Importance: Atherosclerotic cardiovascular disease (ASCVD) continues to be highly prevalent in the US. The 2013 American College of Cardiology and American Heart Association (ACC/AHA) treatment guidelines reevaluated evidence-based practices for reduction of ASCVD in men and women from high-quality randomized trials and meta-analyses recommending the use of statin therapy, aspirin prescription, and lifestyle counseling for adults with ASCVD. Population trends in secondary prevention strategies for patients with ASCVD among primary care settings is currently lacking, limiting ability to evaluate impact of guideline implementation. Objective: To examine temporal and sociodemographic trends in secondary prevention strategies in patients with ASCVD between 2006 and 2016 in a nationally representative, ambulatory care database. Design, Setting, and Participants: This cross-sectional study analyzed data from the National Ambulatory Medical Care Survey (NAMCS), which is an annual survey conducted to represent the national US population and contains information on ambulatory office-based patient visits, including medical conditions, services provided, and demographic characteristics. Participants were adults aged 21 years and older with prevalent ASCVD identified via International Classification of Disease codes between 2006 and 2016. Data were extracted and analyzed in March 2021. Main Outcomes and Measures: Data were separated by calendar year pre-2013 (2006 to 2013) and post-2013 (2014 to 2016). Outcomes included statin therapy, aspirin prescription, and lifestyle counseling (eg, nutrition, exercise, weight reduction) service provided at clinic visits. Results: There were 11033 visits for adults with ASCVD, representing a weighted total of 275.3 million visits nationwide; 40.7% (112.1 million [weighted]) were women, 9.2% (25.4 million [weighted]) were Hispanic, 9.9% (19.0 million [weighted]) were non-Hispanic Black, 90.1% (172.7 million [weighted]) were non-Hispanic White, and 40.6% (112.1 million [weighted]) were from cardiology clinics. Of 11033 patient visits, 5507 patients (49.9%) were prescribed statin therapy, 5165 patients (46.8%) were using aspirin, 2233 patients (20.2%) received lifestyle counseling. Statin therapy increased from 9.3 million individuals (45.3%) in 2006 to 14.9 million individuals (46.5%) in 2016, and aspirin prescriptions increased from 8.5 million individuals (41.3%) in 2006 to 15.2 individuals (47.5%) in 2016. Women were less likely than men to receive medications for secondary prevention: among women, 48.8 million (43.3%) received statins (vs 85.9 million men [52.7%]), 44.7 million (39.8%) received aspirin (vs 79.1 million men [48.5%]), and 25.7 million (22.9%) received lifestyle counseling services (vs 37.5 million men [23.0%]). Conclusions and Relevance: These findings suggest only modest increases in statin and aspirin prescription since 2006; however, lifestyle counseling use decreased in recent years. Women and Black patients continued to be less likely to receive secondary prevention ASCVD treatment. Adherence to guideline-directed secondary prevention recommendations remained low (less than 50%) in patients with ASCVD, especially with regards to lifestyle counseling, suggesting the need for more implementation research..
Objective Experiences of child maltreatment are associated with cardiovascular risk and disease in adulthood; however, the mechanisms underlying these associations are poorly understood. Methods We examined associations between retrospectively self-reported exposure to child maltreatment (Early Trauma Inventory Self-Report Short Form) and inflammatory responses to mental stress among adults (mean age = 50 years) who recently had a myocardial infarction (n = 227). Inflammation was assessed as blood interleukin-6 (IL-6), matrix metalloproteinase-9 (MMP-9), and monocyte chemoattractant protein-1 concentrations, measured before and after a standardized public speaking stress task. We used mixed linear regression models adjusting for cardiovascular disease severity, medication usage, and psychosocial, demographic, and life-style factors. Results In women, increases in IL-6 levels and MMP-9 levels with stress were smaller in those exposed to sexual abuse, relative to those unexposed (IL-6 geometric mean increases = 1.6 [95% confidence interval {CI} = 1.4-1.9] pg/ml versus 2.1 [95% CI = 1.8-2.4] pg/ml; MMP-9 geometric mean increases = 1.0 [95% CI = 0.9-1.2] ng/ml versus 1.2 [95% CI = 1.1-1.4] ng/ml). No differences were noted for emotional or physical abuse. By contrast in men, individuals exposed to sexual abuse had larger IL-6 responses than those not exposed to abuse. Conclusions These findings suggest sex differences in stress response among survivors of a myocardial infarction exposed to abuse early in life. They also underscore the importance of examining sex as an effect modifier of relationships between exposure to early life adversity and inflammatory responses to mental stressors in midlife.
OBJECTIVE: Coronary heart disease is a leading cause of death and disability. Although psychological stress has been identified as an important potential contributor, mechanisms by which stress increases risk of heart disease and mortality are not fully understood. The purpose of this study was to assess mechanisms by which stress acts through the brain and heart to confer increased CHD risk. METHODS: Coronary Heart Disease patients (N=10) underwent cardiac imaging with [Tc-99m] sestamibi single photon emission tomography at rest and during a public speaking mental stress task. Patients returned for a second day and underwent positron emission tomography imaging of the brain, heart, bone marrow, aorta (indicating inflammation) and subcutaneous adipose tissue, after injection of [18F]2-fluoro-2-deoxyglucose for assessment of glucose uptake followed mental stress. Patients with (N=4) and without (N=6) mental stress-induced myocardial ischemia were compared for glucose uptake in brain, heart, adipose tissue and aorta with mental stress. RESULTS: Patients with mental stress-induced ischemia showed a pattern of increased uptake in the heart, medial prefrontal cortex, and adipose tissue with stress. In the heart disease group as a whole, activity increase with stress in the medial prefrontal brain and amygdala correlated with stress-induced increases in spleen (r=0.69, p=0.038; and r=0.69, p=0.04 respectfully). Stress-induced frontal lobe increased uptake correlated with stress-induced aorta uptake (r=0.71, p=0.016). Activity in insula and medial prefrontal cortex was correlated with post-stress activity in bone marrow and adipose tissue. Activity in other brain areas not implicated in stress did not show similar correlations. Increases in medial prefrontal activity with stress correlated with increased cardiac glucose uptake with stress, suggestive of myocardial ischemia (r=0.85, p=0.004). CONCLUSIONS: These findings suggest a link between brain response to stress in key areas mediating emotion and peripheral organs involved in inflammation and hematopoietic activity, as well as myocardial ischemia, in Coronary Heart Disease patients.
Background: Adverse mental health conditions including depression, posttraumatic stress disorder (PTSD), and anxiety are prevalent among patients who survive myocardial infarctions (MI) and are associated with adverse outcomes. The mechanisms underlying these associations, however, are not well understood. Inflammatory pathways may mediate the cardiovascular outcomes of patients with mental health disorders. We examined the bidirectional association between PTSD symptoms and inflammatory biomarkers in a young/middle-aged post MI population. We further examined how this association may differ between women and men as well as between Black and non-Black individuals. Methods: Participants included individuals with early onset MI between the ages 25 and 60. Mental health scores for depression, PTSD, perceived stress, and anxiety as well as inflammatory biomarkers, interleukin-6 (IL-6) and high sensitivity C-reactive protein (hsCRP), were collected at baseline and at six-month follow up. We examined the bidirectional changes in mental health symptoms and inflammatory biomarkers between baseline and follow-up. Results: Among 244 patients in the study (mean age: 50.8, 48.4% female, 64.3% Black), the geometric means for IL-6 level and hsCRP at rest were 1.7 pg/mL and 2.76 mg/L, respectively. Mental health scores at baseline did not consistently predict changes in inflammatory biomarkers at follow-up. However, baseline levels of both IL-6 and hsCRP were robustly associated with an increase in re-experiencing PTSD symptoms at 6 months: in adjusted linear mixed models, there was a 1.58-point increase in re-experiencing PTSD symptoms per unit of baseline hsCRP (p = 0.01) and 2.59-point increase per unit of baseline IL-6 (p = 0.02). Once the analysis was stratified by race, the association was only noted in Black individuals. Baseline inflammation was not associated with change in any of the other mental health symptom scores. Conclusion: Markers of inflammation are associated with an increase in post-event PTSD symptoms in younger or middle-aged patients who experienced an MI, especially Black patients. These results suggest a mechanistic link between inflammation and the development of PTSD among individuals with cardiovascular disease.
Background: Emerging data suggest that young women with coronary heart disease (CHD) are disproportionally vulnerable to the adverse cardiovascular effects of psychological stress. We hypothesized that younger, but not older, women with stable CHD are more likely than their male peers to develop mental stress‐induced myocardial ischemia (MSIMI).
Methods and Results: We studied 686 patients (191 women) with stable coronary heart disease (CHD). Patients underwent 99mTc‐sestamibi myocardial perfusion imaging at rest and with both mental (speech task) and conventional (exercise/pharmacological) stress testing. We compared quantitative (by automated software) and visual parameters of inducible ischemia between women and men and assessed age as an effect modifier. Women had a more‐adverse psychosocial profile than men whereas there were few differences in medical history and CHD risk factors. Both quantitative and visual indicators of ischemia with mental stress were disproportionally larger in younger women. For each 10 years of decreasing age, the total reversibility severity score with mental stress was 9.6 incremental points higher (interaction, P<0.001) and the incidence of MSIMI was 82.6% higher (interaction, P=0.004) in women than in men. Incidence of MSIMI in women ≤50 years was almost 4‐fold higher than in men of similar age and older patients. These results persisted when adjusting for sociodemographic and medical risk factors, psychosocial factors, and medications. There were no significant sex differences in inducible ischemia with conventional stress.
Conclusions: Young women with stable CHD are susceptible to MSIMI, which could play a role in the prognosis of this group.
Post-traumatic stress disorder (PTSD) has been associated with cardiovascular disease (CVD), but the mechanisms remain unclear. Autonomic dysfunction, associated with higher CVD risk, may be triggered by acute PTSD symptoms. We hypothesized that a laboratory-based trauma reminder challenge, which induces acute PTSD symptoms, provokes autonomic dysfunction in a cohort of veteran twins. We investigated PTSD-associated real-time physiologic changes with a simulation of traumatic experiences in which the twins listened to audio recordings of a one-minute neutral script followed by a one-minute trauma script. We examined two heart rate variability metrics: deceleration capacity (DC) and logarithmic low frequency (log-LF) power from beat-to-beat intervals extracted from ambulatory electrocardiograms. We assessed longitudinal PTSD status with a structured clinical interview and the severity with the PTSD Symptoms Scale. We used linear mixed-effects models to examine twin dyads and account for cardiovascular and behavioral risk factors. We examined 238 male Veteran twins (age 68 ± 3 years old, 4% black). PTSD status and acute PTSD symptom severity were not associated with DC or log-LF measured during the neutral session, but were significantly associated with lower DC and log-LF during the traumatic script listening session. Long-standing PTSD was associated with a 0.38 (95% confidence interval, −0.83,-0.08) and 0.79 (−1.30,-0.29) standardized unit lower DC and log-LF, respectively, compared to no history of PTSD. Traumatic reminders in patients with PTSD lead to real-time autonomic dysregulation and suggest a potential causal mechanism for increased CVD risk, based on the well-known relationships between autonomic dysfunction and CVD mortality.
Background: To investigate the cross-sectional and longitudinal relationships between vascular function and circulating progenitor cell (CPC) counts with respect to aging and exposure to risk factors. Methods: In 797 adult participants, CPCs were enumerated by flow cytometry as CD45med mononuclear cells expressing CD34 epitope and its subsets co-expressing CD133, and chemokine C-X-C motif receptor 4 (CXCR4+). Arterial stiffness was evaluated by tonometry-derived pulse wave velocity (PWV) and microvascular function was assessed as digital reactive hyperemia index (RHI). Results: In cross-sectional analyses, for every doubling in CD34+ cell counts, PWV was 15% higher and RHI was 9% lower, after adjusting for baseline characteristics and risk factors (p for all < 0.01). There were significant CPC-by-age-by-risk factor interactions (p <0.05) for both vascular measures. Among younger subjects (< 48 years), CPC counts were higher in those with risk factors and vascular function was better in those with higher compared to those with lower CPC counts (p for all < 0.0l). In contrast, in older participants, CPCs were not higher in those with risk factors, and vascular function was worse compared to the younger age group. A lower CPC count at baseline was an independent predictor of worsening vascular function during 2-year follow-up. Conclusion: A higher CPC count in the presence of risk factors is associated with better vascular function among younger individuals. There is no increase in CPC count with risk factors in older individuals who have worse vascular function. Moreover, a higher CPC count is associated with less vascular dysfunction with aging.
Background: Acute psychological stress can provoke mental stress-induced myocardial ischemia (MSIMI) in coronary artery disease (CAD). Stromal cell-derived factor 1 (SDF1) is released in response to hypoxia, and higher levels of SDF1 are associated with adverse outcomes. We examined whether an increase in SDF1 level in response to mental stress predicts adverse outcomes in CAD patients. Methods: A total of 554 patients with stable CAD (mean age 63 years; 76% male; 26% Black) underwent standardized mental stress testing. Plasma SDF1 levels were measured at rest and 90 minutes after mental stress, and MSIMI was evaluated by 99mTc-sestamibi perfusion imaging. Participants were followed for 5 years for the primary endpoint of composite of death and myocardial infarction (MI) and the secondary endpoint of composite of death, MI, and heart failure hospitalization. Cox hazard models were used to assess the association between SDF1 change and incident adverse events. Results: Mean (standard deviation) SDF1 change with mental stress was +56.0 (230) pg/mL. During follow-up, a rise of 1 standard deviation in SDF1 with mental stress was associated with a 32% higher risk for the primary endpoint of death and MI (95% confidence interval, 6%-64%), independent of the resting SDF1 level, demographic and clinical risk factors, and presence of ischemia. A rise of 1 standard deviation in SDF1 was associated with a 33% (95% confidence interval, 11%-59%) increase in the risk for the secondary endpoint, independent of the resting SDF1 level, demographic, and clinical risk factors and presence of ischemia. Conclusions: An increase in SDF1 level in response to mental stress is associated with a higher risk of adverse events in stable CAD, independent of MSIMI.
Transcutaneous vagus nerve stimulation (t-VNS) is a promising technology for modulating brain function and possibly treating disorders of the central nervous system. While handheld devices are available for t-VNS, stimulation efficacy can only be quantified using expensive imaging or blood biomarker analyses. Additionally, the parameters and 'dosage' recommendations for t-VNS are typically fixed, as there are limited biomarkers that can assess downstream effects of the stimulation outside of clinical settings. In this proof-of-concept study, we evaluated non-invasive peripheral cardiovascular measurements as physiological biomarkers of t-VNS efficacy. Specifically, we hypothesized two physiological biomarkers: (1) the pre-ejection period (PEP) of the heart - a parameter closely linked to sympathetic tone - and (2) the amplitude of peripheral photoplethysmogram (PPG) waveforms - representing changes in vasomotor tone and thus parasympathetic / sympathetic activation. A total of six healthy human subjects participated in the multi-day study, half each undergoing active or sham t-VNS stimulus. The three subjects receiving t-VNS had no decrease in PEP and an increase in PPG amplitude following t-VNS, while the subjects receiving sham stimulus had a decrease in PEP and no change in PPG amplitude. When combined with mental stress (a traumatic script being read back to the subjects), the group with t-VNS had no decrease in PEP and only a slight decrease in PPG amplitude following stimulus, while the group receiving sham stimulus had a decrease in PEP and also a slight decrease in PPG amplitude. These studies suggest that PEP and PPG amplitude measures may provide non-invasive physiological biomarkers of t-VNS efficacy, including in the presence of mental stress.
Coronary heart disease and psychological stress factors such as depression are prevalent and associated with high morbidity/mortality; they are also challenging to manage, especially when treated in isolation of each other. Recent advances support an integrated approach to their management that is built on a foundation of an extensive, multi-component network of neurological structures. In this review, we describe this extensive cardioneural network that encompasses the heart, brain, spinal cord, and ganglia throughout the body, and then discuss ambulatory and laboratory-based non-invasive measures of this network that both measure psychological stress and heart disease severity. Lastly, we discuss their potential transformative clinical and public health applications, and also possible cardioneural interventions such as exercise and biofeedback.