The Evolving Understanding and Approach to Residual Cardiovascular Risk Management

Abstract

Despite unprecedented advances in treatment of atherosclerotic cardiovascular disease, it remains the leading cause of death and disability worldwide. Treatment of major traditional risk factors, including low-density lipoprotein-cholesterol, serves as the foundation of atherosclerotic risk reduction. However, there remains a significant residual risk of cardiovascular events despite optimal risk factor management. Beyond traditional risk factors, other drivers of residual risk have come to the forefront, including inflammatory, pro-thrombotic, and metabolic pathways that contribute to recurrent events and are often unrecognized and not addressed in clinical practice. This review will explore the evidence linking these pathways to atherosclerotic cardiovascular disease and potential future therapeutic options to attenuate residual cardiovascular risk conferred by these pathways.

Keywords: atherosclerosis; cardiovascular disease; cardiovascular risk factors; inflammation; metabolic syndrome; primary prevention; residual risk; secondary prevention.

Figure 1

Pathways of residual cardiovascular risk. The pathways of residual cardiovascular risk, beyond traditional risk factors, with evidence-based therapeutic options. COLCOT, Colchicine Cardiovascular Outcomes Trial; CANTOS, Canakinumab Anti-inflammatory Thrombosis Outcomes Study; JUPITER, Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin; PEGASUS TIMI 54, Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis In Myocardial Infarction 54; THEMIS-PCI, The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study- PCI; COMPASS, Cardiovascular Outcomes for People Using Anticoagulation Strategies; REDUCE-IT, Reduction of Cardiovascular Events With EPA–Intervention; EMPA-REG, Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes trial; CREDENCE, Canagliflozin and Renal Events in Diabetes and Nephropathy Clinical Evaluation; DECLARE TIMI 58, Dapagliflozin Effect on Cardiovascular Events A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Effect of Dapagliflozin 10 mg Once Daily on the Incidence of Cardiovascular Death, Myocardial Infarction or Ischemic Stroke in Patients With Type 2 Diabetes; LEADER, Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results.