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.

Cognitive behavior therapy for insomnia for untreated hypertension with comorbid insomnia disorder: The SLEEPRIGHT clinical trial.

Insomnia and poor sleep are associated with an increased risk of developing cardiovascular disease (CVD) and its precursors, including hypertension. In 2022, the American Heart Association (AHA) added inadequate sleep to its list of health behaviors that increase the risk for CVD. It remains unknown, however, whether the successful treatment of insomnia and inadequate sleep can reduce heightened CVD risk. SLEEPRIGHT is a single-site, prospective clinical trial designed to evaluate whether the successful treatment of insomnia results in improved markers of CVD risk in patients with untreated hypertension and comorbid insomnia disorder. Participants (N = 150) will undergo baseline assessments, followed by a 6-week run-in period after which they will receive cognitive behavior therapy for insomnia (CBT-I), comprised of 6 hourly sessions with an experienced CBT-I therapist over a 6-week period. In addition to measures of insomnia severity, as well as both subjective and objective measures of sleep, the primary outcome measures are nighttime blood pressure (BP) and BP dipping assessed by 24-h ambulatory BP monitoring (ABPM). Secondary outcomes include several CVD risk biomarkers, including clinic BP, lipid profile, vascular endothelial function, arterial stiffness, and sympathetic nervous system (SNS) activity. Data analysis will evaluate the association between improvements in insomnia and sleep with primary and secondary CVD risk biomarker outcomes. The SLEEPRIGHT trial (ClinicalTrials.Gov NCT04009447) will utilize CBT-I, the current gold standard treatment for insomnia disorder, to evaluate whether reducing insomnia severity and improving sleep are accompanied by improved biomarkers of CVD risk in patients with untreated hypertension.

Effects of Lifestyle Modification on Psychosocial Function in Patients With Resistant Hypertension: SECONDARY OUTCOMES FROM THE TRIUMPH RANDOMIZED CLINICAL TRIAL.

PURPOSE: In a secondary analysis of the TRIUMPH clinical trial, psychological outcomes in patients with resistant hypertension (RH) receiving a diet and exercise intervention delivered in a cardiac rehabilitation setting were compared with those receiving a similar prescription of diet and exercise provided in a single counseling session by a health educator. METHODS: One hundred forty patients with RH were randomly assigned to a 4-mo program of dietary counseling, behavioral weight management, and exercise (C-LIFE) or a single counseling session providing standardized education and physician advice (SEPA). Participants completed a battery of questionnaires to assess psychological functioning before and after the intervention. A global measure of psychological functioning was derived from the General Health Questionnaire (GHQ), Perceived Stress Scale (PSS), Medical Outcomes Study 36-item Short Form Health Survey, Spielberger State-Trait Anxiety Inventory, Hospital Anxiety and Depression Scale (HADS), Beck Depression Inventory-II, and Patient-Reported Outcomes Measurement Information System (PROMIS) Anger scale. RESULTS: Participants in the C-LIFE intervention achieved greater improvements in psychological functioning compared with SEPA (C-LIFE: 58.9 [56.1, 61.8] vs SEPA: 66.5 [62.1, 70.9]; P = .024). Greater improvements were especially evident for the GHQ, PSS, and HADS. Examination of mediation revealed that greater weight loss ( B =-0.17, P = .004) and improved oxygen uptake ( B =-0.12, P = .044) were associated with improved psychological functioning. CONCLUSION: Compared with standard education and physician advice, a structured program of diet and exercise not only reduced blood pressure but also improved psychological functioning in patients with RH.

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.

Lifestyle Medicine as a Treatment for Resistant Hypertension.

PURPOSE OF REVIEW: Approximately 10% of the adults with hypertension fail to achieve the recommended blood pressure treatment targets on 3 antihypertensive medications or require ≥ 4 medications to achieve goal. These patients with 'resistant hypertension' have an increased risk of target organ damage, adverse clinical events, and all-cause mortality. Although lifestyle modification is widely recommended as a first-line approach for the management of high blood pressure, the effects of lifestyle modifications in patients with resistant hypertension has not been widely studied. This review aims to provide an overview of the emerging evidence on the benefits of lifestyle modifications in patients with resistant hypertension, reviews potential mechanisms by which lifestyles may reduce blood pressure, and discusses the clinical implications of the recent findings in this field. RECENT FINDINGS: Evidence from single-component randomized clinical trials demonstrated that aerobic exercise, weight loss and dietary modification can reduce clinic and ambulatory blood pressure in patients with resistant hypertension. Moreover, evidence from multi-component trials involving exercise and dietary modification and weight management can facilitate lifestyle change, reduce clinic and ambulatory blood pressure, and improve biomarkers of cardiovascular risk. This new evidence supports the efficacy of lifestyle modifications added to optimized medical therapy in reducing blood pressure and improving cardiovascular risk biomarkers in patients with resistant hypertension. These findings need to be confirmed in larger studies, and the persistence of benefit over extended follow-up needs further study.

Effect of cognitive processing therapy on markers of cardiovascular risk in posttraumatic stress disorder patients: A randomized clinical trial.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is associated with elevated risk of coronary heart disease (CHD); however, the effects of PTSD treatment on CHD biomarkers is unknown. This study examined whether cognitive processing therapy (CPT) improves 24-hourheart rate variability (HRV), a predictor of CHD mortality. METHODS: Individuals between the ages of 40 and 65 years with PTSD (n = 112) were randomized to receive 12 sessions of CPT or a Waiting List (WL) intervention comprised of 6 weekly telephone checks of emotional status. The primary outcome variable was 24-hour HRV estimated from the standard deviation of all normal R-R intervals (SDNN); secondary outcomes were the root mean square of successive differences between heart beats (RMSSD), low-frequency HRV (LF-HRV) and high-frequency HRV (HF-HRV). Secondary outcomes also included 24-hour urinary catecholamine excretion, plasma C-reactive protein (CRP), and flow-mediated dilation (FMD) of the brachial artery. For outcomes, linear mixed longitudinal models were used to estimate mean differences (Mdiff). RESULTS: Participants randomized to the CPT group did not show improved SDNN (Mdiff = 9.8; 95%CI, -2.7 to 22.3; p = 0.12), the primary outcome variable, but showed improved RMSSD (Mdiff = 3.8; 95% CI, 0.5 to 7.1; p = 0.02), LF- HRV (Mdiff =0.3; 95% CI, 0.1 to 0.5; p = 0.01), and HF-HRV (Mdiff = 0.3; 95% CI, 0.0 to 0.6; p = 0.03) compared to WL. There were no differences between groups in catecholamine excretion, FMD, or inflammatory markers. CONCLUSION: Treating PTSD may not only improve quality of life but may also help ameliorate heightened CHD risk characteristics of PTSD.

Sleep Quality, Metabolic Function, Physical Activity, and Neurocognition Among Individuals with Resistant Hypertension.

BACKGROUND: Resistant hypertension (RH) is a major risk factor for stroke, cognitive decline, and dementia. Sleep quality is increasingly suggested to play an important role linking RH to cognitive outcomes, although the mechanisms linking sleep quality to poor cognitive function have yet to be fully delineated. OBJECTIVE: To delineate biobehavioral mechanisms linking sleep quality, metabolic function, and cognitive function among 140 overweight/obese adults with RH in the TRIUMPH clinical trial. METHODS: Sleep quality was indexed using actigraphy measures of sleep quality and sleep fragmentation, as well as self-reported sleep quality from the Pittsburgh Sleep Quality Index (PSQI). Cognitive function was assessed using a 45-minute battery assessing executive function, processing speed, and memory. Participants were randomized to a cardiac rehabilitation-based lifestyle program (C-LIFE) or a standardized education and physician advice condition (SEPA) for 4 months. RESULTS: Better sleep quality at baseline was associated with better executive function (B = 0.18 p = 0.027), as well as greater fitness (B = 0.27, p = 0.007) and lower HBA1c (B = -0.25, p = 0.010). Cross-sectional analyses revealed that the sleep quality executive function association was mediated by HBA1c (B = 0.71 [0.05, 2.05]). C-LIFE improved sleep quality (-1.1 [-1.5, -0.6] versus+-0.1 [-0.8, 0.7]) and actigraphy steps (+922 [529, 1316] versus+56 [-548, 661]), with actigraphy mediating improvements in executive function (B = 0.40 [0.02, 1.07]). CONCLUSION: Better metabolic function and improved physical activity patterns levels play important roles linking sleep quality and executive function in RH.

Nightmares: an independent risk factor for cardiovascular disease?

STUDY OBJECTIVES: Prior work has established associations between post-traumatic stress disorder (PTSD), disrupted sleep, and cardiovascular disease (CVD), but few studies have examined health correlates of nightmares beyond risks conferred by PTSD. This study examined associations between nightmares and CVD in military veterans. METHODS: Participants were veterans (N = 3468; 77% male) serving since September 11, 2001, aged 38 years (SD = 10.4); approximately 30% were diagnosed with PTSD. Nightmare frequency and severity were assessed using the Davidson Trauma Scale (DTS). Self-reported medical issues were assessed using the National Vietnam Veterans Readjustment Study Self-report Medical Questionnaire. Mental health disorders were established using the Structured Clinical Interview for DSM-IV. The sample was stratified by the presence or absence of PTSD. Within-group associations between nightmare frequency and severity and self-reported CVD conditions, adjusting for age, sex, race, current smoking, depression, and sleep duration. RESULTS: Frequent and severe nightmares during the past week were endorsed by 32% and 35% of participants, respectively. Those endorsing nightmares that were frequent, severe, and the combination thereof were more likely to also evidence high blood pressure (ORs 1.42, OR 1.56, and OR 1.47, respectively) and heart problems (OR 1.43, OR 1.48, and OR 1.59, respectively) after adjusting for PTSD diagnosis and other covariates. CONCLUSIONS: Nightmare frequency and severity among veterans are associated with cardiovascular conditions, even after controlling for PTSD diagnosis. Study findings suggest that nightmares may be an independent risk factor for CVD. Additional research is needed to validate these findings using confirmed diagnoses and explore potential mechanisms.

Inflammation moderates the effects of lifestyle modification on neurocognition among individuals with resistant hypertension.

Individuals with resistant hypertension (RH) have the greatest risk of cerebrovascular disease and cognitive impairment among individuals with hypertension. Elevated levels of pro-inflammatory cytokines may represent a critical yet unexamined factor influencing the impact of healthy lifestyle changes on cognitive function. We explored the influence of inflammation on changes in cognition following lifestyle modification among individuals with RH participating in the TRIUMPH clinical trial. One hundred forty participants with RH completed a battery of neurocognitive tests along with the inflammatory marker C-reactive protein (hsCRP) and were subsequently randomized to an intensive 4-month lifestyle modification intervention or to education and physician advice control. Results indicated that the effects of lifestyle modification on Executive Function and Learning were moderated by pre-intervention hsCRP levels (P = .049), with treatment efficacy increasing across levels of baseline inflammation levels (low: d = 0.12; mild: d = 0.43; moderate: d = 0.81). We conclude that inflammatory profiles may help identify individuals more likely to improve executive functioning resulting from lifestyle modification.

Exercise and Escitalopram in the Treatment of Anxiety in Patients with Coronary Heart Disease: One Year Follow-Up of the UNWIND Randomized Clinical Trial.

Anxiety is common among patients with coronary heart disease (CHD) and is associated with a worse prognosis. UNWIND was a 12-week randomized clinical trial comparing exercise and escitalopram to placebo on measures of anxiety, depression, and CHD biomarkers. Primary results of the trial reported that treatment with escitalopram, but not exercise, was associated with significant reductions in anxiety and depression. At 1-year follow-up, participants completed the Hospital Anxiety-Depression Scale-Anxiety (HADS-A) along with the HADS-Depression (HADS-D), the Beck Depression Inventory-II (BDI-II), and the Godin Leisure Time Exercise survey to assess physical activity. Results showed that those patients randomized to escitalopram had lower scores on the HADS-A compared to those randomized to exercise (P = 0.006) and had less depression compared to exercise on the HADS-D (P = 0.004) and BDI-II (P = 0.004). Participants randomized to exercise reported higher levels of physical activity at 1-year compared to those randomized to Placebo (P = 0.039). However, despite reporting being more physically active, those randomized to exercise did not have less anxiety or depression compared to placebo controls. Escitalopram appears to be a safe and effective treatment for anxiety; exercise has many health benefits, but does not appear to be effective in treating anxiety.

Lifestyle modification and cognitive function among individuals with resistant hypertension: cognitive outcomes from the TRIUMPH trial.

BACKGROUND: Resistant hypertension is associated with increased risk of cognitive decline, stroke, and dementia. Lifestyle modification has been suggested to improve cognitive function through its salutary effects on vascular function. METHODS: Participants included 140 patients with resistant hypertension participating in the TRIUMPH trial. Participants were randomized to a cardiac rehabilitation-based lifestyle program (C-LIFE) or a standardized education and physician advice condition (SEPA). Participants completed a 45-min cognitive test battery consisting of tests of Executive Functioning and Learning, Memory, and Processing Speed. Biomarkers of vascular [flow mediated dilation of the brachial artery (FMD)], microvascular, and cerebrovascular function were also collected, in addition to weight, fitness, and ambulatory blood pressure. RESULTS: Participants averaged 63 years of age, 48% women, 59% black, and obese [mean BMI = 36 kg/m 2 (SD = 4)]. Cognitive performance improved across the entire cohort during the 4-month trial [ t -scores pretreatment = 48.9 (48, 50) vs. posttreatment = 50.0 (49, 51), P  < 0.001]. Postintervention Executive Function/Learning composite performance was higher for participants in C-LIFE compared to SEPA ( d  = 0.37, P  = 0.039). C-LIFE intervention effects on Memory and Processing Speed were moderated by sex and baseline stroke risk, respectively ( P  = 0.026 and P  = 0.043 for interactions), such that males and participants with greater stroke risk showed the greatest cognitive changes. FMD [C-LIFE: +0.3% (-0.3, 1.0) vs. SEPA: -1.4% (-2.5, -0.3), P  = 0.022], and microvascular function [C-LIFE: 97 (65, 130) vs. SEPA: 025 (-75, 23), P  < 0.001] were improved in C-LIFE compared with SEPA, whereas cerebrovascular reactivity was not [C-LIFE: -0.2 (-0.4, 0) vs. SEPA: 0.1 (-0.2, 0.4), P  = 0.197). Mediation analyses suggested that increased executive function/learning was associated with reduced ambulatory SBP levels secondary to weight loss [indirect effect: B  = 0.25 (0.03, 0.71)]. CONCLUSION: Lifestyle modification individuals with resistant hypertension improves cognition, which appeared to be associated with reduced ambulatory SBP changes through weight loss. Cognitive improvements were accompanied by parallel improvements in endothelial and microvascular function.

Longer term benefits of exercise and escitalopram in the treatment of anxiety in patients with coronary heart disease: Six month follow-up of the UNWIND randomized clinical trial.

BACKGROUND: Anxiety is a common comorbidity in patients with coronary heart disease (CHD) and is associated with worse prognosis. However, effective treatment for anxiety in CHD patients is uncertain. The UNWIND randomized clinical trial showed that 12-week treatment of escitalopram was better than exercise training or placebo in reducing anxiety in anxious CHD patients. The longer-term benefits of treatment for anxiety are not known. METHODS: Patients were randomized to 12 weeks of Escitalopram (up to 20 mg), Exercise (3 times/wk), or placebo pill. At the conclusion of treatment, participants were followed for 6-months to determine the persistence of benefit on the primary anxiety endpoint assessed by the Hospital Anxiety and Depression Scale-Anxiety scale (HADS-A) and to assess the effects of treatment on major adverse cardiac events over a follow-up period of up to 6 years. RESULTS: Of the 128 participants initially randomized, 120 (94%) were available for follow-up. Participants randomized to the Escitalopram condition exhibited lower HADS-A scores (3.9 [3.1, 4.7]) compared to those randomized to Exercise (5.5 [4.6, 6.3]) (P = .007) and Placebo (5.3 [4.1, 6.5]) (P = .053). Over a median follow-up of 3.2 years (IQR: 2.3, 4.5), there were 29 adverse events but no significant between-group differences. CONCLUSION: In the UNWIND trial, 12 weeks of escitalopram treatment was effective in reducing anxiety. These beneficial effects were sustained for 6 months posttreatment. Although moderate or vigorous physical activity has a number of health benefits, exercise was not an effective treatment for anxiety in patients with CHD.

Cerebrovascular Function, Vascular Risk, and Lifestyle Patterns in Resistant Hypertension.

BACKGROUND: Impaired cerebrovascular reactivity (CVR) and blunted cerebral hemodynamic recruitment are thought to be important mechanisms linking hypertension to cerebrovascular and cognitive outcomes. Few studies have examined cardiovascular or dietary correlates of CVR among hypertensives. OBJECTIVE: To delineate associations between cardiometabolic risk, diet, and cerebrovascular functioning among individuals with resistant hypertension from the TRIUMPH trial (n = 140). METHODS: CVR was assessed by examining changes in tissue oxygenation (tissue oxygenation index [TOI] and oxygenated hemoglobin [HBO2]) using functional near-infrared spectroscopy (fNIRS) during a breath holding test, a standardized CVR assessment to elicit a hypercapnic response. Participants also underwent fNIRS during three cognitive challenge tasks. Vascular function was assessed by measurement of brachial artery flow-mediated dilation and hyperemic flow response. Cardiometabolic fitness was assessed from peak VO2 on an exercise treadmill test and body mass index. Dietary patterns were quantified using the DASH eating score. Cognitive function was assessed using a 45-minute test battery assessing Executive Function, Processing Speed, and Memory. RESULTS: Greater levels fitness (B = 0.30, p = 0.011), DASH compliance (B = 0.19, p = 0.045), and lower obesity (B = -0.30, p = 0.004), associated with greater changes in TOI, whereas greater flow-mediated dilation (B = 0.19, p = 0.031) and lower stroke risk (B = -0.19, p = 0.049) associated with greater HBO2. Similar associations were found for cerebral hemodynamic recruitment, and associations between CVR and cognition were moderated by duration of hypertension. CONCLUSION: Impaired CVR elevated cardiometabolic risk, obesity, vascular function, and fitness among hypertensives.

Effects of Lifestyle Modification on Patients With Resistant Hypertension: Results of the TRIUMPH Randomized Clinical Trial.

BACKGROUND: Although lifestyle modifications generally are effective in lowering blood pressure (BP) among patients with unmedicated hypertension and in those treated with 1 or 2 antihypertensive agents, the value of exercise and diet for lowering BP in patients with resistant hypertension is unknown. METHODS: One hundred forty patients with resistant hypertension (mean age, 63 years; 48% female; 59% Black; 31% with diabetes; 21% with chronic kidney disease) were randomly assigned to a 4-month program of lifestyle modification (C-LIFE [Center-Based Lifestyle Intervention]) including dietary counseling, behavioral weight management, and exercise, or a single counseling session providing SEPA (Standardized Education and Physician Advice). The primary end point was clinic systolic BP; secondary end points included 24-hour ambulatory BP and select cardiovascular disease biomarkers including baroreflex sensitivity to quantify the influence of the baroreflex on heart rate, high-frequency heart rate variability to assess vagally mediated modulation of heart rate, flow-mediated dilation to evaluate endothelial function, pulse wave velocity to assess arterial stiffness, and left ventricular mass to characterize left ventricular structure. RESULTS: Between-group comparisons revealed that the reduction in clinic systolic BP was greater in C-LIFE (-12.5 [95% CI, -14.9 to -10.2] mm Hg) compared with SEPA(-7.1 [-95% CI, 10.4 to -3.7] mm Hg) (P=0.005); 24-hour ambulatory systolic BP also was reduced in C-LIFE (-7.0 [95% CI, -8.5 to -4.0] mm Hg), with no change in SEPA (-0.3 [95% CI, -4.0 to 3.4] mm Hg) (P=0.001). Compared with SEPA, C-LIFE resulted in greater improvements in resting baroreflex sensitivity (2.3 ms/mm Hg [95% CI, 1.3 to 3.3] versus -1.1 ms/mm Hg [95% CI, -2.5 to 0.3]; P<0.001), high-frequency heart rate variability (0.4 ln ms2 [95% CI, 0.2 to 0.6] versus -0.2 ln ms2 [95% CI, -0.5 to 0.1]; P<0.001), and flow-mediated dilation (0.3% [95% CI, -0.3 to 1.0] versus -1.4% [95% CI, -2.5 to -0.3]; P=0.022). There were no between-group differences in pulse wave velocity (P=0.958) or left ventricular mass (P=0.596). CONCLUSIONS: Diet and exercise can lower BP in patients with resistant hypertension. A 4-month structured program of diet and exercise as adjunctive therapy delivered in a cardiac rehabilitation setting results in significant reductions in clinic and ambulatory BP and improvement in selected cardiovascular disease biomarkers. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02342808.

Effect of Exercise, Escitalopram, or Placebo on Anxiety in Patients With Coronary Heart Disease: The Understanding the Benefits of Exercise and Escitalopram in Anxious Patients With Coronary Heart Disease (UNWIND) Randomized Clinical Trial.

Importance: Anxiety is common among patients with coronary heart disease (CHD) and is associated with worse health outcomes; however, effective treatment for anxiety in patients with CHD is uncertain. Objective: To determine whether exercise and escitalopram are better than placebo in reducing symptoms of anxiety as measured by the Hospital Anxiety and Depression-Anxiety Subscale (HADS-A) and in improving CHD risk biomarkers. Design, Setting, and Participants: This randomized clinical trial was conducted between January 2016 and May 2020 in a tertiary care teaching hospital in the US and included 128 outpatients with stable CHD and a diagnosed anxiety disorder or a HADS-A score of 8 or higher who were older than 40 years, sedentary, and not currently receiving mental health treatment. Interventions: Twelve weeks of aerobic exercise 3 times per week at an intensity of 70% to 85% heart rate reserve, escitalopram (up to 20 mg per day), or placebo pill equivalent. Main Outcomes and Measures: The primary outcome was HADS-A score. CHD biomarkers included heart rate variability, baroreflex sensitivity, and flow-mediated dilation, along with 24-hour urinary catecholamines. Results: The study included 128 participants. The mean (SD) age was 64.6 (9.6) years, and 37 participants (29%) were women. Participants randomized to the exercise group and escitalopram group reported greater reductions in HADS-A (exercise, -4.0; 95% CI, -4.7 to -3.2; escitalopram, -5.7; 95% CI, -6.4 to -5.0) compared with those randomized to placebo (-3.5; 95% CI, -4.5 to -2.4; P = .03); participants randomized to escitalopram reported less anxiety compared with those randomized to exercise (-1.67; 95% CI, -2.68 to -0.66; P = .002). Significant postintervention group differences in 24-hour urinary catecholamines were found (exercise z score = 0.05; 95% CI, -0.2 to 0.3; escitalopram z score = -0.24; 95% CI, -0.4 to 0; placebo z score = 0.36; 95% CI, 0 to 0.7), with greater reductions in the exercise group and escitalopram group compared with the placebo group (F1,127 = 4.93; P = .01) and greater reductions in the escitalopram group compared with the exercise group (F1,127 = 4.37; P = .04). All groups achieved comparable but small changes in CHD biomarkers, with no differences between treatment groups. Conclusions and Relevance: Treatment of anxiety with escitalopram was safe and effective for reducing anxiety in patients with CHD. However, the beneficial effects of exercise on anxiety symptoms were less consistent. Exercise and escitalopram did not improve CHD biomarkers of risk, which should prompt further investigation of these interventions on clinical outcomes in patients with anxiety and CHD. Trial Registration: ClinicalTrials.gov Identifier: NCT02516332.

Effects of Acute Exercise on Anxiety Ratings in Patients With Coronary Heart Disease and Elevated Anxiety.

PURPOSE: To explore individual differences in state anxiety following a single, acute bout of aerobic exercise among anxious patients with diagnosed coronary heart disease (CHD). METHODS: One hundred eighteen CHD patients with elevated symptoms of anxiety enrolled in the UNderstanding the Benefits of Exercise and Escitalopram in Anxious Patients WIth coroNary Heart Disease (UNWIND) clinical trial rated their level of anxiety using a 100-mm visual analog scale before and after a symptom-limited exercise treadmill test. A number of exercise (eg, peak oxygen uptake, exercise duration, maximum heart rate, anaerobic threshold) and psychological variables were examined as potential predictors of exercise response. Changes in anxiety and their association with psychological variables were examined using general linear models. RESULTS: Fifty patients (42%) rated a reduction in anxiety relative to their pre-exercise ratings following the exercise treadmill test. While a number of factors were examined, the only factor that distinguished those individuals who reported a reduction in anxiety symptoms compared with those who either remained the same or actually reported an increase in anxiety was a higher pre-exercise visual analog scale anxiety rating. No differences were observed as a function of sex, severity of trait anxiety, the presence of an anxiety disorder, exercise test duration, or age. CONCLUSIONS: Although many variables were examined, only higher baseline anxiety distinguished those who showed a reduction in their visual analog scale ratings from those whose anxiety remained the same or got worse. The extent to which the response to acute exercise predicts the anxiolytic effects of chronic exercise needs further study.

Lifestyle Interventions Reduce the Need for Guideline-Directed Antihypertensive Medication.

BACKGROUND: The 2017 ACC-AHA Hypertension Guideline recommends initiation of antihypertensive drug therapy based on blood pressure (BP) and an assessment of global cardiovascular disease (CVD) risk, but intensive lifestyle modification may lower BP to below recommended thresholds for treatment in some patients. METHODS: We examined the effects of lifestyle modification on calculated CVD risk and on the indications for BP-lowering medications in individuals with untreated hypertension. Participants included 144 adults with BP 130-160/80-99 mm Hg who were randomized to 16 weeks of DASH (Dietary Approaches to Stop Hypertension) diet plus behavioral weight management (DASH + WM), DASH diet alone (DASH), or Usual Care. RESULTS: The mean age of the study cohort was 52.0 years; the average baseline BP was 138 ± 9/86 ± 6 mm Hg. The 10-year CVD risk, as calculated by the Pooled Cohort Equations, was 5.7%. The adjusted 10-year risk fell to 4.4% in the DASH + WM group and to 5.0% in the DASH arm, but was not significantly changed (5.7%) in the Usual Care controls. The percentages of participants with guideline-based indications for antihypertensive drugs fell from 51% to 18% in the DASH + WM group and from 48% to 22% in the DASH group; and did not change significantly (49% to 44%) in the Usual Care group (P = 0.010 for the active intervention groups vs. Usual Care; P = 0.042 for DASH + WM vs. DASH). CONCLUSIONS: These data demonstrate that in men and women with mildly elevated BP, lifestyle interventions can lower the calculated CVD risk and dramatically decrease the number of individuals for whom guideline-directed antihypertensive medication is indicated.

The effect of reducing posttraumatic stress disorder symptoms on cardiovascular risk: Design and methodology of a randomized clinical trial.

Posttraumatic stress disorder (PTSD) has been associated with accelerated progression of coronary heart disease (CHD). However, the underlying pathophysiological pathway has remained elusive and it is unclear whether there is a direct link between PTSD and CHD risk. This paper describes the methods of a randomized controlled trial developed to examine how changes in PTSD symptoms affect CHD disease pathways. One hundred twenty participants with current PTSD and who are free of known CHD will be randomized to receive either an evidence-based treatment for PTSD (Cognitive Processing Therapy; CPT) or a waitlist control (WL). Before and after CPT/WL, participants undergo assessment of CHD risk biomarkers reflecting autonomic nervous system dysregulation, systemic inflammation, and vascular endothelial dysfunction. The primary hypothesis is that individuals who show improvement in PTSD symptoms will show improvement in CHD risk biomarkers, whereas individuals who fail to improve or show worsening PTSD symptoms will have no change or worsening in CHD biomarkers. This study is expected to provide knowledge of the role of both the direct impact of PTSD symptoms on CHD risk pathways and the role of these systems as candidate mechanisms underlying the relationship between PTSD and CHD risk. Further, results will provide guidance on the utility of cognitive therapy as a tool to mitigate the accelerated progression of CHD in PTSD. Clinical Trials Registration: https://clinicaltrials.gov/ct2/show/NCT02736929; Unique identifier: NCT02736929.