Depressive symptoms are associated with clinical outcomes in heart failure with reduced ejection fraction.

AIMS: The objective of this study was to examine associations between elevated depressive symptoms and increased risk of adverse clinical events patients with heart failure and reduced ejection fraction (HFrEF), as well as the potential contribution of health behaviours. METHODS AND RESULTS: One hundred forty-two men and women with HFrEF were enrolled through heart failure (HF) clinics and followed over time. At baseline and 6 months, depressive symptoms were assessed by the Beck Depression Inventory-II (BDI-II) and HFrEF disease activity by B-type natriuretic peptide (BNP). The Self-Care of Heart Failure Index (SCHFI) was used to assess HF self-care behaviours. Proportional hazards regression models assessed the contribution of depressive symptoms and HFrEF disease biomarkers on death or cardiovascular hospitalization. Over a median follow-up period of 4 years, 42 patients (30%) died, and 84 (60%) had cardiovascular hospitalizations. A 10-point higher baseline BDI-II score was associated with a 35% greater risk of death or cardiovascular hospitalization. Higher baseline BDI-II scores were associated with poorer HF self-care maintenance behaviours (R = -0.30, P < 0.001) and fewer daily steps (R = -0.19, P = 0.04), suggesting that elevated depressive symptoms may diminish important health behaviours. Increases in plasma BNP over 6 months were associated with worse outcomes. Changes in BDI-II and plasma BNP over 6 months were positively related (R = 0.25, P = 0.004). CONCLUSIONS: This study confirms that elevated depressive symptoms are associated with an increased likelihood of adverse clinical outcomes in patients with HFrEF. Poor health behaviours may contribute to the adverse association of elevated depressive symptoms with the increased hazard of adverse clinical outcomes.

Association of Depression Symptoms and Biomarkers of Risk on Clinical Outcomes in HFrEF.

BACKGROUND: Prior studies have demonstrated an association of depression with adverse clinical outcomes in patients with HFrEF, but the possible mechanisms responsible for the association are not unserstood. METHODS: 142 men and women with HFrEF were enrolled through HF clinics and followed over time. At baseline and 6-months, depression was assessed by the Beck Depression Inventory (BDI-II) and disease activity by B-type natriuretic peptide (BNP). Proportional Hazards Regression Models assessed the contribution of depressive symptoms and HFrEF disease biomarkers on death or cardiovascular hospitalization. RESULTS: Over a median follow-up period of 4 years, 42 patients (30%) died, and 84 (60%) had cardiovascular hospitalizations. A 10-point higher baseline BDI-II score was associated with a 35% higher hazard of death or cardiovascular hospitalization. Greater baseline BDI-II scores were associated with poorer HF self-care maintenance (R=-0.30, p<0.001) and fewer daily steps (R=-0.19, p=0.04), suggesting that depression may adversely affect important health behaviors. Increases in plasma BNP over 6 months were associated with worse outcomes. Changes in BDI-II score and plasma BNP over 6 months were positively correlated (R=0.25, p=0.004). CONCLUSIONS: This study underscores the importance of elevated depression symptoms and their association with an increased likelihood of adverse clinical outcomes in patients with HFrEF. Health behaviors may play a greater role than direct biobehavioral pathways in the adverse effects of depression on the HF disease trajectory and resultant clinical outcomes.

Vascular α1-Adrenergic Receptor Responsiveness in Masked Hypertension.

BACKGROUND: Masked hypertension (nonhypertensive in the clinic setting but hypertensive outside the clinic during wakefulness) is characterized by increased blood pressure in response to physical and emotional stressors that activate the sympathetic nervous system (SNS). However, no studies have assessed vascular reactivity to a pharmacological SNS challenge in individuals with masked hypertension. METHODS: We analyzed data from 161 adults aged 25 to 45 years (mean ± standard deviation age 33 ± 6 years; 48% were African American and 43% were female). Participants completed ambulatory blood pressure monitoring, and a standardized α 1-adrenergic agonist phenylephrine test that determines the dose of phenylephrine required to increase a participant's mean arterial pressure by 25 mm Hg (PD25). RESULTS: Twenty-one participants were considered to have masked hypertension (clinic systolic blood pressure (SBP) <140 and diastolic blood pressure (DBP) <90 mm Hg but awake SBP ≥135 or DBP ≥85 mm Hg), 28 had sustained hypertension (clinic SBP ≥140 or DBP ≥90 mm Hg and awake SBP ≥135 or DBP ≥85 mm Hg), and 106 had sustained normotension (clinic SBP <140 and DBP <90 mm Hg and awake SBP <135 and DBP <85 mm Hg). After multivariable adjustment, the mean (±SE) PD25 was less in participants with masked hypertension compared with their counterparts with sustained normotension (222.1 ± 33.2 vs. 328.7 ± 15.0; P = 0.012), but similar to that observed in subjects with sustained hypertension (254.8 ± 31.0; P =0.12). CONCLUSIONS: Among young and middle-aged adults, masked hypertension is associated with increased vascular reactivity to a SNS challenge, which may contribute to elevated awake BPs as well as to increased cardiovascular disease risk.

The modifying effects of social support on psychological outcomes in patients with heart failure.

OBJECTIVE: We examined the modifying effects of social support on depressive symptoms and health-related quality of life (QoL) in patients receiving coping skills training (CST). METHOD: We considered the modifying effects of social support in the Coping Effectively with Heart Failure clinical trial, which randomized 179 heart failure (HF) patients to either 4 months of CST or usual care enhanced by HF education (HFE). CST involved training in specific coping techniques, whereas HFE involved education about HF self-management. Social support was assessed by the Enhancing Recovery in Coronary Heart Disease (ENRICHD) Social Support Inventory, QoL was assessed with the Kansas City Cardiomyopathy Questionnaire (KCCQ), and depression was assessed with the Beck Depression Inventory-II (BDI-II). RESULTS: Linear regression models revealed a significant Intervention Group × Baseline Social Support interaction for change in KCCQ total scores (p = .006) and BDI-II scores (p < .001). Participants with low social support assigned to the CST intervention showed large improvements in KCCQ scores (M = 11.2, 95% CI [5.7, 16.8]), whereas low-social-support patients assigned to the HFE controls showed no significant change (M = -0.8, 95% CI [-7.2, 5.6]). Similarly, BDI-II scores in participants with low social support in the CST group showed large reductions (M = -8.7, 95% CI [-11.3, -6.1]) compared with low-social-support HFE participants (M = -3.0, 95% CI [-6.0, -0.1]). CONCLUSIONS: HF patients with low social support benefit substantially from telephone-based CST interventions. Targeting HF patients with low social support for behavioral interventions could prove to be a cost-effective strategy for improving QoL and reducing depression. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Blood pressure reactivity to psychological stress is associated with clinical outcomes in patients with heart failure.

INTRODUCTION: Cardiovascular (CV) reactivity to psychological stress has been implicated in the development and exacerbation of cardiovascular disease (CVD). Although high CV reactivity traditionally is thought to convey greater risk of CVD, the relationship between reactivity and clinical outcomes is inconsistent and may depend on the patient population under investigation. The present study examined CV reactivity in patients with heart failure (HF) and its potential association with long-term clinical outcomes. METHODS: One hundred ninety-nine outpatients diagnosed with HF, with ejection fraction ≤40%, underwent an evaluation of blood pressure (BP) and heart rate reactivity to a laboratory-based simulated public-speaking stressor. Cox proportional hazards regression models were used to examine the prospective association between BP and heart rate reactivity on a combined end point of death or CV hospitalization over a 5-year median follow-up period. RESULTS: Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) reactivity, quantified as continuous variables, were inversely related to risk of death or CV hospitalization (Ps < .01) after controlling for established risk factors, including HF disease severity and etiology. In similar models, heart rate reactivity was unrelated to outcome (P = .12). In models with tertiles of reactivity, high SBP reactivity, compared with intermediate SBP reactivity, was associated with lower risk (hazard ratio [HR] = .498, 95% CI .335-.742, P =.001), whereas low SBP reactivity did not differ from intermediate reactivity. For DBP, high reactivity was marginally associated with lower risk compared with intermediate DBP reactivity (HR = .767, 95% CI .515-1.14, P =.193), whereas low DBP reactivity was associated with greater risk (HR = 1.49, 95% CI 1.027-2.155, P =.0359). No relationship of heart rate reactivity to outcome was identified. CONCLUSIONS: For HF patients with reduced ejection fraction, a robust increase in BP evoked by a laboratory-based psychological challenge was associated with lower risk for adverse CVD events and may be a novel and unique marker of left ventricular systolic reserve that is accompanied by a more favorable long-term prognosis.

Race and sex differences in cardiovascular α-adrenergic and ß-adrenergic receptor responsiveness in men and women with high blood pressure.

OBJECTIVE: Hypertension is associated with unfavorable changes in adrenergic receptor responsiveness, but the relationship of race and sex to adrenergic receptor responsiveness in the development of cardiovascular disease is unclear. This study examined α-adrenergic and ß-adrenergic receptor responsiveness in African-American and white men and women with untreated high blood pressure (BP) (HBP) and with normal BP. METHODS AND RESULTS: The study sample comprised 161 African-American and white men and women in the age range 25-45 years. Isoproterenol, a nonselective ß-adrenergic receptor agonist, was administered intravenously to determine the bolus dose required to increase heart rate by 25 bpm, an index of ß-adrenergic receptor responsiveness. Similarly, phenylephrine, an α1-adrenergic receptor agonist, was administered to determine the bolus dose required to increase BP by 25 mmHg, an index of vascular α1-adrenergic receptor responsiveness. HBP (P < 0.01), male sex (P = 0.04), and higher BMI (P < 0.01) were all associated with reduced ß-adrenergic receptor responsiveness, with a similar trend observed for African-American race (P = 0.07). Conversely, α1-adrenergic receptor responsiveness was increased in association with HBP (P < 0.01), female sex (P < 0.01), and African-American race (P < 0.01). CONCLUSION: In the early stages of hypertension, cardiovascular ß-adrenergic receptors demonstrate blunted responsiveness, whereas conversely α1-adrenergic receptors exhibit increased responsiveness. This pattern of receptor changes is especially evident in men and African-Americans, is exacerbated by obesity, and may contribute to the development of cardiovascular disease.

Effects of Coping Skills Training on Quality of Life, Disease Biomarkers, and Clinical Outcomes in Patients With Heart Failure: A Randomized Clinical Trial.

BACKGROUND: Heart failure (HF) is a chronic disease that compromises patients' quality of life (QoL). Interventions designed to reduce distress and improve disease self-management are needed. We evaluated the efficacy of a telephone-based coping skills training (CST) intervention. METHODS AND RESULTS: This randomized clinical trial involved 180 HF outpatients with reduced ejection fraction. Participants ranged in age from 29 to 87 years (mean=58 years); 27% were women, and 47% were nonwhite. Participants were randomized to either a CST intervention or heart failure education, both delivered over 16 weeks. The primary outcomes were (1) postintervention effects on QoL and HF disease biomarkers (both with α=0.01), and (2) a composite measure of time to death or first hospitalization (with α=0.03) over a median follow-up period of 3 years. CST resulted in greater improvements in QoL compared with heart failure education (P<0.01), including the Kansas City Cardiomyopathy Questionnaire (P=0.009), depressive symptoms (P=0.027), and the 6-minute walk test (P=0.012). However, it did not differentially improve HF disease biomarkers or reduce risk of all-cause hospitalizations or death (hazard ratio=0.84 [95% confidence interval, 0.59-1.12]). Interestingly, exploratory analyses showed that participants randomized to CST experienced a reduction in the composite end point of worsening HF hospitalization or death during the 3-year follow-up period (hazard ratio=0.65 [95% confidence interval, 0.44-0.98]; P=0.040). CONCLUSIONS: CST improved QoL in patients with HF. Monitoring and improving QoL is emerging as an important aspect of the clinical management of HF that can reduce disease burden and may help improve clinical outcomes in this vulnerable patient population. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00873418.

Coping effectively with heart failure (COPE-HF): design and rationale of a telephone-based coping skills intervention.

BACKGROUND: Coping Effectively with Heart Failure (COPE-HF) is an ongoing randomized clinical trial funded by the National Institutes of Health to evaluate if a coping skills training (CST) intervention will result in improved health status and quality of life as well as reduced mortality and hospitalizations compared with a heart failure education (HFE) intervention. METHODS AND RESULTS: Two hundred heart failure (HF) patients recruited from the Duke University Medical Center and the University of North Carolina Hospital system will be randomized to a CST intervention (16 weekly 30-minute telephone counseling sessions including motivational interviewing and individually tailored cognitive behavioral therapy) or to an HFE intervention (16 weekly 30-minute telephone sessions including education and symptom monitoring). Primary outcomes will include postintervention effects on HF biomarkers (B-type natriuretic peptide, ejection fraction) and quality of life, as well as long-term clinical outcomes (hospitalizations and death). Secondary analyses will include an evaluation of treatment effects across subpopulations, and potential mechanisms by which CST may improve clinical outcomes. CONCLUSIONS: COPE-HF is a proof-of-concept study that should provide important insights into the health benefits of a CST intervention designed to enhance HF self-management, improve health behaviors, and reduce psychologic distress.

Worsening depressive symptoms are associated with adverse clinical outcomes in patients with heart failure.

OBJECTIVES: The purpose of this study was to assess the impact of changes in symptoms of depression over a 1-year period on subsequent clinical outcomes in heart failure (HF) patients. BACKGROUND: Emerging evidence shows that clinical depression, which is prevalent among patients with HF, is associated with a poor prognosis. However, it is uncertain how changes in depression symptoms over time may relate to clinical outcomes. METHODS: One-hundred forty-seven HF outpatients with ejection fraction of less than 40% were assessed for depressive symptoms using the Beck Depression Inventory (BDI) at baseline and again 1 year later. Cox proportional hazards regression analyses, controlling for established risk factors, were used to evaluate how changes in depressive symptoms were related to a combined primary end point of death or cardiovascular hospitalization over a median follow-up period of 5 years (with a range of 4 to 7 years and no losses to follow-up). RESULTS: The 1-year change in symptoms of depression, as indicated by higher BDI scores over a 1-year interval (1-point BDI change hazard ratio [HR]: 1.07, 95% confidence interval [CI]: 1.02 to 1.12, p = 0.007), was associated with death or cardiovascular hospitalization after controlling for baseline depression (baseline BDI HR: 1.1, 95% CI: 1.06 to 1.14, p < 0.001) and established risk factors, including HF cause, age, ejection fraction, plasma N-terminal pro-B-type natriuretic peptide level, and prior hospitalizations. CONCLUSIONS: Worsening symptoms of depression are associated with a poorer prognosis in HF patients. Routine assessment of symptoms of depression in HF patients may help to guide appropriate medical management of these patients who are at increased risk for adverse clinical outcomes.

Relationship of depression to death or hospitalization in patients with heart failure.

BACKGROUND: Depression is widely recognized as a risk factor in patients with coronary heart disease. However, patients with heart failure (HF) have been less frequently studied, and the effect of depression on prognosis, independent of disease severity, is uncertain. METHODS: Two hundred four outpatients having a diagnosis of HF, with a ventricular ejection fraction of 40% or less, underwent baseline assessments including evaluation of depressive symptoms using the Beck Depression Inventory and of HF severity determined by plasma N-terminal pro-B-type natriuretic peptide. Cox proportional hazards regression analyses were used to examine the effects of depressive symptoms on a combined primary end point of death and hospitalizations because of cardiovascular disease (hereafter referred to as cardiovascular hospitalization) during a median follow-up of 3 years. RESULTS: Symptoms of depression (Beck Depression Inventory score) were associated with risk of death or cardiovascular hospitalization (P<.001) after controlling for established risk factors including HF disease severity, ejection fraction, HF etiology, age, and medications. Clinically significant symptoms of depression (Beck Depression Inventory score >/=10) were associated with a hazard ratio of 1.56 (95% confidence interval, 1.07-2.29) for the combined end point of death or cardiovascular hospitalization. Contrary to our expectation, antidepressant medication use was associated with increased likelihood of death or cardiovascular hospitalization (hazard ratio, 1.75; 95% confidence interval,1.14-2.68, P =.01) after controlling for severity of depressive symptoms and for established risk factors. CONCLUSIONS: Symptoms of depression were associated with an adverse prognosis in patients with HF after controlling for HF severity. The unexpected association of antidepressant medications with worse clinical outcome suggests that patients with HF requiring an antidepressant medication may need to be monitored more closely.