Fig. 16.1
Pulse wave form from healthy vasculature. P percussion wave, D dicrotic wave. The arrow indicates the dicrotic notch. The reflected wave or dicrotic wave is small and is in diastole, and there is no summation with the percussion wave
Fig. 16.2
Pulse wave form in ISH. Dicrotic wave is earlier and in systole because of accelerated reflection, and there is summation with the first wave. There is augmentation of the systolic pressure because of this summation effect
Age-related decrease (structural and functional) in the arterial compliance is the major pathophysiological mechanism in development of ISH. These changes affect mainly the intima and media [3–5]. Functional properties as well as anatomy of the large vessels are altered due to changes in collagen, ground substance, as well as extracellular protein matrix. The amount of elastin on the arterial walls decrease with aging, which result in fragmented and poorly demarcated media. Atherosclerotic process and calcification of the media also contribute to increasing stiffness and reduced elasticity of the arterial walls. Through the porous internal elastic lamina, undifferentiated smooth muscle cells migrate to the intima and proliferate there, laying down collagen contributing to fibrosis of the intima. This in turn results in increase in arterial wall stiffness. The end result of these processes is decrease in lumen-to-wall ratio and overall cross-sectional luminal area and decrease in arterial stiffness. Changes are predominantly seen in elastic arteries like aorta and larger arteries [6, 7].
These changes cause increase in pulse wave velocity. This results in early return of reflected pressure waves from peripheral reflecting sites, a summation with the first component and an increase in systolic pressure [8]. The widening of the arterial pulse pressure caused by the reflected component is expressed as the “augmentation index” (AIx) [9]. It also causes increased wall stress, augments the processes involved in atherosclerosis, and also predisposes to development of left ventricular hypertrophy (LVH).
16.3 Functional Changes
There is an increase in sympathetic tone with aging. Circulating nor adrenaline levels are high, which is likely due to a lowered beta receptor sensitivity and decreased baroreceptor sensitivity. A preserved alpha-receptor activity in elderly population with an increased sympathetic tone will result in a state of generalized vasoconstriction and increased vasomotor tone [10].
16.3.1 Endothelial Dysfunction
Cardiovascular risk factors especially diabetes, renal dysfunction, dyslipidemia result in endothelial dysfunctionas evident by impaired nitric oxide (NO) production and loss of vasodilator tone. The resultant tonic vasoconstrictive state of the vascular bed results in an amplified reflective wave and systolic augmentation [11–14].
16.4 Epidemiology of ISH
There is a clear linear relationship between age and ISH. The prevalence of ISH is 0.8% in people < 50 years of age and up to 23.6% in persons 80 years of age [17, 18]. Prevalence is more in females and African Americans compared to Caucasians [17, 18]. However, these data are from studies which defined ISH as systolic BP > 160 mmHg and diastolic BP < 90 mmHg as per the WHO guidelines [19, 20]. As indicated earlier, the diagnostic criteria has been redefined with SBP > 140 mmHg and DBP < 90 mmHg by the Sixth Joint National Committee on hypertension [21].
16.5 Morbidity and Mortality of ISH
The deleterious effects of ISH were first demonstrated in 1959 in the Build and Blood Pressure Study. The relation between SBP and mortality was demonstrated in the retrospective analysis of insurance company data. A close relation between mortality and high systolic pressures was demonstrated, which was age independent [22]. This data from retrospective analysis was later confirmed by prospective studies. Data from Multiple Risk factor Intervention Trial (MRFIT) and the US Hypertension Detection and Follow-Up Program confirmed the association between increase in SBP and cardiovascular risk [23, 24]. Every 1 mm increase in SBP has been shown to increase the cardiovascular mortality by 1% in multiple regression analysis. Framingham study data also reiterated the cardiovascular morbidity and mortality. There was a twofold increase in the risk of nonfatal MI and threefold increase in the risk of strokes with ISH in Framingham population [11, 12].
Data from MRFIT trial have confirmed the fact that systolic BP elevation is a more important risk factor for cardiovascular events than diastolic BP.
16.6 Modification of Cardiovascular Complications by Treatment
Table 16.1 summarizes the results of three major randomized placebo-controlled trials in ISH management. Undoubtedly treatment of ISH resulted in significant reduction in cardiovascular morbidity and mortality in treated group [25–27].
Table 16.1
Randomized trials in management of ISH
Study | No. of patients | Age group | Enrollment BP (mean) | Drugs | F/U (years) | Mean BP reduction (S/D) | End point reduction |
|---|---|---|---|---|---|---|---|
MRC | 4396 | 65–74 | 183/91 | Diuretic/atenolol | 5 | −20/−10 | 25% stroke 19% cardiac |
SHEP | 4736 | >60 | 170/77 | Diuretic/atenolol | 4.5 | 11–14/3–4 | 36% stroke 27% MI(NS) |
SYST-EUR | 6403 | 160–219/95 | Nitrendipine/enalapril/diuretic | 2 | 23/7 | 42% fatal stroke 44% nonfatal stroke 26% fatal/nonfatal cardiac events |
16.7 Management of ISH
The diagnosis should be confirmed by at least three different BP measurements. Attention must be paid to detect any evidence of postural hypotension. Rare and potentially curable secondary causes like aortic insufficiency, thyrotoxicosis, anemia, beriberi, arteriovenous fistulae, and Paget’s disease of the bone should be eliminated before making a diagnosis of ISH. Ambulatory BP monitoring is advised in suspected cases of white coat hypertension and in cases demonstrating significant variability in BP recordings.
16.8 Non-pharmacological Management
These include weight reduction, physical activity, restriction of dietary sodium, and moderation of alcohol intake. Low-sodium diet (in the range of 60–90 mmol/day) had appreciable favorable effects on systolic BP in patients with ISH. Reduced dietary sodium also was associated with reduced arterial stiffness and reduction in systolic BP [28–30].
Effect of physical exercise on elderly patients needs further studies, as the current data is inconclusive. Favorable effect of significant lowering of SBP has been noted in a study done in 109 elderly hypertensives, half of them being ISH. SBP was found significantly lower among those who moved more than 5 h a day compared to those with lesser mobility [31]. However, another study did not demonstrate a significant change in arterial stiffness with moderate-intensity exercise for 8 weeks [32]. These lifestyle changes alone may be necessary in mild cases of ISH. These should be continued along with drug therapy in more severe cases of ISH. Drug therapy is indicated in cases with SBP ≥ 160 mmHg in spite of lifestyle changes. Threshold to start drug therapy should be lower, even if the BP is between 140 and 160 mmHg in patients with comorbid conditions like diabetes, coronary artery disease, and features of end-organ damage like left ventricular hypertrophy.
16.9 Selection of Antihypertensive Drug in ISH
Most antihypertensives used in treating young hypertensives can be used in managing elderly with ISH. However, there are some special considerations to be made while treating this patient population. Excessive reduction in blood pressure could result in orthostatic hypotension and increase the risk of falls. To avoid this problem, drug therapy should be started at the lowest dose and carefully titrated up to get the target blood pressure level which is typically a systolic BP of ≤140 mmHg. In fact antihypertensive therapy has been found to improve the clinical outcomes in patients up the age of 80 years in spite of the risk of postural hypotension. Concomitant reduction in diastolic blood pressure might compromise coronary perfusion especially if there is atherosclerotic narrowing of coronary arteries. A lowered coronary perfusion pressure coupled with left ventricular hypertrophy and concomitant increased demands might result in worsening of myocardial demand ischemia.
The pathophysiological mechanisms of ISH would guide the practitioner while choosing the antihypertensive drugs. Selection of the drugs should be individualized based on the presence of comorbid conditions.
Table 16.2 summarizes targeted therapy for ISH based on pathophysiological mechanisms.
Table 16.2
ISH therapy based on pathophysiological mechanisms
Drug class | Pathophysiological target | Desired change | Side effects |
|---|---|---|---|
Diuretics | Sodium sensitivity, blood volume
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