By Harold L. Karpman, MD, FACC, FACP

Clinical Professor of Medicine, David Geffen School of Medicine at UCLA

Dr. Karpman reports no financial relationships relevant to this field of study.

SYNOPSIS: Anxiety disorders are associated with an elevated risk of a range of different cardiovascular events including stroke, coronary heart disease, heart failure, and cardiovascular deaths, but it is unclear whether these disorders are causal in nature.

SOURCE: Emdin CA, Odutayo A, Wong CX, et al. Meta-analysis of anxiety as a risk factor for cardiovascular disease. Am J Cardiol 2016;118:511-519.

Despite the significant amount of published evidence that demonstrates that depression and general psychological stress are associated with incident cardiovascular disease, the association between anxiety and cardiovascular disease is less clear. Previously published studies have demonstrated that anxiety is associated with a high degree of adverse outcomes in heart failure populations.1 However, these results may be secondary to reverse causality in that patients who suffer from severe cardiovascular disease may develop greater anxiety rather than anxiety causing the illness. A meta-analysis of 20 cohort studies demonstrated that anxiety disorders were associated with a 26% higher risk of coronary artery disease.2 However, previous studies demonstrated conflicting results on whether anxiety was associated with the risk of stroke, heart failure, or cardiovascular mortality.3-6

Because of the possible contribution of anxiety disorders to the development of cardiovascular disease, Emdin et al conducted a comprehensive meta-analysis on the association between anxiety and incident cardiovascular disease and death. Forty-six studies comprised of 2,017,126 participants were included in the analysis. A total of 220,253 participants were afflicted with anxiety. The authors had no evidence of interaction between general anxiety and coronary heart disease. However, phobic anxiety was associated with a 41% higher risk of cardiovascular mortality, a 41% higher risk of coronary heart disease, a 71% higher risk of stroke, and a 35% higher risk of heart failure. The authors concluded that their results suggested that, like depression, anxiety should be considered a risk factor for a wide range of cardiovascular diseases.

COMMENTARY

A large body of evidence has demonstrated that depression is a risk factor for cardiovascular disease.5 In a meta-analysis of 21 prospective studies, depression was associated with an 81% higher risk of coronary artery disease.8 The meta-analysis performed by Emdin et al extends previously published studies demonstrating anxiety to be associated with coronary heart disease.2 In the study, anxiety was associated with a 41% higher risk of coronary heart disease, a 71% higher risk of stroke, and a 35% higher risk of heart failure. Although there are multiple biologic pathways by which anxiety may increase the risk of cardiovascular disease, it is not clear whether the associations reported in this meta-analysis are causal. However, even if the associations are not causal, the elevated risk of cardiovascular disease in subjects who suffer from anxiety would support greater screening and more aggressive measures to prevent cardiovascular disease developing in anxiety-ridden patients.

The results of this meta-analysis provide additional support for the concept that anxiety disorders are associated with elevated risks of a range of different cardiovascular events, including stroke, coronary disease, heart failure, and cardiovascular death, and it is unclear as to whether the associations are causal; however, the results certainly would support more general screening and more aggressive measures to prevent cardiovascular disease among subjects presenting with anxiety.

REFERENCES

  1. Tsuchihashi-Makaya M, Kato N, Chishaki A, et al. Anxiety and poor sexual support are independently associated with adverse outcomes in patient with mild heart failure. Circ J 2009;73:282-287.
  2. Roest AM, Martens EJ, de Jonge P, Denollet J. Anxiety and risk of incident coronary heart disease: A meta analysis. J Am Coll Cardiol 2010;56:38-46.
  3. Lambiase MJ, Kubzansky LD, Thurston RC. Prospective study of anxiety and incident stroke. Stroke 2014;45:438-443.
  4. Garfield LD, Scherrer JF, Hauptman PJ, et al. Association of anxiety disorders and depression with incident heart failure. Psychosom Med 2014;76:128-136.
  5. Phillips AC, Batty GD, Gale CR, et al. Generalized anxiety disorder, major depressive disorder and their comorbidity as predictors of all-cause and cardiovascular mortality: The Vietnam experience study. Psychosom Med 2009;71:395-405.
  6. Denollet J, Maas K, Knottnerus A, et al. Anxiety predicted premature all-cause and cardiovascular death in a I0-year follow up of middle-aged women. J Clin Epidemiol 2009;62:452-456.
  7. Emdin CA, Odutayo A, Wong CX, et al. Meta analysis of anxiety as a risk factor for cardiovascular disease. Am J Cardiol 2016;118:511-519.
  8. Nicholson A, Kuper H, Hemingway H. Depression as an aetiologic and prognostic factor in coronary heart disease: A meta-analysis of 6,362 events among 146,538 participants in 54 observational studies. Eur Heart J 2006;27:2763-2774.