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Approximately 65% of adults over 60 years in the USA are hypertensive. Poor dietary habits and sedentary lifestyles are fueling the hypertension epidemic. The effects of higher intakes of fruits and vegetables and whole-grain products on systolic and diastolic blood pressures were analyzed using data at baseline, 6 months, and 12 months on 349 and 573 subjects, respectively, in the control and intervention groups of the Women’s Health Trial: Feasibility Study in Minority Populations. Models for systolic and diastolic blood pressures have been estimated using cross-sectional and longitudinal data in different settings. However, it is important to estimate comprehensive dynamic random effects models that take into account inter-relationships between systolic and diastolic blood pressures as well as the effects of dietary intakes and biomarkers for making robust inferences. There were significantly greater reductions (P

Whereas larger arteries participate in the dampening of blood pressure (BP) oscillations resulting from intermittent ventricular ejection, smaller arteries steadily deliver an adequate supply of blood from the heart to the peripheral organs. Numerous active mechanisms are involved in this process. Cyclic stress acts differently from steady stress, inducing stronger and stiffer material of the vessel wall than under static conditions. Cyclic strain participates in the phenotypic plasticity of smooth muscle cells, initiates transduction mechanisms and induces the transcriptional profile of mechanically induced genes. Finally, the autoregulatory mechanism protecting the brain, heart and kidney from cardiovascular (CV) damage differ markedly according to their localization. Whereas the heart is dependent on pulsatile forces, owing to the diastolic perfusion of coronary arteries, the brain and the kidney are rather influenced by steady mechanical forces. For the kidney, the transmission of pulsatile pressure may greatly contribute to glomerular sclerosis in the elderly.

Chronic kidney disease is a leading global health problem with an increasing prevalence. Hypertension is present in most patients with chronic kidney disease, and hypertension-related nephrosclerosis is a top cause of progressive renal damage and end-stage renal disease. Systolic blood pressure (BP) and pulse pressure, together with nocturnal BP, are the most important factors favoring the progression of renal failure. Consequently, strict control of BP and other cardiovascular risk factors is required, including an adequate degree of suppression of the renin-angiotensin system in every patient.

Changes in vascular structure that accompany hypertension may contribute to hypertensive end-organ damage. Both the macrovascular and microvascular levels should be considered, as interactions between them are believed to be critically important. Regarding the macrocirculation, the article first reviews basic concepts of vascular biomechanics, such as arterial compliance, arterial distensibility, and stress-strain relationships of arterial wall material, and then reviews how hypertension affects the properties of conduit arteries, particularly examining evidence that it accelerates the progressive stiffening that normally occurs with advancing age. High arterial stiffness may increase central systolic and pulse pressure by two different mechanisms: 1) Abnormally high pulse wave velocity may cause pressure waves reflected in the periphery to reach the central aorta in systole, thus augmenting systolic pressure; 2) In the elderly, the interaction of the forward pressure wave with high arterial stiffness is mostly responsible for abnormally high pulse pressure. At the microvascular level, hypertensive disease is characterized by inward eutrophic or hypertrophic arteriolar remodeling and capillary rarefaction. These abnormalities may depend in part on the abnormal transmission of highly pulsatile blood pressure into microvascular networks, especially in highly perfused organs with low vascular resistance, such as the kidney, heart, and brain, where it contributes to hypertensive end-organ damage.

In subjects with chronic kidney disease (CKD), treatment of high systolic blood pressure is a key element in preventing disease progression and the occurrence of cardiovascular (CV) events. This relationship between the large arterial system and kidney function was demonstrated in different renal populations. In subjects with mild to severe renal insufficiency, increased aortic stiffness and reduced creatinine clearance are closely related and are independent of traditional CV risk factors. In renal transplant patients, aortic stiffness is significantly increased irrespective of donor type. Donor age and/or acute rejection contribute independently to the increased stiffness. In the presence of renal dysfunction, an increase in systemic pulse pressure frequently may be observed and transmitted to the glomeruli. This alteration potentially initiates renal damage and favors CV events. In subjects with end-stage renal disease and high CV risk, pharmacologic modulation of the renin-angiotensin system might prevent CKD progression and CV events.

Isolated systolic hypertension is the commonest form of hypertension from middle age onwards. Achieving target systolic blood pressure (BP) control remains difficult in everyday clinical practice and even under clinical trial conditions. Most antihypertensive medicines were designed to lower peripheral vascular resistance, which was considered the haemodynamic determinant of hypertension; most are effective in reducing steady but not pulsatile components of BP. Arterial stiffness, defined via aortic length-specific pulse wave velocity (PWV), is thought to be an important determinant of pulse pressure widening through its effects on the timing and amplitude of pressure wave reflection, and/or the aorta's Windkessel function, or its excess 'reservoir' pressure. Whereas pulse pressure is neither an independent nor consistent cardiovascular risk factor, particularly below the age of about 60 years, PWV has become the most powerful predictor of cardiovascular outcomes including mortality, independent of systolic, pulse, mean or other BP components. PWV is therefore a more direct target for treatment. This review addresses the potential therapeutic options for targeting arterial stiffness and the role of pulse pressure.

Interest in relations between central aortic pressure and cardiovascular disease risk has increased markedly over the past two decades. Numerous studies have shown that higher pulse pressure is associated with increased risk. Further, pulse pressure differs variably and sometimes dramatically between the central aorta and the brachial artery, where blood pressure is generally measured. In light of the potential for variable misclassification of central systolic and pulse pressure by brachial measurements, central blood pressure has emerged as a potentially superior blood pressure measure. This brief review will examine the evidence supporting the use of central pressure to stratify risk and guide therapy in patients with hypertension.

Isolated systolic hypertension is a major health burden that is expanding with the aging of our population. There is evidence that central arterial stiffness contributes to the rise in systolic blood pressure (SBP); at the same time, central arterial stiffening is accelerated in patients with increased SBP. This bidirectional relationship created a controversy in the field on whether arterial stiffness leads to hypertension or vice versa. Given the profound interdependency of arterial stiffness and blood pressure, this question seems intrinsically challenging, or probably naive. The aorta’s function of dampening the pulsatile flow generated by the left ventricle is optimal within a physiological range of distending pressure that secures the required distal flow, keeps the aorta in an optimal mechanical conformation, and minimizes cardiac work. This homeostasis is disturbed by age-associated, minute alterations in aortic hemodynamic and mechanical properties that induce short- and long-term alterations in each other. Hence, it is impossible to detect an “initial insult” at an epidemiological level. Earlier manifestations of these alterations are observed in young adulthood with a sharp decline in aortic strain and distensibility accompanied by an increase in diastolic blood pressure. Subsequently, aortic mechanical reserve is exhausted, and aortic remodeling with wall stiffening and dilatation ensue. These two phenomena affect pulse pressure in opposite directions and different magnitudes. With early remodeling, there is an increase in pulse pressure, due to the dominance of arterial wall stiffness, which in turn accelerates aortic wall stiffness and dilation. With advanced remodeling, which appears to be greater in men, the effect of diameter becomes more pronounced and partially offsets the effect of wall stiffness leading to plateauing in pulse pressure in men and slower increase in pulse pressure (PP) than that of wall stiffness in women. The complex nature of the hemodynamic changes with aging makes the “one-size-fits-all” approach suboptimal and urges for therapies that address the vascular profile that underlies a given blood pressure, rather than the blood pressure values themselves.

High blood pressure, once believed to represent a normal and progressive component of the aging process, is now recognized as a manifestation of structural and physiologic abnormalities of aortic function. Elevated systolic blood pressure and increased pulse pressure unquestionably increase the risk of both fatal and nonfatal cardiovascular events, including stroke, myocardial infarction, and heart failure. Isolated systolic hypertension, defined as a systolic blood pressure >/= 140 mm Hg with a diastolic blood pressure < 90 mm Hg, affects most individuals aged 60 years and older. Several clinical trials have clearly demonstrated that treatment of hypertension significantly reduces the cardiovascular event rate. However, controversy continues as to the choice of antihypertensive agents and combinations of agents. It is both appropriate and necessary to treat elderly hypertensives aggressively to the same target blood pressures identified for younger patients. It is also appropriate to initiate treatment with lower doses of antihypertensive agents and to bring the pressure down more slowly, monitoring for orthostatic hypotension, impaired cognition, and electrolyte abnormalities.

Several studies show that systolic blood pressure is an important predictor of renal disease progression, just as it is linked with cardiovascular consequences in hypertension. In contrast, particularly in older patients, diastolic blood pressure was not independently associated with risk of kidney disease progression in the same studies. Pulse pressure has been shown to be equivalent in predicting renal outcomes, but might not have added value after adjusting for systolic blood pressure. Several cross- sectional studies present a strong correlation of ambulatory blood pressure monitoring values with microalbuminuria, compared with office-based blood pressure measurements. Small, prospective studies have shown an association between loss of nocturnal blood pressure decline and outcomes, including microalbuminuria, accelerated kidney disease progression, and mortality.

Thyroid hormone has well-recognized effects on the cardiovascular system and blood pressure regulation. Blood pressure is altered across the entire spectrum of thyroid disease. The effects of hyperthyroidism include increased cardiac output, contractility, tachycardia, widened pulse pressure, decreased systemic vascular resistance, and increased basal metabolic rate. The manifestations of hypothyroidism are in marked contrast to those of hyperthyroidism and include decreased cardiac output, narrow pulse pressure, increased systemic vascular resistance, and decreased metabolic rate. Although thyroid hormone affects almost all tissues of the body and mediates changes in homeostasis, adaptations of the cardiovascular system can result in changes in blood pressure to accommodate the new demands on the system. In this paper, we review the direct and indirect thyroid hormone-mediated effects on blood pressure.

Hypertension is a major reversible risk factor for cardiovascular complications. According to recent guidelines, hypertension can be subdivided into isolated diastolic, isolated systolic, and systolic and diastolic mixed hypertension using proposed thresholds of various blood pressure components. In the present article, we reviewed the association of cardiovascular outcomes with diastolic blood pressure versus systolic blood pressure and with isolated diastolic hypertension versus systolic and mixed hypertension in observational prospective cohort studies and large-scale individual data-based meta-analysis. Blood pressure was measured either in the clinic or at home or under ambulatory conditions for 24 h in cohort studies. To illustrate the treatment effect of diastolic blood pressure lowering, we also reviewed randomized placebo-controlled outcome trials in diastolic hypertension. Conclusions: The risks conferred by diastolic and systolic blood pressure, irrespective of the methods of blood pressure measurement, are age-dependent. Diastolic blood pressure and isolated diastolic hypertension drive coronary risk in younger subjects, whereas systolic blood pressure is the predominant risk indicator in older people. Reversibility of the risk by diastolic BP lowering treatment in randomized trials confirms that diastolic hypertension is a risk factor that must be treated.

Cardiovascular risk factors (CVRFs) have been shown to induce end organ damage. Until now, the main approach to reduce CVRF-induced end organ damage was by normalization of CVRFs; this approach was found effective to reduce damage and cardiovascular (CV) events. However, a residual risk always remained even when CVRFs were optimally balanced. An additional risk factor which has an immense effect on the progression of end organ damage is aging. Aging is accompanied by gradual stiffening of the arteries which finally leads to CV events. Until recently, the process of arterial aging was considered as unmodifiable, but this has changed. Arterial stiffening caused by the aging process is similar to the changes seen as a result of CVRF-induced arterial damage. Actually, the presence of CVRFs causes faster arterial stiffening, and the extent of damage is proportional to the severity of the CVRF, the length of its existence, the patient's genetic factors, etc. Conventional treatments of osteoporosis and of hormonal decline at menopause are potential additional approaches to positively affect progression of arterial stiffening. The new approach to further decrease progression of arteriosclerosis, thus preventing events, is the prevention of age-associated arterial structural changes. This approach should further decrease age-associated arterial stiffening. A totally new promising approach is to study the possibility of affecting collagen, elastin, and other components of connective tissue that participate in the process of arterial stiffening. Reduction of pulse pressure by intervention in arterial stiffening process by novel methods as breaking collagen cross-links or preventing their formation is an example of future directions in treatment. This field is of enormous potential that might be revolutionary in inducing further significant reduction of cardiovascular events.

Measurement of vascular compliance has assumed increasing importance as a marker of early disease of the vascular wall, a predictor of future vascular disease, and a way to monitor the effects of vasoactive agents on arterial wall stiffness. Vascular compliance can be estimated by several methods: measurement of the pulse pressure, or pulse pressure-stroke volume ratio; analysis of the systolic pulse wave augmentation index and the diastolic pulse wave contour; ultrasonic echo-tracking; and MRI. Because few comparative studies have been done, the physiologic significance of the measures of compliance obtained by each method is uncertain. Antihypertensive drugs may improve vascular compliance by reducing blood pressure, relaxing vascular smooth muscle, or promoting long-term effects on vascular smooth muscle and cardiomyocyte growth and remodeling. Angiotensin converting enzyme (ACE) inhibitors have been reported to improve vascular compliance in nearly all studies, suggesting a beneficial class effect independent of blood pressure reduction. Favorable changes in the vascular wall-lumen ratio of small vessels from subcutaneous gluteal biopsy specimens after treatment with ACE inhibitors and the persistence of improved vascular compliance after withdrawal of therapy indicate that these agents may produce long-term vascular remodeling. Although few studies have been done, angiotensin II receptor antagonists improve vascular compliance, possibly by blocking angiotensin II-mediated cell proliferation and increasing apoptosis via unopposed AT1 receptor stimulation. In contrast, calcium antagonists and beta-blockers have variable effects on vascular compliance, although beta-blockers with intrinsic sympathomimetic activity improve vascular compliance. Diuretics have little effect on vascular compliance beyond their blood pressure-lowering actions, except for spironolactone, which by improving vascular compliance may have contributed to the reduction in heart failure mortality seen in the Randomized Aldactone Evaluation Study.

In conclusion, SBP and pulse pressure are stronger predictors of cardiovascular risk than is DBP in older individuals, and reduction in events has been more impressive in SBP treatment trials. Because of older morbidity trials that primarily used DBP entry criteria, however, treatment decisions should still include DBP goals. Nevertheless, clinicians should be more attentive to treating SBP, especially in patients older than 60 years.

Diastolic pressure, systolic pressure, and pulse pressure have all been assigned the role of the best predictor of cardiovascular events during the 20th century. At the dawn of the new millennium, concepts that draw attention to vascular mechanics reconcile the seemingly conflicting results of epidemiologic studies, better define the hypertensive patient, evaluate more accurately the risk and set its markers, and ultimately optimize treatment through a logical approach that aims at the mechanism and not at the manifestation. Pulse wave analysis and measurement of arterial stiffness are valuable tools in the assessment and management of the hypertensive patient.

Arterial stiffening with age is responsible for isolated systolic hypertension, for elevation of systolic pressure with age, and for the majority of cardiovascular events in the elderly, especially left ventricular failure. Change in brachial pulse pressure with age underestimates change in aortic pulse pressure; change with vasodilator agents, especially nitrates, underestimates beneficial effects of these agents on the heart. New methods based on pulse wave analysis complement sphygmomanometry in assessing ill effects of aging and benefits of drug therapy for hypertension.

In some controlled therapeutic trials for hypertension, a selective reduction of systolic blood pressure has been obtained with long-term treatment. The greatest effects on cardiovascular outcomes stem from a decrease of central blood pressure through a significant reduction of arterial stiffness, wave reflections, or both. Until now, all protocols have used angiotensin II blockade, mainly through angiotensin-converting enzyme inhibition. Cardiovascular outcomes have been significantly improved when compared with controls, but most of them have been treated with beta blockers. Such "de-stiffening" therapies are important to consider and require additional trials.

The hemodialysis population is associated with a very low survival rate, with myocardial infarctions and strokes accounting for most of the increased mortality. Recent observational studies demonstrate a paradoxical relationship between increasing blood pressure and increasing mortality. Hypertension treated with antihypertensive medications unequivocally reduces cerebrovascular risk, but demonstration of a survival benefit for cardiovascular mortality has proven more difficult to demonstrate. Increased pulse pressure is caused by inadequate dialysis treatment that increases arterial wall stiffness and afterload, and decreases coronary perfusion. The disproportionate representation of diastolic dysfunction and coronary artery atherosclerosis may explain why increased pulse pressure is associated with higher cardiovascular risk for the dialysis population. Optimum blood pressure control has not been established, due to a lack of prospective studies targeting blood pressure reduction. Opinion-based recommendations are offered, but goals should be individualized based on a complete assessment of prevailing comorbidities and should target normalization of the pulse pressure.

Isolated systolic hypertension (ISH) is the dominant form of hypertension in the elderly. It is associated with increased arterial pulse pressure, to which an early-returning and magnified pulse-wave reflection makes an important contribution. Treatment of ISH with diuretics, calcium channel blockers (CCBs), and angiotensin II inhibitors is effective in reducing systolic blood pressure, preventing cardiovascular morbid events, and lowering mortality; these agents may have to be used in combination to achieve the systolic blood pressure goal of < 140 mm Hg. Treatment with β-blockers appears to be less effective. The relative efficacy of various classes of antihypertensive drugs for lowering pulse pressure and systolic blood pressure is determined in part by their differing abilities to reduce pulse-wave reflection. In patients with ISH that is refractory to dual or triple therapy, measurement of the reflected wave by applanation tonometry may be useful in determining which additional antihypertensive agent to use.

Isolated systolic hypertension (ISH) is an important cause of strokes and heart failure among the elderly, but it is difficult to control in some elderly patients, even with combination antihypertensive therapy. The presence of a prominent reflection wave in the arterial pulse-wave profile of such patients signifies that adjuvant nitrate therapy may prove effective in lowering pulse pressure. This reflection arises in the muscular arteries and is caused by arterial stiffness associated with hypertension and other cardiovascular risk factors, probably including endothelial dysfunction. By acting directly on the arterial wall, nitrates produce endothelium-independent vasorelaxation. The reflection wave and the contribution this makes to pulse pressure are thereby ablated. Controlled trials of the use of isosorbide mononitrate and isosorbide dinitrate in ISH have shown that these agents decrease systolic blood pressure as well as pulse pressure, and with the mononitrate, efficacy appears to be unimpaired by nitrate tolerance.

Numerous studies performed in the past decade have shown that increased pulse pressure, an indicator of arterial stiffening, is associated with adverse clinical outcomes. Research is now focused on better defining the anatomic and physiologic determinants of increased pulse pressure. Early work considered aortic stiffening to be a passive, irreversible consequence of aging that was accelerated by hypertension. Recent studies suggest that aortic stiffening is dynamic and reversible and that abnormalities in aortic function may play a primary role in the pathogenesis of hypertension. This review summarizes current work on the genesis of increased pulse pressure and abnormal pulsatile load in hypertension, and underscores areas for future research.

Peak-systolic blood pressure (SBP) and end-diastolic blood pressure (DBP) have been considered the exclusive mechanical factors predicting cardiovascular (CV) risk in populations of normotensive and hypertensive subjects. The purpose of this review is to show that in addition to SBP and DBP, other hemodynamic indices that have particular relevance for coronary complications and originate from pulse pressure (PP) should be taken into account, namely brachial PP and, potentially, heart rate (HR). In normotensive and hypertensive populations, increased PP is an independent predictor for myocardial infarction, more powerful than SBP, even in hypertensive subjects under successful antihypertensive drug therapy. Increased HR is an additional CV risk factor, acting particularly through the presence of an enhanced PP x HR product. Such findings, observed during a period in which standard antihypertensive agents are known to reduce SBP and PP to a much lesser extent than DBP, require the development of intervention trials using drugs acting specifically on SBP, PP, and arterial stiffness.

Hypertension is present in 60% to 70% of the population over 60 years of age and may result in cardiovascular complications such as stroke, coronary heart disease, and heart failure. In this review, the role of arterial stiffness, endothelial function, atherosclerosis, and oxidative stress in the pathogenesis of hypertension is discussed extensively. Antihypertensive drug treatment may control high blood pressure and prevent complications. This review summarizes the results of several placebo-controlled and comparative clinical trials that have studied the efficacy of different classes of antihypertensive drugs. ispartof: Current hypertension reports vol:5 issue:5 pages:372-9 ispartof: location:United States status: published

There is a paucity of high quality studies on the prognostic importance of arterial pressure in end-stage renal disease. Furthermore, the optimal timing for blood pressure (BP) measurements (pre- or postdialysis), and the prognostic value of 24-hour ambulatory BP monitoring in these patients remain to be established. In end-stage renal disease patients without diabetes and heart failure, predialysis systolic, diastolic, and pulse pressure are strongly and independently related to left ventricular mass, and the strength of these relationships is higher than that between the corresponding postdialysis values and left ventricular mass. Average predialysis systolic pressure (monthly average) is associated with left ventricular mass as strongly as 24-hour systolic BP, which suggests that the average routine predialysis BP taken over 1 month may be equally representative of the “true” BP (the integrated BP load) than 24-hour ambulatory BP monitoring. Mortality is U shaped in large hemodialysis databases. In the only prospective study that adequately controlled for cardiac function at baseline, it was shown that hypertension is associated with a higher risk of developing congestive heart failure, and that patients with left ventricular hypertrophy or chronic heart failure are at a much higher risk of mortality than patients without these complications. The role of arterial stiffening (pulse pressure) as a cardiovascular risk factor has been firmly established in an analysis of a very large dialysis database in the United States, and by recent studies based on direct measurements of pulse wave velocity.

Isolated systolic hypertension affects over 15% of all people older than 60 years of age. In the elderly, systolic hypertension is a major modifiable cardiovascular risk factor. Systolic blood pressure is associated with higher risk of an adverse outcome. Diastolic blood pressure is inversely correlated with total mortality, independent of systolic blood pressure, highlighting the role of pulse pressure as risk factor. Three placebo-controlled outcome trials on antihypertensive drug treatment in older patients with isolated systolic hypertension have been published: the Systolic Hypertension in the Elderly Program (SHEP), the Systolic Hypertension in Europe (Syst-Eur) Trial, and the Systolic Hypertension in China (Syst-China) Trial. These three trials showed the benefit of antihypertensive drug treatment. A meta-analysis was done by pooling the patients from these three trials with a subset of patients with isolated systolic hypertension from five other trials in the elderly. The pooled results of 15,693 older patients with isolated systolic hypertension prove that antihypertensive drug treatment is justified if systolic blood pressure on repeated clinic measurements is 160 mm Hg or higher. ispartof: Current Hypertension Reports vol:3 issue:4 pages:333-339 ispartof: location:United States status: published

Essential hypertension, particularly systolic hypertension, can be characterized as a disorder of aging. The diverse expressions of this disorder represent the interactions of a genetic script, the environment, chance, and a temporal factor. The temporal factor, namely the telomeres, is biological, intrinsic, and dynamic. Telomere length is heritable, is inversely related to pulse pressure, and can be modified by reactive oxygen species. The incorporation of a temporal factor into models of essential hypertension may provide a heretofore missing link explaining variations in age-dependent increase in pulse pressure.

Systolic hypertension is the most common form of hypertension, especially in individuals aged 60 years or older. Systolic hypertension is a reflection of decreasing compliance of large arteries and is a strong independent risk factor for all cardiovascular diseases. Despite proven benefits of therapy for systolic hypertension, only 25% of patients with this condition are adequately treated to attain target blood pressures. The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of high blood pressure (JNC VI) recommends the use of diuretics and long-acting dihydropyridine calcium channel blockers as first-line therapy for isolated systolic hypertension. Therapy is also guided by comorbid conditions where certain drugs may have additional benefits. The goal of therapy should be a graded reduction in blood pressure to less than 140/90 mm Hg with lower blood pressure targets in patients with coexistent diabetes or renal failure.

Isolated systolic hypertension (ISH) is the most common type of hypertension and the most difficult type to control with antihypertensive therapy. ISH, by definition, is wide pulse pressure hypertension resulting largely from excessive large artery stiffness and representing an independent risk factor for cardiovascular disease in the older aged population. Two major intervention studies of ISH have shown significant benefit in reducing systolic blood pressure with active drug therapy, including thiazide diuretics and calcium receptor antagonists. The optimal treatment strategy is to maximize reduction in systolic blood pressure and to minimize reduction in diastolic blood pressure, thereby reducing pulse pressure. All classes of antihypertensive drugs reduce pulse pressure by means of lowering peripheral resistance, but certain drugs like nitrates, angiotensin converting enzyme inhibitors, and other drugs affecting the renin-angiotensin system have multiple actions that improve large artery stiffness and early wave reflection and are especially useful in treating ISH in the elderly.