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Mar 2024
The microvascular-macrovascular interplay: the next target?
Jan 2024
Targeting residual cardiovascular risk: what’s in the pipeline?
Sep 2023
Remnant cholesterol – evolving evidence
Jul 2023
Call to action on residual stroke risk
Apr 2023
Residual risk in 2023: where to?
Dec 2022
Lipid-related residual risk: lessons from PROMINENT?
Sep 2022
Residual cardiovascular risk: is apolipoprotein B the preferred marker?
Jul 2022
Residual vascular risk in chronic kidney disease: new options on the horizon
Feb 2022
Looking back at 2021 – what made the news?
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

20 May 2024
Reducing residual risk: lower cholesterol and inflammation is better
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

Within the lipid focus, there has been considerable effort to address non-LDL-lipids implicated in this risk. Following disappointment with HDL-targeted therapies, attention was re-directed to elevated triglycerides (TG, a marker for TG-rich lipoproteins and their remnants) as a potential therapeutic target 4. A growing body of evidence from epidemiologic and genetic studies supported this approach 5. Results from recent outcomes studies have, however, been less conclusive, engendering much debate. Perhaps the key take home message from these trials is that unlike LDL, the regulation of TG levels is complex. Novel TG-lowering approaches may offer new insights into this conundrum.

Beyond lipids, attention has increasingly focused on inflammation. Residual inflammatory risk may affect patient outcome by adversely impacting local inflammatory processes after a myocardial infarction, and inflammatory activity influencing atherosclerotic plaque progression 6. Large-scale clinical trials have added to our understanding of the role of inflammation in residual cardiovascular risk. Both CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study) with canakinumab (interleukin-1β inhibition) 7, and COLCOT (Colchicine Cardiovascular Outcomes Trial) and LoDoCo2 (Low Dose Colchicine 2) with colchicine 8, showed that suppressing inflammation, as measured by high-sensitivity C-reactive protein (hsCRP), can improve cardiovascular outcomes among high-risk patients with well-managed LDL-C levels.

As inflammation and hyperlipidaemia act synergistically to drive atherosclerotic progression 9, it is anticipated that targeting both of these residual risk components would yield additional benefit. Indeed, that is the conclusion of the report featured in this month’s Focus. In a previous analysis, the investigators showed the value of hsCRP as a predictor of cardiovascular risk in an analysis of more than 30,000 patients with atherosclerosis who received guideline-directed medical care, including statin therapy (10). In a follow-up study, the relative effect of inflammation and hyperlipidaemia as predictors of cardiovascular risk was investigated using the CLEAR-Outcomes trial (Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen Outcomes Trial) database in over 13,000 patients with statin-intolerance 11. The key finding was that inflammation detected by hsCRP was at least as strong a predictor of cardiovascular events as hyperlipidaemia (detected as either LDL-C or non-HDL-C). Thus, not only is "lower is better" the maxim for LDL-C, but also for hsCRP.

Cumulative insights from recent trials underline the multifactorial nature of residual cardiovascular risk. Targeting inflammation alongside optimal lipid lowering is likely to be central to future therapeutic strategies to reduce residual cardiovascular risk.

1. GBD 2017 DALYs and HALE Collaborators. Global, regional, and national disability-adjusted life-years (DALYs) for 359 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018;392:1859–922.
2. Timmis A, Vardas P, Townsend N, et al. European Society of Cardiology: cardiovascular disease statistics 2021. Eur Heart J 2022;43:716-99.
3. Visseren FLJ, Mach F, Smulders YM, et al. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J 2021;42:3227-337.
4. Libby P. Triglycerides on the rise: should we swap seats on the seesaw? Eur Heart J 2015;36:774-6.
5. Nordestgaard BG. Triglyceride-rich lipoproteins and atherosclerotic cardiovascular disease: new insights from epidemiology, genetics, and biology. Circ Res 2016;118:547-63.
6. Matter MA, Paneni F, Libby P, et al. Inflammation in acute myocardial infarction: the good, the bad and the ugly. Eur Heart J 2024;45:89–103.
7. Ridker PM, Everett BM, Thuren T, et al; CANTOS Trial Group. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med 2017;377:1119–1131.
8. Tardif JC, Kouz S, Waters DD, et al. Efficacy and safety of low-dose colchicine after myocardial infarction. N Engl J Med 2019;381:2497–505.
9. Ridker PM. Targeting residual inflammatory risk: The next frontier for atherosclerosis treatment and prevention. Vascul Pharmacol 2023:153:107238.
10. Ridker PM, Bhatt DL, Pradhan AD, et al. Inflammation and cholesterol as predictors of cardiovascular events among patients receiving statin therapy: a collaborative analysis of three randomized trials. Lancet 2023;401:1293–301.
11. Ridker PM, Lei L, Louie MJ, et al. Inflammation and cholesterol as predictors of cardiovascular events among 13970 contemporary high-risk patients with statin intolerance. Circulation 2024;149:28–35.