The Role of Chronic Inflammation in Cardiovascular Disease

The development of atherosclerosis, or hardening of the arteries, is a process that begins early in life and can culminate decades later in clinical events such as heart attack, coronary artery revascularization (stents and bypass surgery) and stroke. Much basic science and clinical work has been done to understand this process in an effort to identify clinical interventions that can prevent or slow this systemic process.

More than a century ago, early investigators identified both inflammatory cells (part of the immune system) and fatty cholesterol deposits in the inner lining of arteries with established atherosclerotic disease. In terms of these two pathological pathways, our early efforts in atherosclerotic cardiovascular disease prevention focused primarily on reducing the accumulation of lipids in the arterial wall through interventions that lower LDL (bad) cholesterol (dietary change or medication use). 

Since those initial observations, numerous scientific studies led to the notion that atherosclerosis develops following an injury to or dysfunction of the lining of the arterial wall (called the endothelium) that stimulates the immune system causing an inflammatory response to promote repair of the injured artery wall lining. In 1999, a pathologist named Russell Ross published a landmark paper that formally characterized atherosclerosis as an inflammatory disease which starts with endothelial dysfunction that then leads to various degrees of inflammatory response (N Engl J Med. 1999; 340:115–126). Causes of endothelial dysfunction include high levels of LDL cholesterol, cigarette smoking, hypertension and diabetes which later also became clinical targets for primary and secondary prevention of atherosclerotic cardiovascular disease.

In 2002, experts in the field of atherosclerosis convened to discuss markers of inflammation that could be measured during a routine clinical examination to identify individuals at high risk for developing heart disease or stroke (Circulation. 2003;107:499-511.). These blood test markers included high-sensitivity C-reactive protein (hs-CRP), white blood cell (CBC) count and fibrinogen (a precursor to fibrin, the main structural protein of blood clots, that also is an acute phase reactant that can increase dramatically during bouts of inflammation or infection).

Ultimately, hsCRP was identified as a risk marker that could be routinely measured in the blood and was independently associated with the development of cardiovascular events, joining the list of cardiovascular disease risk factors such as cholesterol, smoking, body mass index, diabetes, hypertension, exercise level and family history of premature heart disease. Kenneth H. Cooper, MD, MPH, Founder and Chairman of Cooper Aerobics shares “more than 20 years ago, measuring hsCRP became part of the annual examination at Cooper Clinic in 2004.”

With the use of the hsCRP blood test, researchers were able to quantitatively identify the relationship between inflammation and the risk of experiencing a cardiovascular disease event. In general, levels of hsCRP <1, 1 to 3, and >3 mg/L connote lower, moderate and higher relative cardiovascular risk, respectively, when interpreted in the context of other traditional cardiovascular risk factors. Importantly, hsCRP levels ≥ 2.0 mg/dL (associated with moderate cardiovascular risk) may be present in as any many of 50% of U.S. adults (Journal of the American College of Cardiology Volume 54, Issue 25,  2009, Pages 2388-2395).

Based on this wealth of clinical data, the role of chronic inflammation has now taken center stage in the settings of both primary and secondary prevention of atherosclerotic cardiovascular disease. In 2025, the American College of Cardiology released a scientific statement summarizing these clinical advances and provided a table of consensus recommendations. For individuals without a history of cardiovascular disease (primary prevention group), these experts recommend at least one measurement of hsCRP to assess cardiovascular risk. If it is high, the importance of a healthy diet, regular exercise, cigarette cessation and obtaining/maintaining a healthy weight (all of which have been shown to reduce hsCRP) cannot be over-emphasized. Anti-inflammatory dietary patterns include the Mediterranean diet and the DASH diet. Recommendations for regular physical activity are at least 150 minutes per week of moderate intensity exercise or 75 minutes per week of high intensity exercise. Consideration also ought to be given to treating high LDL cholesterol with statin medication in the setting of a high hsCRP.

For individuals who have already been diagnosed with cardiovascular disease, the presence of an elevated hsCRP may impact treatment recommendations regarding LDL treatment targets (lower in the setting of inflammation). Some clinical trial data suggest the use of other therapies (such as low dose colchicine) specifically focused on reducing inflammation may also be associated with risk reduction in patients with established heart disease.  

The scientific story regarding the link between inflammation and atherosclerotic cardiovascular disease is far from complete. Many evidence gaps remain. Many questions remain to be answered through scientific research including interactions among inflammation, genetics and environmental factors as well as improved health habits and drug prescriptions for cardiovascular disease prevention.

Cooper Clinic’s annual preventive exam includes hsCRP testing as part of the standard blood work. To learn more about Cooper Clinic preventive exams and how an annual exam can help you manage and improve your health, visit cooper-clinic.com or call 866.906.2667.

Article provided by Kenneth H. Cooper, MD, MPH, Founder and Chairman of Cooper Aerobics, and Nina B. Radford, MD, FACC, Cardiologist at Cooper Clinic.