CDC/AHA Workshop on Markers of Inflammation and Cardiovascular Disease

Abstract

1. Of the inflammatory markers identified, C-reactive protein (CRP) has the analyte and assay characteristics that are the most conducive for use in practice. 2. To obtain a CRP concentration in metabolically stable patients, 2 measurements, fasting or nonfasting, should be made (optimally 2 weeks apart) and the results averaged. If the CRP level is Ͼ10 mg/L, then the test should be repeated and the patient examined for sources of infection or inflammation. 3. CRP results should be expressed only as milligrams per liter and expressed to 1 decimal point. 4. Risk assessment should be modeled after the lipids approach via 3 risk categories: low risk, average risk, and high risk. On the basis of the CRP population distributions, the following tertiles are recommended for categorizing patients: low risk, Ͻ1.0 mg/L; average risk, 1.0 to 3.0 mg/L; and high risk, Ͼ3.0 mg/L. It should be recognized that other acute inflammatory conditions may result in mildly to moderately increased CRP levels, such as inflammatory bowel disease, 2 rheumatoid arthritis, 3 and long-term alcoholism. 4 5. Performance goals for CRP measurement, similar to those developed for total cholesterol, HDL and LDL cholesterol, and triglycerides, need to be developed with a view toward better characterization of the total allowable error required to measure CRP reliably. DiscussionThe Laboratory Science Discussion Group was charged with reviewing the available analytical data on inflammatory markers and recommending those, if any, that were ready to move from the research setting into the routine clinical laboratory. The markers were divided into 3 groups of molecules: cytokines and chemokines, soluble adhesion molecules, and acute-phase reactants. The laboratory group primarily focused on the availability of commercial assays, their limitations and strengths, ability to standardize assay results, assay performance, and how results should be interpreted for assessing the risk of future CVD. As our knowledge of the atherosclerotic process has improved in recent years, evidence suggests that after initiation, inflammation plays a significant role in the development of this disease. A variety of markers associated with inflamThis paper represents a summary of a scientific conference sponsored

Systemic Immune Mediators and Lifestyle Changes in the Prevention of Type 2 Diabetes

“…First, we found that in the group with little changes in lifestyle (control group), elevated levels of CRP were associated with increased type 2 diabetes incidence. Elevated CRP is by far the best characterized immunological risk factor for incident type 2 diabetes because international standards for the assessment of CRP levels exist (26,27) and because this association could be confirmed in a range of independent studies (9 -12,14,15). Previous studies have shown that elevated CRP levels indicate increased risk of type 2 diabetes in population-based cohorts (8 -10).…”

Ten‐year alcohol consumption typologies and trajectories of C‐reactive protein, interleukin‐6 and interleukin‐1 receptor antagonist over the following 12 years: a prospective cohort study

“…Values lower than the detection limit [0.154 mg L −1 for CRP (multiplied by 9524 to express the value in mmol L −1 ) and 0.08 pg mL −1 for IL‐6] were assigned a value equal to half the detection limit. We excluded samples with CRP concentrations suggestive of acute inflammation and related bacterial infection (>10 mg L −1 ) 49 ( n = 242). To measure short‐term biological variation and laboratory error, a repeat sample was taken from 150 participants for CRP and 241 participants for IL‐6 at phase 3 [with a mean elapsed time between samples of 32 days (SD 10.5)].…”

Associations of C-reactive protein and interleukin-6 with cognitive symptoms of depression: 12-year follow-up of the Whitehall II study

“…Ceiling effects mainly affected CRP levels for which the upper value was set to 10 mg/L, but upper limits are not defined for IL-6. (Myers et al, 2004) Participants who reported recent colds or flu, or with high CRP levels, were excluded since a high value is considered to indicate acute inflammation and immune activation due to current illness potentially masking the relatively small elevations that may be associated with psychosocial factors or even chronic disease risk. Those acute, and typically large, responses are qualitatively different from the effects of chronic health conditions, such as the ones we adjusted for, and are short-term reactions not representative of the individual.…”

“…At baseline and follow-up, we excluded those with high CRP values (>10mg/L) and those who reported a cold or 'flu' in the last two weeks since these conditions are typically related to short-term large responses not representative of the individual. (Myers et al, 2004) This left 5978 participants with CRP and 5907 with IL-6 data at baseline. Of these, 3339 (CRP) and 3298 (IL-6) also had measurements of cognitive symptoms at baseline and at follow-up.…”