A detailed history and physical examination is essential for identifying risk factors and stratifying patients to target those who need more aggressive therapy to achieve goal BP. Careful measurement of BP should be an integral part of any physical examination in a physician's office. In addition to office BP measurements, 24-hour ambulatory BP monitoring and home BP monitoring are now acceptable methods for evaluating BP more comprehensively on an individual basis. The recently released National Institute of Health and Clinical Excellence (NICE) guidelines published in the United Kingdom recommend that a diagnosis of primary hypertension should be confirmed with 24-hour ambulatory blood pressure monitoring or home blood pressure monitoring rather than by relying solely on office blood pressure measurement. Based on 24-hour ambulatory BP monitoring and office BP readings, 4 patterns of BP have been described (Figure 1). Masked hypertension is defined as normal office BP and elevated home BP.10 Its prevalence ranges from 8% in the general population to as much as 20% in hypertensive patients receiving treatment. Patients with white coat hypertension have an elevated office BP and normal home BP measurements.
Normally, there is a diurnal variation in BP, with a 10% to 20% decrease in systolic BP during sleep, which is described as the normal dipping pattern.
Several prospective trials have demonstrated that home BP is a better predictor of cardiovascular morbidity and mortality than are office BP measurements.
These home BP measurement guidelines recommend that a validated device be used to measure BP at home.
Measures of arterial stiffness such as central (aortic) blood pressure and pulse wave velocity (PWV) can now be measured non-invasively in an outpatient setting. Baseline blood tests are recommended by JNC 7 to identify those individuals at risk for hypertensive events (Table 1). More extensive testing for identifiable causes is not generally indicated unless blood pressure control is not achieved.
Proper technique of BP measurement should be an integral part of the evaluation and management of hypertension. Home blood pressure recording is now recommended as an inexpensive and accurate method of measuring blood pressure.
Patterns of BP based on ambulatory BP monitoring play an important role in altering therapy and outcomes. Laboratory examination helps in stratifying patients who will need more extensive evaluation and aggressive therapy. It is clearly recognized that an increasing BP level is associated with a greater risk of heart attack, stroke, and kidney disease. Data from clinical trials published after the release of JNC 7 have provided new information that will likely be addressed in JNC 8. Educating patients regarding the importance of non-pharmacologic interventions for effective BP control is an important component of reducing cardiovascular risk in the general population. Lifestyle modifications include limiting alcohol intake, increasing physical activity, and reducing sodium intake to <6 g of sodium chloride daily. Weight reduction of as little as 10 to 12 pounds in an obese hypertensive patient can have a considerable effect on elevated BP. Table 4 lists lifestyle modifications for which evidence-based data are available to support BP reductions. The ALLHAT trial was designed to compare antihypertensive therapy using an ACE inhibitor, a dihydropyridine calcium antagonist, and an alpha-adrenergic blocker with treatment with an oral diuretic, chlorthalidone, as the standard of therapy. Trial-design issues subsequently generated significant debate regarding the ALLHAT results, particularly the magnitude of the differences noted. In addition to thiazide diuretics, JNC 7 guidelines also recommend ACE inhibitors, angiotensin receptor blockers (ARBs), beta blockers, and calcium channel blockers as first-line therapy for hypertension. Since the release of JNC 7, new information has emerged in the area of anti-hypertensive therapy. In the Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial, which included hypertensive adults at high risk for cardiovascular events, patients were randomly assigned to receive the ACE inhibitor benazepril plus either the calcium channel blocker amlodipine or the diuretic hydrochlorothiazide.28 There was significant reduction in morbidity and mortality in patients in the benazepril plus calcium channel blocker group compared to conventional diuretic based therapy. Data from large intervention trials in hypertension clearly demonstrate that patients enrolled in these trials required an average of more than 2 medications for blood pressure control.19,24 It is also true that about two-thirds of patients with hypertension required more than 1 anti-hypertensive medication for BP control. Classification of hypertension is based on BP levels as well as comorbidities such as heart disease, diabetes, and renal disease. Lifestyle intervention should be recommended for patients with prehypertension and all stages of hypertension.
Approximately 5% of patients with hypertension have a secondary etiology that leads to an elevation in blood pressure.
Renovascular disease: New onset of uncontrolled hypertension or acute worsening of previously well-controlled hypertension in an older individual could likely be due to renal artery stenosis as a result of atherosclerotic renal artery disease.
Pheochromocytoma: These are chromaffin cell tumors that arise in the adrenal medulla or sympathetic ganglia and cause excess production and secretion of catecholamines. Coarctation of aorta: These patients present with radiofemoral pulse delay and a relatively weaker pulse in the legs compared to arms. Balloon angioplasty in patients with FMD; medical management with ACE inhibitor or ARB in combination with a diuretic for patients with atherosclerotic renal artery disease.
Plasma aldosterone renin ratio, salt loading test for confirmation, CT scan of adrenal and adrenal vein sampling for localization.
In a patient with adrenal hyperplasia or bilateral functional adrenal adenoma, medical therapy with aldosterone antagonist. In a patient with unilateral functional adenoma, adrenalectomy of the affected adrenal gland. Plasma metanephrines, 24-hour urinary metanephrines and catecholamines, CT, MRI, metaiodobenzylguanidine scan if CT or MRI are not conclusive. Balloon angioplasty in patient with FMD; medical management with ACE inhibitor or ARB in combination with a diuretic for patient with atherosclerotic renal artery disease. A careful history and physical examination of patients with hypertension provides important clues that help in the diagnosis of secondary hypertension. Some forms of secondary hypertension are potentially curable when the underlying pathology is treated.
Resistant hypertension (RH) is defined as blood pressure that remains above goal in spite of the concurrent use of 3 antihypertensive agents of different classes. Recent American Heart Association (AHA) guidelines also include patients who are well controlled but require 4 or more medications as having resistant hypertension.
Resistant hypertension can be thus broadly divided into pseudo-resistant hypertension and true resistant hypertension (Table 8).32 Among patients with pseudo-resistant hypertension, sub-optimal anti-hypertensive therapy has been identified as an important cause leading to uncontrolled hypertension. Obstructive sleep apnea (OSA) is increasingly being recognized as an important cause for the development of resistant hypertension.
Management of resistant hypertension includes a detailed history, accurate BP measurement, recommending lower dietary salt intake, and other lifestyle interventions. Baroreceptor activation therapy is performed using a Rheos baroreflex hypertension therapy system which is surgically implanted in the subclavicular region. The Symplicity renal denervation system uses a catheter to perform radiofrequency ablation when applied to the lumen of renal arteries through a femoral access. These interventions are not yet FDA approved but hold promise to lower blood pressure in patients with resistant hypertension. Approximately 1% of Americans with hypertension are estimated to be affected by hypertensive crises. Hypertensive emergencies are more common in patients with essential hypertension (20%-30% in Caucasians and 80% in African Americans).
Patients with hypertensive emergencies may present with hypertensive encephalopathy, intracerebral hemorrhage, acute myocardial infarction, acute left ventricular failure with pulmonary edema, unstable angina pectoris, dissecting aortic aneurysm, or eclampsia. Underlying history of hypertension is an important factor in patients who develop hypertensive crisis. Triaging patients with hypertensive emergencies early and initiating parenteral antihypertensive therapy helps to limit target organ damage. Overly rapid lowering of BP to normal levels in patients with hypertensive emergencies should be avoided as it can cause renal, cerebral, and coronary ischemia.
It must be emphasized that accurate measurement of blood pressure is of fundamental importance in management of hypertension. Egan BM, Zhao Y, Axon RN: US trends in prevalence, awareness, treatment, and control of hypertension, 1988-2008. Sarafidis PA, Li S, Chen SC, et al: Hypertension awareness, treatment, and control in chronic kidney disease. Pickering TG, Davidson KW, Rafey MA, et al: Masked hypertension: are those with normal office but elevated ambulatory blood pressure at risk? Verdecchia P, Reboldi GP, Angeli F, et al: Short- and long-term incidence of stroke in white-coat hypertension. Pogue V, Rahman M, Phillips R, et al: Disparate estimates of hypertension control from ambulatory and clinic blood pressure measurements in hypertensive kidney disease. Beckett NS, Peters R, Fletcher AE, et al: Treatment of hypertension in patients 80 years of age or older. Appel LJ, Wright JT Jr, Greene T, et al: Intensive blood-pressure control in hypertensive chronic kidney disease. The ACCORD Study Group: Effects of intensive blood-pressure control in type 2 diabetes mellitus. Appel LJ, Moore TJ, Obarzanek E, et al: A clinical trial of the effects of dietary patterns on blood pressure.
Julius S, Nesbitt SD, Egan BM, et al: Feasibility of treating prehypertension with an angiotensin-receptor blocker. PROGRESS Collaborative Group: Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack.
Che Q, Schreiber MJ Jr, Rafey MA: Beta-blockers for hypertension: are they going out of style? Jamerson K, Weber MA, Bakris GL et al: Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. Yusuf S, Teo KK, Pogue J et al: Telmisartan, ramipril, or both in patients at high risk for vascular events.
Blood pressure is the lateral pressure exerted on the wall of the artery as the blood flows through the vessel. In 2003, the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7) redefined high blood pressure. In the clinical setting systolic blood pressure represents cardiac output and diastolic blood pressure represents peripheral vascular resistance. The best technology used an electrocardiogram to signal the control box to listen to the blood pressure sounds. This type of pattern is considered a dipping pattern because the blood pressure is normal during the sleeping hours. At one level, the hemodynamic determinants of blood pressure (BP) are cardiac output (Q) and peripheral vascular resistance (PVR). The figure to the right illustrates the hemodynamic factors that each blood pressure control mechanism affects. The natural history of the course of hypertension is less complex than the control of blood pressure. Stress is implicated in the etiology of hypertension by either over reactive catecholamine response or periods of increased catecholamine response. Sodium (Na+) has a role in the etiology of hypertension because of its relationship to fluid shifts.
The exact mechanism for low potassium and calcium intake in the etiology of hypertension is uncertain. Obesity is associated with hypertension because of the excess work the body has to do to transport a larger body mass and insulin resistance. In the early stages of high blood pressure, the pressure cycles from transient periods of high and low blood pressure. As more of the environmental influences remain, the blood pressure eventually becomes more high than low. After the blood pressure remains elevated for a period of time, the arterial system will change to stabilize the blood pressure at the higher pressures. Note: these stages of hypertension may be different from the JNC7 stages which are listed as values rather than pathology.
The predominant type of exercise used in most exercise and blood pressure studies is cardiovascular exercise.
In the exercise treatment of high blood pressure, both acute and training studies have been reported. Using ambulatory blood pressure technology we found that systolic blood pressure can be reduced (red section of the graph on the right) 5-8 mm Hg for 11 to 12 hours following exercise. Diastolic blood pressure, not pictured, can be reduced 6-8 mm Hg for 6-8 hours following exercise. In training studies, the range of blood pressure reduction is 5-25 for systolic and 3-25 for diastolic. However, patients with hypertension reduce, on the average, 11 for systolic and 8 for diastolic.
In addition to lowering blood pressure a significant number of patients can stop taking their blood pressure medications.
The figure to the left summarizes only three studies that utilized resistance training for hypertensive patients. These results may not be surprising considering the cardiovascular response to dynamic and static work.
Systolic blood pressure increases more in dynamic work because the cardiac output demand is larger. Resistance work can be made more dynamic and may result in different blood pressure responses for muscle endurance vs. In 2004, the traditional exercise prescription which was based on 1284 hypertensive patients in 74 exercise training studies, was modified to include physical activity and the accumulation of physical activity. For our first study, we asked 28 people to accumulate any type of physical activity over a 12 hour period.
This figure illustrates the blood pressure differences between the physical activity and control treatments. Our next study took us into the laboratory to control the accumulation of activity and to compare the blood pressure reductions to continuous work. HERITAGE Family Study was a four center genetic study observing the link between exercise effectiveness and genetics.
One mechanism of blood pressure has been considered an increase in Nitric Oxide, specifically, eNOS. No significant changes in blood pressure were detected based on the variations of the eNOS genes.
The angiotensinogen (AGT) and angiotensin converting enzyme (ACE) genetics were also observed in the HERITAGE study during submaximal exercise. Transforming growth factor (TGF) phenotypes were observed of TGF role in target-organ damage from hypertension.
Hagberg and colleagues divided 18 hypertensive subjects into their genotypes for high blood pressure.
After 9 months of exercise (40 minutes of exercise per session at 75% to 85% of VO2 max) he observed their reduction in systolic blood pressure. Women are more successful than men in reducing both systolic and diastolic blood pressure with exercise. Asian and Pacific Islanders are more effective in reducing blood pressure with exercise than Caucasians. People in the early stages of high blood pressure, where the peripheral vascular resistance is normal, are more effective in reducing blood pressure with exercise than people in the later stages. The people with higher blood pressures exhibit the larger reductions in blood pressure, whereas people with more normal blood pressures hardly show any reduction in blood pressure with exercise.
What does this mean when comparing people at the different stages of high blood pressure?
Intensity of Exercise is an important aspect of the exercise prescription to determine the outcome.
This figure summarizes the blood pressure reduction found for studies that utilized intensities above 75% of VO2max vs. In the hemodynamic determinants of blood pressure, exercise reduces the elevated component. To consider what reduces the hemodynamic determinants of blood pressure, the next level of blood pressure control should be considered. The contribution of the sympathetic (SE) and parasympathetic (VE) nervous systems are illustrated before and after training in hypertensive and normotensive rats.
It obvious that the amount of sympathetic activity is reduced with training and the amount of parasympathetic activity is increased in both normotensive and hypertensive groups. The sensitivity of the baroreflex can be increased with training as summarized in the figure to the left. Exercise training of the neural component accounts for a 30% decrease in sympathetic outflow to the skeletal muscle vascular beds. Exercise training of the vascular component is an attenuation of the vascular response to sympathetic vasoconstriction and perhaps a local circulating vasodilator substance. Patients should be seated with their arm bared, supported, and at the heart level.A A The right and left arms should have similar pressures in apparently health adults. Patients should not have smoked or ingested caffeine within 30 minutes before the measurement. The approximate cuff size must be used to ensure an accurate measurement.A A A cuff that is too small will measure blood pressure too high. Measurements should be taken with a mercury sphygmomanometer, a recently calibrated aneriod manometer, or a calibrated electrical device. Inflate the cuff rapidly.A A Deflate the cuff slowly (2-3 mmHg per second) until systolic pressure is found, then deflate the cuff faster for diastolic pressure. Both systolic and diastolic blood pressures should be recorded.A A The disappearance of sound (fifth phase) should be used for the diastolic reading. Two or more readings separated by 2 minutes should be averaged.A A If the first two readings differ by more than 5 mmHg, additional reading should be obtained.
Targeting the systolic blood pressure is the focus of the therapy because systolic blood pressure is more related to the end organ diseases than the diastolic blood pressure.
The goal of antihypertensive pharmacology is to reduce blood pressure through one or more of the blood pressure control mechanisms. The primary classes (with subclasses) of antihypertensive medications are summarized in the chart below.
See the 7th Report for a summary of drug and trade names, dosage and daily frequency of these meds.
The Potassium-Sparing Diuretics, on the other hand, act like aldosterone receptor antagonists at the distal tubule to block aldosterone-sensitive Na+ reabsorption. Aldosterone Receptor Antagonists are considered potassium sparing diuretics even though it is considered a separate class of antihypertensive medications.
Unlike apha1-blockers that act at the vascular level, alpha2 agonists act at the level of the central nervous system. Vasodilators obviously act to decrease peripheral vascular resistance in the control of blood pressure. To summarize, the antihypertensive medications target either cardiac output (blue arrows) or peripheral vascular resistance (black arrows).
There are two exercise presriptions for hypertension; both from the American College of Sports Medicine. The purpose of this meta-analysis was to evaluate the relationship between blood lutein and zeaxanthin concentration and the risk of age-related cataract (ARC). Characteristics of studies of blood lutein and zeaxanthin and risk of age-related cataract. Forest plots of relative risks (RR) and 95% confidence interval (CI) for highest-versus-lowest category of blood concentrations of lutein and zeaxanthin and nuclear cataract risk.
Stratified analysis of the association between serum level of lutein and zeaxanthin and nuclear cataract. Forest plots of relative risks (RR) and 95% confidence interval (CI) for highest-versus-lowest category of blood concentrations of lutein and zeaxanthin and subcapsular cataract risk. The funnel plots for the studies evaluating blood lutein and zeaxanthin concentrations and their association with different subtypes of ARC revealed symmetry. There is a continuous, consistent, and independent relationship between elevated BP and risk of cardiovascular events.
The metabolic syndrome, with insulin resistance and elevation in insulin levels, leads to increased sympathetic activity and hypertension. The history should include details of dietary salt intake and should explore lifestyle patterns and social and psychosocial stressors that could potentially affect BP levels.
Because inaccuracies in blood pressure measurement can occur frequently in clinical practice, the following guidelines should be followed when measuring a patient's BP.9 The patient should be seated comfortably with the back supported and the upper arm bared without constrictive clothing. Twenty-four-hour ambulatory BP monitoring is indicated to rule out white-coat hypertension, to uncover apparent drug resistance (office resistance), to better define resistant hypertension, to identify hypotensive symptoms while the patient is being treated with anti-hypertensive medications, to monitor episodic hypertension, and to identify autonomic dysfunction states. Studies done in patients with sustained hypertension for more than 40 years have consistently demonstrated that this condition is closely related to target organ damage and worse cardiac and renal outcomes.
Although there are no outcome trials available in patients with masked hypertension, the fact that elevated ambulatory BP is closely related to cardiovascular events implies that its risk profile is similar to that of sustained hypertension. The prevalence of white coat hypertension has been reported to be 12% to 18% in the general population.
Abnormalities in the normal nocturnal dipping pattern of BP have been associated with worse cardiovascular outcomes, even in subjects who are normotensive.12 A 24-hour ambulatory BP measurement remains the only technique to assess the dipping status of patients. Blood pressure measurements using such validated devices should be taken before an office visit, with at least 2 morning and 2 evening readings everyday for 1 week (but discarding the readings of the first day), which gives a total of 12 BP readings over a week, based on which clinical decisions can be made. Preliminary data from clinical studies indicate that these measures of arterial stiffness may provide better prognostic indices and therapeutic targets in hypertensive patients.15,16 Interventional trials that can test the potential value of treating to a predefined central blood pressure goal for a given brachial blood pressure will clarify the utility of these measures in the future clinical management of hypertension. In addition, laboratory tests can provide clues to the etiology in those with resistant or secondary hypertension (Table 2). In addition, JNC 7 guidelines do recognize and incorporate the importance of increased cardiovascular risk across a broad spectrum of BP values, as well as a high lifetime risk of developing hypertension (Figure 2). The Hypertension in the Very Elderly Trial (HYVET) trial is the first study that clearly demonstrated the benefits of anti-hypertensive therapy in older patients with hypertension.18 In this study, lowering BP in patients with hypertension (mean age of 84 years) lowered the risk of both stroke and all-cause mortality. Appropriate nutritional counseling can encourage a diet with reduced total fat and cholesterol intake, in addition to providing an adequate daily intake of potassium, calcium, and magnesium. The effects of implementing these modifications are both dose dependent and time dependent and could be greater for some patients.
The Framingham study demonstrates that if prehypertension is left untreated, these patients go on to develop hypertension. The alpha-adrenergic blocker arm of this study was discontinued early in the trial because it was observed that patients receiving an alpha-adrenergic blocker as monotherapy demonstrated twice the risk of congestive heart failure when compared with those treated with an oral diuretic. Nevertheless, it was concluded from this trial that diuretic therapy is as effective as a calcium channel blocker or an ACE inhibitor from the standpoint of the primary outcome of the trial, and diuretic therapy is superior for select subgroup analyses.
Based on evidence of improved outcomes, JNC 7 has recommended several medications for compelling indications (Tables 5 and 6).
Clinical trials like ASCOT and several meta-analyses have demonstrated that a beta-blocker may not be an appropriate first line medication. Fixed-dose combinations of 2-3 classes of antihypertensive medications are now approved for management of hypertension. In some conditions, hypertension is potentially curable when the underlying cause is treated.
Impaired renal function can worsen blood pressure control by reducing sodium and water excretion, and leading to volume overload and hypertension.
In younger women, fibromuscular dysplasia of renal arteries could lead to uncontrolled hypertension. These patients may also complain of muscle cramping and weakness if they develop severe hypokalemia. Patients may present clinically with wide fluctuations in blood pressure, sustained hypertension, or with abrupt paroxysms of hypertension. Recent data suggest that the incidence rate of resistant hypertension is 2% in patients who were newly diagnosed with hypertension and receiving therapy. In the ALLHAT study more than 25% of patients remained on sub-optimal therapy during the course of the study, although their blood pressures were elevated and anti-hypertensive therapy was provided free of cost as part of the study.
In this condition, the measured cuff pressure is inappropriately higher than true intra-arterial blood pressure due to excessive arteriosclerosis and arterial stiffness which is common in the elderly. Several studies have reported a strong correlation between obstructive sleep apnea and hypertension.33 Several mechanisms are hypothesized to explain this association, including chronic night time hypoxemia, altered chemoreceptor stimulation, and activation of the sympathetic and renin-angiotensin systems.
Food and medications that interfere with hypertension therapy or cause elevation of blood pressure should be discontinued. The electrodes connected to this device are attached to the carotid body on each side of the neck.
Factors such as renal failure, heart failure, cerebrovascular accidents, and nonadherence to antihypertensive therapy are associated with hypertensive crisis.
When evaluating patients with severe hypertension, it is important to distinguish hypertensive urgency from hypertensive emergency as the treatment plan is based on the diagnosis. Although a majority of patients with hypertension remain asymptomatic, a careful early evaluation identifies those with or at risk for target organ damage with left ventricular hypertrophy and microalbuminuria, both of which portend serious future cardiovascular and renal events. It is also important to identify the modifiable risk factors that can help improve blood pressure control and reduce cardiovascular and renal damage. Systolic blood pressure is the pressure on the vessel walls during systole whereas diastolic blood pressure is the pressure on the vessel walls during diastole. The top of each line is systolic pressure and the bottom of each line is diastolic pressure.
This pattern is termed, non-dipping and is considered more severe than nocturnal dipping hypertension. The classic catecholamine response is an increase in heart rate, stroke volume, cardiac output and vasoconstriction. Increases in Na+ are associated with increases in fluid, increases in blood volume, and increases in cardiac output. We placed an accelerometer on their waist to measure their energy expenditure for the 12 hour period, as well as an ambulatory blood pressure monitor on them to record blood pressures every 15 minutes for the 12 hour period after the physical activity. The subjects were divided into groups with normal blood pressure (n=8), prehypertension (n=10) and hypertension (n=10).
But, this figure illustrates the duration of the blood pressure reduction for the accumulation of walking was four hours longer than for continuous walking. The centers were Texas A & M, Laval University, University of Minnesota, and Indiana University. Thus, the polymorphism of Glu298Asp (eNOS) was observed in blood pressure reduction in 471 caucasian subjects from 99 family units.
Systolic blood pressure response to 50 Watts of cycle ergometry is illustrated to the left before and after training.
Comparing studies for men and women, 100% of the studies observing women reported a decrease in systolic blood pressure whereas only 72% of the studies observing men reported reductions. Over 90% of the studies targeting Asians and Pacific Islander reported blood pressure reductions; whereas only 65% of those targeting Caucasians reported reductions. When it comes to the sodium (Na+) to potassium (K+) ratio, ita€™s found in the blood; serum to be exact. People in the borderline stages have lower blood pressures than people in the more advanced stages. Selective beta blockers target the heart directly whereas non-selective beta blockers have more total body effects. That is, if cardiac output is the elevated determinant, cardiac output will decrease with exercise treatment.
Does the change in baroreceptor activity result in lower pressures or does the change in sympathetic activity result in more sensitive baroreceptor activity?
When the baroreceptors are regulated around a lower pressure, there is less sympathetic activity. Aldosterone in the hormone responsible for sodium and water reabsorption as well as potassium secretion in the kidneys. Norepinepherine is the neurotransmitter activating both the apha1 and alpha2 receptors that stimulate smooth muscle contraction. ACE inhibitors inhibit the formation of Angiotensin II whereas ARBs block the angiotensin II receptors on the vasculature and myocardium. If the source of the hypertension as diagnosed in medical practice, medications that target the source of the hypertension could be targeted.
MEDLINE, EMBASE, ISI and Cochrane Library were searched to identify relevant studies up to April 2013.
IntroductionCataract is a clouding or opacification of the lens inside the eye that obstructs the passage of light .
Study CharacteristicsTable 1 shows the design features and participant characteristics of the eight identified studies of blood lutein and zeaxanthin levels and risk of cataract. Blood Lutein and Zeaxanthin and Subcapsular CataractFour studies respectively reported blood levels of lutein and zeaxanthin (Figure 4). Objective assessment of crystalline lens opacity level by measuring ocular light scattering with a double-pass system.
This was clearly demonstrated in a meta-analysis that included 1,000,000 individuals with no history of vascular disease. Despite the increase in prevalence, recent data from the National Health and Nutrition Examination Survey (NHANES) demonstrate an improvement in blood pressure control (50%) among Americans with hypertension.3 However, the blood pressure control rate remains suboptimal in people who have serious comorbid conditions such as chronic kidney disease. The remainder of these patients have hypertension caused by renovascular disease, primary aldosteronism, etc.
Guyton's hypothesis, there is impaired excretion of sodium ions by tubular epithelial cells in the kidney.
In patients with obstructive sleep apnea, activation of the sympathetic and renin angiotensin systems has been defined as a possible mechanism for elevation in BP. Ophthalmologic assessment and funduscopic examination are simple techniques to identify the severity of disease and target organ damage by grading retinal changes. Twenty-four-hour ambulatory BP monitoring also helps identify abnormal patterns in blood pressure that could remain undetected if a patient is evaluated based on physician office blood pressure measurements alone. In fact, patients with masked hypertension might have a worse outcome because they are not easily identified and do not receive adequate therapy.
Initially, this was thought to be a benign condition, because prospective trials evaluating white coat hypertension have shown less target-organ damage (increased left ventricular mass, carotid media intimal thickness) than that with sustained hypertension. Nocturnal hypertension defines a pattern of BP where BP measured during sleep is higher than that measured when the patient is awake. Guidelines of the European Society of Hypertension have incorporated measurement of PWV for risk stratification of patients with hypertension.
In an effort to highlight this relationship between elevated BP and cardiovascular disease, a revised classification of hypertension has been provided by JNC 7 (Table 3).
In recent years however, large clinical trials performed in patients with kidney disease and diabetes have failed to demonstrate clear benefit with intense blood pressure control.
However, aggressive efforts are needed to ensure optimal adherence to these recommendations.
The Dietary Approaches to Stop Hypertension (DASH) trial has provided substantial data that a diet rich in fruits, nuts, vegetables, and low-fat dairy products and with an emphasis on fish and chicken rather than red meat lowered BP even without weight reduction and was particularly effective in those who also restricted sodium chloride intake.22 Dietary recommendations must be made on an individualized basis and should be well supported with continued educational and counseling efforts. Also, a combination of 2 or more lifestyle modifications can help patients achieve even better results.
Current recommendations center on nonpharmacologic interventions, which include lifestyle modifications such as weight reduction, increased physical activity, and reduced dietary salt intake. The diuretic, calcium antagonist, and angiotensin-converting enzyme (ACE) inhibitor groups were continued to an average follow-up of 4.9 years, at which time no differences were noted among groups with regard to the primary outcome (fatal coronary disease or nonfatal myocardial infarction) or all-cause mortality. A critical look at the trial design suggests a more prudent conclusion that diuretics should be part of all antihypertensive regimens unless they are clearly contraindicated. These include beta blockers and aldosterone antagonists in patients with cardiac disease, ACE inhibitors and ARBs in patients with chronic kidney disease, and diuretics and calcium channel blockers in patients with isolated systolic hypertension. These combinations offer superior efficacy as each agent in the combination blocks the counter regulatory system activity triggered by the other. In the Modification of Diet in Renal Disease (MDRD) study, the prevalence of hypertension increased linearly from 65% to 95% as the glomerular filtration rate declined progressively toward end-stage renal disease.30 Both hypertension and CKD are independently associated with increased cardiovascular mortality and the effect is amplified in CKD patients with hypertension.
Significant renal artery stenosis leads to hypoperfusion of the kidney that results in activation of the renin-angiotensin-aldosterone system leading to retention of sodium and water and worsening blood pressure control.
In Cushing syndrome, prolonged exposure to endogenous or exogenous cortisol leads to elevated blood pressure. Elevations in blood pressure may be associated with palpitations, headache, pallor, tremor and diaphoresis. Results from NHANES survey reveal that prevalence of resistant hypertension in US adults is nearly 9%. In patients who have uncontrolled hypertension despite being on adequate anti-hypertensive therapy, it is important to confirm the diagnosis with home BP monitoring or 24-hour ambulatory BP measurement. The thickened and calcified arteries that result from arteriosclerosis are not compressed adequately during inflation of the blood pressure cuff. Frequent night-time hypoxia and hypercapnia also appear to stimulate aldosterone production independent of plasma renin levels. Early identification of these patients and achieving BP goals could reverse early end-organ damage and improve outcomes in these patients.
Certain classes of medications appear to have a more beneficial effect than others in managing high-risk patients with hypertension leading to the recommendation of compelling indications. The green arrows indicates the system primarily increases blood pressure, whereas the red arrow indicates the system primarily decreases blood pressure. These acute studies may provide information on the long-term training effects of exercise. Diastolic blood pressure decreases in dynamic work because the peripheral resistance is reduced, yet increased in static work because the muscle contraction increases resistance to blood flow.
Mode was modified to include more general endurance physical activities beyond the specific dynamic cardiovascular endurance exercise; and resistance was recommended as a supplement to physical activity. We asked them to wear both monitors; one day with no activity (the control day) and the other day with activity. As expected, the people with normal blood pressure had no difference following physical activity. One day they would walk for the entire 40 minutes continuously (long); and the other day they split the 40 minutes into four 10 minute sessions (accumulation). Thus, the accumulation of short sessions of physical activity appeared better than one single continuous session. However, because high blood pressure has a genetic component, perhaps the effectiveness of treatment also has a genetic component. Families totaled 239 caucasian men and 253 caucasian women from 99 nuclear families and 91 African American men and 179 African American women from 105 nuclear families. The blood pressure reductions were small, but signficant considering the number of subjects.
The HERITAGE study, however, focused on the normotensive adults and found no sigficant interactions between the races. Yet, those people who are borderline are more effective than those in the later stages at reducing blood pressure with exercise. In any case, the primary action of both types of beta blockers is to blunt heart rate, contractility and consequently cardiac output. Similarly, if peripheral vascular resistance is elevated, peripheral vascular resistance will decrease with exercise treatment.
Normotensive rats move from the NS (sedentary) curve to the NT curve (trained) whereas hypertensive rats move from the HS (sedentary) curve to the HT curve (trained) with training. The lower sympathetic activity can not only affect peripheral vascular resistance, but cardiac output as well. ACE Inhibitors also result in a naturesis and diuresis (via decreasing aldosterone) which is prevented with the use of ARBs.
The 1993 recommendations are based on 72 studies with 1284 patients; whereas the 2004 recommendations are based on 8 physical activity studies, of which only one was for hypertension. Meta-analysis was conducted to obtain pooled relative risks (RRs) for the highest-versus-lowest categories of blood lutein and zeaxanthin concentrations. Age-related cataract (ARC) is the leading causes of blindness and vision impairment worldwide .
Of the included studies, three were conducted in the USA, three in Europe and two in India.
Pooled analyses showed no significant heterogeneity in the association between these two carotenoids and subcapsular cataract. To maintain salt and water homoeostasis, the body adopts a pressure-natriuresis approach that ultimately leads to an elevation in BP. The arm should be supported at the level of the heart, and the bladder of the BP cuff should encircle at least 80% of the arm circumference. Clinical studies evaluating cardiovascular outcomes have consistently demonstrated a lower morbidity with white coat hypertension, supporting a more benign course. In the African American Study of Kidney Disease and Hypertension (AASK), an abnormal dipping pattern was detected in 80% of patients and nocturnal hypertension was found in 40%.13 All of these patients with an abnormal dipping pattern and nocturnal hypertension had hypertension that was apparently well controlled based on office BP readings. Home blood pressure monitoring provides an inexpensive alternative to 24-hour ambulatory BP monitoring which is not yet widely available. The European Society of Hypertension (ESH) and European Society of Cardiology (ESC) 2009 guidelines have embraced the concept of global cardiovascular risk in recommending that patients be classified not only in relation to grades of hypertension but also in terms of total cardiovascular risk, which represents cumulative risk from the coexistence of multiple factors and target organ damage.17 These guidelines stress that the threshold for hypertension and subsequent drug therapy should remain flexible and should be a function of each patient's individual and total cardiovascular risk. Lifestyle modifications not only reduce BP but also enhance the efficacy of antihypertensive drugs and decrease cardiovascular risk. However, compared with the diuretic (chlorthalidone) group, the calcium antagonist (amlodipine) group had a significantly higher cumulative incidence of heart failure, and the ACE inhibitor (lisinopril) group had significantly higher incidences of heart failure, stroke, and angina pectoris. Further, there was concern that diuretics might worsen glucose tolerance and insulin resistance. In addition, single fixed-dose combination improves adherence to medications and BP control. Patients may also present with acute worsening in renal function, asymmetric kidney size, or flash pulmonary edema; a systolic diastolic bruit may be heard over the epigastrium. In addition, these patients may also present with moon facies, prominent supraclavicular fat pad, buffalo hump, truncal obesity, and purple striae. Patients with resistant hypertension are at a significantly higher risk for cardiovascular events compared to those with non-resistant hypertension.
In a Spanish cohort of patients who were defined as having resistant hypertension based on the American Heart Association (AHA) criteria and who underwent 24-hour ambulatory BP measurement, 37.5% patients were found to have white coat hypertension. Rapid lowering of BP to near normal levels is avoided as it could lead to renal, cerebral and coronary ischemia. Analysis of the data from Framingham Heart study demonstrates that a 2-mmHg reduction in blood pressure would result in 14% reduction in the risk of stroke and transient ischemic attacks, and a 6% reduction in risk of coronary heart disease. Thus anti-hypertensive therapy should be tailored and personalized based on an individual's health profile.
The types of physical activity these subjects performed ranged from cycling to gardening, mowing the lawn, cleaning the house, and brisk walking. Familes were concidered the natural mother and father with three offspring >17 years old for the caucasian (C) families and at least two first degree relatives for the African Amercian (AA) families. There were also racial differences; with African Americans having higher blood pressures and larger reductions in blood pressures. When cardiac output is reduced in adults without heart disease, physical work capacity is lowered. The figure to the left illustrates the additive blood pressure redution when physical activity and diet are added to weight loss of 10 kg.
It was estimated that 20 million people older than 40 years were visually impaired due to ARC in the United States . Animal studies and studies evaluating Mendelian forms of syndromes that manifest as hypertension and hypotension, such as Bartter's syndrome and Liddle's syndrome, have provided insight into the pathophysiology of hypertension.8 These data confirm that the basic problem in conditions leading to alteration in BP lies in the genetic alteration of sodium transport in renal epithelial cells. Based on these studies, it has been hypothesized that white coat hypertension represents an intermediate risk state between normotension and sustained hypertension.
One of the main drawbacks in home blood pressure measurement when compared to 24-hour ambulatory BP monitoring, is that sleep time blood pressures cannot be recorded and therefore those patients with abnormal dipping pattern in blood pressure and nocturnal hypertension will be missed. Smoking cessation should therefore be strongly encouraged for all patients, and education, counseling, and medication should be provided as needed. There is some evidence from clinical trials suggesting that the addition of an aldosterone antagonist to an existing anti-hypertensive regimen a”€ even in those patients with normal or low aldosterone levels a”€ improves blood pressure levels.
It has been proposed that an acute increase in humoral factors leads to systemic vasoconstriction and increased vascular resistance causing elevation in blood pressure. These patients require monitoring in intensive care units and parenteral anti-hypertensive medications (Table 9).
The effective management of hypertension is therefore an important primary health care objective in managing cardiovascular and renal disease. For instance, in patients with hypertension associated with unusual features such as early onset of severe hypertension or clinical features such as palpitations and diaphoresis, further evaluation for secondary hypertension is recommended as these conditions are potentially curable.
The total time for the accumulation of physical activity over the 12 hour period was approximately four hours. The people with prehypertension decreased their systolic blood pressure 6 mm Hg for 6 hours whereas the people with high blood pressure decreased their systolic blood pressure 13 mm Hg for 8 hours. Exercise training-induced blood pressure and plasma lipid improvements in hypertensives may be genotype dependent.
Training was 20 weeks of computer controlled cycle ergometry, 3 days a week for 60 minutes each session. The inability to exercise may compromise the potential to reduce blood pressure through physical activity.
Although new therapeutic methods emerged in recent years and most ARC cases can be cured, the high treatment costs and increasing demands for therapy will challenge the long-term economic stability of health care systems . Cataract cases were ascertained based on lens photography in five studies, on slit lamp in two and on review of medical records in one. Similarly, inconsistencies in stratified variables also did not affect the overall pooled estimate for blood lutein and zeaxanthin and subcapsular cataract.
Several factors including aging, sympathetic overactivity, toxins, and a low nephron number have been proposed as factors that could ultimately damage the renal tubules and alter epithelial cells, resulting in defective sodium excretion. In patients with OSA and resistant hypertension, treatment with aldosterone antagonists and non-invasive positive pressure ventilatory support (NIPPV) may improve blood pressure control.
In contrast, for patients with hypertensive urgency, blood pressure can be lowered gradually over 24-48 hours. On the other hand, patients with severely elevated hypertension and with evidence of target organ dysfunction or damage need to be triaged early and started on parenteral antihypertensive therapy to lower cardiovascular and renal morbidity and mortality. These new recommendations were based on eight studies, of which only one study observed subjects with high blood pressure; and was limited only to women.
This, difference between prehypertension and hypertension is not surprising as the people with hypertension had higher pressures and thus, more to reduce with physical activity.
The cycle ergometers were programed to start at 55% of VO2max and progress to 75% VO2max by the sixth week of training.
The information for African-Americans is limited despite the fact that African-Americans have the highest rate of hypertension. In other words, your client who is taking beta blockers may not be able to exercise hard enough to reduce blood pressure. A stronger association between nuclear cataract and blood zeaxanthin might be noted for the studies conducted in the European Nations. With the rapidly aging population, ARC has brought a massive burden on health care and become an important public health issue.
Four studies used the criteria of Lens Opacities Classification System (LOCS) to classify ARC, whereas the Early Treatment Diabetic Retinopathy Study (ETDRS) criteria and the Wisconsin Cataract Grading System (WCGS) criteria were applied in one study and two studies, respectively. If secondary hypertension is suspected it should be thoroughly investigated, as in some instances, such as pheochromocytoma or adrenal adenoma, this may be of curable etiology. What was surprising was mowing the lawn, gardening and cleaning the house were just as effective as traditional cycling and brisk walking. Of the 744 subjects, 507 (166 African Americans) completed the blood pressure aspects of the study.
Blood lutein and zeaxanthin were also noted to lead towards a decrease in the risk of cortical cataract and subcapsular cataract; however, these pooled RRs were not statistically significant, with the exception of a marginal association between lutein and subcapsular cataract. Thus, identifying modifiable factors available to prevent or delay the development of ARC is a crucial strategy.Light-initiated oxidative damages are hypothesized to be the mechanism involved in ARC . In all of the included studies, levels of lutein and zeaxanthin were measured in blood samples by high-performance liquid chromatography (HPLC).
Our results suggest that high blood lutein and zeaxanthin are significantly associated with a decrease in the risk of nuclear cataract. The xanthophyll carotenoids lutein and zeaxanthin are uniquely concentrated in the lens, where they can attenuate photochemical damage by filtering high-energy short-wavelength light [6,7]. All of the studies adjusted for age and smoking, six adjusted for gender and body mass index (BMI) and four adjusted for intake of alcohol. In any case, the beta blocker is not the best medication for people who want to do physical activity to help control blood pressure. In addition, they serve to protect the lens from oxidative damage by scavenging reactive oxygen species (ROS), indicating that these carotenoids may play a potentially important role in the prevention of ARC .
Other adjustment factors included serum cholesterol, education, iris color, blood pressure, social class, and history of diabetes.
TGF-beta1 gene-race interactions for resting and exercise blood pressure in the HERITAGE Family Study Journal of Applied Physiology 91:1808-1813, 2001.
Numerous epidemiological studies have investigated the relationship between dietary intake and blood levels of lutein and zeaxanthin and the risk of ARC [9,10].
Because the accuracy of dietary intake measurements is greatly influenced by the different dietary assessment methods across the studies and the individual differences in utilization and absorption, blood concentrations appears to be a stronger predictor of nutritional status [11,12]. AGM M235T and ACE ID polymorphisms and exercise blood pressure in the HERITAGE Family Study American Journal of Physiology, Heart and Circulatory Physiology 279:H368-H374, 2000. Many studies reported that high serum concentrations in lutein and zeaxanthin were inversely associated with the prevalence of ARC; however, others failed to find such association or the results regarding certain subtypes of ARC were inconsistent [13,14]. Therefore, we conducted this meta-analysis to evaluate the relationship between serum concentration of lutein and zeaxanthin and risk of difference ARC subtypes. Search StrategyWe searched MEDLINE, EMBASE, ISI Web of Science and Cochrane Library for relevant articles up to April 2013. Following MeSH words and text words were used: “lutein”, “zeaxanthin”, “xanthophyll”, or “carotenoid”, together with each of the following words “cataract”, “age-related cataract”, “ARC”, or “lens opacities”.
Blood Lutein and Zeaxanthin and Cortical CataractFive studies reported data on blood lutein concentration with cortical cataract, and four studies reported blood zeaxanthin (Figure 3). Besides, manual searches of references cited by the retrieved articles were performed for additional literature.
Results of subgroup analysis showed that none of the variables examined markedly influenced the shape of such association. We extracted the name of the first author, year of publication, country of origin, study design, characteristics of the study population (sample size, distribution of age, sex and ethnicity), diagnostic method of ARC, classification and grading systems for ARC, blood concentration assessment methods, fully adjusted odds ratio or relative risk, and the adjustment factors. If a study provided several risk estimates, the most completely adjusted estimate was extracted. ConclusionsOur meta-analysis demonstrated that increased blood concentrations of lutein and zeaxanthin might be associated with a reduced risk of nuclear cataract. However, there is insufficient evidence to support a significantly inverse relationship between blood lutein or zeaxanthin level and risk of other subtypes of ARC. Meanwhile, there are only a few observational studies published about the association between blood concentrations of these carotenoids and ARC, which also limits the power of meta-analysis.
Therefore, longer-term, large-scale, prospective controlled intervention studies are needed to clarify further the impact of lutein and zeaxanthin on the development of ARC. Literature SearchOur search resulted in a total of 1615 references, of which 1558 were excluded after abstract review (Figure 1).
Of the 57 articles that were considered as potentially relevant studies and were then retrieved for full-text review, eight studies (seven cross-sectional studies and one cohort study) met the inclusion criteria and were included in the meta-analysis [12,13,14,18,19,20,21,22].
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