Responses to comments
Abstract:
1. Line 9: Remove the word adjusted and line 7 after MI and add "adjusting for…"
=> We agree with the comment, and have addressed this sentence.
2. Line 8: Change "the association" to "this association" and add "also adjusting for gender" after the word "non-smokers".
=> We agree with the comment, and have addressed this sentence.
Study Sample:
3. While the cases were drawn from all hospitals in Erie and Niagara counties, the controls were identified from lists provided by New York State Department of Motor Vehicles and Health Care Financing Administration lists. This may lead to potential selection bias, which needs to be discussed. (Page 2: methods, page 9: discussion)
=> We added a few statements to clarify the reasons why we chose controls from two different sources. In addition, we added the following paragraph statements to discuss the potential bias.
“Our control group, recruited from two different sources, consisted of a sub-sample of the overall controls from “The Western New York Health Study (WNYHS)”. To determine whether the control sample from the WNYHS was of a selected nature, we compared selected characteristics of our participants with those of participants aged 35-79 years from the National Health and Nutrition Examination Survey (NHANES III) conducted in the United States between 1988 and 1994.There were no major differences in the characteristics considered between participants in the WNYHS and those of the NHANES III.” The comparison is summarized in table A (see below)
4. There are 2 control groups for different age groups; need to show descriptive tables and analysis stratified by these age groups.
=> The controls are actually a large single group. We do not have a single source where we can get the controls. In other words, the HCFA files are not available for people younger than 65 years. In fact, there was not a big difference in the general characteristics of the sample by the two age groups (see descriptive tables B and C below). Since there was only a few numbers of participants in the age group 65 or higher (n= 222), we did not analyze the data stratified by these age groups.
5. On page 2, need to mention why only white participants were included.
=> This section has been addressed in the manuscript. We added the following statements in this section:
“Non-white participants were excluded due to their small numbers. Blacks and others numbered 118 out 1603 of the total population. In addition, there was a big difference in characteristics between the white and non-whites. Thus, present study assessed the association between periodontal disease and myocardial infarction among only white participants.”
Statistical Analysis: 6. Paragraph 1: Delete the section on crude analysis, which is not relevant (Page 5)
=> We agree with the comment, and have addressed this section.
7. Paragraph 2:Mention which covariates were included and how these were selected (Page 5) => We agree with the comment, and have addressed this section. The following statements were inserted in the manuscript.
“All covariates available in this study were entered into the model one at a time. Covariates included age, gender, educational level, BMI, lifetime physical activity, smoking status, pack-years of cigarette smoking, drinking status, family history of heart disease, hypertension or high blood pressure, high blood cholesterol, diabetes, use of hormone replacement therapy (for women), menopausal status (for women), and plaque and calculus indices. Variables that contributed to the change in the estimate of the association between periodontal disease and MI were retained. In addition, standard risk factors for cardiovascular disease were retained in the model regardless of their contribution to change in the estimate.”
8. Confounder selection should include standard cardiovascular risk factors such as obesity, physical activity and parsimonious models should be based on change in estimate rather than p-values (Page 5)
=> We added standard risk factors for CVD such as BMI and physical activity in the model irrespective of their contribution to the change in the estimate of the association.
9. The choice of a continuous measure of clinical attachment loss quartiles and >3 mm mean are unusual. The choice needs to be justified and alternative measures based on other common criteria also need to be presented (Page 8)
=> We agree with the comments, and have addressed this section. The following statements were added in the manuscript to explain the choice of this measurement:
“The periodontal measurement CAL was chosen in the present study because it reflects a well established of periodontal disease in both clinical research and clinical practice. We decided to use the continuous variable in order to provide the maximal statistical power for the analyses. In addition, we used a definition of >= 3 mm for severe disease as it has been used in prior studies (24).“ We eliminated the quartile analysis, as it measures same thing, and it was redundant.
Tables:
10. Table 1: Add Race/Ethnicity distribution
=> We restricted out study sample to white participants only, since we had a very few numbers of the other races (black and others).
11. Table 1: Why is the term "Lifetime Physical Activity" used when it is hours per week? (Page 3)
=> This term was clarified and addressed in the manuscript. The following sentence was added in:
“…, and self-report on frequency of physical activities in hours per week throughout the participant’s entire life (“lifetime physical activities”) were determined”
12. Table 2: The analysis in table 2 should be repeated in non-smokers
=> We have updated the table 2 based on the comments on question No 9.
13. The analysis for women should also control for Hormone Replacement Therapy and Menopause status.
=> Hormone replacement therapy and menopausal status did not contribute to the change in the estimate of the association in the analysis for women. Thus, these variables were dropped from the model.
14. Table 3: The sample size and number of cases should be listed separately for smokers and non- smokers.
=> We agree with the comment, and have addressed this table.
Discussion:
15. Page 9: It is not clear why the population is considered to be at high risk of developing the outcome, and why this is important in a case control study. Also, radiographic measurements seem to be erroneously mentioned here.
=> We rephrased the sentence in the manuscript as follow:
It included a population at high risk of developing the outcome (i.e. men and women aged 35 to 69 years) so that a large number of MI cases were covered in this case-control design. In addition, detailed information on clinical measurements of periodontal disease, smoking, and a wide variety of potential confounders was collected and was able to be evaluated.
16. Page 10-11, paragraph 2 (last sentences on page 10): Fewer smokers or fewer perio cases do not imply underestimation of the association.
=> We restated these sentences as follow:
“Concerning smoking status, participants (either MI cases or controls) were overall less likely to be smokers than non-participants. Since smoking is a strong risk factor for periodontal disease, we might assume that both MI case and control participants had better periodontal status than the MI case and control non- participants. In such case, our findings might represent an underestimation of the true association, and these findings may be generalizable only to populations with similar characteristics.” Table A. Comparison between NHANES III (1988-1994) data with the Western New York Health Study participants.
Total Men Women Characteristics WNYH NHANES WNYHS NHANES WNYHS NHANES S Age (years) 52.4 59.2 51.8 60.7 52.9 57.8 BMI (kg/m2) 27.4 28.3 27.4 28.3 27.4 28.3 Serum Cholesterol (mg/dL) 213.6 216.6 211.3 210.9 215.7 222.0 Serum Glucose (mg/dL) 105.8 107.2 108.1 111.4 103.7 103.2 Self reported Stroke 2.7 2.3 3.0 2.9 2.5 1.7 Self reported Diabetes 7.7 9.7 7.1 11.9 8.2 7.5 Self reported Hypertension 32.3 37.7 32.7 40.9 32.0 34.6 Abstainers 13.6 10.0 5.9 4.1 20.8 15.4 Former Drinkers 36.5 25.8 32.6 24.9 40.2 26.6 Current Drinkers 49.9 64.3 61.5 71.1 39.0 57.4 Non daily 44.4 55.2 53.6 58.4 35.8 52.3 Daily 5.5 9.1 7.9 12.7 3.2 5.7 Table B. Characteristics of Myocardial Infarction (MI) Cases and Controls by Gender in Participants aged 35 to 64 years
Men Women
Characteristics MI Cases (n=378) Controls (n=256) MI Cases (n= 105) Controls (n=400)
Age (years) 52.3 ± 7.2 50.9 ± 7.7 52.6 ± 7.1 50.5 ± 7.5
BMI (kg/m2) 29.1 ± 4.9 28.6± 4.5 29.5 ± 5.9 27.7 ± 6.1
Education (years) 13.6 ± 2.2 14.4 ± 2.3 13.1 ± 1.7 13.9 ± 2.3
Lifetime Physical Activity (hours/week) 5.1 ± 1.7 5.1 ± 1.8 4.7 ± 2.0 4.9 ± 1.7
Smoking status (n and %)
Never smoked 95 (25.2) 111 (43.5) 30 (28.6) 203 (50.8)
Former smoker 226 (59.9) 109 (42.7) 50 (47.6) 149 (37.3)
Current smoker 56 (14.9) 35 (13.7) 25 (23.8) 48 (12.0)
Pack-years of cigarettes (pack/year) 24.7 ± 23.1 11.7 ± 19.0 22.0± 24.0 8.4 ± 14.4
Drinking status
Abstainer or irregular 14 (3.7) 6 (2.4) 9 (8.6) 41 (10.3)
Non-current 103 (27.4) 57 (22.4) 55 (52.4) 130 (32.7)
5 Current 259 (68.9) 192 (75.3) 41 (39.0) 226 (56.9)
Family history of heart disease 229 (74.6) 168 (70.3) 77 (85.6) 302 (79.7)
Hypertension or high blood pressure 166 (44.3) 65 (25.4) 57 (54.3) 85 (21.3)
High blood cholesterol 253 (68.6) 82 (32.0) 74 (72.5) 117 (29.5)
Diabetes 51 (13.6) 15 (5.9) 21 (20.0) 10 (2.5)
Use of HRT -- -- 47 (45.2) 146 (37.1)
CAL ≥ 3 mm (n; %) 138 (36.5) 44 (17.2) 36 (34.3) 32 (8.0)
Mean CAL (mm) 3.1 ± 1.3 2.4 ± 0.9 2.9 ± 1.1 2.3 ± 0.5
Plaque Index (0,1) 0.6 ± 0.3 0.5 ± 0.3 0.6 ± 0.3 0.4 ± 0.3
Calculus Index (0,1,2) 1.1 ± 0.7 0.8 ± 0.7 1.2 ± 0.7 0.6 ± 0.6
Significant differences between cases and controls indicated in bold type
NO BIG DIFFERENCE BETWEEN THE WHOLE GROUP OF CONTROLS AND THE SUBGROUP OF 35 TO 64 years.
6 Table C. Characteristics of Myocardial Infarction (MI) Cases and Controls by Gender in Participants aged 65 or older
Men Women
Characteristics MI Cases (n=65) Controls (n=129) MI Cases (n= 26) Controls (n=102)
Age (years) 67.2± 1.5 67.6 ± 1.9 67.2 ± 1.7 68.1 ± 1.6
BMI (kg/m2) 28.7± 4.4 28.8 ± 4.8 29.3 ± 5.8 28.0 ± 5.2
Education (years) 13.4 ± 2.4 13.8 ± 2.6 13.1 ± 2.3 12.9 ± 2.4
Lifetime Physical Activity (hours/week) 5.7 ± 1.8 5.7 ± 1.6 5.2 ± 1.7 5.3 ± 1.6
Smoking status (n and %)
Never smoked 21 (32.3) 48 (37.2) 16 (61.5) 62 (60.8)
Former smoker 41 (63.1) 72 (55.8) 10 (38.5) 32 (31.4)
Current smoker 3 (4.6) 9 (7.0) 0 8 (7.8)
Pack-years of cigarettes (pack/year) 17.4± 19.4 15.8 ± 21.0 13.1 ± 19.9 8.6 ± 15.9
Drinking status
Abstainer or irregular 7 (10.8) 4 (3.1) 6 (23.1) 18 (17.6) Non-current 7 (10.8) 23 (18.1) 10 (38.5) 31 (30.4) 7 Current 51 (78.5) 100 (78.7) 10 (38.5) 53 (52.0)
Family history of heart disease 48 (82.8) 94 (76.4) 20 (83.3) 81 (83.5) Hypertension or high blood pressure 35 (56.9) 50 (38.8) 15 (60) 36 (35.3) High blood cholesterol 36 (55.4) 43 (33.6) 21 (80.8) 42 (41.2) Diabetes 11 (17.2) 12 (9.4) 4 (15.4) 6 (5.9) Use of HRT -- -- 4 (16.0) 47 (47.0) CAL ≥ 3 mm (n; %) 24 (36.9) 37 (28.7) 8 (30.8) 13 (12.7) Mean CAL (mm) 3.1 ± 1.3 2.8 ± 1.1 2.8 ± 1.6 2.4 ± 0.6 Plaque Index (0,1) 0.7 ± 0.3 0.6 ± 0.3 0.6 ± 0.3 0.5 ± 0.3 Calculus Index (0,1,2) 1.0 ± 0.7 0.9 ± 0.7 1.0 ± 0.7 0.7 ± 0.6
Significant differences between cases and controls indicated in bold type
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