Newsletter 3

Recent data from the Egyptian National Hypertension Project, the first cross sectional national hypertension survey in a developing country, showed that 26.3% of adult Egyptians suffer from high blood pressure(1). The prevalence rate exceeds 50% in individuals above the age of 60 years. The management of such large number of patients should be within the domain of the general practitioner and should consist of the following components:

1. Establish the Presence of Hypertension: This requires repeated and accurate BP measurements. Transient elevations of BP can occur secondary to drug intake, emotions, painful stimuli, distended urinary bladder, cigarette smoking or white coat effect.

2. Assess the Need for Pharmacological Therapy: Unless there is a hypertensive emergency or urgency, life style modifications should be advised and patients followed initially for a period of few weeks to six months without drug intervention. Early initiation of pharmacological treatments is indicated in patients with target organ damage, e.g., left ventricular hypertrophy, optic fundus changes, proteinuria, coronary artery disease or when there are associated cardiovascular risk factors, e.g., diabetes mellitus, family history, hypercholesterolemia, cigarette smoking, etc.

3. Life Style Modification: Weight reduction, physical exercise, alcohol moderation, stress management, salt restriction, and other dietary measures are part of treatment strategy. Diet rich in fruits and vegetables and low in animal fat can reduce BP (2).

4. Drug Treatment: Treatment can be started by a diuretic, beta-adrenergic blocker, angiotensin converting enzyme inhibitor, a calcium antagonist or a combination. Choice of therapy is guided by patients hemodynamic, risk profile and associated diseases. Diuretics are the least expensive antihypertensive drugs, can be given to all patients, specially the elderly, obese, blacks, those with early renal impairment, systolic hypertension or heart failure. Beta adrenergic blockers are recommended to hypertensive patients with hyperkinetic circulation or associated coronary artery disease. Angiotensin converting enzyme inhibitors are given to diabetic hypertensives, hyperurecemia or heart failure. Calcium antagonists are recommended to coronary patients, elderly, systolic hypertension or in the presence of metabolic disturbances.

5. Follow-Up: Majority of antihypertensive drugs require ~8 weeks in order to achieve their maximum hypertensive action (3). Unless there is a need for its rapid lowering, BP should be checked after 2-4 weeks after intitiation of treatment and then every 4-8 weeks until control of BP is achieved. Then patients should be seen every 3-4 months regularly. If the patients did not tolerate the drug or if it fails to control hypertension after 6-8 weeks of administration, another agent from a different group is tried. It is recommended to start with a small dose and to increase the dose after 4-8 weeks or add another agent if BP control is not achieved. Lifestyle modification and control of other risk factors should be stressed.

1. Ibrahim M. M., Rizk H., Appel L. J., et al. Hypertension Prevalence Awareness, Treatment and Control in Egypt: Results from the Egyptian Hypertension Project. Hypertension 2995; 26: 886-890

2. Appel L; I, Moore T.J., Obarzanek E., et al. Dietary intervention in Hypertension. N Eng. J Med. 1997; 336:1117-24.

3. Ibrahim M.M., Mossallam R. Clinical Evaluation of Atenolol in Hypertensive Patients. Circulation 19~l; 62: 1036-44.

M. Mohsen Ibrahim, MD
Professor and Chairman of the Cardiology
Department-Cairo University.
Principal Investigator the Egyptian National
Hypertension Project

RIGHT VENTRICUlAR FILLING DYNAMCS IN SYSTEMIC HYPERTENSION
Kamel H. (MD), Hamouda M.S.(MD), Mahmoud 5. (M.D), acid Badr S. (M.D),
Cardiac department, Tanta University

Fifty hypertensive patients & 30 matched normals tindenvent echo-Doppler study to assess right ventricular (RV) & left ventricular (LV) filling characteristics & their interactions. Both RV & LV wall thickness were significantly higher in hypertensives than normal (P < 0.01). Mitral & tricuspid EIA ratio, RV & LV peak filling rate (PFR) nortualized to end diastolic volume (EDV) & PFR normalized to stroke volume (SV) were significantly lower in hypertensives than normals (P< 0.01). Further, PFR normalized to SV produced closer relation between RV & LV filling in both hypertensives & normals than did PFR normalized toEDV.

In conclusion, RV filling is abnormal in patients with LV filling impairment, sitggesting ventricular diastolicinterdependence. Also, normalization of PFR to SV may be the preferable method in evaluating RV & LV filling dynamics.

EFFICACY AND SAFETY OF AMLODIIPINE IN HYPERTENSIVE PATIENTS WITH RENAL IMPAIRMENT
Dr. Solimau Gharieb MD*, Dr. Mohamed EL Borady Msc, Dr. Medhat El Refaee MD*, Dr. Omar E 1 Khashaab M D * *
* Cardiology Department-Cairo University,
* *General Medicine Department-Cairo University

Amlodipine, one of the second generation of calcium antagonists, has slow, smooth onset, and ultralong duration of action. Many studies had been done abroad, but this study was designed to apply Amlodipine on Egyptian hypertensive patients with renal impairment to see its outcome. Thirty patients with mild to moderate hypertension and mild to tuoderate renal impairment joined this study.

After two weeks of placebo treatment, amlodipine 5 mg was given to all patients for ten weeks. The dose was increased to 10 mg after four weeks if there is inadequate control of the blood pressure.

Echocardiography, glomerular filtration rate (GFR), and various laboratory fimetions tests were done before and after treatment.

Amlodipine produced significant (P< 0.01) blood pressure reduction the study. GFR was significantly increased after the end of the study (P <0.01). All other laboratory functions and echocar-diographic measurements showed variation. Adverse events (24 %) were mild to moderate, and tolerated with all patients, except one patient whowas discontin, , ied from the study due to severe headache.

Amodipine can be used safely in hypertensive patients with renal impairment, and moreover it leads to improvement of GFR in these patients.

HYPERTENSWE HEART DISEASE ROLE OF OXYGEN FREE RADICALS
Kamal, S. Mansour (M.D); Abd Allah A. Ali (M.D); Amai M. Abd EL-Moneim (M.D)* and Laila M. El-Moghawri
Cardiology and Clinical Pathology *
Departments, Zagazig Faculty of Medicine Saudi Arabia

Oxygen free radicals (0FR) activity was investigated in 15 normal controls and 45 patients with essential hypertension (15 itneomplicated. 15 with LVH. and 15 with LVH and heart failure). They were subjected to clinical and ECG examination. biochemical investigation, plasma lipid peroxides and selenium measurement, and complete Echo-Doppler examination. All subjects were nonsmokers, free from other cardiovascular or medical diseases and not receiving drugs known to affect OFR activity. The study groups were matched as regards age, sex and height.

It was found that OFR activity as assessed by plasma lipid peroxides showed significant and highly significant increase in patients with LVH and in those with heart failure respectively, while it was comparable to controls in uncomplicated patients. Plasma selenium was low in patients with high OFR activity and normal in those with normal OFR activity.

Lipid peroxides level showed negative correlation with selenium level. Lipid peroxides level showed positive correlation with severity of hypertension and left ventricular mass and negative correlation with left ventricular systolic function indices (.F., F.S and AT/ET). We can conclude that OFR activity is normal in uncomplicated hypertension, increases in presence of LVH and more profound increase occurs when heart failure develops. It was suggested that OFR scavengers may be considered as an additional new line of treatment of hypertensive heart disease especially in presence of LVII and/or LV failure.

Abstracts of World Literature

Role of Superoxide in Angiotensin II-Induced but Not Catecholamine - Induced Hypertension
Jorn Bech Laursen, MD; Sanjay Rajagoppalan, MD; Zorina Galis, PhD; Margarent Tarpey, MD; Bruce A. Freeman, PhD; David G. Harrison, MD

Background - The major source of superoxide (02-) in vascular tissues is an 0NADH/NADPH- dependent, membrane- bound oxidase. We have previously shown that this oxidase is activated in angiotensin II- but not norcpinephrine -induced hypertension . We hypothesized that hypertension associated with chronically elevated angiotensin II might be caused in part by vascular 02 production.

Methods and Results - We produced hypertension in rats by a 5-day infusion of angiotensin II or norepinephrine. Rats were also treated with liposome-encapsulated superoxide dismutase (SOD) or empty liposomes. Arterial pressure was measured in conscious rats under baseline conditions and during bolus injections of either acctylcholine or nitroprusside. Vascular. 02- production was assessed by lucigenin chemiluminescence.

In vitrovascular relaxations were examined in organ chambers. Norepinephrine infusion increased blood pressure to a similar extent as angiotensin II infusion (179±5 and 189±4 mm Hg, respectively)

In contrast, angiotensin-II induced hypertension was associated with increased vascular 02-production. whereas norepineph rine-induced hypertension was not. Treatment with liposome encapsulated SOD reduced blood pressure by mm Hg in angiotensin II-infused rats while having no effect on blood pressure in control rats or rats with norepinephrine-induced hypertension.

Similarly, liposome-encapsulated SOD enhanced in vivo hypotensive responses to acetylcholine and in vitro responses to endothelium -dependent vasodilators in angiotensin II-treated rats.

Conclusions - Hypertension caused by chronically elevated angiotensin II is mediated in part by 02 likely via degradation of endothelium -derived NO. Increased vascular 02-may contribute to vascular disease in high reninlangiotensin II states.

(Circulation 1997; 95:588-593)

Key Words hypertension angiotensin endothelium derived factors

Sex-and Age - Related Antihypertensive Effects of Amlodipine
Robert A. Kioner, MD, PhD, James R. Sowers, MD, Geraid F. DiBona, MD, Michael Gaffney, PhD, and Marilee Wein, RPh
for the Amiodipine Cardiovascular Community Trial Study Group*

This community-based study assessed whether there were age, sex, or racial differences in response to amlodipine 5 to 10 mg once daily in patients with mild to moderate essential hypertension., This prospective, pen-label trial had a 2-week placebo period, a 4-week upward drug titration/efficacy period, and a 12-week drug maintenance period.

here were 1,084 evaluable patients (mean age 55.5 years; 65% men and 35% women; 79% white and 21% black; 75% < 65 and 25%>65 years old ). At the end of the titration I efficacy phase, the mean±SD blood pressure (BP) decreased by-16.3±12.3/-12.5±5.9 mm Hg, (p < 0.0001). Amlodipine proditced a goal BP response (sitting diastolic BP < 90 tn Hg, or a 10 mm Hg decrease ) in 86.0% of patients overall. The BP response was greater in women (91.4%) than in men (83.0%, P< 0.00 1), and greater in those > 65 years old (91.5%) than in those < 65 years old (84.1%, P < 0.01); however, it was similer between whites and blacks (86.0% vs 85.9%, respectively, p=NS).

The sex difference in BP response could not be fully explained by difference in age, weight, dose (mg/kg), race, baseline BP, or compliance, and there were no differences among women based on use of hormone replacement therapy. Amlodipine was well tolerated; mild to moderate edema was the most common adverse effect .

Thus, amlodipine was effective and safe as once-a-day monotherapy in the treatment of mild to moderate hypertension in a community-based population. Women had a greater BP response to amlodipine.

(Am I Cardiol 1996; 77:713-722)

PREDICTIVE VALUE OF AMBULATORY BLOOD PRESSURE SHORTLY AFTER WITHDRAWAL OF ANTIHYPERTENSIVE DRUGS IN PRIMARY CARE PATIENTS
Frank W Beitman, Wilfred F Heesen, Ronald H J Kok, Andries J Smit, Johan F May, Pieter A de Graeff, Tjeerd K Havinga, Frits H Schuurrnan, Enno van der Veur,Kong I Lie, Be~tty Meyboom - de Jong

Objective - To determine whether ambulatory blood pressure eight weeks after withdrawal of antihypertensive medication is a more sensitive measure than seated blood pressure to predict blood pressure in the long term.

Design - Patients with previously untreated diastolic hypertension were treated with antihypertensive drugs for one year; these were with-drawn in patients with well controlled blood pressure, who were then followed for one year. Setting - Primary care.

Subjects - 29 patients fulfilling the criteria for withdrawal of antihypertensive drugs.

Main outcome measures - Sensitivity, specificity, and positive and negative predictive value of seated and ambulatory blood pressure eight weeks after withdrawal of antihypertensive drugs.

Results- Eight weeks after withdrawal of medication mean diastolic blood pressure returned to the pretreatment level on ambulatory measurements but not on seated measurements. One year after withdrawal of medication, mean diastolic blood pressure had returned to the pretreatment level both for seated and ambulatory blood pressure.

For ambulatory blood pressure, the sensitivity and the positive predictive value eight weeks after withdrawal of medication were superior to those for seated blood pressure; specificity and negative predictive value were comparable for both types of measurement. Receiver operating characteristic curves showed that the results were not dependent on the cut off values that were used

Conclusion - Ambulatory blood pressure eight weeks after withdrawal of antihypertensive drugs predicts long term blood pressure better than measurements made when the patient is seated.

Forthcoming Research

FORMULATION OF BLOOD PRESSURE NORMS AND PERCENTILES FOR EGYPTIAN CHILDREN AND ADOLESCENTS

The need for measuring blood pressure in children and adolescents and discerning normal from elevated or reduced levels cannot be Overemphasized. This is especially so when it is noticed that over the past 4 decades the etiology of hypertension in children and adolescents has slowly but significantly changed. Earlier in the 40's 80% of childhood hypertension was considered secondary to a cause lurking behind the elevated blood pressure.

With the passage of time essential hypertension started to be discovered much earlier than previously thought, so that by the mid 70's nearly 45% of hypertension in childhood was thought to be essential, with no causal etiologic agent found.

As hypertension has been found to be affected by race and colour, dietary habits and life style, as well as rural and urban factors, and as hypertension risk factors according to the NHP statistical analysis, have been found to be more common in certain geographic areas & populations, the norms for blood pressure measurement must consequently differ as well from, one population to another. This is especially so when considering children and adolescents.

In general a child's blood pressure is considered elevated if it is found to be above the 90th centile for age and height on more than one occasion. The child is considered potentially hypertensive and needs investigation if his blood pressure is above the 90th centile on 3 separate occasions over a 6 months' period. He is considered definitely hypertensive and needs investigation and treatment if his blood pressure is above the 95th centile from the outset.

In defining childhood and adolescent hypertension in Egypt, it becomes mandatory' therefore to draw up percentile charts for normal blood pressure and its variations from the aboriginal population under scrutiny. Accordingly we have drawn-up a suggested plan of action to undertake this important piece of research information.

Suggested plan of Action

A) Premises:

22 hospitals in different geographic areas of Egypt whether University teaching Hospitals from the Ministry of Health or from the Armed Forces arc to be chosen. The suggested names of the hospitals are:

1- Cairo University Paediatric Hospital.
2 -Shatby Hospital, Alexandria University.
3- Ain-Shams University, Children's Hospital.
4- El-Azhar University' Children's Hospital.
5- Asslut University Children's Hospital.
6- Maadi Armed Forces Hospital Paediatric Department.
7- Tanta University Paediatric Department.
8- Mansoura University Cardiology and Paediatrie Department.
9- Suez Canal University Cardiology and Paediatric Department.
10- Banha University Paediatric Department.
1 1-Zagazig University' Paediatric Department.
12- Souhag, University Paediatric and Cardiology Departments.
13- Minia University Hospital Cardiology and Paediatrie Departments.
14- Ghamra Family's Hospital.
15- Aswan General Hospital.
16- Fayoum General Hospital.
17- Matrouh General Hospital.
18- Beni-Suef General Hospital.
19- Hurghada General Hospital.
20- Arish General Hospital.
21- Siwa General Hospital.
22- Kharga General Hospital.

B) Personnel

A team of 3 physicians and 3 nurses will be recruited from each of the above hospitals where possible. The team should contain a cardiologist, a paediatrician and if possible a paediatric cardiologist. Each hospital is to act as a nucleus for blood pressure uleasurement in its area. A course of 1-2 weeks comparable to the one done by the EHS is to be held for all personnel involved to get acclimatized to the project and equipment and to develop the team spirit needed for performance.

C) Candidates and patients:

1- Neonates and low birth weight infants, computed to age and centiles.
2- Out-patient department patients attending for 3-6 months.
3- In-patients to the paediatric hospital or department for 3-6 months.
4- 16 schools in the geographic locality of the hospital:
a) 4 secondary schools, 2 for girls and 2 for boys.
b) 4 preparatory schools, 2 for girls and 2 for boys.
c) 4 primary' schools, 2 for girls and 2 for boys and if coeducation 4 schools are to be chosen.
d) 4 kinder-garden for boys and girls.

D) Criteria for the enlisting hospital:
1- Presence of the previously mentioned personnel or at least their equivalent
2- Presence of cardiac, paediatric, neonatal and low birth weight units.
3- Influx of a minimum of 100 patients per week for 3 months whether IP or OP.

E) Criteria for enlisting schools:

1- Co-operative head master, or headmistress and teachers..
2- At, least 500 pupils per school.
3- An area in the school premises for installing equipment during the sun'ey

F) Protocol of Blood Pressure Measurement:

1- Immediately after examination one after 3 minutes and another after 2 hours
2- Korotkoff sounds 1,4 and 5 should be recorded for each patient at each examination.
3- An atherosclerotic risk sheet should be filled in for each patient.
4- Hypertensive children according to the above mentioned criteria are to be referred to the hospital appointed for 3 readings over 6 months period after preliminary testing as indicated (editorials EHS news Letter).

In such hypertensive patients both arms and lower limbs should have blood pressure checking.

G) Project Sheets-.

1- Atherosclerotic risk sheet.
2- Egyptian percentile charts for height and weight (Abbassy et al).,
3- Blood pressure record including Kl,K4,K5.

H) Equipment:

1- Blood pressure apparatus.
2- Blood pressure cuffs of different sizes.
3 - Digital oscillometers or dynamitic apparatuses.
4- Stethoscopes.
5- Examination couches.
6- Desks and chairs for patients and doctors.

I) Contacts to be done before the project:

1- M.P.H. to alert hospitals to the project.
2- University hospital directors and Deans to absent staff for part of the day for the survey.
3- Ministry of education to alert schools.
4- School medical officers and headmaster/mistress for permission to start project.
5- Consent of parents when needed.
6- T.V., and media alerting by a comprehensive advertisement.

J) Financial Help:

1- T.V. advertisement to recruit funds.
2- Bankers donations where possible.
3-U.S. Aid Organization.
4- Egyptian Hypertension Society.
5- Egyptian Society of Paediatric Cardiologists.

EHS NEWS

* The first continuing medical education (CME) course of the Egyptian Society of hypertension (EHS) was held on the 5 th of January 1997. The chairman of organizing committee was Prof. Adel Zaki of Cairo University. The speakers at the meeting were:

1- Prof. Mohsen Ibrahim, President of the EHS.
2- Profs. Adel Zaki, Fouad El Naway, Sherif El Tobgy, Soliman Gharib, Wafaa El Aroussy and Hossam Kandil.

The meeting was attended by 149 physicians in addition to some of the Registrars and house physicians of Cairo University's Hospitals. This good turn-out can be credited to proper preparation by a newspaper advertisement, posters in all University hospitals and the hospitals of both the Ministry of Public Health and the Armed Forces In addition the printing of the booklet on "Hypertension its diagnosis and treatment" and its distribution among the participants helped ill arousing their interest.

Furthermore it was announced at the beginning of the meeting that there will be an examination at the end of the conference and a prize of LE 500 for the physician who scores the highest marks in the examination. The meeting started by an introductory talk by Prof. Mohsen Ibrahim on the usefulness of proper and accurate blood pressure measurement. This was followed by a series of lectures each of 20-30 minutes and comprising the definition of hypertension, investigations needed to venfiT its presence and cause, a discussion of endocrine hypertension, hypertension in tlte elderly and how to manage emergency hypertension.

Following the lectures, there was an open discussion between the participants and speakers and this was followed by a film and colour slide., n how to measure blood pressure. At the end of the conference a multiple choice uestic)u. examination (MCO) was held for the participants.

Two physicians who scored the highest mark in the examination (22 out of 23) were Dr. Dalia El Rameessy and Dr. Sameh Salama each of whom received LE 250 for their excellent performance. The 4 th Annual breakfast of the EHS during the Holy Month of Ramadan took place on 24 th of January 1997 at the Ramses Hilton Hotel and was attended by nearly all members of the Society.

After breakfast and welcoming of the guests Prof Mohsen Ibrahim gave a word of thanks to the following 5 members for their distinguished services to the Society:

1- Engineerl Fikry.Abdel-Wahab, Vice-President of the Executive Board of Mak Tourism Development Company for his supenision of the Fund-raising Committees activities.
2- Mr. Alv Dabbouss,Vice-President of the Arab International Batik for his Financial support to the Society.
3- Prof Mohamed Hamed, Editor of the EHS Newsletter for his diligent efforts in publishing the Newsletter regularly.
4- Prof. Khairy Abdel Dayem, Vice-Dean of the Faculty of Medicine, Am-Shams University for organizing the 2 nd Meeting of the EHS in December 1996.
5- Dr. Hossam Kandil, for his creative production of a video film to alert the laety to the problem of hypertension.

This was followed by a resume of the Society's activities of the past year given by Prof. Mohsen Ibrahim, President of the EHS and then the heads of the following sub-committees made their comments:

1- Fund raising committee: Prof. Omar Awaad.
2- Training committee: Prof Adel Zaki.
3- Media and Advertising committee: Dr. Hossam Kandil andDr. Hassan Khalid.
4- The drug efficacy committee: Prof. Hussein Pizk and Prof. Soliman Gharib.
5- The Newsletter committee: Prof. Mohamed Hamed.

Following that Prof Wafaa El Aroussy, Treasurer of the Society gave a report on the promising financial situation of the Society.

Finally, a Ramadan talk on old memories and reminiscences was given by Prof. Abdel Moneim Hassaballah as the dessert of the meeting.

A number of society members have been assigned to receive free of charge the Journal (Hypertension) which is the official journal of the American Heart Association. This senTice has been offered both by the Pharmaceutical. Firms of Egypt and the special boosting of the American Heart Association, which has agreed to deduct 50% of the subscription of the Journal for members of the EHS. Prof. Mohsen Ibrahim President of the EHS is due to fly to Washington in April 1997 where he will lecture on cardiovascular risk factors in Egyptian Hypertensives based on data obtained from the NHP. The same talk will be delivered in June in Canada.

On his way back in July, Prof. 1brahim will stop over in London, U.K. ,where he will give a talk on hypertension in Egyptian Nubians. Dr. Salwa Morcos received the first prize of the Young Investigator's Awards during the 24 th Annual Meeting of the Egyptian Society of Cardiology for her work on Vascular hypertrophy in Hypertensives. An agreement has been reached with Glaxo-Wellcome Pharmaceutical Company which has generously offered to sponsor the Physician Education Program for the coming year.

This agreement entails that Glaxo-Wellcome will print out, free of charge, all programs concerning Continuing Medical Education, as well as reprinting the booklet "Short Review of Hypertension and Guidelines for its Management in Egypt". The company has also agreed to provide education tools and audio-visual aids to be made available its the lecture hall of the Society's premises.

The following continuing medical education meetings (CME) are scheduled to be held in the following cities at the dates appointed:
1- Mansoura 10-11th April.
2-Dammieta 10-11th July.
3- Port-Said 4 and 5th September.
4- Minia 6 and 7th November.

A letter has been sent to His Excellency the Minister of Public Health and Population, informing him of the above dates, which are being sponsored by Glaxo-Wellcome Company. So also has a letter been sent to all directors of medical services in the different Governorates of Egypt informing them of these Coming events, and of the sponsoring of Glaxo-Wellcome Egypt of all expenses likely to be incurred by the attendants of these meetings. Glaxo-Wellcome will also present a prize for the best physician in each of the meetings mentioned above. The meeting of the European Society of Hypertension is due to take place in Milan, Italy from June 13 th to 18 th 1997. The general assembly of the EHS is to meet on the 16 th of May 1997 for elections to the Board of Directors. Prof Mohamed Hamed, Editor of the Newsletter has had his name and C.V. published as a biographee in the 14 th Edition of the famous journal "Who's Who in the World" on page 567.

CALENDAR

*Year*	*Month*	*Days*	*Meeting*	*Venue*	*Correspondence*
1997	June	28	17 th Council Conference of the world Hypertension league	Montreal Quebec Canada	Dr. Patrick J.Mulrow Secretary General, WHL Medical College of Ohio P0 Box 10008 Toledo, OH 43699-0008. USA
1997	July	20-24	12 th International Interdisciplinary Conference on Hypertension in Blacks.	London England	International society on Hypertension in Blacks. Inc. 2045 Manchester Street. NE Atlanta, GA 30324-4110, USA e-mail: ishib@aol. com
1997	August	8-13	2nd Hypertension Summer School	Castine, Maine. USA	Conference Coordinator
1997			2nd Hypertension Summer School	American Heart Association	7272 Gereenville Avenue Dallas, TX 75231 - 4596, USA