BACKGROUND: White blood cell (WBC) count is, like C-reactive protein (CRP), a clinical marker of inflammation and predicts cardiovascular disease and mortality in middle-aged populations. Limited data exist on the association between WBC count and mortality in the oldest old. Moreover, because CRP and WBC count are closely linked, it is not known whether WBC count and CRP are independent risk factors for mortality. We assessed the independent predictive value of WBC count and CRP levels in relation to mortality, both vascular and nonvascular, in very old participants.
METHODS: A total of 599 women and men were evaluated longitudinally in the Leiden 85-plus Study. Blood samples and medical information were collected at age 85, and all participants were visited annually until age 90 or death. Mortality risks were estimated with Cox proportional hazard models.
RESULTS: Increasing WBC count was associated with an increased risk for all-cause mortality (hazard ratio, HR [95% confidence interval, CI] = 1.26 [1.15-1.38]) after adjustment for sex and smoking status. CRP levels were also associated with an increased risk for mortality (HR [95% CI] = 1.22 [1.10-1.35]). The association between increasing WBC count and mortality remained significant after adjustment for CRP levels (HR [95% CI] = 1.20 [1.09-1.33]), whereas also the relation between increasing CRP levels and mortality remained significant after adjustment for WBC count (HR [95% CI] = 1.17 [1.05-1.30]).
CONCLUSION: Our results suggest that WBC count and CRP levels both independently predict mortality in the oldest old.
Gerontol A Biol Sci Med Sci. 2010 Jan 27. [
White Blood Cell Count and C-Reactive Protein Are Independent Predictors of Mortality in the Oldest Old.
Willems JM, Trompet S, Blauw GJ, Westendorp RG, de Craen AJ.
Department of Gerontology and Geriatrics, C-2-R, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands
Friday
Wednesday
C-Reactive Protein and B-Type Natriuretic Peptide Predict Hospitalization for Heart Failure and Cardiovascular Death
Background: Heart failure (HF) is an important cause of morbidity in patients with acute coronary syndromes (ACS). C-reactive protein (CRP) has been implicated in experimental models as exacerbating myocardial injury, but data regarding the clinical relationship of high-sensitivity CRP (hsCRP) and B-type natriuretic peptide (BNP) concentrations with the risk of HF after ACS are few.
Methods: PROVE IT–TIMI 22 randomized 4162 patients who had been stabilized after ACS to either intensive or moderate statin therapy. hsCRP and BNP were measured 30 days after randomization. Hospitalizations for HF and cardiovascular death occurring after day 30 were assessed for a mean follow-up of 24 months.
Results: Patients who developed HF had higher concentrations of hsCRP (3.7 mg/L vs 1.9 mg/L, P < 0.001) and BNP (59 ng/L vs 22 ng/L, P < 0.0001). HF increased in a stepwise manner with hsCRP quartile [adjusted hazard ratio (HRadj) for Q4 vs Q1, 2.5; P = 0.01] and BNP quartile (HRadj for Q4 vs Q1, 5.8; P < 0.001), with similar results obtained for HF and cardiovascular death. In a multivariable analysis, higher concentrations of hsCRP and BNP were both independently associated with HF [HRadj, 1.9 for hsCRP >2.0 mg/L (P = 0.01) and 4.2 for BNP >80 ng/L (P < 0.001)]. Patients with increases in both markers were at the greatest risk of HF, compared with patients without an increased marker concentration (HRadj, 8.3; P = 0.01). The benefit of intensive statin therapy in reducing HF was consistent among all patients, regardless of hsCRP or BNP concentration.
Conclusions: Both hsCRP and BNP measured 30 days after ACS are independently associated with the risk of HF and cardiovascular death, with the greatest risk occurring when both markers are increased.
TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis St., Boston, MA 02115.
Methods: PROVE IT–TIMI 22 randomized 4162 patients who had been stabilized after ACS to either intensive or moderate statin therapy. hsCRP and BNP were measured 30 days after randomization. Hospitalizations for HF and cardiovascular death occurring after day 30 were assessed for a mean follow-up of 24 months.
Results: Patients who developed HF had higher concentrations of hsCRP (3.7 mg/L vs 1.9 mg/L, P < 0.001) and BNP (59 ng/L vs 22 ng/L, P < 0.0001). HF increased in a stepwise manner with hsCRP quartile [adjusted hazard ratio (HRadj) for Q4 vs Q1, 2.5; P = 0.01] and BNP quartile (HRadj for Q4 vs Q1, 5.8; P < 0.001), with similar results obtained for HF and cardiovascular death. In a multivariable analysis, higher concentrations of hsCRP and BNP were both independently associated with HF [HRadj, 1.9 for hsCRP >2.0 mg/L (P = 0.01) and 4.2 for BNP >80 ng/L (P < 0.001)]. Patients with increases in both markers were at the greatest risk of HF, compared with patients without an increased marker concentration (HRadj, 8.3; P = 0.01). The benefit of intensive statin therapy in reducing HF was consistent among all patients, regardless of hsCRP or BNP concentration.
Conclusions: Both hsCRP and BNP measured 30 days after ACS are independently associated with the risk of HF and cardiovascular death, with the greatest risk occurring when both markers are increased.
TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis St., Boston, MA 02115.
Monday
C-REACTIVE PROTEIN MODULATES HUMAN LUNG FIBROBLAST MIGRATION
C-reactive protein (CRP) has been classically used as a marker of inflammation. The aim of this study was to investigate the effect of CRP on migration of human fetal lung fibroblasts (HFL-1) to human plasma fibronectin (HFn). Using the blindwell chamber technique, CRP inhibited HFL-1 migration in a dose-dependent fashion (at 1 μ g/mL, inhibition: 32.5% ± 7.1%; P < .05). Western blot analysis showed that CRP inhibited the p38 mitogen-activated protein kinase (MAPK) activity in the presence of HFn. Moreover, the MAPK inhibitors SB202190 (25 μ M) and SB203580 (25 μ M) inhibited HFn-induced cell migration, suggesting an important role of p38 MAPK in HFn-induced migration. Taken together, these results suggest that the inhibitory effect of CRP is mediated by blocking MAPK. In summary, this study demonstrates that CRP directly modulates human lung fibroblasts migration. Thus, CRP may contribute to regulation of wound healing and may be endogenous antifibrotic factor acting on lung fibrosis.
Published in: Experimental Lung Research, Volume 35, Issue 1 February 2009 , pages 48 - 58
Keywords: lung fibroblast; C-reactive protein MAPK; migration
Published in: Experimental Lung Research, Volume 35, Issue 1 February 2009 , pages 48 - 58
Keywords: lung fibroblast; C-reactive protein MAPK; migration
Saturday
The effect of C-reactive protein on functional outcome in ischemic stroke patients.
This study was performed to evaluate the effect of C-reactive protein (CRP) measured within 24 hr after stroke onset on functional outcome in ischemic stroke patients. The medical records of 28 first-ever hemiplegic ischemic stroke patients with the lesions on the middle cerebral arterial territory were reviewed. Subjects were classified into experimental group (serum C-reactive protein >or= 0.5 mg/dL) and control group (serum CRP<0.5 mg/dL) based on the level of serum CRP measured within 24 hr after stroke onset. Serum CRP measured within 24 hr after stroke onset was significantly correlated with functional scales in ischemic stroke patients
Int J Neurosci. 2009;119(3):336-44
Ryu SR, Choi IS, Bian RX, Kim JH, Han JY, Lee SG.
Department of Physical & Rehabilitation Medicine, Research Institute of Medical Sciences, Chonnam National University Medical School & Hospital, Hak-Dong, Dong-Gu, Gwangju City, Republic of Korea.
Int J Neurosci. 2009;119(3):336-44
Ryu SR, Choi IS, Bian RX, Kim JH, Han JY, Lee SG.
Department of Physical & Rehabilitation Medicine, Research Institute of Medical Sciences, Chonnam National University Medical School & Hospital, Hak-Dong, Dong-Gu, Gwangju City, Republic of Korea.
Tuesday
Human C-reactive protein promotes oxidized low-density lipoprotein uptake and matrix metalloproteinase-9 release in wistar rats
C-reactive protein (CRP) is present in the atherosclerotic plaques and appears to promote atherogenesis. Intraplaque CRP colocalizes with oxidized low-density lipoprotein (ox-LDL) and macrophages in human atherosclerotic lesions . MMP-9 has been implicated in plaque rupture.
C-reactive protein (CRP) promotes ox-LDL uptake and MMP induction in vitro, however, these have not been investigated in vivo. We examined the effect of CRP on ox-LDL uptake and MMP-9 production in vivo in Wistar rats. C-Reactive Protein CRP significantly increased ox-LDL uptake in the peritoneal and sterile pouch macrophages compared to human serum albumin (huSA). CRP also significantly increased intracellular cholesterol ester accumulation compared to huSA . The increased uptake of ox- LDL by CRP was inhibited by pretreatment with antibodies to CD32, CD64, CD36 and fucoidin, suggesting uptake by both scavenger receptors and Fc gamma receptors.
Furthermore, CRP treatment increased MMP-9 activity in macrophages compared to huSA, which was abrogated by inhibitors to p38MAP kinase, ERK and NFKb, but not JNK prior to hCRP treatment. Since ox-LDL uptake by macrophages contribute to foam cell formation and MMP release to plaque instability, this study provides novel in-vivo evidence for the role of CRP in atherosclerosis.
J Lipid Res. 2008 Feb 2
C-reactive protein (CRP) promotes ox-LDL uptake and MMP induction in vitro, however, these have not been investigated in vivo. We examined the effect of CRP on ox-LDL uptake and MMP-9 production in vivo in Wistar rats. C-Reactive Protein CRP significantly increased ox-LDL uptake in the peritoneal and sterile pouch macrophages compared to human serum albumin (huSA). CRP also significantly increased intracellular cholesterol ester accumulation compared to huSA . The increased uptake of ox- LDL by CRP was inhibited by pretreatment with antibodies to CD32, CD64, CD36 and fucoidin, suggesting uptake by both scavenger receptors and Fc gamma receptors.
Furthermore, CRP treatment increased MMP-9 activity in macrophages compared to huSA, which was abrogated by inhibitors to p38MAP kinase, ERK and NFKb, but not JNK prior to hCRP treatment. Since ox-LDL uptake by macrophages contribute to foam cell formation and MMP release to plaque instability, this study provides novel in-vivo evidence for the role of CRP in atherosclerosis.
J Lipid Res. 2008 Feb 2
Wednesday
C-Reactive Protein and All-Cause Mortality in a Large Hospital-Based Cohort
BACKGROUND: C-reactive protein (CRP), an acutephase protein , is a sensitive systemic marker of inflammation and acute-phase reactions. Testing C-Reactive Protein CRP concentrations at hospital admission may provide information about disease risk and overall survival.
METHODS: All first-ever transmittals to the department of medical and chemical laboratory diagnostics for determination of low-sensitivity CRP (n = 274 515, 44.5% male, median age 51 years) between January 1991 and July 2003 were included [median follow-up time: 4.4 years (interquartile range, 2.3-7.4 years)]. The primary endpoint was all-cause mortality. Multivariate Cox regression adjusted for sex and age was applied for analysis.
RESULTS: Compared to individuals within the reference category (CRP <5 mg/L), hazard ratios (HR) for all-cause mortality increased from 1.4 (5-10 mg/L category) to 3.3 in the highest category (>80 mg/L, all P <0.001). CRP was associated with various causes of death. The relation of CRP to cancer death was stronger than to vascular death . Younger patients with increased CRP had relatively far worse outcome than older patients (maximal HR: 60 years: 1.7-3.7). Interestingly, both short- and long-term mortality were associated with increasing CRP concentrations (>80 mg/L: HR 22.8 vs 1.4).
CONCLUSION: Measurement of low-sensitivity CRP at hospital admission allowed for the identification of patients at increased risk of unfavorable outcome. Our findings indicate that close attention should be paid to hospitalized patients with high C-reactive protein not only because of very substantial short-term risk, but also long-term excess risk, the basis for which needs to be determined.
Marsik C, Kazemi-Shirazi L, Joukhadar C, Schickbauer T, Winkler S, Wagner OF, Endler G. Department of Medical and Chemical Laboratory Diagnostics. Clin Chem. 2007 Dec 21
METHODS: All first-ever transmittals to the department of medical and chemical laboratory diagnostics for determination of low-sensitivity CRP (n = 274 515, 44.5% male, median age 51 years) between January 1991 and July 2003 were included [median follow-up time: 4.4 years (interquartile range, 2.3-7.4 years)]. The primary endpoint was all-cause mortality. Multivariate Cox regression adjusted for sex and age was applied for analysis.
RESULTS: Compared to individuals within the reference category (CRP <5 mg/L), hazard ratios (HR) for all-cause mortality increased from 1.4 (5-10 mg/L category) to 3.3 in the highest category (>80 mg/L, all P <0.001). CRP was associated with various causes of death. The relation of CRP to cancer death was stronger than to vascular death . Younger patients with increased CRP had relatively far worse outcome than older patients (maximal HR: 60 years: 1.7-3.7). Interestingly, both short- and long-term mortality were associated with increasing CRP concentrations (>80 mg/L: HR 22.8 vs 1.4).
CONCLUSION: Measurement of low-sensitivity CRP at hospital admission allowed for the identification of patients at increased risk of unfavorable outcome. Our findings indicate that close attention should be paid to hospitalized patients with high C-reactive protein not only because of very substantial short-term risk, but also long-term excess risk, the basis for which needs to be determined.
Marsik C, Kazemi-Shirazi L, Joukhadar C, Schickbauer T, Winkler S, Wagner OF, Endler G. Department of Medical and Chemical Laboratory Diagnostics. Clin Chem. 2007 Dec 21
Strawberry Intake, Lipids, C-Reactive Protein, and the Risk of Cardiovascular Disease in Women
Objective: There is indirect evidence suggesting that strawberries, containing several key nutrients, may be associated with the risk of cardiovascular disease (CVD). In the Women’s Health Study, we examined strawberry intake for both its prospective association with CVD risk in 38,176 women and its cross-sectional association with lipids and C-reactive protein (CRP) in a subset of 26,966 women.
Methods: Strawberry intake was assessed from a baseline semiquantitative food frequency questionnaire, along with other self-reported lifestyle, clinical and dietary factors. Participants returned baseline bloods which were assayed for lipids and CRP . We computed the relative risks (RRs) for total CVD (1,004 cases) (including confirmed myocardial infarction , stroke, revascularization , and cardiovascular death) occurring during 10.9 years of follow-up.
Results: At baseline, 25.6%, 41.9%, 24.8%, and 7.7% of women reported corresponding strawberry intake of none, 1–3 servings/month, 1 serving/week, and 2 servings/week. For total CVD, the multivariate RRs (95% confidence intervals) for increasing categories of strawberry intake were 1.00 (ref), 1.01 (0.85–1.19), 0.95 (0.77–1.17), and 1.27 (0.94–1.72) (P, trend = 0.06). We found a similar lack of an association for individual cardiovascular endpoints and comparing mean levels of lipids and C-reactive protein by category of strawberry intake. However, women consuming 2 servings/week versus none had a borderline significant, multivariate 14% lower likelihood of an elevated C-reactive protein of 3 mg/L.
Conclusions: Strawberry intake was unassociated with the risk of incident CVD, lipids , or CRP in middle-aged and older women, though higher strawberry intake may slightly reduce the likelihood of having elevated C-reactive protein levels. Additional epidemiologic data are needed to clarify any role of strawberries in CVD prevention.
Journal of the American College of Nutrition, Vol. 26, No. 4, 303-310 (2007)
Published by the American College of Nutrition
Divisions of Preventive Medicine and Aging, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School (H.D.S., J.M.G., J.E.B)
Department of Ambulatory Care and Prevention, Harvard Medical School (J.E.B)
Department of Epidemiology, Harvard School of Public Health (H.D.S., J.E.B.), Boston, MA
Clinical Nutrition and Risk Factor Modification Center, St Michael’s Hospital (D.J.A.J.), Toronto, Ontario, CANADA
Methods: Strawberry intake was assessed from a baseline semiquantitative food frequency questionnaire, along with other self-reported lifestyle, clinical and dietary factors. Participants returned baseline bloods which were assayed for lipids and CRP . We computed the relative risks (RRs) for total CVD (1,004 cases) (including confirmed myocardial infarction , stroke, revascularization , and cardiovascular death) occurring during 10.9 years of follow-up.
Results: At baseline, 25.6%, 41.9%, 24.8%, and 7.7% of women reported corresponding strawberry intake of none, 1–3 servings/month, 1 serving/week, and 2 servings/week. For total CVD, the multivariate RRs (95% confidence intervals) for increasing categories of strawberry intake were 1.00 (ref), 1.01 (0.85–1.19), 0.95 (0.77–1.17), and 1.27 (0.94–1.72) (P, trend = 0.06). We found a similar lack of an association for individual cardiovascular endpoints and comparing mean levels of lipids and C-reactive protein by category of strawberry intake. However, women consuming 2 servings/week versus none had a borderline significant, multivariate 14% lower likelihood of an elevated C-reactive protein of 3 mg/L.
Conclusions: Strawberry intake was unassociated with the risk of incident CVD, lipids , or CRP in middle-aged and older women, though higher strawberry intake may slightly reduce the likelihood of having elevated C-reactive protein levels. Additional epidemiologic data are needed to clarify any role of strawberries in CVD prevention.
Journal of the American College of Nutrition, Vol. 26, No. 4, 303-310 (2007)
Published by the American College of Nutrition
Divisions of Preventive Medicine and Aging, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School (H.D.S., J.M.G., J.E.B)
Department of Ambulatory Care and Prevention, Harvard Medical School (J.E.B)
Department of Epidemiology, Harvard School of Public Health (H.D.S., J.E.B.), Boston, MA
Clinical Nutrition and Risk Factor Modification Center, St Michael’s Hospital (D.J.A.J.), Toronto, Ontario, CANADA
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