DESIGNACIÓN DE TEMPLE

This thesis will not analyse heart rate variability data directly but this mechanism is implicated in several pathways and may be important as a potential explanation for any observed associations.

The heart rate is controlled by the autonomic nervous system with sympathetic (S) nerves increasing heart rate and parasympathetic (PS) fibres in the vagus nerve slowing the heart. Heart rate variability (HRV) refers to the beat-to-beat variation in the heart rate that occurs largely due to parasympathetic innervation. HRV is therefore a measure o f sympathetic/parasympathetic balance and, since Askelrod described the method o f power spectrum analysis, it has become an accessible technique for examining the influence o f the autonomic nervous system on the heart

Decreased heart rate variability (HRV) is seen as a sign o f distress analogous to the non-reactive fetal heart trace. Decreased HRV has been shown to be a predictor of mortality after and also to predict CHD incidence*'^ and all-cause mortality^

Resting heart rate is considered a crude measure of cardiac autonomic control and has also been shown to be an independent risk factor for CHD*^^. The suggested pathway for HRV is that increased sympathetic and decreased parasympathetic tone are associated with increased risk o f arrhythmias via a direct effect on heart rate and because PS tone increases myocardial threshold and protects the heart against arrhythmias in acute ischaemia. HRV is therefore a mechanism that could contribute to an acute event at an advanced stage o f atherosclerosis. It is not easy to envisage a direct role o f HRV in the early development o f atherosclerosis. Some authors have suggested that HRV, as a measure o f cardiac vagal tone, is a marker o f a wider dysregulation o f the sympathetic/parasympathetic system and hence an index o f stress^^^. This increased sympathetic drive would impact earlier in the pathogenesis o f CHD. Increase in circulating catecholamines may change haemodynamics so that shear forces in arteries are increased, leading to endothelial injury and plaque development.

Research linking HRV with psychological distress has fallen into several groups: the role o f HRV in mediating the association between distress symptoms and prognosis in established CHD; evidence for a disturbance o f HRV in psychiatric populations; and studies linking psychological distress to altered HRV in healthy populations.

Research in cardiac patients provides the strongest evidence that HRV may be important in mediating the effect o f anxiety or depressive symptoms on the heart. Frasure-Smith showed that depressive symptoms posed a greater risk in those with premature ventricular

contractions (PVC), which predispose to life-threatening a r r h y t h m i a s S i n c e then evidence has accumulated that CHD patients with depressive symptoms show disturbances in In a recent study, Carney reported that improvement of depressive symptoms following cognitive behaviour therapy resulted in only modest improvement in HRV indices There is also evidence that anxiety may also be associated with decrease in HRV. Frasure-Smith did not demonstrate an association between anxiety and arrhythmic d e a t h s b u t Moser found a higher prevalence of ventricular fibrillation associated with anxiety during the hospital stay o f post-infarct patients^^\ A recent study by Watkins has raised the issue of whether associations between depressive symptoms and reduced HRV may be due to co-morbid anxiety, demonstrating that reduced baroreflex cardiac control was related to anxiety but not depression in post-MI patients’*^.The previous studies showing an association between HRV and depression had not adjusted for anxiety.

An important role for anxiety influencing HRV is supported by studies on psychiatric patients. Evidence linking reduced HRV to depressive illness in non-cardiac patients is patchy and contradictory. The role of anxiety seems to be more important even in populations o f patients with major depressive illness’ Additional studies on anxiety patients give further evidence o f reduced HRV, in both generalised anxiety disorder’ and panic disorder’ The published studies are very small, often with highly selected populations, including volunteer groups, and give few details concerning the selection of controls.

There have been few studies in non-clinical populations, using similar measures of depressive symptoms to those that have been shown to predict CHD incidence, and the published are often s m a l l R e p o r t s are contradictory, but there is evidence o f reduced HRV in men and women with a high score on the B D l’^’. In an important study in healthy men, Kawachi demonstrated a linear trend with decreasing HRV with increasing scores on the CCEI phobic anxiety scale’^^. The effect was apparent across the whole range of scores. Together with the findings that phobic anxiety predicted sudden cardiac death, this is consistent with the hypothesis that the high levels o f anxiety experienced in phobic attacks increase the risk o f sudden cardiac death by altering HRV.

Summary

There is evidence linking anxiety to reduced heart rate variability in both non-clinical and patient populations. It is at present unclear whether similar associations with depressive symptoms, which have been demonstrated convincingly only in cardiac patients, are independent of co-morbid anxiety. This emphasises the importance of, and difficulty in, separating the effects o f the different components of distress. A review of psychosocial influences on cardiac autonomic function reported positive associations across a range of psychosocial variables, indicating a lack of specificity in the observed associations*^^.

All studies were cross-sectional and subsequent CHD events were not analysed, so that the effect of these variations on subsequent prognosis is only speculation at present. The current data on HRV are more compatible with the second acceleration model, rather than an atherogenic role.