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Jan 2021
Omega-3 fatty acids for residual cardiovascular risk: more questions than answers
Oct 2020
Targeting triglycerides: Novel agents expand the field
Jul 2020
Why multidrug approaches are needed in NASH: insights with pemafibrate
Jun 2020
Triglyceride-rich remnant lipoproteins: a new therapeutic target in aortic valve stenosis?
Mar 2020
Lowering triglycerides or low-density lipoprotein cholesterol: which provides greater clinical benefit?
Feb 2020
The omega-3 fatty acid conundrum
Jul 2019
International Expert Consensus on Selective Peroxisome Proliferator-Activated Receptor Alpha Modulator (SPPARMα): New opportunities for targeting modifiable residual cardiovascular risk
Nov 2018
Residual cardiovascular risk: triglyceride metabolism and genetics provide a key
Jul 2018
The clinical gap for managing residual cardiovascular risk: will new approaches make the difference?
Apr 2018
Residual cardiovascular risk: refocus on a multifactorial approach
Feb 2018
Optimizing treatment benefit: the tenet of personalized medicine
Jan 2018
Addressing residual cardiovascular risk – back to basics?
Dec 2017
Residual risk of heart failure: how to address this global epidemic?
Oct 2017
Remnants and residual cardiovascular risk: triglycerides or cholesterol?
Jul 2017
Targeting residual cardiovascular risk: lipids and beyond…
Jun 2017
Why we need to re-focus on Latin America.
Apr 2017
Residual cardiovascular risk in the Middle East: a perfect storm in the making
Feb 2017
A global call to action on residual cardiovascular risk
Dec 2016
SPPARM?: more than one way to tackle residual risk
Oct 2016
Remnants linked with diabetic myocardial dysfunction
Sep 2016
New study links elevated triglycerides with plaque progression
Aug 2016
Atherogenic dyslipidaemia: a risk factor for silent coronary artery disease
Jul 2016
SPPARM?: a concept becomes clinical reality
Jun 2016
Remnant cholesterol back in the news
May 2016
Back to the future: triglycerides revisited
Apr 2016
Unravelling the heritability of triglycerides and coronary risk
Mar 2016
Will residual cardiovascular risk meet its nemesis in 2016?
Feb 2016
Tackling residual cardiovascular risk: a case for targeting postprandial triglycerides?
Jan 2016
Looking back at 2015: lipid highlights
Dec 2015
Legacy effects in cardiovascular prevention
Nov 2015
Residual cardiovascular risk: it’s not just lipids!
Oct 2015
Addressing residual vascular risk: beyond pharmacotherapy
Sep 2015
Back to basics: triglyceride-rich lipoproteins, remnants and residual vascular risk
Jul 2015
Beyond the PCSK9 decade: what's next?
Jun 2015
Targeting triglycerides: what lies on the horizon for novel therapies?
May 2015
Do we need new lipid biomarkers for residual cardiovascular risk?
Apr 2015
The Residual Risk Debate Hots Up: Lowering LDL-C or lowering remnant cholesterol?
Mar 2015
Call for action on stroke
Feb 2015
Triglycerides: the tide has turned
Jan 2015
Post IMPROVE-IT: Where to now for residual risk?
Dec 2014
R3i publishes new Call to Action paper: Residual Microvascular Risk in Type 2 Diabetes in 2014: Is it Time for a Re-Think?
Sep 2014
Targeting residual vascular risk: round-up from ESC Congress 2014 and beyond
Jul 2014
Lipid-related residual cardiovascular risk: a new therapeutic target on the horizon
Mar 2014
Non-HDL-C and residual cardiovascular risk: the Lp(a) perspective
Feb 2014
REALIST Micro, atherogenic dyslipidaemia and residual microvascular risk
Jan 2014
Looking back at 2013: what have we learned about residual vascular risk?
Dec 2013
Long-overdue US guidelines for lipid management oversimplify the evidence
Nov 2013
Triglycerides and residual cardiovascular risk: where now?
Oct 2013
How to target residual cardiovascular risk?
Sep 2013
The Residual Vascular Risk Conundrum: Why we should target atherogenic dyslipidaemia
Jul 2013
Targeting atherogenic dyslipidemia: we need to do better
Apr 2013
Is PCSK9- targeted therapy the new hope for residual risk?
Mar 2013
Scope for multifocal approaches for reducing residual cardiovascular risk?
Feb 2013
Renewing the R3i call to action: Now more than ever we need to target and treat residual cardiovascular risk
Jan 2013
Time for a re-think on guidelines to reduce residual microvascular risk in diabetes?
Jan 2013
Addressing the residual burden of CVD in renal impairment: do PPARa agonists provide an answer?
Jan 2013
Re-evaluating options for residual risk post-HPS2-THRIVE : are SPPARMs the answer?
Dec 2012
Dysfunctional HDL: an additional target for reducing residual risk
Nov 2012
Egg consumption: a hidden residual risk factor
Oct 2012
Call to action: re-emphasising the importance of targeting residual vascular risk
Jun 2012
Time to prioritise atherogenic dyslipidaemia to reduce residual microvascular risk?
Jan 2012
Residual vascular risk in chronic kidney disease: an overlooked high-risk group
Dec 2011
Introducing the HDL Resource Center: HDL science now available for clinicians
Oct 2011
Targeting reverse cholesterol transport: the future of residual vascular risk reduction?
Sep 2011
After SPARCL: Targeting cardio-cerebrovascular metabolic risk and thrombosis to reduce residual risk of stroke
Jul 2011
Challenging the conventional wisdom: Lessons from the FIELD study on diabetic nephropathy
Jul 2010
ACCORD Eye Study: a milestone in residual microvascular risk reduction for patients with type 2 diabetes
May 2010
Lipids and residual risk of coronary heart disease in statin-treated patients
Mar 2010
ACCORD Lipid Study brings new hope to people with type 2 diabetes and atherogenic dyslipidemia
Mar 2010
Reducing residual risk of diabetic nephropathy: the role of lipoproteins
Dec 2009
ARBITER 6-HALTS: Implications for residual cardiovascular risk
Nov 2009
Microvascular event risk reduction in type 2 diabetes: New evidence from the FIELD study
Aug 2009
Fasting versus nonfasting triglycerides: Importance of triglyceride-regulating genetic polymorphisms to residual cardiovascular risk
Jul 2009
Residual risk of microvascular complications of diabetes: is intensive multitherapy the solution?
Apr 2009
Reducing residual vascular risk: modifiable and non modifiable residual vascular risk factors
Jan 2009
Micro- and macrovascular residual risk: one of the most challenging health problems of the moment
Nov 2008
Treated dyslipidemic patients remain at high residual risk of vascular events

R3i Editorial

19 December 2019
Focus on stroke: more input to address residual cardiovascular risk
Prof. Jean Charles Fruchart, Prof. Michel Hermans, Prof. Pierre Amarenco
An Editorial from the R3i Trustees
Prof. Jean Charles Fruchart, Prof. Michel Hermans, Prof. Pierre Amarenco Stroke is a leading cause of death worldwide, second only to ischaemic heart disease. Yet, while there has been a decline in stroke mortality over the last three decades, stroke prevalence has increased, in part due to ageing populations and better risk factor management resulting in improved survival. Thus, the burden posed by the morbidity and associated disability of recurrent stroke and associated cardiovascular events is substantial.1

Hypercholesterolaemia, globally the eighth most important indicator of stroke mortality in 2017,1 is one example where there has been improved management. In line with the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines,2 the AHA/American Stroke Association recommended intensive statin therapy to reduce the risk of stroke and cardiovascular events in patients with ischaemic stroke or transient ischaemic attack (TIA), of presumed atherosclerotic origin.3 These guidelines, however, fall short in defining low-density lipoprotein cholesterol (LDL-C) targets in this very high risk group.

This uncertainty was the focus of the Treat Stroke to Target Study,4 discussed as this month’s Landmark study. Despite being prematurely stopped for a number of administrative reasons, the study showed significant reduction in cardiovascular events in patients with a prior ischaemic stroke or TIA of atherosclerotic origin assigned to a lower LDL-C target (≤70 mg/dL or ≤1.87 mmol/L) compared with those assigned to a higher target (90 to 110 mg/dL or 2.3 to 2.8 mmol/L). Most of these events were cerebral infarctions or strokes of uncertain origin. Moreover, given the patient population – patients were enrolled in France and South Korea – there was no heterogeneity across the two countries with respect to the main study findings. While the number of intracranial haemorrhage events was higher in the lower-target group than in the higher-target group, the 95% confidence interval suggested that the between-group difference was not significant.

However, the advent of highly efficacious LDL-C lowering non-statin therapies, including anti-PCSK9 (proprotein convertase subtilisin/kexin type 9 monoclonal antibody therapy, now means that it is possible to attain LDL-C levels well below 70 mg/dL. Cardiovascular outcomes studies with these agents have also demonstrated substantial reduction in the risk of ischaemic stroke, by 25% in patients with established cardiovascular disease (median LDL-C on evolocumab 30 mg/dL or 0.78 mmol/L),5 and 27% in those with acute coronary syndrome (mean on-treatment LDL-C 53 mg/dL or 1.37 mmol/L), against a background of intense statin therapy (± ezetimibe).6 Taking this evidence on board, the 2019 Joint European Society of Cardiology/European Atherosclerosis Society Dyslipidaemia Guidelines have recommended an LDL-C goal of <50 mg/dL (<1.4 mmol/L) for patients at very high risk of cardiovascular events.7 These new findings and recommendations make the case for a new study testing the efficacy and safety of a lower LDL-C target in patients with ischaemic stroke and TIA, although whether this is feasible either practically or ethically may be questioned.

Finally, while a lower LDL-C target, against a background of best evidence-based treatment, is better for clinical outcomes, it is also clear that these very high-risk patients continue to experience cardiovascular events. This scenario highlights the need for renewed efforts to address this persistently high residual cardiovascular risk, focusing on other targets. Of the possible candidates for lipid targets, remnant cholesterol may have potential, especially in the light of recent evidence linking a higher risk of ischaemic stroke with higher remnant cholesterol levels.8

Residual cardiovascular risk in very high-risk patients continues to be a key challenge for the clinical community.


1. Avan A, Digaleh H, Di Napoli M et al. Socioeconomic status and stroke incidence, prevalence, mortality, and worldwide burden: an ecological analysis from the Global Burden of Disease Study 2017. BMC Med 2019;17 (1):191.
2. Stone NJ, Robinson J, Lichtenstein AH et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014;129(25 Suppl 2):S1-45.
3. Kernan WN, Ovbiagele B, Black HR et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014;45:2160-236.
4. Amarenco P, Kim JS, Labreuche J et al. A comparison of two LDL cholesterol targets after ischemic stroke. N Engl J Med 2019; DOI: 10.1056/NEJMoa1910355.
5. Sabatine MS, Giugliano RP, Keech AC et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017;376:1713-22.
6. Schwartz GG, Steg PG, Szarek M et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med 2018;379:2097-107.
7. Mach F, Baigent C, Catapano AL et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2019. doi: 10.1093/eurheartj/ehz455. [Epub ahead of print]
8. Varbo A, Nordestgaard BG. Remnant cholesterol and risk of ischemic stroke in 112,512 individuals from the general population. Ann Neurol 2019;85:550-9.