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Nov 2021
New ACC guidance addresses unmet clinical needs for high-risk patients with mild to moderate hypertriglyceridemia
Sep 2021
Residual vascular risk: What matters?
Aug 2021
Understanding vein graft failure: a role for PPARalpha in pathobiology
May 2021
Residual cardiovascular risk: how to identify?
Apr 2021
Metabolic syndrome and COVID-19
Mar 2021
Elevated triglyceride: linking ASCVD and dementia
Feb 2021
Does SPPARMα offer new opportunities in metabolic syndrome and NAFLD?
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
Dec 2019
Focus on stroke: more input to address residual cardiovascular risk
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

21 February 2022
Looking back at 2021 – what made the news?
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 2021 was an exciting time in the lipid field, especially with increased recognition of the importance of triglyceride (TG)-rich lipoproteins and their remnants to atherosclerotic cardiovascular disease (ASCVD) risk. Renewed thinking about the contribution of these lipoproteins to residual cardiovascular risk catalysed new expert consensus and clinical guidance 1,2. These provided pragmatic criteria for hypertriglyceridemia and focused on how best to manage elevated TG in the clinic, highly relevant with the ongoing development of novel therapies targeting different proteins involved in the regulation of TG metabolism. In addition, results from the PESA (Progression of Early Subclinical Atherosclerosis) study prompted reconsideration of the level at which TG should be targeted for therapeutic intervention, given that at TG levels of 100-149 mg/dL there was already evidence of subclinical atherosclerosis in a low-risk cohort with ‘normal’ LDL-C levels, according to guideline-recommended goals 3.

Remnant cholesterol was very much a ‘rising star’ in recent research. From the PREDIMED study, an observational dietary intervention trial in people without ASCVD, we learnt that remnant cholesterol levels were associated with cardiovascular outcomes independent of other risk factors, whereas this was not the case for LDL-C 4. Added to this, a pooled analysis of over 17,000 individuals without cardiovascular disease showed that levels of remnant cholesterol associated with incident ASCVD independent of traditional cardiovascular risk factors, including LDL-C, non-high-density lipoprotein cholesterol or apolipoprotein B levels. Moreover, the excess risk due to elevated remnant cholesterol was apparent even at low LDL-C levels 5.

Importantly, the focus extended beyond ischemic heart disease. Elevated remnant cholesterol levels promoted atherosclerosis progression, assessed by carotid intima media thickness, by up to 2-fold among patients with ischemic stroke, when compared with those in the highest versus lowest quartiles 6. A study by Danish investigators also highlighted the association of remnant cholesterol with risk for peripheral artery disease (PAD) 7, for too long a neglected manifestation of ASCVD, but an increasingly important contributor to the global burden of cardiovascular disease 8,9. In this general population study, remnant cholesterol levels ≥1.5 mmol/L (≥58 mg/dL) were associated with about 5-fold higher risk for PAD events compared with lower levels 7.

From the clinical perspective, the question is how best to manage this risk. Of the available options, further analyses from REDUCE-IT have provided novel insights. High-dose icosapent ethyl reduced the residual risk of coronary revascularizations in statin-treated patients with hypertriglyceridemia (10). Preliminary reports also indicated that this treatment reduced the residual risk for ischemic stroke and PAD outcomes 11,12, highly relevant given the long-term socioeconomic burden that each of these cardiovascular complications poses for healthcare systems. Full publication of these two analyses is eagerly awaited.

2021 has also been an exciting year for the Residual Risk Reduction Initiative (R3i) Foundation as we build on our pillars of education, research, and advocacy. We continue to expand educational resources, free to download on the website. The latest resources include a booklet and accompanying slide set focused on ‘Triglyceride-rich lipoproteins and ASCVD’ [] which provide critical information on this rapidly evolving area. And on a final note, the R3i , together with the International Atherosclerosis Society, was the recipient of a key award from Cardiovascular Diabetology for the landmark Consensus Statement on Selective Peroxisome Proliferator‑Activated Receptor alpha Modulators (SPPARMα) [].

The R3i will continue to build on these strengths in 2022.

1. Ginsberg HN, Packard CJ, Chapman MJ, et al. Triglyceride-rich lipoproteins and their remnants: metabolic insights, role in atherosclerotic cardiovascular disease, and emerging therapeutic strategies-a consensus statement from the European Atherosclerosis Society. Eur Heart J 2021; 42:4791-806.
2. Virani SS, Morris PB, Agarwala A et al. 2021 ACC Expert Consensus Decision Pathway on the Management of ASCVD Risk Reduction in Patients with Persistent Hypertriglyceridemia. A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol 2021:78:960-93.
3. Raposeiras-Roubin S, Rosselló X, Oliva B et al. Triglycerides and residual atherosclerotic risk. J Am Coll Cardiol 2021;22: 3031-41.
4. Castañer O, Pintó X, Subirana I et al. Remnant cholesterol, not LDL cholesterol, is associated with incident cardiovascular disease. J Am Coll Cardiol 2020;76: 2712-24.
5. Quispe R, Martin S, Michos ED et al. Remnant cholesterol predicts cardiovascular disease beyond LDL and ApoB: a primary prevention study. Eur Heart J 2021;42:4324-32.
6. Qian S, You S, Sun Y, et al. Remnant cholesterol and common carotid artery intima-media thickness in patients with ischemic stroke. Circ Cardiovasc Imaging 2021;144:e010953.
7. Wadström BN, Wulff AB, Pedersen KM, et al. Elevated remnant cholesterol increases the risk of peripheral artery disease, myocardial infarction, and ischaemic stroke: a cohort-based study. Eur Heart J 2021;ehab705. doi: 10.1093/eurheartj/ehab705.
8. Song P, Rudan D, Zhu Y, et al. Global, regional, and national prevalence and risk factors for peripheral artery disease in 2015: an updated systematic review and analysis. Lancet Glob Health 2019;78:e1020-30.
9. Fowkes FGR, Aboyans V, Fowkes FJI. Peripheral artery disease: epidemiology and global perspectives. Nat Rev Cardiol 2016;14:156–70.
10. Peterson BE, Bhatt DL, Steg Ph.G, et al. Reduction in revascularization with icosapent ethyl: insights from REDUCE-IT REVASC. Circulation 2020; do 10.1161/CIRCULATIONAHA.120.050276.
11. Bhatt DL, Steg PG, Miller M, et al. Reduction in Ischemic Stroke With Icosapent Ethyl - Insights From REDUCE-IT. Stroke 2021; 52 (Suppl_1). INTERNATIONAL STROKE CONFERENCE 2021 ORAL ABSTRACTS.
12. Bhatt DL, et al. Benefits of icosapent ethyl in patients with prior peripheral artery disease: REDUCE-IT PAD. Rapid Fire Oral Session, American Heart Association Scientific Sessions 13-15 November 2021.