Joint risk factor within target range and hazard of premature mortality in people with obesity

Individuals with obesity are at higher risk for premature mortality compared to the general population. However, whether achieving multiple modifiable risk factors within target ranges is associated with attenuated excess mortality risk in obesity remains unclear. We included 83,505 participants with obesity and 143,198 individuals without obesity from the UK Biobank, all free of baseline cancer and cardiovascular disease (CVD). The main exposure was the number of risk factors within target range, including glycated hemoglobin < 48 mmol/mol, low-density lipoprotein cholesterol (LDL-C) < 2.5 mmol/L, absence of albuminuria, non-current smoker, and systolic blood pressure < 140 mmHg and diastolic blood pressure < 90 mmHg. Cox proportional hazards models adjusted for age, sex, ethnicity, education, socioeconomic status, alcohol intake, healthy diet score, and physical activity were used to evaluate the association between the degree of risk factor within target range and risks of all-cause, cancer, CVD, and other-cause premature mortality. Fine-Gray competing risk models were performed as sensitivity analyses. The proportional hazards assumption was verified using Schoenfeld residuals. Among individuals with obesity, each additional risk factor within target range was associated with 17%, 11%, 28%, and 16% lower risks of all-cause, cancer, CVD, and other-cause premature mortality, respectively. Participants with obesity who achieved all five risk factors had 47%, 38%, 63%, and 47% lower risks compared to those meeting ≤ 2 factors. However, as the number of risk factors within target range increased, the excess mortality risks progressively diminished. Individuals with obesity meeting all 5 factors showed risks approaching those of individuals without obesity, particularly for CVD and other-cause mortality. Achieving multiple modifiable risk factors within target ranges was associated with substantially lower premature mortality risk among individuals with obesity.