Investigating the incidence and risk factors of hypertension: A multicentre retrospective cohort study in Tabuk, Saudi Arabia.

BACKGROUND: Hypertension is a major global health concern affecting approximately 1.13 billion people worldwide, with most of them residing in developing countries. The aim of this study was to determine the incidence of different stages of hypertension and its associated modifiable and non-modifiable risk factors among patients in military-setting hospitals in Tabuk, Saudi Arabia.
METHODS: This retrospective cohort study was conducted at two hospitals in Tabuk, Saudi Arabia. The data were collected from hospital electronic records from 1 January 2019 to 31 December 2019. The blood pressure levels of patients from the last three separate medical visits were recorded. Descriptive statistics and multinomial logistic regression were used for the data analysis.
RESULTS: The study included 884 hypertensive patients. The incidences of stage of elevated BP, stage 1, stage 2, and hypertension crisis were 60.0, 29.5, 7.0, and 3.5 cases per 1000 persons. Multivariate analysis indicated that progression from the stage of elevated blood pressure to hypertension crisis was significantly associated with advanced age (odds ratio [OR] = 3.62, 95% confidence interval [CI] = 1.99-8.42), male sex (OR = 2.84, 95% CI: 0.57-5.92), and a positive family history of hypertension (OR = 1.95, 95% CI: 1.23-3.09). Other key determinants of the development of stage of elevated blood pressure to hypertension crisis were current smoking status (OR = 1.74, 95% CI: 1.23-4.76), and physical inactivity (OR = 6.48, 95% CI: 2.46-9.14).
CONCLUSION: The incidence stage of elevated blood pressure was high among the patients investigated at armed forces hospitals in Tabuk, Saudi Arabia. The logistic regression model proposed in the present study can be used to predict the development of different stages of hypertension. Age, sex, marital status, family history, smoking status, and physical activity play an important role in the development of hypertension. Better strategies to improve awareness, screening, treatment, and management of hypertension are required in Saudi Arabia.

Introduction

Hypertension is a common noncommunicable disease with a massive global impact. It increases the risk of several medical conditions such as cardiac diseases, congestive cardiac failure, stroke, retinal haemorrhage, and kidney diseases [1]. Socioeconomic problems have changed the lifestyle of people in low- and middle-income countries, which has increased the risk of developing hypertension [2]. Rapid urbanisation in Saudi Arabia over the past two decades, has led to an increase in incidence of hypertension [3]. Research studies have shown that hypertension imposes direct economic burden on both the patient and the health care system, by increasing the need for hospitalisation, physician consultations, laboratory investigations, and prescribed medications [4].

Hypertension has a complex aetiology, with different incidence, prevalence, and fatality rates depending on the race and ethnicity. Several studies have investigated the incidence of hypertension with emphasis on different races and ethnicities; however, the results obtained were dependent on the definition of hypertension followed in the individual study. A prospective, population-based cohort study conducted in six communities in the United States reported that the crude incidence rate of hypertension per 1000 person-years, was 56.8 for whites, 84.9 for Blacks, 65.7 for Hispanics, and 52.2 for Chinese [5]. In Eastern Mediterranean Region countries, the incidence of hypertension has been revealed to reach up to 25% in the adult population, while in the American continent, this has been shown to range from 14% to 40% among people aged 35 to 64 years [6].

Several risk factors have been associated with hypertension. These factors vary from country to country, and even prone to variations in socio-demographics of the same region. Previous epidemiological studies have reported the determinants of hypertension as both modifiable and non-modifiable risk factors [7-9]. Studies in Saudi Arabian populations, have explored relevant risk factors for hypertension, including age, sex, sociodemographic factors, family history, and behavioural and lifestyle characteristics, but these studies were limited to cross-sectional data [10, 11]. Therefore, incidence of hypertension and associated risk factors need to be defined and addressed in a representative large sample of the rapidly expanding Saudi Arabian population.

King Salman Armed Hospital (KSAFH) and King Khalid Military Hospital (KKMH) are two military hospitals in the city of Tabuk in Saudi Arabia. An increase in the incidence of cardiovascular diseases, stroke, and renal diseases, such as chronic renal failure has been reported in these two hospitals in the last 5 years with hypertension being the leading cause of morbidity, mortality and a high number of hospital admissions in both the hospitals. This observation made it necessary to explore more about hypertension, its incidence, and associated risk factors. To the best of our knowledge, the current retrospective cohort study on hypertension and related risk factors is the first study of this type to be conducted in this region and is vital for the establishment of successful hypertension prevention strategies. The results of this study can be extrapolated to other regions of Saudi Arabia as well as in the Gulf region which has similar demographics and an increased incidence of diseases which are considered to be complicated by hypertension.

Materials and methods

Study cohort

A hospital-based retrospective cohort study was conducted using a common registry program. Patients registered at KSAFH’s nephrology, cardiology, and internal medicine departments and KKMH’s family medicine clinic between 1 January 2019 and 31 December 2019 were selected. Both inpatients and outpatients from these departments during the study period were considered. The majority of hypertensive patients were referred to these departments for treatment of hypertension according to the hospital policy. All patients aged 18 years or older and diagnosed with hypertension according to the 2017 guidelines of American College of Cardiology/American Heart Association (ACC/AHA 2017) were included in this study cohort. A total of three blood pressure (BP) readings were taken for every patient during the study period. Patients with a diagnosis of hypertension for less than 6 months, pregnant women, and patients with missing medical information were excluded from this study. If a patient had more than three BP measurements, only the last three measurements were used. The study cohort consisted of exposed and non-exposed groups. Subjects with a mean BP measurement falling within a defined stage of hypertension were considered in the exposed group.

Sample size

The sample size was calculated using the public domain software Epi Info version 7.2 developed by the Centers for Disease Control and Prevention. The parameters used in the sample size calculation were chosen arbitrarily owing to resource constraints. The parameters were two-sided significance level (1-alpha): 95, power (1-beta, the % chance of detecting): 80, ratio of sample size -unexposed/exposed: 1, percentage of unexposed with outcome: 5, percentage of exposed with outcome: 10, odds ratio: 2.1, risk/prevalence ratio: 2, and risk/prevalence difference: 5. Thereby, the calculated sample size was 950.

Operational definitions

Hypertension

According to the 2017 guidelines on hypertension by the American College of Cardiology/American Heart Association (ACC/AHA 2017), hypertension was defined as systolic blood pressure (SBP) ≥130 mmHg, diastolic blood pressure (DBP) ≥80 mmHg or taking any prescribed antihypertensive drugs to control BP. For the present study, patients were classified into four stages according to their BP levels on the basis of the ACC/AHA guidelines [12]:

Stage of Elevated BP: SBP between 120–129 mmHg and DBP <80 mmHg;

Stage 1: SBP between 130‐139 mmHg or DBP between 80‐89 mmHg;

Stage 2: SBP ≥ 140 mmHg or DBP ≥ 90 mmHg;

Hypertension crisis: SBP > 180 mmHg and/or DBP > 120 mmHg.

Risk factors for hypertension

Hypertension does not have an exact cause except in case of secondary hypertension. Several factors affect the incidence of this disease. Some are modifiable, whereas others are not modifiable. Modifiable risk factors are mostly include lifestyle choices, such as smoking, poor physical activity, and employment status. However, some individuals are at a higher risk of hypertension, regardless of their lifestyle. These are non-modifiable risk factors, such as age, sex, marital status, race/ethnicity, and family history of hypertension [13-15]. In the current study, a family history of hypertension was defined as having one or more close family members with high BP and smoking status was defined as never smoked, past smoker, or current smoker. Physical activity was defined as exercise performance for at least 30 minutes per day for 5 days in a week.

Incidence rate

The incidence rate measures the frequency of new cases of disease in a population. It considers the sum of the time that each person remained under observation and at risk of developing the outcome under investigation [16]. It is calculated as:

Relative risk

The relative risk or risk ratio is used when the study involves comparing the likelihood or chance of an event occurring between two groups [17]. It is calculated as:

Data collection tool and measurement

When examining patients, all physicians had access to the hospital’s electronic records, which contained complete information of patient’s previous visits, current medical conditions including their BP readings, and their current drug list and comorbidities. An appropriate diagnosis of hypertension was defined as ICD-10 code on the hospital electronic record system. A structured data collection tool was developed based on a comprehensive literature review, which consisted of baseline demographic information, medical history, and BP. All the questions in the tool were close-ended. The BP of the patients was recorded by well-trained nurses using an automatic BP monitor. The mean follow-up interval for the current study was 3 months.

Data entry and data management

Data were collected from hospital electronic records by an experienced research assistant. The coding of continuous and categorical variables was performed and reviewed for any discrepancies. The data collection process was followed by two investigators, and the consistency of the entered data was cross-checked. Data that did not meet quality control inspections were excluded from the analysis. Data management and analysis were performed using the Statistical Package for Social Sciences version 23.0, for Windows (SPSS Inc., Chicago, USA).

Statistical analysis

The results were summarised as frequencies and percentages for qualitative variables and means and standard deviations (SDs) for quantitative variables. The incidence rates and relative risk ratios for the different stages of hypertension were calculated. For analysis purposes, the mean BP measurement of the three visits was used to assign the stages of hypertension. Multinomial logistic regression analysis was performed to investigate the potential determinants of the different stages of hypertension. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Statistical significance was set at p < 0.05.

Ethical approval

As King Khalid Military Hospital is a part of King Salman Armed Forces Hospital, a single research and ethics committee is responsible for all ethical concerns of both the hospitals. Ethical approval for this study was obtained from the local research and ethics committee at King Salman Armed Forces Hospital under project number KSAFH-REC-2020-375. The informed consent was waived due to the retrospective nature of the study and the analysis used anonymous clinical data.

Results

Data from the last three separate medical visits of all known hypertensive patients between 1 January 2019 and 31 December 2019 were collected. The variables utilized in the study were defined by the author in the data collection tool. The flow chart below shows the collected data (Fig 1).

Fig 1

Flow chart of the study cohort.

Table 1 shows the overall profile of the 884 patients included in the final analysis. Patients were grouped according to stages of hypertension. More than half of the patients were aged between 38–47 years (52.0%). The majority of the patients were males (66.5%). More than 90% of the patients were Saudi Arabian (93.4%). Almost two-fifths of the patients had a positive family history of hypertension (44.6%). Four out of ten patients did not engage in any form of physical activity (42.0%).

Table 1

Selected characteristics of the study population grouped by stages of hypertension (n = 884).

Variables	Stage of Elevated BP 530 (%)	Stage 1 HTN 261 (%)	Stage 2 HTN 62 (%)	HTN Crisis 31 (%)	Total 884 (%)
Age
18–27 years	38 (7.2)	8 (3.1)	4 (6.5)	3 (9.7)	53 (6.0)
28–37 years	84 (15.8)	11 (4.2)	10 (16.1)	5 (16.1)	110 (12.4)
38–47 years	344 (64.9)	56 (21.5)	44 (71.0)	16 (51.6)	460 (52.0)
≥ 48 years	64 (12.1)	186 (71.3)	4 (6.5)	7 (22.6)	261(29.5)
Sex
Male	337 (63.6)	195 (74.7)	39 (62.9)	17 (54.8)	588 (66.5)
Female	193 (36.4)	66 (25.3)	23 (37.1)	14 (45.2)	296 (33.5)
Marital status
Single	72 (13.6)	30 (11.5)	15 (24.2)	9 (29.0)	126 (14.3)
Married	423 (79.8)	197 (75.5)	34 (54.8)	14 (45.2)	688 (75.6)
Divorced	27 (5.1)	23 (8.8)	10 (16.1)	3 (9.7)	63 (7.1)
Widowed	8 (1.5)	11 (4.2)	3 (4.8)	5 (16.1)	27 (3.1)
Nationality
Saudi	493 (93.0)	248 (95.0)	57 (91.9)	28 (90.3)	826 (93.4)
Non-Saudi	37 (7.0)	13 (5.0)	5 (8.1)	3 (9.7)	58 (6.6)
Employment
Employed	386 (72.8)	193 (73.9)	51 (82.3)	19 (61.3)	649 (73.4)
Unemployed	144 (27.2)	68 (26.1)	11 (17.7)	12 (38.7)	235 (26.6)
Family History of HTN
Yes	192 (36.2)	133 (51.0)	44 (71.0)	25 (80.6)	394 (44.6)
No	338 (63.8)	128 (49.0)	18 (28.0)	6 (19.4)	490 (55.4)
Smoking status
Never Smoked	214 (40.4)	83 (31.8)	31 (50.0)	16 (51.6)	344 (38.9)
Past Smoker	121 (22.8)	69 (26.4)	16 (25.8)	7 (22.6)	213 (24.1)
Current Smoker	195 (36.8)	109 (41.8)	15 (24.2)	8 (25.8)	327 (37.0)
Physical activity
Yes	431 (81.3)	59 (22.6)	15 (24.2)	8 (25.8)	513 (58.0)
No	99 (18.7)	202 (77.4)	47 (75.8)	23 (74.2)	371 (42.0)

Abbreviations: BP-blood pressure, HTN-Hypertension.

Table 2 shows the mean systolic and diastolic blood pressures (mmHg) at different visits among the studied population.

Table 2

Mean systolic and diastolic blood pressure at different visits (mm hg) and incidence of hypertension.

Stages of Hypertension	Visit 1		Visit 2		Visit 3
	SBP (Mean ± SD)	DBP (Mean ± SD)	SBP (Mean ± SD)	DBP (Mean ± SD)	SBP (Mean ± SD)	DBP (Mean ± SD)
Stage of Elevated BP	122.66 ± 5.23	74.22 ± 2.81	123.83 ± 5.44	73.33 ± 2.98	123.91 ± 5.56	74.60 ± 2.89
Stage 1 HTN	132.05 ± 5.42	84.53 ± 2.78	134.85 ± 5.79	85.36 ± 2.88	133.98 ± 5.83	83.68 ± 2.92
Stage 2 HTN	146.01 ± 3.29	92.52 ± 3.22	150.70 ± 3.06	93.02 ± 3.28	145.78 ± 3.01	98.33 ± 2.84
Hypertension crisis	180.26 ± 4.36	125.78 ± 3.76	189.64 ± 5.63	132.16 ± 4.97	185.37 ± 5.19	127.96 ± 3.48

Abbreviations: BP-blood pressure, SBP-systolic blood pressure, DBP- diastolic blood pressure, HT-hypertension, SD- standard deviation, CI-confidence interval.

Fig 2 shows the incidence of hypertension within the four stages of BP defined in this study. Stage of elevated BP: SBP 120–129 mmHg and DBP<80 mmHg; stage1: SBP 130–139 mmHg or DBP 80–89 mmHg; stage 2: SBP≥140 mmHg or DBP≥90 mmHg; hypertension crisis: SBP > 180 mmHg and/or DBP > 120 mmHg. The incidence rate was reported as per 1,000 person-years. Error bars represent 95% confidence intervals for the incidence rate (Fig 2). The incidence rates according to BP stage were as follows:

Fig 2

Incidence of different stages of hypertension and corresponding 95% confidence intervals.

Incidence of stage of elevated BP = 530/884 = 60.0 new cases of stage of elevated BP per 1000 persons.

Incidence of stage 1 hypertension = 261/884 = 29.5 new cases of stage 1 hypertension per 1000 persons.

Incidence of stage 2 hypertension = 62/884 = 7.01 new cases of stage 2 hypertension per 1000 persons.

Incidence of hypertension crisis = 31/884 = 3.50 new cases of hypertension crisis per 1000 persons.

Table 3 shows the relative risk of different stages of hypertension by age, sex, and family history of hypertension. The risk of hypertension crisis was found to increase by 5.9 times in old age (≥48 years) compared to young age. Males were 1.6 times more likely to develop stage 2 hypertension than females. A positive family history of hypertension was associated with a 151% increase in the risk of hypertension crisis (Table 3).

Table 3

Relative risk of hypertension by age, sex, and family history of hypertension.

Risk Factors	Relative Risk (95% CI for RR)
	Stage 1 HTN	Stage 2 HTN	Hypertension Crisis
Age
18–27 years	1.21 (1.01–1.45)	0.49 (0.26–0.95)	1.28 (0.62–2.62)
28–37 years	1.33 (1.17–1.49)	0.31 (0.17–0.54)	1.35 (0.81–2.27)
38–47 years	0.97 (0.87–1.06)	0.25 (0.19–0.32)	1.68 (1.11–2.51)
≥48 years	0.33 (0.26–0.41)	0.32 (0.17–0.59)	5.92 (4.72–7.42)
Sex
Male	0.82 (0.68–0.98)	1.67 (0.53–2.85)	1.37 (0.93–2.02)
Female	1.13 (1.01–1.26)	1.17 (1.07–1.27)	0.96 (0.92–1.01)
Family History of Hypertension
Yes	0.77 (0.69–0.87)	1.41 (1.12–1.74)	1.51 (1.0.3–2.23)
No	1.44 (1.23–1.69)	0.86 (0.79–0.94)	0.95 (0.91–0.99)

Abbreviations: RR-relative risk, CI-confidence interval, HTN-hypertension. Note: The reference category is the stage of elevated blood pressure.

Table 4 reports the output of the multinomial logistic regression model. The main effect model was used on different stages of hypertension by considering the above stated risk factors. The results of the analysis indicated that the fitted model was good, with χ2 = 594.97, p-value = 0.992 (deviance criterion used), and Nagelkerke R2 = 0.731. Additionally, the test of the full model against the constant model showed a significant result, χ2 = 772.87, p-value < 0.0001, suggesting that the above mentioned risk factors as a group satisfactorily distinguished the four stages of hypertension.

Table 4

Multinomial logistic regression differentiating stage of elevated blood pressure from stage 1 hypertension, stage 2 hypertension, and hypertension crisis.

		Stage 1 Hypertension				Stage 2 Hypertension				Hypertension Crisis
Variables	Categories	B	Wald χ2-Statistics	OR (95% CI)	P-value	B	Wald χ2-Statistics	OR (95% CI)	P-value	B	Wald χ2-Statistics	OR (95% CI)	P-value
Age	28–37 years	0.71	2.48	0.65 (0.23–1.75)	0.369	0.49	1.96	0.78 (0.34–1.75)	0.375	0.53	1.74	0.89 (0.33–2.42)	0.271
	38–47 years	0.99	3.49	0.63 (0.26–1.49)	0.496	1.78	8.90	1.93 (0.26–2.49)	0.293	1.79	2.82	1.58 (0.41–2.42)*	0.026*
	≥ 48 years	1.29	3.91	5.00 (1.63–15.36)*	0.01*	1.93	4.36	6.00 (2.48–9.56)*	0.005*	2.17	8.68	3.62 (1.99–8.42)*	0.04*
Sex	Male	1.71	10.44	5.54 (1.96–15.67)*	0.001*	1.67	7.36	3.69 (1.68–7.78)*	<0.001*	1.21	4.61	2.84 (0.57–5.92)*	0.001*
Marital status	Married	1.56	10.23	1.20 (0.67–2.15)*	0.478	1.31	6.13	1.58 (0.89–3.25)*	0.001*	1.79	5.21	1.83 (0.43–3.64)*	<0.001*
	Divorced	1.63	5.81	1.02 (1.15–7.04)*	0.013*	1.54	7.32	1.62 (1.46–6.42)*	0.02*	1.58	2.73	0.55 (0.14–2.06)	0.789
	Widowed	0.76	1.83	2.16 (0.55–8.47)	0.371	0.94	1.36	3.13 (0.63–7.93)	0.74	1.48	5.39	1.24 (0.26–5.90)*	<0.001*
Nationality	Saudi	0.57	0.62	3.24 (0.89–11.73)	0.401	0.71	0.89	6.24 (1.37–12.39)	0.879	1.11	1.49	0.31 (0.09–1.08)	0.065
Employment	Unemployed	0.31	0.74	0.49 (0.23–1.05)	0.318	0.48	0.91	0.91 (0.41–1.29)	0.53	0.53	1.73	0.69 (0.30–1.58)	0.380
Family History of Hypertension	Yes	0.85	18.19	2.35 (1.59–5.48)*	0.008*	0.70	12.34	3.78 (1.23–6.74)*	<0.001*	0.67	8.09	1.95 (1.23–3.09)*	0.004*
Smoking status	Past Smoker	-0.67	1.99	0.51 (0.20–1.30)	0.254	-0.56	2.31	0.70 (0.16–2.96)	0.158	-0.74	1.89	0.47 (0.16–1.37)	0.169
	Current Smoker	1.35	0.60	1.70 (0.29–3.72)*	*0.036	2.64	0.37	2.38 (0.87–6.21)*	0.023*	3.44	7.74	1.74 (1.23–4.76)*	0.002*
Physical activity	No	1.12	9.56	3.01 (1.51–6.27)*	*0.02	1.82	8.23	2.51 (1.12–5.97)*	0.002*	1.64	10.28	6.48 (2.46–9.14)*	0.035*

Reference categories: 1) Hypertension: stage of elevated blood pressure; 2) Age: 18–27 years, 3) Sex: female; 4) Marital status: single; 5) Nationality: non-Saudi; 6) Employment: employed; 7) Family history of hypertension: no; 8) Smoking status: never smoked; 9) Physical activity: yes.

Abbreviations: OR-Odds Ratio, CI-Confidence Interval.

Note:

* represents significant p-value <0.05.

The analysis revealed that the increasing risk of hypertension with age was apparent only when comparing participants in the upper age stratum (≥48 years) with those in the lower stratum (<28 years). Male subjects were more likely to have stage 1 (OR = 5.54, 95% CI: 1.96–15.67) and stage 2 (OR = 3.69, 95% CI: 1.68–7.78) hypertension. Subjects with a positive family history of hypertension were more prone to develop stage 1 hypertension (OR = 2.35, 95% CI: 1.59–5.48). Lastly, the subjects who had no physical activity were more likely to develop stage 1 hypertension (OR = 3.01, 95% CI: 1.51–6.27) and hypertension crisis (OR = 6.48, 95% CI: 2.46–9.14) (Table 4).

Discussion

This retrospective cohort study is among the few to determine the incidence of different stages of hypertension in a broadly inclusive population of subjects recruited into medical care at military-setting hospitals. The major findings of this study included the following: (1) the incidence of stage of elevated BP (60.0 cases per 1000 persons) during one year of the study period and (2) older age, male sex, marital status, positive family history, current smoking status, and physical inactivity were significantly associated with an increased risk of hypertension in the study population.

The present study revealed that the incidence of hypertension was high among the studied populations. This finding agrees with results from previous studies conducted in the Gulf region and other developing countries [18, 19]. An increase in BP with age is considered a universal aspect of human aging and the present study supported the fact that advancing age is an important risk factor for hypertension. This finding was also in agreement with results from previous studies conducted in developed and developing countries with different sociodemographics, varied cultures, and geographically diverse populations [20-22].

Globally, the impact of sex on the incidence of hypertension has been reported in several studies [23, 24]. This study explored the association between sex and hypertension. Men were more likely to develop hypertension than women. This result confirmed the findings of other regional and national studies that described the tendency of males to have a higher BP [25, 26]. The present study did not show any association between nationality and hypertension. According to this study, the incidence of hypertension was not linked to employment status. This was contrary to what has been reported in the previous studies regarding this association [27].

In addition, our results revealed the association between the incidence of hypertension and marital status. Married individuals were more likely to have stage 2 hypertension and a hypertension crisis. Previous studies have shown that hypertension is significantly more common among married and divorced individuals [28]. In contrast, some studies have found that never-married individuals are at a high risk of developing hypertension [29, 30]. Moreover, the present study highlighted that genetic factors are important risk factors for hypertension. Individuals with a positive family history of hypertension were discovered to be more likely to develop stage 2 hypertension crisis in the current study. This result is in line with other studies that reported that the involvement of genetic factors may cause an individual to be at increased risk of developing hypertension [31, 32].

Smoking status was another risk factor associated with the incidence of hypertension in this study. Population-based research studies have found that the incidence of hypertension is higher among current smokers [33, 34]. Lack of physical activity was also identified as an important modifiable risk factor and it was revealed that individuals with a sedentary lifestyle were more likely to develop hypertension. This finding supports the results of previous studies showing that physical inactivity increases the risk of hypertension [35, 36]. The shift in hypertension from one stage to another could be attributed to poor adherence to medication or any other poor lifestyle habit.

Strengths and limitations of the study

Most previous studies have investigated predictors of hypertension using separate models. However, this study investigated four stages of hypertension using the same model. The major strength of this study is that it is a cohort study which attempted to establish how the associations between the outcomes (stages of hypertension) and the suspected predictors vary according to the level of outcome. This study also has its limitations. Not all risk factors related to hypertension were included in this study due to resource constraints. In addition, the current study did not include data related to hypertension, such as symptoms, check-up visits, elevated blood lipids, circulating inflammatory markers, oxidative stress markers, antihypertensive treatment, etc. There could have been a misclassification bias created in abstracting records which was overcome by cross-checking the data entered by the two investigators.

Conclusion

The present study demonstrated that the incidence of stage of elevated BP was high among the studied patients at military-setting hospitals in Tabuk, Saudi Arabia. Age, sex, marital status, family history, smoking status, and physical activity were significant predictors of hypertension development. The findings of this study will bridge the existing knowledge gap in literature regarding hypertension and will be of significance not only for the region of study but also for the other parts of Saudi Arabia, the Gulf region, and possibly other developing countries.

We proposed a logistic regression model to predict the progression of different stages of hypertension in this study. These results strongly support the adoption of standardised systemic hypertension screening for patients and highlight the need to introduce evidence-based noncommunicable disease prevention approaches in the Tabuk region of Saudi Arabia. Further prospective multicentre cohort studies evaluating hypertension and its complications in Saudi Arabia are highly recommended.

16 Apr 2021

PONE-D-21-07004

Incidence and Risk Factors of Hypertension: A Multicentre Retrospective Cohort Study in Tabuk, Saudi Arabia

PLOS ONE

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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: Partly

**********

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

Reviewer #1: Yes

Reviewer #2: No

**********

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: Thank you for a thorough study of the epidemiology of hypertension in an understudied population. I have a few comments:

-First of all, the paper needs thorough language editing.

-In the methodology, it is stated that patients were included with hypertension diagnosed according to ICD-10. ICD-10 is a disease coding/classification system, not a set of diagnostic criteria. The criteria used (ACC/AHA 2017) should be mentioned instead.

-I couldn't find a clear mention of how long the (mean) follow up interval was anywhere. Please include, because a short interval would be a limitation that needs mentioning.

-References should be provided for the parameters used in the sample size calculation such as the odds ratio, risk/prevalence ratio, etc, or at least some justification for their choice if arbitrary.

-Since this is effectively a time-series analysis, I think a multivariate cox proportionate hazards model would be appropriate to include to help disentangle the effect of confounding variables.

-In the results, I couldn't help but notice that so few patients are over 47, which is not very representative of the hypertensive patient population. The reason for this should be clarified.

-Some essential data such as the presence and type of antihypertensive treatment are not included in the analysis. This should at least be mentioned in the limitations. It would also be useful to mention the reason for presentation, e.g. checkup visit, symptoms, etc if possible.

Overall, the study provides much needed data about hypertensive risk factors in the Saudi Arabian population, and would be useful to publish after the above considerations.

Reviewer #2: 1- GENERAL COMMENT

The strength of the current research is studying all the stages of hypertension aiming to identify the incidence rate and the predictors associated with hypertension, which is an interesting subject. There are very few studies dealing with the incidence of hypertension and changes in blood pressure over time. although the difficulty of studying the incidence rate of hypertension lie in the diversity of the incidence rate of hypertension with the regions.

The manuscript needs English editing since there are several typos and grammatical errors.

2- INTRODUCTION

2.1. The authors should elaborate more on the previous research that includes the incidence of hypertension in different ethnicities. For example, the CARLA-Cohort study.

Lacruz ME, Kluttig A, Hartwig S, Löer M, Tiller D, Greiser KH, Werdan K, Haerting J. Prevalence and Incidence of Hypertension in the General Adult Population: Results of the CARLA-Cohort Study. Medicine (Baltimore). 2015 Jun;94(22):e952. doi: 10.1097/MD.0000000000000952. PMID: 26039136

2.2. It is advised to cite previous studies about the incidence rate of hypertension in the Gulf area.

3. MATERIALS AND METHODS

3.1. The methods were not written in sufficient detail to allow the study to be replicated. The study design was reported as a retrospective cohort, therefore this should be explained, and the two cohorts should be defined; the exposed cohort and the non-exposed one.

3.1. The recruitment of the patients was described as from the nephrology, cardiology and internal medicine departments. Was the recruitment from the outpatient clinics or the inpatient department? This issue was not clear.

3.2. The patients had three blood pressure measurements, if the patient has more than 3 measurements, what did the authors do? It should be stated that the last three measurements were used in the methods section. Did you mean these measurements? What is the minimum interval allowed between these three measurements? All these details should be mentioned in the methods section.

3.3. Why did the authors exclude the diagnosis of hypertension in less than 6 months? This might bias the results.

3.4. Regarding the operational definitions, the referee suggests removing the paragraph that defines the blood pressure, which is found on page 2, line 41-44.

3.5. The inclusion criteria were not clear in the Methods section. It should be written in details.

3.6. How did the authors adjust for the change of age overtime of the study of one year?

3.7. Regarding the calculation of the incidence rate,

• The equations of incidence rate and relative risk should be supported by the related references.

• The way of calculation of the incidence rate should be written in the methods more comprehensively, and in the results as well. For example, how did the authors diagnose the new cases of hypertension? How many new cases did the authors diagnose? Then, put the incidence rate equation defining both the numerator and denominator, to find out the incidence rate.

3.8. All the risk factors should be defined and cited. For example, the physical activity was defined but not referenced, while the family history of hypertension, smoking status were not defined nor referenced. The referee suggests applying these in the operational definition.

4. RESULTS

4.1. The stage of elevated BP according to ACC guidelines 2017, is stated in different contexts of the manuscript as ELEVATED HYPERTENSION, which needs to be corrected through the manuscript to THE STAGE OF ELEVATED BP, because it does not fulfil the criteria of hypertension. The same error was found in figure 1.

4.2. In all stages of BP STATED in figure 1, the total cases were demonstrated. The new cases should be mentioned as well.

4.3. The legend of Table 2 stated the mean systolic and diastolic BP and the incidence of hypertension. There is no incidence of hypertension in this table.

4.4. In Figure 2, it is advised to highlight the equation of each stage defining the numerator and denominator till you calculate the incidence rate. Importantly, mention the new cases.

4.5. On page 7, it was mentioned that there is an increasing risk of stage 2 with age. Nevertheless, not only stage 2, but also stage 1 and the hypertensive crisis.

4.6. Table 4 needs important modifications:

4.6.1. It is very important to mention the p-value for each relation of the table, and highlighting the significant ones.

4.6.2. The table depicted 4 relationships as significant, meanwhile, they need to be double-checked for the significance because the CI of the odds ratio (OR) ranging from below 1 to above 1, which in many situations refers to a non-significant relationship. It is advised to consult a statistician to solve this issue. The four relations are the marital status and stage 1, the marital status and hypertensive crisis, the current smoking and stage one, and the current smoking and stage 2.

4.6.3. Why the elevated BP stage was not included in table 3 and 4. It is better to be added.

5. DISCUSSION

5.1. It needs to be comprehensive.

5.2. All the risk factors should be discussed in more details. As unemployment and nationality/race were not mentioned.

5.3. It will be valuable to mention the black race as an important subgroup.

5.4. All the references used in the discussion should be explained in detail trying to explain the similarities and differences with the current study.

6. CONCLUSION

6.1. It should be reconstructed to highlight the main findings and support the study results. The conclusion in the abstract should be matched with the manuscript conclusion.

**********

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Reviewer #1: No

Reviewer #2: Yes: Hussein M. Ismail

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14 Nov 2021

08/11/2021

Emily Chenette

Editor-in-Chief

PLOS One

Dear Editor:

I wish to resubmit a research article for publication in PLOS One, titled “Investigating the incidence and risk factors of hypertension: a multicentre retrospective cohort study in Tabuk, Saudi Arabia.” The paper was coauthored by Nasrin S Saiyed, Bandar Al Qahtani, Attiya Mohammed Al Zahrani, Yassir Birema, and Ibrahim Al Hariri.

This study aimed to determine the incidence of different stages of hypertension and its associated modifiable and non-modifiable risk factors among patients attending two different hospitals in Tabuk, Saudi Arabia. We believe that our study makes a significant contribution to the literature because there have been studies in the past in Saudi Arabian populations exploring the relevant risk factors for hypertension, but all these studies were cross-sectional in design. To the best of our knowledge, the current retrospective cohort study on hypertension and related risk factors is the first study of this type to be conducted in the region of Tabuk in Saudi Arabia.

Further, we believe that this paper will be of interest to the readership of your journal because the results of this study can be extended and applied to other regions of Saudi Arabia as well as in the Gulf region which has similar demographics and an increased incidence of diseases which are complicated by hypertension. In addition, we have also proposed a logistic regression model which can predict the progression of different stages of hypertension and will be highly beneficial for medical practitioners.

We appreciate the time and effort that you and the reviewers have dedicated to providing your valuable feedback on my manuscript. We are grateful to the reviewers for their insightful comments on my paper. We have been able to incorporate changes to reflect most of the suggestions provided by the reviewers. We have highlighted the changes within the manuscript. Here is a point-by-point response to the reviewers’ comments and concerns.

Comment 1: Thank you for stating the following in the Funding Section of your manuscript: "The study was fully funded by Research Unit, Academic Affairs Department, King Salman Armed Forces Hospital Tabuk, Saudi Arabia." We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows: "NO" Please include your amended statements within your cover letter; we will change the online submission form on your behalf.

Response: The statement related to funding was removed from the manuscript. The Funding Statement for the online submission is as follows:

“The study was fully funded by Research Unit, Academic Affairs Department, King Salman Armed Forces Hospital Tabuk, Kingdom of Saudi Arabia.”

Comment 2: We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/dataavailability#loc-unacceptable-data-access-restrictions.

In your revised cover letter, please address the following prompts:

a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent.

b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories.

We will update your Data Availability statement on your behalf to reflect the information you provide.

Response: The data used to support the findings of this study are available from King Salman Armed Forces Hospital and King Khalid Military Hospital but restrictions apply to the availability of these data as it contains potentially identifying patient information. Data are however available from first author upon reasonable request and with permission of research and ethics committee at King Salman Armed Forces Hospital. The data sharing statement is as follows:

“The data used to support the findings of this study are available from King Salman Armed Forces Hospital and King Khalid Military Hospital but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from first author upon reasonable request and with permission of research and ethics committee at King Salman Armed Forces Hospital.”

Comment 3. 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

Response: The ORCID id is updated. The ORCID id for the corresponding author Dr. Umar Yagoub is 0000-0003-1427-251X.

Comment 4. Your ethics statement should only 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 ensure that your ethics statement is included in your manuscript, as the ethics statement entered into the online submission form will not be published alongside your manuscript.

Response: The ethics statement is moved to the Methods section of the manuscript.

Comment 5. Please ensure that you refer to Figure 1 in your text as, if accepted, production will need this reference to link the reader to the figure.

Response: Change has been made to the manuscript. The figure is referred in the text.

Comment 6. Is the manuscript presented in an intelligible fashion and written in standard English? / the Paper needs thorough language editing.

Response: The manuscript has been edited by professional language editor for English editing. The language editing certificate is attached with this email.

Comment 7. In the methodology, it is stated that patients were included with hypertension diagnosed according to ICD10. ICD-10 is a disease coding/classification system, not a set of diagnostic criteria. The criteria used (ACC/AHA 2017) should be mentioned instead.

Response: Correction is made in the manuscript. All patients aged 18 years and older with diagnosed hypertension according to American College of Cardiology/American Heart Association (ACC/AHA 2017) were included in the study cohort. Whose disease coding were done according to ICD‐10 (International Statistical Classification of Diseases and Related Health Problems 10th Revision).

Comment 8. I couldn't find a clear mention of how long the (mean) follow up interval was anywhere. Please include, because a short interval would be a limitation that needs mentioning.

Response: The mean follow-up interval for the current study was 3 months.

Comment 9. References should be provided for the parameters used in the sample size calculation such as the odds ratio, risk/prevalence ratio, etc., or at least some justification for their choice if arbitrary.

Response: Limited resources were the primary reason for the choice of the sample size.

Comment 10. Since this is effectively a time-series analysis, I think a multivariate cox proportionate hazards model would be appropriate to include to help disentangle the effect of confounding variables.

Response: Here the logistic regression analysis is used because the follow-up for all the patients is complete and have no censored data. Also, the logistic regression result can be presented to better visualize the differences in the number of events between groups.

Comment 11. In the results, I couldn't help but notice that so few patients are over 47, which is not very representative of the hypertensive patient population. The reason for this should be clarified.

Response: Overall, 81.5% patients in the cohort aged 38 years and older had hypertension in the current study, which shows a representative of the hypertensive patient population.

Comment 12. Some essential data such as the presence and type of antihypertensive treatment are not included in the analysis. This should at least be mentioned in the limitations. It would also be useful to mention the reason for presentation, e.g. checkup visit, symptoms, etc. if possible.

Response: As due to resources constraints we didn’t collect the data related checkup visit, symptoms, the presence and type of antihypertensive treatment for the current study. These are now added in the limitations.

Comment 13. The authors should elaborate more on the previous research that includes the incidence of hypertension in different ethnicities. For example, the CARLA-Cohort study.

Response: Comparisons between different studies reporting incidence rates of hypertension are problematic due to diverse definitions used and differences in the population structure, especially, variances in age range. The CARLA-Cohort study is discussed in the introduction.

Comment 14. It is advised to cite previous studies about the incidence rate of hypertension in the Gulf area.

Response: Cited in the Discussion Section.

Comment 15. The methods were not written in sufficient detail to allow the study to be replicated. The study design was reported as a retrospective cohort, therefore this should be explained, and the two cohorts should be defined; the exposed cohort and the non-exposed one.

Response: Changes have been made in the manuscript.

Comment 16. The recruitment of the patients was described as from the nephrology, cardiology and internal medicine departments. Was the recruitment from the outpatient clinics or the inpatient department? This issue was not clear.

Response: The patients were recruited from both outpatient clinics and the inpatient departments. Added in the methodology.

Comment 17. The patients had three blood pressure measurements, if the patient has more than 3 measurements, what did the authors do? It should be stated that the last three measurements were used in the methods section. Did you mean these measurements? What is the minimum interval allowed between these three measurements? All these details should be mentioned in the methods section.

Response: The patients had three blood pressure measurements, if the patient has more than 3 measurements then only last three measurements were used for the study. The rest blood pressure measurements did not consider in the study. The changes in the methodology is made.

Comment 18. Why did the authors exclude the diagnosis of hypertension in less than 6 months? This might bias the results.

Response: Most of the newly diagnosed hypertensive patients didn’t have three visits in 6 months that is the reason for exclusion.

Comment 19. Regarding the operational definitions, the referee suggests removing the paragraph that defines the blood pressure, which is found on page 2, line 41-44.

Response: Removed from the manuscript.

Comment 20. The inclusion criteria were not clear in the Methods section. It should be written in details.

Response: The inclusion criteria in the manuscript is rewritten.

Comment 21. How did the authors adjust for the change of age over time of the study of one year?

Response: Crude incidence rates are calculated for the same.

Comment 22. Regarding the calculation of the incidence rate, the equations of incidence rate and relative risk should be supported by the related references.

Response: References cited in the manuscript.

Comment 23. The way of calculation of the incidence rate should be written in the methods more comprehensively, and in the results as well. For example, how did the authors diagnose the new cases of hypertension? How many new cases did the authors diagnose? Then, put the incidence rate equation defining both the numerator and denominator, to find out the incidence rate.

Response: When examining patients, all physicians have access to the hospital's electronic records. The electronic medical record in the hospital keeps track of a patient's previous visits, current medical conditions including their blood pressure readings, as well as their current drug list and comorbidities. Appropriate diagnosis of hypertension was defined as an ICD-10 code on the hospital electronic record system.

Calculations for the incidence rates for the different stages of hypertension were made under the table no. 2.

Comment 23. All the risk factors should be defined and cited. For example, the physical activity was defined but not referenced, while the family history of hypertension, smoking status were not defined nor referenced. The referee suggests applying these in the operational definition.

Response: Changes have been made in the manuscript.

Comment 24. In the results section, the stage of elevated BP according to ACC guidelines 2017, is stated in different contexts of the manuscript as ELEVATED HYPERTENSION, which needs to be corrected through the manuscript to THE STAGE OF ELEVATED BP, because it does not fulfil the criteria of hypertension. The same error was found in figure 1.

Response: Agreed, the correction is made in the manuscript.

Comment 25. In the results section, in all stages of BP STATED in figure 1, the total cases were demonstrated. The new cases should be mentioned as well.

Response: In the figure 1, new cases were mentioned as events.

Comment 26. In the results section, the legend of Table 2 stated the mean systolic and diastolic BP and the incidence of hypertension. There is no incidence of hypertension in this table. In Figure 2, it is advised to highlight the equation of each stage defining the numerator and denominator till you calculate the incidence rate. Importantly, mention the new cases.

Response: Agreed, the calculation of incidence rate is mentioned under table 2 with new cases for each stages of hypertension.

Comment 27. On page 7, it was mentioned that there is an increasing risk of stage 2 with age. Nevertheless, not only stage 2, but also stage 1 and the hypertensive crisis.

Response: Agreed, correction has been done in the manuscript.

Comment 28. Table 4 needs important modifications: It is very important to mention the p-value for each relation of the table, and highlighting the significant ones.

Response: The p-values for each categories is added in table.

Comment 29. The table depicted 4 relationships as significant, meanwhile, they need to be double-checked for the significance because the CI of the odds ratio (OR) ranging from below 1 to above 1, which in many situations refers to a non-significant relationship. It is advised to consult a statistician to solve this issue. The four relations are the marital status and stage 1, the marital status and hypertensive crisis, the current smoking and stage one, and the current smoking and stage 2.

Response: The justification from the statistician is quoted as follows:

Two measures of 'significance' p value and the confidence interval. Although it may have met the threshold for p value 'statistical significance' what a small OR and CI touching or crossing 0 are concluding that the effect itself is very small.

Comment 30. Why the elevated BP stage was not included in table 3 and 4. It is better to be added.

Response: The elevated BP stage was not included in table 3 and 4 because it is the reference category.

Comment 31. In the discussion section, it needs to be comprehensive.

Response: Changes have been made in the discussion section of the manuscript.

Comment 32. All the risk factors should be discussed in more details. As unemployment and nationality/race were not mentioned.

Response: Changes have been made in the discussion section of the manuscript.

Comment 33. It will be valuable to mention the black race as an important subgroup.

Response: As we did not include the race category in the study we are unable to quote about the black race. Only nationality of the subject included in the research. Which is either Saudi or non-Saudi.

Comment 34. All the references used in the discussion should be explained in detail trying to explain the similarities and differences with the current study.

Response: Changes have been made in the discussion section of the manuscript.

Comment 35. In the conclusion section, it should be reconstructed to highlight the main findings and support the study results. The conclusion in the abstract should be matched with the manuscript conclusion.

Response: Changes have been made in the discussion section of the manuscript.

This manuscript has not been published or presented elsewhere in part or in entirety and is not under consideration by another journal. All study participants provided informed consent, and the study design was approved by the appropriate ethics review board. We have read and understood your journal’s policies, and we believe that neither the manuscript nor the study violates any of these. There are no conflicts of interest to declare.

Thank you for your consideration. I look forward to hearing from you.

Sincerely,

Umar Yagoub

Research Department, King Salman Armed Forces Hospital,

Tabuk, Saudi Arabia

mohammedumar2001@yahoo.com

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

21 Dec 2021

Investigating the incidence and risk factors of hypertension: a multicentre retrospective cohort study in Tabuk, Saudi Arabia

PONE-D-21-07004R1

Dear Dr. Mohamed,

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

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Manal S. Fawzy, Ph.D., M.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

The authors have adequately addressed the concerns raised by the reviewers. Thank you

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

**********

2. 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: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. 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: Yes

**********

5. 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: Yes

**********

6. 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: (No Response)

Reviewer #2: (No Response)

**********

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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: Yes: Hussein M. Ismail

27 Dec 2021

PONE-D-21-07004R1

Investigating the incidence and risk factors of hypertension: a multicentre retrospective cohort study in Tabuk, Saudi Arabia

Dear Dr. Yagoub:

I'm 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 let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, 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.

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on behalf of

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