Based on the Suggestions of Reviewer 1 and 2, the Following Changes Have Been Made in The

Dear Editor,

Based on the suggestions of Reviewer 1 and 2, the following changes have been made in the manuscript

We would like to thank them for their informative and useful comments and contributions on our paper.

Reviewer #1: This is an interesting study evaluating prevalence of CVD on people over 45 in an urban Turkish city by means of a two step approach based on in-person questionnaire administration and neurologic visit including review of medical records and of CT exams. The Authors conclude that prevalence in Turkey is lower than that reported in Western countries, but in line with that reported in other Mediterranean countries. Prevalence rate in women was higher than in men, in contrast with what was commonly reported by other studies.
The following points should be addressed.
1. How was defined the study population and how was obtained the population list to perform random selection. Was the random sample stratified by age and sex? The 30 sampled clinics seem to be used to identify the subjects: were they randomly selected too? It is not clear were people were interviewed: at home, in the clinic or both?
The study population included those >45 years, living in the city center of Denizli (among the 138, 000 people, the minimum sample size was calculated to be 1220, with an ideal sample size calculated as being 2x1220 = 2440, using the 95% confidence internal, p = 0.08% and α = 0.5). In order to reach the selected sample group, we applied to Health Headship and obtained all Family Health Center (FHC) addresses in the city center. There are 118 Family Health Centers, and 30 were randomly chosen with the systematic sampling method. People >45 years were recorded in the 30 FHCs (81 people for each FHC), and were chosen with systematic sampling method. All individuals were questioned in their homes, with the questionnaire being filled out by the researchers themselves.

(These sentences are added to the materials and methods). Thank you for your input.

2. It is not clear what the Authors mean with the term CVD: did they include TIA and chronic vascular disease as well? Was the evidence of a clinically evident stroke used only? Based on Figure 1, it seems that the diagnosis had to be confirmed at least by one among medical records, CT scan or Neurological evaluation. However, detailed criteria should be reported. How did they assess vascular risk factors? Did they rely on diagnoses reported in medical history, on therapy or whatever else?

-Definition of CVD is described in detailes and added to the materials and methods (We defined CVD according to the WHO criteria as “rapidly developing clinical signs of focal (at times global) disturbance of cerebral function lasting more than 24h or leading to death with no apparent cause other than that of vascular origin” (1). By applying this definition transient ischemic attack (TIA), which is defined last less 24 hours (by conventional clinical definitions), and patients with CVD symptoms caused by subdural hemorrhage, tumors, poisoning or trauma are excluded).

We did not include TIA but we included chronic vascular diseases. This expression is added to the manuscript.

Diagnosis of CVD is made according to clinical, radiological or medical evidence:

- Our questionnaire was modified using Reference 5, and contained 8 questions for the detection of CVD, which attempted to detect paresis, dysarthria, parestesia, vision loss, facial palsy, and comprehension loss. Those answering ‘Yes’ or ‘Don’t Know’ to one or more questions were deemed possible CVD candidates; they were requisitioned and examined by a neurologist, with their hospital medical records also being reviewed. Cranial imaging was performed on those who needed it. The diagnosis of CVD was excluded for those answering ‘No’ to all questions, as it was doubtful to the neurologist using the questionnaire and examining the patients.

- Risk factors were recorded according to medical history, medical records, and the drugs they use. HT is described according to Joint National Committee 7 [6], HL is desribed according to Adult Treatment Panel III [7], DM is described according to European Association of Diabetes [8] guidelines”.

These references are added to the references.

Thank you for your contribution.

3. Prevalence comparisons between genders must be standardized by age.

The mean age was 72.4 ± 8.7 (56 - 86) among females and 71.3 ± 7.3 (58 - 80) among males. Since the ages were similar, we did not compare them.
4. Prevalence of Diabetes mellitus is incredibly high and need be explained.

The prevalence of DM is higher at people who have CVD, not at total populaton. This group is older than 55 years old. The mean age of this group is 71, so we think that the prevalence of DM was found high.

5. Table 5 reports comparisons with other studies. However, due to different age criteria for inclusion in the studies, those figures might hardly be interpreted. Standardization by age and sex in comparable age subsets should be reported.

Yes you are right, Since there is no standardization acoording to age and sex at the literature, we deleted table 5. Thank you for your input.

Reviewer #2: This study evaluated the prevalence of CVD in Denizli, Western Anatolia, Turkey. The prevalence rate was found at 0.9%, higher among females (1.21% vs. 0.68% in males).
The study has a number of limitations:
1. Introduction is a bit confused, and repetitive, especially regarding stroke definition.

We reviewed the introduction and wrote it again clearly.

Definition of CVD is made again and enlarged according to WHO. This sentence added to the methods:

We defined CVD according to the WHO criteria as “rapidly developing clinical signs of focal (at times global) disturbance of cerebral function lasting more than 24h or leading to death with no apparent cause other than that of vascular origin” [1]. By applying this definition transient ischemic attack (TIA), which is defined last less 24 hours (by conventional clinical definitions), and patients with CVD symptoms caused by subdural hemorrhage, tumors, poisoning or trauma are excluded.

The sentence “is a focal or global neurological impairment of sudden onset lasting more than 24 hours [1,2]. CVD is of presumed vascular origin, may result in death, one of the leading causes of disability and is the third common cause of mortality following cardiac diseases and cancer” is excluded. Accordingly, reference 1 is changed. According to your suggestion, we deleted the sentence “It is a cause of mortality in acute phase. Surviving patients may face various degrees of disability and may need asistance for the rest of their lives. “ Thank you for your contribution.

2. Methods are unclear. When the Authors describe the population of Denizli (479,381), they write that the "questionnaire was modified and performed to all individuals", but afterwards the study sample is described as randomly selected, and consisting of 2440 people.

We described the methods in details and added these sentences:

-The study population included those >45 years, living in the city center of Denizli (among the 138, 000 people, the minimum sample size was calculated to be 1220, with an ideal sample size calculated as being 2x1220 = 2440, using the 95% confidence internal, p = 0.08% and α = 0.5). In order to reach the selected sample group, we applied to Health Headship and obtained all Family Health Center (FHC) addresses in the city center. There are 118 Family Health Centers, and 30 were randomly chosen with the systematic sampling method. People >45 years were recorded in the 30 FHCs (81 people for each FHC), and were chosen with systematic sampling method. All individuals were questioned in their homes, with the questionnaire being filled out by the researchers themselves.

- Our questionnaire was modified using Reference 5, and contained 8 questions for the detection of CVD, which attempted to detect paresis, dysarthria, parestesia, vision loss, facial palsy, and comprehension loss. Those answering ‘Yes’ or ‘Don’t Know’ to one or more questions were deemed possible CVD candidates; they were requisitioned and examined by a neurologist, with their hospital medical records also being reviewed. Cranial imaging was performed on those who needed it. The diagnosis of CVD was excluded for those answering ‘No’ to all questions, as it was doubtful to the neurologist using the questionnaire and examining the patients.

Data including age, gender, education status, hypertension (HT), hyperlipidemia (HL), diabetes mellitus (DM), smoking, cardiac diseases, and use of medications were recorded as well.

3. Confidence intervals for rates are not given.

Thank you for your input. We added confidence intervals to the table 4 and also mentioned them at the results part.

4. No attempt was made to evaluate even a sample of subjects negative to the questionnaire.

The diagnosis of CVD was excluded for those answering ‘No’ to all questions, as it was doubtful to the neurologist using the questionnaire again and examining the patients. All studies excluded subjects using same method in the literature.

5. Definition and assessment of risk factors is lacking.

Additonal sentences for risk factors added to materials and methods:

Risk factors were observed in medical records, along with the use of past medications.

HT is described according to Joint National Committee 7 [6], HL is desribed according to Adult Treatment Panel III [7], DM is described according to European Association of Diabetes [8] guidelines.

New references were added to the References.
6. The low number of cases means that multiple regression analyses are a bit problematic.

Regression analyses were performed to 2441 persons. According to these analysis; older age and females were found excess risk for CVD.

7. English should be carefully reviewed for grammar, syntax, and usage.
English is reviewed.

Again we would like to thank reviewer 1 and 2 for their informative and useful comments and contributions on our paper.

Yours sincerely,

Dr. Çağatay Öncel