THE PRESIDENT'S MESSAGE:

Egyptian Physician's Knowledge & Attitudes Towards Hypertension Egyptian Physicians Hypertension Survey

Data from the Egyptian National hypertension Project (NHP) - the first cross sectional hypertension (HT) survey in an Arab country - showed very high prevalence rates of HT in adult Egyptians (26.3%). Equally alarming were the very low rates of HT awareness, treatment and control, which were respectively 37.5%, 23.9% and 8%. In order to explain possible causes of low treatment and control and identify Egyptian physician knowledge and attitudes toward HT, a nationwide Egyptian physician's survey was conducted on a representative sample of 198 Egyptian physicians and 1940 hypertensive patients. Samples of physicians were 39% in Cairo, 16% in Alexandria, 32% in the Delta and 13% in Upper Egypt. Fifty eight percent of physicians had a master or doctorate degree and 90% were males, the majority (92%) had a special interest in HT and 33% were seeing more than 10 hypertensive patients per week. Forty six percent of physicians consider their treatment target SBP=130 mmHg and 67% consider target DBP=85 mmHg. Fifty three percent thought that two weeks is the appropriate time to achieve target PP, 10% discontinue treatment after normalization of BP, while 66% changed their antihypertensive drug in 3 months. Poor patient compliance was considered by 46% a major issue in treatment of HT and 32% believed that 40% of their patients do not comply with treatment. Causes of poor compliance were: cost in 71%, absence of symptoms in 56%, side effects in 51%, forgetfulness in 405 and doctor's advice in 5%. Eighty three percent of patients stated that they ever changed antihypertensive drug therapy. Seventy nine percent of patients stated that they ever stopped the antihypertensive drug therapy. Reasons behind stopping therapy from the patients perspective were side effects in 34%, normalization of BP in 27% and cost of therapy in 14%).

We can conclude from this study in a highly selected sample of Egyptian physicians and patients that:

1-The majority had a fair knowledge of HT and considers poor patient compliance an important issue in treatment

2- A major cause of poor compliance from the doctors' perspective was the cost while from the patients' point of view it was the side effects of drug therapy

M. Mohsen Ibrahim, MD
Prof. & Chairman,
Department of Cardiovascular Medicine - Cairo University
President of Egyptian Hypertension Society

Editorial

ISOLATED SYSTOLIC HYPERTENSION
Mahmoud Hassanein M.D. Professor of Cardiology-
Alexandria University.

Introduction
There appears to be an unwarranted over-reliance on diastolic blood pressure in clinical medicine, with too much emphasis on the diastolic component of blood pressure and too little on systolic blood pressure in cardiovascular risk assessment and in evaluation for treatment.

In men of all ages in the Framingham study ^(l) the incidence of CIID, stroke, cardiac failure and peripheral artery disease was substantially higher for Isolated Systolic Hypertension (JSH) than isolated diastolic hypertension. Combined systolic and diastolic hypertension carried only a marginally greater risk than ISH. Every SD increase in systolic blood pressure in men increased cardiovascular disease risk 40% to 50%, whereas for diastolic blood pressure the increment was 30% to 35%.

Definition of Isolated Systolic Hypertension:

In the Syst-Eur trial and in the Framingham study, a systolic blood pressure of 160 mm Hg or more with a diastolic Wood pressure of less than 95 mm Hg was used to define ISH. The SHEP trial used the same systolic pressure but a diastolic pressure of less than 90 mm Hg. However JNC VI defines ISH as systolic blood pressure equal or greater than 140 mm Hg and diastolic blood pressure less than 40 mm Hg.

How frequent is Isolated Systolic Hypertension?

The prevalence of ISH rises with each decade of age in both sexes but is relatively uncommon until age 45. Beyond age 55 the prevalence increases in both sexes with the rise among females being steeper than among males. From the Framingham cohort, it has been reported that ISH occurs in 14% of men and 23% in women over age 65, and that ISH accounted for 57% of all hypertensive conditions in men and 65% in women.

Mechanisms of Isolated Systolic Hypertension

The main mechanism is the reduction in compliance of large arteries with age: there is loss of elasticity. This means that the pressure produced by systole is no longer buffered, and systolic pressure rises. At the same time, the loss of elasticity leads to a lesser elastic recoil in the blood vessel walls during diastole, so diastolic pressure tends to fall and thus the pulse pressure widens.

Treatment

Data from the Systolic Hypertension in the Elderly Program (SHEP)⁽²⁾ demonstrated that treatment of ISH with diuretic- based drug therapy produces remarkable declines in stroke and CHD. The' relative risk reduction was 27% for CHD, 36% for stroke and 32% for all cardiovascular disease. The risk of patients developing heart failure was halved. The Syst-Eur Study ⁽³⁾ a similar study to SHEP - but the active agent used was the dihydropyridine calcium antagonist nitrendipine, was stopped prematurely because it reached its goals after the second of the four planned interim analyses. The patients in the active treatment group had 42% (P=0.003) fewer fatal and nonfatal strokes compared with those given placebo.

Conclusions

The evidence for benefit in treating elderly patients with Isolated Systolic Hypertension is overwhelming. Diuretics are preferred because they have significantly reduced multiple endpoint events. In addition long acting dihydropyridine calcium antagonists have proved effective in the Syst-Eur trial. Drugs that exaggerate postural changes in blood pressure (peripheral adrenergic blockers, alpha-blockers and high dose diuretics) or drugs that can cause cognitive dysfunction (central alpha 2-antagonists) should be used with caution.

References
1. Kannel WB. Epidemiology of essential hypertension; the Framingham experience. Proc R Coll Phys Edinb 1991; 21: 273 - 87.
2. SHEP cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension: Final Results. JAMA 1991; 265: 8255-54.
3. Stoessen JA et al. For the Systolic Hypertension - Europe (Syst - Eur) Trial investigators. Lancet 1997; 350: 757 - 64.

Abstracts of World Literature

Insulin-like growth factor binding proteins in arterial hypertension: Relationship to left ventricular hypertrophy.
Diez J; Laviades C; Martinez E; Gil MJ; Monreal I;
Fernandez J; Prieto J Department of Internal
Medicine' University of Navarra' Pamplona' Spain.

OBJECTIVE: It was reported previously that circulating insulin-like growth factor I levels are abnormally elevated in patients with essential hypertension and left ventricular hypertrophy. Tissue availability of the factor depends on the distribution of the circulating bound factor between its high- and low-molecular mass binding proteins' only the latter being able to cross the endothelium. The aim of this study was to investigate whether the presence of the different serum binding proteins is altered in patients with essential hypertension and left ventricular hypertrophy. DESIGN: The study was performed in 30 never-treated patients with essential hypertension and 30 age- and sex-matched normotensive subjects. Patients were separated into two groups according to the presence or the absence of echocardiographically determined left ventricular hypertrophy. METHODS: Plasma insulin-like growth factor I levels were determined by specific radioimmunoassay. The different molecular forms of its serum binding proteins were analyzed by Western blotting using [1251 labeled insulin- like growth factor I. A densitometric scanning of the blots was performed to analyze the quantitative relationships between the different forms of binding proteins. RESULTS: Insulin- like growth factor I levels were significantly higher in the hypertensive patients with than in the hypertensive patients without left ventricular hypertrophy or in the normotensive subjects. Compared with the normotensive subjects' both hypertensive patients subgroups exhibited increased high- molecular mass binding protein type 3 and decreased low- molecular mass binding proteins types 1 and 2. However' changes in the binding proteins were more marked in the hypertensive patients without than in the hypertensive patients with left ventricular hypertrophy. Accordingly' the ratio of low- to high-molecular mass binding proteins (an index of insulin-like growth factor I bioavailability) was higher in the hypertensive patients with than in the hypertensive patients without left ventricular hypertrophy. CONCLUSIONS: These results show that the distribution of the molecular forms of serum insulin-like growth factor binding proteins is altered in patients with essential hypertension' independently of insulin4ike growth factor I levels. This suggests that regulation of the binding proteins is abnormal in essential hypertension. Whether the tissue availability of circulating insulin-like growth factor I is higher in hypertensive patients with than in hypertensive patients without left ventricular hypertrophy merits further investigation.

J Hypertens 13:349-55, 1995 Mar

Circadian Blood Pressure Changes and Myocardial lschemia in Hypertensive Patients With Coronary Artery Disease
Sante D. Pierdomenico, MD, Anna Bucci, MD, Fabrizio Costantini, MD, Domenico Lapenna, MD Franco Cuccumilo, MD, Andrea Mezzetti, MD
Centro per lo Studio dell'Ipertensione Arteriosa, delle Disilpidemie e dell'Arteriosclerosi, Dipartimento di Medicina e Scienze dell'Invecchiamento, University
G. D'Annunzio, Chieti Italy

Objectives: We sought to evaluate whether different circadian blood pressure (BP) changes could influence the occurrence of ischemic episodes in untreated and treated hypertensive patients with stable coronary artery disease (CAD). Background. In hypertensive patients with CAD the occurrence of myocardial, ischemia could be influenced by either high or low BP values. Ambulatory monitoring has shown that circadian BP profile is not uniform in hypertensive patients. Methods: Twenty-one patients with a nighttime BP fall <10% ("nondippers"), 35 with a nighttime BP fall between >10% and <20% ("dippers") and 14 with a nighttime BP fall >20% ("overdippers") with CAD underwent simultaneous ambulatory BP and electrocardiographic monitoring before and during drug therapy with nitrates and atenolol or verapamil in a prospective, randomized, open, blinded end point design. Results: Daytime BP was not significantly different among the groups both before and during therapy. Nighttime BP was different by definition. Treatment significantly reduced BP values in each group (p < 0.05). Daytime ischemic episodes did not differ among the groups either before or during therapy. Drug therapy significantly reduced daytime ischemia (p < 0.05). In untreated patients, nighttime ischemia was more frequent in nondippers than in dippers and overdippers (p <0.05). Drug therapy significantly reduced nocturnal ischemia in nondippers (p <0.05), had no significant effect in dippers and significantly increased nighttime ischemia in overdippers (p < 0.05). During treatment, nighttime ischemia was more frequent in overdippers than in dippers and nondippers (p < 0.05). The same results were achieved when ischemic episodes were defined with more restrictive criteria (ST segment depression [greater than or equal t]2 mm). Conclusions, Circadian BP changes can influence the occurrence of myocardial ischemia in untreated and treated hypertensive patients with CAD. Nocturnal ischemia was found to be more frequent in nondippers among untreated patients and in overdippers among treated patients potentially suggesting different therapeutic approaches based on circadian BP profile.

JACC Vol.31, No.7, June 1998:1627-34

Influence of Left Ventricular Geometric Patterns on Prognosis in Patients With or Without Coronary Artery Disease
Jalal K Ghali, MD, FACC, Youlian Liao, MD, Richard
S. Cooper, MD, FACC
Section of Cardiology, Department of Medicine,
Louisiana State University Medical School,
Shreveport, Louisiana, USA & Department of
Preventive Medicine and Epidemiology, Loyola
University Medical Center, Maywood, Illinois, USA

Objectives: We sought to examine patterns of left ventricular (LV) geometry as determined by echocardiography and their association with mortality in patients with or without coronary artery disease (CAD). Background: The independent prognostic role of LV geometry remains uncertain. Methods: We performed a cohort study based on 988 consecutive patients who underwent both coronary arteriography for presumed CAD and echocardiography and were followed up for a mean of 9 years (range 5 to 13). Patients were classified into four LV geometry patterns: normal, concentric remodeling, eccentric LV hypertrophy LVH) and concentric LVH. Results: Patients with concentric LVH consistently showed the largest increase in LV posterior wall and septal thickness and LV mass index, as well as relative wall thickness (RWT), regardless of status of the coronary arteries. This pattern conferred the highest risk of both all-cause and cardiac mortality. Eccentric LVH moderately increased the risk of death compared with normal geometry; no substantial increase in mortality was noted in-patients with concentric remodeling. When LV index and RWT were analyzed as continuous measures and considered in the same Cox proportional hazards model, increases in LV mass were independently associated with risk, but this outcome was less clear for RWT. Conclusions: In this series of patients referred to coronary angiography for suspected CAD, LVH conferred most of the predictive information from echocardiography. Patients with both LVH and abnormal WT (concentric LVH) represent a group with the greatest mortality risk. Concentric remodeling may not be associated with increased risk of death because the predictive value of RWT is not as strong as for LV mass.

(J Am Coll Cardiol 1998;3 1:1635-40)

Abstracts of Local Literature

STUDY OF LV LATE POTENTlALS IN SYSTEMIC HYPERTENSION WITH LEFT VENTRICULAR HYPERTROPHY
Darahim, H. EI Ghetany and H. Ezz el Din Cardiology
Department, Am Shams University, Cairo, Egypt

Hypertensive patients with left ventricular hypertrophy (LVH) have a higher incidence of premature cardiovascular death. It has been recently demonstrated that ventricular arrhythmias influence mortality in hypertensive patients with LVH. It is therefore important to determine whether hypertensive LVH provides an arrhythmognic substrate i.e. ventricular late potentials (VLP). The aim of this work was to study the prevalence of VLP in the setting of hypertension and their relation to hypertensive LVH.

Subjects and methods: The study included 70 sex matched subjects who were divided into 3 groups; group A: 30 hypertensives with LVH, Group B: hypertensives without LVH, and group C: 20 normotensive control subjects. Patients with ischaemic heart disease, cardiomyopathies, mitral valve prolapse, bundle branch block or atrial flutter were excluded. All patients underwent history taking and physical exam, 12 lead surface ECG, echocardiography and signal averaged ECG (SAECG). LVH diagnosis was based on M-mode Lv mass index determination, SAECG was done in the time domain using 40 -HZ, high pass filtering with residual noise of 0.3 uV. VLP were diagnosed if at least 2 of the following criteria were met with: 1 - QRS duration > 114 ms, 2- Root mean square voltage of last 40 ms < 20 uV, 3- Low amplitude signal duration> 38 ins

Results: The prevalence of VLP in hypertensive patients with LVH was 20% while it was 0% in both hypertensive patients without LVH and in control subjects (p value <0.05). The prevalence of VLP in the subgroup with eccentric LVH was 33% and in the subgroup with concentric LVH was 19%. The prevalence of VLP in all hypertensive patients was 12%. Hypertensive patients with VLP tended to have a higher prevalence of echocardiographic LVH (p value <0.000001). Age, sex, blood pressure levels, duration of hypertension, grade of hypertension LV ejection fraction, diastolic dysfunction and electrocardiographic LVH were not predictors of VLP in hypertensive patients.

Conclusion: VLP in the setting of hypertension tended to occur more with LVH and particularly with eccentric pattern of hypertrophy

Abstract presented in the 27" meeting of the Egyptian Hypertension Society, 1996

Nocturnal diastolic blood pressure influences left atrial size in uncomplicated hypertension
Ayman Fakher, Antonio Petrocelli, Annibale Izzo,
Cinzia Liberato & Maurizio Galderisi
Dept of Clinical and Experimental Medicine, Federico
II University of Naples, Italy

Our aim was to determine the relations of 24-hour blood pressure (BP) and its different phases with left atrial size. A total of 130 subjects (mean age) not taking cardiac drugs were studied by M-mode and Doppler echocardiography and ambulatory BP recording. Subjects (excluding those with coronary artery or valvular heart disease, heart failure or diabetes) were classified into 2 groups: 25 normotensives and 105 hypertensives (history of antihypertensive treatment and office diastolic BP > 90 mmHg). The 2 groups were comparable in terms of sex, age and heart rate, whereas body mass index (p < 0.01), office BP, average 24 hour BP, and average daytime and nighttime BP (all p <0.00001) were higher in hypertensives. Hypertensives also had increased left atrial dimension, left atrial/Aortic root ratio (both p < 0.001) and left ventricular (LV) mass indexed for height (p < 0.00001). Positive correlations of left atrial dimension were found with office BP, average 24 hour BP, average daytime and nighttime systolic and diastolic BP LV mass index, and Doppler derived EIA ratio. In a multivariate model that included potentially confounding factors, only body mass index (p< 0.00001) average nighttime diastolic BP (p < 0.00001) and male sex (p< 0.01) were independent predictors of left atrial size in the pooled population.

In conclusion: left atrial size is more closely related to ambulatory rather than office BP measurements, and high average nighttime diastolic BP is a powerful marker of left atrial enlargement in arterial hypertension.

Abstract presented in the 25th meeting of the Egyptian Society of Cardiology, 1998

The Role of Calcium Antagonists & Angiotensin Converting Enzyme Inhibitors in modulating Pro- oxidant - antioxidant & Thrombo- atherogenic
Profiles in oxidatively stressed rats
Amr AM Okda, Awatif Hilal, Omnia Nayel, Nabil El
Bahie, Samy Hammady & Omayma EI-Sakka

Beyond hemodynamic considerations, an imbalance between NO & reactive oxygen species may be an important pathogenic event in many vascular disorders characteristic to diabetes, atherosclerosis, restenosis.. etc. In hypertension, blood pressure level is much demarcated by such an imbalance which also promotes alterations in structure of end- organs and is implicated in the clinical complications of hypertension particularly coronary artery disease. No wonder in this study antihypertensives were scrutinized for their ability to modulate oxidative stress in atherogenic rat model alone Or when sut4ected to additional hazardous risk of either cigarette smoke exposure or iron loading. Results revealed that the probed drugs whether, [Ca Antagonists; Amlodepine (5 mg/Kg/day). Lacidipine (3mg/Kg/day)] or [ACE Inhibitors; Captopril (35 mg/Kg/day) - Perindopril (l mg 1Kg/day)], when administrated orally for 2 month were able to significantly decrease lipid peroxidation as indexed by the decrease in plasma MDA & increase antioxidant buffering capacity as indexed by the increase in GSH, SOD & Catalase in heart, in all the studied risk groups. They further significantly improved the concurrent endothelial dysfunction as evidence by their suppression to plasma vWF & were capable to moreover diminish the extent of aortic histopathological lesions. The improvement detected was more significant by lipophilic (lacidipine) > hydrophilic (amlodipine) Ca antagonists & with sulfhydryl containing (Captopril) > nonsulfhydryl containing ACEIs. The merits of possessing antihypertensives with inherent antioxidant potential is discussed and its impact in improving the vascular dysfunction in hypertension is raised.

Do You Know That?

In hypertensive emergencies or pseudoemergencies, short acting nifedepine capsule given acutely sublingual or oral is better abandoned. This is because it induces uncontrolled drop in blood pressure - peripheral vasodilatation that produce steal phenomenon in certain blood vessels - reflexive cardioacceleration due to excessive catecholamine release. This is abet to end in neurological deficit or cardiac ischemic events specially in hypertensives with target organ impairment.

JAMA 1996; 2 76:13328-31.

EHS NEWS

The Egyptian Society of Hypertension in collaboration with the Ministry of Public Health and the International Society and Federation of Cardiology as well as the International Academy of cardiovascular diseases organized a meeting, which is the first of its kind to be held in Egypt "The International Symposium on Heart Disease, From Molecules to Patient Care" addressed the molecular biology of heart diseases. Over 30 foreign specialists in the field of molecular biology held lectures, in which they explained the link between laboratory research and clinical applications. The meeting was a resounding success. Due to the great demand of the audience, another meeting about molecular biology is scheduled to take place next December.

CALENDAR

Running the test of time, ACEIs have been coined as one of the most beneficial innovation in Cardiovascular Pharmaco-armamentarium. May be that is why so many members do exist while others are still added to the family every day. This makes selection between classes & subclasses look puzzling, so that the clinician has to weigh it out right whenever he individually tailors therapy to each particular case.

In this respect, one of the available option in the phosphinic acid prodrug-ester class of ACE inhibitors of which fosinopril is considered a unique member The part bio-available gets completely de-esterified in the liver and within the GIT mucosa into biologically active diacids fosinoprilate, It induces peak pressor response from 3-6 hrs following administration and with an effective t ½ averaged 11.5 hrs. Beyond this fosinprilate possess a peak-through ratio of approximately 64%, which tends to optimize patient's compliance.

Interesting enough fosinoprilate possess a dual balanced elimination that is set roughly in half; 44%, via renal & 46% hepatic route when used in healthy individuals. The merit of this is evidence in renal insufficiency or hepatic impairment. This entails that when one route of elimination lessens the other route compensates so that the total clearance of the agent is nearly preserved and remains approximately constant despite the available disorder.

So, in patients with renal damage, particularly those with diabetic nephropathy or secondary to cardiac insults as in CHF or post AMI, though clearance gets 50% slower than in normal yet hepatobiliary elimination compensates. While reciprocally, in hepatic insufficiency (whether biliary, alcoholic cirrhosis.. .etc) does not necessarily warrants the downward adjustment of drug daily dose, because renal excretion will take over.

Realizing this unique pharmacokinetic potentiality has encourage its use in the "Fosinopril Amlodipine Cardiovascular Events Trial" [FACET] in hypertensive patients with NIDDM. This randomized open label, blinded end point clinical trial contrasts primarily the metabolic profile [serum lipid & diabetic control] & secondary the C.V. events & renal function outcome. It enrolled 380 patients [followed -up averaged 28 years] whose fasting serum glucose:> 140 mg/dl & BP: 140/90 mmHg [after 3 readings] or 160/195 mmHg [after 2 readings] with albuminuria < 40 µg/min & serum creatinine <1.5 mg/dl.

Results revealed that both randomized therapies were as effective in controlling B.P & had similar effect on surrogate measures of renal function, lipid profile & diabetes control but that fosinopril caused a 51% reduction in risk of major C.V events compared to amlodepine.

FACET adds this to the growing evidence that ACE inhibitors may be preferred in preventing renal implications & cardiovascular events in diabetic hypertensives specially when kinetic weight by a drug such as fosinopril.
1. Kidney International 1991: 31: 58-64.
2. Clin Pharmacol Ther 1991: 49; 457-67.
3. Clin Pharmacol Ther 1995; 58 : 660-5.
4. Med Intern Mex. 1996; 12: 66-72.
5. AJH 1996:9:633-43.
Clin Cardiol 1997: 20 (Suppl 11)11-10-11
6. Kidney International 1991: 31: 58-64.
7. Clin Pharmacol Ther 1991 : 49; 457-67.
8. Clin Pharmacol Ther 1995; 58 : 660-5.
9. Med Intern Mex. 1996; 12: 66-72
10. MH 1996: 9: 633-43.

Ongoing Research

THE EFFECT OF FOSINOPRIL ON THE STRUCTURAL AND FUNCTIONAL REGENERATION OF DENUDED ENDOTHEUUM OF RABBIT'S FEMORAL ARWRY
M.D. Thesis conducted in Pharmacol & Drug Toxicol Dept Faculty of Medicine, University of
Alexandria by Nagwa Noor El- Din. And supervised by M. Tharwat Ghoneim, Mohamed A. Sobhi, Omnia
A. Nayel, Anisa A. Melis, El Deeb M. El Deeb

Objective: Endothelial injury secondary to pressure constrains has been implicated in the functional and structural derangement characteristic to many vascular disorders, of these hypertension has been enrolled. Subsequently, antihypertensives capable of enhancing endothelial repair would be expected to beneficially curtail the etiopathological cascade of events perpetuating hypertension. The experimental design probed in the structural regenerative capacity, possibly by Fosinopril on rabbit's femoral artery subjected to endothelial denudation, as assessed histologically by LM & scanning EM. The functional regenerative capacity was also delineated by constructing dose-response curve to ACHA-induced endothelial dependent relaxation of phenylephrine contracted rings from control undenuded, control denuded- treated & denuded Fosinopril-treated rabbits after 1,2, 4 weeks of regeneration. The IC₅₀ and the E max are calculated and correlated to serum concentration of vWF [a marker of endothelial injury] & pro-oxidant antioxidant profile [MDA versus SOD & GSH] in treated & untreated groups, so as unravel the regenerative potentials of Fosinopril.