Implications of obesity and metabolic health on coronary heart disease: an analysis of 157,159 participants in the UK Biobank

Background Adiposity frequently occurs with or without metabolic abnormalities. However, cardiovascular preventive measures are often considered only when the former appears. We have previously demonstrated that excess adiposity (overweight and obesity) in metabolically healthy individuals had similar adverse effects on arterial stiffness (a proxy for vascular health) compared to those of normal BMI with markers of metabolic dysfunction. Excess adiposity may reflect an earlier transitional state in cardiovascular disease prior to the onset of overt metabolic dysfunction. Purpose To assess the independent and joint effects of body-mass index (BMI) and metabolic health on the risk of coronary heart disease, in men and women, and to what extent vascular health (arterial stiffness) mediates any association. Methods UK Biobank participants with BMI and arterial stiffness index (ASI) recorded at initial assessment between 2006-2010, free from cardiovascular diseases and not underweight (BMI<18.5kg/m2) were included. Participants were stratified by sex, and categorised by BMI (normal, overweight or obesity) and presence of metabolic abnormalities (hypertension, diabetes or dyslipidaemia). The primary outcome was the risk of incident fatal or non-fatal coronary heart disease (CHD), assessed by multivariate-adjusted cox regression. Results Of 157,159 participants, 55.3% were women, 42.6% were overweight and 24.2% were obese. Over a mean follow-up of 12.4 years (SD 2.4), there were 11,641 incident CHD events among 10.6% of men (n=7,430) and 4.8% of women (n=4,211). Compared to individuals with normal BMI and no metabolic abnormality (ref group), increasing BMI even in the absence of metabolic abnormality was associated with increasing risk of CHD in men (HR 1.73, 95% CI 1.41 – 2.12) and women (HR 1.76, 95% CI 1.42 – 2.19; p-value <0.001 for both). Among individuals with metabolic abnormalities and normal BMI, their hazard ratios were 1.68, 95% CI 1.49 – 1.89 for men; HR 2.10 95% CI 1.84 – 2.40 for women. The highest risk was observed in individuals with obesity and metabolic abnormalities (HR 2.80, 95% CI 2.51 – 3.13 for men; HR 3.69, 95% CI 3.26 – 4.17 for women). The relationship between BMI and the risk of CHD was modestly attenuated after adjusting for ASI at baseline for both men and women, with or without metabolic abnormality. Conclusion Worsening BMI even in the absence of metabolic abnormalities is independently associated with higher risk for CHD in both men and women. This is further exacerbated when metabolic dysfunction is present, suggesting that normalising BMI per se in the presence of metabolic derangement may not attenuate the excess risk, with additional risk factor management needed. Taken together, our findings suggest that the presence of excess BMI alone should warrant consideration of primary prevention strategies. Furthermore, normalising BMI before metabolic dysfunction occurs may have significant public health gains.