Brian Mossop Brian Mossop

C-reactive Protein: The Good, The Bad, and The Ugly

When something’s wrong with the body, the innate immune system kicks into high gear, sending inflammatory molecules through the body, which help recruit macrophages – the cellular garbage collectors – to the scene. Recent publications show systemic inflammation goes hand-in-hand with cardiovascular disease (CVD) and atherosclerotic vessels. Researchers have been trying to pinpoint which inflammatory markers could potentially be used as biomarkers for CVD risk or progression. Current efforts have zeroed in on one marker in particular, the C-reactive protein, in the hopes of finding a way to assess a person’s risk for CVD both non-invasively and well before a cardiovascular event occurs. Preliminary evidence has shown that in the normal population, the higher the C-reactive protein level, the higher the risk for CVD. But what exactly is a normal population? These days, a full serving of heart disease often comes with a heaping side of Type II diabetes, rheumatoid arthritis, or chronic kidney disease, creating a so-called “co-morbidity” of chronic diseases. Not surprisingly, these secondary disease states also affect the levels of C-reactive protein in the blood. So when a patient has more than one chronic condition, how useful is measuring the C-reactive protein level in predicting CVD risk?

When something’s wrong with the body, the innate immune system kicks into high gear, sending inflammatory molecules through the body, which help recruit macrophages – the cellular garbage collectors – to the scene. Recent publications show systemic inflammation goes hand-in-hand with cardiovascular disease (CVD) and atherosclerotic vessels. Researchers have been trying to pinpoint which inflammatory markers could potentially be used as biomarkers for CVD risk or progression. Current efforts have zeroed in on one marker in particular, the C-reactive protein, in the hopes of finding a way to assess a person’s risk for CVD both non-invasively and well before a cardiovascular event occurs. Preliminary evidence has shown that in the normal population, the higher the C-reactive protein level, the higher the risk for CVD. But what exactly is a normal population? These days, a full serving of heart disease often comes with a heaping side of Type II diabetes, rheumatoid arthritis, or chronic kidney disease, creating a so-called “co-morbidity” of chronic diseases. Not surprisingly, these secondary disease states also affect the levels of C-reactive protein in the blood. So when a patient has more than one chronic condition, how useful is measuring the C-reactive protein level in predicting CVD risk?

A new study published this week in PLoS One by a group at Kings College, London, took a look at people with rheumatoid arthritis (RA), an inflammatory joint condition that also coincides with remarkably elevated C-reactive protein levels. According to the authors, along with swollen joints, sufferers of rheumatoid arthritis are also twice as likely to have a heart attack.

The researchers looked at three subclinical measures of CVD: flow mediated dilation (measures endothelial cell function), intima-medial thickness (measures arterial wall thickness), and pulse wave velocity (measures large artery stiffness), in people with RA and healthy control subjects. The RA group was further subdivided into three tiers according to how much C-reactive protein was circulating in the patient’s blood during a baseline reading.

If C-reactive protein was in fact causing CVD in rheumatoid arthritis patients, the subclinical CVD measures should incrementally change as the level of C-reactive protein increases. However, the researchers found that two of the subclinical measures didn’t change at all as the level of C-reactive protein increased in those with rheumatoid arthritis. The third subclinical measure – the flow mediated dilation value, which measures how responsive endothelial cells are – actually improved as C-reactive protein levels rose, suggesting that the protein may offer a protective function in a chronic state of inflammation.

I’m always scouring scientific papers looking for the next great thing in biomarkers. After all, if a simple blood test can tell us who’s at risk for certain diseases, we could make great strides in diagnosis and treatment of affected people. But I think this paper shows that biomarker readings are not so straightforward. In the complicated web of chronic disease we’re now spinning, we need to better understand how cardiovascular disease biomarkers – particularly inflammatory markers -- change when people have more than one chronic medical condition.

http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010242#pone-0010242-t001

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Brian Mossop Brian Mossop

New Biomarkers for Diabetes

Obesity (determined by BMI) and blood glucose levels are by far the best predictors of whether a person will develop diabetes. Yet doctors are always on high alert for new biomarkers that may be more sensitive indicators of which patients will develop diabetes in the near future. The idea of using biomarkers to predict diabetes is not entirely new. Glycated hemoglobin (HbA1C) values are now routinely being monitored to screen for at-risk patients. However, a new study in PLoS One shows that several new biomarkers in the blood may further our understanding of exactly who’s at risk for diabetes, and increase our knowledge of the etiology of the disease.

Obesity (determined by BMI) and blood glucose levels are by far the best predictors of whether a person will develop diabetes. Yet doctors are always on high alert for new biomarkers that may be more sensitive indicators of which patients will develop diabetes in the near future. The idea of using biomarkers to predict diabetes is not entirely new. Glycated hemoglobin (HbA1C) values are now routinely being monitored to screen for at-risk patients. However, a new study in PLoS One shows that several new biomarkers in the blood may further our understanding of exactly who’s at risk for diabetes, and increase our knowledge of the etiology of the disease.

Veikko Salomaa and colleagues from the Department of Chronic Disease Prevention at the National Institute for Health and Welfare in Helsinki, Finland, tested nearly 13,000 people and found almost 600 cases of diabetes during routine follow-up exams.

According to the study, low levels of adiponectin, and high levels of apoB, C-reactive protein (CRP), and insulin, increase the chance that a woman will develop diabetes. When these factors were measured, proper diabetes prediction increased by 14% compared to when doctors only use classic risk factors, such as BMI and blood glucose levels, to predict disease.

The biomarkers that best predicted diabetes in men were low adiponectin, and high levels of CRP, interleukin-1 receptor antagonist, and ferritin. Accounting for these biomarkers led to a 25% increase in correct diabetes detection in the cohort.

read the study here.

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