Factors associated with stroke among adult patients with hypertension in Ayder Comprehensive Specialized Hospital, Tigray, Ethiopia, 2018: A case-control study.

BACKGROUND: Globally, the burden of stroke is increasing at an alarming rate. Factors associated with stroke among hypertensive patients are not consistent across different studies and there are limited studies particularly to hypertensive stroke in the particular setting. This study aimed to assess factors associated with stroke among patients with hypertension in Ayder Comprehensive Specialized Hospital, Mekelle, Tigray, Ethiopia, in 2018.
METHODS: Hospital-based case-control study was conducted from February to April 2018. Cases were adult hypertensive patients with stroke and controls were adult hypertensive patients without a stroke. Cases and controls were identified from the patient's card review. Using a systematic random sampling technique 89 cases and 356 controls were included in this study. Record review, physical measurement, and interview techniques were used to collect data. Data was entered and analyzed by using SPSS version 23. Variables with a p-value of less than 0.25 in the bivariate logistic regression were selected for multivariable logistic regression. The adjusted odds ratio and 95% confidence interval were used to determine the association. P-value <0.05 was used to declare statistical significance.
RESULTS: The mean age of cases and controls were 56.3 years (SD±13.53) and 51.9 years (SD±12.67) respectively. Lost to follow-up (AOR = 2.474, 95%CI: 1.368-4.929), alcohol drinking (AOR = 2.440, 95%CI: 1.291-4.613), use of excessive salt in diet (AOR = 3.249, 95%CI: (1.544-6.837), medication non-adherence (AOR = 3.967, 95%CI: 2.256-6.973), uncontrolled systolic blood pressure, (AOR = 3.196, 95%CI: 1.60-6.382), uncontrolled diastolic blood pressure (AOR = 2.204, 95%CI: 1.130-4.297) and high cholesterol level (AOR = 2.413, 95%CI: 1.319-4.414) were found to be significant factors.
CONCLUSION: Lost to follow-up, alcohol drinking, uses of excessive salt in diet, medication non-adherence, and uncontrolled systolic and diastolic blood pressure were associated with stroke. Health education on lifestyle practices and hypertension-related complications in each follow-up visit is very essential for improving the primary stroke prevention.

Introduction

Stroke is a chronic non-communicable disease (NCD) that causes a sudden global focal neurological deficit resulting from infraction or spontaneous hemorrhage in the brain [1]. Stroke leads to multiple social and cognitive impacts like communication difficulty, memory loss, walking difficulty, depression and paralysis [2]. The incidence of a stroke in the past four decades (1970–2010) was increased by 100% in low and middle-income countries, but it was decreased by 42% in developed countries [3]. In 2013, there were 6.5 million stroke deaths, 113 million disability-adjusted life years due to stroke. Developing countries account for 75.2% of all stroke mortality and 81.0% of all stroke-related disability-adjusted life years [4].

In addition to the health consequence cardiovascular disease and stroke has a major impact on economic development. World Economic Forum and world health organization (WHO) forecasts above 7 trillion American dollars will be lost over the period 2011–2025 in low and middle-income countries (LMIC) [5].

The American heart association plans to reduce disease and deaths from stroke by 20 percent in 2020 by focusing on seven key health factors and behaviors that decrease the risk of stroke, those are not-smoking, physical activity, healthy diet, body weight, and control of cholesterol, blood pressure, and blood sugar [6].

Different studies in different parts of the world stated the factors associated with stroke were age, sex, and smoking, low physical exercise, obesity, alcohol, anti-hypertensive medication non-adherence, uncontrolled blood pressure, being diabetic, and cholesterol level [5, 7–12]. But the above factors are different across the studies.

In 2015/16-2019/20 the Ethiopian health sector development program projects to decrease by 12.5% premature mortality from non-communicable disease (NCDs) [13]. In Ethiopia currently, stroke is one of the greatest public health problems, accounts for 7% of total deaths [14]. Study in Mekelle, Ethiopia showed that the stroke was the third most common cause of medical intensive care unit admission (15.2%) and the first cause of death, which accounts for 17% of all deaths in the medical intensive care unit [15]. Similarly, hypertension is responsible for 66.2% of all stroke admission and 38% of all stroke were on anti-hypertensive treatment [16].

In Ethiopia, although admission of stroke patients to the hospitals due to hypertension is increased from time to time, there are limited findings that aim to explore those factors.

Therefore, this study aims to assess the factors associated with stroke among hypertensive patients at Ayder Comprehensive Specialized Hospital, Mekelle, Ethiopia, 2018.

Materials and methods

Study setting

Ayder Comprehensive Specialized Hospital (ACSH) is found in Mekelle, Tigray regional state, Ethiopia. Mekelle is found at 783 Km north of Addis Ababa. Ayder Comprehensive Specialized Hospital is the biggest hospital in the region and begins its referral as well as non-referral services in 2008. ACSH serves service for around 9 million populations in its catchment areas of the Tigray, Afar, and parts of the Amhara regional states in Ethiopia. Ayder Comprehensive Specialized Hospital has a capacity of about 500 beds in four major departments and other specialty units. The patient flow of ACSH is above170, 000 per year. The hospital provides hypertensive service in the cardiac unit and stroke service in a neurology unit. Medical ward, medical intensive care unit, cardiac unit and diabetic unit were the study units [17].

Study design and period

A case-control study design was conducted from February to April 2018.

Population and sampling

Cases were all sampled adult hypertensive patients with stroke diagnosed by the neurologist (consultant internist) or confirmed by brain imaging (CT-scan) or MRI and Controls were all sampled adult hypertensive patients without clinical evidence of stroke and without a history of stroke available in ACSH during the data collection period. Cases with less than three follow-ups for hypertension treatment before first stroke occurrence and controls with less than three follow-ups for hypertension treatment were excluded. Pregnant mothers were also excluded from both cases and controls. The sample size was calculated using Epi Info version 7 statistical software using the following assumptions: a proportion of 10.7% and 24.1% of greater alcohol consumption was considered for controls and cases respectively [8] at 95% CI, 80% power. The case to control ratio was 1:4. Using those information 81 cases and 324 controls were selected but after adding a 10% non-response rate the total sample becomes 445 of which 89 were cases and 356 were controls. Finally eligible cases and controls recruited using a systematic sampling technique.

Data collection procedure

Record review was used to identify cases and controls. Information on socio-demographic data and behavioral risk factors for stroke were obtained from the patient or close relative (for unconscious participant) by interview.

Medical history like clinical duration of hypertension, type of stroke, the presence of stroke, and complication other than stroke was taken from the patient record. Height, weight, blood pressure, total cholesterol level and fasting blood sugar were taken during data collection.

During data collection, data collector measures weight, height, blood pressure, as follows. Weight was measured in light closing and without shoes by calibrated UNICEF Seca digital weighing scale. Stadiometer in centimeter in erect position at a precision of 0.1cm without shoes was used to measure height. Mercury sphygmomanometer was used to measure blood pressure average of two measurements 5 minutes apart was recorded for those who we take BP during the data collection.

Assessment and definition of variables

Outcome variable: Stroke

Independent variables

Scio-demographic included: age, sex, marital status, occupation, residency and educational status.

Behavioral factors included: Physical exercise, Smoking, alcohol, frequency of follow-up, excessive salt in diet, fatty food use, loss to follow-up, medication adherence

physical exercise physically active- if patients make regular physical activities 30 minutes and above, 5 days and above per week physically inactive- if patient is made physical exercise less than 30 minutes per week or less than 5 days per week [18]. Medication adherence was assessed using Morisky medication adherence score to anti-hypertensive medications having eight questions each with yes = 0 and No = l, adherent if they score 7–8 and non-adherent if they score < = 6 [19].

Alcohol drinker- a person who drinks 10.5 units of alcohol and above per week [18].

Physical measurements and clinical factors: Fasting blood glucose (FBG), cholesterol level, blood pressure control, body mass index (BMI) and comorbidities. Normal FBG <126 mg/dl, raised FBG > = 126 mg/dl [8].

Cholesterol level: normal if less than 200 and high cholesterol level 200 and above, BMI: underweight (less than 18.5), normal (18.5–24.9), overweight (25–29.9) and obese (30 and above). Systolic blood pressure: controlled (<140) and uncontrolled (> = 140), diastolic blood pressure: controlled (<90) and uncontrolled (> = 90) [20].

Data analysis and management

Data were cleaned, coded, entered and analyzed using SPSS version 23. Summary statistics: frequencies and tables were used to present for categorical variables and mean for continuous variables in both cases and controls.

First bivariate logistic regression was done to assess the association between each independent variable and the dependent variable. Variable with a P-value < 0.25 significance level in bivariate logistic regression was taken to multivariable logistic regression. Finally, multivariable logistic regression was used to assess the association between independent variables with the dependent variable and to control confounding variables. Adjusted odds ratio and P-value <0.05 and with 95% CI were used to declare statistical significance.

Ethics approval and consent to participate

Ethical clearance was obtained from Mekelle University, College of health science institutional review board (ERC 1295/2018). Official permission was obtained from ACSH chief executive director and study participants were informed about the purpose of the study. The information was collected after obtaining written informed consent from the participant (relatives for patients who were critically ill). The respondents were informed as they have the right to refuse or discontinue participation at any time if unwanted. The information was recorded anonymously and confidentiality and beneficence were assured throughout the study period.

Results

Socio-demographic characteristics of the respondents

All 445 selected participants (89 cases and 356 controls) have participated in the study and the response rate was 100%. The mean age of cases was 56.3years (SD±13.53) and 51.9 years (SD±12.67) for controls.

The majority of subjects 64% in cases and 66% in controls were married. Thirty (33.3%) of the cases and 117(32.9%) of controls were self-employed (Table 1).

Table 1

Socio demographic characteristics of the study participants.

		Control		Cases
Variables	Categories	Frequency	Percentage	Frequency	Percentage
Sex	Male	170	47.8	46	51.7
	Female	186	52.2	43	48.3
Age(in years)	<45	116	32.6	23	25.8
	45–65	185	52	39	43.8
	>65	55	15.4	27	30.3
Religion	Orthodox Christian	278	78.1	69	77.5
	Muslim	61	17.1	17	19.1
	Other	17	4.8	3	3.4
Ethnicity	Tigray	316	88.8	81	91
	Amhara	22	6.2	4	4.5
	Afar	15	4.2	4	4.5
	Other	3	0.8	-	-
Marital status	Married	235	66	57	64
	Single	64	18	16	18
	Divorce	25	7	6	6.7
	Widowed	32	9	10	11.2
Educational status	No formal education	138	38.8	31	34.8
	Primary school	65	18.3	25	29.2
	Secondary school	42	11.8	9	10.1
	Diploma	29	8.1	6	6.7
	University and above	82	23	17	19.1
Occupation	Farmer	73	20.5	15	16.9
	Household	27	7.6	5	5.6
	Governmental employee	100	28.1	20	22.5
	Non-Governmental employee	32	9	15	16.9
	Self-employee	117	32.9	30	33.7
	Other	7	2	4	4.5
Residency	Rural	85	23.9	21	24.7
	Urban	271	76.1	67	75.3

Behavioral factors of the respondents

Out of 89 cases and 356 controls, 32(36%) of cases and 49(13.8%) controls were current alcohol drinkers. Twenty-two (24.7%) cases and 28(7.9%) of controls did not reduce salt in their diet. In this study, 66.3% of the cases and 29.8% of controls were non-adherent to medication. Sixty-three (70.8%) and 245(68.8%) controls were not on regular exercise. Thirty two (36%) of cases and 46 (12.9%) of controls had lost to follow up. Fifty-two (58.4%) of cases and 215 (60.4%) of controls had every two months follow-up (Table 2).

Table 2

Behavioral factors results of the participants.

		Control		Cases
Variables	Categories	Frequency	Percentage	Frequency	Percentage
Have you ever smoke cigarette	Yes	10	2.8	2	2.2
	No	346	97.2	87	97.8
Smoking after you diagnosed hypertension	Yes	3	0.8	0	0
	No	353	99.2	89	100
Regular physical exercise	Yes	111	31.2	26	29.2
	No	245	68.8	63	70.8
Medication non-adherence	Yes	106	29.8	59	66.3
	No	250	70.2	30	33.7
Have ever drink alcohol	Yes	255	71.6	67	75.3
	No	101	28.4	22	24.7
Current alcohol drink	Yes	49	13.8	32	36
	No	307	86.2	57	64
Do reduce salt in diet	Yes	328	92.1	67	75.3
	No	28	7.9	22	24.7
Do you eat fatty diet	Yes	71	19.9	27	30.3
	No	285	80.1	62	69.7
Lost to follow-up	Yes	46	12.9	32	36
	No	310	87.1	57	64
Frequency of follow-up	1month	85	23.9	21	23.6
	2month	215	60.4	52	58.4
	3month	56	15.7	16	18

Physical measurements and clinical characteristics of the respondents

Among the study participants, 13 (14.6%) of cases and 60 (16.9%) of controls were overweight. The clinical characteristics of patients showed that 5 (5.6%%) of cases and 25 (7%) of controls of the participants had a family history of stroke (Table 3).

Table 3

Clinical and anthropometric measurements of the study participants.

		Controls		Cases
Variables	Categories	Frequency	Percentage	Frequency	Percentage
Duration of diagnosis HTN	<4year	249	69.9	53	59.6
	> = 4year	107	30.1	36	40.4
Cholesterol level	Normal	282	79.2	56	62.9
	High level	74	20.8	33	37.1
Blood glucose level	Normal	304	85.4	75	84.3
	High level	52	14.6	14	15.7
BMI	18.5–24.9	288	80.9	74	83.1
	25–29.9	60	16.9	13	14.6
	> = 30	8	2.2	2	2.2
Systolic BP	Controlled	156	43.8	15	16.9
	Uncontrolled	200	56.2	74	83.1
Diastolic BP	Controlled	163	45.8	18	20.2
	uncontrolled	193	54.2	71	79.8
Comorbidities	Yes	67	19.5	22	24.7
	No	277	80.5	67	75.3
Family history of stroke	Yes	25	7	5	5.6
	No	331	93	84	94.4

The mean of the clinical duration of hypertension was 4.65 ± 3.3 years for cases and 3.94±3.18 years for controls. The mean of total cholesterol was 198±34 among cases and 182±27 for controls. The mean systolic blood pressure was 150±14 in the case and 145±17 in the controls. The mean diastolic blood pressure was 92±7 in the case and 90±9 in the controls.

Types of stroke and method used to diagnosis

The type of stroke (ischemic or hemorrhagic) and the tool by what they identified could be diagnosed was from the patient’s chart. Out of 89 cases, 29 were ischemic stroke cases and 60 were a hemorrhagic stroke. From all stroke 80% were diagnosed by CT scan, 4.5% by MRI and 15.7% clinically.

Bivariate and multivariable logistic regression for factors associated with stroke among hypertensive patients

The bivariate logistic regression result reveals that age, lost to follow-up, alcohol drinkers after he/she knows their hypertensive status, use of excessive salt in diet, use of fatty diet, medication non-adherence, high cholesterol level, and uncontrolled systolic and diastolic blood pressure were found be significant predictors of stroke (Table 4).

Table 4

Bivariate and multivariable logistic regression result of the study.

Variables	Category	Cases%	Controls%	COR (95%CI)	AOR(95%CI)
Age (years)	<45	23(25.8%)	116(32.6%	1	1
	45–65	39(43.8%)	185(52%)	1.063(0.604–1.871)	.811(.418–1.573)
	>65	27(30.3%)	55(15.4%)	2.476(1.303–4.705)*	1.779(.836–3.787)
Have you ever lost to follow up	Yes	32(36%)	46(12.9%)	3.783(2.222–6.442)*	2.59(1.368–4.929)*
	No	57(64%)	310(87.1%)	1	1
Have you drink alcohol after you diagnosed	Yes	32(36%)	49(13.8%)	3.517(2.075–5.961)*	2.44(1.291–4.613)*
	No	57(64%)	307(86.2%)	1	1
Do you reduce salt in diet	Yes	67(75.3%)	328(92.1%)	1	1
	No	22(24.7%)	28(7.9%)	3.846(2.075–7.130)*	3.25(1.544–6.837)*
Do you eat fatty foods	Yes	27(30.3%)	71(19.9%)	1.748(1.038–2.944)*	1.39(.733–2.63)
	No	62(69.7%)	285(80.1%)	1	1
Medication adherence	No adherent	59(66.3%)	106(29.8%)	4.638(2.828–7.607)*	3.97(2.256–6.973)*
	Adherent	30(33.7%)	250(70.2%)	1	1
Cholesterol level	Normal	56(62.9%)	282(79.2%)	1	1
	High level	33(37.1%)	74(20.8%)	4.560(2.313–8.989)*	2.41(1.319–4.414)*
Systolic blood pressure	Controlled	15(16.9%)	156(43.8%)	1	1
	Uncontrolled	74(83.1%)	200(56.2%)	3.848(2.126–6.964)*	3.19(1.60–6.382)*
Diastolic blood pressure	Controlled	18(20.2%)	163(45.8%)	1	1
	Uncontrolled	71(79.8%)	193(54.2%)	3.331(1.907–5.818)*	2.2(1.130–4.297)

Multivariable logistic regression lost to follow up (AOR = 2.474, 95% CI: 1.368–4.929), alcohol drinkers after he/she know their hypertensive status (AOR = 2.440, 95%CI: 1.291–4.613), use of excessive salt- in diet (AOR = 3.249, 95%CI: 1.544–6.837), medication non-adherence (AOR = 3.967, 95%CI: 2.256–6.973), high cholesterol level (AOR = 2.413, 95%CI: 1.319–4.414), uncontrolled systolic (AOR = 3.196, 95%CI: 1.60–6.382) and diastolic blood pressure (AOR = 2.204, 95%CI: 1.130–4.297) were found be significant predictors of stroke(Table 4).

Discussion

This case-control study aimed to identify factors associated with stroke among hypertensive patients in Ayder comprehensive specialized hospital, Tigray, north Ethiopia. Lost to follow-up, current alcohol drinking, eating salty foods, medication non- adherence, high cholesterol level, uncontrolled systolic and diastolic blood pressure were significant factors for stroke.

In this study, patients who had a history of loss to follow up were 2.5 times more likely to be at high risk for stroke than their counterparts (AOR = 2.474, 95% CI: 1.368–4.929). This finding is in agreement with a study conducted in Germany [21]. This similarity might be due to missing their routine medications and lifestyle modification counseling leads to uncontrolled hypertension.

Hypertensive patients, who were alcohol drinkers, were 2.44 times more likely to be at high risk for stroke (AOR = 2.440, 95%CI: 1.291–4.613). This finding is in line to a study conducted in Nigeria [8] and in 32 countries (INTERSTROKE) [7]. This similarity might be due to alcohol has a direct impact on raising blood pressure.

Hypertensive patients who did not reduce salt in diet were around 3.2 times more likely to be at high risk for stroke (AOR = 3.249, 95%CI: 1.544–6.837). This is similar with a study done in 32 countries (INTERSTROKE) [7]. It is due to the fact salt has an impact on raising blood pressure on circulation then can cause a stroke.

In this study medication none-adhered were 4 times (AOR = 3.967, 95%CI: 2.256–6.973) more likely to be at high risk for stroke than the medication adherent hypertensive patients. This finding is in line with a study done in Bangladesh, Germany [21, 22].

Patients with high cholesterol levels were 2.4 times (AOR = 2.413, 95%CI: 1.319–4.414) more likely to be at high risk for stroke than patients with low cholesterol levels. This finding is consistent with a study conducted in Nigeria and Tanzania [8, 23]. This might due to cholesterol have a direct impact on block blood circulation and can cause a stroke. But study Erbil reveals that there was no statistically significant difference between the groups with and without stroke with respect to Cholesterol variation [9]. This might be due to sample size, study design difference.

Result of this study showed that uncontrolled systolic blood pressure is 3.2 times more likely at high risk for the development of stroke (AOR = 3.196, 95%CI: 1.60–6.382) and uncontrolled diastolic blood pressure were 2.2 times more likely for the development of stroke (AOR = 2.204, 95%CI: 1.130–4.297) this in lines with a study done in Puget [24]. This might be related to the fact that uncontrolled blood pressure cause hemorrhage in the brain and blockage in the blood vessel.

Conclusion

Among hypertensive patients, alcohol consumption loss to follow up, excessive salt use in diet, high cholesterol level, uncontrolled systolic and diastolic blood pressure were found to be associated with stroke. Therefore, further intervention and prevention mechanism are essential for improving the primary stroke prevention.

Limitations of the study

Control subjects were not recruited from the general population, so selection bias of control subjects may also have affected the findings of this study. Two blood pressure readings were taken from the patient’s record review hence no information was available on how BP was measured. A case-control study design was used which does not allow for the temporal relationship to be established.

SPSS data of the questionnaire results.

(XLSX)

Click here for additional data file.

English and Tigrigna version questionnaires of the study.

(DOCX)

Click here for additional data file.

12 Dec 2019

PONE-D-19-31261

Factors associated with Stroke among Adult Patients with Hypertension in Ayder Comprehensive Specialized Hospital, Tigray, Ethiopia, 2018 A Case Control Study

PLOS ONE

Dear Dr. Mekonen,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

We would appreciate receiving your revised manuscript by Jan 26 2020 11:59PM. When you are ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.

A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.

An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

We look forward to receiving your revised manuscript.

Kind regards,

HASNAIN SEYED EHTESHAM

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements:

Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

In your Methods section please provide a rationale for excluding pregnant women.

Thank you for stating the following financial disclosure:

[no funding].

Please provide an amended Funding Statement that declares *all* the funding or sources of support received during this specific study (whether external or internal to your organization) as detailed online in our guide for authors at http://journals.plos.org/plosone/s/submit-now.

Please state what role the funders took in the study.  If any authors received a salary from any of your funders, please state which authors and which funder. If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."

Please include your amended statements within your cover letter; we will change the online submission form on your behalf.

4. PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager. Please see the following video for instructions on linking an ORCID iD to your Editorial Manager account: https://www.youtube.com/watch?v=_xcclfuvtxQ

5. Your ethics statement must appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please move it to the Methods section and delete it from any other section. Please also ensure that your ethics statement is included in your manuscript, as the ethics section of your online submission will not be published alongside your manuscript.

6.Please include your tables as part of your main manuscript and remove the individual files. Please note that supplementary tables (should remain/ be uploaded) as separate "supporting information" files

7. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information.

8. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide.

9.   We suggest you thoroughly copyedit your manuscript for language usage, spelling, and grammar. If you do not know anyone who can help you do this, you may wish to consider employing a professional scientific editing service.

Whilst you may use any professional scientific editing service of your choice, PLOS has partnered with both American Journal Experts (AJE) and Editage to provide discounted services to PLOS authors. Both organizations have experience helping authors meet PLOS guidelines and can provide language editing, translation, manuscript formatting, and figure formatting to ensure your manuscript meets our submission guidelines. To take advantage of our partnership with AJE, visit the AJE website (http://learn.aje.com/plos/) for a 15% discount off AJE services. To take advantage of our partnership with Editage, visit the Editage website (www.editage.com) and enter referral code PLOSEDIT for a 15% discount off Editage services.  If the PLOS editorial team finds any language issues in text that either AJE or Editage has edited, the service provider will re-edit the text for free.

Upon resubmission, please provide the following:

The name of the colleague or the details of the professional service that edited your manuscript

A copy of your manuscript showing your changes by either highlighting them or using track changes (uploaded as a *supporting information* file)

A clean copy of the edited manuscript (uploaded as the new *manuscript* file)

Additional Editor Comments (if provided):

Major Revision

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: No

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: I Don't Know

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: No

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: No

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Manuscript #: PONE–D- 31261

Title: Factors associated with stroke among Adult patients with Hypertension in Ayder Comprehensive Specialized Hospital, Tigray, Ethiopia, 2018. A Case Control study.

Review:

1. The article is well written. However, since the authors are working on the factors associated with stroke, a range of the age group taken (Minimum & maximum age in adults) instead of the mean age would be more informative to further identify the incidence of stroke, whether more common in young adults or older adults.

2. The inclusion of some more parameters like Gender, Socioeconomic status, dietary habits (Consumption of more Fatty or non fatty food), profession (Stressful/ non stressful), life style (Sedentary/ Active), & family history will make this study and identification of factors more meaningful.

Reviewer #2: I have gone through the manuscript entitled "Factors associated with Stroke among Adult Patients with Hypertension in Ayder Comprehensive Specialized Hospital, Tigray, Ethiopia, 2018 A Case Control Study". The article in contention is not acceptable in its present form.

Comments:

1. Usage of English language is not up to the mark, there are several spelling mistakes, grammatical and typo error in this manuscript.

2. There is only one reference of 2018 and no reference of 2019 and the referencing is not as per journal format.

3. Annexure I is only available but other supporting tables are not in readable format.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files to be viewed.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org. Please note that Supporting Information files do not need this step.

Submitted filename: renamed_3b9c1.docx

Click here for additional data file.

14 Jan 2020

Response to Reviewers

PONE-D-19-31261

Title: Factors associated with Stroke among Adult Patients with Hypertension in Ayder Comprehensive Specialized Hospital, Tigray, Ethiopia, 2018: A case-control study

PLOS ONE

Point by point response to Reviewers Comments:-

Sr. No. Reviewers' Comments Response to Comments

Academic Editor comments

1 Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at http://www.plosone.org/attachments/PLOSOne_formatting_sample_main_body.pdf and http://www.plosone.org/attachments/PLOSOne_formatting_sample_title_authors_affiliations.pdf

We accept the comment and we made correction accordingly.

2 In your Methods section please provide a rationale for excluding pregnant women. Pregnant women were excluded because:

1. Hypertensive mothers increases the risk of stroke during pregnancy due to the pregnancy itself increase the chance of stroke because of physiological effect (hormonal change) so, this physiological change can affect the our result.

2. Anthropometric measurement(weight) is difficult in pregnant mother in order to calculate body mass index (BMI) of the participant.

3 Please provide an amended Funding Statement that declares *all* the funding or sources of support received during this specific study (whether external or internal to your organization) as detailed online in our guide for authors at http://journals.plos.org/plosone/s/submit-now.

The crossponding author gets fund from Mekelle University (from internal organization) but the funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."

4 PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. I have created ORCID iD and validated in the editorial manager.

5 Your ethics statement must appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please move it to the Methods section and delete it from any other section. Please also ensure that your ethics statement is included in your manuscript, as the ethics section of your online submission will not be published alongside your manuscript We corrected it. Ethical statement is now in methods section

6 Please include your tables as part of your main manuscript and remove the individual files. Please note that supplementary tables (should remain/ be uploaded) as separate "supporting information" files We accepted your comment. Now tables are within the main manscript and individual tables are removed.

7 Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information

We accept the comments and sugestions. We made correction accordingly

8 We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide. We changed our idea and the data is now available in "supporting information" files

9 We suggest you thoroughly copyedit your manuscript for language usage, spelling, and grammar. If you do not know anyone who can help you do this, you may wish to consider employing a professional scientific editing service. We accept the comment and we made corrections regarding the grammatical and punctuation errors throughout the whole document.

Reviewer#1

1 The article is well written. However, since the authors are working on the factors associated with stroke, a range of the age group taken (Minimum & maximum age in adults) instead of the mean age would be more informative to further identify the incidence of stroke, whether more common in young adults or older adults. The range of the age group we take is based on previous similar published articles. We searched many articles to get the appropriate age categories finally we believe that this age categories was suitable for our study. In the previous studies age greater than 65 years were high risk for stroke and they used similar categories of age.

2 The inclusion of some more parameters like Gender, Socioeconomic status, dietary habits (Consumption of more Fatty or non fatty food), profession (Stressful/ non stressful), life style (Sedentary/ Active), & family history will make this study and identification of factors more meaningful. We assessed sex (Male, Female), dietery habits (Did you eat diet high in fat such as Fatty meal and animal product)(Yes, No), profession(occupation)(Farmer, House wife, Government employee, Non-Government organization employee, Self-employee, Other), physical exercise was assed using two questions (i.e How many days do you do regular physical exercise in a week __and On average how much time do you spend during those exercise in a typical day_) finally it was diactomized in to physically active and phyisically inactive and family history of stroke(Yes, No). The socio economic status of the participants, actualy average montlty income was in our questioner but almost in all the questioner the value was missing it may be due to most patients have no fixed monthly income especially participants from the rular area finally due to high missing value we didn’t consider for analysis.

Reviewer#2

1 Usage of English language is not up to the mark, there are several spelling mistakes, grammatical and typo error in this manuscript. We accept the comments and we made corrections on the grammatical and punctuation errors throughout the whole document.

2 There is only one reference of 2018 and no reference of 2019 and the referencing is not as per journal format. We made uptodated informations in our paper.

3 Annexure I is only available but other supporting tables are not in readable format. I accepted your comment. Now tables are within the main manscript and individual tables are removed. We made corrections based on the journal format and in areadable form.

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

22 Jan 2020

Factors associated with Stroke among Adult Patients with Hypertension in Ayder Comprehensive Specialized Hospital, Tigray, Ethiopia, 2018 A Case Control Study

PONE-D-19-31261R1

Dear Dr. mekonen,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.

Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

With kind regards,

HASNAIN SEYED EHTESHAM

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

I have gone through the revised manuscript and also the author's response to the comments of the reviewers. Clarification about age group selection is acceptable. Similarly, inclusion criterion has been explained. Grammatical and language corrections have been made; tables have become more understandable. I recommend publication of this manuscript.

Reviewers' comments:

4 Feb 2020

PONE-D-19-31261R1

Factors associated with Stroke among Adult Patients with Hypertension in Ayder Comprehensive Specialized Hospital, Tigray, Ethiopia, 2018: A Case-Control Study

Dear Dr. Mekonen:

I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

For any other questions or concerns, please email plosone@plos.org.

Thank you for submitting your work to PLOS ONE.

With kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Prof HASNAIN SEYED EHTESHAM

Academic Editor

PLOS ONE