Inflammation in CVD

Examine the case against inflammation
Inflammation is a major, independent driver of CVD risk.1,2
Inflammation
Nearly 1 in 2 patients have a residual inflammatory risk, despite high-intensity lipid management.3
Patients
Inflammatory risk can be detected using the prognostic biomarker hsCRP (≥ 2 mg/L).1,3
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Inflamattion in CVD

Outcomes

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Does CV inflammation increase the risk of mortality?

The evidence is mounting: Inflammation is not only associated with increased CV risk and worse CV outcomes, it’s also a key suspect in CV death.1,2

Connecting the clues

Elevated levels of inflammation in CVD are associated with increased risk of CV death in patients with ASCVD and prior MI:

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2.5x increased risk of CV death
for patients with inflammation compared to those without, in individuals with or at high risk of ASCVD1*
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44% increase in the risk of CV death
in patients with prior MI and inflammation2†
Footnotes+
* A collaborative analysis of 31,245 statin-treated patients who had or were at high risk of atherosclerotic disease from across the PROMINENT (n = 9,988), REDUCE-IT (n = 8,179), and STRENGTH (n = 13,078) trials found that residual inflammatory risk was significantly associated with CV mortality (highest hsCRP quartile [> 4.2 to > 4.8 mg/L] versus lowest [< 1.1 to < 1.2 mg/L], adjusted HR 2.68, 95% CI [2.22, 3.23]; p < 0.0001).1

† Adjusted for age, sex, time since myocardial infarction, hemoglobin, eGFR, undertaken procedures, comorbidities and ongoing medications. Compared with hsCRP < 2 mg/L, patients with hsCRP ≥ 2 mg/L had a 1.44 (95% CI [1.29, 1.60]) higher risk of CV death.2

Inflammation leaves its fingerprints across many serious CV events

In patients with ASCVD

Inflammation can increase the risk of MACE, hospitalization for heart failure, and all-cause mortality:

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⬆30% risk of MACE
in patients with inflammation (hsCRP ≥ 2 mg/L) versus those without4*
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⬆24% risk of hospitalization for heart failure
in patients with inflammation (hsCRP ≥ 2 mg/L) versus those without4†
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⬆35% risk of all-cause mortality
in patients with inflammation (hsCRP ≥ 2 mg/L) versus those without4‡

In patients with prior MI

Inflammation can increase the risk of MACE and all-cause mortality:

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⬆28% risk of MACE
in patients with inflammation (hsCRP ≥ 2 mg/L) versus those without2¶
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⬆42% risk of all-cause mortality
in patients with inflammation (hsCRP ≥ 2 mg/L) versus those without2§
Footnotes+
* The adjusted relative rate of events in participants with hsCRP ≥ 2 mg/L (vs. hsCRP < 2 mg/L) was 30% higher for MACE (adjusted HR 1.30; 95% CI [1.27, 1.33]). Adjusted for age, sex, time since ASCVD, eGFR, albuminuria, comorbidities, undertaken procedures, and ongoing medications.4

† The adjusted relative rate of events in participants with hsCRP ≥ 2 mg/L (vs. hsCRP < 2 mg/L) was 24% higher for heart failure (HR 1.24; 95% CI [1.20, 1.30]). Adjusted for age, sex, time since ASCVD, eGFR, albuminuria, comorbidities, undertaken procedures, and ongoing medications.4

‡ The adjusted relative rate of events in participants with hsCRP ≥ 2 mg/L (vs. hsCRP < 2 mg/L) was 35% higher for all-cause mortality (HR 1.35; 95% CI [1.31, 1.39]). Adjusted for age, sex, time since ASCVD, eGFR, albuminuria, comorbidities, undertaken procedures, and ongoing medications.4

¶ Adjusted for age, sex, time since myocardial infarction, hemoglobin, eGFR, comorbidities, undertaken procedures, and ongoing medications. Compared with hsCRP < 2 mg/L, patients with hsCRP ≥ 2 mg/L had a 1.28 (95% CI [1.18, 1.38]) higher risk of MACEs.2

§ Adjusted for age, sex, time since myocardial infarction, hemoglobin, eGFR, comorbidities, undertaken procedures, and ongoing medications. Compared with hsCRP < 2 mg/L, patients with hsCRP ≥ 2 mg/L had a 1.42 (95% CI [1.31, 1.53]) higher risk of MACEs.2

The real-world evidence is clear

A real-world Swedish study of 17,464 MI patients uncovered more evidence supporting the case against inflammation. As well as demonstrating the prognostic significance of hsCRP levels, the study found that most patients with MI exhibited elevated hsCRP levels.2

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hsCRP Level and the Risk of Death or Recurrent Cardiovascular Events in Patients With Myocardial Infarction: a Healthcare‐Based Study

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The evidence is mounting and clear— inflammation is deadly.1,2,4

Prevalence

Prevalence

Does CV inflammation hide in plain sight?

Even with optimal therapy, the threat of a CV event still looms for many patients. It’s time to uncover the silent instigator of residual CV risk.3,4

Suspect at large: The dangers of inflammation in CVD

Despite optimal control of traditional risk factors, many patients with CVD remain at risk of experiencing life-threatening CV events.3,4

The deeper we dig, the clearer the pattern becomes. For instance, despite the routine use of lipid-lowering, blood pressure-lowering, and antithrombotic therapy, patients with ASCVD still face a substantial risk of experiencing recurrent CV events, with 30% experiencing a MACE over a decade.4

Inflammatory risk refers to the risk driven by CV inflammation even after traditional risk factors are well controlled. CV inflammation plays a central role in the pathophysiology of atherosclerosis and contributes independently to future CV events.3

Combined data across the PROVE-IT, IMPROVE-IT, and SPIRE-1/2 trials, which included patients with/at high risk of CVD

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~1 in 2 CVD patients have an inflammatory risk*

Despite high-intensity lipid management with statins and PCSK9i, 46% of patients have a residual inflammatory risk. hsCRP can help you distinguish between CVD patients with residual risk driven by traditional risk factors and those with risk driven by inflammation.3

Footnotes+
* As calculated by Ridker PM across the PROVE-IT (n = 4,162), IMPROVE-IT (n = 18,144), and SPIRE-1/SPIRE-2 trials (n = 9,738; trial data were combined for analysis due to design similarity); patients with CVD received high-intensity statins, high-intensity statins plus ezetimibe, or high-intensity statins plus PCSK9 inhibition, respectively. Of these patients, 33% had inflammatory risk alone (hsCRP ≥ 2 mg/L), whereas 13% had a mix of inflammatory and cholesterol risk (LDL-C ≥ 1.81 mmol/L [70 mg/dL]).3

Inflammation is a key instigator in the onset, progression, and manifestation of CVD5,6

In ASCVD, every step of atherogenesis, from the early development of endothelial cell dysfunction to plaque formation and progression to rupture is driven by inflammation.5

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ENDOTHELIAL CELL DYSFUNCTION
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PLAQUE FORMATION
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PLAQUE RUPTURE

Understanding Risk

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Is CV inflammation as dangerous as the other suspects?

In CVD, we often point the finger at two culprits: high blood pressure and cholesterol. But a new suspect has emerged—inflammation. Though overlooked and underestimated, inflammation could be just as big a predictor of heart disease.7*

It acts alone: Inflammation is an independent risk factor in CVD1†

In a combined analysis of three major multinational trials of 31,245 statin-treated patients with—or at high risk of—ASCVD, the risk of MACE, CV death, and all-cause death were significantly higher among those with inflammation than those without, irrespective of LDL- C levels.1†

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Further evidence for independence

The presence of inflammation (hsCRP ≥ 2 mg/L) predicted CV events independently of LDL-C in statin-treated patients with ASCVD and CKD in a substudy of the CANTOS trial.8‡§

View Abstract

These findings show that inflammation acts independently to increase CV risk and warrants the same clinical attention as traditional risk factors.1,3,9

The verdict is in

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When it comes to future heart health, the presence of inflammation is a red flag. A meta-analysis conducted by the Emerging Risk Factor Collaboration found inflammation to be as strong a predictor of heart disease as traditional risk factors in patients with CVD.7*
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Results from the CANTOS substudy also suggest that, in statin-treated patients with ASCVD and CKD, inflammation is as big a threat as cholesterol when it comes to risk of recurrent CV events.8¶
The verdict? Inflammation is just as strong a predictor of heart disease as usual suspects like cholesterol.1,3,9*
Footnotes+
* Adjusted for age, sex, smoking status, history of diabetes, BMI, log triglycerides and alcohol consumption (based on 91,990 participants from 31 studies with 5,373 CHD events). Adjusted RRs for coronary heart disease per 1-SD higher levels of each risk factor were 1.37 (95% CI [1.27, 1.48]) with CRP concentration, 1.28 [1.16, 1.40] with non-HDL-C concentration, and 1.35 [1.25, 1.45] with systolic blood pressure.7

† An analysis of 31,245 statin-treated patients across the PROMINENT (n = 9,988), REDUCE-IT (n = 8,179), and STRENGTH (n = 13,078) trials, which enrolled patients with or at high risk of ASCVD and moderately elevated triglycerides (2.26–5.65 mmol/L [200–500 mg/dL]). Risks of MACE, CV death, and all-cause death were significantly higher in those with hsCRP ≥ 2 mg/L than in those with hsCRP < 2 mg/L, irrespective of LDL-C strata (all p values ≤ 0.0001).1

‡ A CANTOS substudy evaluating the contributions of residual cholesterol risk (assessed via LDL-C and non-HDL-C) and residual inflammatory risk (assessed by hsCRP and IL-6) as determinants of MACE and total mortality in 9,151 stable statin-treated post-MI patients followed for up to 5 years (median 3.7 years). Results were stratified by baseline eGFR above or below 60 mL/min/1.73 m2 (all participants had eGFR > 30 mL/ min/1.73 m2).8

§ Among those with eGFR < 60 mL/min/1.73 m2 increasing quartiles of hsCRP significantly predicted recurrent MACE [HR comparing the top to bottom quartile for hsCRP 1.50 (p = 0.021)] whereas increasing quartiles of LDL-C did not [HR comparing the top to bottom quartile for LDL-C 1.04 (p = 0.80)].8

¶ Among 9,151 stable post-MI patients receiving statins in the CANTOS trial (medial follow-up 3.7 years), residual inflammatory and cholesterol risk were assessed by hsCRP/IL-6 and LDL-C/non-HDL-C, respectively. In those with eGFR < 60 mL/min/1.73m2, increasing quartiles of hsCRP significantly predicted recurrent MACE [HR comparing the top to bottom quartile for hsCRP 1.50 (p = 0.021)] whereas increasing quartiles of LDL-C did not [HR comparing the top to bottom quartile for LDL-C 1.04 (p = 0.80)].8

Screening

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Can we catch inflammation in the act?

Discover how hsCRP can expose the danger of inflammatory risk in CVD*

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Inflammation leaves a trail. Inflammatory risk can be detected using the prognostic biomarker hsCRP (≥ 2 mg/L).1,3

Footnotes+
* The adjusted relative rate of events in participants with hsCRP ≥ 2 mg/L (vs. hsCRP < 2 mg/L) was 30% higher for MACE (adjusted HR 1.30; 95% CI [1.27, 1.33]). Adjusted for age, sex, time since ASCVD, eGFR, albuminuria, comorbidities, undertaken procedures, and ongoing medications.4

† The adjusted relative rate of events in participants with hsCRP ≥ 2 mg/L (vs. hsCRP < 2 mg/L) was 24% higher for heart failure (HR 1.24; 95% CI [1.20, 1.30]). Adjusted for age, sex, time since ASCVD, eGFR, albuminuria, comorbidities, undertaken procedures, and ongoing medications.4

‡ The adjusted relative rate of events in participants with hsCRP ≥ 2 mg/L (vs. hsCRP < 2 mg/L) was 35% higher for all-cause mortality (HR 1.35; 95% CI [1.31, 1.39]). Adjusted for age, sex, time since ASCVD, eGFR, albuminuria, comorbidities, undertaken procedures, and ongoing medications.4
ACC SCIENTIFIC STATEMENT

Inflammation and Cardiovascular Disease: 2025 American College of Cardiology (ACC) Scientific Statement16

With the aim to inform clinicians about areas where scientific evidence is new and evolving or where sufficient data are more limited, this 2025 Scientific Statement concluded with a call to action on inflammation and CVD:

"The evidence linking chronic, low-grade inflammation to the initiation and progression of ASCVD is robust, and several seminal randomized controlled clinical trials demonstrate that targeting inflammation reduces cardiovascular risk independent of lipid lowering. We have thus entered an era when the evidence linking inflammation with ASCVD is no longer exploratory but is compelling and clinically actionable. Yet, clinicians will not treat what they do not measure. Therefore, the time has come for clinical practice guidelines to implement broad screening of primary and secondary prevention patients for hsCRP, in combination with LDL cholesterol, and to embrace anti-inflammatory interventions in patients with established ASCVD and evidence of residual inflammatory risk, regardless of LDL cholesterol level."
American College of Cardiology

Selected consensus recommendations

Evaluation and risk assessment biomarkers

  • Because clinicians will not treat what they do not measure, universal screening of hsCRP in both primary and secondary prevention patients, in combination with cholesterol, represents a major clinical opportunity and is therefore recommended.

Secondary prevention: hsCRP screening

  • Among individuals with known cardiovascular disease both treated and not treated with statins, hsCRP is at least as powerful a predictor of recurrent vascular events as that of LDL cholesterol, demonstrating the importance of “residual inflammatory risk” in contemporary practice.
  • Among individuals taking statin therapy, consideration should be given to increase dosage into the higher intensity range if hsCRP levels remain > 2 mg/L, irrespective of LDL cholesterol.
“The time for taking action has now arrived.”
— ACC Scientific Statement

For complete recommendations, including for hsCRP screening in primary prevention, please see the full publication.

View publication

The evidence is clear: hsCRP levels of ≥ 2 mg/L are associated with higher CV risk.4,7 Spot the danger early.

hsCRP ≥ 2 mg/L = decorative icon

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To manage CV risk effectively, you need the full picture. As inflammatory risk in CVD often hides in plain sight, an hsCRP test can bring it into clinical focus.3
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Measuring hsCRP to detect inflammatory risk is essential to identify CVD patients at high CV risk due to inflammation, enabling optimal CV risk management.3
hsCRP is your early warning system. Use the prognostic biomarker hsCRP to identify CVD patients that may require intensified care.3

Useful resources for healthcare professionals

CCS Dyslipidemia Guidelines and Resources
Visit
Inflammation and Cardiovascular Disease: 2025 ACC Scientific Statement: A Report of the American College of Cardiology
Visit
Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines
Visit
2024 ESC Guidelines for the management of chronic coronary syndromes
Visit

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References

  1. Ridker PM, et al. Inflammation and cholesterol as predictors of cardiovascular events among patients receiving statin therapy: a collaborative analysis of three randomised trials. Lancet. 2023;401(10384):1293-1301.
  2. Carrero JJ, et al. hsCRP Level and the Risk of Death or Recurrent Cardiovascular Events in Patients With Myocardial Infarction: a Healthcare-Based Study. J Am Heart Assoc. 2019;8(11):e012638.
  3. Ridker PM. Clinician's Guide to Reducing Inflammation to Reduce Atherothrombotic Risk: JACC Review Topic of the Week. J Am Coll Cardiol. 2018;72(25):3320-3331.
  4. Mazhar F, et al. Systemic inflammation and health outcomes in patients receiving treatment for atherosclerotic cardiovascular disease. Eur Heart J. 2024;45(44):4719-4730.
  5. Alfaddagh A, et al. Inflammation and cardiovascular disease: From mechanisms to therapeutics. Am J Prev Cardiol. 2020;4:100130.
  6. Henein MY, et al. The Role of Inflammation in Cardiovascular Disease. Int J Mol Sci. 2022;23(21):12906.
  7. Emerging Risk Factors Collaboration Group. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet. 2010;375(9709):132-140.
  8. Ridker PM, et al. Inflammation drives residual risk in chronic kidney disease: a CANTOS substudy. Eur Heart J. 2022;43(46):4832-4844.
  9. Zubiran R, et al. Recent Advances in Targeted Management of Inflammation In Atherosclerosis: A Narrative Review. Cardiol Ther. 2024;13(3):465-491.
  10. Pohanka M. Diagnoses Based on C-Reactive Protein Point-of-Care Tests. Biosensors (Basel). 2022;12(5).
  11. Buckley DI, et al. C-reactive protein as a risk factor for coronary heart disease: a systematic review and meta-analyses for the U.S. Preventive Services Task Force. Ann Intern Med. 2009;151(7):483-495.
  12. Ridker PM, et al. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med. 2002;347(20):1557-1565.
  13. Pearson GJ, et al. 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in Adults. Can J Cardiol. 2021;37(8):1129-1150.
  14. Vrints C, et al. 2024 ESC Guidelines for the management of chronic coronary syndromes. Eur Heart J. 2024;45(36):3415-3537.
  15. Grundy SM, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139(25):e1082-e1143.
  16. Mensah GA, et al. Inflammation and Cardiovascular Disease: 2025 ACC Scientific Statement: A Report of the American College of Cardiology. J Am Coll Cardiol. 2025;0(0).