The complications of SH are the clinical outcomes that result from the effect of chronic BP elevation. SH is a risk factor for all clinical manifestations of atherosclerosis which include coronary artery disease, CCF, stroke, renal disease and peripheral arterial disease. Hypertensive heart disease is the result of structural and functional adaptations53 which may eventually progress to any of the following: left ventricular hypertrophy,54 diastolic dysfunction,53 CCF, coronary artery disease54 and cardiac arrhythmias.54 Individuals with left ventricular hypertrophy are at increased risk of the following:55 CCF, stroke and sudden death.
Higher systolic blood pressure (SBP) contributes more to these changes than diastolic blood pressure (DBP). It provides an explanation for closer approximation of cardiovascular risk to SBP and pulse pressure.
31 2.7 METHODS OF ASSESSING LVH
Left ventricular hypertrophy (LVH) can be diagnosed using electrocardiography (ECG) and echocardiography.
(1) Electrocardiography (ECG) remains the conventional method, despite low sensitivity compounded by increasing age and body weight. Araoye criteria being the most sensitive in Blacks.56
(2) Echocardiography: Over four decades ago, Falase et al established its relevance in the Nigerian setting.57 It is a non- invasive technique that evaluates cardiac anatomy with images and recordings produced by sound energy. M-mode and two-dimensional (2D) echocardiography provides comprehensive wall, chamber and LV mass measurements, together with indices of systolic and diastolic function while it remains readily available, cheap and wholly non-invasive.
AMBULATORY BLOOD PRESSURE MONITORS
It is an easy to wear, non-invasive, silent, compact, reliable and lightweight BP measuring device. It measures about 4 by 3 by 1 inch (10 by 8 by 3 cm) and weighs about 4 lb (2 kg). It can be worn on a belt or in a pouch and are connected to a sphygmomanometer cuff on the upper arm by a plastic tube. It is fully automatic, computerized for operation and data analysis. It can record BP for 24 hours or longer while patients go about their normal daily activities. There are two basic types of monitors: oscillometric and auscultatory. These are different based on method used for BP recording. Auscultatory devices use a microphone to detect Korotkoff sounds and to register BP values. Oscillometric devices analyze oscillations at the cuff, detect the mean arterial pressure at the point of peak oscillations: SBP and DBP are derived by means of validated
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proprietary algorithms.58 The monitor using either method does not differ significantly if properly validated59,60 Most monitors use the oscillometric technique. Oscillometric devices have been used in clinical and research purpose with good results.61 The auscultatory method loses accuracy in patients with congestive heart failure, obesity, aortic regurgitation, pregnancy and other high output states while the oscillometric devices are less accurate in children as well as in the elderly patients. Both techniques are less accurate in patients with cardiac arrhythmias especially atrial fibrillation. So, such patients should not be monitored to avoid unreliable results.
These quantitative types of information are derived from an ABPM study:
1) Estimates of average SBP and DBP, pulse pressure and heart rate.
2) Quantification of circadian fluctuations of these same variables (SBP, DBP, pulse pressure and heart rate).
3) Estimation of short-term blood pressure variability (BPV).
INTERPRETATION OF ABPM
Table 2 shows the definition of SH by ABPM levels.9 The ESH guidelines for the management of SH set the cut-off limits for normal ABP as 135/85, 120/70, 130/80mmHg for the day-time, night-time and mean 24 hour ABP respectively.
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Table 2: Definition of systemic hypertension by ABP levels9
Ambulatory BP Systolic BP(mmHg) Diastolic BP(mmHg)
Day-time(awake) ≥ 135 and/or ≥ 85
Night-time(asleep) ≥120 and/or ≥ 70
24-hr ≥ 130 and/or ≥ 80
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Recommended Normal Limits for ABPM from different Guidelines
Table 3 shows the recommended normal limits for ABPM from different guidelines. Accepted normal ABP range was determined on the basis of data from several population-based data banks on normotensive persons.
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Table 3: Recommended Normal Limits for ABPM from different Guidelines
Guidelines Mean 24-hr (mmHg) Day-time (mmHg) Night-time (mmHg)
ESH9 <130/80 <135/85 <120/70
JNC-8 62 _____ <135/85 <120/75
CANADIAN63 <130/80 <135/85 <120/75
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IDACO STUDY64 <125/75 <130/85 <120/70
BLOOD PRESSURE DIPPING PATTERNS
Quantification of circadian fluctuations of DBP and SBP: In the general population, BP falls on average by 10 – 20% of daytime values during sleep. However, in some individuals nocturnal decrease in BP is blunted or BP even increases. Remarkably, non-dipping profile of BP is
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frequently accompanied by increased nocturnal mean BP levels (i.e. night-time BP > 125/75 mmHg).22 Proposed mechanisms for non-dipping pattern of BP and nocturnal hypertension include an increased sympathetic activity during night-time,25 a decreased renal sodium excretory ability,26 salt sensitivity,27 altered breathing patterns during sleep (i.e. obstructive sleep apnoea), leptin and insulin resistance,28 endothelial dysfunction and glucocorticoid use.
The classification of dipping and non-dipping was first introduced by O’Brien following a frequent history of stroke in the non-dippers than in dippers.65 ABPM was thus classified as follows:66,67
(1) Normal dipping pattern (dipper) occurs when the reduction in the mean SBP during the night period is greater than or equal 10% but lesser than 20% of mean SBP during the day(that is: ≥10% but <20%).
(2) Non-dipping pattern (non-dipper) occurs when the reduction in the mean SBP during the night is greater than or equal to 0% but lesser than 10% of mean SBP during the day (that is ≥ 0% but <10%). The non-dipping BP pattern has been associated with factors such as advanced age, stress, poor social support, low socio-economic status, gender, sleep quality and quantity, apnoea, anger/temperament and personality types. There is a growing body of evidence linking a non-dipping BP pattern with target organ damage and higher risk of cardiac and extracardiac morbidity and mortality.67,68,69,
In particular, non-dippers with essential hypertension have been found to have more advanced left ventricular hypertrophy, left ventricular mass and left ventricular mass index, carotid artery atherosclerotic plaques, carotid artery wall thickness, silent cerebral infarct, stroke, cognitive impairment and microalbuminuria.17 An association between a non-dipping BP profile and an
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increased risk of target organ damage at the cardiac, renal, vascular and cerebrovascular levels in subjects with uncomplicated essential hypertension has been documented.
(3) Extreme dipping pattern (extreme dippers) occurs when night-time SBP fall is greater than or equal to 20% (that is ≥20%) of the mean day-time SBP.
(4) Reverse dipping pattern (reverse dipper, also known as risers or inverted dippers) occurs when mean night-time BP is greater than mean of day-time BP and the nocturnal dip is less than 0%. 70 Target organ damage has also been found to be linked with the risers and the extreme dippers.70 The risers have greater risk of intracranial hemorrhage and fatal stroke while the extreme dippers have greater risk of silent cerebral infarct and cerebral ischemia.71
Early Morning BP Rise/ Surge: This rise has been attributed to the recovery of the reduction in sympathetic activity and the increase in the vagal drive that occurred during the night-time as individual wakes up to assume daily activities. When this increase is exaggerated as found in some patients with SH, it is referred to as early morning surge. Early morning surge has been linked with the peak incidence of myocardial infarction, sudden death and stroke.
BLOOD PRESSURE SUBGROUPS
4 blood pressure subgroups have been described based on the office BP and ambulatory blood pressure measuring methods:
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(1) Individuals who were normotensive by both methods were referred to as truly normotensive individuals.
(2) Individuals who were hypertensive by both methods were referred to as those with true or sustained hypertension.
(3) Individuals who were hypertensive by clinic measurement and normotensive by ambulatory measurement were referred to as those with white coat hypertension (WCH).
WCH is therefore, defined as SBP of equal or greater than 140mmHg and or DBP of equal or greater than 90mmHg when measured in office and normal daytime ambulatory SBP of lesser than 135mmHg and or DBP of lesser than 85mmHg.
(4) Individuals who were normotensive by clinic measurement and hypertensive by ambulatory measurement were classified as those with masked hypertension (MH).
From a clinical point of view, the first 2 groups are easy to deal with, because both methods give the same classification. Of more interest are the groups in which there is disparity between office BP and ambulatory BP. The individuals with white-coat hypertension have been extensively studied and found to have a relatively low risk of cardiovascular morbidity.
Whereas, masked hypertension which also known by other names such as: “reverse white-coat hypertension”, “white-coat normotension or “undetected ambulatory hypertension” has been well-studied. It was proposed that the phenomenon should be called “masked hypertension,” by Pickering and colleagues in 2002 on the grounds that the hypertension was not detected in the clinic or the physician’s office.72 Grassi et al have shown a marked sympathetic overdrive in masked hypertension, possibly contributing to target organ damage.73
40 BLOOD PRESSURE LOAD
BP load is the percentage of elevated readings during awake and sleep period or over the 24- hour period. The threshold values typically used for this calculation are systolic readings of equal or above 140mmHg and diastolic readings of equal or above 90mmHg for awake periods and 120mmHg and 80mmHg for sleep readings respectively.74 These were the cut-off values used for this study.
Typically, there is a fall in both SBP and DBP during sleep of approximately 13% for SBP and 17% for DBP.75 Most studies have used the definition of a decrease in BP of less 10% as being abnormal. The lesser one dips, the greater the cardiovascular risk. Risk is greatest in reverse dippers.
BLOOD PRESSURE VARIABILITY (BPV)
Definition of Blood Pressure Variability:9 SBP and DBP variability are assessed as the standard deviation of the mean (co-efficient of variation) of 24-hour ambulatory SBP and DBP recordings.
BP is characterized by significant short-term fluctuations occurring within 24 hour (that is from beat-to-beat, minute-to-minute, hour-to-hour and from day-to-night) as a result of complex interactions between behavioural, environmental, humoral and neural central or reflex influences. Importantly, BP variations have also been shown to occur over more prolonged periods of time (i.e. between days, weeks, months, seasons and even years), which appear not to
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be a random phenomenon but rather the result of several interacting factors and mechanisms yet not completely identified.76
The concept of Blood Pressure variability (BPV) was introduced more than 30 years ago but gained interest in recent years on the background of the evidence provided by observational studies and post hoc analyses of clinical trials indicating that the adverse cardiovascular consequences of SH may not only depend on absolute BP values but also on BPV. When assessed either in the short or in the long term and independently of mean BP levels, an increasing BPV has been shown to be associated with development, progression and severity of cardiac, vascular and renal organ damage and with an increased risk of CV events and mortality.77
MEASURES OF BLOOD PRESSURE VARIABILITY BPV can be obtained through the following methods:
1) Continuous beat-to-beat BP recordings
2) Repeated conventional office BP (OBP) measures 3) 24-h ambulatory BP monitoring (ABPM)
4) Home BP monitoring (HBPM).
HBPM has great value in the evaluation and management of SH, because it provides a large number of readings in an ambulatory setting but evidence supporting its ability to predict outcome is scarce.9Fluctuations in BP can also be assessed over different time intervals i.e. in the very short term (beat-by-beat), in the short term (within the 24-h period) or in the long term (day-by-day, visit-to visit or between seasons). Thus, depending on the time interval and the method
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employed for its measurement, the clinical significance and prognostic implications of a measure of BPV may substantially differ as well as the mechanisms and determinants influencing each type of BPV.78
ASSESSMENT OF BPV
A proper analysis of the fast and short-lasting changes in BP requires a continuous recording of BP on a beat-by-beat basis.79 Over the years, intra-arterial Oxford method80 was the only available method for continuous ambulatory beat-to-beat BP monitoring over 24 hours, and it was by using this technique that different components of BPV were first identified. However, because of concerns over its invasive nature and methodological difficulties, the vascular unloading technique was developed81 and this paved the way to ensemble noninvasive devices for continuous BP measurement, which was based on the Penaz method82 through the use of cuffs equipped with an infrared photoplethysmograph and sophisticated technology for quantification of BP, these devices allow measuring BP levels in a beat-to-beat basis, thus giving the possibility of tracking fast variations in BP values either spontaneously occurring or during stimulated conditions in the laboratory setting.83 Analysis of BPV from continuous recordings not only allows assessment of BP in terms of its standard deviation, but it also offers the possibility to separately assess its oscillatory components characterized by a different oscillation frequency, through the application of frequency domain analysis.84 It is thus possible to estimate variance of BP in the high frequency (0.15Hz – 0.5 Hz), low frequency (0.05Hz – 0.15 Hz) and very low frequency (0.025Hz – 0.05 Hz) regions of BP spectrum, allowing a more in-depth analysis of the mechanisms of autonomic cardiovascular modulation underlying overall BP variations as well as the autonomic adjustments in response to antihypertensive therapy.84
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However, the use of intermittent, non-invasive 24-h ABP monitor for BP monitoring in ambulant subjects showed the dynamic behavior of BP values over the 24-h period.85 These recordings allowed identification of both beat-by-beat and day–night BP variations.85From these recordings, it is possible to perform the calculation of standard deviation (SD) of average systolic, diastolic, and mean arterial pressure values over the 24-h period, or during the daytime and night-time sub-periods.86 More recently, the calculation of the “ weighted ” SD of the 24-h mean value (i.e. the average of daytime and night-time BP SD, each weighted for the duration of the day and night periods, respectively) has been proposed in order to exclude day – night BP changes from the quantification of overall 24 h SD.87 Other measures of BPV are the calculation of the ‘residual BPV’ remaining after exclusion of the slower components of the 24-h BP profile through spectral analysis;88and the average of the absolute differences between consecutive measurements(average real variability).89These parameters, which focus on short-term BP changes and are not affected by the dipping phenomenon, have been shown to be better predictors of organ damage and CV risk than the conventional 24-h SD.90
MECHANISMS AND DETERMINANTS OF BPV
Central And Reflex Autonomic Modulation: BP variations in the very short and in the short term (that is within the 24 hours) are largely influenced by the central and reflex autonomic modulation (that is an increased central sympathetic drive and reduced arterial and cardio-pulmonary reflexes);91 elastic properties of arteries (that is, a reduced arterial compliance)92 and also the effects of humoural (angiotensin II, insulin, bradykinin, nitric oxide, endothelin-1), rheological (i.e. blood viscosity) and emotional factors like psychological stress of diverse nature
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and duration cannot be overemphasized. Even though behavioural influences (i.e. sleep, physical activity, postural changes) may induce marked variations in BP over the 24 hour period, spontaneous and rhythmic BP fluctuations at different frequencies also occur independently on behaviour throughout the day and night, presumably because of influences originating in the central nervous system.93 In addition, fluctuations in BP also occur in response to the mechanical forces generated by ventilation. Finally, variations in BP caused by neural or non-neural influences are opposed throughout the 24 hour by arterial and cardio-pulmonary reflexes, whose reduced efficacy may thus result in increased BPV. Variations in BP occurring within the 24 hour period also include slower BP fluctuations occurring between day and night, which are significantly influenced both by the subject’s level of activity during daytime and by the sleep/wakefulness cycle. Other determinants of BPV are genetic and behavioural or social factors.
Genetic Factors: Genetic predisposition to BPV is implicated in differences among races. It is also noted that the monogenic disorders that increase distal and collecting tubule sodium reabsorption or cause the secretion of sodium retaining hormones like mineralocorticoid cause salt-sensitive hypertension.94,69 Also, the behavioural or social factors show some selectivity in the manifestation of the complications associated with them.
Behavioural Or Social Factors: Behavioural or social factors such as high salt diet is a major contributor to sustained elevation of BP.95 Dietary habits and calorie intake are potent risk factors for BP changes. Intake of very high calorie diets, polyunsaturated fatty acids and inadequate consumption of antioxidants-rich fresh fruits lead to changes in BP. The influence of dietary habits on cardiovascular state and function were clearly shown in the Dietary Approach to Stop Hypertension (DASH) trials.94 Nicotine in cigarette causes an increase of 10 – 20mmHg
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per stick in the day-time BP. It also has a long term effect of atherosclerosis on blood vessels.
Alcohol alters the diurnal profile of BP and may cause an increase risk of cardiac events in hypertensive patients.96Caffeine produces transient changes in BP but habituates over time. It does not increase the risk of developing hypertension but its transient elevation effect could have long-term cardiovascular consequences.96
PROGNOSTIC SIGNIFICANCE OF SHORT-TERM BPV
Studies have shown that in general populations or hypertensive patients only, elevated nocturnal BP are prognostically superior to awake or 24-hour BP means in predicting CV morbidity and mortality,10 the development of CV events97 and overall mortality.13 The nocturnal BP level represents the patient’s true BP status because it is devoid of the pressor effects of physical activity, emotional stress and other environmental factors that are usually occurring during the day. The prognostic role of night-time BP levels as well as the relevance of a “non-dipping”
pattern of BP has been explored in the past. Subjects in whom nocturnal decrease in BP is blunted have been reported to have a higher prevalence of subclinical organ damage98 and an increased risk of CV events99 and mortality100 which is even higher in the risers or inverted dippers.
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INDICATIONS FOR AMBULATORY BLOOD PRESSURE MONITORING9 1. Suspicion of white coat hypertension (WCH).
2. Suspicion of masked hypertension.
3. Identification of white-coat effect in hypertensive patients.
4. Considerable variability of office BP over the same or different visits.
5. Autonomic, postural, post-prandial, siesta- and drug-induced hypotension.
6. Suspected eclampsia in pregnant women.
7. Identification of true and false resistant hypertension.
8. A guide to determining the efficacy of drug treatment over 24 hours.
SPECIFIC INDICATIONS FOR ABPM
1. Marked discordance between office BP and home BP.
2. Assessment of dipping status.
3. Suspicion of nocturnal hypertension or absence of dipping.
4. Assessment BPV.
(1) White coat hypertension: From the first use of home and ABPM, it became apparent that measuring a patient's BP in the clinic or office could raise their BP above their mean ambulatory pressure as a result of the white coat phenomenon.101,102 In patients with normal BP, day-time
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ABP may be a little higher than OBP, but in those with SH, day-time ABP is usually lower than OBP.
Based on some population studies, the overall prevalence of WCH averaged 13% (range 9 – 16%) and it amounted to about 32% (range 25 – 46%) among hypertensive patients.103 Factors related to increased prevalence of WCH are age, female sex and non-smoking habit. Prevalence of WCH is lower in the case of target organ damage or when OBP is based on repeated measurements or when measured by a nurse or another healthcare provider.
The risks of cardiovascular event in patients with WCH is less, when compared with established SH and possibly small when compared with people with normal BP. WCH is usually a precursor to SH and should be considered in newly diagnosed hypertensive subjects especially before antihypertensive treatment is prescribed (this could lead to fewer drugs being prescribed).
(2) Stage 1 hypertension: Patients whose BP is considered to be borderline may also benefit from ambulatory monitoring, especially young patients in whom lifelong drug treatment may otherwise be prescribed inappropriately and who may be penalized in terms of insurance or employment if the diagnosis of SH is misapplied.
(3) Nocturnal hypertension: Ambulatory measurement is the only non-invasive technique through which BP can be monitored during sleep. The relevance of nocturnal hypertension is still controversial, but there is increasing evidence that nocturnal BP may provide important information for example, BP at night is independently associated with end organ damage above the risk associated with daytime values.65It has also been shown that the absence of a night-time drop in BP is associated with target organ involvement, and it may be a useful clue to the presence of secondary hypertension. Nocturnal hypertension is particularly common in chronic
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kidney disease patient patients presumably because of increased cardiac output and increased systemic vascular resistance.
(4) Considering treatment in elderly patients: The results of the ambulatory study of the systolic hypertension in Europe trial showed OBP measurement in elderly people may produce systolic BP that are 20 mmHg higher than daytime ABP,10 leading to an overestimation of the occurrence of isolated systolic hypertension among elderly patients and probably excessive treatment. Moreover, results from this study also show that ambulatory SBP is a better predictor of cardiovascular risk than office SBP.104Various ambulatory patterns are found among elderly people, including a number of hypotensive states associated with baroreceptor or autonomic failure. These BP patterns include WCH, isolated systolic hypertension, postural hypotension, post-prandial hypotension, daytime hypotension and nocturnal hypertension, drug induced hypotension, and autonomic failure. Since elderly people can be particularly susceptible to the adverse effects of drug treatment given to lower BP, identifying hypotension is particularly important.105
(5) Hypertension resistant to treatment: Hypertension is defined as resistant to treatment when a therapeutic strategy that includes appropriate lifestyle measures plus a diuretic and two other antihypertensive drugs belonging to different classes at optimally tolerated doses fail to lower SBP and DBP values to less than 140 and 90 mmHg respectively. Depending on the population examined and the level of medical screening, the prevalence of resistant hypertension has been reported to range from 5 – 30% of the overall hypertensive population, with figures less than 10% probably representing the true prevalence.103 In these patients, ambulatory monitoring may indicate that the apparent lack of response is caused by the white coat phenomenon;