Residual risk in vascular disease and heart failure: Risk factors and individualized prevention

Despite the routine use of lipid- and blood pressure-lowering therapies, anticoagulation, and heart failure medication, many patients with cardiovascular disease remain at high risk of recurrent cardiovascular events. This is referred to as residual risk. This thesis identifies several risk factors that contribute to this residual risk. It was shown that patients with low-grade inflammation, as measured by high plasma concentrations of C-reactive protein (CRP), have a one-and-a-half to two-and-a-half times greater risk of recurrent cardiovascular events. Also, it was shown that patients with the metabolic syndrome, a cluster of obesity-related metabolic disturbances, have a 32% higher risk of heart failure. In addition, this thesis demonstrates how prediction models can be used to predict residual risk and the effects of treatment for individual patients. The LIFE-HF model was developed, and it was shown how this model can be used to accurately predict the life expectancy and lifetime benefit from medication for individual patients with heart failure. Existing prediction models were used to estimate the effects of colchicine (an anti-inflammatory agent) and icosapent ethyl (a triglyceride-lowering drug) for individual patients. This showed that in 68-70% of patients, colchicine was expected to more effectively reduce residual risk than intensified lipid- or blood pressure-lowering therapy. Icosapent ethyl lowers residual risk by 22-38%, depending on a patient’s residual risk at the start of the treatment. Finally, the results of all relevant studies on lipid-lowering therapies were combined to show that the effects of low-density lipoprotein cholesterol (LDL-C) reduction remain stable over time in patients who already have a history of cardiovascular disease (secondary prevention), but decrease with increasing age in patients who only have a high risk of developing cardiovascular disease in the future (primary prevention).