Psychological distress and ischaemic heart disease: Cause or consequence? Evidence from a large prospective cohort study

Background Ischaemic heart disease (IHD) incidence is elevated in people reporting psychological distress. The extent to which this relationship is causal or related to reverse causality-that is, undiagnosed disease causing distress-is unclear. We quantified the relationship between psychological distress and IHD, with consideration of confounding and undiagnosed disease. Methods Questionnaire data (2006-2009) from 151 811 cardiovascular disease-free and cancer-free Australian general population members aged ≥45years (45 and Up Study) were linked to hospitalisation and mortality data, to December 2013. A two-stage approach estimated HRs for incident IHD (IHD-related hospitalisation or death) for low (Kessler-10 scores: 10-<12), mild (12-<16), moderate (16-<22) and high (22-50) psychological distress, adjusting for demographic and behavioural characteristics, and then restricting to those with no/minor functioning limitations (likely free from undiagnosed disease). Results Over 859 396 person-years, 5230 incident IHD events occurred (rate: 6.09/1000person-years). IHD risk was increased for mild (age-adjusted and sex-adjusted HR: 1.18, 95% CI 1.11 to 1.26), moderate (1.36, 1.25 to 1.47), and high (1.69, 1.52 to 1.88) versus low distress. HRs attenuated to 1.15 (1.08 to 1.22), 1.26 (1.16 to 1.37) and 1.41 (1.26 to 1.57) after adjustment for demographic and behavioural characteristics and were further attenuated by 35%-41% in those with no/minor limitations, leaving a significant but relatively weak doseresponse relationship: 1.11 (1.02 to 1.20), 1.21 (1.08 to 1.37) and 1.24 (1.02 to 1.51) for mild, moderate and high versus low distress, respectively. The observed adjustment-related attenuation suggests measurement error/residual confounding likely contribute to the remaining association. Conclusion A substantial part of the distress-IHD association is explained by confounding and functional limitations, an indicator of undiagnosed disease.Emphasis should be on psychological distress as a marker of healthcare need and IHD risk, rather than a causative factor.