To :
Cc:

Bcc: 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 qui ntiles and 3 strata. I will be able to provide furt her information in this regard.

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

Thank you

Naila Khalil , MBBS, MPH, PhD
Assistant Professor, Center for Global Health Systems, Management, and P olicy Boonshoft School of Medicine, Wright State Universi ty 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 P olicy Boonshoft School of Medicine, Wright State Universi ty 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.Den nis@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. Al so, I noted that you mention preliminary analysis by quintiles. You stat e 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 infor mation about the two preliminary analysis results by the different group s. This information may help us provide a more detailed picture when pr esenting 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) P trend



### 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 Disease d 

### ( 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 signif icant 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 exerci se, diabetes, and total hip BMD.

b 

# ICD9 Code: All deaths due to CV D, 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 deaths2Table 3.Hazard Ratio (HR) and 95% Confidence Interval ofMortality by Blood lead levels in quintilesBlood Lead Levels(μg/dL)<4456-7>7ReferentQuintile 2Quintile 3Quintile 4Quintile 5P trendNumber of deaths, n (row %)30 (24)22 (18)21 (17)23 (19)27 (22)0.087All Cause Deatha(122)1.00.80 (0.45,1.42)0.70 (0.39, 1.24)0.60 (0.34, 1.06)1.20 (0.69, 2.09)§0.905Cardiovascular Diseaseb(53)1.00.90 (0.39, 0.11)0.62 (0.24, .60)0.74 (0.32,1.68)1.48 (0.65, 3.36)0.609Coronary HeartDiseased(23)1.01.96 (0.54, 7.10)0.56 (0.10,3.07)0.44 (0.08, 2.48)3.05 (0.88,10.50)0.394Strokef(20)1.00.65 (0.12, 3.55)1.15 (0.12, 3.55)1.13 (0.32,4.07)1.03 (0.24, 4.50)*0.761Cancerh(38)1.01.44 (0.52, 3.98)1.22 (0.44, 3.42)0.81(0.28, 2.40)1.57 (0.55,4.52)0.832All Other Deathsj(31)1.00.41 (0.13, 1.33)0.79 (0.19, 1.46)0.30 (1.09, 0.97)0.62 (0.21, 0.81)#0.214§All cause mortalityspline 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 knotsignificant at p=0.002, and Wald Test not significant at p=0.0077, Wald test formarginal spline significant at p= 0.0047,3

0 1 2 3 4051015LEAD VALUErelative hazard Median splineFigure 2.Multivariate adjusted relative hazard (left axis) of mortality associated with blood lead levels between 1 μg/dL and 15 μg/dL.4 0 .5 1 1.5 Percentage of SOF Population

0 5 10 15 20

Hazard Ratio051015Blood Lead LevelPercent Median splineAll Cause DeathFigure 3.Multivariate adjusted relative hazard (left axis) of mortality associated with blood lead levels between 1 μg/dL and 15μg/dL. Histogram of blood lead levels is superimposed in the background and displayed on the right axis.