Introduction.
Major depressive disorder (MDD) is associated with coronary heart disease, but the underlying mechanisms are unclear. Coronary flow reserve (CFR) in response to adenosine is an index of coronary microvascular dysfunction which predisposes to myocardial ischemia. We examined the relationship between MDD and CFR in a genetically informative sample.
Methods.
We studied 141 twin pairs drawn from the Vietnam Era Twin Registry who were born between 1946 and 1956 (mean age 54). For all twins, a lifetime history of MDD was determined with the Structured Clinical Interview for Psychiatry Disorders; 53 pairs were discordant for MDD and 88 pairs were free of MDD. Standard cardiovascular risk factors were obtained by interview and examination. We performed myocardial perfusion imaging and blood flow quantitation with [13N] ammonia positron emission tomography at rest and after adenosine stress. A perfusion defect score summed the number and severity of defects across 20 myocardial regions. CFR was measured as the ratio of maximum flow to baseline flow at rest. Mixed-effect and GEE models were used to conduct matched-pair analyses.
Results.
There was no difference in the distribution of abnormal scans, in summed rest or stress defect scores, and in heart rate/blood pressure responses to adenosine between twins with and without MDD. Among the DZ twin pairs discordant for MDD, the mean CFR was lower in twins with MDD than their brothers without MDD (2.36 ± 0.66 vs 2.75 ± 0.90; p=0.03); no significant difference in mean CFR was found in MZ discordant pairs (2.90±0.78 vs 2.64±0.64, p=0.13). The zygosity by MDD interaction was significant (p=0.01). Results did not change substantially after adjusting for cardiovascular disease risk factors and antidepressant use (adjusted interaction p=0.007). There were no differences in myocardial perfusion comparing twins in discordant pairs with twins in healthy pairs.
Conclusions.
MDD is associated with lower CFR in spite of no differences in visible perfusion defects, suggesting microvascular dysfunction. This association is largely due to shared genetic liability between depression and CFR, suggesting a common underlying pathophysiological process linking depression and coronary microvascular dysfunction.
This research has received full or partial funding support from the American Heart Association, AHA National Center.
P1712Diagnostic performance of coronary flow reserve ratio for the detection of coronary artery disease on 13N-ammonia positron emission tomography
