course of dexamethasone on multiple cardiovascular biomarkers and to determine whether suppression of morning cortisol in response to low-dose dexamethasone is correlated with cardiovascular risk markers in healthy volunteers. Design:We conducted a randomized, double-blind, placebo-controlled study. Setting:The study took place in a tertiary care hospital. Study subjects: Twenty-five healthy male volunteers, ages 19 -39 yr, participated in the study.Intervention: Subjects received either 3 mg dexamethasone twice daily or placebo for 5 d. Subjects also underwent a low-dose (0.5 mg) overnight dexamethasone suppression test. Measures:Parameters examined before and after the 5-d intervention included heart rate, blood pressure, weight, fasting lipid variables, homocysteine, renin, aldosterone, insulin resistance (homeostasis model assessment), high-sensitivity C-reactive protein, B-type natriuretic peptide, flow-mediated and nitroglycerin-mediated brachial artery dilatation, and heart rate recovery after exercise. All measurements were done in the morning hours in the fasting state.Results: Dexamethasone increased systolic blood pressure, weight, B-type natriuretic peptide, and high-density-lipoprotein-cholesterol. Dexamethasone decreased resting heart rate, high-sensitivity Creactive protein, and aldosterone and tended to attenuate nitroglycerin-mediated vasodilatation. There was no effect on flow-mediated vasodilatation, diastolic blood pressure, triglycerides, low-densitylipoprotein-cholesterol, nonesterified fatty acids, homocysteine, or heart rate recovery. The response of circulating cortisol to low-dose dexamethasone had no significant correlation with any of the cardiovascular risk markers. Conclusions

Background-The diagnostic and prognostic values of plasma B-type natriuretic peptide (BNP) testing are established. However, the range of plasma BNP levels present in the setting of chronic, stable systolic heart failure (HF) is unclear. Methods and Results-We followed up 558 consecutive ambulatory patients with chronic, stable systolic HF (left ventricular ejection fraction Ͻ50%) treated at a specialized outpatient HF clinic between November 2001 and February 2003. Retrospective chart review was performed to determine clinical and functional data at the time of BNP testing (Biosite Triage). The clinical characteristics of patients with plasma BNP levels Ͻ100 pg/mL and those with Ն100 pg/mL were compared. In our cohort, 60 patients were considered asymptomatic, and their plasma BNP levels ranged from 5 to 572 pg/mL (median, 147 pg/mL). Of the remaining 498 symptomatic (NYHA functional class II-III) patients, 106 (21.3%) had plasma BNP levels in the "normal" diagnostic range (Ͻ100 pg/mL). Patients in this "normal BNP" subgroup were more likely to be younger, to be female, to have nonischemic pathogenesis, and to have better-preserved cardiac and renal function and less likely to have atrial fibrillation. Conclusions-In the ambulatory care setting, both symptomatic and asymptomatic patients with chronic, stable systolic HF may present with a wide range of plasma BNP levels. In a subset of symptomatic patients (up to 21% in our cohort), plasma BNP levels are below what would be considered "diagnostic" (Ͻ100 pg/mL

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