Metabolic health and cardiometabolic risk clusters: implications for prediction, prevention, and treatment

Among 20 leading global risk factors for years of life lost in 2040, reference forecasts point to three metabolic risks—high blood pressure, high BMI, and high fasting plasma glucose—as being the top risk variables. Building upon these and other risk factors, the concept of metabolic health is attracting much attention in the scientific community. It focuses on the aggregation of important risk factors, which allows the identification of subphenotypes, such as people with metabolically unhealthy normal weight or metabolically healthy obesity, who strongly differ in their risk of cardiometabolic diseases. Since 2018, studies that used anthropometrics, metabolic characteristics, and genetics in the setting of cluster analyses proposed novel metabolic subphenotypes among patients at high risk (eg, those with diabetes). The crucial point now is whether these subphenotyping strategies are superior to established cardiometabolic risk stratification methods regarding the prediction, prevention, and treatment of cardiometabolic diseases. In this Review, we carefully address this point and conclude, firstly, regarding cardiometabolic risk stratification, in the general population both the concept of metabolic health and the cluster approaches are not superior to established risk prediction models. However, both subphenotyping approaches might be informative to improve the prediction of cardiometabolic risk in subgroups of individuals, such as those in different BMI categories or people with diabetes. Secondly, the applicability of the concepts by treating physicians and communication of the cardiometabolic risk with patients is easiest using the concept of metabolic health. Finally, the approaches to identify cardiometabolic risk clusters in particular have provided some evidence that they could be used to allocate individuals to specific pathophysiological risk groups, but whether this allocation is helpful for prevention and treatment still needs to be determined.