For several years now I’ve been screening many of my patients for inflammation with their annual physical examination using blood test known as high sensitivity c-reactive protein or hsCRP. HsCRP is an inflammatory marker that has proven useful as a marker for cardiovascular risk in some individuals. Inflammation occurs when there is tissue damage. In general, ongoing inflammation is not good for one’s health. In the case of arthritis, inflammation affects bones and joints. In the case of infection, inflammation results when the immune system responds to a pathogen. In the case of cancer, inflammation occurs as cancerous cells invade healthy tissues and cause damage. More recently, inflammation has been identified as an important factor in atherosclerosis, the process that leads to cholesterol plaque accumulation in blood vessels resulting in heart attack, stroke, and peripheral vascular disease.
Moderate risk hsCRP 1-3 mg/L
CRP is an acute phase reactant, so its level may go up with infection or trauma. However, in general, hsCRP levels tend to be relatively stable over time, compared with other inflammatory markers. Multiple studies have demonstrated the relationship between hsCRP elevation and cardiovascular disease. In fact, with respect to cardiovascular risk, hsCRP is said to be more predictive of cardiovascular events than LDL cholesterol levels. Three levels of risk have been identified:Low risk hsCRP < 1 mg/L
Moderate risk hsCRP 1-3 mg/L
High risk hsCRP >3 mg/LIn the Jupiter trial healthy men and women with normal LDL cholesterol (<130) but elevated hsCRP (>2 mg/L) were randomized to receive 20 mg of Rosuvastatin or placebo. The trial was halted early when the treatment group was found to have significantly lower risk of cardiovascular events in the 1.9 years that the subjects were studied. The reduction in risk correlated with a reduction in LDL cholesterol and hsCRP levels.
In my patient population it is my experience that about 25 percent of my patients have hsCRP levels that exceed the 3 mg/L threshold for “high risk.” About 5 to 10% of my screened patients have levels that substantially exceed 3mg/L. As a generalist, I have been tasked to take action with these particular patients, bringing them back in to the office for a thorough history to exclude occult infection, ordering additional tests to screen for occult rheumatologic disorders, and to make sure cancer prevention guidelines have been followed—and at times doing additional work-ups.
Elevated CRP has also been associated with diabetes and metabolic syndrome. One patient in her 50s had an hsCRP of 28. This patient also had new onset diabetes, with a hemoglobin A1C of 8.1, LDL cholesterol of 136, and BMI of 42. After losing 70 pounds (over one year) and with resolution of her diabetes my patient’s hsCRP came down to 3. A statin was started in addition to aspirin therapy. In this case the crp did not alter my practice, though it did raise my level of concern.
Another healthy patient in her forties had a level of 3.5 mg/L. The patient, who is vegan, had an LDL of 80, an HDL of 78, a normal glucose, does not smoke, and has a body mass index of 23. Framingham risk was calculated at less than 1 percent. My patient had astutely read of an association of between elevated CRP and Alzheimer’s Disease risk (which has been described). Unfortunately, there is no clear and proven intervention to reduce this patient’s potential health risk, which is still likely low. I placed her on aspirin 81 mg daily.
Within the realm of using hsCRP for the purpose of primary prevention medical knowledge is based primarily on cardiovascular trials and outcomes. According to one expert author CRP may be at least 50% genetically pre-determined. In the case of my healthy patient in her 40’s this seems likely. I was reassured to read a summary in Circulation noting that while a relationship between high crp and cardiovascular death has been demonstrated, elevated hsCRP has not been linked to increased mortality from other causes (like cancer). At least this finding will allow me to focus on cardiovascular health when hsCRP is high, as opposed to engaging in a wild goose chase to detect occult illness.
HsCRP measurement is currently recommended only in individuals who are at intermediate risk for cardiovascular disease (defined as 10 to 20 percent chance of having a cardiovascular event in ten years). In this population it can prompt more aggressive management of risk factors, including beginning a statin for only marginally elevated cholesterol. One review in the Annals of Internal Medicine noted that while high hsCRP levels in women with intermediate or high Framingham risk correlated with worse cardiovascular outcomes, high levels in women deemed to be at low risk by Framingham did not correlate with substantially high vascular risk. Despite this finding, at times I have still found it helpful to check hsCRP within a low risk population. The test is inexpensive, it can help as a motivator to prompt lifestyle change that could prevent future increased risk, and 20 percent of heart disease may occur in those with no traditional risk factors. As a novel risk factor hsCRP has become one of many variables known to contribute to cardiovascular health. However, as an isolated finding it still may have limited utility, raising questions that at this time still have no clear cut answers.