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WHITE BLOOD CELL COUNT SECULAR TREND AND MORTALITY: THE BALTIMORE LONGITUDINAL STUDY OF AGING

WHITE BLOOD CELL COUNT SECULAR TREND AND MORTALITY: THE BALTIMORE LONGITUDINAL STUDY OF AGING . C.Ruggiero; E.J.Metter; A.Cherubini; M.Maggio; R.Sen; S.S.Najjar; G.B.Windham; A.Ble; U.Senin; L.Ferrucci. The Gerontological Society of America’s The 59 ° Annual Scientific Meeting. BACKGROUND.

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WHITE BLOOD CELL COUNT SECULAR TREND AND MORTALITY: THE BALTIMORE LONGITUDINAL STUDY OF AGING

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  1. WHITE BLOOD CELL COUNT SECULAR TREND AND MORTALITY:THE BALTIMORE LONGITUDINAL STUDY OF AGING C.Ruggiero; E.J.Metter; A.Cherubini; M.Maggio; R.Sen; S.S.Najjar; G.B.Windham; A.Ble; U.Senin; L.Ferrucci. The Gerontological Society of America’s The 59° Annual Scientific Meeting

  2. BACKGROUND White Blood Cell (WBC) count is a marker of inflammation- risk factor for morbidity and specific and all-cause mortality (Coller BS, 2005; Margolis KL, 2005; Brown DW, 2004)- strong predictor of incident cardiovascular and cerebrovascular events (Danesh J,1998)- negative prognostic factor in CHD patients (Wheeler JG , 2004)

  3. BACKGROUND • Does WBC count directly enhance the atherothrombotic process? • macrophages and phagocytes activation • platelet aggregation • - microvascular resistance and obstruction • Does WBC count simply mark a negative cardiovascular risk profile? • smoking behavior • sedentary lifestyle • infective agents and sanitary conditions

  4. AIMS OF THE STUDY • Investigate the trend in WBC count in the BLSA participants from 1958 to 2002 • 2) Estimate the relationship between WBC count and mortality • 3) Examine the relationship between WBC count and mortality over successive decades

  5. 1958 2002 Men 2002 1978 Women STUDY POPULATION 2803 persons (1083 women and 1720 men) Evaluation time:2 years Follow-up time Men: 22 ± 13.6 years (6 visits median) Women: 13 ± 7.9 years (3 visits median) Total Evaluations: >16.000

  6. METHODS WBC count (cells/mm3): standard automated method in the same clinical laboratory; differential WBC count in a subgroup (40% of visits) Vital status (died or alive): telephone follow-up, correspondence with inactive participants or their relatives, searches of the National Death Index Cause of death: consensus of 3 physicians based on revision of death certificates, medical records, correspondences and other available information

  7. BASELINE FEATURES * p<0.05

  8. Men -114 cells/year - 48 cells/year - 48 cells/year - 6 cells/year RESULTS (1) A downward trend in WBC count was observed over the period 1958-2002 in men and women enrolled in successive decades Women

  9. Men RESULTS (1) Secular WBC downward trend according to age at the initial evaluation in successive cohorts The secular WBC count decline was independent of age, gender, race, smoking, BMI and physical activity.

  10. RESULTS (2) Non linerar relationship between WBC count and all-cause mortality Linear relationship between WBC count and cardiovascular mortality WBC count has no effect on cancer mortality

  11. Time to event White Blood Cell Count, (group) <3,500 3,501-6,000 6,001-10,000 >10,000 Person-Years, (n) 345 18,726 26,730 2,547 Rate/1000 person-years 14.5 13.7 22.7 30.2 Risk Ratio (95%C.I.) 1.40 (0.6, 3.4) 1.0 (Ref) 1.54 (1.3, 1.8) 1.99 (1.5, 2.6) Adjusted Risk Ratio (95%C.I.) * 1.53 (0.6, 3.7) 1.0 (Ref) 1.24 (1.1,1.4) 1.76 (1.3, 2.3) Adjusted Risk Ratio (95% C.I.)‡ - 1.0 (Ref) 1.28 (1.0, 1.6) 1.62 (0.9, 2.8) RESULTS (2) *Cox proportional hazard model adjusted for age, sex, race, BMI and smoking; ‡Cox proportional hazard model adjusted for age, sex, race, BMI, smoking, physical activity, systolic and diastolic blood pressure, cholesterol, triglyceride and diabetes.

  12. RESULTS (2) Model 1: adjusted for age, date, sex, race; Model 2: adjusted for all covariates in Model 1 and BMI, physical activity, smoking, blood pressure, cholesterol, triglycerides, diabetes; Model 3: adjusted for all covariates in Model 2 and neutrophils.

  13. 60 47.7 3,500-6,000 >10,000 50 6,001-10,000 40.6 31.1 40 29.1 Rate/1000 persons 35.1 30 21.8 26.1 14.8 20 9.0 8.6 12.8 10 5.8 0 1960-1969 1970-1979 1980-1989 1990-2002 RESULTS (3) Age-adjusted mortality rate in each WBC group across successive decades

  14. 2,5 >10,000 6,001-10,000 (Ref) 3,500-6,000 2 1.6 1.5 1.4 1,5 1.2 Mortality risk ratio 1.3 1 1.2 1.1 1.0 0,5 0 1960-1969 1970-1979 1980-1989 1990-2002 RESULTS (3) Mortality risk ratios among the WBC groups across decades Risk ratios adjusted for age, sex, smoking, race, BMI, blood pressure, cholesterol, diabetes.

  15. CONCLUSION (1) A WBC count downward trend was observed in the BLSA participants from 1958 to 2002 The relationship between WBC count and all-cause mortality was non-linear Participants with WBC 3,500-6,000 cells/mm3 had the lowest mortality risk and it significantly increased above WBC >6,000 cells/mm3 The downward secular trend in WBC count was not a strong determinant of the mortality decline

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