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Subject: Fw: Blood lead mortality study: Khalil et al., 2009

From: Naila Khalil <khalil_naila@yahoo.com>

To: Dennis Kotchmar/RTP/USEPA/US@EPA

Date: 07/03/2010 10:39 AM

Subject: Fw: Re: Blood lead mortality study: Khalil et al., 2009

Dr Kotchmar,

Please find attached lead mortality analyses by quintiles and 3 strata. I will be able to provide further 

information in this regard.

It would be my privilege to contribute to the Pb Integrated Science Assessment in any capacity.

Thank you 

Naila Khalil, MBBS, MPH, PhD

Assistant Professor,

Center for Global Health Systems, Management, and Policy

Boonshoft School of Medicine, Wright State University

3123 Research Blvd., Suite 200,Kettering, OH 45420

Phone: (937) 258-5555,ext 562, Fax: (937) 258-5544

E-mail: naila.khalil@wright.edu, 

--- On Thu, 7/1/10, Naila Khalil <khalil_naila@yahoo.com> wrote:

From: Naila Khalil <khalil_naila@yahoo.com>

Subject: Re: Blood lead mortality study: Khalil et al., 2009

To: Kotchmar.Dennis@epamail.epa.gov

Cc: "dr jane cauley" <jcauley@edc.pitt.edu>

Date: Thursday, July 1, 2010, 1:15 PM

Dr Kotchmar, 

I appreciate your inquiry. I will be able to email you the two analyses by 6th July.

Sincerely,
Naila Khalil, MBBS, MPH, PhD

Assistant Professor,

Center for Global Health Systems, Management, and Policy

Boonshoft School of Medicine, Wright State University

3123 Research Blvd., Suite 200,Kettering, OH 45420

Phone: (937) 258-5555,ext 562, Fax: (937) 258-5544

E-mail: naila.khalil@wright.edu, 

--- On Thu, 7/1/10, Kotchmar.Dennis@epamail.epa.gov <Kotchmar.Dennis@epamail.epa.gov> 

wrote:

From: Kotchmar.Dennis@epamail.epa.gov <Kotchmar.Dennis@epamail.epa.gov>

Subject: Blood lead mortality study: Khalil et al., 2009

To: khalil_naila@yahoo.com

Date: Thursday, July 1, 2010, 12:44 PM

Our office is starting work on a new Pb Integrated Science Assessment

( formerly called Air Quality Criteria Documents) . In starting to read

your above referenced paper for inclusion , I noted that you mention

preliminary analysis for three groups; low, less or equal to 3 ug/dL;

medium 4-7; and high greater than or equal to 8. Also, I noted that you

mention preliminary analysis by quintiles. You state that the mortality

outcome was only significant at the greater than 8 blood lead, and

therefore combine them.

If possible, we would like more quantitative information about the two

preliminary analysis results by the different groups. This information

may help us provide a more detailed picture when presenting your study.

Thank you. I look forward to hearing from you.

Dennis J. Kotchmar M.D.

National Center for Environmental Assessment

United States Environmental Protection Agency

919-541-4158

kotchmar.dennis@epa.gov
1

Table 3. Hazard Ratio (HR) and 95% Confidence Interval of Mortality by Blood lead levels in 3 

strata 

Blood lead levels (μg/dL) Ptrend

Number of deaths (row %)

<3

30 (25)

4-7

66 (54)

≥7

26 (21) 0.035*

All Cause Death a (122) 1.0

0.69

(0.44, 1.09)

1.19 §

(0.68, 2.08) 0.681

 Cardiovascular Disease b (53) 1.0

0.75

(0.38, 1.49)

1.24 

(0.54,2.89) 0.660

 Coronary Heart Diseased (23) 1.0

0.94

(0.30, 2.98)

3.47 #

(1.01,11.85) 0.047

 Stroke f (20) 1.0

1.02

(0.33, 3.21)

0.74 

(0.15, 3.57) 0.721

Cancer h (38) 1.0

1.12

(0.48, 2.64)

1.63

 (0.57, 4.68) 0.369

All Other Deaths j (31) 1.0

0.45

(0.21, 1.00)

0.79 

(0.28, 2.21) 0.400

*Chi square p-value 

§ Wald Test for spline for third knot significant at 0.023, and third knot marginal spline at 0.047. 

# Wald Test for marginal spline for third knot significant at 0.038. 
Superscripts from original paper (Khalil et al., 2009, 487258): 

Khalil N; Wilson JW; Talbott EO; Morrow LA; Hochberg MC; Hillier 

TA; Muldoon SB; Cummings SR; Cauley JA (2009). Association 

of blood lead concentrations with mortality in older women: a 

prospective cohort study. Environ Health Global Access Sci 

Source, 8: 15. doi:10.1186/1476-069x-8-15 

*Chi -square p-value only for percentage of deaths in two blood 

lead strata, the rest are hazards ratio p values. 

a,c,e,g,i,k The multivariate model included the following: age, clinic, 

BMI, education, smoking, alcohol intake, estrogen use, 

hypertension, walking for exercise, diabetes, and total hip BMD. 

b

 ICD9 Code: All deaths due to CVD, including all diseases of 

circulatory system except those involving veins and lymphatics: 

425,429.2, 440–444,428,401–404,410–414,430–438, and 798. 

d

 ICD9 Code: deaths due to coronary heart disease: 410–414. 

f

 ICD9 Code: Deaths due to stroke: 430–438. 

h

 ICD9 Code: Deaths due to cancer: 140–239. 

j

 ICD9 Code: All other deaths: Non CVD and non cancer deaths
2

Table 3. Hazard Ratio (HR) and 95% Confidence Interval of Mortality by Blood lead levels in quintiles 

Blood Lead Levels (μg/dL)

<4 4 5 6-7 >

Referent Quintile 2 Quintile 3 Quintile 4 Quint

Number of deaths, n (row %) 30 (24) 22 (18) 21 (17) 23 (19) 27 (All Cause Death a (122) 1.0 0.80 (0.45,1.42) 0.70 (0.39, 1.24) 0.60 (0.34, 1.06) 1.20 (0.6Cardiovascular Disease b (53) 1.0 0.90 (0.39, 0.11) 0.62 (0.24, .60) 0.74 (0.32,1.68) 1.48 (0.6Coronary Heart Diseased (23) 1.0 1.96 (0.54, 7.10) 0.56 (0.10,3.07) 0.44 (0.08, 2.48) 3.05 (0.8Stroke f (20) 1.0 0.65 (0.12, 3.55) 1.15 (0.12, 3.55) 1.13 (0.32,4.07) 1.03 (0.2Cancer h (38) 1.0 1.44 (0.52, 3.98) 1.22 (0.44, 3.42) 0.81(0.28, 2.40) 1.57 (0.5All Other Deaths j (31) 1.0 0.41 (0.13, 1.33) 0.79 (0.19, 1.46) 0.30 (1.09, 0.97) 0.62 (0.2§ All cause mortality spline for fifth knot significant at p=0.009, and Wald Test significant at p=0.0843 

* Stroke mortality spline for fifth knot significant at p=0.010, and Wald Test not significant at p=0.180 

# Mortality from other causes spline for fifth knot significant at p=0.002, and Wald Test not significant at p=

marginal spline significant at p= 0.0047 , 
3

01234

0 5 10 15

LEAD VALUE

relative hazard Median spline

Figure 2. Multivariate adjusted relative hazard (left axis) of mortality associated with blood lead levels between 
4

0 .51 1.5

Percentage of SOF Population

05 10 15 20

Hazard Ratio

0 5 10 15

Blood Lead Level

Percent Median spline

All Cause Death

Figure 3. Multivariate adjusted relative hazard (left axis) of mortality associated with blood lead levels between 

μg/dL. Histogram of blood lead levels is superimposed in the background and displayed on the right axis.