Causes of death in people with cardiovascular disease: a prospective UK Biobank cohort study

Cardiovascular disease (CVD) mortality has substantially improved over recent decades. Some evidence indicates this has been paralleled by an increasing proportion of non-cardiovascular mortality in people with CVD. However, the contemporary causes of death across a broad spectrum of CVDs, either alone or in combination, remains unclear. We analysed cardiovascular, infection, cancer and other causes of death prior to the COVID-19 pandemic in 493,280 participants in the prospective UK Biobank study. Studied CVDs included baseline: abdominal aortic aneurysm, atrial fibrillation, coronary artery disease, heart failure, hypertension, peripheral vascular disease, stroke, valvular heart disease and venous thromboembolic disease; we separately considered cardiovascular multimorbidity defined as the total number of these baseline CVDs. Crude mortality rates and Poisson regression analysis were used to quantify the absolute and relative risk of cause-specific death. Associations are reported as incidence rate ratios (IRR) with 95% CIs. During a median follow-up of 10.9 [IQR 10.1-11.6] years per participant, there were 27,729 deaths (20.4% primarily attributed to CVD, 53.6% to cancer, 5.0% to infection and 21.0% to other causes). As the number of co-morbid CVDs increased, the proportion of cardiovascular and infection-related deaths increased, whereas cancer and other deaths decreased. Accrual of multiple CVDs was associated with marked increases in relative risk of infection and cardiovascular death; versus those without CVD, people with three or more CVDs, the relative risk of cardiovascular death increased most (IRR 3.89; 95%CI 3.59-4.21), followed by infection (4.41; 3.44-5.64), with other (2.01; 1.72-2.35) and cancer (1.52; 1.35-1.72) being substantially less increased. All studied CVDs except atrial fibrillation were independently associated with increased risk of infection death, with heart failure (2.73; 1.60-4.66) and valvular heart disease (3.09; 2.38-4.00) posing the greatest risk. In conclusion, causes of death vary substantially between differing baseline CVDs, and according to the number of baseline CVDs, with non-cardiovascular deaths due to cancer and infection making an important contribution. Holistic and personalized care are likely to be important tools for continuing to improve outcomes in people with CVD.