1

PREVALENCE AND FACTORS ASSOCIATED WITH

PRESENCE

OF MICROALBUMINURIA IN PATIENTS WITH

ESSENTIAL

HYPERTENSION SEEN AT THE GENERAL

OUTPATIENT

CLINIC OF FEDERAL MEDICAL CENTRE,

ABEOKUTA.

A DISSERTATION SUBMITTED TO THE NATIONAL

POSTGRADUATE MEDICAL COLLEGE OF NIGERIA

IN PARTIAL FULFILMENT OF THE REQUIREMENTS

FOR THE AWARD OF FELLOWSHIP OF THE

COLLEGE IN FAMILY MEDICINE

BY

IGE, ADEGBOLA MEEDEEN

M.B; B.S ( Ibadan) 2001

NOVEMBER 2011

2

SUMMARY

Background

Systemic hypertension (HTN) has been recognized as a very common cardiovascular disease

(CVD) and a major risk factor in the development of congestive heart failure, ischaemic heart

disease, chronic renal failure and stroke.

Some patients with essential/primary HTN (EHTN) manifest microalbuminuria (MAL) - an

abnormal (30–300mg/24hours) urinary albumin excretion. MAL is considered as independent

predictor of cardiovascular (CV) morbidity and mortality. Its level has also been found to

correlate with blood pressure (BP) levels. Several studies conducted among Caucasians showed

different prevalence rates. Early treatment of patients with MAL has been shown to prevent

significant CV morbidity and mortality

However, despite the strong prognosticating index of MAL in hypertension, it is not yet done

routinely for hypertensive patients in Nigeria. Hence, the need for this study.

Objective

The general objective of the study is to describe the prevalence and factors associated with

presence of microalbuminuria among adult Nigerian patients with essential hypertension in

order to inform early detection and control practices.

Methods

3

Using a systematic sampling method with a sampling interval of 3, a total of 395 patients with

essential HTN were screened for MAL using Micral test strip-II. Those with overt proteinuria

were first excluded by testing their freshly passed morning urine with Combur-test strip. Both

test strips are in-vitro diagnostic test strips from Roche Diagnostics for semi-quantitative

estimation of microalbumin, and for estimation of urinary PH, protein and glucose respectively.

Data were however analyzed for three hundred and sixty (360), the actual sample size. Twenty-

five subjects did not complete the study.

Results

The prevalence rate of MAL was 77.5%. Although not statistically significant, MAL was

observed to be more prevalent in females than males and majority of the patients were above

60 years. MAL was positively correlated with systolic BP, diastolic BP, mean arterial pressure

and age. Body mass index (BMI), waist hip ratio (WHR), sex and family history of HTN did

not show any significant association with MAL.

Conclusion

The study showed that there is a high prevalence of microalbuminuria in adult Nigerian

hypertensive patients. It also revealed that MAL is influenced by a number of factors in these

patients.

Therefore, routine screening for MAL in all hypertensive patients is advocated and the presence

of MAL in any hypertensive patient (old or new) calls for a more aggressive and comprehensive

management and follow-up.

4

However, it is suggested that a large multi-centre case-control study be conducted to establish

the prognostic significance of MAL in this environment.

5

CHAPTER ONE

INTRODUCTION

Hypertension (HTN) is an important worldwide public health challenge because of its high and

increasing prevalence and concomitant risks of cardiovascular (CV) and renal diseases. In fact,

it has been described as the most powerful, highly prevalent, independent, modifiable risk

factor for cardiovascular disease (CVD) at the population level.1,2 The burden of HTN

worldwide is so enormous that it has been projected that the approximately one billion (15-

20%) of the world’s population currently being affected3-8 will increase to 1.56 billion by year

2025 and sub-Sahara African shall be the most affected.

Hypertension (HTN) is a common condition amongst Nigerians. The prevalence is alarmingly

on the increase6,9 as a result of westernization and urbanization. Some patients with essential

HTN (EHTN) manifest microalbuminuria (MAL) – an abnormal (30-300mg/24hours) urinary

albumin excretion. It has long been established that albuminuria is the principal marker for

chronic kidney disease (CKD).10-14 In fact, MAL is regarded as the most sensitive parameter

for the detection of early kidney damage.

More recently, MAL has become widely recognized as an independent risk indicator for CVD

morbidity and mortality for patients with HTN and diabetes. 13,15,16,17,18, 19, 20,21

CVD morbidity and mortality as well as CKD are preventable if hypertensive nephropathy is

detected at the microalbuminuric stage and appropriate pharmacotherapy and other measures

are instituted. Studies have overwhelmingly shown that pharmacologic blockade of renin-

angiotensin-aldosterone system (RAAS) by Angiotensin Converting Enzyme Inhibitors (ACE-

I) and/or Angiotensin Receptor Blockers (ARB) provides effective reduction of MAL and

6

blood pressure (BP), and long term prevention of CV events beyond BP

reduction.22,23,24,25,26,27,28,29,30-33 This agents are capable of preventing, reversing or slowing

down progression of hypertensive or diabetic nephropathy.10

Surprisingly, a very wide gap exists between what is known and what is currently being

practiced. Despite compelling data and the well known correlation between MAL and CV risks,

at present only a minority of patients with diabetes and very rarely individuals with HTN are

screened for microalbuminuria15,34 especially in a developing country like Nigeria.

The prevalence of MAL in essential HTN has been determined by several studies and different

prevalence rates have been reported among Caucasians.16,35,36 Only very few of such studies

have been carried out in Nigeria.37,38 Hence, early detection of MAL via simple, point-of-care

screening method shall be the focus of this study. Also emphasis shall be laid on the clinical

pattern of MAL, vis-a-vis influencing factors, among the subjects. This will enable early risk

stratification of hypertensives and institution of the right choice of drugs and other measures

to forestall CVD progression. This brightens the management outcome, betters the prognosis,

improves the quality of life, increases life expectancy and more importantly helps prevent

expenditure of the scarce Nigerian health resources on the management of hypertensive

complications notably cardiac, cardiovascular, retinal and renal.

Family Physicians who, as doctors of first contact, diagnose and initiate antihypertensive

therapy in most cases are well placed for this cost effective, result oriented and secondary

preventive step towards reversing the trend of CKD and CVD.

7

AIM AND OBJECTIVES OF THE STUDY

General Objective (Aim)

The general objective of the study is to describe the prevalence and factors associated with

presence of microalbuminuria among adult Nigerian patients with essential hypertension in

order to inform early detection and control practices.

Specific Objectives

The specific objectives are;

1. To determine the prevalence of MAL among patient with essential HTN.

2. To describe the sociodemographic and clinical characteristics of these patients.

3. To identify factors associated with presence of MAL in the study population.

8

JUSTIFICATION FOR THE STUDY

Hypertension is the most important modifiable risk factor for CVD which is a leading cause of

death in Western Countries35,39 accounting for more than one third of all deaths.35 This is due

mainly to the steady increase in the prevalence of hypertension and diabetes both of which have

now reached the proportion of worldwide epidemic. Unfortunately, this epidemic is projected

to continue unabated such that by year 2025, 1.56billion of the world population will be

hypertensive. This will translate to a further rise in the number of deaths from CV

complications and CKD.35 Recent epidemiological survey reported a range of 31-44%

prevalence of hypertension (HTN) in the Western world.40

Unfortunately, HTN is also the commonest risk factor for CKD, the prevalence of which is also

alarmingly on the increase.41

By virtue of the ever increasing rate of urbanization and westernization, the prevalence of HTN

among black populations is expected to rise sharply. As such, by the end of the next 2 decades,

the consequent CVD mortality and morbidity shall be overwhelming for the African economy.

Sub-Sahara Africa, which includes Nigeria, will be the most affected.

Nigeria with her perennial health concerns with infectious diseases needs to be highly proactive

towards prevention of non-communicable diseases and their consequences. This mandates the

need for an early identification of patients who are at increase risk of CVD and CKD for a

better stratification.35 Early identification of those who are at risk is of paramount importance

because it could set the stage for a more rational therapeutic approach by allowing direct

additional measures to those who need them the most.39

Early detection of microalbuminuria (MAL) via a simple, inexpensive and highly sensitive

screening method for CVD risk stratification and hence aggressive therapeutic approach has

9

been recommended by the JNC-VII and ESH –ESC.35,39 Different prevalence rates (5-40%)

have been reported among Caucasians.

There is a dearth of studies on the prevalence of MAL and its clinical pattern among patients

with essential HTN with an implied consequence of very poor CVD risk stratification in this

part of the world, hence the choice of the title.

10

CHAPTER TWO

LITERATURE REVIEW

2.1 HYPERTENSION

2.1.1 Hypertension: Definition and Epidemiology

Hypertension – persistent elevation of BP and its unpleasant consequences were first

recognized in the late 1800s42 but the cut-off of 140/90mmHg was chosen in the early 1900s

based on the fact that only 5-10% of the US population had BP in that range.42 Also, it was

recognized from the start that BP in this range were almost inevitably accompanied by

arteriolosclerosis and renal changes on microscopic examination.42

No single definition of HTN is universally acceptable. It is often defined as a persistent

elevation of arterial BP with values equal to or greater than140/90mmHg.43 This definition

does not take into account the age of the patient or the presence of pre-existing complications

of HTN. Absolute BP level however varies with age, sex, race and numerous other factors.

Hence, a more useful and practical definition is “the level of BP at which the benefits of

treatment outweigh the costs and hazard.44

HTN is responsible for high morbidity and mortality and affects millions of people the world

over11 especially during the most productive period of their lives. It is a highly prevalent

disorder world wide affecting about 30% and 44% of adult population in the US and Western

Europe respectively.45 African – American blacks have higher prevalence (32.6%).

11

High prevalence rates have also been documented across African populations. HTN in sub-

Sahara Africa is a wide-spread problem of immense economic importance because of its high

prevalence in urban areas, frequent misdiagnosis, and severity of its complications. Recently,

prevalence rates of 27.6%, 28.7% and 30% were respectively reported from Congo, Ghana and

Zimbabwe.45,46 Edwards et al in a study conducted in 2008 in Tanzania reported even a higher

prevalence (34.3% & 39.1%) among men and women respectively in urban district.1 In

Nigeria, HTN like elsewhere, is more prevalent in the urban than in rural communities. In a

recent study, Adedoyin et al9 reported a crude prevalence of 36.6% in a semi-urban community

with a male to female ratio of 1.7 to 1. This is quite higher than the 14.2% prevalence in the

urban adults reported by Akinkugbe et al in 1997.47

2.1.2 Classification of Hypertension

HTN can be classified by three methods namely48,49 : (1) BP levels (2) Extent of organ damage

and (3) Aetiology

Blood pressure levels:43,49 A very simple and useful classification can be derived from the

Joint National Committee on Prevention, Detection, Evaluation and Treatment of HTN (JNC).

According to JNC V1, BP is classified as Optimum (<120/80mmHg); Normal

(<130/85mmHg), High normal (130-139/85-89mmHg); stage I HTN (140-159/90-99mmHg),

stage II HTN (160-179/100-109 mmHg) and stage III HTN (>180/110mmHg). The latest report

of the JNC, JNC VII, has little modification to the JNC VI. In JNC VII, the normal and high

normal levels of JNC VI are grouped together as the pre-hypertensive stage. Stage I is still the

same while stages II and III are grouped together as stage II.

12

Pre-hypertension stage is not a disease category. Rather, it emphasizes individuals that are at

risk of progression to HTN and the need for lifestyle modifications as important preventive

strategies.43,49,50

WHO/ISH 2004 guideline still retains the old classification of Grade I-III which corresponds

to stage I-III of JNC VI.

Table 1: JNC VI Classification of HTN

Category Systolic Bp (mmHg) Diastolic BP (mmHg)

Optimal < 120 < 80

Normal < 130 < 85

High Normal 130 – 139 85 – 89

Hypertension

Stage I (Mild) 140 – 159 90 – 99

Stage II (Moderate) 160 – 179 100 – 109

Stage III (Severe) ≥180 ≥ 110

Table 2: JNC VII Classification of HTN

Category Systolic Bp (mmHg) Diastolic BP (mmHg)

Normal < 120 < 80

Pre-Hypertension 120 – 139 80 – 89

13

Hypertension

Stage I 140 – 159 90 – 99

Stage II > 160 > 100

NB:

The above values are accepted if patients are not taking anti-hypertensive drugs and not acutely

ill.

Values are based on average of two or more readings taken at each of the two or more visits

after an initial screening.

When systolic and diastolic BP fall into different categories, the higher category is selected for

the classification.

Extent of organ damage:48,49 Stages one to three:

In stage one, there are no objective signs of organ damage

In stage two, there is at least one of the signs of organ involvement. The organs normally

involved are the heart, brain, retina and the kidneys.

In stage three, there are signs and symptoms of damage to the various organs.

Aetiology:44,49 By aetiology, HTN can be classified into

a) Essential or Primary HTN in which no specific underlying cause can be defined. This

accounts for about 90-95% of the causes of HTN. Several factors,44,49 ranging from genetic,

14

humoral, cell membrane defect, foetal to environmental have been implicated in the

pathogenesis of essential HTN. The kidneys are also well implicated.

b) Secondary HTN in which the HTN can be shown to be a consequence of a specific disease

or abnormality. This accounts for about 5-10% of the cases and causes may be renal,

endocrine, pregnancy and drug induced, etc.

2.1.3 AETIOLOGY OF ESSENTIAL HTN

The aetiology of EHTN is unknown. However, quite a number of factors have been implicated

and theories postulated as discussed below.

The Kidney in Essential HTN

The kidney appears to be both culprit and victim in the hypertensive process. Researchers have

proposed that the presence of abnormal kidney function is a common initiating factor in most

forms of arterial HTN, including EHTN. On the other hand, the renal vasculature is well known

to suffer the consequences of persistently elevated BP.

The kidneys are important in the regulation of BP through the role they play by pressure

natriuresis in opposing increases in BP.51 An increase in BP is compensated for by an increase

in renal excretion of water and salt. Thus any alteration of renal perfusion or abnormal renal

function could provoke the development of HTN. Further sodium retention would then

aggravate this situation by fostering development of volume dependant HTN.51

Detailed studies with arteriography and biopsy have shown both structural damage and

functional derangements reflecting intraglomerular HTN in almost all hypertensive persons

15

including those with apparently mild disease51 and even in some normotensive children of

hypertensive parents.44,51

The renal vasculature has been implicated in the development of EHTN and functional

vasoconstriction is present in many patients with mild HTN.51

Furthermore, the sympathetic nervous system is also thought to play a role in the development

of EHTN.51 Increased sympathetic activity, as a consequence of stress or primary sympathetic

dysfunction, may induce renal vasoconstriction which facilitate sodium retention.

Genetic Factors

Data supporting role of genetics can be found in animal studies as well as in population studies

in human.52 One approach has been to assess the correlation of blood pressure in families

(Family aggregation). From these studies, genetic factors have a strong correlation with the

development of HTN.52 In addition, most studies support the concept that the inheritance is

probably multi-factorial or that an elevated BP may represent one of the phenotypic expressions

of a number of different genetic defects.52,53

Finally, both monogenic defects (e.g. glucocorticoid remediable aldosteronism and Liddle’s

syndrome) and susceptibility genes (e.g. the angiotensinogen and alpha adducing genes) have

now been reported which have as one of their consequences, an increased arterial

pressure.52

Foetal Factors

16

Some studies have shown a relationship between lower birth-weight and subsequent higher

BP.54 This relationship may be due to foetal adaptation to intrauterine under nutrition with long-

term changes in blood vessel structure or in the function of crucial hormonal system.44,54

Life Style and Environmental Factors

Among the several environmental factors that have been proposed, the following seem to be

the most important:

a. Obesity: There is a positive correlation between obesity, especially central obesity and

arterial BP. A gain in weight is associated with an increased frequency of higher BPs

in persons with normal BP, and weight loss in obese persons with HTN lowers arterial

BP.55

b. Alcohol intake: Heavy alcohol intake (>6 units or 48g/day) is associated with an

increase in BP, and reduction in intake can reduce BP.44

c. Sodium intake: Some studies have suggested a positive correlation between salt intake

and BP levels, although other studies found the relationship to be weak. There are some

evidences that a high potassium diet can protect against the effect of a high sodium

intake.14,56

d. Stress: Though acute stress or pain can raise BP, the relationship between chronic stress

and BP has been difficult to establish.44,54

Humoral Mechanisms

17

The autonomic nervous system, as well as renin-angiotensin-aldosterone, natriuretic peptide,

endothelins and kallikrein – kinin system, play a role in the physiologic regulation of BP44 and

have been implicated in the pathogenesis of primary HTN.

The vascular endothelium also produces other vasoactive substances such as nitric oxides and

growth factors.44 Nitric oxide is a potent vasodilator that influences local autoregulation and

other vital organ functions.

The growth factors include platelet-derived growth factor (PDGF), fibroblast growth factor

(FGP) and insulin growth factor (IGF). Each of these factors plays an important role in the

atherogenesis and target organ damage.44

Role of Renin: This is an enzyme secreted in the juxtaglomerular cells of the kidney. The end

product of the action of renin on its substrate is the generation of the peptide angiotensin II.27

,44,56,57 The range of plasma renin activities observed in hypertensives is broader than in

normotensive individuals. In consequence, some hypertensive patients have been defined as

having low-renin and others as having high-renin primary HTN.44

Insulin Resistance

Insulin resistance and/or hyper-insulinaemia have been suggested as responsible for the

increased arterial pressure in some people.

Hyper insulinaemia can increase arterial BP by one or more of four mechanisms.44

First, hyperinsulinaemia produces renal sodium retention (at least acutely) and increases

sympathetic activity. Another mechanism is the vascular smooth muscle cell hypertrophy

secondary to the mitogenic action of insulin.

18

Third, insulin also modifies ion transport across the cell membrane, thereby potentially

increasing the cytosolic calcium levels of insulin sensitive vascular or renal tissue.

Finally, insulin resistance may be a maker for another pathologic process, e.g. non-modulation,

which could be the primary mechanism in increasing BP.44

Cell Membrane Defects

This hypothesis derives most of its data from studies on circulating red blood cells (RBC) in

which abnormalities in the transport of sodium across the cell membrane have been

documented.44 It has been assumed that this abnormality in sodium transport reflects a defect

in the cell membrane occurring in perhaps all the cells of the body, particularly the vascular

smooth muscle cells. This defect leads to an abnormal accumulation of calcium in vascular

smooth muscle cells, resulting in a heightened vascular responsiveness to vasoconstrictor

agents.44 This defect has been proposed to be present in 35 to 50% of primary hypertensive

individuals on the basis of studies using red blood cells.44

2.1.4 Clinical Features of Hypertension

HTN has been described as a silent killer.44 Majority of patients with HTN have no specific

symptoms referable to the elevated BP. Symptoms that bring the patients to the physician are

in most cases related to complications of HTN and the underlying disease in the case of

secondary HTN. A few present with symptoms related to the elevated pressure and these

include dizziness, palpitations and fatigability. Headache, which is occipital and present when

patient wakes up and disappears with time is a feature of severe HTN.44,56 A strong family

history of HTN with intermittent high BP in the past favours diagnosis of essential HTN.48,56

19

Symptoms referable to vascular disease include epistaxis, haematuria, blurring of vision due to

retinal changes, episodes of weakness or dizziness from transient cerebral ischaemia, angina

pectoris and dyspnoea due to cardiac failure. Pain due to aortic dissection or a leaking aneurysm

is an occasional presenting symptoms.44,56

Some symptoms related to the underlying diseases in secondary HTN are : 44,56

Polyuria, polydypsia, muscle weakness, secondary to hypokalaemia in patients with

primary aldosteronism.

Weight gain and emotional lability in patients with Cushing’s syndrome

Episodic headaches, palpitations, diaphoresis and postural dizziness in those with

phaeochromocytoma.

2.1.5 Complications of Hypertension

HTN is a major risk factor for coronary, cerebral and renal vascular disease, leading to half of

all death in the United States.44,56 The higher the levels of BP, the more likely that various

CVD will develop prematurely through acceleration of atherosclerosis, the pathological

hallmark of uncontrolled HTN.

In the Framingham cohort study, the risk of developing coronary disease rose progressively

with increasing systolic or diastolic pressure both in the middle aged and the elderly. If

untreated, about 50% of hypertensive patients will die of coronary heart disease or congestive

cardiac failure; about 33% of stroke and 10-15% of renal failure.44,56

Benign hypertensive nephrosclerosis is characterized by two types of renal lesions:

Hyperplastic elastic arteriolosclerosis which is most marked in the interlobular arteries and

hyaline arteriolosclerosis primarily involving the afferent arterioles.

20

The malignant phase of arterial HTN is characterized by marked elevation in blood pressure

with widespread acute arteriolar injury. The changes are more marked in the retina and kidneys

with fibrinoid necrosis and mucoid intimal proliferation of the afferent arterioles being the

hallmark of malignant nephrosclerosis. Nephrosclerosis results in a substantial decline in renal

function that is usually accompanied by microhaematuria and proteinuria.44,58

Functional consequences of nephrosclerosis include progressive increase in renal vascular

resistance and a progressive decrease in effective renal plasma flow.44,58 Initially, glomerular

filtration rate (GFR) is maintained probably at the expense of increased intraglomerular

pressure in each nephron. Progressive destruction of renal arterioles and glomeruli will lead to

a progressive reduction in GFR and will facilitate the appearance of proteinuria. In patients

with long standing HTN, a loss of concentrating ability of the kidneys may be manifested by

nocturia, a decreased creatinine clearance and albuminuria. As HTN induced nephrosclerosis

proceeds, the plasma creatinine level begins to rise and eventually renal insufficiency with

uraemia develops in 10-20% of patients.44,58

Those with rapidly accelerating HTN or malignant HTN die more frequently of renal failure as

do those who are diabetic, once proteinuria or other evidences of nephropathy develop.44

Blacks suffer more renal damage, leading to a significantly greater incidence of end-stage renal

disease (ESRD) requiring chronic dialysis.44 Essential HTN is an important cause of ESRD in

blacks. Records from Republic of Congo showed that HTN, both benign and malignant, is the

most common preventable cause of ESRD.41

21

2.2 ALBUMINURIA IN ESSENTIAL HTN

2.2.1 Definition: The occurrence of MAL in non-diabetic patients with primary HTN was

first described by Parving et al in 1974.17,35 It is defined as an abnormally elevated urinary

albumin excretion, in the absence of clinical proteinuria, ranging from 30 to 300mg/24hours or

20 to 200µg/minute.34 In spot urine specimen, MAL may also be defined as urinary albumin

excretion of 20-200mg/L or urinary albumin-creatinine ratio (UACR) of 3-30mg/mmol. The

normal urinary albumin excretion is in the range of 1-22mg/24 hours with an average of 4-

9mg/24hours.

2.2.2 Microalbuminuria in Essential Hypertension

MAL is a well recognized marker of CV complications in HTN and the most sensitive

parameter for the detection of early kidney damage (stage I & II of CKD).22

The prevalence of MAL in patients with primary HTN ranges between 5% and 40%.35,36

Current prevalence of MAL in hypertensive patients is higher than previously reported, ranging

in different countries between 53% and 71% with the highest rate in patients with uncontrolled

HTN34 as demonstrated in i-SEARCH, a broad-based international survey.

This wide variability is due to the duration and severity of HTN, age and sex distribution and

concomitant CV risk factors.36 Other factors are the patient selection procedures, the existence

of prior treatment associated with adequate or inadequate control of HTN by drug therapy, the

type of which may highly influence albuminuria.59,60

2.2.3 Risk factors for Microalbuminuria in Essential Hypertension

22

Various factors, as highlighted below, have been shown to increase the risk of MAL in

individuals with essential HTN:

Level of BP and duration of HTN: Urinary albumin excretion is closely related to the level of

the clinical BP.61 This trend towards stronger correlations for the systolic BP than for diastolic

BP. Also the longer the duration before diagnosis or before achieving good BP control, the

higher the risk of developing MAL.

Pulse pressure (PP): Isolated systolic HTN (SBP >/= 140) and pulse pressure (SBP minus

DBP) are directly related to MAL independent of diastolic BP and several other

correlations.62,63 As demonstrated by Massimo et al62, PP was linearly related to the urinary

albumin excretion (UAE) in both sexes. Several epidemiological and clinical studies reported

that high PP and isolated systolic HTN are associated with signs of target organ damage and

CV disease even in the presence of low – normal diastolic BP.62,63

Gender: It has been reported that men show higher UAE than women independent of BP,

tobacco habit and BMI.61,63

Obesity: Previous studies have reported greater prevalence of MAL among obese (BMI >/=

30) than among lean subjects.61,64 In hypertensive patients, BMI has also been described to be

associated with UAE.61,65

Smoking: Current and former hypertensive smokers have a marked risk of proteinuria

compared to hypertensive non smokers.21,66 However microalbuminuric effect consequent

upon smoking seems reversible upon smoking discontinuation except in chronic smokers.66

Increasing evidence suggest that chronic smoking is implicated in all aspects of the progression

of renal disease as it increases the risk of MAL and accelerates the rate of progression from

MAL to macroalbuminuria and subsequently renal failure.

23

Alternative medicine: In the developing world, up to 80% of the population uses traditional

medicine for primary health care. In the industrialized countries, adaptations of traditional

medicine, termed complementary alternative medicine (CAM), are used by a growing number

of patients for preventive or palliative care.67 These unconventional medications may be an

important risk for the development of acute and chronic kidney injury because of several

factors: (a) These products rarely meet the essential standard, (b) many of these products

contain undisclosed over-the-counter or prescription drugs or can be adulterated with hormones

and glandular extracts and (c) they can also be contaminated by pesticides and heavy metals.

These factors, inter alia, predispose users to various kidney toxicity that results ultimately in

irreversible renal disease.67

Finally, by virtue of various organ ageing and probably due to co-morbidity e.g DM, older age

hypertensives are at increased risk of MAL compared to the younger one with similar other

risk factors.

2.2.4 Mechanisms of Albuminuria in Essential Hypertension

Albuminuria is one of the manifestations of renal insufficiency in essential HTN. Clinically

apparent proteinuria in essential HTN is associated with increased CV and cerebrovascular

disease and is an independent predictor of morbidity and mortality.34 Subclinical elevation of

albumin excretion is seen more frequently than clinical proteinuria in primary HTN and the

level of MAL correlates with the BP level.10,15,34

The transglomerular passage of albumin (molecular weight 69,000) and other macromolecules

are determined (a) by their molecular size, shape and electrical charge, (b) by the size and

charge-selectivity properties of the glomerular filter and (c) by renal haemodynamics.

24

The glomerular filtration of albumin molecule is restricted by the size and electrostatic

hindrance of the negatively charged glomerular filter. Loss of charge and size-selective

properties of the glomerular filter explains the proteinuria of various diseases.44

The increased urinary albumin excretion in HTN has been explained by several factors:44

(i) Renal haemodynamics changes

(ii) Permeability-selectivity changes of the glomerular filter and/or insufficient tubular

reabsorption of albumin

(iii) Structural arteriolar and glomerular changes due to nephrosclerosis.

In established essential HTN, renal vascular resistance is characteristically elevated, renal

plasma flow reduced but GFR is usually maintained, presumably due to predominant efferent

arteriolar vasoconstriction leading to increased filtration fraction.44 Angiotensin II is said to

be involved in this auto-regulation of GFR and is believed to help maintain GFR by constricting

the efferent arterioles thereby increasing transcapillary hydrostatic pressure difference which

also results in increased protein filtration. Proteinuria therefore does not necessarily have to be

attributed to glomerular injury in states with reduced renal plasma flow and increased filtration

fraction. Angiotensin II has been shown to increase albumin excretion rate in HTN either by

elevating glomerular capillary pressure or by increasing the permeability of the glomerular

capillary to albumin or by both mechanisms.10

Albuminuria in HTN may also be due to nephrosclerosis, that is arteriolosclerosis especially

involving the inter-lobular artery and the efferent arterioles.

It has also been postulated that the proteinuria in HTN may be secondary to irreversible

structural glomerular changes from vascular damage leading to mild ischaemia or complete

25

sclerosis. In addition to this structural damage, the unchanged nephrons are subjected to hyper-

filtration with enhancement of proteinuria and glomerular injury.44

Clinical proteinuria which is usually not reversible by antihypertensive therapy may be due to

predominantly structural vascular and glomerular changes while MAL, which is often

reversible38, may be caused by predominantly functional haemodynamic changes.

Recent studies have described a glomerular permeability-independent mechanisms by which

albuminuria may occur: “ The albumin degradation pathway ”.10 The factors governing the

manifestation of albuminuria in HTN and diabetes have drawn important link between (a) up-

regulated renin-angiotensin system and increased transforming growth factor (TGF-β1)

expression and (b) disrupted albumin processing by the kidney.10,68

Lucinda et al reported that albumin filtered by the kidney is endocytosed by proximal tubular

cells and degraded into peptides in lysosomes. These peptides are exocytosed back into the

tubular lumen and excreted in the urine. Changes in the post-glomerular handling of albumin

are therefore implicated in the induction of albuminuria in hypertensive and diabetic states.10

2.2.5 Detection of Microalbuminuria

Urinary albumin excretion varies from day to day and is affected by factors such as posture,

exercise and BP.10,69 For this reasons, the collection of two to three non-consecutive urine

samples has been recommended to obtain a reliable result.

For screening purposes, measurement of the urinary albumin concentration of the first morning

urine has been suggested since this specimen is thought to vary least.64,70,71 However, some

other studies have shown that any urine sample can be used.

26

Laboratory methods available for detecting MAL include Radioimmunoassay, Laser

immunonephelometry, Enzyme immunoassay, Immunoturbidimetry, Fluorescent

immunoassay and High performance liquid chromatography.72,73 Radioimmunoassay is

probably the most accurate method but it is very expensive.

In addition to these laboratory techniques for quantitative determination of urinary albumin

levels, newly developed semi-quantitative screening methods base on immuno-reaction are

also available. The Micral-Test II strip74 (Roche Diagnostics) is an immunochemical strip

specific for albuminuria.72 In different multicenter studies, Giusepper et al71,75 demonstrated a

sensitivity of 95.2% and specificity of 84.7% while Mogensen et al71,76 reported 96.7%

sensitivity and 80% specificity when compared with the gold standard. It has been found to be

highly sensitive, effective, relatively cheap and rapid tool for detecting MAL. Studies 64,71,75,76

have shown that MAL measurement alone using Micral-Test strip is the choice method for

rapid, reliable point-of-care screening. The gold standard (24hours urine albumin estimation)

and UACR are not economically justifiable as they are too cumbersome and complex to

perform both for the researchers and the patients 75-77 Therefore, measurement of microalbumin

alone in a clean catch spot morning urine sample is more convenient in daily clinical

practice.72,78

The Micral-Test is a semi-quantitative immunoassay strip specific for albuminuria. It consists

of reagent pads. Urine is drawn by a chromatographic process through the wick fleece to the

buffer fleece, where the sample is adjusted into alkaline PH. In the conjugate fleece, albumin

in the urine binds to a soluble conjugate of albumin antibody and B-Galactosidase. Excess

antibody is then bound to immobilized albumin in the capture matrix and thus is effectively

removed from the sample, so that only albumin bound to the antibody-enzyme complex reaches

the colour substrate pad. The substrate is Chlorophenol Red Galactoside, which turns red when

27

the galactose is split by the B-Galactosidase. The intensity of the colour produced is

proportional to the albumin concentration in the urine. The colour formed after the specified

time is compared with the reference chart on the vial comprising of four colour blocks

corresponding to albumin concentrations of 0, 20, 50, and 100mg/L.74 Concentrations are read

after sixty (60) seconds of removing the strip from the urine. The strip is in contact with the

urine at a specific level on the strip for five (5) seconds only. Shorter contact time results in

under estimation of the albumin concentration and vice versa.65

Figure 1: COMPONENTS OF THE MICRAL TEST STRIP

28

2.2.6 Prognostic Implications and Clinical Pattern of Microalbuminuria in

Hypertension

MAL has prognostic implication in HTN. The presence of MAL in patients with HTN carries

an increased risk for CV morbidity and mortality.79 Mathew79 in his review observed that CV

complications such as coronary artery diseases, peripheral artery disease and retinopathy were

more frequent in patients with MAL. Bjorin et al22 in the LIFE study also reported that

hypertensive patients with MAL have an increased thickness of the carotid intimal and medial

layers suggesting a greater degree of atherosclerosis.

A recent attempt at explaining the relationship between MAL and various CV and renal

findings such as LVH, carotid thickening and renal injury implicated the role of Angiotensin

II and Transforming Growth Factor (TGF-β1).10 Increased TGF-β1 and angiotensin II in HTN

and diabetes can lead to increased collagen IV and fibronectin production as well as decreased

lysosomal activity. Collagen IV and fibronectin promote hypertrophy and/or fibrosis in the

kidney, heart and other vascular beds while the decreased lysosomal enzyme activity especially

cathepsin with the consequent impaired post-glomerular albumin degradation results in MAL.

Therefore, MAL could signal the presence of generalized atherosclerosis with the kidneys as

the window.

A wide variety of data have shown positive correlation between MAL and several other clinical

factors such as mean arterial pressure (MAP), Body mass index (BMI), smoking, alcohol

consumption, family history of HTN/CKD and herbal therapy.

At the end of this proposed study, the prevalence of MAL as well as the associated factors

should be clearly highlighted and risk stratification of patients with essential HTN in this

environment can be recommended. Risk stratification with early institution of the appropriate

strategies for the optimum quality of life of these patients is of paramount importance to a

29

family physician. By virtue of training, Family Physicians holistically care, not only for the

disease but also for the effect of the illness on the index patient as well as the family.

2.3 CONTROL OF MAL WITH REFERENCE TO USE OF ANTI-

HYPERTENSIVE AGENTS

MAL has been found in varying proportion of patient with EHTN. Using sensitive methods of

urinary albumin quantification. Maria et al61 and Volpe et al80, have shown that urinary albumin

excretion (UAE) rate is significantly and positively correlated to the level of arterial pressure.

This suggests that MAL might be a consequence of HTN.

Therefore, control of BP would lead to reduction in UAE in patients with HTN.

This has been shown to be the case in some studies.51,61,80

Several classes of antihypertensive drugs with varied mode of action are currently available for

the control of hypertension. Some of the widely used therapeutic classes include the following:

Diuretic – mainly Thiazide diuretics.

Alpha–adrenoceptor antagonists e.g. Prazocin

β–Adrenoceptor antagonists e.g. Propranolol, Atenolol.

Vasodilators e.g. Hydrallazine.

Calcium channel blockers e.g. Nifedipine, Amlodipine.

Central acting drugs e.g. Methyldopa, Reserpine.

Angiotensin Converting Enzyme Inhibits (ACE–I) e.g. Captopril, Lisinopril.

Angiotensin Receptor Blockers (ARB ) e.g. Losartan, Candesartan

30

These groups of antihypertensive drugs also show different actions regarding kidney function.

This has led to the question of differences concerning reduction of MAL by these different

agents. Different groups of workers have tried to find out the effect of certain antihypertensive

agents on excretion of albumin by the kidneys. More recent studies23-33,81-85 have clearly shown

that ACE–I and ARB significantly reduced UAE in EHTN than any other group despite similar

antihypertensive efficacy.

These agents (ACE–I & ARB) have also been shown to reduce MAL in Non-Insulin Dependent

and Insulin Dependent Diabetics with incipient diabetic nephropathy (persistent MAL) and

postpone or even prevent progression to clinical overt diabetic nephropathy.87-89,90-93

Also in hypertensive diabetics with overt proteinuria, ACE–I & ARB have been shown to

reduce protein excretion and that the anti-proteinuric effect is independent of the effect on

systemic BP. The mechanism of the beneficial effects of ACE-I and ARB on proteinuria in

patients with pre-existing renal disease as well as in patients with EHTN is believed to be

through the reduction of intraglomerular pressure and hyperfiltration. The reduction of

systemic BP may certainly play a role through reduction of filtration pressure. These findings

suggest that screening and intervention programmes instituted early are likely to have life-

saving effects. And this leads to a considerable economic gain by reducing the rate of

progression to overt hypertensive/diabetic nephropathy with its attendant morbidity and

economic burden on the patient and family.

31

CHAPTER THREE

MATERIALS AND METHOD

Study Site

The study was carried out at the General Outpatient Clinic (GOPC) of Federal Medical Centre,

Abeokuta. The Centre is a relatively young tertiary institution established in 1993 by the

Federal Government of Nigeria to cater for the health need of the people of Ogun State and its

neighboring states in South West Nigeria. The state has a population of about 3.7 million and

a land area of about 16,409.2 square kilometer going by the 2006 population census.

The hospital has a total of 200 bed spaces and runs residency programme in family medicine,

internal medicine, paediatrics and obstetrics and gynaecology. The GOPC is run by the

department of family medicine and its attendance was 15,494 in the year 2008 with a monthly

average of 1291. The total number of hypertension cases seen over this period was 5412

translating to 34.9% of GOPC attendance. The GOPC is located close to the main gate of the

hospital. It has 4 consulting rooms and a waiting room with facilities to accommodate up to

100 patients at a time. It is managed by the medical and non-medical teams comprising of the

doctors, nurses, records and administrative officers. It has both account and records units

attached to it. All the other units such as laboratory, physiotherapy e.t.c are used centrally.

Study Population

The entire 5412 adult male and female patients aged 18years and above with HTN attending

the GOPC of the hospital. The selection (inclusion and exclusion) criteria are as under listed:

Inclusion Criteria

32

Adult male and female patients aged 18years and above with essential HTN, either newly

diagnosed or already on treatment, attending the GOPC of the hospital. All subjects who

voluntarily signed the informed consent.

Exclusion Criteria

History was obtained from all subjects and complete physical examination was carried out to

exclude secondary hypertension and other causes of MAL. Reference was made to old records

where necessary. Urinalysis was done using the Combur strip. These in addition to clinical

evaluation as highlighted above were used to exclude the under listed:

1. Urinary tract infection (UTI): ) other causes of proteinuria

2. Chronic renal disease ) ,,

3. Congestive cardiac failure ) ,,

4. Diabetes mellitus ) ,,

5. Acute febrile illnesses and emergency conditions ) ,,

6. Pregnancy ) ,,

7. Evidence of secondary HTN

8. Macroalbuminuria

9. Refusal to give consent

Study Design

33

This research was a hospital based cross sectional descriptive study.

Sample Size

Sample size was calculated using the formula:94

nf = n / { 1+ n/N }

Where:

nf = Desired sample size when the study population to be represented is less than 10,000

n = z2 p q / d2 = Desired sample size when the study population to be represented is greater

than 10,000

N = Entire hypertensive population attending GOPC of FMCA = 5412

z = Standard normal deviate often set at 1.96. This corresponds to 95% confidence interval

(CI)

p = Prevalence (Prevalence of MAL among patient with essential HTN)

q = 1.0 – p

d = Degree of accuracy desired

To calculate the minimum sample size for this study,

z = 1.96

p = 41%. (Odili in Jos.37)

34

d = 0.05. Since the degree of accuracy desired is 95%

Since

n = (1.96)2 x 0.41 x 0.59 / (0.05)2 = 382.77 .

Hence

nf = (382.77) / [ 1 + (382.77 / 5412) ] = 357.48

This was approximated to 360

Adding 10% attrition value, a total of 395.373 was obtained. Based on this, the estimated

sample size will be approximated to 395 subjects.

Sampling Method

A systematic sampling method was employed. The first subject was selected by balloting once

at the outset of the study. On subsequent days, subjects were recruited as they presented to the

GOPC. With a monthly average of 451 hypertensive patients, a total of 1353 hypertensive

subjects could be recruited in three months. This gave a sampling interval of 3. Therefore,

35

every 3rd patient with essential HTN who presented at the GOPC and met the selection criteria

was enrolled into the study. All enrolled subjects gave informed consent to participate in the

study.

Materials

The materials used included the following:

A semi-structured questionnaire was used. Its validity and reliability were assessed

through a pre-test in a similar setting at the hypertensive clinic of the medical outpatient

department (MOPD) of the hospital. About 30 subjects were selected haphazardly95 and the

questionnaire was administered to them. Necessary amendment was then made on the

questionnaire based on the outcome of the pre-test before finally adopted for the study. The

questionnaire contained various items including sociodemographic characteristics, medical

history, physical examination and investigations (urine tests). Also serial number and coded

hospital number were represented. For absolute confidentiality, Alphabets A-I respectively

represented figures 1-9 while J stood for zero in the coded hospital number. The research

assistants were well informed about this.

Patient’s case note (GOPC): Used in addition to history and physical examination to rule

out secondary causes of HTN and other chronic conditions as highlighted under exclusion

criteria.

Accosson Mercury Sphygmomanometer: For BP measurement in millimeters of

mercury.

Littmann’s Stethoscope: BP measurement and auscultation during physical examination.

Urine testing strips:

(a) Combur–Test from Roche Diagnostics, Mannheim, Germany: For urinalysis

36

(b) Micral–Test II from Roche Diagnostics, Mannheim, Germany: For MAL

estimation

Sterile universal bottles: To collect early morning urine sample

Refrigerator: To store the heat sensitive Micral–Test II strip at +2oC to +8oC

Standard weighing scale from Surgifriend Medicals, England: For weight measurement

in Kilometer (Kg).

Stadiometer from Surgifriend Medicals, England: For height measurement in centimeter

Tape measure: To measure waist and hip circumference in centimeters (cm).

Stop watch: For timing during urine testing for MAL with the Micral–Test II strip.

37

DATA COLLECTION PROCEDURE

Protocol -1: Clinical Evaluation

Baseline clinical and demographic characteristic were obtained from all qualified subjects

using the semi-structured questionnaire.

With the subject seated and rested for 5minutes, BP was measured in the right arm by the

researcher aided by trained research assistants using Accosson® mercury sphygmomanometer

(cuff size 12.5 x 40cm). Systolic and diastolic BP were measured at Korotkoff phases I & V

respectively. The mean of two BP measurements taken at an interval of at least 2 minutes61 was

used. Blood pressure ≥140/90mmHg was taken as hypertension.

Mean arterial pressure (MAP) was calculated thus:

MAP = Diastolic BP + 1/3Pulse Pressure

Subjects were weighed in light clothes without shoes or other items such as handset, bunch of

keys etc using Surgifriend Medicals’ standard weighing scale to the nearest 0.1kg. The

weight was read with the subject standing still in the middle of the scale’s platform without

touching anything with body weight equally distributed on both feet.96,97 Height was

measured with the Stadiometer to the nearest centimeter (cm) with subject standing erect,

position the head in the Frankfort horizontal plane (i.e looking straight ahead), heels together,

arms to the side, shoulders relaxed and putting on neither shoes nor head wear. Heels,

buttocks, scapulae (shoulder blades), and occiput were against the vertical board of the

stadiometer. The headboard of the stadiometer was then lowered upon the highest point of the

head with enough pressure to compress the hair. The measurement was read with the eye at

the same level with the headboard to avoid errors due to parallax.96,97 Body mass index

38

(BMI) was calculated using the formula BMI = weight (kg) / height2 (m2). (Normal range is

18.5-24.9kg/m2)

The waist circumference (cm) was measured with a tape measure as the horizontal

circumference midway between the lowest rib and the iliac crest. Hip circumference is the

maximum circumference around the buttock posteriorly and the pubic symphysis anteriorly to

the nearest centimeter.

Waist–Hip ratio (WHR) = Waist circumference / Hip circumference

Normal is 1.0 for male and 0.8 for female

Protocol-2 : Screening for Microalbuminuria

All tests were personally carried out by the researcher according to the manufacturer’s direction

on the strip leaflets. Macroalbuminuria, glycosuria, microhaematuria, urinary evidence of

urinary tract infection (UTI) were first ruled out using the Combur-Test Strip. All patients

whose urine samples were negative for macroalbuminuria were further screened for

microalbuminuria using Micral-Test II Strip.

The Micral-Test Strip was immersed in clean catch spot morning urine sample such that the

fluid level was just between the two black bars on the strip, making sure that it didn’t touch the

side of the vessel in the process. Timing with stopwatch, the test strip was withdrawn after 5

seconds and placed across the top of the specimen bottle. After 1 minute, the colour of the test

pad above the inscription “Micral” was compared with the colour scale on the test strip

container label.

39

MAL was said to be positive when a urine sample produced a reaction colour corresponding to

20mg/L albumin (threshold for MAL) or more. The reaction colours range from white (MAL

<20mg/L) to deep pink (MAL >100mg/L).

DATA ANALYSIS AND PRESENTATION

Data was analyzed using SPSS software version 15.0 (SPSS, Inc. Chicago, Illinois).

Tables and charts were used as appropriate.

Continuous variables were presented as mean values and standard deviations. Categorical

variables were presented as frequencies. Chi-squared test was used to assess differences in

categorical variables while continuous variables were analyzed using z-test or t-test as

appropriate. A multivariate regression analysis was performed to identify independent factors

associated with MAL.

All the results from the regression model were shown as odds ratio with corresponding 95%

confidence intervals. All statistical tests were two-tailed and P-values < 0.05 were considered

statistically significant.

ETHICAL CLEARANCE AND APPROVAL

Approval and ethical clearance were obtained from FMC, Abeokuta Health Research ethics

committee. Informed written consent was obtained from the subjects prior to clinical evaluation

having duly informed them about the study. A copy of the consent form is attached as appendix-

II

40

FUNDING

Funding of the study was exclusively at the expense of the researcher. No subject bore any cost

that was directly related to the study.

41

CHAPTER FOUR

RESULTS

4.1 SOCIO-DEMOGRAPHIC DATA

4.1.1 AGE AND SEX DISTRIBUTION

Three hundred and ninety-five (395) patients with EHTN were screened. This comprised of the

minimum sample size of three hundred and sixty (360) and a 10% attrition rate of thirty five

(35) subjects. Data were however analyzed for the first three hundred and sixty (360)

respondents representing the actual sample size for the study.

There were one hundred and forty-two (142) males (39.4%) and two hundred and eighteen

(218) females (60.6%) aged between 25 and 107 years. There were more females than males

with a female to male ratio of 3:2. This shows that more female patients were present for daily

follow-up in the clinic [ Table 3, page 38 and Figure 2, page 40 ].

The characteristics of the patients are shown in Tables 3 and 4. It was observed that the mean

age of the patients with HTN was 57.24 ± 12.17 years with majority of the patients ≥60 years.

Expectedly, there were fewer patients in the age group 30-44 years.

42

Table 3: MEAN CLINICAL CHARACTERISTICS OF PATIENTS STUDIED

No of Patients Age (Yrs)

Mean ±

SEM

Duration of

Hypertension

(Yrs)

Mean ± SEM

Blood pressure mmHg

Mean ± SEM

State of Blood Pressure

Control

Level of MAL

(Mg/l)

Average number of

Drugs per patient

Males

Females

Systolic Diastolic Mean

Arterial

Controlld Stage I Stage II 20-50 51-100 >100 1

2

3

142

39.4

%

218

60.6%

73.48

± 15.10

21.09

± 12.24

159.50

± 21.09

92.38

± 12.85

113.16

± 18.89

89

(24.7%)

125

(34.7%)

146

(40.6%)

63

(31.5%)

65

(33.5%)

69

(35%)

6

(1.7%)

169

46.9

%

39

10.8%

43

Table 4: CLINICAL CHARACTERISTICS OF PATIENTS STUDIED USING THE AGE GROUPS

Age

group

(years)

No. of

Patients

No.

Females

No.

Males

Mean weight (kg) Mean Blood Pressure

9mmHg)

Average

Duration

of HTN

(years)

No. of

patients

on mono

therapy

No. of

patients

on

Multiple

therapy

Females Males Systolic Diastolic Mean

arterial

<30-34 12 7 5 66.2 72.8 150 98 118.8

1.41 0 2 (0.9%)

35-39 15 9 6 85.6 77.8 153 94 114.6

10.60 0 7(3.3%)

40-44 28 21 7 80.9 74.14 143 91 117.3

7.07 0 14(6.5%)

45-49 40 26 14 77.0 77.7 155 97 107.06

7.61 1 (0.5%) 21(9.8%)

50-54 41 25 16 77.7 77.3 158 95 110.1

15.92 0 22(10.2%)

44

55-59 48 23 25 78.8 76.3 159 94 114.0

9.94 2 (0.9%) 28(13.0%)

60-64 66 38 28 66.7 77.68 166 94 114.8

14.56 0 47(21.9%)

65+ 110 69 41 66.7 70.0 163 86 113.1

13.49 2 (0.9%) 69(32.1%)

45

Figure 2: AGE AND SEX DISTRIBUTION OF THE PATIENTS SCREENED

0

20

40

60

80

100

120

<30-34 35-39 40-44 45-49 50-54 55-59 60-64 65+

AGE GROUP OF PATIENTS

NU

MB

ER

OF

PA

TIE

NT

S

males

females

46

4.1.2 SOCIAL STATUS.

The result of social status of the patients is shown in Table 5. Two hundred and thirty five

(65.3%) of the patients were married while four (1.1%) were single. Others were either

widowed (23.3%) or divorced / separated (10.3%).

One hundred and fourteen (31.7%) had no formal education, sixty –eight (18.9%) of the

patients had primary education, while one hundred and sixteen (32.4%) of the patients had post

secondary school education.

In terms of occupation, ninety (25%) of the patients were traders, sixty–seven (18.6%) were

pensioners, thirty-eight were business personnels (10.6%), thirty-four were civil servants

(9.4%) and others were professionals (3.9%), farmers (2.8%) and students (0.6%)

The religion predominantly practiced by the patients were Islam (127 patients – 35.3%) and

Christianity (233 patients – 64.7%). Also, most of the patients were Yoruba (89.4%), twenty

four (6.7%) were Igbo and only one of the patients was Hausa. The remaining thirteen (3.6%)

of the patients belong to other ethnic groups.

47

Table 5: SOCIO-ECONOMIC STATUS OF STUDY PARTICIPANTS

STATUS PATIENTS

Frequency Percentage (%)

MARITAL

Single 4 1.1

Married 235 65.3

Divorced/ separated 37 10.3

Widowed 84 23.3

EDUCATIONAL

Nil 114 31.7

Primary 68 18.9

Secondary 62 17.2

Post Secondary 116 32.4

OCCUPATION

Pensioner 67 18.6

Unemployed / retired 26 7.2

48

Artisan / Skilled labour 27 7.5

Trading 90 25

Business 38 10.6

Civil servant 34 9.4

Professional 32 8.9

Others 46 12.8

RELIGION

Islam 127 35.3

Christianity 233 64.7

ETHNIC GROUP

Yoruba 322 89.4

Hausa 1 0.3

Igbo 24 6.7

Others 13 3.6

4.1.3 ANTHROPOMETRY

49

The mean weight of the patients was 73.48+15.10 kilograms while the mean height of the

patients was 1.65+0.09 meters. Table 6 shows other anthropometric characteristics of the

patients. The mean hip and waist measurements of the patients were 96.76+13.56 and 103.77+

13.39 respectively.

Correspondingly, the mean BMI and waist-hip ratio (WHR) of the patients were 26.79+5.65

and 0.93+0.06 (Table 6).

One hundred and forty-two (142) of the patients had normal BMI status, while one hundred

and eighteen (118) patients were overweight and eleven (11) patients had under-weight BMI

(Figure 3). 89 patients were in the obesity category, out of which 59 were mild, 14 moderate

and 16 morbid in obesity.

Obesity was more among the female patients than males (Figure 4)

50

Table 6: ANTHROPOMETRY CHARACTERISTICS OF THE PATIENTS STUDIED

Mean BMI kgm-2

Mean Height (m)

Mean waist

circumference

Mean Hip

circumference

Mean WHR

26.79 ± 18.89

1.65 ± 0.09

96.76 ± 13.56

103.77± 13.39

0.93 ± 0.06

51

FIGURE 3: BODY MASS INDEX AND WAIST-HIP RATIO STATUS OF PATIENTS STUDIED

52

BMI status

0

50

100

150

200

250

underw

ieght

normal

overw

eight

mild

obes

ity

moder

ate

obesity

mobid

obes

ity

normal

high

NU

MB

ER

OF

PA

TIE

NT

S

Body Mass Index

(BMI)

Waist- Hip Ratio

(WHR)

53

FIGURE 4: BODY MASS INDEX AND WAIST –HIP RATIO STATUS AMONG MALE AND FEMALE

0

50

100

150

200

250

un

derw

ieg

ht

no

rma

l

ov

erw

eig

ht

mil

d o

be

sit

y

mo

de

rate

ob

es

ity

mo

bid

ob

es

ity

no

rma

l

hig

h

BMI status WHR status

NU

MB

ER

OF

PA

TIE

NT

S

female

male

54

4.1.4 CLINICAL FINDINGS

The mean systolic and diastolic BP and mean arterial pressure (MAP) of the patients in this

study were 159.50+21.09, 92.38+12.85 and 113.16+18.89mmHg respectively (Table 3).

This study showed that 146 (40.6%) of the patients were at stage-II of JNC-VII essential HTN

while 125 (34.7%) were at stage-I. Only 89 (24.7%) of the patients had their BP under control.

Among these patients, EHTN was more prevalent as age increases (Tables 3 and 4).

The duration of HTN since diagnosis ranged between less than a year and 40years (Figure 5).

Majority of the patients were diagnosed less than ten years ago while only few of them had

been diagnosed of HTN more than 30years ago (Figure 5)

Two hundred and seventy-nine (279) of the patients (77.5%, Figure 6) were positive to MAL

test and this was more evidenced in patients between the age group 60years and above.

MAL level of the patients was between 20 to above 100mg/L (Table 3). Sixty three of the

patients had between 20-50mg/L while 65 and 69 of the patients had between 51-100 and above

100mg/L level of MAL respectively.

Also, occurrence and level of MAL tend to increase in the patients with EHTN as the age of

the patients increases (Figure 7).

Smoking and Alcohol drinking were among the obvious risk factors observed for MAL among

the patients with EHTN in this study. As at the time of data collection, ten (2.8%) of the patients

claimed that they smoked daily. Number of sticks smoked per day was between 1 and 10. Three

of the patients claimed to smoke 5 sticks per day while 7 patients smoked 10 sticks per day.

The duration (in years) of smoking among the patients was minimum of one and maximum of

40 years (Table 7).

55

Thirty-three (9.1%) of the patients claimed to have smoked in the past for between 1 and 40

years. 17 of them smoked for >11< 40 years while the remaining 16 smoked for less than 10

years. In addition, the number of sticks smoked per day was between 1 and 20 out of which 20

of the patients claimed to have smoked between 1-5 sticks daily and 8 patients claimed between

11 and 20 sticks per day (Table 7).

Twenty-three (23) of the patients later stopped smoking for as long as between one and forty

years to the time of this study. Seventeen of them stopped about 40 years prior while the other

16 subjects stopped less than ten years ago (Table 7).

Alcohol consumption among the respondents is shown in Table 8. Only 45 patients claimed to

consume alcohol (alcoholic wine, beer and gin). Beer as a brand of alcohol was more frequent

among the patients than other brands with alcoholic wine and gin being the least consumed.

Most of them (34) have consumed alcohol for over 10 years while 30 of them stopped alcohol

10 years earlier. Only five (5) patients were still taking alcohol up till less than a month prior

to this study.

Since significant ingestion of alcohol is defined as more than 4 units (32g or big bottle of beer)

per day for men and more than 2 units per day for women, most of these patients (>34)

consumed medically significant quantity of alcohol.

Consumption of herbal preparation was prevalent among the patients studied (293; 81.4%).

Herbal preparations were taken regularly by 177 (60.4%) of the patients while 116 (39.6%)

took the products occasionally (Table 9).

56

Figure 5: DURATION OF HYPERTENSION SINCE DIAGNOSIS

0

20

40

60

80

100

120

140

160

<1 1-4 5-9 10-14 15-19 20-24 25-29 30-34 35-40

NU

MB

ER O

F PA

TIEN

TS

57

DURATION IN YEARS

58

FIGURE 6: DISTRIBUTION OF PATIENTS WITH ESSENTIAL HYPERTENSION

WITH RESPECT TO MICRAL TEST

positive

77%

negative

23%

59

FIGURE 7: AGE DISTRIBUTION AND LEVEL OF MICROALBUMINURIA IN PATIENTS STUDIED

TABLE 7: PREVALENCE OF CIGARETTE SMOKING AMONG PATIENTS WITH ESSENTIAL HYPERTENSION

SMOKING PRESENTLY

SMOKED IN THE PAST

Smoke as

at present

No. sticks per day Years smoking Smoke in

the past

No. sticks per day Years smoked Years stopped

smoking

Yes No sticks Patients years patients Yes No Sticks patients years Patients years patients

60

10

350

1-5

3

1-10

1

33

327

1-5

20

1-10

16

1-10

16

10-20

7

11-20

1

6-10

5

11-20

8

11-20

4

11-15

-

21-30

1

11-15

1

21-30

8

21-30

2

20 +

-

31-40 +

7

20 +

7

31-40 +

1

31-40

1

TABLE 8: PREVALENCE OF ALCOHOL CONSUMPTION AMONG PATIENTS WITH ESSENTIAL HYPERTENSION

61

PRESENTLY

IN THE PAST

Take

Alcohol?

Brand Duration Alcohol in

the past

Duration Years stopped Alcohol

Yes No Wine 1 years patients Yes No Years patients years patients

45

315

Beer

38

1-10 11

34

326

1-10 16 >1 5

Gin 2 11-20 17 11- 20 11 1-10 16

Beer +

Gin

2 21-30 8 21- 30 12 11-20 4

All 2 31-40 + 9 31-

40+

5 21-40+ 9

62

TABLE 9: CONSUMPTION OF HERBAL PREPARATION AMONG PATIENTS

WITH ESSENTIAL HYPERTENSION

Take Herbal Preparations

How Often

Yes

No

Occasionally

Regularly

63

293

67 116 177

64

4.2 ASSOCIATION OF RISK FACTORS WITH MAL AMONG PATIENTS WITH ESSENTIAL

HYPERTENSION

4.2.1 MAL AND HERBAL CONSUMPTION

Association of risk factors with MAL was observed among the patients studied in this research (Table 10).

Majority (234; 83.9%) of the patients who tested positive to Micral test have taken herbal preparations at one time

or the other. Only 45 patients, though positive to Micral test did not take herbal preparations.

Further analysis showed that more patients who took herbal preparations regularly had >100mg/L level of MAL

(Figure 8).

65

TABLE 10: ASSOCIATION OF HERBAL PREPARATION CONSUMPTION WITH

MICROALBUMINURIA AMONG PATIENTS WITH ESSENTIAL HYPERTENSION.

CONSUMPTION OF HERBAL PREPARATION

Micral test Yes No

Positive 234 45

Negative 59 22

X2 Value

8.91, (p< 0.05)

Level of microalbuminuria

20 - 50 mg/l 50-100 mg/l >100mg/l

Take herbs 74 77 83

No herbs 8 7 30

66

Figure 8: A BAR CHART COMPARING LEVEL OF ALCOHOL CONSUMPTION WITH DEGREE OF

MAL

0

5

10

15

20

25

30

35

40

20-50mg/l 50-100mg/l >100mg/l

Level of Microalbuminoria

Nu

mb

er o

f P

ati

en

ts

ocassionaly

regularly

67

4.2.2 MAL AND ALCOHOL CONSUMPTION

Out of 45 patients who consumed alcohol, 36 were positive to Micral test with 10 patients having between 20-

50mg/L level of MAL, 19 patients having between 51-100mg/L level and 7 patients had above 100mg/L level

(Table 11).

68

TABLE 11: ASSOCIATION OF ALCOHOL CONSUMPTION WITH MICROALBUMINURIA

AMONG PATIENTS WITH ESSENTIAL HYPERTENSION.

ALCOHOL CONSUMPTION

Micral test

Positive 36

Negative 9

X2 Value

8.38 (p< 0.05)

Level of microalbuminuria

20 - 50 mg/l 50-100 mg/l >100mg/l

Take alcohol 10 19 7

69

4.2.3 MAL AND SMOKING

All the patients (10) who were still smoking at the time of data collection were positive to micral test of which

most of them (6) smoked between 6-10 sticks per day with 51-100mg/L level of MAL. Patients (7) who have

been smoking for over 30 years were predominantly among the patients that were positive to micral test with 4

of them having MAL level of >100mg/L (Table 12).

MAL was not however significantly associated with patients smoking in the past. Although, 21 of out of 33

patients who claimed to have smoked in the past were positive to mal test, this was not statiscally significant

(Table 13).

70

TABLE 12: ASSOCIATION OF SMOKING (PRESENTLY) WITH MICROALBUMINURIA AMONG

PATIENTS WITH ESSENTIAL HYPERTENSION.

SMOKING AT PRESENT

Micral test Yes

Positive 10

Negative -

Sticks per day

1-5 6-10 >10

No. of patients 3 6 1

Level of microalbuminuria

Sticks per day 20 - 50 mg/l 50-100 mg/l >100mg/l

1-5 1 2 0

6-10 0 3 3

>10 0 0 1

Level of microalbuminuria

How long been

smoking 20 - 50 mg/l 50-100 mg/l >100mg/l

1-10 1 0 0

71

11-20 1 0 0

21-30 0 1 0

30-40+ 1 2 4

TABLE 13: ASSOCIATION OF SMOKING (IN THE PAST) WITH MICROALBUMINURIA AMONG

PATIENTS WITH ESSENTIAL HYPERTENSION.

SMOKED IN THE PAST

MAL

Negative Positive

Yes 12 21

No 76 251

X2 value 2.09, P = 0.147

72

4.2.4 COMBINATION OF RISK FACTORS (ALCOHOL, SMOKING AND HERBS) AMONG MAL

POSITIVE SUBJECTS

As depicted in Table 13B (page 63), two hundred and thirty-eight (85.3%) of MAL positive patients were taking

herbal preparations without smoking or taking alcohol.

Thirty-three (11.8%) subjects took herbal preparations as well as drank alcohol while six (2.2%) subjects

combined herbs consumption with smoking.

Only two of the MAL positive patients indulged in all of these three factors (smoking, alcohol and herbs

consumption).

73

TABLE 13B: PROPORTION OF MAL POSITIVE SUBJECTS THAT SMOKED, DRANK ALCOHOL

AND/OR CONSUMED HERBS.

FACTORS

PROPORTION OF MAL POSITIVE SUBJECTS

All factors (herbs, smoking &

alcohol)

2 (0.7%)

Herbs & smoking 6 (2.2%)

Herbs & alcohol 33 (11.8%)

Herbs only 238 (85.3%)

74

4.3 INFLUENCE OF AGE, GENDER AND BLOOD PRESSURE ON MICROALBUMINURIA AMONG

THE STUDY POPULATION.

In this study, significant positive association existed between age of the patients and MAL (X2 4.93; P value

0.026) (Table 14). Ninety four (94) patients out of one hundred and ten (110) that were above 65 years of age

were positive to Micral test. Also a progressive increase in the percentage of the number of patients with MAL

occurred as age of the patients increased.

It was noted that the prominence of MAL among these patients with EHTN was significantly associated with

level of systolic and diastolic BP. There was a progressive increase in the proportion of patients with MAL (X2

9.43; P value 0.002 and X2 10.09, P value 0.001 for systolic and diastolic BP respectively) as the level of systolic

and diastolic BP increased (Table 14). Also, the stage of HTN in patients studied was strongly associated with

MAL. Highest number (124) of patients with mal had stage II HTN, while the least number (61) of patient

positive to MAL were at the normal/controlled stage of HTN. Also number of patients positive to MAL increased

as the HTN status of the patients increased (Table 15).

Gender of the patients however did not have any significant association with MAL (Table 14).

75

Table 14: ASSOCIATION OF RISK FACTORS WITH MAL AMONG THE STUDY GROUP

MICRAL TEST

Status

Age

Negative Positive

<30-34 1 (0.3%) 11 (3.1%)

35 – 39 6 (1.7%) 9 (2.5%)

40 – 44 11(3.1%) 17 (4.8%)

45 – 49 10 (2.8%) 30 (8.4%)

50 – 54 10 (2.8%) 29 (8.1%)

55 – 59 10 (2.8%) 38 (10.6%)

60 – 64 12 (3.4%) 54 (15.1%)

65 + 18 (5.0%) 94 (26.1%)

X2 = 4.93 P value 0.026

Gender

Male 35 (9.0%) 110 (30.8%)

Female 46 (12.9%) 169 (47.3%)

X2 = 0.065 P value 0.795

Systolic BP

Normal 12 (3.4%) 20 (5.7%)

76

Stage I 35 (9.7%) 100 (27.5%)

Stage II 31 (8.8%) 160 (44.8%)

X2 = 9.43 P value 0.002

Diastolic BP

Normal 28 ( 7.9%) 61 (17.3%)

Stage I 30 (8.5%) 92 (26.1%)

Stage II 20 (5.7%) 129 (34.6%)

X2 = 10.09 P value 0.001

Table 15: ASSOCIATION OF HTN STAGE WITH MAL

HTN CATEGORY

MAL

Negative Positive

77

Normal/Controlled 28 61

Stage I 28 97

Stage II 22 124

X2 value 8.75, P = 0.003

78

4. 4 ASSOCIATION OF AGE CATEGORY WITH MICROALBUMINURIA

The association between ages of patients with essential hypertension and MAL can further be shown by

categorizing respondents into clinical groups of (a) young (<45years), (b) middle age (≥45-64years) and (c)

elderly (>65years). Percentage of patients positive to Micral test increased significantly (P = 0.022) as the age

of the patients increased. Highest percentage of 83.9 was observed among the elderly, 78.2% among the middle

age while 67.2 % among the young (Table 14).

79

Table 16: AGE CATEGORY VERSUS MICROALBUMINURIA

Age category MAL

Negative Positive

Young( < 45 years) 18 37 (67.2 %*)

Middle age( 45 – 64 years) 42 151 (78.2%*)

Elderly ( ≥ 65 years) 18 94 (83.9%*)

X2 value 5.63, P = 0.022

*Percentage of patients positive to mal within each age category

Further analysis showed that MAL correlated positively and significantly with age, SBP, DBP and MAP with

respective r and p values of ( r = 0.113, P = 0.033 ), ( r = 0.200, P = 0.0001 ), ( r = 0.187, P = 0.0001 ) and ( r =

0.227, P = 0.0001 ) (Table 17).BMI, WHR and Pulse Pressure did not show any significant correlation with MAL

(Table 17).

80

TABLE 17: CORRELATION COEFFICIENT BETWEEN MAL AND OTHER PARAMETERS IN

HYPERTENSIVE PATIENTS

r value P value

Age 0.113 0.033

SBP (mmHg) 0.200 0.0001

DBP (mmHg) 0.187 0.0001

PP (mmHg) 0.095 0.074

MAP (mmHg) 0.227 0.0001

BMI (kgm-2) 0.023 0.664

WHR 0.005 0.924

81

Multiple regression analysis using microalbuminuric status as a dependent nominal variable, showed the

following parameters as significantly related independent variables: SBP (P=0.0001), and DBP (P=0.0001) (Table

18).

As depicted in Table 19, the SBP, DBP and MAP were significantly higher in hypertensives with MAL than in

hypertensives without MAL.

82

Table 18: MULTIPLE REGRESSION ANALYSIS USING MICROALBUMINURIC STATUS AS

DEPENDENT VARIABLE

P value

Age 0.260

SBP (mmHg) 0.0001

DBP (mmHg) 0.0001

PP (mmHg) 0.751

MAP (mmHg) 0.585

BMI (kgm-2) 0.212

WHR 0.445

83

Table 19: CLINICAL CHARACTERISTICS OF PATIENTS WITH OR WITHOUT MAL

Characteristics Microalbuminuric Normoalbuminuric T value P value

WHR 0.931±0.06 0.931±0.08 0.096 0.924

BMI (kgm-2) 26.84±5.76 26.52±5.32 0.45 0.650

PP (mmHg) 68.00±1.13 63.65±2.16 1.78 0.077

MAP (mmHg) 116.18±0.78 109.04± 4.69 0.0001

SBP (mmHg) 161.52±1.26 151.47±2.09 4.11 0.0001

DBP (mmHg) 93.51±0.75 87.82±1.38 3.61 0.0001

84

CHAPTER FIVE

DISCUSSION

The prevalence of MAL in this study was found to be 77.5%. The figure is somewhat high and much more than

a range of 5-40% reported in literature from previous studies.16,35,36,98,99 Nevertheless, it is keeping with the current

prevalence of MAL in recent studies in which a higher range of 53-71% was reported.80,100 The wide variability

in prevalence observed in both the old and recent studies is due to factors such as cut-off value for HTN, severity

of disease, age and sex distribution and presence or otherwise of concomitant CV risk factors. Other factors are

patient selection procedures, sample size, method of determination of MAL, duration of HTN and existence of

prior treatment associated with adequate or inadequate control of HTN by drug therapy, the type of which may

highly influence albuminuria.16,101

A high prevalence was demonstrated by Bohm et al in i-SEARCH study, a broad based international survey

conducted in 2007 in which approximately 22,000 hypertensive patients with or without CV disease were

recruited at 1750 study centers.80,100 The highest rate was found in patients with uncontrolled HTN.

This work showed a trend towards older age hypertensives. 176 patients (48.9%) of the respondents were above

60 years out of which 62.5% (110 patients) were well over 65 years. Odili37 in her study in Jos got a prevalence

of 41%. But she recruited only 105 subjects with mean age of 45.5+10.11 as against 360 subjects with mean age

of 73.48+15.10 in this study.

Quite obvious in Table 3 is the poor level of BP control in the study group. Only 89 patients (24.7%) had

controlled HTN while the remaining 271 patients (75.3%) were at either JNC VII stage I (34.7%) or stage II

(40.6%) despite drug therapy. This high level of uncontrolled HTN may be attributable to various reasons ranging

85

from poor drug adherence for financial reasons to poor information on the chronicity of the disease resulting in

some patients going on drug holidays.

The level of BP (JNC VII staging) and duration of HTN is another strong factor to consider in explaining the high

prevalence of MAL in this study. Alfonso et al and several other researchers10,15,17,61,102 were able to demonstrate

a direct relationship/variation between MAL and level/duration of HTN. The mean duration of HTN (in years) in

this study was 21.09+12.24 while 146 patients (40.6%), the largest group, were in stage II HTN.

The level of consumption of herbal preparation is another strong factor that could have influenced the high

prevalence of MAL obtained in this study.67,103 Most of the prevalence rates of MAL quoted in the literature were

from studies among the Caucasians in advanced countries.16,35,36 In these enlightened populations, the use of

medicaments are generally controlled. The few adopted complementary alternate medicine (CAM) have a

reasonable scientific back up. In the study population however, 293 (81.4%) of the subjects have taken various

types of herbal preparations and a larger percentage (60.4%) did so on regular basis.

The prevalence of MAL in any study has been shown in the literature to be influenced by the choice/type of

laboratory method employed in detecting MAL.75 Generally, the standard quantitative methods such as

Radioimmunoassay (Gold standard), Laser immunonephelometry, Immunoturbidimetry etc have much higher

specificity with greater reduction in false positive rate than the qualitative and semi-quantitative methods79 such

as the one (Micral test) used in this study.

When the Micral test strip is used, two to three non-consecutive urine samples have been recommended to increase

the reliability of the result.10,69 In this study however, only one urine specimen was used in order to cut cost.

There was no significant relationship/correlation between MAL and gender of the patients’ family history of

HTN, BMI, WHR and PP. There are conflicting reports from studies on the correlation between MAL and age

and gender of the patients. While Leoncini et al20 showed that MAL is independently associated with male gender

86

and older age, Odili et al37 and Olatunde et al98 found no association between MAL and gender, age of the patients

and BMI. Except for multiple regression analysis, most of the other relevant statistical tools used in the previous

studies showed significant positive association between MAL and PP.62 This research work however found no

such positive association. Massimo et al62 was able to establish in his study that PP and isolated systolic HTN are

directly related to MAL independent of diastolic BP and other correlates. PP, which is calculated as systolic minus

diastolic BP, tends to be more significant with high rate of isolated systolic HTN. Most of the subjects in this

study were however above 60years of age and had both systolic and diastolic HTN.

This study found a statistically significant difference in the means of the SBP, DBP and MAP of the

microalbuminuric hypertensive patients compared with normoalbuminuric hypertensive ones. There was also a

significant and positive correlation between MAL and SBP, DBP, MAP and age of the patients. These findings

are partly in keeping with the report of the study by Massimo et al.62 These authors found that MAP and isolated

systolic HTN were significantly related to urinary albumin excretion (UAE) and prevalence of MAL. Olatunde

et al98 also reported a significant and positive correlation between MAL and SBP but not DBP.

Although SBP has remained a more consistent determinant of MAL in hypertensives,62 some other studies have

also implicated DBP and PP. de-la-Sierra et al 104 reported that patients with MAL showed significantly higher

values for 24 hours, day-time and night-time SBP and DBP compared with hypertensives with normal UAE. A

study of 134 women and 212 men conducted by Leoncini et al among newly diagnosed hypertensive patients

showed that DBP was independently correlated with UAE.69

Smoking has been shown to be a strong risk factor for MAL in patients with EHTN. As shown by this study, all

of the ten respondents who were still smoking as at the time of this study tested positive to MAL. Also 63.6% (21

patients) of those who have stopped smoking had MAL. Halimi et al66 worked extensively on effect of smoking

on proteinuria and his findings were similar to those in this study. He reported that current smoking and past

87

smoking were associated with high and similar risk of proteinuria even when the pack-year was reduced. From

the study, Halimi and co-workers concluded that smoking (currently or in the past) represented the most powerful

risk for MAL among men and women, even when normotensive and hypertensive subjects were analyzed

separately and even when a different cut-off for HTN was used.

88

RELEVANCE OF THE STUDY TO FAMILY MEDICINE

Family Physicians as the doctors of first contact can not afford to miss out any important prognosis-influencing

measure in the course of providing highly professional, holistic, comprehensive and continuous care for which

the specialty is noted for. Management of HTN falls in the category of continuous care. Numerous studies have

provided evidence that MAL is a strong, independent and the most sensitive predictor of CV events and

progressive nephropathy. The risk for CV morbidity and mortality is linearly related to urinary albumin excretion

and the reduction of albuminuria (at microalbuminuric stage) using anti-RAAS anti-hypertensives

correspondingly parallels reduction or reversal in CV risk.23-25,28,30,35 Family physicians who diagnose and initiate

management in most cases are well placed for this simple step towards reversing the trend of CVD and CKD.

Hence CVD risk stratification by means of MAL screening at diagnosis and at intervals during therapy should be

inculcated into the routine care of patients with primary HTN. This will ultimately reduce the short and long term

economic burden on the nation and, more importantly, the family which is the focus of care in Family Medicine.

89

LIMITATIONS OF THE STUDY

The limitations of the study are:

First is the cost of the study. Micral test strip which is the basic unit for this research work is not readily

available in our country, Nigeria. Therefore, the cost is very high (N350 per unit). Because of this enormous

cost, Micral testing was done once in each subject as against the preferred twice-thrice to increase validity.

Secondly, some of the patients that were labeled primary hypertensives might indeed be secondary

hypertensives. This could have been avoided if facilities were readily available and affordable for extensive

investigations.

Lastly, the study was conducted in a tertiary hospital and cross-sectional in design. The inference drawn from

the results should be taken with caution when comparing with community survey.

90

CONCLUSION

This study has shown that:

There is a high prevalence (77.5%) of MAL among adult Nigeria hypertensive patients.

Essential hypertensive patients who smoke, take excess alcohol, consume herbal preparations, in older ages

(>60years) and with higher SBP, DBP and MAP are at increased direct risk of MAL.

91

RECOMMENDATIONS

1. Routine screening of MAL in newly diagnosed and old hypertensive patients and further check-ups at intervals

during follow-up.

2. Essential hypertensive patients should be categorized at diagnosis into high or low risk for MAL based on

age, SBP, DBP and /or MAP.

3. Larger (community based) studies with longitudinal follow-up are advocated to really establish: (1) the

importance of MAL in non-diabetic essential hypertensives and (2) to demonstrate MAL reversibility or

modifiability of ACE-I and ARB for better first contact management of hypertension.

92

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APPENDICES I: QUESTIONNAIRE

PREVALENCE AND FACTORS ASSOCIATED WITH PRESENCE OF MICROALBUMINURIA IN

PATIENTS WITH ESSENTIAL HYPERTENSION SEEN AT THE GENERAL OUTPATIENT CLINIC OF

FEDERAL MEDICAL CENTRE, ABEOKUTA.

Dear respondent,

Kindly respond to the questions set out below to the best of your knowledge and be reassured that your responses

will be treated with utmost confidentiality. This study borders on testing a sample of your early morning urine for

the presence of minute proteins (microalbuminuria) as a means of early detection of hypertensive kidney damage.

At this stage, further kidney damage due to hypertension can be prevented, reversed or at least significantly

slowed down for a better quality of life. An interviewer who is versed in both the local language (Yoruba) and

English will assist you through the course of the questionnaire.

SERIAL NO…………………………………..

CODED HOSPITAL NO……………………...

DATE ………………………………………...

A) DEMOGRAPHIC DATA

1) Age: …………………………… years

2) Sex: (i) Male (ii) Female

3) Marital status: (i) Single (ii) Married (iii) Divorced/Separated (iv) Widowed

4) Level of Education: (i) None (ii) Primary (iii) Secondary (iv) Postsecondary

5) Occupation: (i) Student (ii) Pensioner (iii) Unemployed /Retired

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(iv) Artisan/Skilled Labour (v) Unskilled labour (vi) Trading (vii) Business (viii)

Housewife (ix) Civil servant (x) Professional (xi) Police/Military (xii) Farmer

(xiii) Others: specify

6) Religion: (i) Islam (ii) Christianity (iii) Traditional belief (iv) Others 7) Ethnic

group: (i) Yoruba (ii) Hausa (iii) Igbo (iv) Others

B) SOCIAL HISTORY

1) Do you smoke cigarette currently? (i) Yes (ii) No

2) If yes, how many sticks per day on the average? ....................................................................

3) For how long have you been smoking? ...................................................................................

4) If no to question (1), have you smoked cigarette in the past? (i) Yes (ii) No

5) If yes, how many sticks per day on the average? ....................................................................

6) For how long did you smoke? ………………………………………………………………

7) How long ago did you stop smoking? ....................................................................................

8) Why did you stop smoking?………………………………………………………………….

9) Do you take Alcohol currently? (i) Yes (ii) No

10) If yes:

Brand Quantity/week Duration

(i) Beer ……………….. ………………..

(ii) Gin/Local gin/Whisky ……………….. ……………….

(iii) Alcoholic Wine ………………... ……………….

(iv) Palm wine ………………... ………………..

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11) If no, have you taken alcohol in the past? (i) Yes (ii) No

12) If yes, for how long were you on alcohol?..........................................................

13) How long ago did you stop?...............................................................................

14) Why did you stop taking alcohol?………………………………………………

C) MEDICAL HISTORY

1) How long ago were you diagnosed as hypertensive?...................................................................

2) Are you on any antihypertensive drug(s)? (i) Yes (ii) No (iii) I don’t know

3) If yes, name them and how long on each of them:

Name (s) Duration

(i) ………………………….. ………………………………………...

(ii) …………………………... ..……………………………………….

(iii) …………………………... ………………………………………...

(iv) Drug names not known

4) How often do you take your drugs? (i) Regularly (ii) Not regularly

5) If not regularly, why? (i) Often forget (ii) No money to buy drug (iii) Drugs not readily

available (iv) Don’t have any symptoms (v) Thought I have been cured (vi) Too

many drugs to take / Multiple dosaging (vii) Tight job schedule

6) For (5ii), who pays for the drugs? (i) self (ii) Children (iii) spouse (iv) Relatives

7) How would you rate your family’s support? (i) Good (iv) Fair (iv) Poor (V) None

8) Is any member of your family hypertensive? (i) Yes (ii) No (iii) I don’t know

9) If yes, state relationship to you…………………………………………………….........

10) Do you have any other chronic medical disease(s)? (i) Yes (ii) No (iii) I don’t know

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11) If yes, name it/them:

Name Duration since diagnosed

(i) …………………………………………………. …………………………………...

(ii) ………………………………………………..... ……………………………………

(iii) …………………………………………………. ……………………………………

12) Do you take herbal preparation/concussion? (i) Yes (ii) No

13) If yes, how often? (i) Occasionally (ii) Regularly

14) Date of Last normal menstrual period (for women only) ………………………………..

D) PHYSICAL EXAMINATION

1) Systolic blood pressure (mmHg; average of 2 readings)………………………………….

2) Diastolic blood pressure (mmHg; average of 2 readings)………………………………...

3) Mean arterial pressure (mmHg)……………………………………………………………

4) Weight (Kg)………………………………………………………………………………..

5) Height (m)………………………………………………………………………………….

6) Body mass index (BMI, Kg/m 2) …………………………………………………………..

7) Waist circumference (cm)…………………………………………………………………..

8) Hip circumference (cm)……………………………………………………………………

9) Waist/Hip ratio (WHR) ……………………………………………………………………

E) INVESTIGATIONS

1) Urinalysis: + Appearance……………………………………….

+ PH………………………………………………..

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+ Specific gravity………………………………….

+ Proteinuria………………………………………

+ Glucose…………………………………………..

+ Red blood cells…………………………………..

+ White blood cells………………………………..

+ Nitrite…………………………………………….

2) Micral-Test assay for microalbuminuria (i) Negative (ii) Positive

(iii) If positive, what is the level: (a) 20-50mg/L

(b) 51-100mg/L (c) >100mg/L

APPENDIX II: INFORMED CONSENT

Consent to participate in the Study Titled: PREVALENCE AND FACTORS ASSOCIATED WITH

PRESENCE OF MICROALBUMINURIA IN PATIENTS WITH ESSENTIAL HYPERTENSION SEEN AT

THE GENERAL OUTPATIENT CLINIC OF FEDERAL MEDICAL CENTRE, ABEOKUTA.

Dear Sir/Ma,

Your consent is being sought to participate in this study. Hypertension is a silent killer that can damage virtually

every organ in the body including the brain, heart and the kidneys. The kidneys are often involved early in

hypertensive organ damage and also serve as a predictor of other organ damage by hypertension.

This study is therefore aimed at early detection of hypertensive kidney damage as a secondary preventive measure

to reduce occurrence of cardiovascular and chronic kidney disease.

108

If you consent, a questionnaire will be administered; height, weight, waist and hip circumference measurements

shall be taken and about 15mls of morning urine sample taken for laboratory analysis at no cost to you.

All these procedures are not harmful. Your refusal to participate will not in any way affect your normal care by

me or any member of this hospital. You are also free to opt out at any stage of the study. All information obtained

in this study is strictly confidential. Your responses will be identified by a study code number. Your name will

not be used in this study. If any information is published, there will not be any information which would identify

you as a participant.

Kindly indicate your decision by signing in the space below.

Thank you.

Yours sincerely,

DR IGE A.M

I wish to participate____________________________________________

(Date and Signature or Thumbprint of Participant)

____________________________________________

(Date and Signature or Thumbprint of Witness)

109

FIGURES: 1 COMPONENTS OF THE MICRAL TEST STRIP

Colour

Block

Wick Buffer Capture Cover Carrier

fleece fleece matrix foil foil

Conjugate Substrate

fleece film