Determinants of the acute phase protein CRP in myocardial infarction survivors

Background: C-reactive protein (CRP), a sensitive marker of the acute phase response, has been associated with future cardiovascular endpoints independent of other risk factors such as body mass index (BMI), age and cholesterol levels. Risk assessment in populations at risk of cardiovascular disease is usually based on one or two measurements. Variation of CRP among certain subgroups of the population, however, has not been examined in detail. The purpose of this thesis is to study associations between time-invariant patient characteristics and mean high sensitivity (hs)-CRP concentrations and parameters that influence the variation of hs-CRP in a joint analysis. Additionally, associations between parameters that might impact hs-CRP in the 24 hours before the blood draw, such as environmental tobacco smoke exposure, alcohol consumption or extreme stress or anger, were examined. Moreover, the short-term impact of ambient air pollution on hs-CRP was studied. Methods: This thesis is based on AIRGENE, a multi centre study conducted in six European cities. Hs-CRP was measured repeatedly up to eight times every four to six weeks in 1,003 myocardial infarction (MI) survivors. At the first visit data on health status, medication intake and smoking history were collected by questionnaire. Blood pressure and BMI were measured and a blood serum sample was drawn. An additional blood sample was drawn at each visit for the determination of hs-CRP and data on life-style in the 24 hours before the visit were collected. In each city, hourly data on particle number concentrations, mass concentrations of particulate matter (PM) <10μm (PM10) and <2. 5μm (PM2.5), gaseous pollutants and meteorological data were collected at central monitoring sites. Results: BMI was one of the strongest determinants with higher geometric mean hs-CRP concentrations in overweight and obese patients. Regarding age, a U-shaped relationship with the lowest hs-CRP level in the group of 50 to 59 year olds was found. Variation of hs-CRP within patients was only slightly lower than between patients. Patients who reported the presence of angina pectoris, emphysema and congestive heart failure showed a lower variation (-11.0, -24.9 and -41.6% variation, respectively) while the geometric mean concentration seemed not to be affected. For patients with baseline glycosylised haemoglobin (HbA1c) levels of 6.5% and above, on the other hand, our data revealed higher hs-CRP (geometric mean: 26.2, confidence interval: 7.2; 48.6) and a higher variation (20.7% variation, p-value 0.0034). Results were similar, although not as pronounced, for the diagnosis of type 2 diabetes. Variation was also higher in males compared to females and smokers compared to non-smokers (24.8 and 27.3%, respectively) with a lower geometric mean concentration in males and a higher one in smokers. Patients reporting the intake of statins or other lipid-lowering drugs showed significantly lower hs-CRP and also less variation. Patients using angiotensine converting enzyme (ACE)-inhibitors on the other hand, a higher variation was found while geometric mean concentrations seemed not to be associated with medication intake. Life-style parameters in the 24 hours preceding blood draw did not have a major impact on hs-CRP. No association was seen between ambient air pollutants and hs-CRP concentrations. Conclusion: This work confirms and extends published results on the association between patient characteristics and intake of medication and hs-CRP concentrations in a panel of male and female MI survivors. The higher variation found in males, smokers and subjects with elevated HbA1c concentrations indicates that basing preventive medical measures on a single measurement of hs-CRP might not be sufficient. It is conceivable that individuals with a generally higher level of inflammatory markers, and/or a higher variation, for example patients with diabetes, might react more strongly to environmental factors such as air pollution. The lack of association between air pollution and hs-CRP in these data is possibly due to a widespread intake of statins in this population of MI survivors.