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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

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

slide2

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)

slide3

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
slide4

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
slide5

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

slide6

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

slide8

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

slide9

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.

slide10

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

slide11

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.

slide12

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.

slide13

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

slide14

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.

slide15

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