Weight change and the incidence of cardiovascular diseases in adults with normal weight, overweight and obesity without chronic diseases; emulating trials using electronic health records

ABSTRACT Background Cross sectional measures of body mass index (BMI) are associated with cardiovascular disease (CVD) incidence, but less is known about whether weight change affects the risk of CVD. Methods We estimated the effect of 2-year weight change interventions on 7-year risk of CVD, by emulating hypothetical target trials using electronic health records. We identified 138.567 individuals in England between 1998 and 2016, aged 45-69 years old, free of chronic diseases at baseline. We performed pooled logistic regression, using inverse-probability weighting to adjust for baseline and time-varying variables. Each individual was classified into a weight loss, maintenance, or gain group. Findings In the normal weight, both weight loss and gain were associated with increased risk for CVD [HR vs weight maintenance=1.53 (1.18-1.98) and 1.43 (1.19-1.71 respectively)]. Among overweight individuals, both weight loss and gain groups, compared to weight maintenance, had a moderately higher risk of CVD [HR=1.20 (0.99–1.44) and 1.17 (0.99–1.38), respectively]. In the obese, weight loss had a lower risk lower risk of CHD [HR =0.66 (0.49–0.89)] and a moderately lower risk of CVD [HR =0.90 (0.72–1.13)]. When we assumed that a chronic disease occurred 1-3 years before the recorded date, estimates for weight loss and gain were attenuated among overweight individuals and estimates for weight loss were stronger among individuals with obesity. Interpretation Among individuals with obesity, the weight loss group had a lower risk of CHD and moderately lower risk of CVD. Weight gain increased the risk of CVD across BMI groups.