Inflammation as a Target: hs-CRP Guidelines & Colchicine in Cardiac Health

By Dr. Steven Long, DO, MHA, CPT
 Beyond Health | Precision Medicine for High-Performance Living

For decades, cardiology focused almost exclusively on cholesterol and blood pressure. Lower LDL, lower systolic BP, reduce events. That strategy worked—statins, antihypertensives, and lifestyle changes cut cardiovascular mortality significantly. But in spite of optimized LDL and blood pressure control, a large portion of patients still suffer recurrent heart attacks and strokes.

What explains this residual cardiovascular risk? Increasingly, the answer is inflammation.

Two new developments—recent guidelines elevating high-sensitivity C-reactive protein (hs-CRP) and the FDA approval of colchicine for coronary artery disease—signal a major paradigm shift. Cardiologists are now recognizing inflammation not just as a risk marker, but as a therapeutic target.

This blog reviews the latest evidence, explains why hs-CRP matters, and explores how colchicine works at the cellular level to reduce vascular inflammation.

hs-CRP: From “Interesting” to Clinically Actionable

The Old View

For years, hs-CRP was considered intriguing but “optional.” Some clinicians measured it, others dismissed it. The skepticism was understandable—CRP is a nonspecific marker. It rises with infection, arthritis, obesity, or even after a hard workout. Could it really help guide cardiac care?

The New Consensus

The 2025 American College of Cardiology (ACC) Scientific Statement fundamentally re-framed hs-CRP. The panel concluded:

• Elevated hs-CRP consistently predicts recurrent cardiovascular events—even in statin-treated patients with optimal LDL cholesterol (Mensah et al., 2025).
• hs-CRP is at least as predictive as LDL for secondary events in patients with established coronary artery disease.
• Chronic inflammation is not incidental—it is causal in atherosclerosis progression and plaque destabilization.

Other groups, including the European Society of Cardiology, have made similar moves. The position is shifting from “hs-CRP is exploratory” to “hs-CRP is clinically relevant.”

How to Use It

• Primary prevention: In intermediate-risk patients, hs-CRP can clarify risk category and support statin initiation.
• Secondary prevention: In patients with known CAD, hs-CRP identifies residual inflammatory risk—helping stratify who might benefit from anti-inflammatory strategies.
• Universal screening? Some experts now advocate routine hs-CRP measurement in all CAD patients, much like LDL, though consensus is not yet universal.

Interpretation

• <1 mg/L → Low residual risk
• 1–3 mg/L → Moderate
• 3 mg/L → High

Values must be repeated if elevated, and interpreted in context (exclude acute infection).

Why Inflammation Matters in Atherosclerosis

The traditional “lipid hypothesis” describes cholesterol buildup in the arterial wall, but lipids alone don’t explain why some plaques rupture while others remain stable. Inflammation fills that gap.

• Endothelial dysfunction: Inflammatory cytokines impair nitric oxide signaling, reducing vascular reactivity.
• Foam cell formation: Macrophages engulf LDL particles, becoming foam cells that perpetuate inflammation.
• Plaque instability: Inflammatory enzymes (MMPs) degrade the fibrous cap of plaques, making them prone to rupture.
• Thrombosis: Plaque rupture releases tissue factor, activating clotting cascades and triggering acute coronary syndromes.

In short: cholesterol initiates, inflammation accelerates and destabilizes. That’s why controlling lipids alone is not enough.

Colchicine: Old Drug, New Target

Mechanism of Action

Colchicine is best known as a gout medication, but its cellular effects map directly onto the inflammatory pathways that drive atherosclerosis.

1. Microtubule disruption
2. Colchicine binds tubulin, preventing microtubule polymerization.
3. This inhibits neutrophil adhesion, migration, and activation at vascular injury sites.
4. NLRP3 inflammasome inhibition
5. The NLRP3 inflammasome activates caspase-1, leading to IL-1β and IL-18 release.
6. These cytokines amplify vascular inflammation and stimulate hepatic CRP production.
7. Colchicine suppresses NLRP3 activation, lowering IL-1β and IL-6 signaling (Alunno et al., 2024).
8. Reduced endothelial adhesion molecule expression
9. Less neutrophil infiltration into plaques.
10. Plaque stabilization
11. Lower inflammation means fewer cap-degrading enzymes, thicker fibrous caps, and more stable plaques.

Clinical Evidence

• LoDoCo2 (2020): In stable CAD patients, colchicine 0.5 mg daily reduced composite cardiovascular events by 31% (Nidorf et al., 2020).
• COLCOT (2019): In post-MI patients, colchicine lowered rates of stroke, MI, and urgent revascularization (Tardif et al., 2019).
• Meta-analyses: Confirm consistent reduction in MACE, independent of LDL lowering, with relatively low rates of serious adverse events (Nelson et al., 2023).

FDA Approval

In 2023, colchicine (0.5 mg/day) was FDA-approved for reducing risk of cardiovascular events in adults with established ASCVD or multiple risk factors (UIC Drug Information Group, 2024).

Risks and Practical Considerations

• GI upset (diarrhea, nausea) in ~10%, usually transient (ACC, 2024).
• Drug interactions: With CYP3A4 or P-gp inhibitors (e.g. clarithromycin, cyclosporine).
• Renal/hepatic impairment: Increased risk of myopathy and toxicity.
• Statin co-use: Low-dose colchicine is generally safe but monitor for muscle symptoms.
• Long-term safety: Large follow-ups show no increase in infections or cancer when used in properly selected patients (Nidorf et al., 2024).

Beyond Health’s Perspective

At Beyond Health, we view hs-CRP and colchicine as part of a broader precision cardiometabolic approach:

1. Stratify risk: We measure hs-CRP in stable patients with known CAD or intermediate risk. Persistent hs-CRP >2 mg/L indicates elevated inflammatory burden.
2. Lifestyle first: Nutrition (Mediterranean/omega-3 rich), resistance + Zone 2 training, sleep, and stress management reduce inflammation upstream.
3. Targeted pharmacology: In select patients with high residual inflammatory risk, colchicine offers a powerful adjunct to statins, antiplatelets, and blood pressure control.
4. Continuous monitoring: Re-check hs-CRP, monitor side effects, and individualize therapy. Inflammation is dynamic—management should be too.

Summary

• hs-CRP has evolved from an “optional add-on” to a validated marker of residual cardiovascular risk.
• Colchicine has emerged as the first FDA-approved anti-inflammatory drug for secondary prevention in coronary artery disease.
• Mechanistically, colchicine stabilizes plaques and reduces cytokine-driven vascular inflammation.
• At Beyond Health, we combine hs-CRP monitoring, lifestyle interventions, and selective use of colchicine to address both lipids and inflammation—two sides of the same disease process.

The next frontier in cardiology is clear: treat cholesterol, control blood pressure, optimize metabolism—and don’t ignore inflammation.

References

1. Mensah, G. A., et al. (2025). Inflammation and Cardiovascular Disease: 2025 ACC Scientific Statement. J Am Coll Cardiol, 86(10), 1205–1222.
2. Hartley, L., et al. (2025). Baseline hs-CRP and cardiovascular events in stable patients. eBioMedicine, 110, 105428.
3. Mehta, A., et al. (2025). High-sensitivity CRP in atherosclerotic cardiovascular disease: measure or not? USC Journal of Cardiology, 31(2), 145–153.
4. Alunno, A., et al. (2024). Colchicine and cardiovascular prevention. Eur J Intern Med, 111, 12–20.
5. Nidorf, S. M., et al. (2020). Colchicine in patients with chronic coronary disease. N Engl J Med, 383, 1838–1847.
6. Tardif, J. C., et al. (2019). Colchicine after myocardial infarction. N Engl J Med, 381, 2497–2505.
7. Nelson, K., et al. (2023). Low-dose colchicine for secondary prevention of coronary disease. J Am Coll Cardiol, 81(15), 1440–1451.
8. UIC Drug Information Group. (2024). What is the role of colchicine in reducing the risk of cardiovascular events? University of Illinois at Chicago.
9. American College of Cardiology. (2024). Low-dose colchicine for ASCVD: Ten points to remember. ACC.org.
10. Nidorf, S. M., et al. (2024). Long-term safety of low-dose colchicine. Eur Heart J, 45(18), 1596–1606.