Inflammation: The Central Force in Cardiovascular Disease—and What To Do About It

For much of the past century, cardiovascular disease (CVD) prevention has rested on the pillars of cholesterol, blood pressure, and lifestyle management. But what if a major risk—and opportunity—has been hiding in plain sight? The latest 2025 Scientific Statement from the American College of Cardiology (ACC) sets out a compelling case for chronic, low-grade inflammation as the missing link in heart disease prevention, diagnosis, and care(1). This article explains what the evidence shows, how it fits with clinical decision-making, and why men seeking optimal cardiovascular health should insist on comprehensive evaluation.

The Missing Layer: Residual Inflammatory Risk

Routine bloodwork tells only half the story. Even after optimizing cholesterol and blood pressure, many people are left with what experts call “residual inflammatory risk”: ongoing, silent inflammation in the arterial walls that drives the formation and instability of plaque, and determines whether a cardiac event will strike without warning. This process can be tracked with high-sensitivity C-reactive protein (hsCRP), a biomarker that is now as well-established as LDL cholesterol for forecasting future heart attacks and strokes.

The 2025 ACC Statement reviews decades of data and new clinical trials, showing that chronic inflammation is no longer a marginal theory but a clinical reality. Elevated hsCRP is defined by most labs as 2 mg/L or above, confers increased risk even when cholesterol is considered “normal.” One large cohort study of nearly 28,000 healthy women found a wider spread of future CVD risk predicted by hsCRP than by LDL cholesterol, confirming the value of testing both.

Landmark Clinical Trials: Shifting from Cholesterol Alone

Research has shown that targeting chronic inflammation lowers cardiovascular risk—sometimes independently of cholesterol. Randomized clinical trials like JUPITER, CANTOS, and COLCOT have demonstrated that:

• Statin therapy reduces both LDL and hsCRP, cutting first-time event risk even in people with normal cholesterol if hsCRP is high.

• Colchicine—a low-cost, longtime gout medication—reduces recurrent events in people with established heart disease by 25% when used alongside standard therapy. It is now FDA-approved for this specific purpose.

• Canakinumab, an IL-1β inhibitor, reduced vascular events in CANTOS in patients with prior MI and persistent inflammation, but due to cost and risk of infection, it is not clinically available for CVD prevention.

By contrast, not every anti-inflammatory agent found benefit. For example, low-dose methotrexate did not reduce events, reminding clinicians that only therapies shown to impact IL-6 and hsCRP, the critical inflammatory mediators, yield substantial gains.

Clinical Practice: Time to Update the Standard of Care

The updated recommendations are clear: routine screening of hsCRP—along with cholesterol and blood pressure—should be standard in both primary and secondary prevention(1). The logic is simple: you cannot treat what you do not measure. For those at increased inflammatory risk (hsCRP above 2 or 3 mg/L on repeat testing and not explained by acute illness), intervention is warranted. The ACC statement lays out the approach:

1. Lifestyle First, Targeted Where It Matters

Anti-inflammatory diets (such as Mediterranean and DASH), regular physical activity, sustained weight management, and quitting smoking are all supported by strong evidence. The PREDIMED trial, involving 7,447 participants, found a Mediterranean diet supplemented with olive oil or nuts substantially reduced cardiovascular events,results likely mediated by reduced systemic inflammation. Higher levels of omega-3 fatty acids, especially from fatty fish, as well as plant-based foods, nuts, and legumes, repeatedly show lower rates of CVD. Conversely, diets rich in red/processed meats, refined carbohydrates, and sugary beverages drive inflammation up. The author also believes that the Greeks are greek orthodox and as such fast often, which may contribute to their lower inflammation levels.

2. Pharmacologic Options Informed by Inflammatory Risk

• Statins: Useful even in those with “healthy” cholesterol if hsCRP remains high. Take regular vitamin K tests if on warfarin and other statins.

• Colchicine (0.5 mg daily): Now clinically proven for reducing risk in people with stable coronary disease, but should be avoided in those with significant liver or kidney disease or when taking certain antibiotic or antifungal medications.

• Novel Agents: Ongoing trials are studying IL-6 inhibitors and specialized pro-resolving lipid mediators, but current therapy should focus on agents with evidence of outcome benefit.

3. Imaging: Useful, but Not (Yet) in Routine Practice

Cutting-edge imaging can detect vascular inflammation directly (via advances in coronary CT and perivascular fat phenotyping), but these are not yet standard tools. The strongest noninvasive test widely available remains hsCRP, combined with risk stratification.

Special Considerations: Who Is Most at Risk?

The prevalence of heightened inflammatory risk is significant—30-50% of adults may have elevated hsCRP, with spikes in the overweight, smokers, and those living sedentary lifestyles. CVD events are on the rise among those lacking traditional risk factors—what’s now labeled “SMuRF-less but inflamed.” This means that many with normal blood sugar, healthy cholesterol, and no hypertension are still at high risk because of unchecked inflammation.

Implementation research highlights the need to encourage regular hsCRP testing in routine care, especially for men over 40 and anyone with a family history of premature CVD. Direct-to-consumer interest, as well as clinic-initiated comprehensive panels, help address this key gap.

Inflammation Beyond the Heart: Heart Failure, Pericarditis, and Beyond

The role of inflammation does not end with heart attacks. Chronic inflammatory pathways affect heart failure, with recent trials exploring both diet (omega-3 supplementation) and targeted immunomodulators. Recurrent pericarditis—a stubborn, often painful inflammation of the sac around the heart—can now be treated with IL-1 blockers in resistant cases, though these remain reserved for particular scenarios.

Looking Forward: Future Therapies and Evidence Gaps

New research is exploring how genetics (notably clonal hematopoiesis), the gut microbiome, and social factors drive inflammation and CVD risk. Multi-marker strategies that combine new proteins and imaging modalities with classical risk factors may help individualize prevention. But universal hsCRP screening and thorough behavioral intervention are changes that can be—and ought to be—adopted now.

What Does This Mean for Men Focused on Long-Term Health?

For men seeking to move beyond the basics, The Mas Clinic’s approach tracks closely with the new ACC guidance. Assessing and addressing inflammation is fundamental. Rather than wait for symptoms or rely solely on traditional risk factors, patients at The Mas Clinic can expect:

• Routine measurement of hsCRP and cholesterol.

• Detailed dietary, exercise, and risk stratification discussion.

• Medication where benefits (statin, colchicine) are likely to outweigh risks.

• Clear attention to evidence-based lifestyle change, with individual coaching.

Putting Prevention Into Practice

Managing chronic, low-grade inflammation is critical for preventing CVD, especially for men wanting to add healthy, active years to their lives. Action starts with measurement—and continues with a comprehensive, personalized plan. While research continues on novel therapies and molecular mechanisms, the opportunity to safeguard cardiovascular health is available today for those who embrace a comprehensive approach.

References

1. Mensah GA, Arnold N, Prabhu SD, Ridker PM, Welty FK. Inflammation and cardiovascular disease: 2025 ACC scientific statement.