Chronic financial stress and cardiovascular disease risk: A prospective cohort study and Mendelian randomization analysis

Background and aims: The associations between chronic stress and incident CVDs and related mechanisms remain understudied. This study examined these associations and explored the potential mediators, including metabolism, body composition, immunity, lifestyle, and cognitive function. Methods: We analyzed 399,998 participants without prior CVDs including stroke, coronary heart disease, myocardial infarction, or heart failure from the UK Biobank cohort. The multivariable Cox proportional hazards model was conducted to evaluate the associations between chronic stress and incident CVDs. Two-sample Mendelian randomization (MR) was used to further examine their associations. Candidate mediators included factors of metabolism, body composition, immunity, lifestyle, and cognitive function. Results: Chronic stress from serious illness/injury/assault of the participants or financial difficulties was associated with increased risk of CVDs, as revealed by the multivariable Cox proportional hazards model. MR analysis showed that only chronic stress from financial difficulties was associated with elevated risks of stroke (OR = 1.86, 95 %CI: 1.10–3.14), coronary heart disease (OR = 1.05, 1.02–1.07), myocardial infarction (OR = 1.03, 1.02–1.05), and heart failure (OR = 5.02, 2.60–9.71). Four groups of mediators collectively accounted for 19.30 %–34.40 % of the effects of chronic stress from financial difficulties on incident CVDs: Body composition explained 6.20 %–16.10 % (waist-to-height ratio: 14.80 %–26.20 % and hip-to-height ratio: 8.08 %–12.80 %), followed by lifestyle: 5.70 %–9.00 % (smoking: 3.94 %–6.68 %, sedentary behaviors: 1.59 %–3.71 %, sleep: 2.33 %–4.07 %, and refrain grain intake: 1.08 %–1.18 %), immunity: 4.60 %–8.60 % (lymphocyte count: 1.69 %–2.89 % and CRP: 7.62 %–12.10 %), and metabolism: 1.70 %–7.90 % (HbA1c: 5.39 %–8.91 %). The waist-to-height ratio was the strongest mediator. Conclusions: Chronic stress from financial difficulties is associated with elevated CVDs risk, which is mediated by body composition, lifestyle, immunity, and metabolism factors.