Introduction
Traditionally, blood pressure (BP) is measured using the auscultatory method with a sphygmomanometer and stethoscope. According to the American College of Cardiology/American Heart Association (ACC/AHA), normal systolic and diastolic blood pressure for adults is <120 mm Hg and <80 mm Hg, respectively.[1] In patients 65 years of age and older, the target blood pressure is < 130/80 mmHg.[2] Higher blood pressures earn the progressively severe labels of elevated blood pressure, stage I hypertension, stage II hypertension, and hypertensive crisis.[1]
It is well known that an increase in blood pressure accompanies advanced age. This increase in BP is due to complex and varied components, which are not only due to aging factors but also to unique environment and lifestyle factors. With advanced age, microscopic and macroscopic changes to the heart, vascular system, and autonomic nervous system may occur, which can dramatically affect blood pressure. This activity aims to begin to understand how aging can affect blood pressure.
Organ Systems Involved
An abrupt rise in or a prolonged elevation of blood pressure is a significant risk factor for end-organ damage in the heart, kidneys, brain, and vasculature. Outlined below is a non-exhaustive list of possible outcomes of chronic hypertension.[3]
Vascular System
Kidney
Cerebrovascular System
Stroke
Hemorrhage
Lacunar infarcts
Vascular dementia
Retinopathy
Heart
Mechanism
Physiologic changes associated with aging lead to an increase in systolic blood pressure (SBP), mean arterial pressure (MAP), and pulse pressure (PP), as well as a decreased ability to respond to abrupt hemodynamic changes.
The increased blood pressure seen with aging is most likely related to arterial changes, as aging results in the narrowing of the vessel lumen and stiffening of the vessel walls through a process known as atherosclerosis. Atherosclerosis leads to structural alterations, including increased vascular calcification, causing earlier reflected pressure waves during blood pressure wave propagation. The pressure wave arrives back from the aortic root during systole and contributes to the increase in systolic blood pressure. Diastolic blood pressure (DBP) tends to increase up to 50 years of age due to the rise in arteriolar resistance. The large artery stiffening occurring later in life contributes to wider pulse pressure, including a decreased diastolic blood pressure. The increase in arteriolar resistance, in combination with large artery stiffening, leads to a significant increase in systolic blood pressure, pulse pressure, and mean arterial pressure. The most prevalent class of hypertension in patients greater than 50 years old is isolated systolic hypertension (ISH), which occurs de novo or from prolonged HTN.[4]
The decreased ability to appropriately respond to abrupt hemodynamic changes is rooted in many pathophysiological factors, including a change in heart structure and function and a decrease in the autonomic regulation of blood pressure. Left ventricular hypertrophy and a decrease in left ventricle compliance correlate with a reduction in cardiac performance and in the ability to increase systolic blood pressure in response to stress. The autonomic system plays a key role in maintaining blood pressure through physiologic responses to standing, volume depletion, and increased cardiac output during stress. With a decrease in the autonomic regulation of blood pressure, there is a significant impact on physiologic adaption. One example includes the high prevalence of orthostatic hypotension among the elderly population.[5]
Related Testing
The arterial pressure waveform is representative of arterial pressure throughout a cardiac cycle and is a useful indicator of arterial wall stiffening. The waveform can be broken into two distinct phases; systolic and diastolic. The systolic phase characteristically demonstrates a rapid upstroke caused by the opening of the aortic valve and left ventricular ejection, followed by a quick decline. In contrast, the diastolic phase demonstrates a gradual decline of arterial pressure and run-off of blood flow into the peripheral circulation. The demarcation of these two phases is a dicrotic notch formed by the closing of the aortic valve.
Two different waves form the arterial pressure wave: a forward wave and a reflected wave. The forward wave represents blood flow from the left ventricle during contraction. The reflected or reverse wave is created by structures that cause impedance (e.g., branch points, direction changes). The speed of the wave is known as the pulse wave velocity. In a young artery, the reflected wave reflects to the aortic root during diastole. In an older, stiffened artery, the reflected wave reflects to the aortic root during systole because it has an increased pulse wave velocity, allowing it to contribute to the forward wave resulting in an increased peak forward wave. Depending on the device used, a pulse wave velocity greater than 10 to 12 m/sec indicates arterial wall stiffening.[6]
Other test modalities for increased arterial pressure include but are not limited to regular blood pressure checks with a sphygmomanometer, ankle-brachial index, angiography, and stress testing.
Pathophysiology
The primary factors contributing to hypertension in the elderly population are changes in arterial and arteriolar stiffness, with large artery stiffness occurring due to arteriosclerosis calcification and structural alterations. Notably, structural changes in large arteries observed in systolic hypertension are similar to those resulting from aging, making it difficult to differentiate between arterial changes due to disease and those due to aging.[7]
Arterial Stiffening
Stiffening of the arteries is one of the hallmarks of aging. In younger individuals, the peripheral arterial system is more rigid than the central arterial system. With time, this finding reverses, and older individuals have greater central artery stiffness compared to peripheral arteries. This reversal and increased stiffening of the larger central arteries is multifactorial in etiology. Changes in structural components, increased reactive oxygen species, inflammatory changes, and endothelial dysfunction are among the causes of the changes in arterial structure and function seen with aging.[8]
Increased Elastin Degradation and Collagen Deposition
The ratio of collagen to elastin increases with age leading to an increase in arterial stiffness. This change may also be present in ventricular smooth muscle cells. In the ventricular wall, a decrease in elastin results in a less compliant heart wall, leading to an increase in diastolic filling pressure. There are many hypotheses for why this change occurs in older populations, including material fatigue and various signaling pathways leading to the destruction of elastin and increased collagen deposition. Recent studies have shown that angiotensin II, along with the activation of TGF-B1 and matrix metalloproteinases are some of the signaling molecules that may be involved.[8]
Inflammatory Mediators
An increase in the levels of inflammatory mediators seen with aging leads to the production of reactive oxygen species, which may lead to endothelial damage predisposing the vascular system to atherosclerosis.[9] Atherosclerosis presents with endothelial injury or dysfunction. It is a slow process by which large-to-medium-sized arteries (e.g., abdominal aorta, popliteal artery, carotid artery, coronary artery) undergo thickening of the intimal layer of blood vessel walls, leading to less compliant arteries. This process initiates endothelial damage, permitting lipid transport through the innermost layer of arteries, the intima, into the lumen of the vessels. These lipids are then oxidized and consumed by macrophages, resulting in the formation of foam cells and fatty streaks. Subsequently, an inflammatory and healing process ensues. An increase in various growth factors allows for the recruitment and proliferation of smooth muscle cells, which form a fibrous cap with a lipid core.
Reduced Left Ventricular Compliance
A decrease in left ventricular compliance and cardiac reserve is widely seen throughout the aging population. Factors affecting left ventricular function include preload, afterload, and contractility. With age, cardiac myocytes tend to hypertrophy and decrease in number. The left ventricle becomes stiffer and, therefore, its compliance decreases. Ventricular stiffening results from many processes, including alteration in structural proteins, an increase in inflammatory mediators, and increases in glycation end products. Another notable change to the left ventricle is prolonged isovolumetric relaxation time. This increase in relaxation time is associated with alterations in calcium signaling. Healthy, older adult hearts have less cardiac sarcoplasmic reticulum ATPase resulting in lower calcium content. This causes an increased dependency on L-type calcium channels, which explains the efficacy of hypertensive medications used to block these channels.
With aging, there is a decrease in chronotropic, lusitropic, and inotropic responses. A reduced response to atropine due to increased parasympathetic vagal tone and decreased sympathetic tone is a typical finding. These changes may be a direct result of suppressed cAMP production, decreased beta-receptor function and number, and increased G protein activity. Due to these changes, older adults present with elevated production and levels of circulating catecholamines and stress-stimulated levels of epinephrine and norepinephrine.[9]
Other pathophysiologic factors contributing to increased blood pressure with aging include decreased baroreceptor sensitivity, increased responsiveness to SNS stimuli, altered renal and sodium metabolism, and altered renin-aldosterone relationship.[10]
Previously, increasing BP was thought to be unavoidable as we age. However, this is not the case for the elderly in secluded communities and rural, underdeveloped areas. A high salt diet in developed regions of the world is believed to induce vascular smooth muscle cell changes, leading to collagen accumulation in large artery walls and increased arterial stiffness.[7]
Postprandial Hypotension
Postprandial hypotension (PPH) is defined as a decrease in blood pressure that occurs 1 to 2 hours after eating. PPH typically affects older adults, especially those with hypertension or autonomic nervous system diseases such as Parkinson disease. PPH is thought to be caused by an increased concentration of vasoactive GI peptides or insulin-related vasodilation.[11]
Orthostatic Hypotension
Orthostatic hypotension, also called postural hypotension, is defined as a decrease in SBP by 20 mmHg or a decrease in DBP by 10 mmHg within three minutes of standing. Orthostatic hypotension is due to an inadequate response to postural changes in blood pressure with many possible causes, including ANS dysfunction, cardiac problems, medication side effects, age-related changes, or temporary dysregulation of blood volume.[12]
Clinical Significance
With a rapidly growing aging population, clinicians must understand and treat age-related vascular changes. The co-morbidities associated with hypertension in this group can cause many debilitating, if not fatal, outcomes such as stroke, myocardial infarction, aortic dissection/aneurysms, chronic kidney disease, coronary artery disease, and vascular dementia.
Early detection and treatment of hypertension may prevent or slow end-organ damage while it is in a reversible stage. When encountering a patient with hypertension, many factors come into play when choosing the best treatment option. Healthy lifestyle changes (diet, physical activity, smoking cessation, and stress management) are the first-line options. If the patient continues to be hypertensive after implementing these changes on follow-up, medical management is an appropriate option.
Five major classes of antihypertensive agents available for use have been shown to reduce cardiovascular events in the elderly population. These include beta-blockers, calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and diuretics.[13]
Clinically Significant Studies
Framingham Heart Study
Followed patients for 30 years and demonstrated that SBP shows a continuous increase between the ages of 30 to 84. In contrast, DBP has a varying pattern with aging - increasing until the fifth decade, then slowly decreasing from ages 60 to 84. This gives a steep rise in pulse pressure with aging. The outcome of this study proved that cardiovascular risk is positively, continuously, and independently associated with rising blood pressure.
[14]This study also demonstrated a higher prevalence of isolated systolic hypertension in older women than men. Elderly hypertensive women were shown to have stiffer large arteries and higher pulse pressure, with the increased arterial stiffness occurring after menopause.
[15]
Third National Health & Nutrition Examination Survey (NHANES III)
Almost 80% of those with elevated blood pressure over 50 years of age have, at least on a single occasion, systolic HTN - characterized as SBP > 140 mmHg. Additionally, while DBP has been used as the primary determinant of hypertension-associated cardiovascular risk, studies have shown it to be an independent risk factor. In the elderly, high SBP and high PP have been shown to be more powerful independent predictors of risk.
[16]
The Multiple Risk Factor Intervention Trial (MRFIT)
This trial showed that the risk of death from coronary heart disease was greater with each increment of SBP. Individuals with isolated systolic hypertension are at the most significant risk of death from coronary heart disease. The risk of stroke was also strongly related to systolic blood pressure and isolated systolic hypertension.
[17]
A meta-analysis including data from multiple major trials concluded the danger of cardiovascular complications associated with widening pulse pressure. This meta-analysis determined that the best predictor of increased cardiovascular risk is increased pulse pressure. As pulse pressure is defined as systolic blood pressure - diastolic blood pressure, an increase in pulse pressure results from a decreased diastolic and increased systolic blood pressure.[18]
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Disclosure: Joel Singh declares no relevant financial relationships with ineligible companies.
Disclosure: Tran Nguyen declares no relevant financial relationships with ineligible companies.
Disclosure: Connor Kerndt declares no relevant financial relationships with ineligible companies.
Disclosure: Amit Dhamoon declares no relevant financial relationships with ineligible companies.
