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Abstract

  1. Top of page
  2. Abstract
  3. Pathophysiology of Arteriosclerosis and Systolic Hypertension
  4. PP Amplification and CVD Risk
  5. Treatment of BP: The Age Factor
  6. Discussion
  7. Conclusions
  8. Disclosures
  9. References

There is a linear change in blood pressure (BP) with the advancement of age from predominantly diastolic BP (DBP) in the young to predominantly systolic BP (SBP) in the old. This change is caused by the stiffening of the large arteries and the loss of elastic recoil as a result of replacement of the elastic fibers with collagen fibers. The result of this ageing process leads to an increase in pulse wave velocity and widening of pulse pressure. These hemodynamic changes are associated with an increased incidence in cardiovascular diseases (CVDs) and strokes. Recently, an inverse relationship with stroke risk was noted when the DBP was <71 mm Hg in persons older than 60 years. Accordingly, when treating SBP in the elderly, care should be taken not to lower the DBP below this level in order to minimize the risk for CVD and stoke.

Several epidemiologic studies have shown that the blood pressure (BP) changes with the advancement of age, from predominantly diastolic BP (DBP) in the young to predominantly systolic BP (SBP) in the elderly. This change is due to the replacement of the elastic fibers with collagen fibers in the large arteries of the body resulting in the stiffening of these vessels and the loss of compliance and the elastic recoil. These changes lead to the augmentation of pulse wave velocity (PWV) and the widening of pulse pressure (PP). As a result of the increase of the ageing population, the focus has now shifted from the treatment of DBP to the treatment of SBP, since SBP is the predominant pressure in these patients.[1] Some authors have even gone to the extreme, stating that “systolic blood pressure is all that matters.”[2] This is a significant departure from the early years when the focus was on the treatment of DBP, since the SBP was considered a normal consequence of the ageing process. Even the reports of the National Committees on the Detection, Evaluation, and Treatment of High Blood Pressure did not emphasize the treatment of SBP until their 5th report in 1993.[3] Recently, it has been suggested that in treating hypertension, the age of the person should be considered because of the hemodynamic changes of BP with age.[4] The significance of BP change and its implications for cardiovascular disease (CVD) and stroke was first reported by the Framingham Heart Study investigators.[5] Other investigators also, used BP in correlation with various age subgroups to determine its association with the risk of CVD and stroke.[6, 7] It has been speculated that if age was used as a continuous variable, it could have offered a clearer picture at which age SBP exceeds DBP with respect to stroke risk. This concept was tested in a recent study[4] and will be briefly discussed in this commentary.

Pathophysiology of Arteriosclerosis and Systolic Hypertension

  1. Top of page
  2. Abstract
  3. Pathophysiology of Arteriosclerosis and Systolic Hypertension
  4. PP Amplification and CVD Risk
  5. Treatment of BP: The Age Factor
  6. Discussion
  7. Conclusions
  8. Disclosures
  9. References

The large arteries in young persons possess two functions: (1) to act as conduits that transfer blood to vital organs and tissues, and (2) to act as cushions to smooth out the pulsatile blood flow produced by the intermittent contractions of the heart into a continuous and steady blood flow.[8] However, as the person ages, these functions of the large arteries are modified by arteriosclerosis, which is a consequence of the ageing of blood vessels. The primary cause of arteriosclerosis is the fragmentation of the elastic lamellae, which become thinned and frayed and are replaced with collagen tissue. The fracturing of the elastic fibers is the result of the fatiguing effect produced by the cycling stress of the pulsatile blood flow. In a young person, the elastic aorta expands during systole and absorbs part of the stroke volume.[9] During diastole it recoils back and sends the retained blood volume distally, thus converting the intermittent blood flow into a continuous steady flow. In an elderly person, the elasticity and compliance of the aorta is lost and most of the stroke volume is transmitted distally during systole with practically no blood flow during diastole. The direct result of this function is an increase in SBP, a decrease in DBP, and a widening of PP. This process is accelerated in the presence of hypertension. These latter changes in the older person lead to acceleration of the pulse wave velocity (PWV), which is a surrogate diagnostic characteristic of arteriosclerosis. In addition, the morphology of the pulse wave also changes (Figure 1).The pressure wave is a composite of the incident (forward) wave generated by the contraction of the heart and the reflected (backward) wave generated by the small vessels and arterioles. In young persons, the reflected wave travels slower and reaches the central aorta in early diastole, leading to augmentation of the DBP, which is useful for the perfusion of coronary arteries. In older persons, the reflected wave travels a lot faster and reaches the central aorta in late systole, thus augmenting the central aortic SBP, which increases the pressure load on the left ventricle and leads to the development of left ventricular hypertrophy (LVH). This increase in central SBP has been shown to be associated with a higher incidence of CVD and strokes.[10] The pulsatile stress produced by the intermittent action of the heart has been demonstrated recently to increase the media layer of the small muscular arteries and to decrease their lumen, which further accelerates the PWV in older persons.[11] Pathophysiologically, the central (aortic and carotid) pressure is more relevant than the peripheral (brachial) pressure for the pathogenesis of CVD. It is the aortic SBP that the left ventricle encounters during systole (afterload), whereas the DBP is responsible for the coronary artery perfusion.[12]

image

Figure 1. The configuration of the arterial waveforms in younger (left) and older (right) persons is shown. The arterial waveforms are composite waves (top heavy line) composed of a forward wave (dashed line) and a backward reflective wave (dotted line). The vertical line represents the closure of the aortic valve. The top solid line indicates the peak systolic blood pressure (SBP) in the younger and older person together with the augmentation pressure. The reflected wave in the younger person returns to the aortic root early in diastole augmenting diastolic blood pressure, which helps the perfusion of coronary arteries, whereas in the older person it returns to the aortic root late in systole, augmenting the SBP and increasing the left ventricular outflow pressure. Due to the arterial stiffness, pulse wave velocity (PWW) is increased in the older person (12 m/s) compared with the younger person (8 m/s). Adapted with permission from Franklin.[9]

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PP Amplification and CVD Risk

  1. Top of page
  2. Abstract
  3. Pathophysiology of Arteriosclerosis and Systolic Hypertension
  4. PP Amplification and CVD Risk
  5. Treatment of BP: The Age Factor
  6. Discussion
  7. Conclusions
  8. Disclosures
  9. References

The shape of the pressure wave changes as it travels down the aorta, resulting in augmentation of the peripheral SBP and PP as the distance from the heart increases, in contrast to DBP and mean arterial pressure (MAP), which change very little for the same distance from the heart. The pulse amplification is the result of arterial stiffness and the merging of the forward and reflected pressure waves, leading to an increase in PP.[13] The degree of SBP augmentation can be calculated from the difference between the first and second systolic peak of central aortic SBP and it is higher in older than younger persons (Figure 1). From the augmentation of SBP (AP) and PP, the augmentation index (AIx) can be calculated as AIx = AP/PP. Clinical evidence from the Strong Heart Study indicates that the peripheral PP is associated with a higher incidence of cardiovascular mortality independent of LVH and systolic dysfunction of the heart, in the absence of overt coronary heart disease.[14] In addition, the 5-year follow-up of these patients showed that the noninvasively measured central PP was a better predictor of incident CVD than brachial PP for being a better representative of left ventricular pressure load. A meta-analysis of studies in older persons also showed that PP was more strongly related to increased cardiovascular complications than MAP.[15] Moreover, an increased AIx has been shown to be independently associated with a higher risk of short- and long-term cardiovascular events in patients undergoing percutaneous coronary interventions.[16]

Treatment of BP: The Age Factor

  1. Top of page
  2. Abstract
  3. Pathophysiology of Arteriosclerosis and Systolic Hypertension
  4. PP Amplification and CVD Risk
  5. Treatment of BP: The Age Factor
  6. Discussion
  7. Conclusions
  8. Disclosures
  9. References

The brain and the heart are protected against stroke and myocardial infarction through wide fluctuations of BP by the autoregulation of cerebral and coronary artery circulation. Cerebral autoregulation (CA) is the intrinsic capacity of the cerebral vessels to maintain a constant cerebral blood flow (CBF) for the metabolic needs of the brain.[17] The CBF is also regulated by the arterial carbon dioxide level of the brain as well. The CA consists of two components: the static and the dynamic component. The static CA regulates CBF during gradual and progressive increases in BP,[18] whereas the dynamic CA regulates the CBF during rapid changes in BP.[18] It has been demonstrated in a recent study using transcranial Doppler that the CBF remains constant through wide changes in MAP ranging from 60 to 150 mm Hg (Figure 2) or from 40 to 125 mm Hg.[19] In addition, two recent studies in animals and humans using transcranial Doppler and near-infrared spectroscopy have shown that the lower limit of MAP for CA was 66 to 69 mm Hg.[20, 21] All of these studies show that the CBF is not seriously affected with low DBP and this could, perhaps, explain the lack of a J-curve effect for stroke incidence with low DBP in contrast to the heart, which is susceptible to a J-curve effect of low DBP, since the DBP is responsible for coronary artery perfusion.[22] However, a recent study showed that there might be a J-curve effect for stroke risk with DBP <71 mm Hg in older persons.[4] In this study, 68,551 patients aged 19 to 78 years from several European countries free of CVD and not taking antihypertensive drugs at study entry were followed for 13.2 years. The data showed an inverse relationship between DBP and old age. In this study, when the DBP dropped to <71 mm Hg there was a significant increase in stroke risk for patients 60 to 78 years old and not for younger patients. Besides age, there was a sex difference in stroke risk with lowering of MAP, with men becoming more sensitive than women (69 vs 73 years). In addition, there was a significant association between PP and stroke risk, which was independent of age and remained significant after multivariate adjustments. The importance of increased PP as a cardiovascular risk has also been demonstrated by other investigators.[13-16] These studies show that older patients are susceptible to lower DBP than younger patients and this should be considered when treating hypertension in the elderly.

image

Figure 2. An autoregulatory plateau is seen between 60 to 150 mm Hg of mean arterial pressure (MAP). This autoregulatory plateau is maintained through changes in cerebral vascular resistance (CVR). Once the limits of autoregulation are reached, CVR cannot correct for further changes in pressure as demonstrated by the MAP limits of <60 (lower limit) and >150 mm Hg (upper limit). Adapted with permission from Lucas and colleagues.[17]

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Discussion

  1. Top of page
  2. Abstract
  3. Pathophysiology of Arteriosclerosis and Systolic Hypertension
  4. PP Amplification and CVD Risk
  5. Treatment of BP: The Age Factor
  6. Discussion
  7. Conclusions
  8. Disclosures
  9. References

New evidence suggests that there is an interaction between age and DBP regarding CA for patients older than 60 years.[4] Similar findings in the shift of BP with age have been reported by other investigators with respect to CVD and stroke risk.[23, 24] In the study by Vishram and colleagues,[4] as well as Safar and associates,[23] DBP was the strongest predictor of CVD risk in persons younger than 50 years, whereas in persons 60 years and older, SBP was the strongest predictor. In persons aged 50 to 59 years, both pressures were equally important. Another significant finding from the study by Vishram and colleagues[4] is the J-curve effect of DBP with stroke risk in participants older than 60 years, when their DBP dropped to <71 mm Hg. Such an association is not commonly seen with strokes, in contrast to CVD,[22, 25-27] although it has been reported by some investigators.[28] This is important when treating elevated SBP in the elderly. Kannel and coworkers[29] showed that the incidence of cardiovascular events increased with a decrease in DBP <80 mm Hg when the SBP remained ≥140 mm Hg. Similar increases in CVD and stroke were reported by Fagard and colleagues,[30] when the DBP level dropped to ≤55 mm Hg due mostly to the widening of PP. In the study by Kannel and associates,[29] the 10-year risk ratio (RR) of cardiovascular events for men and women was 1.22 (95% confidence interval [CI], 0.97–1.50) with PP 46 to 55 mm Hg. The RR increased to 1.66 (95% CI, 1.32–2.07) with a PP 55.5 to 136 mm Hg. The significance of PP as a stroke[6, 24, 31, 32] and cardiovascular risk has also been demonstrated by other investigators.[13-16] This higher cardiovascular risk has been attributed to the increased pulsatile burden on the heart and blood vessels caused by the wide PP.[31] In this regard, the Framingham study tracked the age and sex of 4993 participants for 28 years and demonstrated that the SBP and PP became higher with older age, they were higher in older women than men of similar age, and were associated with an increase in cardiovascular risk.[31] Given that both PP and chronological age are positively associated with high risk for CVD and strokes, PP may be regarded as an index of arterial ageing. This could suggest that the chronological age as determined by calendar time is distinct from biologic age, which is a progressive and irreversible process of deterioration of the vitality of organ systems.[32] In addition, an inverse association has been found between PP and telomere length, suggesting that the biologic age of persons with wide PP is more advanced than their chronological age would indicate.[32] With respect to the interrelationship of BP with age regarding the treatment of hypertension, it appears that both SBP and DBP are important up to the age of 50 years, after which the value of the SBP supersedes the value of DBP. Therefore, when treating BP in older persons, attention should be paid to not lower the DBP below 71 mm Hg to avoid the risk of CVD and stroke, which increase significantly below this DBP level. Several studies have shown that the aggressive lowering of BP did not produce the expected results and that milder lowering of BP in older people to 150/90 mm Hg has been shown to reduce the risk of stroke and myocardial infarction. The new European guidelines now recommend that the BP of older persons be reduced to ≤150 to 140/90 mm Hg,[33] in contrast to previous stricter guidelines recommending BP reduction to <140/90 mm Hg and for persons with high cardiovascular risk to <130/80 mm Hg.

Conclusions

  1. Top of page
  2. Abstract
  3. Pathophysiology of Arteriosclerosis and Systolic Hypertension
  4. PP Amplification and CVD Risk
  5. Treatment of BP: The Age Factor
  6. Discussion
  7. Conclusions
  8. Disclosures
  9. References

Regarding drug selection for the treatment of high BP in older patients, drugs that block the renin-angiotensin-aldosterone system (RAAS) and calcium channel blockers (CCB) either alone or in combination are preferable as first-line treatment, since these drugs were effective in lowering the central SBP and PP compared with old β-blockers (atenolol) and thiazide diuretics in the Conduit Artery Function Evaluation (CAFÉ) study.[34] Supporting the superior role of the combination of RAAS blockers with CCBs are the results of a recent study in which the combination of RAAS blockers with CCBs was more effective in reducing BP and cardiovascular complications in high-risk hypertensive Japanese patients than high-dose RAAS blockers.[35]

References

  1. Top of page
  2. Abstract
  3. Pathophysiology of Arteriosclerosis and Systolic Hypertension
  4. PP Amplification and CVD Risk
  5. Treatment of BP: The Age Factor
  6. Discussion
  7. Conclusions
  8. Disclosures
  9. References
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