Residual macrovascular risk in 2013: what have we learned?

Jean-Charles Fruchart, Jean Davignon, Michel P Hermans, Khalid Al-Rubeaan, Pierre Amarenco, Gerd Assmann, Philip Barter, John Betteridge, Eric Bruckert, Ada Cuevas, Michel Farnier, Ele Ferrannini, Paola Fioretto, Jacques Genest, Henry N Ginsberg, Antonio M Gotto, Dayi Hu, Takashi Kadowaki, Tatsuhiko Kodama, Michel Krempf, Yuji Matsuzawa, Jesús Millán Núñez-Cortés, Carlos Calvo Monfil, Hisao Ogawa, Jorge Plutzky, Daniel J Rader, Shaukat Sadikot, Raul D Santos, Evgeny Shlyakhto, Piyamitr Sritara, Rody Sy, Alan Tall, Chee Eng Tan, Lale Tokgözoğlu, Peter P Toth, Paul Valensi, Christoph Wanner, Alberto Zambon, Junren Zhu, Paul Zimmet, for the Residual Risk Reduction Initiative (R3i)

Cardiovascular disease poses a major challenge for the 21st century, exacerbated by the pandemics of obesity, metabolic syndrome and type 2 diabetes. While best standards of care, including high-dose statins, can ameliorate the risk of vascular complications, patients remain at high risk of cardiovascular events. The Residual Risk Reduction Initiative (R3i) has previously highlighted atherogenic dyslipidaemia, defined as the imbalance between proatherogenic triglyceride-rich apolipoprotein B-containing-lipoproteins and antiatherogenic apolipoprotein A-I-lipoproteins (as in high-density lipoprotein, HDL), as an important modifiable contributor to lipid-related residual cardiovascular risk, especially in insulin-resistant conditions. As part of its mission to improve awareness and clinical management of atherogenic dyslipidaemia, the R3i has identified three key priorities for action: i) to improve recognition of atherogenic dyslipidaemia in patients at high cardiometabolic risk with or without diabetes; ii) to improve implementation and adherence to guideline-based therapies; and iii) to improve therapeutic strategies for managing atherogenic dyslipidaemia. The R3i believes that monitoring of non-HDL cholesterol provides a simple, practical tool for treatment decisions regarding the management of lipid-related residual cardiovascular risk. Addition of a fibrate, niacin (North and South America), omega-3 fatty acids or ezetimibe are all options for combination with a statin to further reduce non-HDL cholesterol, although lacking in hard evidence for cardiovascular outcome benefits. Several emerging treatments may offer promise. These include the next generation peroxisome proliferator-activated receptorα agonists, cholesteryl ester transfer protein inhibitors and monoclonal antibody therapy targeting proprotein convertase subtilisin/kexin type 9. However, long-term outcomes and safety data are clearly needed. In conclusion, the R3i believes that ongoing trials with these novel treatments may help to define the optimal management of atherogenic dyslipidaemia to reduce the clinical and socioeconomic burden of residual cardiovascular risk.