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Anxiety and new onset of cardiovascular disease: critical review and meta-analysis

  • Neeltje M. Batelaan (a1), Adrie Seldenrijk (a1), Mariska Bot (a1), Anton J. L. M. van Balkom (a1) and Brenda W. J. H. Penninx (a1)...



Anxiety has been associated with new-onset cardiovascular disease (CVD), but the quality of this relationship is unclear. Only if anxiety is a causal, independent cardiovascular risk factor might it be a target for CVD prevention.


To determine and examine the independent association and causality between anxiety and incident CVD.


PubMed, EMBASE and PsycINFO databases were searched up to October 2013. A review of Hill's criteria for causality and random effects meta-analysis were conducted of prospective, population-based studies examining anxiety and incident CVD in people free from CVD at baseline.


The meta-analysis comprised 37 papers (n = 1 565 699). The follow-up ranged from 1 to 24 years. Anxiety was associated with a 52% increased incidence of CVD (hazard ratio = 1.52, 95% CI 1.36–1.71). The risk seemed independent of traditional risk factors and depression. The evaluation of Hill's criteria largely argued in favour of causality.


Anxiety may be of interest for CVD prevention. Future research should examine biological and behavioural underpinnings of the association in order to identify targets for intervention.

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Corresponding author

Dr Neeltje M. Batelaan, Department of Psychiatry VU University Medical Center, A.J. Ernststraat 1187, 1081 HL Amsterdam, The Netherlands. Email:


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B.W.J.H.P. is supported by an NWO-VICI grant 91811602.

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Anxiety and new onset of cardiovascular disease: critical review and meta-analysis

  • Neeltje M. Batelaan (a1), Adrie Seldenrijk (a1), Mariska Bot (a1), Anton J. L. M. van Balkom (a1) and Brenda W. J. H. Penninx (a1)...
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Anxiety and new onset of cardiovascular disease: critical review and meta-analysis

Zulijana M Anastasova, Psychiatrist, Mercy University Hospital Journal Club, Cork
Michele J Hill, Psychiatrist, Mercy University Hospital Journal Club, Cork
16 March 2016

We read with interest the recent paper by Batelaan et al 1 evaluating the relationship between anxiety and cardiovascular disease at our weekly Journal Club. The authors found that anxiety is associated with a 52% increased incidence of CVD, that the relationship appeared to be causal, and independent of depression and traditional risk factors. Their definition of anxiety ranged from self-reported symptoms to post traumatic stress disorder. The magnitude of the association was similar to that of obesity. Their definition of anxiety ranged from self-reported symptoms to post traumatic stress disorder.

This is very important, as stress and anxiety are the leading cause of workplace absenteeism and do not receive the same level of attention at a government or societal level as obesity. If anxiety is indeed as potent a risk factor for CVD as obesity, one would hope that a comparable system level approach to its management, involving media campaigns, schools and workplaces, would naturally follow.

The authors stopped short of this recommendation, instead promoting further examination of the biological and behavioural underpinnings of their association, and in the meantime encouraging healthy life habits. While we recognise the importance of improved understanding of underlying mechanisms, surely, with the ready availability of effective treatments for anxiety at a primary prevention level (eg. Mindfulness, Positive Psychology), and secondary prevention level (eg. Psychotherapy, SSRIs), it might indeed be sensible to strongly encourage experimental studies, despite the challenge involved, particularly in view of the fact that this was identified as a gap in the knowledge on the area?

Another issue raised was the inclusion of PTSD in the study. PTSD has been associated with elevated basal heart rates and bood pressure 2. It has been moved from the Anxiety Disorders section to the Trauma and Stressor Related Disorders section in DSM V 3 and differs greatly in its biology from anxiety in terms of central noradrenergic effects and sympathoadrenal axis activity 4. The subgroup analysis in Batelaan et al’s study showed no differences between pooled hazard ratios in studies examining PTSD versus anxiety, however the proportion of positive studies was higher in the PTSD group (five out of six studies comprising a fifth of the overall population studied). If future efforts are to focus on biological underpinnings of the association between anxiety and CVD, it stands to reason that PTSD ought to be excluded.

1.Batelaan N, Seldenrijk A, Bot M, van Balkom A, Penninx B

Anxiety and new onset of cardiovascular disease: critical review and meta-analysis

Br J of Psychiatry (2016) 208, 223-231

2. Buckley TC, Kaloupek DG

A meta-analytic examination of basal cardiovascular activity in posttraumatic stress disorder

Psychosom Med. 2001 Jul-Aug; 63(4):585-94.


4. Bedi US, Arora R

Cardiovascular manifestations of posttraumatic stress disorder

J Natl Med Assoc. 2007 Jun;99(6):642-9.

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Conflict of interest: None Declared

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