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Registry of the Egyptian specialized hypertension clinics: Sex‐related differences in clinical characteristics and hypertension management among low socioeconomic hypertensive patients

Abstract Hypertension is a major modifiable risk factor for cardiovascular disease (CVD) which is a leading cause of death in developing countries affecting both genders. Gender dissimilarity in clinical characteristics and hypertension (HTN) management among hypertensive patients has been reported in several reports before. The aim was to detect sex differences in clinical characteristics and HTN management among Egyptian hypertensive patients. Data from 4701 hypertensive patients attending 9 university located Specialized Hypertension clinic (SHC) were collected from October 2014 to September 2017. The collected data included demographics, cardiovascular risk profile, hypertension‐related history, anthropometric and blood pressure (BP) measurements, antihypertensive medications used, number of patients attending the follow‐up visits, and HTN control rate. Females represented 58.5% of the recruited patients, they were younger, with higher BMI, lower education level, and employment rate compared with males. Females had lower mean office systolic and diastolic BP than males (144.2 ± 22.6 vs. 146.5 ± 22.0 mmHg and 88.1 ± 13.0 vs. 89.9 ± 12.6 mmHg, respectively) and lower rate of uncontrolled BP (54.8% vs. 61.1% in males P < .001). Antihypertensive drugs were comparable among both sexes except for angiotensin converting enzyme inhibitors which were more prescribed in males. Compliance to antihypertensive medications was better in females (63.6% vs. 60.1% in males, P = .015). To conclude, Egyptian hypertensive females have different clinical characteristics as compared to their counterpart males with better BP control, adherence to antihypertensive medications, lower systolic and diastolic BP, and no major differences in the prescribed antihypertensive distribution.

living in developing countries. 1 By 2010, the worldwide prevalence reached 31.1% with 7.7% increase of prevalence in developing countries and 2.6% decrease in developed countries when compared to year 2000. 3 HTN is the most common modifiable risk factor for cardiovascular disease which is the leading cause of death in women. 4 The predicted global prevalence of HTN in women at 2025 is 29.5% with 13% predicted increase in worldwide prevalence of HTN in women from 2000 to 2025% versus 11% in male. 1 In general, women showed better awareness, treatment, and control rate of HTN than men both in economically developed and developing countries. 4 Data from the Egyptian National Hypertension Project (NHP) showed that prevalence of HTN was 26.3% among Egyptian adults with an awareness rate of 37.5% with 23.9% of patients receiving antihypertensive medications and control rate of only 8%. 5 Specialized hypertension clinics (SHCs) are outpatient clinics specialized in treating hypertensive Egyptian patients. They were launched in 2014 in 9 university hospitals across Egypt. A wellformed and electronically coded registry website was initiated for data entry and data from 4700 hypertensive patients were collected until 2017. 6 Since CVD is the leading cause of death in Egyptians (48.1%) and specifically in women (50.1%) 7 and HTN is an important preventable risk factor, it looks appealing to address the characteristics of HTN in Egyptian women. The aim is to study the sex-related differences in HTN clinical characteristics, treatment, and control among patients visiting the SHCs.

| ME THODS
The Egyptian SHCs began in 9 university hospitals, distributed along Patients were interrogated about history and duration of HTN, risk factors and associated co-morbid conditions (eg, chronic obstructive airway disease, peripheral arterial disease, diabetes mellitus, coronary artery disease, chronic kidney disease, cerebrovascular disease), type, side effects and compliance to antihypertensive medications and consumption of other drugs that may affect the BP (eg, nasal decongestants, non-steroidal anti-inflammatory drugs (NSAID), corticosteroids, or oral contraceptive pills (OCPs). Smoking was defined as actively smoking or utilizing tobacco within the past 6 months.
Examination included anthropometric measurements (body weight, height, and waist circumference) and supine and standing heart rate and blood pressure (BP). The body mass index (BMI) was calculated as the weight in kilograms divided by the height in meters square.
Obesity was defined as a body mass index (BMI) ≥ 30 kg/m 2 . 8 Waist circumference (WC) measurements were taken using a measuring tape. WC was measured from the horizontal plane midway between the lowest lateral border of the rib cage and iliac crest with cutoff value of 93.5 cm for men and 92.5 cm for women. 9 The BP was measured according to the standardized protocols using digitalized BP measuring devices (OMRON M-6, Japan), which is an FDA certified device. To reduce within-patient variability, patients were asked to rest for 5 minutes then BP was measured in the sitting position, three times in each arm, 1 minute apart. The first reading was omitted, and the next two readings were averaged. The arm with the higher BP was considered the reference arm in the follow-up visits. Standing BP was recorded once in the first visit after two minutes of standing. Hypertension was defined as systolic BP (SBP) ≥140 mmHg, and/or diastolic BP (DBP) ≥90 mmHg, and/or the use of antihypertensive medications. and/or a random plasma glucose of 200 mg/dl or higher. All measurements were taken at least twice. 11 Patients were also considered diabetics if they were previously diagnosed and are receiving anti-diabetic agents.
Dyslipidemia was considered when low density lipoprotein (LDL) cholesterol was ≥ 130 mg/dl, or high density lipoprotein (HDL) cholesterol ≤ 50 mg/dl in women and ≤ 40 mg/dl in men, increased triglycerides (TG) ≥150 mg/dl, or if the patient is currently receiving a lipid lowering agent. 12 A cardiovascular global risk was assessed based on the Egyptian guidelines risk scoring system for hypertensive patients. 13

| Statistical analysis
Statistical analysis was performed using SPSS 20 version. Qualitative data are presented as frequency and percentage while quantitative data are presented as mean and standard deviation. Chi-square test was used to compare a 2x2 categorical data, and Student's t test was used to compare continuous variables between two groups. P-value of ≤ .05 is considered significant.

| RE SULTS
The study included 4701 Egyptian hypertensive patients, 2753 (58.6%) of them were females. Table 1 shows the demographic characteristics of males and females. Hypertensive females were younger, heavier, and less educated than hypertensive males. As more than three quarters of female patients were housewives, and as the clinic was in the morning at the working times, more hypertensive females visited the SHC as compared to males.
Female showed lower systolic and diastolic blood pressure values and had a higher rate of BP control compared with males.
Despite the fact that most of the patients (n = 3859, 82.0%) were already known to have HTN before the first presentation to SHCs, yet only one third (34.6%) underwent previous HTN-related investigations and females were less investigated. Most females (62.5%) were in the low-and intermediate-risk categories, while half males were in the high-and very high-risk categories ( Table 2).
Among those who were prescribed drugs (n = 2949), 19.9% (n = 587) were non-compliant to their medications and compliance was better in females as compared to males (Table 3). More than one third of the patients were using other medications that were known to elevate the BP. Table 4 shows the sex-related differences in the co-morbidities.
Females had significantly lower prevalence of CAD, heart failure, and COPD but higher prevalence of thyroid diseases and arthritis.
More than half of the patients (n = 2699, 57.4%) who came to the SHC had uncontrolled HTN (Table 5 and Figure 1). Females with uncontrolled HTN had a bigger BMI and higher supine DBP and HR as compared to their counterpart males (Table 5).
After the first visit, all patients were asked to come to follow up their BP, but only a quarter of them (n = 1182, 25.1%) were compliant to their 2nd visit and even less patients came in the 3rd visit (n = 547, 11.6%). A progressively less number of patients attended

| DISCUSS ION
HTN is a major controllable risk factor for CVD morbidity and mortality worldwide. There has been a paradigm shift in the prevalence of HTN from high-income to low-and middle-income countries in the preceding few decades. 14 Given the high economic burden of HTN-related disabilities, a global target of reducing its prevalence by 25% at year 2025 compared with 2010 has been adopted. 15 The current study is the first nationwide study that addresses sex-related differences in demographics, clinical characteristics, and HTN management among hypertensive Egyptians. It showed that females had a lower systolic (144.2 vs. 146.5 mmHg, P =.001) and a lower diastolic blood pressure (88.1 vs. 89.9 mmHg, P <.001) compared with males. Females had better BP control rate (45.2% vs. 38.9%, P <.001) and better compliance to antihypertensive medications (63.6% vs.60.1%, P =.015).
Since 2007, HTN had become the leading risk factor for DALYs (disability-adjusted life years) in women. 2 Women are more susceptible to die from HTN-related CVD than men with the greatest lifetime risk of CVD in hypertensive women is between the age of 41-55. 16,17 Despite the increase in absolute burden of HTN for both genders globally, there has been a decrease in absolute burden of HTN in women in the Middle East and North Africa. 3 Each 1-SD decrease in 24-hour systolic BP in women is accompanied by a higher reduction of preventable CV events as compared to men (35.9% vs. 24.2%). 18 The global age standardized prevalence of HTN is higher in men than women (24.1% vs. 20.1%) which has been the same in all specific age-groups below the age of 50 years. 3,14 However, above the age of 50 years there is an increase in the prevalence of HTN The change of HTN prevalence in women with age is attributable to multiple factors. 19 Sex hormonal changes with menopause may play an important role as it is associated with pronounced increase in systolic BP and pulse pressure after menopause compared with men of the same age-group. 20 However, other factors may also contribute to this phenomenon including genetic predisposition, aging, obesity, and arterial stiffness. 19 However, the main mechanisms underlying sex-related difference in HTN is still unknown, but this may be related  25 However, other reports from Germany, 23 Turkey, 26 and National Health and Nutrition Examination Study (NHANES) 29 showed that treatment rates were significantly higher in females than males. This discrepancy may be related to the lower education level and the lower rate of employment in our female cohort which may be associated with limited access to health care facilities. This may also explain why hypertensive females were less subjected to HTN-related investigations compared with males.
Apart from discouragement of renin-angiotensin blocker use during childbearing period, there should be no sex-specific preference in the choice of available antihypertensive medications. 23 However, disparities in the prescribed medications among both genders have been reported. It was found that females were more likely prescribed diuretics and β-blockers while males were more likely prescribed rennin-angiotensin and calcium channel blockers. 16,27 This disparity of prescribed medications may be explained by the difference in comorbidities between both genders which influence the choice of the prescribed antihypertensive medications and the fact that drugs have sex-related side effect as it was found that females experience more dry cough with ACE inhibitors and more lower limb edema with calcium channel blockers. 30,31 On the other hand, beta blockers are associated with sexual dysfunction in men, an adverse effect which is rarely reported by women on β-blockers. 32 Similar to a German study addressing the gender gap in HTN, 23 our study showed no difference in drug distribution between both genders except for ARBS which was more prescribed in males than females.
Adherence to the antihypertensive medications is crucial to achieve guidelines recommended BP goals. However, adherence is affected by multiple factors interacting together in different ways. 33 Such factors include the class of the prescribed drug and whether it is a single (whether monotherapy or combination pill) or multiple pills with the highest discontinuation rate reported with diuretics monotherapy. 34 Also, adherence is affected by associated diseases and their nature with better compliance seen in patients with associated CVD compared with those with non-CVD. 33 Our study showed bet- Karelia in east of Finland and then applied all over Finland. 35 The North Karelia project was associated with significant reduction in mean systolic pressure in both genders and more than 80% reduction in the annual age-adjusted cardiovascular mortality proving the efficacy of such program. 35 Another useful program for the prevention of cardiovascular diseases within integration of hypertension management is the HEART program of the WHO. 36 Applying this stepwise strategic approach for the diagnosis, management and follow-up may improve the overall health care provided and the compliance of hypertensive patients. Initiation of such programs in Egypt should be tailored to target the sex-related differences demonstrated in this study and develops a protocol to overcome the poor adherence to follow up visits present in both sexes.

| CON CLUS ION
This study demonstrates the sex-based differences in demographic, clinical characteristics, and HTN management among Egyptian hypertensive patients. Despite the lower education level, employment rate, and the larger BMI, Egyptian hypertensive females showed a better BP control rate, a lower systolic and diastolic BP, and a better adherence to the antihypertensive medications.