NEW YORK – New research suggests that risk of cardiovascular and metabolic diseases such as coronary artery disease, atrial fibrillation, and type 2 diabetes is linked to depressed mood, no matter the genetic risk for these conditions.
"Overall, lower burden of depressed mood was independently associated with lower risk of CAD and T2D across the cardiometabolic polygenic risk spectrum," senior author Pradeep Natarajan, a researcher affiliated with Massachusetts General Hospital, the Broad Institute, and Harvard, and his colleagues wrote in a study published in Nature Cardiovascular Research on Monday. They noted that "polygenic risk was independently associated with the corresponding outcome" for all three conditions.
For their analyses, the investigators tapped into data for nearly 360,500 genotyped participants of European ancestry in the UK Biobank to search for ties between cardiometabolic disease and depression. After removing individuals with missing data, they were left with genotyping profiles for 328,152 individuals, which they analyzed using established polygenic risk scores for CAD, atrial fibrillation, and T2D.
Along with genetic risk profiles, the team had access to information on actual heart disease or diabetes events in the participants across a follow-up time of more than a decade to almost 12 years. Together, the data indicated that participants who reported having a depressed mood only infrequently tended to be at lower risk of cardiovascular or metabolic conditions, particularly CAD and T2D, independent of other documented lifestyle-related risk factors.
"Although lifestyle behaviors also stratify polygenic risk of cardiometabolic disease, frequency of depressed mood was associated with cardiometabolic outcomes independent of these lifestyle factors," the authors reported, adding that "findings of this study may have implications for improving individual- and population-level cardiometabolic health."
T2D risk appeared to be roughly 33 percent lower in a subset of 250,072 UK Biobank participants with low depression frequency compared to 12,623 individuals in the high frequency group, for example. Similarly, the researchers reported that atrial fibrillation risk dipped some 20 percent in a low depression group comprised of 250,553 individuals relative to the 12,927 high depression individuals included in the analysis.
Most notably, the team estimated that CAD risk was roughly 34 percent lower in a subset of 244,919 individuals classified as having low frequency of depressed mood compared to the 12,400 individuals reporting depressed mood at high frequency. That association was particularly pronounced in women, who were also more apt to report a depressed mood in general.
"Individuals with greater frequency of depressed mood were younger at baseline, more likely to be female, and more likely to be current smokers; reported less vegetable and fresh fruit intake, exercise, and sleep; and had higher body mass index, higher C-reactive protein, and higher baseline prevalence of CAD, hypertension, hypercholesterolemia, and T2D," the authors wrote.
They noted that additional research is needed to explore the possibility that cardiometabolic disease risk could be dialed down to some extent by better managing mental health factors such as depressed mood.
The study represents "the first evidence that depression and its severity increase susceptibility to coronary artery disease and type 2 diabetes beyond lifestyle risk factors and genetic susceptibility to these diseases," Scott Ritchie and Michael Inouye, genomics researchers at the University of Cambridge and the Cambridge Baker Systems Genomics Initiative in the UK and in Australia, wrote in a related editorial.
"The role of depression in the development and management of cardiometabolic disease risk remains an active area of investigation," they wrote, noting that future research is needed to explore the clinical applicability of the findings, to understand depression-related cardiometabolic susceptibility not explained by polygenic risk, and to search for similar associations in other populations.