Research paperThe relationship between phobic anxiety and 2-year readmission after Acute Coronary Syndrome: What is the role of heart rate variability?
Introduction
Over the past three decades, the association between mental health and cardiovascular disease (CVD) has been extensively examined. Mental health has been established as a major contributor to incident Coronary Heart Disease (CHD, the most common form of CVD) (Rugulies, 2002, Wulsin and Singal, 2003), conferring a level of risk that is comparable to that of risk factors such as smoking and elevated blood lipids (Rozanski et al., 2005). Depression, in particular, has now been recommended to be elevated to risk factor status by the American Heart Association given the poor prognosis in those with existing CHD (Barefoot et al., 2000, Lichtman et al., 2014, Nicholson et al., 2006, Rosengren et al., 2004, Rugulies, 2002, Wulsin and Singal, 2003). Yet, there is still much less evidence about the role of anxiety in recurrent CVD risk.
When investigating generalised anxiety as a construct, meta-analytic evidence has demonstrated that following a cardiac event, anxious patients are at elevated risk of adverse events (odds ratio (OR) fixed, 1.36; 95% CI 1.18–1.56), all-cause mortality (OR fixed, 1.47; 95% CI 1.02–2.13), cardiac mortality (OR fixed, 1.23; 95% CI, 1.03–1.47), and new cardiac events (OR fixed, 1.71; 95% CI, 1.31–2.23) (Roest et al., 2010). When the evidence has been further investigated, specific symptoms of anxiety have been shown to be of particular prognostic relevance. For example, somatic subtypes of anxiety disorders can predict incident CHD (Nabi et al., 2010), while cognitive subtypes can predict in-hospital ischaemic and arrhythmic complications in Acute Coronary Syndrome (ACS) patients (Huffman et al., 2008). This association was found to occur independent of depressive symptoms. Interestingly, a recent population-based study showed that individuals reporting a fear disorder, when compared to individuals with a pure “distress” disorder, were at increased risk of heart disease (OR:1.3; 95%CI:1.0–1.6) (Roest et al., 2017). Phobic anxiety has been shown to be a particularly potent predictor of sudden cardiac death (Albert et al., 2005) and poor prognosis following ACS. However, data that shed light on the biological underpinnings that drive poor outcomes in the short and long term post-ACS period are far from definitive.
Various biological risk markers have been proposed to explain the association between anxiety and cardiac-related complications including dysregulation of the hypothalamic-pituitary-adrenal axis, platelet aggregation, pro-inflammatory responses and autonomic nervous system (ANS) dysfunction (Hsia et al., 2009, Huikuri and Stein, 2012, Kleiger et al., 2005). A marker of ANS activity, heart rate variability (HRV), is known to be an important marker of prognosis among post-myocardial infarction (MI) patients with anxiety disorders. HRV, which indexes sympathovagal balance, is frequently lower in CHD patients with anxiety disorders, compared to those without.
Given that few studies of the ACS populations have longitudinal data on HRV and granular mental health measures, it is unclear to what extent autonomic dysfunction is driving the association between phobic anxiety and key outcomes following a cardiac event, like hospital readmission; a key marker of functioning that is of relevance to clinicians, health providers and policy makers.
Using data from a well-established cohort study (the ADVENT study), the aim of this study was therefore to determine whether phobic anxiety was characterized by autonomic dysfunction (heart rate variability) in the short (1-month) and longer term (12-months), following ACS and whether this modified the effect on all-cause hospital readmission over 2 years.
Section snippets
Sample
Study participants were those enrolled in the ADVENT cohort study, the methods for which have been previously reported (Oldroyd et al., 2013). Briefly, the study's primary aim was to examine the role of somatic and cognitive subtypes of depression and anxiety as predictors of health-related quality of life. Between January 2013 and June 2014, ACS patients admitted to the cardiac unit (Monash Heart), of a large public hospital located in Eastern Melbourne in the state of Victoria, Australia,
Autonomic characteristics of phobic anxiety
Univariate regression analyses revealed significant cross-sectional associations between phobic anxiety score and 7 HRV indices. These included: lower Average RR (Coefficient: −6.6 [95% CIs: −12.3, −0.3]), SDRR (Coefficient: −1.3 [95% CIs: −2.3, −0.3]), RMSSD (Coefficient: −1.5 [95% CIs: −3.0, −0.0), SDSD (Coefficient: −1.5 [95% CIs: −3.0, −0.05]), pRR50 (Coefficient: −0.0 [95% CIs: −0.0, −0.0), LF Power (ms2)(Coefficient: −47.4 [95% CIs: −89.1, −6.2]), and HF Power (ms2) (Coefficient: −207.2
Discussion
Findings from this study indicate, first, that phobic anxiety exhibited in the month after ACS is characterised by reductions in measures of sympathetic and parasympathetic activity (e.g. Low Frequency, High Frequency) and cardiac vagal modulation (e.g. pRR50) in the short but not long term. The presence of comorbid depressive symptoms appeared to explain much of the association. Second, the presence of phobic anxiety at T0 was a predictor of all cause hospital readmission in the ensuing 2
Contributors
AO, CBT, DLH, BO conceptualised the study. JO, AO, CBT, DL, BO oversaw the conduct of the study. ET & JO collected the data. ET, JO, ST cleaned the data. DLH adjudicated the HRV data. AO, AJS & ST analysed and assisted with interpreting the data. AO led the writing and revisions of the manuscripts. All authors contributed to the writing and have approved the final article.
Role of funding source
The ADVENT study was funded by a National Health and Medical Research Council Project Grant (APP1021294). AO is supported by a Future Leader Fellowship (101160) from the Heart Foundation, Australia. ET is supported by a Postgraduate Scholarship from the National Health and Medical Research Council (1113920). Neither the NHMRC nor Heart Foundation had any input into the study design, enactment or findings.
Conflicts of interest
The authors have no conflicts to declare.
Acknowledgments
We thank all ADVENT participants, study sites and project staff for their involvement.
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