Age at Type 2 Diabetes Diagnosis, Depression, and Risk of Cardiovascular Disease: Findings from the Women's Health Initiative

Cardiovascular diseases (CVD) are a leading cause of morbidity and mortality globally and in the United States (US). Type 2 Diabetes (T2D), which affects over 37 million Americans, and depression, impacting more than 21 million US adults, have been identified as significant risk factors for CVD. Epidemiological evidence suggests a bidirectional relationship between T2D and depression. However, their compounded risk on CVD is largely understudied, with no study to date assessing the interaction between T2D or age at T2D diagnosis and depression and their impact on CVD risk. This study aimed to investigate how age at T2D diagnosis and potential interactions with depression can impact the relationship between T2D and cardiovascular events among participants in the Women’s Health Initiative (WHI) cohort. WHI is a large, multi-racial cohort of postmenopausal women in the US. At baseline and follow-up, participants self-reported their depression status (Yes/No), T2D status (Yes/No), and the age group they were diagnosed with T2D. Based on this information, we categorized age at onset into early (30-49) versus late (>=50). We also categorized our T2D duration into five years intervals. Incident CVD events (i.e., any CVD event, CHD, CHF, MI, and stroke) were all adjudicated outcomes and binary in nature (Yes/No). Cox proportional hazard regression models were used to estimate the unadjusted and adjusted hazard ratios (HR) and their 95% confidence intervals (95% CI) for the association between Age at T2D and incident CVD, considering depression as an effect modifier. After adjusting for numerous crucial covariates, we found that individuals with early onset T2D (30-49) who also have depression are at a heightened risk for CHF compared to their counterparts with depression and late (>=50) onset T2D. We also found that individuals with a longer duration of T2D who also had depression were at a progressively increasing risk of any CVDs with every five-year increase in the duration of T2D. These results support the bidirectional relationship between T2D and depression and their compounded risk on CVD. Our study emphasizes the need for a comprehensive, multidisciplinary approach to care.